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Chronic hypoxia can be observed in the heart under physiological or pathophysiological states, including embryonic development or cyanotic congenital heart disease. The aim of the present study was to examine gene expression profiles of chronically hypoxic myocardium and to explore the pathophysiological mechanisms by which the heart adapts to chronic hypoxia. Raw data from the next‑generation sequencing data set GSE36761 were downloaded from the Gene Expression Omnibus database. The data set comprised 30specimens, including 8 healthy myocardia and 22 tetralogy of Fallot (TOF) congenital cardiac malformations; only 7 original data sets of healthy myocardia were obtained, and 5/22 TOFs were excluded. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of differentially expressed genes (DEGs) were performed. Furthermore, network analysis of DEGs using Cytoscape software based on protein‑protein interaction (PPI) data was also conducted. A total of 1,260 DEGs were selected, of which 926 DEGs were enriched in 83 GO biological process terms, including extracellular matrix organization, regeneration and monocyte chemotaxis. Furthermore, 406 DEGs were enriched in 13 KEGG pathways, including cytokine‑cytokine receptor interaction, focal adhesion and apoptosis. PPI network analysis indicated that six hub genes with correlated degree scores >25 among nodes were identified, including G protein subunit 4, C‑C motif chemokine receptor (CCR)1, CCR2, platelet factor 4, catenin 1 and Jun proto‑oncogene (JUN). Of these, JUN was enriched in GO terms of regeneration and neuron projection regeneration, and in KEGG pathways of focal adhesion, apoptosis and Chagas disease (American trypanosomiasis). The present bioinformatics analysis of these DEGs and hub genes may provide a molecular insight to the role of diverse genes in the pathophysiology of chronically hypoxic myocardium and in myocardial adaptation to chronic hypoxia. | [
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The prevalence of mental health disorders such as depression is high. Depression is a multifactorial disorder and its underlying mechanisms remain unclear. Competing endogenous RNA (ceRNA) regulation has been reported to serve important roles in human disease. In the present study, ceRNA networks for depression and the corresponding normal physiological states were constructed. Further analysis of the ceRNA networks revealed that ceRNA regulation may be important for depression. Hub ceRNAs including high mobility group nucleosomal binding domain 3, peroxisome proliferator‑activated receptor‑ coactivator 1 and leukemia inhibitory factor receptor‑ were associated with depression. A common core ceRNA network was identified by comparison analysis. Functional analysis suggested that these ceRNAs may be implicated in depression. Differential expression analysis revealed that ceRNAs in the obtained ceRNA interaction networks were significantly enriched with significantly differentially expressed genes. A total of 8 key functional modules for depression were identified, and small target molecules were screened. ceRNA protocadherin‑ subfamily C2 in module1 and ceRNA Cyclin‑dependent kinase 6 in module 3 were reported to be implicated in the occurrence and development of depressive disorders. Thus, the present analysis may provide insight into the pathogenesis of depression and improve its treatment. | [
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Previous studies demonstrated that estrogen receptor(ER) signaling alleviates systemic inflammation in animal models, and suggested that ER‑selective agonists may deactivate microglia and suppress T cell activity via downregulation of nuclear factor ‑light‑chain‑enhancer of activated Bcells (NF‑B). In the present study, the role of ER in lipopolysaccharide (LPS)‑induced inflammation and association with NF‑B activity were investigated in PC‑3 and DU145 prostate cancer cell lines. Cells were treated with LPS to induce inflammation, and ELISA was performed to determine the expression levels of inflammatory cytokines, including tumor necrosis factor‑ (TNF‑), monocyte chemoattractant protein1 (MCP‑1), interleukin (IL)‑1 and IL‑6. MTT and Transwell assays, and AnnexinV/propidium iodide staining were conducted to measure cell viability, apoptosis and migration, respectively. Protein expression was determined via western blot analysis. LPS‑induced inflammation resulted in elevated expression levels of TNF‑, IL‑1, MCP‑1 and IL‑6 compared with controls. ER overexpression significantly inhibited the LPS‑induced production of TNF‑, IL‑1, MCP‑1 and IL‑6. In addition, the results indicated that ER suppressed viability and migration, and induced apoptosis in prostate cancer cells, which was further demonstrated by altered expression of proliferating cell nuclear antigen, B‑cell lymphoma2‑associated X protein, caspase‑3, E‑cadherin and matrix metalloproteinase‑2. These effects were reversed by treatment with the ER antagonist PHTPP or ER‑specific short interfering RNA. ER overexpression reduced the expression levels of p65 and phosphorylated NF‑B inhibitor(IB), but not total IB expression in LPS‑treated cells. In conclusion, ER suppressed the viability and migration of the PC‑3 and DU145 prostate cancer cell lines and induced apoptosis. Furthermore, it reduced inflammation and suppressed the activation of the NF‑B pathway, suggesting that ER may serve roles as an anti‑inflammatory and anticancer agent in prostate cancer. | [
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Dendritic cells (DCs), as professional antigen‑presenting cells are essential for the initial activation of adaptive antitumor immunity. CD1d is considered to present phospholipid and glycosphingolipid antigens to NKT cells. However, it is currently unknown whether CD1d expression on DCs is capable of enhancing antitumor immunity, particularly T‑cell related immunity. We observed that CD1d was predominantly expressed on DCs in 3LL tumor‑bearing mice, whilst a deficiency of CD1d promoted tumor growth. Notably, CD1d expression on DCs was not only required for presenting antigen to NKT cells, but also markedly promoted CD4+T and CD8+Tcell activation, particularly cytotoxic Tcells. All the Tcells (NKT, CD4+T and CD8+Tcells) upregulated CD69, CD107a and IFN‑ after the adoptive transfer of CD1d‑positive DCs (CD1d+DCs) and tumor growth was suppressed. With regard to the mechanism, we revealed that CD1d+DCs were concomitant with a higher expression of costimulatory molecules (CD40, CD80 and CD86) and MHCI/II, which are essential for DCs to presentantigens to Tcells. Consistently, CD1d+DCs displayed stronger activation‑associated‑ERK1/2 and NF‑B signals; whereas JAK2‑STAT3/6 signaling was required for maintaining a high level of CD1d on DCs. In lung cancer patients, the antitumor activities of all the Tcells were enhanced with the increase of CD1d+DCs. Analysis of TCGA data revealed that high levels of CD1d indicated better outcomes for patients. Collectively, CD1d enhanced DC‑based antitumor immunity, not only by targeting NKT, but also by activating CD4+T and CD8+Tcells. CD1d+DCs may be superior to the bulk population of DCs in cancer immunotherapy. | [
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Reports of the ameliorative effect of angelicin on sex hormone deficiency‑induced osteoporosis have highlighted this compound as a candidate for the treatment of osteoporosis. However, the molecular mechanisms of action of angelicin on osteoblast differentiation have not been thoroughly researched. The aim of the present study was to evaluate the effect of angelicin on the proliferation, differentiation and mineralization of rat calvarial osteoblasts using a Cell Counting Kit‑8, alkaline phosphatase activity and the expression of osteogenic genes and proteins. Treatment with angelicin promoted the proliferation, matrix mineralization and upregulation of osteogenic marker genes including collagen type I 1 and bone ‑carboxyglutamate in fetal rat calvarial osteoblasts. Furthermore, angelicin promoted the expression of ‑catenin and runt related transcription factor 2, which serve a vital role in the Wnt/‑catenin signaling pathway. Consistently, the osteogenic effect of angelicin was attenuated by the use of a Wnt inhibitor. Moreover, angelicin increased the expression of estrogen receptor (ER), which also serves a key role in osteoblast differentiation. Taken together, these results demonstrated that angelicin may promote osteoblast differentiation through activation of ER and the Wnt/‑catenin signaling pathway. | [
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The cholinergic anti‑inflammatory pathway is considered an attractive approach for the alleviation of inflammatory diseases. Sepsis is characterized by systemic inflammation and widespread organ injury, especially that in the lung. In the present study, we explored the effects of an 7nAChR agonist, PNU‑282987, on sepsis‑induced lung injury and investigated the mechanisms of PNU‑282987 in response to lipopolysaccharide (LPS) stimulation in peritoneal macrophages. Sepsis was induced in C57BL/6 mice via cecal ligation puncture (CLP). Fifty mice were randomly divided into five groups: The sham group treated with vehicle, the sham group treated with PNU‑282987, the CLP group treated with vehicle, and the CLP group treated with PNU‑282987 (1mg/kg) 1h before or 2h after surgery. All mice were sacrificed at 12 or 24h after CLP. Both pre‑ and post‑CLP treatment with PNU‑282987 significantly attenuated sepsis‑induced lung injury and the release of IL‑6 in the bronchoalveolar lavage fluid (BALF). Pre‑treatment with PNU‑282987 also inhibited sepsis‑increased TNF‑ and IL‑6 production, while post‑CLP treatment only inhibited IL‑6 production in the lung tissue. Neither pre‑ nor post‑CLP treatment with PNU‑282987 affected IL‑6 release in the serum. Furthermore, pretreatment with PNU‑282987 resulted in reductions in TNF‑ and IL‑6 release in a dose‑ and time‑dependent manner and decreased the phosphorylation levels of p38, JNK and ERK under LPS conditions in peritoneal macrophages. Our results demonstrate that activation of 7nAChR alleviates sepsis‑induced lung injury; this effect is associated with the suppression of inflammatory responses via the MAPK pathway, suggesting that 7nAChR is a potential therapeutic target for the treatment of sepsis. | [
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] |
Osteosarcoma (OS) is the predominant form of primary bone malignancy in children and adolescents. Although the combination of chemotherapy and modified surgical therapy leads to marked improvements in the survival rate, the therapeutic outcomes remain unsatisfactory. Therefore, the identification of novel drugs with higher efficacy and fewer side‑effects is urgently required. Proteasome inhibitors have been approved by the Food and Drug Administration (FDA) for the treatment of certain cancers, although none of them are directed against OS. Non‑covalent proteasome inhibitors, such as PI‑1840, are superior to covalent ones in numerous respects in view of their chemical structure; however, to date, no studies have been published on the effects of non‑covalent proteasome inhibitors on OS cells. In the present study, the antineoplastic effects of PI‑1840 were systematically evaluated in the OS cell lines, MG‑63 and U2‑OS. Cell viability and morphological changes were assessed by Cell Counting Kit‑8 (CCK‑8) and live/dead assays. The cell cycle was analyzed using flow cytometry (FCM) and western blot analysis (assessing the levels of the proteins p21, p27, and the tyrosine kinase, WEE1). The extent of cell apoptosis and autophagy were assessed by FCM, western blot analysis [of the apoptosis‑associated proteins, microtubule‑associated protein 1 light chain3 (LC3) and Beclin1], and mRFP‑GFP‑LC3 adenovirus transfection assay. Transwell and wound healing assays, and western blot analysis of the matrix metalloproteinases (MMPs)2 and 9were performed to preliminarily evaluate the migration and invasion capability of the cells. In the present study, our results revealed that PI‑1840 inhibited the proliferation of OS cells and induced apoptosis, partly due to attenuation of the nuclear factor‑B (NF‑B) pathway. In addition, PI‑1840‑induced autophagy was detected, and inhibiting the autophagy of the OS cells led to an increase in the survival rate of the U2‑OS cells rather than of the MG‑63 cells. Furthermore, PI‑1840 attenuated the migration and invasion capabilities of the OS cells. In conclusion, the present study revealed PI‑1840 to be a promising drug for the treatment of OS. | [
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Abdominal aortic aneurysm (AAA) is an asymptomatic, potentially lethal disease whose ruptures have a high mortality rate. An effective pharmacological approach to decrease expansion or prevent the rupture of AAAs in humans remains lacking. Previous studies have suggested that activator protein1 (c‑Jun/AP‑1) and C/EBP homologous protein (Chop) are involved in the development of AAA. The purpose of the present study was to investigate whether c‑Jun/AP‑1 mediates Chop overexpression in AAA. c‑Jun/AP‑1 and Chop protein levels were determined in an angiotensin II (Ang II)‑induced AAA model using apolipoprotein E‑deficient mice. Additionally, mouse aortic smooth muscle cells (MOVAS cell line) were treated with Ang II. Apoptosis was evaluated via TUNEL assay, MOVAS cell migration ability was assessed by monolayer wound healing assay and the levels of c‑Jun/AP‑1 and Chop were determined by western blotting, immunofluorescence and immunocytochemical assays. Following c‑Jun silencing using c‑Jun‑specific small interfering (si)RNA, Chop expression was evaluated. Furthermore, chromatin immunoprecipitation (ChIP) was used to investigate whether c‑Jun/Ap‑1 binds directly to the DNA damage‑inducible transcript 3 protein (Ddit3) promoter. It was observed that c‑Jun/AP‑1 and Chop were synchronously overexpressed in Ang II‑induced AAA and Ang II‑treated cells, and that apoptosis and migration were induced by Ang II. In addition, Chop was suppressed when c‑Jun was silenced by targeted siRNA. Notably, the ChIP assay demonstrated that the DNA fragments pulled down by primary antibodies against c‑Jun/Ap‑1 were able to be amplified by (Ddit3) promoter‑specific primers. c‑Jun/AP‑1 may therefore mediate Chop expression in MOVAS cells via Ddit3. These results suggested that c‑Jun/AP‑1 may be a novel target for AAA therapy. | [
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The zinc finger protein Snail1 is an important factor in the regulation of the epithelial‑mesenchymal transition (EMT) of hepatocellular carcinoma (HCC) cells. The present study demonstrated that the expression of Snail1 in HCC tissues was significantly higher compared with its expression in tissues adjacent to primary sites, as determined via western blotting. Furthermore, the results of a dual luciferase assay revealed that hsa‑microRNA(miR)199a‑5p negatively regulated the protein expression of Snail1 by binding to its 3' untranslated region. However, in a comparative analysis of primary HCC and its metastatic tissues using reverse transcription‑quantitative polymerase chain reaction and western blotting, it was demonstrated that the expression of hsa‑miR199a‑5p and Snail1 in HCC metastatic tissues were significantly higher compared with primary lesions and an association between them identified that hsa‑miR199a‑5p lost its ability to negatively regulate Snail1. This result is contradictive to the fact that hsa‑miR199a‑5p inhibits the expression of the Snail1 protein. The present study hypothesized that the aberrant expression of long non‑coding RNA was the cause of hsa‑miR199a‑5p inactivation based on loss of function rather than a reduction in content. The data collected in the present study confirmed the hypothesis that AB209371 binds to hsa‑miR199a‑5p and weakened the inhibitory effect of hsa‑miR199a‑5p on Snail1 expression. In addition, an invitro EMT model was established in the present study by inducing HCC cells with TGF‑1. The results revealed that AB209371 silencing effectively reversed the hsa‑miR199a‑5p mediated inhibition of EMT by negatively regulating Snail1 protein expression. Therefore, AB209371 silencing in combination with hsa‑miR199a‑5p expression may serve as an effective means to inhibit EMT in HCC cells. The present study also revealed that hsa‑miR199a‑5p/Snail1 exhibits a dominant regulatory effect in the EMT of HCC cells via a Snail1 recovery experiment. In conclusion, to the best of our knowledge, the present study confirmed for the first time that the high expression of AB209371 is favorable for the EMT in HCC cells and may be a direct cause of hsa‑miR199a‑5p inactivation (an HCC metastasis suppressor). Additionally, AB209371 silencing combined with hsa‑miR199a‑5p overexpression may be an effective means to inhibit the metastasis of HCC and the EMT of HCC cells. | [
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Cisplatin (CDDP)‑based combination chemotherapy is the standard for muscle‑invasive bladder cancer (MIBC). However, nearly all patients undergoing CDDP chemotherapy become refractory due to the development of CDDP resistance. Therefore, clarification of the mechanisms of CDDP resistance is urgently needed. The transcribed ultraconserved regions (T‑UCRs) are a novel class of non‑coding RNAs that are highly conserved across species and are associated with carcinogenesis and cancer progression. In addition, emerging evidence has shown the involvement of androgen receptor (AR) signals in urothelial carcinoma (UC) progression. The aim of the present study was to investigate the expression of transcribed ultraconserved region Uc.63+, and to analyze the effects of Uc.63+ on AR expression and CDDP resistance in UC. Quantitative reverse transcription‑polymerase chain reaction (qRT‑PCR) revealed that the expression of Uc.63+ was higher in UC tissues than that in non‑neoplastic bladder tissues and 15types of normal tissue. An MTT assay revealed that Uc.63+ was involved in cell proliferation. Western blotting demonstrated that the expression of AR was disrupted by the overexpression or knockdown of Uc.63+ in AR‑positive UMUC3cells. Furthermore, knockdown of Uc.63+ increased sensitivity to CDDP in UMUC3cells. Conversely, overexpression of Uc.63+ had no effect on CDDP sensitivity in AR‑negative RT112cells. Additionally, we observed that the expression of Uc.63+ was increased in CDDP‑resistant UMUC3cells (UMUC3‑CR) in comparison with that in parental UMUC3cells. Knockdown of Uc.63+ re‑sensitized the UMUC3‑CR cells to CDDP. These results indicated that Uc.63+ may be a promising therapeutic target to overcome CDDP resistance in UC. | [
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Circular RNAs (circRNAs) are endogenous non‑coding RNAs implicated in atherosclerosis. The aim of the present study was to explore the function of circRNA‑0044073 in atherosclerosis. Reverse transcription quantitative polymerase chain reaction assays were used to measure the expression levels of circRNA‑0044073, microRNA (miRNA/miR)‑107, janus kinase 1 (JAK1), signal transducer and activator of transcription 3 (STAT3), B‑cell lymphoma 2 (Bcl‑2) and v‑myc avian myelocytomatosis viral oncogene homolog (c‑myc) in in blood cells from patients with atherosclerosis. RNA pull‑down and luciferase reporter assays were then used to determine the association between circRNA and miR expression, and miR and gene expression, respectively. Matrigel invasion assay and flow cytometry were used to analyze cell invasion and cell cycle. Western blot analysis and ELISA were used to evaluate the expression levels of proteins. It was identified that the expression of circRNA‑0044073 was upregulated and the expression of miR‑107 was downregulated in atherosclerotic blood cells. Overexpression of circRNA‑0044073 promoted the proliferation of human vascular smooth muscle cells (HUVSMCs) and human vascular endothelial cells (HUVECs), while overexpression of miR‑107 inhibited their proliferation. In addition, circRNA‑0044073 suppressed the levels of miR‑107 via a sponge mechanism. Lipopolysaccharide (LPS) affected the proliferation of HUVSMCs and HUVECs, and also resulted in changes in circRNA‑0044073 expression levels. CircRNA‑0044073 promoted the proliferation and invasion of HUVSMCs and HUVECs in spite of the opposite effect observed with LPS treatment. The JAK/STAT signaling pathway was activated in patients with atherosclerosis. CircRNA‑0044073 favored the activation of the JAK/STAT signaling pathway and inflammation in HUVSMCs and HUVECs. These data indicate that circRNA‑0044073 is upregulated in atherosclerosis and promotes the proliferation and invasion of cells by targeting miR‑107 and activating the JAK/STAT signaling pathway, potentially offering a target for novel treatment strategies against atherosclerosis. | [
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The aim of the present study was to investigate whether miRNA‑146a regulated the function of Th17 cell differentiation to modulate cervical cancer cell growth and apoptosis. miR‑146a expression was increased in human cervical cancer. Both overall survival (OS) and disease‑free survival (DFS) of low miR‑146a expression were higher than those of high miR‑146a expression. Additionally, IL‑17a expression was lower in patients with high miR‑146a expression compared to that of patients with lower miR‑146a expression. In a co‑culture of cervical cancer and CD4+ T cells, downregulation of miR‑146a inhibited cell growth and induced apoptosis of cervical cancer cells, while overexpression of miR‑146a promoted cell growth and reduced apoptosis of cervical cancer cells. Downregulation of miR‑146a induced TRAF6 and NF‑B protein expression, increased IL‑6, IL‑17A and IL‑21 levels, and enhanced p‑STAT3 protein expression. The inhibition of TRAF6 attenuated the effects of anti‑miR‑146a on the function of Th17 cell differentiation to modulate cervical cancer cell growth and apoptosis. Collectively, miR‑146a regulated the function of Th17 cell differentiation to modulate cervical cancer cell growth and apoptosis through NF‑B signaling by targeting TRAF6. miR‑146a may function as an oncogene in cervical cancer via Th17 cell differentiation by targeting TRAF6. | [
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Redd1 is a stress response protein that functions as a repressor of mTORC1, a central regulator of protein translation, resulting in the inhibition of cell growth and metabolism. However, paradoxically, high Redd1 expression favors cancer progression and generates resistance to cancer therapy. Herein, we revealed that constitutive overexpression of Redd1 induced HSP27 and HSP70 expression in lung cancer cells. The expression of Redd1, HSP27 and HSP70 was highly increased in lung cancer tissues compared with that in normal lung tissues. Inhibition of HSP27 or HSP70 suppressed AKT phosphorylation, which was induced by constitutive overexpression of Redd1 and enhanced the inhibitory effects on viability of Redd1‑overexpressing cells. Inhibition of AKT phosphorylation resulted in a decrease of HSP27 and HSP70 expression in Redd1‑overexpressing cells. These data indicated that HSPs and AKT in Redd1‑overexpressing cells positively regulated the function and expression of each other and were involved in lung cancer cell survival. Knockdown of HSP27, HSP70 or AKT enhanced ionizing radiation (IR) sensitivity, particularly in lung cancer cells in which Redd1 was stably overexpressed. Collectively, constitutive overexpression of Redd1 led to HSP27 and HSP70 induction and AKT activation, which were involved in lung cancer cell survival and resistance to IR, suggesting that Redd1 may be used as a therapeutic target for lung cancer. | [
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Ginsenoside Rb1 (GRb1), one of the major active saponins isolated from ginseng, has recently been reported to protect various organs against ischemia/reperfusion (IR) injury; however, the mechanisms underlying these protective effects following intestinal IR (IIR) remain unclear. The present study aimed to evaluate the effects of GRb1 on IIR injury and determine the mechanisms involved in these effects. Sprague Dawley rats were subjected to 75min of superior mesenteric artery occlusion, followed by 3h of reperfusion. GRb1 (15mg/kg) was administered intraperitoneally 1h prior to the induction of IIR, with or without intravenous administration of Wortmannin [WM; a phosphoinositide 3‑kinase (PI3K) inhibitor, 0.6mg/kg]. The degree of intestinal injury and oxidative stress‑induced damage was determined by histopathologic evaluation and measurement of the serum activity levels of D‑lactate, diamine oxidase and endotoxin, and the levels of malondialdehyde (MDA), superoxide dismutase (SOD) and 8‑iso‑prostaglandin F2 (8‑iso‑PGF2). The protein expression levels of p85, phosphorylated (p)‑p85, protein kinase B (Akt), p‑Akt and nuclear factor erythroid 2‑related factor 2 (Nrf2) were determined via western blotting, and the concentrations of tumor necrosis factor‑ (TNF‑), interleukin (IL)‑1 and IL‑6 were measured via ELISA. It was revealed that IIR led to severe intestinal injury (as determined by significant increases in intestinal Chiu scores), which was accompanied with disruptions in the integrity of the intestinal mucosal barrier. IIR also increased the expression levels of TNF‑, IL‑1, IL‑6, MDA and 8‑iso‑PGF2 in the intestine, and decreased those of SOD. GRb1 reduced intestinal histological injury, and suppressed inflammatory responses and oxidative stress. Additionally, the protective effects of GRb1 were eliminated by WM. These findings indicated that GRb1 may ameliorate IIR injury by activating the PI3K/protein kinase B/Nrf2 pathway. | [
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Numerous microRNAs (miRNAs) have been identified as aberrantly expressed in osteosarcoma (OS). miRNAs serve important roles in the pathogenesis of OS as oncogenes or tumor suppressors. Recent studies revealed that miR‑708‑5p (miR‑708) was dysregulated in various types of human cancer; however, its roles and underlying molecular mechanisms in OS remain unknown. Therefore, the present study aimed to determine miR‑708 expression in OS, investigate the roles of miR‑708 in the progression of OS and reveal the potential mechanisms involved. It was demonstrated using reverse transcription‑polymerase chain reaction that miR‑708 was downregulated in OS tissues and cell lines. Cell Counting Kit‑8 and Transwell assays revealed that miR‑708 overexpression suppressed the proliferation and invasion of OS cells invitro. Additionally, zinc finger E‑box binding homeobox1 (ZEB1) was validated as a direct target gene of miR‑708 in OS cells. ZEB1 was upregulated in OS tissues; elevated ZEB1 expression was negatively correlated with the levels of miR‑708 expression. Rescue experiments indicated that ZEB1 reintroduction significantly counteracted the inhibitory effects of miR‑708 overexpression on the proliferation and invasion of OS cells. The findings may improve understanding of the roles of miR‑708 in the development of OS, and suggest that miR‑708 may be a potential novel therapeutic target in the treatment of patients with this disease. | [
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] |
Estrogen receptor (ER) is an important ER subtype in lung adenocarcinoma. However, the functions and mechanisms of ER have not been fully elucidated. The aim of the present study was to investigate the biological effects and relevant mechanisms of ER in lung adenocarcinoma. The protein expression of ER was found to be higher in lung adenocarcinoma tissues compared with that in adjacent non‑cancerous tissues (n=75, P<0.001). Of note, ER protein expression was significantly correlated with tumor size (P=0.018), lymph node metastasis (P=0.041), clinical stage (P=0.041) and differentiation (P<0.001). In addition, ER protein expression in A549 cells was found to be higher compared with that in human bronchial epithelial cells (HBEs). Furthermore, knockdown of ER expression inhibited colony formation and cell invasion in vitro, whereas the number of metastatic tumors in the lungs of mice was decreased in vivo. Western blot analysis demonstrated that the expression of phosphorylated extracellular signal‑regulated kinase (pERK), matrix metalloproteinase (MMP)‑2 and MMP‑9 was decreased by downregulation of ER. Therefore, ER may play an important role in lung adenocarcinoma progression via the MEK/ERK signaling axis, and it may represent a novel therapeutic target for lung adenocarcinoma in the future. | [
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Castration‑resistant prostate cancer (CRPC) is a major challenge in the treatment of prostate cancer (PCa). Phospholipase C (PLC), an oncogene, has been found to be involved in the carcinogenesis, tumor proliferation and migration of several types of cancer. The effects, however, of PLC on CRPC remains unclear. In the present study, the expression of PLC and glioma‑associated homolog (Gli)‑1/Gli‑2 in benign prostatic hyperplasia (BPH), PCa and CRPC tissues and cells was investigated, and the correlations between PLC and Gli‑1/Gli‑2 in CRPC tissues and cell lines were further explored. In addition, the effect of PLC on cell proliferation and invasion was assessed in CRPC cell lines, and the sensitivity of EN‑R and 22RV1 cells to enzalutamide following the downregulation of PLC expression was determined using lentivirus‑mediated shPLC and/or treatment with specific Gli inhibitor GANT61. It was found that the PLC expression was excessively upregulated in the majority of CRPC tissues, and PLC positivity was linked to poor progression‑free survival (PFS) and overall survival (OS) in patients with PCa. Furthermore, PLC knockdown significantly suppressed CRPC cell proliferation and invasion. Of note, it was found that PLC knockdown increased the sensitivity of CRPC cells to enzalutamide in vitro by suppressing androgen receptor (AR) activities via the non‑canonical Hedgehog/Gli‑2 and p‑STAT3 signaling pathways. PLC knockdown was shown to increase the sensitivity of CRPC cell xenografts to enzalutamide in vivo. Finally, the combination of PLC knockdown with GANT61 significantly sensitized CRPC cells to enzalutamide. Collectively, the results of the present study suggest that PLC is a potential therapeutic target for CRPC. | [
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Programmed death‑ligand 1 (PD‑L1), an immune co‑stimulatory molecule, is expressed on various cancer cells and the surface of immune cells. Its overexpression on tumor cells suppresses the immune response to promote tumor cell immune escape. The present study demonstrated that PD‑L1 was critical in head and neck squamous cell carcinoma (HNSCC) carcinogenesis. Immunohistochemical analysis of HNSCC tissue microarrays revealed that PD‑L1 was overexpressed in tumor tissue, and its expression increased as tumor malignancy progressed (from grade I to IV). Subsequently, the expression of PD‑L1 was knocked down or overexpressed in the HNSCC cell lines Cal‑27 and Fadu. It was demonstrated that PD‑L1 significantly induced HNSCC cell proliferation and colony forming ability. Cell proliferation was also promoted in Cal‑27 cell xenograft BALB/c nude mice. In addition, it was determined by western blotting that the PD‑L1‑mediated increase in HNSCC cell proliferation may have been associated with the activation of mammalian target of rapamycin (mTOR) signaling pathway. Furthermore, mTOR inhibitor (rapamycin) prevented the increase in proliferation. Based on these results, it was concluded that PD‑L1 promoted cell proliferation of HNSCC cells through mTOR signaling, and blocking PD‑L1 may be conducive in HNSCC therapy. | [
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Tropomodulin 3 (TMOD3) is a member of the pointed‑end capping protein family that contributes to invasion and metastasis in several types of malignancies. TMOD3 has been found to be crucial for membranous skeleton and embryonic development; however, little is known regarding the role of TMOD3 in liver cancer progression. In addition, to the best of our knowledge, no previous studies have investigated the mechanism underlying the TMOD3‑regulated promotion of liver cancer. The aim of the present study was to determine whether TMOD3 is associated with liver cancer progression. TMOD3 expression was found to be elevated in liver cancer cells and tissues. In the in vitro experiments, liver cancer cell proliferation, invasion and migration were inhibited by TMOD3 knockdown and promoted by ectopic expression of TMOD3. Furthermore, mechanistic analysis indicated that TMOD3 overexpression activated mitogen‑activated protein kinase (MAPK)/extracellular signal‑regulated kinase (ERK) signaling and increased the levels of other targets of this pathway, including matrix metalloproteinase (MMP)2, MMP9 and cyclin D1. TMOD3 overexpression was associated with changes in liver cancer cell morphology and altered expression of epithelial and mesenchymal markers. High TMOD3 expression was hypothesized to promote epithelial‑to‑mesenchymal transition in liver cancer cells. In conclusion, TMOD3 was shown to promote liver cancer cell growth, invasion and migration through the MAPK/ERK signaling pathway, and it may serve as a candidate biomarker and therapeutic target in liver cancer. | [
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Sirtuin 1 (Sirt1) exerts its cardioprotective effects in various cardiovascular diseases via multiple cellular activities. However, the therapeutic implications of Sirt1 in hypoxic cardiomyocytes and the underlying mechanisms remain elusive. The present study investigated whether Sirt1 regulates autophagy and apoptosis in hypoxic H9C2 cardiomyocytes and in an experimental hypoxic mouse model. Right ventricular outflow tract biopsies were obtained from patients with cyanotic or acyanotic congenital heart diseases. Adenovirus Ad‑Sirt1 was used to activate Sirt1 and Ad‑Sh‑Sirt1 was used to inhibit Sirt1 expression in H9C2 cells, in order to investigate the effect of Sirt1 on cellular autophagy and apoptosis. SRT1720, a pharmacological activator of Sirt1 and EX‑527, a Sirt1 antagonist, were administered to mice to explore the role of Sirt1 in hypoxic cardiomyocytes in vivo. The levels of autophagy and apoptosis‑related proteins were evaluated using western blotting. Apoptosis was investigated by TUNEL staining and Annexin V/7‑aminoactinomycin D flow cytometry analysis. Heart tissue samples from cyanotic patients exhibited increased autophagy and apoptosis, as well as elevated Sirt1 levels, compared with the noncyanotic control samples. The data from the western blot analysis revealed that Sirt1 promoted autophagic flux and reduced apoptosis in hypoxic H9C2 cells. In addition, Sirt1 activated AMP‑activated protein kinase (AMPK), and the AMPK inhibitor Compound C abolished the effect of Sirt1 on autophagy activation. Further exploration of the mechanism revealed that Sirt1 protects hypoxic cardiomyocytes from apoptosis, at least in part, through inositol requiring kinase enzyme 1 (IRE1). Consistent with the in vitro results, treatment with the Sirt1 activator SRT1720 activated AMPK, inhibited IRE1, enhanced autophagy, and decreased apoptosis in the heart tissues of normoxic mice compared with the hypoxia control group. Opposite changes were observed in hypoxic mice treated with the Sirt1 inhibitor EX‑527. These results suggested that Sirt1 promoted autophagy via AMPK activation and reduced hypoxia‑induced apoptosis via the IRE1 pathway, to protect cardiomyocytes from hypoxic stress. | [
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Insufficient invasion of trophoblasts is known to be associated with preeclampsia (PE) development. Recently, microRNAs (miRNAs) have been reported to serve important roles in the pathogenesis of PE. However, little is known regarding the regulation of trophoblastic invasion by miRNAs. The aim of the present study was to explore the role of miRNAs in trophoblastic invasion and the underlying molecular mechanism. Using a miRNA microarray, miRNAs putatively involved in the pathophysiology of PE were examined between normal and preeclamptic placentas. Validation analysis of miR‑142‑3p level in placenta specimens was performed using reverse transcription‑quantitative polymerase chain reaction(RT‑qPCR). Then, the regulation of miR‑142‑3p on trophoblast cells migration and invasion was evaluated using wound healing and transwell migration assays. Furthermore, the target gene of miR‑142‑3p and the downstream signaling pathway were also investigated. Microarray analysis and RT‑qPCR revealed that miR‑142‑3p was significantly upregulated in placenta specimens from patients with PE. Its overexpression inhibited trophoblast cell invasion and migration, whereas its knockdown enhanced trophoblast cell invasion and migration. In addition, overexpression of miR‑142‑3p inhibited the mRNA expression and the activities of matrix metalloproteinase‑2 (MMP2) and MMP9, which are closely associated with cell invasion and migration, while inhibition of miR‑142‑3p had the opposite result. Subsequent analyses demonstrated that transforming growth factor‑1 (TGF‑1) was a direct and functional target of miR‑142‑3p. Notably, the knockdown of TGF‑1 effectively reversed the enhancement of miR‑142‑3p inhibitor on trophoblast cell invasion and migration. Finally, the present study confirmed that miR‑142‑3p inhibitor enhanced cell invasion and migration by reactivating the TGF‑1/Smad3 signaling pathway. Taken together, the results of the present study suggest that miR‑142‑3p may serve an important role in human placental development by suppressing trophoblast cell invasion and migration through disruption of the TGF‑1/smad3 signaling pathway, suggesting that knockdown of miR‑142‑3p may provide a novel therapy for PE. | [
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] |
Phospholipase C (PLC) and anaerobic glycolysis were determined to be involved in the development of human urinary bladder cancer (UBC), but the mechanisms remain unclear. In the present study, 64 bladder cancer specimens and 42 adjacent tissue specimens were obtained from 64 patients, and immunochemistry indicated that PLC and lactate dehydrogenase (LDHA) are overexpressed in UBC. PLC and LDHA were demonstrated to be positively correlated at transcription levels, indicating that one of these two genes may be regulated by another. To elucidate the mechanisms, PLC was knocked down in T24 cells by short hairpin RNA, and then signal transducer and activator of transcription 3 (STAT3) phosphorylation and LDHA were determined to be downregulated, which indicated that PLC may serve roles upstream of LDHA through STAT3 to regulate glycolysis in UBC. Furthermore, chromatin immunoprecipitation and luciferase reporter assays were performed to confirm that STAT3 could bind to the promoter of the LDHA gene to enhance its expression. A xenograft tumor mouse model also demonstrated similar results as the in vitro experiments, further confirming the role of PLC in regulating bladder cell growth in vivo. Collectively, the present study demonstrated that PLC may regulate glycolysis through the STAT3/LDHA pathway to take part in the development of human UBC. | [
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Wound healing begins immediately after surgery with a modification of the microenvironment via a well‑orchestrated interaction between cells, cytokines and growth factors. Some of these growth factors and cytokines have mitogenic effects on cancer cells, which may lead to enhanced cancer cell proliferation and early metastatic events. The present study aimed to investigate the effects of wound fluid (WF) on the head and neck squamous carcinoma cell lines FaDu and HLaC78 in vitro. WF was harvested from 7 patients who had undergone a planned neck dissection. The presence of cytokines and growth factors was evaluated with the dot blot assay. Proliferation and cell viability were investigated via MTT assay and Ki-67 staining. Cell invasion was measured via tree‑dimensional invasion assay. Western blotting was used to investigate STAT 3 activation. WF contained several cytokines and growth factors responsible for pro‑ and anti‑inflammation, chemotaxis, proliferation and angiogenesis. The proliferation effect of WF on FaDu and HLaC78 was concentration dependent. Media with 40% WF resulted in the highest proliferation effect. FaDu and HLaC78 exhibited enhanced motility after cultivation with 40% WF compared with cultivation with expansion medium. Cultivating cancer cells with WF had no advantageous effect on cell viability after the paclitaxel treatment. Western blot analysis revealed enhanced activation of the STAT3 signaling pathway by WF in both FaDu and HLaC78. In conclusion, surgery leads to excessive release of mitogenic factors. The contact of non‑resected cancer cells and these factors may have a negative impact on patient outcome. Future investigations should specifically focus on the inhibition of mitogenic factors following cancer surgery in order to prevent early metastasis and cancer recurrence. | [
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Protein phosphatase of regenerating liver‑3 (PRL‑3) is considered to be metastasis‑associated phosphatase and is associated with a poor prognosis. Additionally, tumor‑associated macrophages (TAMs) participate in cancer progression. A previous study demonstrated that PRL‑3 promotes invasion and metastasis by inducing TAM infiltration. However, the underlying mechanism has not been elucidated. In the present study, western blot analysis, polymerase chain reaction, immunohistochemistry, ELISA, mouse model experiments and functional experiments were performed to confirm that the interaction between TAMs and colorectal cancer (CRC) cells induced epithelial‑mesenchymal transition (EMT)‑associated features in CRC cells by activating mitogen‑activated protein kinase (MAPK) pathways in TAMs and upregulating the expression of interleukin (IL)‑6 and IL‑8. The neutralization of IL‑6 and IL‑8 reduced EMT and the invasive and migratory abilities of CRC cells. Therefore, IL‑6 and IL‑8 were considered important factors in EMT, and in CRC invasion and metastasis. In addition, increased angiogenesis was observed after TAMs were co‑cultured with CRC cells that overexpress PRL‑3. Vascular endothelial growth factor‑A was significantly upregulated, and the nuclear factor‑B (NF‑B) signaling pathway was activated in CRC cells after co‑culture. Moreover, nude mice injected with CRC cells with high PRL‑3 expression levels tended to generate larger xenografts. Immunohistochemistry results from xenografted CRC cells overexpressing PRL‑3 also confirmed the activation of MAPK pathways in xenografts. Overall, the findings indicate that PRL‑3 promotes CRC cell invasion and metastasis by activating MAPK pathways in TAMs to initiate the EMT, and PRL‑3 promotes angiogenesis by activating the NF‑B pathway in CRC cells. | [
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There is growing evidence supporting dysregulated microRNAs (miRNAs) as potential prognostic biomarkers in cancer. The present study aimed to identify an miRNA model set with prognostic power for patients with gastric adenocarcinoma. miRNA‑seq data from 155 patients and 37 controls were downloaded from The Cancer Genome Atlas (TCGA) database for a comprehensive analysis of miRNA expression profiles and were used as training data. A total of 5 prognostic miRNAs, which have not been previously reported, were identified using univariate and multivariate Cox regression analyses. A separate 155‑patient TCGA cohort was used as a validation set for evaluation of the risk model. Patients in the training set were assigned into high‑ and low‑risk groups according to the 5‑miRNA signature risk scores. Kaplan‑Meier survival analyses demonstrated that patients with high risk scores had significantly shorter survival times than those with low risk scores. The risk model validation confirmed the prognostic ability of this 5‑miRNA signature in predicting the risk status of patients. Stratification analysis for clinical prognostic variables demonstrated recurrence and age were significant prognostic factors in the low‑ and high‑risk groups, respectively. In conclusion, the present 5‑miRNA signature is a potential independent risk factor for patient outcomes. The risk model based on the 5‑miRNA signature performed well in predicting overall survival time in patients with gastric adenocarcinoma. | [
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Biological pacemakers that combine cell‑based and gene‑based therapies are a promising treatment for sick sinus syndrome or severe atrioventricular block. The current study aimed to induce differentiation of adipose tissue‑derived stem cells (ADSCs) into cardiac pacemaker cells through co‑expression of the transcription factors insulin gene enhancer binding protein 1 (ISL‑1) and T‑box18 (Tbx18). ADSCs were transfected with green fluorescent protein, ISL‑1, Tbx18 or ISL‑1+Tbx18 ?uorescent protein lentiviral vectors, and subsequently co‑cultured with neonatal rat ventricular cardiomyocytes invitro for 7days. The potential for regulating the differentiation of ADSCs into pacemaker‑like cells was evaluated by cell morphology, beating rate, reverse transcription‑quantitative polymerase chain reaction, western blotting, immunofluorescence and electrophysiological activity. ADSCs were successfully transformed into spontaneously beating cells that exhibited a behavior similar to that of co‑cultured pacemaker cells. This effect was significantly increased in the combined ISL‑1 and Tbx18 group. These results provide a potential strategy for enriching the cardiac pacemaker cell population from ADSCs. | [
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] |
Hydrogen sulfide (H2S) is an endogenous gaseous signaling molecule that plays important roles in the cardiovascular system. In our previous studies, we demonstrated that H2S regulates lipid metabolism. In the present study, we aimed to explore the mechanisms through which H2S regulates lipid metabolism in HepG2 cells invitro. Treatment of the HepG2 cells with H2S inhibited the expression of proprotein convertase subtilisin/kexin type 9 (PCSK9) and increased the level of low‑density lipoprotein receptor (LDLR) in a time‑ and dose‑dependent manner. The knockdown of PCSK9 by siRNA effectively increased the levels of LDLR and 1,1'‑dioctadecyl‑3,3,3',3'‑tetramethyl‑indocarbocyanine perchlorate‑labeled LDL (DiI‑LDL) uptake in the H2S‑treated HepG2 cells. Furthermore, the phosphoinositide 3‑kinase (PI3K)/protein kinase B (Akt)‑sterol regulatory element binding proteins 2 (SREBP‑2) signaling pathway was confirmed to be involved in H2S‑regulated PCSK9 expression. Notably, the HepG2 cells were incubated with 30% serum and DiI‑LDL for 24 h, and the results revealed that H2S increased lipid uptake, but caused no increase in lipid accumulation. On the whole, the findings of this study demonstrate that H2S is involved in the regulation of lipid metabolism in HepG2 cells through the regulation of the expression of PCSK9 via the PI3K/Akt‑SREBP‑2 signaling pathway. To the very best of our knowledge, this study is the first to report that H2S can regulate the expression of PCSK9. | [
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The aim of the present study was to examine the protective effect of caveolin‑1 (Cav‑1) in the penehyclidine hydrochloride (PHC)‑based inhibition of lipopolysaccharide (LPS)‑induced acute lung injury (ALI) invivo and invitro, in addition to the potential underlying mechanisms. Invivo, an ALI rat model was established via intratracheal administration of LPS (5mg/kg), and PHC (2mg/kg) was administered 30min following LPS treatment. Invitro, the Cav‑1 gene was knocked down by small interfering (si)RNA in J774A.1 cells. Cells were incubated with LPS (1g/ml) for 2h, and subsequently incubated with PHC (2g/ml) for an additional 2h. Lung injury was assessed by lung histology and the ratio of polymorphonuclear leukocytes (PMNs) to total cells was assessed in bronchoalveolar lavage fluid (BALF), myeloperoxidase (MPO) activity, BALF protein content and lung wet/dry (W/D) ratio. The levels of pro‑inflammatory factors, including tumor necrosis factor‑ (TNF‑), interleukin (IL)‑6 and IL‑1, in the sera of rats and cell culture supernatant were determined by ELISA. The protein expression levels of Cav‑1, toll‑like receptor 4 (TLR4), phosphorylated (p)‑p38 mitogen activated protein kinases (p38 MAPKs) and nuclear factor kappa‑light‑chain‑enhancer of activated B cells transcription factor p65 subunit (NF‑B p65) in lung tissues and J774A.1 cells were analyzed by western blot analysis. The results indicated that PHC effectively alleviated lung injury by decreasing neutrophil infiltration and protein concentration in BALF, and the lung W/D ratio and MPO activity and pro‑inflammatory cytokine production induced by LPS. Furthermore, PHC significantly decreased the degrees of histopathological changes and pulmonary dysfunction. Invitro, treatment with PHC inhibited pro‑inflammatory cytokine levels and MPO activity in LPS‑stimulated J774A.1 cells. However, the results in the J774A.1 cells with Cav‑1 gene knockdown were contrary. In addition, PHC decreased TLR4, p‑p38 MAPKs and nuclear NF‑B p65 expression levels and upregulated the expression level of Cav‑1, invivo and invitro. These data demonstrated that PHC exhibited a protective effect against LPS‑induced ALI in rats and LPS‑stimulated J774A.1 cells, which may be due to the inhibition of p38 MAPKs phosphorylation and TLR4/NF‑B signaling pathway by Cav‑1 upregulation. | [
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] |
Chronic rhinosinusitis with nasal polyps (CRSwNP) is one of the most prevalent chronic diseases. In patients with CRSwNP, the present study performed comprehensive bioinformatics analyses to characterize the transcriptome profiles of mRNAs and long non‑coding RNAs (lncRNAs). A total of 265differentially expressed lncRNAs and 994mRNAs were identified. The majority of up‑ and downregulated differentially expressed genes were significantly enriched in the biological process of 'signal transduction'. The most significantly enriched molecular function was 'protein binding' and the most significantly enriched cellular component was 'membrane'. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis led to identification of several significantly enriched pathways [false discovery rate (FDR)<0.05], including 'cytokine‑cytokine receptor interaction' (FDR=3.94x1016) and 'cell adhesion molecules' (CAMs) (FDR=1.28x10‑5). Key differentially expressed lncRNAs were identified, including lncRNA XLOC_010280, which regulates chemokine (C‑C motif) ligand 18 (CCL18) and in?ammation, and RP11‑798M19.6, which regulates polypeptide N‑acetylgalactosaminyltransferase7 (GALNT7) and cell proliferation. Based on the results of reverse transcription‑quantitative polymerase chain reaction, except for CCL8, neural precursor cell expressed developmentally downregulated gene 4‑like and GALNT7, the expression of 3other selected genes was consistent with the results of integrated analysis. The results of the present study provide a foundation for future investigations into mRNAs and lncRNAs as diagnostic and therapeutic targets in CRSwNP. | [
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MicroRNAs (miRNA/miRs) have been demonstrated to be critical post‑transcriptional modulators of gene expression during tumorigenesis. Numerous miRNAs have been revealed to be downregulated in human epithelial ovarian cancer (EOC). In the present study, it was observed that the expression of miR‑145 was decreased in EOC tissues and cell lines. Overexpression of miR‑145 inhibited the proliferation, migration and invasion of EOC cells. The D‑type cyclin 2, cyclin D2 (CCND2), and E2F transcription factor 3 (E2F3) were confirmed to be targets of miR‑145. In addition, restoration of these 2genes significantly reversed the tumor suppressive effects of miR‑145. Collectively, the results indicated that miR‑145 serves a critical role in suppressing the biological behavior of EOC cells by targeting CCND2 and E2F3. Therefore, miR‑145 was suggested to be a potential miRNA‑based therapeutic target in ovarian cancer. | [
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The present study investigated the effect of poly(ADP‑ribose) glycohydrolase (PARG) on the immune response in tumour metastases of colon carcinoma. CT26 cells were transfected with lentivirus PARG‑short hairpin RNA (shRNA). A liver metastasis model of colon carcinoma was successfully established by splenic subcapsular inoculation of the various groups of CT26 cells into BALB/c mice. Next, changes in the liver metastases of colon carcinoma nodules and alterations in the survival times were observed in tumour‑bearing mice. The numbers of B220+DEC205+ dendritic cells (B220+DEC205+DC) and CD11c+CD11b+ dendritic cells (CD11c+CD11b+DC) in the spleen and liver were measured by the double‑label immunofluorescence assay. The distribution pattern of CD4+T cells and CD8+T cells in the spleen and liver was investigated by immunofluorescence staining. The expression levels of PARG, PARP and nuclear factor‑B (NF‑B) proteins in spleen transplant tumours and liver metastases of colon carcinoma were detected by western blotting. An ELISA was used to detect the levels of IL‑10 and TGF‑ in the serum of tumour‑bearing mice and from the supernatant of tumour cells. The numbers and grading of metastatic liver nodules in the PARG‑silenced group were clearly lower than those in the control group. The survival time of the PARG‑silenced group mice was longer than that in the control group. In the PARG‑silenced group, the levels of B220+DEC205+DC in the spleen and liver were lower and the numbers of CD11c+CD11b+DC in the spleen and liver were more than those in the control group. The ratio of CD4+/CD8+ in the spleen and liver in the PARG‑silenced group was increased compared with that in the control group (P<0.05). The levels of PARG, PARP and NF‑B in spleen transplant tumours and liver metastases of colon carcinoma were lower in the PARG‑silenced group than in the control group. In addition, the levels of IL‑10 and TGF‑ in the serum of tumour‑bearing mice and supernatants of tumour cells were both reduced in the PARG‑silenced group compared with those in the control group. The present research suggests that the liver metastases of colon carcinoma could be restrained by silencing PARG. Likely, the silencing of PARG could suppress the expression of PARP and NF‑B and subsequently suppress the secretion of IL‑10 and TGF‑, finally affecting the proliferation and differentiation of DC and T cells. | [
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] |
The aim of the present study was to investigate the potential anticancer effects of microRNA-216a on the growth of human breast cancer and the possible underlying mechanisms. The results demonstrated that serum microRNA-216a was significantly decreased in patients with breast cancer compared with healthy controls. MicroRNA-216a overexpression led to a decrease in cell proliferation and migration, as well as increases in apoptosis, caspase-3/8 activities, Bax expression and p53 protein expression in MCF-7 cells. It was also revealed that microRNA-216a suppressed Wnt and -catenin expression in MCF-7 cells. The anticancer effects of microRNA-216a were reversed by anti-microRNA-216a by promoting the Wnt/-catenin signaling pathway. Inactivation of the Wnt pathway increased the anticancer effects of microRNA-216a in MCF-7 cells. Collectively, the results of the present study indicated that microRNA-216a suppressed the growth of human breast cancer cells by targeting the Wnt/‑catenin signaling pathway. | [
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BACKGROUND: Normal aging is associated with changes in cognitive function that are non-pathological and are not necessarily indicative of future neurocognitive disease. Low cognitive and brain reserve and limited cognitive stimulation are associated with increased risk of dementia. Emerging evidence now suggests that subtle cognitive changes, detectable years before criteria for mild cognitive impairment are met, may be predictive of future dementia. Important for intervention and reduction in disease risk, research also suggests that engaging in stimulating mental activity throughout adulthood builds cognitive and brain reserve and reduces dementia risk. Therefore, midlife (defined here as 40 to 65 years) may be a suitable time to introduce cognitive interventions for maintaining cognitive function and, in the longer term, possibly preventing or delaying the onset of clinical dementia.OBJECTIVES: To evaluate the effects of computerised cognitive training interventions lasting at least 12 weeks for maintaining or improving cognitive function in cognitively healthy people in midlife.SEARCH METHODS: We searched up to 31 March 2018 in ALOIS (www.medicine.ox.ac.uk/alois), the specialised register of the Cochrane Dementia and Cognitive Improvement Group (CDCIG). We ran additional searches in MEDLINE, Embase, PsycINFO, CINAHL, ClinicalTrials.gov, and the WHO Portal/ICTRP at www.apps.who.int/trialsearch, to ensure that the search was as comprehensive and as up-to-date as possible, to identify published, unpublished, and ongoing trials.SELECTION CRITERIA: We included randomised controlled trials (RCTs) or quasi-RCTs, published or unpublished, reported in any language. Participants were cognitively healthy people between 40 and 65 years of age (80% of study population within this age range). Experimental interventions adhered to the following criteria: intervention was any form of interactive computerised cognitive intervention - including computer exercises, computer games, mobile devices, gaming console, and virtual reality - that involved repeated practice on standardised exercises of specified cognitive domain(s) for the purpose of enhancing cognitive function; duration of the intervention was at least 12 weeks; cognitive outcomes were measured; and cognitive training interventions were compared with active or inactive control interventions.DATA COLLECTION AND ANALYSIS: For preliminary screening of search results, we used a 'crowd' method to identify RCTs. At least two review authors working independently screened remaining citations against inclusion criteria; independently extracted data; and assessed the quality of the included trial, using the Cochrane risk of bias assessment tool. We used GRADE to describe the overall quality of the evidence.MAIN RESULTS: We identified one eligible study that examined the effect of computerised cognitive training (CCT) in 6742 participants over 50 years of age, with training and follow-up duration of six months. We considered the study to be at high risk of attrition bias and the overall quality of the evidence to be low.Researchers provided no data on our primary outcome. Results indicate that there may be a small advantage for the CCT group for executive function (mean difference (MD) -1.57, 95% confidence interval (CI) -1.85 to -1.29; participants = 3994; low-quality evidence) and a very small advantage for the control group for working memory (MD 0.09, 95% CI 0.03 to 0.15; participants = 5831; low-quality evidence). The intervention may have had little or no effect on episodic memory (MD -0.03, 95% CI -0.10 to 0.04; participants = 3090; low-quality evidence).AUTHORS' CONCLUSIONS: We found low-quality evidence from only one study. We are unable to determine whether computerised cognitive training is effective in maintaining global cognitive function among healthy adults in midlife. We strongly recommend that high-quality studies be undertaken to investigate the effectiveness and acceptability of cognitive training in midlife, using interventions that last long enough that they may have enduring effects on cognitive and brain reserve, and with investigators following up long enough to assess effects on clinically important outcomes in later life. | [
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BACKGROUND: The number of people living with dementia is increasing rapidly. Clinical dementia does not develop suddenly, but rather is preceded by a period of cognitive decline beyond normal age-related change. People at this intermediate stage between normal cognitive function and clinical dementia are often described as having mild cognitive impairment (MCI). Considerable research and clinical efforts have been directed toward finding disease-modifying interventions that may prevent or delay progression from MCI to clinical dementia.OBJECTIVES: To evaluate the effects of at least 12 weeks of computerised cognitive training (CCT) on maintaining or improving cognitive function and preventing dementia in people with mild cognitive impairment.SEARCH METHODS: We searched to 31 May 2018 in ALOIS (www.medicine.ox.ac.uk/alois) and ran additional searches in MEDLINE, Embase, PsycINFO, CINAHL, ClinicalTrials.gov, and the WHO portal/ICTRP (www.apps.who.int/trialsearch) to identify published, unpublished, and ongoing trials.SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs in which cognitive training via interactive computerised technology was compared with an active or inactive control intervention. Experimental computerised cognitive training (CCT) interventions had to adhere to the following criteria: minimum intervention duration of 12 weeks; any form of interactive computerised cognitive training, including computer exercises, computer games, mobile devices, gaming console, and virtual reality. Participants were adults with a diagnosis of mild cognitive impairment (MCI) or mild neurocognitive disorder (MND), or otherwise at high risk of cognitive decline.DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed risk of bias of the included RCTs. We expressed treatment effects as mean differences (MDs) or standardised mean differences (SMDs) for continuous outcomes and as risk ratios (RRs) for dichotomous outcomes. We used the GRADE approach to describe the overall quality of evidence for each outcome.MAIN RESULTS: Eight RCTs with a total of 660 participants met review inclusion criteria. Duration of the included trials varied from 12 weeks to 18 months. Only one trial used an inactive control. Most studies were at unclear or high risk of bias in several domains. Overall, our ability to draw conclusions was hampered by very low-quality evidence. Almost all results were very imprecise; there were also problems related to risk of bias, inconsistency between trials, and indirectness of the evidence.No trial provided data on incident dementia. For comparisons of CCT with both active and inactive controls, the quality of evidence on our other primary outcome of global cognitive function immediately after the intervention period was very low. Therefore, we were unable to draw any conclusions about this outcome.Due to very low quality of evidence, we were also unable to determine whether there was any effect of CCT compared to active control on our secondary outcomes of episodic memory, working memory, executive function, depression, functional performance, and mortality. We found low-quality evidence suggesting that there is probably no effect on speed of processing (SMD 0.20, 95% confidence interval (CI) -0.16 to 0.56; 2 studies; 119 participants), verbal fluency (SMD -0.16, 95% CI -0.76 to 0.44; 3 studies; 150 participants), or quality of life (mean difference (MD) 0.40, 95% CI -1.85 to 2.65; 1 study; 19 participants).When CCT was compared with inactive control, we obtained data on five secondary outcomes, including episodic memory, executive function, verbal fluency, depression, and functional performance. We found very low-quality evidence; therefore, we were unable to draw any conclusions about these outcomes.AUTHORS' CONCLUSIONS: Currently available evidence does not allow us to determine whether or not computerised cognitive training will prevent clinical dementia or improve or maintain cognitive function in those who already have evidence of cognitive impairment. Small numbers of trials, small samples, risk of bias, inconsistency between trials, and highly imprecise results mean that it is not possible to derive any implications for clinical practice, despite some observed large effect sizes from individual studies. Direct adverse events are unlikely to occur, although the time and sometimes the money involved in computerised cognitive training programmes may represent significant burdens. Further research is necessary and should concentrate on improving methodological rigour, selecting suitable outcomes measures, and assessing generalisability and persistence of any effects. Trials with long-term follow-up are needed to determine the potential of this intervention to reduce the risk of dementia. | [
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Silver (Ag)-based nanoparticles (NPs) with a high potential of Ag+ release have been known to be capable of promoting bacteria inactivation and the wound healing process; however, keeping a steady flux of high levels of Ag+ in Ag-based NPs is still challenging. Herein, a novel strategy in terms of altering the intrinsic electronic structure of Ag NPs was attempted to facilitate Ag oxidation and boost the Ag+ flux, as results of improved antibacterial and wound healing performance of Ag NPs. Gold (Au), platinum (Pt), and palladium (Pd) were doped into Ag NPs to tune their d band centers to upshift toward the Fermi level, and the formed Pd-Ag alloy NPs showed the largest shift, followed by Pt-Ag and Au-Ag NPs, as determined by density function theory calculation and ultraviolet photoemission spectroscopy measurement. Further X-ray photoelectron spectroscopy analysis indicates that a larger upshift could induce less electron filling in the antibonding orbital and a higher Ag oxidation level, leading to the more remarkable Ag+ release as determined by inductively coupled plasma optical emission spectrometry. All these alloy Ag NPs could more efficiently inhibit bacterial growth and accelerate the wound healing process than pure Ag NPs, and their antibacterial activity and wound healing performance were progressively proportional to the upshift values of the d band center. Taken together, tuning the d band center to upshift toward the Fermi level becomes a feasible strategy for designing therapeutic Ag-based NPs with a promising antibacterial and wound healing performance. | [
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The investigation of nondoped exciplex blends of 2,4,6-tris[3-(diphenylphosphinyl)phenyl]-1,3,5-triazine (PO-T2T), working as the one-electron acceptor molecule, with different electron donors is reported. The emissions of these exciplexes span from the blue to orange-red regions, showing clear contribution from thermally activated delayed fluorescence (TADF) and delayed fluorescence originated from nongeminate recombination of charge carriers created by the dissociation of optically generated exciplexes. We focus our studies on the properties of TADF in these systems, covering in particular the physical meaning of the different transient components observed in their luminescence decays. Our results unravel the intricate role of reverse intersystem crossing due to spin-orbit coupling and possibly also due to hyperfine interactions and internal conversion, which affect the efficiency of the TADF mechanism. Remarkable performances are obtained in prototype organic light-emitting diodes fabricated with some of these blends. Green exciplex blends, in particular, exhibited the current efficiency of 60 cd A-1, power efficiency of 71 lm W-1, and external quantum efficiency of 20%. We believe that our results will contribute significantly to highlight the potential advantages of intermolecular exciplexes in the area of organic light-emitting diodes. | [
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The relationship between dietary intake and overweight-risk was assessed in 4349 children aged 3-5 years. Eating and sedentary behaviours were assessed by questionnaire. Logistic regressions were used. Children who consumed daily soft-drinks were 1.52 times more likely to be obese, and 72% more likely to be classified as overweight children. | [
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Hepatitis B virus (HBV) remains a leading cause of chronic hepatitis, maternal complications, and neonatal deaths in sub-Saharan Africa. Pregnant women serve as a major reservoir for the persistence and ongoing transmission of hepatitis B virus and HIV in a generalized heterosexual epidemic. The aim of this study is to assess the epidemiology of Hepatitis B infection among pregnant women in South West-Nigeria. This is a cross-sectional study of 353 pregnant women across 10 health facilities in the region. Results showed that of the 353 pregnant women tested, 37 were positive for the HBV antigen giving a prevalence estimate of 10.5% (95% CI: 7.5%-14.2%). We found significant negative association between odds of HBV infection and knowledge of HBV transmission through sex (OR: 0.30: 95%CI-0.11-0.82) and a positive association with blood transfusion in the past three months (OR: 9.5: 95% CI-1.58-57.14). Findings strongly suggest high endemicity of HBV and the possible implication of blood transfusion as a major route of ongoing HBV transmission among pregnant women in south-western Nigeria. We recommend further study of a prospective design to investigate the possible causal link between blood transfusion and the risk of HBV infection among pregnant women in Nigeria. | [
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The current study aimed to determine the prognostic values of personality traits for common psychological problems in a large sample of Iranian adult. In a large sample of healthy people (n = 4763) who lived in Isfahan province; the NEO-FFI was used to assess the personality traits; depression and anxiety were assessed using the "Hospital Anxiety and Depression Scale (HADS)" also stress was measured through Persian validated version of General Health Questionnaire (GHQ-12). Receiver Operating Characteristics Curve (ROC) analysis was used as main statistical method for data analysis. ROC analysis showed neuroticism was the best predictor for all psychological problems with highest area under the curve (AUC) (95% confidence interval) for stress, 0.837 (0.837-0.851), anxiety 0.861 (0.847-0.876) and depression 0.833 (0.820-0.846) (p < .001) and the corresponding cut-off points (sensitivity, specificity), were 21.5 (77%, 66%), 22.5 (81%, 77%) and 20.5 (77%, 74%), respectively. Other personality traits were significant protective factors for being affected with psychological problems (p < .001). Similar findings were observed separately in women and men. The present study showed that the neuroticism is significant risk factor for being affected with three psychological problems while other traits are significant protective factors. Personality traits are useful indices for screening psychological problems and an effective pathway toward prevention in general population. | [
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Bangladesh is currently going through a nutritional transition with rapid increase in overnutrition while undernutrition is still remaining prevalent. Nevertheless, population-based data on demographic, socio-economic and lifestyle factors associated with underweight and overweight among adult population is scarce. Employing a nationwide cross-sectional survey, we collected anthropometric, demographic, socio-economic, lifestyle and dietary information from 12,180 adults aged ?35 years. Body Mass Index (BMI) was calculated using standard formula and categorized into underweight (<18.50), normal weight (18.50-22.99), and overweight (?23.00). Multivariable multinomial logistic regression was performed to identify factors associated with underweight and overweight. Overall, prevalence of underweight and overweight was 18.1% (95% CI: 17.5-18.8) and 33.7% (95% CI: 32.9-34.6), respectively. All the demographic, socio-economic, dietary and lifestyle factors showed significant association with nutritional status in bivariate analysis. In adjusted analysis, factors showing significant positive association with underweight included female gender (ARRR-1.38, 95% CI: 1.11-1.71), older age [compared to 35-39 years age group, ARRR (95% CI) for ? 70 years is 2.32 (1.89-2.86), for 60-69 years is 1.62 (1.36-1.93), for 50-59 years 1.34 (1.13-1.58) and for 40-49 years 1.05 (0.87-1.15)] and smoking habit (ARRR-1.32, 95% CI: 1.14-1.52) while factors showing significant inverse association with underweight included higher household wealth [compared to lowest wealth quintile, ARRR (95% CI) for highest quintile is 0.68 (0.55-0.84), for second highest quintile 0.77 (0.65-0.91), for middle quintile 0.81 (0.69-0.94) and for second lowest quintile 0.89 (0.77-1.03)], urban residence (ARRR-0.66, 95% CI: 0.66-0.90), and more frequent meat/fish and fruits consumption (ARRR-0.76, 95% CI: 0.65-0.90). On the other hand, factors significantly associated with increased risk of overweight included female gender (ARRR-1.35, 95% CI: 1.12-1.63), higher household wealth [compared to lowest wealth quintile, ARRR (95% CI) for highest quintile is 2.27 (1.93-2.68), for second highest quintile 1.67 (1.44-1.94), for middle quintile 1.26 (1.10-1.46) and for second lowest quintile 1.07 (0.93-1.24), excess food availability [compared to food shortage, ARRR (95% CI) for excess food in the household is 1.29 (1.12-1.47) and for no shortage/no excess is 1.23 (1.09-1.38) and more frequent fruits consumption [compared to no fruits, ARRR (95% CI) for 5-7 days per week consumption is 1.61 (1.41-1.83) and for 3-4 days per week is 1.28 (1.16-1.41) and factors significantly associated with decreased risk of overweight included older age [compared to 35-39 years age group, ARRR (95% CI) for ? 70 years is 0.77 (0.64-0.93), for 60-69 years is 0.82 (0.71-0.94), for 50-59 years 0.91 (0.80-1.04) and for 40-49 years 1.01 (0.89-1.15)] and smoking (ARRR-0.76, 95% CI: 0.68-0.86). Both underweight and overweight are prevalent in Bangladeshi adult population. Several demographic, socio-economic, dietary and lifestyle factors are associated with underweight and overweight in Bangladesh. Population level impact of these factors should be examined to design suitable public health and nutrition interventions to address this dual challenge. | [
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INTRODUCTION: The aim of this study was to evaluate the microbial contamination of cell phone in dental and engineering schools and also investigating the effect of an antibacterial spray.METHOD AND MATERIALS: A questionnaire was completed by participants, including the pattern of using mobile phones and their disinfection. The number of participants was 120 students and professors in each of dental and engineering schools. Swabs from mobile phones of the participants were taken and plated on culture medium. The t-test, Chi-Square with the SPSS 11.5 program were used in data analysis.RESULTS: In total, 240 mobile phones were cultured for microorganisms, while 65.8% (n = 158) were culture-positive. One hundred percent of professors, 98% of students' dental school and 72% of professors and 62% of students of engineering, believe that mobile can serve as a source of pathogens.The most commonly cultured organisms were Staphylococcus Aureus, Escherichia coli, Enterococcus Faecalis, and Pseudomonas. The current study showed that none of the mobile phones of the professors and students of the engineering university was infected by Pseudomonas and Candida albicans.CONCLUSION: The results of this study showed that mobile phones may act as an important source of nosocomial pathogens. | [
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Acute respiratory infections (ARI) are a major public health problem and one of the commonest reasons for visiting primary health care centers (PHC). In developing countries, seventy-five percent of the cases are treated with antibiotics, although the majority are caused by viral infection. Our aim was to observe the pattern of physician practices with respect to ARI, in comparison to WHO protocols and to provide recommendations for health promotion enhancement. The study was conducted in Makkah PHC centers, for 2 months. A total 14 PHC centers were randomly selected. And 908 prescriptions were obtained randomly from general practitioners (GP) and analyzed. We found that males were 522 and females were and 386. Weights were not recorded in 224 (24.7%) cases. In 87 cases (9.6%) no diagnosis was recorded. In 515 (62.34%) of cases, antibiotics were prescribed; most of these cases were of simple common cold, with antibiotics not recommended. To conclude, many physicians in Makkah are not following the WHO guidelines for Acute Respiratory Infection. Educational health programs should be conducted to sensitize the physicians regarding the appropriate method of diagnosis and rational use of antibiotics. | [
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] |
The objective of this study is to assess whether adult children's migration is associated with overall well-being of left-behind elderly parents in Nepal. A cross-sectional house-to-house survey was conducted among 260 community-dwelling elderly residents of Krishnapur municipality, Nepal. Binary logistic regression was used to identify whether migration of adult children was associated with elderly parent's self-reported chronic diseases, depressive symptoms, perceived loneliness and social support. More than half of the study household (51.2%) had at least one adult migrant child. Compared to participants without a migrant child, participants with a migrant child had higher odds of self-reported chronic diseases (OR = 1.79, 95%CI: 0.91-3.54), presence of depressive symptoms (OR = 1.07, 95%CI: 0.64-1.77), and self-perceived loneliness (OR = 1.23, 95%CI: 1.06-1.42) but except for loneliness, the odds ratio for other indicators of well-being were not statistically significant. Although the literature posits an inverse relationship between adult children's migration and the overall well-being of the elderly parents, in our study, adult children's migration was not associated with inverse health outcomes among study participants. However, from a policy perspective, it should be understood that these observations may be transient since the family structure of Nepalese society is rapidly changing. | [
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Ebola viruses (family: Filoviridae) are the cause of Ebola virus disease (EVD), a highly fatal illness characterised by haemorrhagic fever syndrome in both humans and non-human primates (NHPs). West Africa was the epicentre of the 2013-2015 EVD epidemic which caused the death of over 11,000 people, including eight casualties in southern Nigeria. Antibodies to filoviruses have been detected among NHPs in some countries, but there is no documented evidence of exposures to filoviruses among NHPs in Nigeria. From August 2015 to February 2017, a total of 142 serum samples were obtained from individual captive and wild animals, belonging to 11 NHP species, in southern Nigeria, and screened for species-specific antibodies to filoviruses belonging to the species; Zaire ebolavirus [Ebola virus (EBOV)], Sudan ebolavirus [Sudan virus (SUDV)], and Marburg marburgvirus [Ravn virus (RAVV)]-using a modified filovirus species-specific ELISA technique. Of the sera tested, 2.1% (3/142) were positive for antibodies to EBOV. The entire 142 sera were negative for SUDV or RAVV. These findings point to the existence of natural exposures of NHPs in southern Nigeria to EBOV. There is need to discourage, the uncontrolled hunting of NHPs in Nigeria for public health safety. | [
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The extent to which sports injuries contribute to the burden of injury among adolescents in low- and middle-income countries (LMICs) is unknown. The goal of this study was to estimate the incidence of sports injuries among adolescents in Africa. Data from the World Health Organization Global School-Based Student Health surveys were used to estimate the annual number of African adolescents sustaining sports injuries. Gender-stratified injury rates were calculated and applied to every African country's adolescent population to estimate country-specific and continent-wide injury totals. A total of 21,858 males and 24,691 females from 14 countries were included in the analysis. Country-specific annual sports injury rates ranged from 13.5% to 38.1% in males and 5.2% to 20.2% in females. Weighted average sports injury rates for males and females were 23.7% (95% CI 23.1%-24.2%) and 12.5% (95% CI 12.1%-12.9%), respectively. When these rates were extrapolated to the adolescent populations of the African continent, an estimated 15,477,798 (95% CI 15,085,955-15,804,333) males and 7,943,625 (95% CI 7,689,429-8,197,821) females sustained sports injuries. Our findings suggest that over 23 million African adolescents sustained sports injuries annually. Further work will help to more precisely define the burden of sports injuries in LMICs and the role that surgery can play in mitigating this burden. | [
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Episodes of adenolymphangitis (ADL) are a recurrent clinical aspect of lymphatic filariasis (LF) and a risk factor for progression of lymphedema. Inter-digital entry lesions, often found on the web spaces between the toes of those suffering from lymphedema, have been shown to contribute to the occurrence of ADL episodes. Use of antifungal cream on lesions is often promoted as a critical component of lymphedema management. Our objective was to estimate the observed effect of antifungal cream use on ADL episodes according to treatment regimen among a cohort of lymphedema patients enrolled in a morbidity management program. We estimated this effect using marginal structural models for time varying confounding. In this longitudinal study, we estimate that for every one-unit increase in the number of times one was compliant to cream use through 12 months, there was a 23% (RR = 0.77 (0.62, 0.96)) decrease in the number of ADL episodes at 18 months, however the RR's were not statistically significant at other study time points. Traditionally adjusted models produced a non-significant RR closer to the null at all time points. This is the first study to estimate the effect of a regimen of antifungal cream on the frequency of ADL episodes. This study also highlights the importance of the consideration and proper handling of time-varying confounders in longitudinal observational studies. | [
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] |
Self-rated health (SRH) is an essential global measure of general health and quality of life, and a predictor of the mortality and morbidity of populations. We assessed the SRH and identified associated factors among women in Riyadh, the capital of Saudi Arabia, using a cross-sectional survey conducted on a sample of women aged 18 years and older. Univariate and multivariate logistic regression analyses were conducted to identify factors that are significantly associated with SRH. Overall, 36.6% (n = 329) of participating women reported poor SRH. Higher body mass index (BMI), physical inactivity, greater number of morbidities, and reporting ill-being/likely depression were significantly associated with poor SRH. The findings from this study suggest that health status, lifestyle factors, and psychosocial conditions are associated with SRH in this population. Focusing on these factors suggests a turning point for public health policies and interventions to improve the health and quality of life of this group of women. | [
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This prospective study assessed the prevalence and genetic analysis of - and -thalassemia and sickle cell anemia (SCA) in Southwest Iran. Hematological indices were measured in 17,581 couples living in Khuzestan Province, Southwest Iran. Individuals with mean corpuscular volume <80, mean corpuscular hemoglobin <27, hemoglobin A2 ?3/5 were considered as -thalassemia traits. Prevalence of minor -thalassemia, -thalassemia, SCA, iron deficiency anemia, and silent thalassemia were respectively identified in 995 (5.6%), 1169 (6.65%), 1240 (7.05%), 911 (5.18%), and 1134 (6.45%) individuals using a multiplex amplification refractory mutation system, and direct DNA sequencing of globin genes. Three codons IVS-II-1 (G ? A; 26%; n = 13), IVS-I-1 (G ? T; 16%; n = 8), and IVS-I-110 (G ? A; 14%; n = 7) were the most frequent mutants and IVS-II-1 was the most common -thalassemia mutation. Also, based on a gap-polymerase chain reaction assay, genotype frequencies of -globin mutations were -3.7 kb (50%; n = 25), Med/thal (12%; n = 6), and -4.2/ (10%; n = 5), which were the most frequent deletion mutants (72% in total). The most common deletion (50%) was -3.7 kb. Our data suggest that the population of Southwest Iran is at high risk of - and -thalassemia caused by these deletion mutants and SCA. Our findings will be useful for developing an efficient control program and genetic counseling. | [
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Cystic echinococcosis (CE) is recognised worldwide as a neglected disease of public health concern, particularly in low- and middle-income countries. The objectives of this study were to describe, using a questionnaire survey, the characteristics, attitudes, knowledge, and practices of patients with CE from Basrah Province, Iraq. We interviewed 50 patients, 31 female and 19 male, of whom, 74% originated from rural areas. Approximately half (48%) of the participants reported slaughtering livestock at home for their families' consumption; 78% indicated the presence of a large number of stray dogs roaming freely about their village; 86% reported that they never boiled water prior to drinking it; and 26% reported not washing vegetables prior to eating them. Although a large proportion of the participants (72%) had heard of hydatid disease prior to becoming ill, over half (57%) were not aware how the disease was transmitted from animals to humans. This study highlighted a gap in health education efforts regarding CE in Southern Iraq, with a lack of counselling of patients on how to prevent reinfection. An intensive control programme should be implemented and founded on health education to reduce CE disease in Basrah. | [
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Waterborne diseases, such as hepatitis A and E, are a major public health concern in most developing countries, indicating the need for proper outbreak prevention, surveillance, and timely management. This study presents data regarding the prevalence and epidemiological characteristics of hepatitis A and E outbreaks as well as water quality in Kashmir, India, during 2015-2017. Hepatitis outbreaks were initially investigated by rapid response teams, under the Integrated Disease Surveillance Programme. Suspected cases were further evaluated by blood sampling to confirm the disease along with water sampling evaluation. Between 2015 and 2017, 23 disease outbreaks were recorded; among these, four outbreaks occurred in 2015, 12 in 2016, and seven in 2017. Specifically, 12 of the total outbreaks were concerned with hepatitis A infection, 10 concerned hepatitis E infection, and one involved eight cases of jaundice with neither hepatitis A virus nor hepatitis A virus detected in blood sampling. Overall, during the aforementioned period, 393 cases of hepatitis A or E were detected. Regarding water quality, which was evaluated using the most probable number method for counting coliform, 38 of 50 water samples were found to be unfit for human consumption and one source was found to be suspicious. This study of prevalence and epidemiology of hepatitis A and E along with its relationship with water quality and socioeconomic factors, such as poor hygiene and lack of access to safe water, aids toward the implementation of effective preventive sanitary measures and public health actions. | [
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] |
Early mobilization (EM) is practiced for intensive care unit (ICU) patients in many hospitals in the Eastern Province in Saudi Arabia. Respiratory care professionals' knowledge about using EM was, therefore, surveyed and investigated to improve and update its practice and ultimately to develop related regulations and policies. A survey including 156 respiratory care professionals was conducted using a validated questionnaire. The focus was on collecting information on participants' relevant backgrounds and on proper use of EM. Knowledge and proper use of EM were calculated in relation to participants' demographic and professional characteristics. The statistical analysis using analysis of variance and Student t-test showed that factors that affected knowledge of EM were the respiratory care professional's age, gender, nationality, and years of experience in intensive care medicine. How many patients these professionals treated using EM also significantly correlated with their knowledge of EM. The survey showed the extent of respiratory care professionals' knowledge about the proper use of EM. More importantly, the survey also identified important shortfalls in practice of some experienced medical practitioners. | [
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] |
Antidepressant prescribing patterns have changed globally over the past few years, with conventional drugs including tricyclic antidepressants and monoamine oxidase inhibitors being replaced by selective serotonin reuptake inhibitors (SSRIs) and novel antidepressants. The objective of this study was to assess antidepressant utilization in Iran from 2006 to 2013 and to show Iran's situation in antidepressant consumption compared with other countries. A cross-sectional study was undertaken using prescription claims data from Iranian insurance agencies. In addition, total antidepressant sales data were obtained from the databank of the national regulatory authority. Medicines were classified according to the Anatomic Therapeutic Chemical (ATC-2012 edition) System. The Organisation for Economic Co-operation and Development data were used to compare national results from Iran with other countries. Antidepressant sales were four-fold higher than those of prescribed antidepressants [24 defined daily doses (DDD)/1000 inhabitants/day were sold whereas 6 DDD/1000 inhabitants/day were prescribed in 2013]. The trend in antidepressant prescriptions and consumption showed increasing use of SSRIs (N06AB). Nortriptyline, fluoxetine, and citalopram accounted for more than 60% of all prescriptions each year. The type of adverse reactions with new expensive antidepressants may seem convincing for the growing tendency toward using these medicines, but considering their high costs, health policymakers have to be aware of the risk of overprescription of newer antidepressant. Drivers of over-the-counter purchase of antidepressants need to be explored. | [
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Rapid detection of drug resistance in Mycobacterium tuberculosis is important for the successful treatment of tuberculosis. Fluoroquinolone and aminoglycoside resistance detection by molecular methods becomes more complex due to cross resistance among them. Thus, we aimed to determine cross-resistance and mutations in resistance genes for these drugs. A total of 336 multidrug-resistant tuberculosis (MDR-TB) cases received in Mycobacteriology laboratory were screened for phenotypic drug sensitivity testing for second-line drugs, i.e., ofloxacin, amikacin, kanamycin, and capreomycin. Molecular characterization of resistance was done by DNA sequencing of gyrA gene for fluoroquinolones (FQ), and multiplex allele-specific polymerase chain reaction (PCR) and PCR restriction fragment length polymorphism (RFLP) of rrs gene for aminoglycosides. Of 336 MDR-TB isolates, 12 were extensively drug-resistant tuberculosis and 219 were sensitive to all the drugs tested. Ofloxacin, amikacin, kanamycin, and capreomycin resistance was detected in 101 (30.1%), 23 (6.8%), 27 (8.1%), and 19 (5.6%) cases, respectively. Eight different mutations were detected in gyrA gene in ofloxacin-resistant isolates and A1401G nucleotide change in rrs gene were seen in 55.6% (15/27), 65.2% (15/23), and 68.4% (13/29) for kanamycin-, amikacin-, and capreomycin-resistant isolates, respectively. Information on second-line drug resistance-associated mutations could potentially be used for development of newer rapid diagnostic tests. | [
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] |
OBJECTIVES: This study aimed to understand the epidemiology of meningitis cases admitted to hospitals in Oman and to identify any changing microbial patterns from the introduction of the new vaccines.METHODS: A retrospective analysis of all cases of meningitis reported through a national surveillance system. Meningitis is a notifiable disease.RESULTS: Of a total of 581 cases of meningitis from the period between January 1, 2005 and December 31, 2013, 15% (88) were confirmed to be bacterial in origin and 7.2% (42/581) viral. In 50.9% (296) of patients with suspected pyogenic meningitis, no specific bacterial pathogen were identified, and in 26% of cases (151) a cerebrospinal fluid study could not be undertaken. Among 88 cases with confirmed bacterial pathogens the organisms identified were Streptococcus pneumoniae (65.9%), Neisseria meningitides (18.2%), Haemophilus influenzae (6.8%), and other organisms (9.1%). The peak incidence was in children <2 years of age (39.4%). It showed notable decline in H. influenzae cases as well as pneumococcal meningitis cases, possibly indicative of the successful immunization program.CONCLUSION: A drop in H. Influenzae and pneumococcal meningitis cases was possibly the effect of the introduction of vaccines. It shows the need for improving diagnostic accuracy, laboratory capacities, and quality of surveillance reporting. | [
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The purpose of thisin vitrostudy was to evaluate the influence of a new proposal of implant design and surgical protocol on primary stability in different bone densities. Four groups were tested (n=9): G1 - tapered, cone morse, ? 4.3 mm x 10 mm in length (Alvim CM); G2 - experimental tapered; G3 - cylindrical, cone morse, ? 4.0 mm x 11 mm in length (Titamax CM) and G4 - experimental cylindrical. The experimental implants were obtained from a design change in the respective commercial models. The insertion was performed in polyurethane (PU) blocks 0.24 g/cm3(20 pcf) and 0.64 g/cm3(40 pcf), according to different surgical protocols. The primary stability was measured by means of insertion torque (IT) and pullout test. Data were analyzed by ANOVA, Tukey's test (=0.05) and Pearson's correlation. For IT and pullout, conventional and experimental implants showed no difference between them when inserted in the 20 pcf PU (p>0.05). In the 40 pcf PU, the modified implants exhibited greater IT (p<0.05) and lower pullout (p<0.05) compared to the respective conventional models. The implant design tested associated with the surgical protocol, positively influenced primary stability in higher density bones. | [
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This study evaluated gloss and color changes of esthetic restorative materials subjected to different acidic beverages. Specimens of resin composites (Z350XT (Z350), IPS Empress Direct (ED), Charisma Diamond (CD)) were prepared and the initial surface gloss and color (E) were measured (n=10). Then, the specimens were immersed in 4 mL of each of the different beverages (cranberry juice; Coca-Cola; coffee or artificial saliva) during 15 min, 3x/day for 14 days and new gloss and color readings were obtained. Color change was evaluated with the E formula and gloss change values were obtained by the formula: (final gloss - initial gloss). Data was submitted to two-way ANOVA followed by Tukey's post hoc test (a=0.05). CD showed the lowest color change among resin composites. The highest E values were obtained after immersion in coffee and cranberry juice. Coffee promoted the highest gloss change (worst gloss retention), followed by cranberry juice, Coca-cola and artificial saliva (p<0.05). The type of beverage significantly influenced the gloss of resin composites. Coca-cola reduced gloss of the three resin composites in a similar manner. Coffee affected the ED gloss more than that of Z350 and CD, while cranberry juice affected Z350 more than ED and CD. Saliva had a more pronounced effect on the gloss retention of CD than ED. The beverages used in this study influenced the optical surface properties of the composites studied. | [
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The aim of this study was to evaluate different conditioning protocols and sonic/ultrasonic application of an infiltrant resin (IR) in artificial white spot lesions (AWSL). the V/L surfaces of 48 molars were induced to an AWSL and divided in 6 groups, according to the conditioning protocols and application technique: 15% hydrochloric acid (HA) + manual application of the IR; HA + 37% phosphoric acid (PA) + manual application of the IR; HA + ultrasonic application (U) of the IR; HA + sonic application (S) of the IR; PA+HA+S; and PA+HA+U. For the Penetration Depth (PD), the crowns were etched with HA for 120s. The IR Icon (DMG) was applied according to the manufacturer`s instructions. The crowns were dye penetrated (0.1% red fluorophore rhodamine B isothiocyanate for 12h) and bleached with 30% hydrogen peroxide for 12 h. The discs were immersed in a 50% ethanol solution, containing 100 M of sodium fluorescein. The PD (in m) was measured using confocal laser scanning microscopy (20x). The bond strength (BS) was performed by michoshear test (0.5 mm/min). Data were submitted to 2-way ANOVA and Tukey (=0.05). For BS, the interaction was not significant (p>0.05). For PD, the main factors were significant (application - p<0.001; conditioning technique - p=0.003). The ultrasonic application showed the highest PD values. PA+HA presented higher results than HA. The sonic/ultrasonic applications and the use of phosphoric acid prior to hydrochloric acid improved PD of the infiltrant resin. Conditioning protocols or application techniques did not influence BS values. | [
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The use of two-implant overdentures improves mastication of edentulous elderly patients. However, little is known about the effects of single-implant overdentures (SIO) on oral perception and masticatory function in such elders. This study compared the effects of conventional complete dentures (CD) and SIO on the oral sensorimotor ability (OSA), masticatory function, and nutritional intake of elderly people with residual alveolar mandibular height classified as Class III or IV according to the American College of Prosthodontics. Twelve elders first received new conventional CD, which were later converted to SIO. All variables were evaluated after use of each prosthesis for 2 months. To evaluate OSA, elders closed their eyes and orally identified test pieces prepared from raw carrots. A kinesiographic device was used to measure chewing movements during mastication of a test material (Optocal). Masticatory performance (MP) was determined with the sieving method, and a 3-day food diary verified nutrient intake based on a standard Brazilian Food Composition Table. Data were analyzed using the Wilcoxon signed rank test and Student's paired t test (P < 0.05). OSA results did not differ according to prosthesis type. However, opening and closing velocities during chewing and MP increased after SIO insertion (P < 0.05). Although no difference was observed in the intake of most nutrients, sodium ingestion decreased after SIO insertion (P < 0.05). SIO use had no effect on OSA, but significantly improved mastication and sodium intake of elders with decreased residual ridges height (Brazilian Registry of Clinical Trials #RBR-3kgttj). | [
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Plant bioflavonoids are widely present in the human diet and have various protective properties. In this study, we have demonstrated the capacity of delphinidin and luteolin to increase human telomerase reverse transcriptase (hTERT) expression level and act as protective agents against halogenated boroxine-induced genotoxic damage. Halogenated boroxine K2(B3O3F4OH) (HB), is a novel compound with potential for the treatment of both benign and malignant skin changes. In vivo and in vitro studies have confirmed the inhibitory effects of HB on carcinoma cell proliferation and cell cycle progression as well as enzyme inhibition. However, minor genotoxic effects of HB are registered in higher applied concentrations, but those can be suppressed by in vitro addition of delphinidin and luteolin in appropriate concentrations. Fresh peripheral blood samples were cultivated for 72 h followed by independent and concomitant treatments of HB with luteolin or delphinidin. We analyzed the differences in relative hTERT expression between series of treatments compared with controls, which were based on normalized ratios with housekeeping genes. The obtained results have shown that selected bioflavonoids induce upregulation of hTERT that may contribute to the repair of genotoxic damage in vitro. | [
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] |
The emergence of nontoxic, eco-friendly, and biocompatible polymers derived from natural sources has added a new and exciting dimension to the development of low-cost and scalable biomaterials for tissue engineering applications. Here, we have developed a mechanically strong and durable hydrogel composed of an eco-friendly biopolymer that exists within the cell walls of fruits and plants. Its trade name is pectin, and it bears many similarities with natural polysaccharides in the native extracellular matrix. Specifically, we have employed a new pathway to transform pectin into a ultraviolet (UV)-cross-linkable pectin methacrylate (PEMA) polymer. To endow this hydrogel matrix with cell differentiation and cell spreading properties, we have also incorporated thiolated gelatin into the system. Notably, we were able to fine-tune the compressive modulus of this hydrogel in the range ?0.5 to ?24 kPa: advantageously, our results demonstrated that the hydrogels can support growth and viability for a wide range of three-dimensionally (3D) encapsulated cells that include muscle progenitor (C2C12), neural progenitor (PC12), and human mesenchymal stem cells (hMSCs). Our results also indicate that PEMA-gelatin-encapsulated hMSCs can facilitate the formation of bonelike apatite after 5 weeks in culture. Finally, we have demonstrated that PEMA-gelatin can yield micropatterned cell-laden 3D constructs through UV light-assisted lithography. The simplicity, scalability, processability, tunability, bioactivity, and low-cost features of this new hydrogel system highlight its potential as a stem cell carrier that is capable of bridging the gap between clinic and laboratory. | [
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] |
Self-assembled nanostructures of amphiphilic peptides have a wide range of applications in bioimaging and delivery systems. In this study, we design and synthesize a biocompatible amphiphilic peptide (C-3) consisting of an RVRRFFF sequence and a nitrobenzoxadiazole fluorophore that can self-assemble into stable micelles for specifically detecting furin, a kind of proprotein convertase with promoting tumor progression. The self-assembly of C-3 with a -sheet nanostructure is capable of a rapid and specific response to furin in only 5 min in aqueous solution because of the existence of the RVRR motif in the C-3 molecule. The C-3 nanostructures thus can selectively distinguish high furin-expressing cancer cells, like MDA-MB-231 cells, a kind of human breast cancer cells, from normal cells. Furthermore, the C-3 self-assembly can stay in living cells for a long time and are capable of durable detection of intracellular furin, being good for tracer analysis. To our knowledge, this is the first example of self-assembly of a soluble amphiphilic peptide that can selectively detect furin in high furin-expressing live cells. | [
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We previously isolated a monocrotophos-degrading strain Starkeya sp. YW6, which could also degrade propham. Here, we show that strain YW6 metabolizes propham via a pathway in which propham is initially hydrolyzed to aniline and then converted to catechol, which is then oxidized via an ortho-cleavage pathway. The novel amidase gene mmH was cloned from strain YW6 and expressed in Escherichia coli BL21(DE3). MmH, which exhibits aryl acylamidase activity, was purified for enzymatic analysis. Bioinformatic analysis confirmed that MmH belongs to the amidase signature (AS) enzyme family and shares 26-50% identity with several AS family members. MmH (molecular mass of 53 kDa) was most active at 40 C and pH 8.0 and showed high activity toward propham, with Kcat and Km values of 33.4 s-1 and 16.9 M, respectively. These characteristics make MmH suitable for novel amide biosynthesis and environmental remediation. | [
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] |
Gymnemic acid (GA) is an herbal ingredient that can improve glucose metabolism in patients with diabetes mellitus. In this study, we evaluated the ameliorative effects of GA on insulin resistance (IR) and identified the mechanisms in type 2 diabetes mellitus (T2DM) rats and IR HepG2 cells. GA effectively enhanced glucose uptake in IR HepG2 cells from 11.9 1.09 to 14.7 1.38 mmol/L and lowered fasting blood glucose (blood glucose levels in groups treated with GA at 40 and 80 mg/kg/day were reduced by 15.2% and 26.7%, respectively) and oral glucose tolerance. Both in vivo and in vitro, GA downregulated the expression of endoplasmic reticulum (ER) stress indicator proteins such as ORP150, p-c-Jun, p-PERK, and p-eIF2. In addition, the improvement of ER stress regulated the insulin signal transduction proteins, reducing p-IRS-1(ser) levels and increasing p-IRS-1(tyr) in GA-treated T2DM rats and IR HepG2 cells. In summary, the mechanism underlying the hypoglycemic effects of GA may be associated with alleviation of ER stress and facilitation of insulin signal transduction in T2DM rats and IR HepG2 cells. | [
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Bile acids, synthesized in the liver and metabolized by microbiota, have emerged as important signaling molecules regulating immune responses and cell proliferation. However, the crosstalk among nutrition, microbiota, and bile acids remains unclear. Our study indicated that undernutrition in weaning piglets led to intestinal atrophy, increased colonic production, and systemic accumulation of lithocholic acid (LCA), deoxycholic acid (DCA), or their conjugated forms, which might be associated with decreased Lactobacillus abundance. Moreover, undernutrition led to increased portal fibroblast growth factor 19 ( FGF19) level, upregulated hepatic heterodimer partner ( SHP), and downregulated cholesterol 7a-hydroxylase ( CYP7A1) expression. The detrimental effects of DCA and LCA on proliferation and barrier function were confirmed in porcine enterocytes, whereas their roles in weaning piglets warrant further research. In summary, undernutrition in weaning piglets led to increased secondary bile acids production, which might be related to altered gut microbiome and enhanced farnesoid X receptor (FXR) signaling while CYP7A1 expression was suppressed. | [
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] |
Optical super-resolution techniques reach unprecedented spatial resolution down to a few nanometers. However, efficient multiplexing strategies for the simultaneous detection of hundreds of molecular species are still elusive. Here, we introduce an entirely new approach to multiplexed super-resolution microscopy by designing the blinking behavior of targets with engineered binding frequency and duration in DNA-PAINT. We assay this kinetic barcoding approach in silico and in vitro using DNA origami structures, show the applicability for multiplexed RNA and protein detection in cells, and finally experimentally demonstrate 124-plex super-resolution imaging within minutes. | [
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Introduction: Introduction: child excess weight has been associated with obesity in adulthood and, as a consequence, increased risk of death due to cardiometabolic factors. Objective: to identify whether BMI reflects changes in the content and distribution of fat/adipose tissue and the cardiometabolic risk in children between six and nine years old. Material and methods: participants were 537 children (59.8% women) randomly selected. BMI, waist circumference (WC), waist-height index (WHI), body composition, nutritional status and cardiometabolic risk were determined. Student's t-test, one-way ANOVA, Pearson's correlation, Chi-square and diagnostic concordance were applied. An alpha ? 0.05 was considered. Results: direct and significant correlations between nutritional status and the anthropometric parameters studied are shown, except for the percentage of adiposity. There were significant variations (p < 0.05) in the percentage of fat and adiposity according to nutritional status of the sample. In addition, there was consistency between the variation of the nutritional status with the cardiometabolic risk evaluated trough WC and WHI. Conclusion: BMI identifies the differences in the amount of fat/adipose tissue in the children between six and nine years old when categorized according to nutritional status. In addition, it reflects direct association with cardiometabolic risk. | [
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Introduction: Introduction: a short version of the Mini Nutritional Assessment Large Form (MNA-LF) called Mini Nutritional Assessment Short Form (MNA-SF) is available for nutritional screening of the elderly. This MNA-SF allows the use of the circumference of the calf (CC) or body mass index (BMI) and shows a good correlation with the MNA-LF. However, only a few researches that have analyzed the validity of the MNA-SF can be found. Objective: to analyze the validity of the MNA-SF (including two different methods, based on the BMI (MNA-SF [BMI]) or using the calf circumference (MNA-SF [CC]). Design: study of diagnostic tests with 255 subjects over 65 years of age. The Chang method was used as gold standard. Cohen's Kappa index, sensitivity and specificity, positive and negative predictive values, the Youden index and the validity index were calculated. Results: the Kappa indexes for the Chang method were very low when comparing the results with those of the MNA-SF versions (IMC and CP) (0.335 and 0.286, respectively). The following validity results were obtained for MNA-SF (IMC) and MNA-SF (CP): sensitivity 70% and 67%, specificity 68% and 66% and Youden index 0.38 and 0.33, respectively, correctly classifying to 68.5% and 66.5% of the elderly. Conclusions: MNA SF is a useful tool (easy, non-invasive and quick to complete) but very limited for nutritional screening. | [
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Introduction: Introduction: the dietary intake patterns of children should be monitored because of their influence on health in adulthood. It is now widely accepted that childhood nutrition is linked to specific diseases such as obesity and to risk factors for cardiovascular disease in adulthood. Therefore, knowledge of dietary intake during childhood may be useful to identify possible risk factors for disease in adulthood. The main focus of research into children's diets has been the contribution of macronutrients and micronutrients. Objective: several indices have been developed for assessing the diet quality of previously defined population groups. The aim of the present study was to compare the nutritional status of Andalusian children and adolescents and examine the relationship between their diet quality and socio-demographic or lifestyle factors. Results and conclusions: the food intake of the younger children in this study was closer to RDIs compared with the adolescents, who generally reported a lower energy supply in their diet than the recommended. The mean (SD) diet quality score was 12.1 (1.9) for the younger children (6-9 years) and 9.4 (3.2) for the older group (10-17 years), a statistically significant difference. A good correlation was found between energy intake (MJ/kg body weight) and estimated energy (MET MJ/kg body weight). | [
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Introduction: Background: physical activity in type 1 diabetic patients allows a better control of glycaemia and glycosylated hemoglobin, helps to maintain a residual endocrine pancreatic mass and optimizes subsequent insulin requirements. These improvements might be due in part to increases in anti-inflammatory cytokines that could help to minimize -cell destruction. However, type, intensity and frequency of exercise for type 1 diabetic patients remain to be established. Case report: we present the case of a 48-year-old man diagnosed with type 1 diabetes at the age of 23. He is a professional alpinist and recently was recruited in a program of the Yuri Gagarin Cosmonaut Training Center (Russia) to be the first diabetic astronaut. Metabolic and inflammatory responses were assessed after performing two extreme activities. Discussion: well programmed extreme activities accompanied by a correct dietetic intervention can reduce the adverse metabolic and inflammatory processes that appear due to exercise and diabetes. | [
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] |
Introduction: Background: primary trimethylaminuria or fish odor syndrome is a genetic metabolopathy characterized by the accumulation of trimethylamine, a very volatile compound in body secretions. Case report: we present the case of a healthy 8-month-old patient who, after the introduction of fish in the diet, starts a bad body odor that does not disappear with bathing. The mother visits the pediatrician repeatedly but no disorder is identified. The diagnosis is delayed until the patient is three years old. Due to maternal insistence, the patient is referred to our hospital unit, where genetic diagnostic tests are performed, enabling the paternal diagnosis that had gone unnoticed for 35 years and detecting three different mutations in the family. Discussion: primary trimethylaminuria is a genetic disease with specific symptomatology of bad body odor that can go unnoticed for many years. An adequate clinical suspicion and the request of adequate complementary tests allow its diagnosis and facilitate its clinical management. | [
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Introduction: Introduction: sedentary behavior is an important target for health promotion. In this systematic review, we aimed to provide evidence to support decisions about measurement approach choices for subjectively assessing sedentary behavior in pediatric population, adopting objective methods as the reference. Methods: in this systematic review with meta-analysis, published studies were retrieved from electronic databases: Medline (PubMed), Web of Science, Embase, SPORTDiscus, BioMed Central and SCOPUS. We considered studies evaluating sedentary behavior agreement through questionnaire and/or diary in comparison with an objective measure. A total of six inclusion criteria were used. We synthesized the data using correlation coefficients (r) as an indicator of agreement estimates. The review protocol is registered in the PROSPERO database (CRD42014015138). Results: a total of 14 studies met the inclusion criteria with ages ranging from 3 to 17.5 years and provided 17 agreement analyses. Thirteen of these agreement analyses (76.5%) reported correlation coefficients. We found two major groups of sedentary activities: screen time (47.1%) and sedentary behaviors (52.9%). The pooled agreement between questionnaires and accelerometers for assessing self-reported screen time was negative (r = -0.15; CI 95%: -0.17 to -0.13). Conversely, when the sedentary behavior was assessed by questionnaires and accelerometers, the pooled agreement was positive for parent-reporting (r = 0.09; CI 95%: 0.04 to 0.13) and self-reporting (r = 0.43; CI 95%: 0.40 to 0.47) in children and adolescents, respectively. Conclusion: questionnaires have positive agreement with accelerometers for assessing sedentary behavior, whereas the agreement is negative for assessing screen time. Self-reported questionnaires are recommended methods to measure sedentary behavior in adolescents. | [
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] |
Introduction: Introduction: different diets during pregnancy might have an impact on the health as reflected by the birth weight of the newborn. The consumption of meat and meat products during pregnancy and its relationship with the newborn health status have been studied by several authors. The studies carried out show inconsistent results. Objective: to analyse the association between maternal dietary intake of meat and meat products and the risk of small for gestational age (SGA) newborn. Methods: a matched case-control study of 518 cases and controls of pregnant women was performed in Spain. Cases were women with a SGA newborn. Data about demographic characteristics and diet were collected. Meat consumption was gathered through a validated food frequency questionnaire. Meat and meat products intakes were categorized in quintiles (Q1-Q5).The association between maternal meat and meat product intakes and SGA was assessed by logistic regression models with adjustment for confounding factors. Results: an intake of meat products above 6.8 g/day was associated with a lower risk of SGA delivery (OR = 0.7; 95% CI, 0.53-0.93) after adjusting for smoking, body mass index, previous preterm-low birth weight, newborn gender and adherence to Mediterranean diet. Conclusions: meat consumption was not associated with SGA, whereas meat products showed a moderate protective relationship. | [
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Introduction: Background: the relationship of uric acid and the development of cardiometabolic diseases has been studied in recent years. However, the controversy continues to consider this finding as an independent risk factor for cardiovascular disease at early ages. The objective was to establish the prevalence of serum levels of altered uric acid and its association with the metabolic syndrome components in adolescents from Bucaramanga, Colombia. Methods: an analytical cross-sectional study, nested in a population cohort, with a sample of 494 re-contacted adolescents from the original study. The dependent variables were metabolic syndrome and its component criteria. The main independent variable was uric acid values, classified into two categories: uric acid at risk (values greater than 5.5 mg/dl) and high uric acid (greater than 6.5 mg/dl). Logistic regression models were used, adjusted for sex, age and body mass index to determine the association between the variables of interest. Results: the prevalence of uric acid at risk was 37.25% (CI 95%, 32.9-41.5) and the proportion of high uric acid was 18.42% (CI 95%, 14.9-21, 8), significantly higher in men than in women (p < 0.0001). Adolescents with high levels of uric acid were more likely to have abdominal obesity (OR: 3.03, CI 95% 1.38-6.64), high blood pressure (OR: 1.11, CI 95%, 1.05-2.07), hypertriglyceridemia (OR: 4.94, CI 95%, 2.98-8.19) and altered fasting glycemia (OR: 5.15, CI 95%, 3.42-11.05). Conclusions: the results suggest the existence of a positive relationship between the presence of high levels of uric acid and metabolic cardio-risk factors. | [
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Physiological changes in pregnancy may cause taste dysfunction. The aim of this study was to determine and compare gustatory function of pregnant women with nonpregnant women and also to investigate the effect of pregnancy on gustatory function. It was a case-control study of consecutive 70 healthy pregnant women (cases) and 70 healthy nonpregnant women (control). Participants scored their taste perception on a visual analogue scale (1-10) and their gustatory function was assessed using "taste strips" impregnated with graded concentration of sweet, sour, salty, and bitter taste substances applied on tongue surfaces. Subjective mean gustatory score, correct identification of taste in the strips and total taste strip (TTS) score were compared between both groups and analysis was done using appropriate statistics. The mean age of pregnant women (30.5 [3.9]) and controls (28.5 [6.6]) were comparable. Twenty-one (30%) pregnant women changed their diet in first trimester due to change in taste sensation. Almost all cases developed craving for spicy and salty foods and, aversions to fish, beans, and vegetables. There was a significant difference in the subjective rating of taste perception between the 2 groups ( P = .037). About 2.9% of pregnant women have hypogeusia. There was a significant difference between pregnant and nonpregnant women in sour taste ( P = .006; 2.90 [0.71] vs 3.92 [0.82]) and TTS ( P = .02; 27.50 [3.48] vs 29.21 [2.69]) scores, respectively. In conclusion, gustatory function was reduced in pregnancy compared to nonpregnant women and this led to dietary change in some pregnant women. | [
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OBJECTIVE: The aim of this study was to evaluate the effects of repetitive transcranial magnetic stimulation (rTMS) on the post-stroke recovery of lower limb motor function.DATA SOURCES: We searched the databases of PubMed, Cochrane Library, and Embase. The randomized controlled trials were published by 25 January 2019.REVIEW METHODS: We included randomized controlled trials that evaluated the effects of rTMS on lower limb motor recovery in patients with stroke. Two reviewers independently screened the searched records, extracted data, and assessed the risk of bias. The treatment effect sizes were pooled in a meta-analysis by using the RevMan 5.3 software. The internal validity was assessed using topics suggested by the Physiotherapy Evidence Database (PEDro).RESULTS: Eight studies with 169 participants were included in the meta-analysis. Pooled estimates demonstrated that rTMS significantly improved the body function of the lower limbs (standardized mean difference (SMD) = 0.66; P < 0.01), lower limb activity (SMD = 0.66; P < 0.01), and motor-evoked potential (SMD = 1.13; P < 0.01). The subgroup analyses results also revealed that rTMS improved walking speed (SMD = 1.13) and lower limb scores on the Fugl-Meyer Assessment scale (SMD = 0.63). We found no significant differences between the groups in different mean post-stroke time or stimulation mode over lower limb motor recovery. Only one study reported mild adverse effects.CONCLUSION: rTMS may have short-term therapeutic effects on the lower limbs of patients with stroke. Furthermore, the application of rTMS is safe. However, this evidence is limited by a potential risk of bias. | [
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] |
Aim: This study aimed at detecting and quantifying Merkel cell polyomavirus (MCPyV) viral loads in the peripheral blood of healthy Pakistani individuals. Patients & methods: A total of 221 whole blood samples obtained from healthy individuals were examined by qPCR. Results & conclusion: MCPyV was detected in the peripheral blood of 31.2% healthy individuals. The rate of MCPyV positivity decreased from young (36%), to middle (33.7%) and elder (25.3%) age groups. Our data revealed higher prevalence of MCPyV in women (43.93%) than men (25.80%). The MCPyV viral load was calculated in the range of 0.06 -11copies/ng of isolated DNA. The MCPyV viral load increased from young (median=3.35) to elder (median=5.66) age groups. The MCPyV circulate at a higher frequency by residing dormant in certain blood cells, which might act as potential vehicles for the spread of MCPyV infection among general population. | [
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] |
Malignant hyperthermia (MH) is an uncommon, autosomal dominant disorder of skeletal muscle, triggered by inhalational anaesthetics or depolarizing muscle relaxants. Masseter muscle rigidity (MMR) can be regarded as potentially a preceding sign for an MH reaction. Susceptibility to MH can be determined by the in vitro contracture test (IVCT) or DNA analysis where a familial variant is known. Our aims were to review patients with MMR, where IVCT and DNA analysis had been undertaken, to determine if DNA analysis could be used as an initial screening tool for MH susceptibility, and, by reviewing standard monitored variables (SMVs), to determine if any clinical characteristics could be used to differentiate between MMR patients who are MH susceptible (MHS) and those who are not. Patients with MMR were identified from the Palmerston North Hospital MH Reactions Database. IVCT and DNA analysis results were documented. DNA testing was performed retrospectively in the majority of patients as many patients had presented before DNA analysis was available. Forty-one patients were analysed. Fourteen were DNA positive/IVCT positive and six DNA positive only (48% in total), seven were IVCT positive/DNA negative and 14 were IVCT normal. Increased creatine kinase (>18,000 units/L) was consistent with MH susceptibility. Severity of MMR was not linked to MH susceptibility. This study confirmed that DNA analysis can be used as a first-line test for MH susceptibility in patients presenting with MMR (consistent with European MH Group recommendations). Creatine kinase was the only SMV that was significantly different between MHS and MH normal individuals. | [
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Intermittent pneumatic compression (IPC) to the lower limbs is widely used as a mechanical means to prevent deep vein thrombosis in hospitalised patients. Due to a theoretical concern about impairing blood flow, thromboembolic-deterrent stockings and IPC are considered contraindicated for patients with peripheral vascular diseases by some clinicians. This study assessed whether IPC would alter peripheral limb muscle tissue oxygenation (StO2), and whether such changes were different during 10 minutes of sequential and single-compartment compressions. Twenty volunteers were randomised to have their left or right arm treated with a sequential or single-compartment IPC for 10 minutes, using the contralateral arm without compression as an intraparticipant control. After a five-minute wash-out period, the procedure was repeated on the same arm using the alternative mode of IPC. Both hands' thenar muscles StO2 was monitored every twominutes for 10minutes using the same near-infrared spectroscopy StO2 monitor. Both sequential (3.5%, 95% confidence intervals (CI) 2.7-4.2; p < 0.001) and single-compartment IPC (1.6%, 95% CI 0.4-2.8; p = 0.039) significantly increased muscle StO2 within 10 minutes compared to no compression; and the increments were higher during sequential compressions compared to during single-compartment compressions (2.1%, 95% CI 0.7-3.5; p = 0.023). This mechanistic study showed that both modes of IPC increased upper limb muscle StO2 compared to no compression, but the StO2 increments were higher with the multiple-chamber sequential compressions mode. Contrary to the theoretical concern that IPC may impair peripheral limb tissue oxygenation, our results showed that IPC actually increases oxygenation of the peripheral limb muscles, especially during the sequential compressions mode. | [
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The provision of appropriate discharge analgesia can be challenging and is often prescribed by some of the most junior members of the medical team. Opioid abuse has been considered a growing public health crisis and physician overprescribing is a major contributor. In 2015 an initial audit of discharge analgesia at the Royal Perth Hospital led to the development of discharge analgesia guidelines. Compliance with these guidelines was assessed by a follow-up audit in 2016, which showed improved practice. This audit assesses discharge analgesia prescribing practices two years following guideline implementation. Dispensing data were obtained for analgesic medication over a three-month period from April to July 2017 and 100 unique patients were chosen using computer generated randomisation. Patients' medical records were assessed against the hospital's Postoperative Inpatients Discharge Analgesia Guidelines. The data collected were then compared with equivalent data from the previous 2015 and 2016 audits. Overall 83.4% of the 170 discharge analgesia prescriptions written were compliant with guidelines. The highest overall compliance rates were achieved for paracetamol (100%, up from 95.9% in 2016), celecoxib (96%, down from 100% in 2016), and oxycodone immediate release (IR) (74%, down from 88.9% in 2016). The quantity of oxycodone IR given on discharge complied with quantity guidelines in only 56% of cases. Overall there has been a significant and sustained improvement in appropriateness of discharge analgesia prescribing since 2015, though the results from 2017 show less compliance than 2016 and that achieving compliance with quantity guidelines is an ongoing challenge. This demonstrates the challenge of obtaining high adherence to guidelines over a longer time period. | [
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Major bleeding in noncardiac surgery is common and associated with serious complications. The antifibrinolytic agent tranexamic acid (TXA) reduces bleeding and may reduce the risk of these complications. TXA also may have immunomodulatory effects that could reduce surgical site infection. Clinical trials of TXA in noncardiac surgery have been insufficiently powered to evaluate its efficacy and safety. Therefore, large randomised controlled trials of its use in noncardiac surgery are required. To ensure that future clinical trials are feasible and acceptable, we undertook a survey of Fellows of the Australian and New Zealand College of Anaesthetists (ANZCA). Our aims were to ascertain current patterns of TXA administration and to assess the acceptability of randomising patients to intravenous TXA or placebo. A 12-item survey was electronically mailed to 1001 ANZCA Fellows. Two hundred and eighty nine responses were received and analysed (response rate 29%). Ninety-eight percent of respondents had used intravenous TXA in noncardiac surgery; 67% give TXA routinely for lower limb arthroplasty, with smaller proportions giving TXA for spinal surgery (40%) and other major orthopaedic surgery (28%). Almost half (49%) give TXA routinely for major trauma surgery. Thirty-six percent indicated that they did not give TXA for major vascular, abdominal, pelvic or thoracic surgery. The majority administered TXA as a single, fixed dose. Fifty-seven percent agreed that there is uncertainty about the relative risks and benefits of perioperative TXA in noncardiac surgery and 87% agreed that large definitive trials determining the safety and efficacy of perioperative TXA in noncardiac surgery are required. These results indicate that for ANZCA Fellows the use of TXA in noncardiac surgery is highly variable, that there is uncertainty about the safety and efficacy of TXA, and that a large trial would be acceptable. | [
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] |
Electrical cardioversion (ECV) is a potentially life-saving treatment for haemodynamically unstable new-onset atrial fibrillation (AF); however, its efficacy is unsatisfactory. We aimed to elucidate the factors associated with successful ECV and prognosis in patients with AF. This retrospective observational study was conducted in two mixed intensive care units (ICUs) in a university hospital. Patients with new-onset AF who received ECV in the ICU were enrolled. We defined an ECV session as consecutive shocks within 15 minutes. The success of ECV was evaluated five minutes after the session. We analysed the factors associated with successful ECV and ICU mortality. Eighty-five AF patients who received ECV were included. ECV was successful in 41 (48%) patients, and 11 patients (13%) maintained sinus rhythm until ICU discharge. A serum potassium level ?3.8 mol/L was independently associated with successful ECV in multivariate analysis (odds ratio (OR), 3.13; 95% confidence interval (CI), 1.07-9.11; p = 0.04). Maintenance of sinus rhythm until ICU discharge was significantly associated with ICU survival (OR 9.35; 95% CI 1.02-85.78, p = 0.048). ECV was successful in 48% of patients with new-onset AF developed in the ICU. A serum potassium level ?3.8 mol/L was independently associated with successful ECV, and sinus rhythm maintained until ICU discharge was independently associated with ICU survival. These results suggested that maintaining a high serum potassium level may be important when considering the effectiveness of ECV for AF in the ICU. | [
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Most medical practitioners are not specifically trained to diagnose or manage in-flight medical incidents, yet there may occur a moral obligation to do so when least expected. We felt that knowledge of the frequency of emergency versus non-serious medical incidents, in addition to the clinical spectrum of incidents most often encountered, would be of interest to medical practitioners and, in particular, critical care physicians, who happen to find themselves asked to assist with such events. To this end we collaborated with the Department of Medical Services of a major Australian airline to define the incidence, severity, and type of all in-flight medical events encountered over the course of a year's flights. We audited in-flight medical data collected over a continuous 12-month period, which covered 131,890 international and domestic flight sectors transporting more than 27 million passengers. There was an average of 296 medical events per month (3555 in total) making the per-flight incidence of a medical event approximately 1:40 (2.7%). Of these in-flight incidents, 915 (26%) were graded as emergencies, with the commonest descriptors of such incidents being either loss of consciousness (37%) or a suspected cardiovascular event (12%). Six of these 915 emergencies proved fatal. Twenty-one flights were diverted due to medical incidents (<0.016% of all flights), with 52% of these attributed to suspected cardiac events. In this series, medical in-flight events were recorded in approximately one in 40 flights, whereas medical emergencies occurred in approximately one in 150 flights. | [
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] |
We report a case series of anaphylaxis to chlorhexidine-coated central venous catheters (CVCs) when used in cardiac surgical patients in our institution. Our experience, together with increasing reports of anaphylaxis to chlorhexidine-coated CVCs from other sources indicates that chlorhexidine-coated CVCs are not without additional risk. Attempts to lower rates of catheter-related bloodstream infection has led to the widespread adoption of chlorhexidine-coated CVCs in the perioperative and critical care setting, including for routine cardiac surgery. However, closer scrutiny indicates that there is lack of strong evidence demonstrating a meaningful reduction in rates of sepsis or serious morbidity, especially with CVC dwell times of less than seven days. Given the lack of clear benefit, we recommend non-coated CVCs for routine cardiac surgery, with even consideration for chlorhexidine-coated CVCs when specifically indicated for patients at high risk of CVC infection. | [
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We report three precautionary cases of perioperative anaphylaxis to chlorhexidine isopropyl alcohol antiseptic wipes (CAW). In two cases, the patients were inadvertently re-exposed to CAW despite known chlorhexidine hypersensitivity. Chlorhexidine has been described as 'the hidden allergen'. As a result, patients may suffer multiple reactions before chlorhexidine is confirmed as the cause. Healthcare workers may not recognize that products they use for common clinical steps contain chlorhexidine. These cases highlight the need for constant vigilance to facilitate the safe management of patients with a history of chlorhexidine anaphylaxis. | [
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Modern near-infrared spectroscopy technology is increasingly adopted to measure cerebral tissue oxygen saturation. However, the normal range of cerebral tissue oxygen saturation in adults with such technology is unknown. We sought to measure cerebral tissue oxygen saturation in healthy volunteers using the novel O3 Regional Oximetry device (Masimo Corporation, Irvine, CA, USA) and assess its relationship with key physical and haemodynamic characteristics. For ?5 minutes, we continuously recorded cerebral tissue oxygen saturation, pulse oximetry, cardiac index and mean arterial pressure. We assessed for differences in cerebral tissue oxygen saturation between hemispheres, sex, skin type, comorbidity or smoking status, and for associations between cerebral tissue oxygen saturation and age, height, weight, SpO2and haemodynamic parameters. We recorded >32,000 observations in 98 volunteers aged 22 to 60 years, including 41 (42%) males. One-fifth had one or more co morbidities ( n=22, 22.5%), one-tenth were either current or former-smokers ( n=13, 13%), and most had a Fitzpatrick skin type of 3 or lower ( n=84, 86%). The mean combined average cerebral tissue oxygen saturation was 67.6% (95% confidence interval 66.8%-68.6%). We found statistically significant differences in cerebral tissue oxygen saturation according to hemisphere and an association between cerebral tissue oxygen saturation and mean arterial pressure and cardiac index. The combined average cerebral tissue oxygen saturation in 98 healthy volunteers was 67.6% with a narrow confidence interval and no combined average cerebral tissue oxygen saturation was below 56%. We also observed statistically significant yet quantitatively small cerebral tissue oxygen saturation differences between hemispheres, and an association between cerebral tissue oxygen saturation and mean arterial pressure and cardiac index. | [
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] |
The TEG 5000 and novel TEG 6s measure the viscoelasticity of whole blood during in vitro clot formation. The two devices measure similar coagulation variables but utilize distinctly different technologies. This study aimed to determine the correlation and agreement between the thrombelastographic parameters obtained by the two devices during liver transplant surgery. We obtained blood samples at six predefined intervals during the surgery of 10 consecutive patients. Two operators proficient in the use of the TEG 6s and TEG 5000 systems performed thrombelastographic measurements on each sample: non-citrated TEG 5000, citrated TEG 5000 and citrated TEG 6s. Agreement and correlation were assessed using Bland Altman plots and Lin's concordance correlation. There was considerable inter-device variability for the different parameters measured by the TEG 5000 and TEG 6s devices. Acceptable agreement was observed when results were within the normal reference ranges. However, with increasing coagulopathy, agreement was poor and results could not be considered interchangeable. Although each of the three tests appeared reliable for qualitative detection of abnormalities of clot formation during liver transplant surgery, we found their quantitative results were not interchangeable. | [
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Intravenous fluids are commonly administered for patients having colonoscopy despite relatively little data to support this practice. It is unclear what, if any, effect crystalloid administration has on stroke volume and cardiac output in patients who are fasting and have had bowel preparation agents. We aimed to assess the physiological effect of 10 ml/kg of crystalloid administration in colonoscopy patients on haemodynamic parameters including stroke volume, stroke volume variation and cardiac output, as measured with transthoracic echocardiography. Our secondary aims were to determine whether stroke volume variation predicted fluid responsiveness in gastrointestinal endoscopy patients and whether these haemodynamic measures are different in fasting patients with bowel preparation (colonoscopy patients) compared to fasting patients alone (gastroscopy patients). We recruited 54 patients having elective gastrointestinal endoscopy (25 colonoscopy, 29 gastroscopy). All patients had stroke volume, cardiac output and stroke volume variation measured with transthoracic echocardiography at baseline. In colonoscopy patients, stroke volume, cardiac output and stroke volume variation were remeasured after 10 ml/kg of intravenous crystalloid. Administration of 10 ml/kg of crystalloid increases stroke volume by 19.6 ml ( p < 0.00005) and cardiac output by 0.81 l/min ( p < 0.001). Stroke volume variation reduced from 23% to 14% after fluid administration ( p < 0.0011). The optimum threshold of stroke volume variation to predict fluid responsiveness was 21% with a sensitivity of 77.8% and specificity of 62.5%. Administration of 10 ml/kg of crystalloid increases stroke volume and cardiac output, and reduces stroke volume variation in fasting elective colonoscopy patients. | [
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] |
OBJECTIVE: To investigate the level of agreement of the behavioural mapping method with an accelerometer to measure physical activity of hospitalized patients.DESIGN: A prospective single-centre observational study.SETTING: A university medical centre in the Netherlands.SUBJECTS: Patients admitted to the hospital.MAIN MEASURES: Physical activity of participants was measured for one day from 9 AM to 4 PM with the behavioural mapping method and an accelerometer simultaneously. The level of agreement between the percentages spent lying, sitting and moving from both measures was evaluated using the Bland-Altman method and by calculating Intraclass Correlation Coefficients.RESULTS: In total, 30 patients were included. Mean (SD) age was 63.0 (16.8) years and the majority of patients were men (n = 18). The mean percentage of time (SD) spent lying was 47.2 (23.3) and 49.7 (29.8); sitting 42.6 (20.5) and 40.0 (26.2); and active 10.2 (6.1) and 10.3 (8.3) according to the accelerometer and observations, respectively. The Intraclass Correlation Coefficient and mean difference (SD) between the two measures were 0.852 and -2.56 (19.33) for lying; 0.836 and 2.60 (17.72) for sitting; and 0.782 and -0.065 (6.23) for moving. The mean difference between the two measures is small (?2.6%) for all three physical activity levels. On patient level, the variation between both measures is large with differences above and below the mean of ?20% being common.CONCLUSION: The overall level of agreement between the behavioural mapping method and an accelerometer to identify the physical activity levels 'lying', 'sitting' and 'moving' of hospitalized patients is reasonable. | [
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BACKGROUND: Antibacterial peptidyl derivative - Cystapep 1, was previously found to be active both against antibiotic-resistant staphylococci and streptococci as well as antibioticsusceptible strains of these species. Therefore, it is a promising lead compound to search for new antimicrobial peptidomimetics.OBJECTIVES: We focused on identifying structural elements that are responsible for the biological activity of Cystapep 1 and its five analogues. We tried to find an answer to the question about the mechanism of action of the tested compounds. Therefore, we have investigated in details the possibility of interacting these compounds with biological membrane mimetics.METHODS: The subject compounds were synthesized in solution, purified and characterized by HPLC and mass spectrometry. Then, the staphylococci susceptibility tests were performed and their cytotoxicity was established. The results of Cystapep 1 and its analogues interactions with model target were examined using the DSC and ITC techniques. At the end the spatial structures of the tested peptidomimetics using NMR technique were obtained.RESULTS: Antimicrobial and cytotoxicity tests show that Cystapep 1 and its peptidomimetic V are good drug candidates. DSC and ITC studies indicate that disruption of membrane is not the only possible mechanism of action of Cystapep 1-like compounds. For Cystapep 1 itself, a multi-step mechanism of interaction with a negatively charged membrane is observed, which indicates other processes occurring alongside the binding process. The conformational analysis indicated the presence of a hydrophobic cluster, composed of certain side chains, only in the structures of active peptidomimetics. This can facilitate the anchoring of the peptidyl derivatives to the bacterial membrane.CONCLUSION: An increase in hydrophobicity of the peptidomimetics improved the antimicrobial activity against S. aureus, however there is no simple correlation between the biological activity and the strength of interactions of the peptidyl with bacterial membrane. | [
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] |
BACKGROUND & OBJECTIVE: New diaryl-substituted pyrimidinedione compounds, their thioxo derivatives as well as their bicyclic thiazole compounds were synthesized and characterized.METHODS: The glycosylamino derivatives of the synthesized disubstituted derivatives of the pyrimidine scaffold were also prepared via reaction of the N3-amino derivatives with a number of monosaccharides followed by acetylation.RESULTS: The anticancer activity of the synthesized compounds was studied against human liver cancer (HepG2) and RPE-1cell lines. Compounds 2a, 2b, 3a and 12 showed potent activities with IC50 results comparable to that of doxorubicin.CONCLUSION: Docking investigations into Cyclin-dependent kinase 2 (CDK-2) enzyme, a potential target for cancer medication, were also reported showing the possible binding interaction into the enzyme active site to support their activity behavior. | [
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BACKGROUND: Bis-heterocycles especially those containing pyrazole moiety display much better antibacterial activity than mono heterocycles.OBJECTIVE: Herein, we synthesised a series of new bis-pyrazoles and investigated their antimicrobial agents.METHODS: A novel series of bis-pyrazole derivatives have been synthesized in good yield by coupling reaction of cyanoacetic acid {4-[(2-cyano-acetyl)-hydrazonomethyl]-benzylidene}-hydrazide with a number of diazonium salts of aromatic amines in DMF in the presence of NaOH. Refluxing of the produced hydrazones with hydrazine-hydrate in ethanolic solution afforded the respective bis-pyrazoles. On the other hand, the reaction of bis(cyanoacetic acid hydrazide) derivative with a diversity of hydrazonoyl chlorides in dioxane under reflux gave bis-pyrazoles.RESULTS: The structures of all the products were discussed and assured from all possible spectral data as well as for the elemental analysis. In addition, the results of the antimicrobial activity examination of selected derivatives revealed a high strength of some tested compounds compared to standard bactericides and fungicides utilized. Molecular docking of the newly synthesized compounds into the Enoyl ACP reductase active site supported the in vitro antimicrobial activity. All the tested compounds could fit in the enzyme binding pocket with significant binding affinities (-7.040 to -9.141 Kcal/mol).CONCLUSION: The good results of the antimicrobial examination of the newly synthesized bis-pyrazoles comprise the considerable evidence of the importance of bis-heterocyclic compounds which encourages us to continue designing and synthesising a novel series with potent biological activity in the future. | [
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Over the past two decades, many researchers have concluded that a diet rich in polyphenolic compounds plays an important therapeutic role in reducing the risk of cancer, cardiovascular disease, inflammation, diabetes, and other degenerative diseases. Polyphenolic compounds have been reported to be involved in neutralization of reactive oxygen species and charged radicals, and have anticarcinogenic effects, hepatoprotective effects, low-glycaemic response, and other benefits. The benefits of fruits and vegetables may be partly attributable to polyphenolic compounds, which have antioxidant and free radical scavenging properties. Fruits such as apples contain a variety of phytochemicals, including (+)-catechin and (-)-epicatechin, phlorizin, phloretin quercetin, cyanidin-3-Ogalactoside, chlorogenic acid, and p-coumaric acid, all of which are strong antioxidants. Phloretin, a natural phenolic compound, is a dihydrochalcone, which is present in the apple. It exhibits a wide variety of activities such as antioxidative, anti-inflammatory, anti-microbial, anti-allergic, anticarcinogenic, anti-thrombotic, and hepatoprotective, besides being involved in the activation of apoptotic associated gene expression and signal transduction in molecular pathways. Despite a multitude of clinical studies, new efforts are needed in clinical research to determine the complete therapeutic potential of phloretin. | [
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] |
BACKGROUND: In this study, the essential oil composition and cytotoxic activities of five Artemisia species were determined.METHODS: The collected plants were water-distilled separately to obtain oils which were then subjected to gas chromatography (GC) and gas chromatography/mass spectrometry GC/MS analyses to identify their compositions. Cancer cells were exposed to different concentrations of samples and cell viability was measured using AlamarBlue assay. Apoptotic cells were analyzed by propidium iodide (PI) staining and flow cytometry.RESULTS & CONCLUSION: To study the amount of pro-apoptotic proteins and the apoptosis mechanism, Western blot method was used. Although all samples were cytotoxic at the highest concentration, the oil of A. kulbadica showed the strongest activity among other plants. Carvacrol (IC50 21.11 g/ml) had the most cytotoxic effects among other components. Carvacrol, 1,8-cineole and 4-terpineole caused an increase in the amount of Bax protein and cleaved peroxisome proliferator-activated receptors (PPAR) and caspase proteins in DU 145 cells. | [
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] |
OBJECTIVE: Sleep is unequally distributed in the US population. People with low socioeconomic status report worse quality and shorter sleep than people with high socioeconomic status. Past research hypothesized that a potential reason for this link could be exposure to material hardship. This study examines the associations between several material hardships and sleep outcomes.METHODS: We use population-representative cross-sectional data (n = 730) from the Michigan Recession and Recovery Study collected in 2013 and examine the associations between 6 indicators of material hardship (employment instability, financial problems, housing instability, food insecurity, forgone medical care, and the total number of material hardships reported) and 3 sleep outcomes (short sleep, sleep problems, and nonrestorative sleep). We build multivariable logistic regression models controlling for respondents' characteristics and light pollution near their residence.RESULTS: In unadjusted models, all material hardships were associated with negative sleep outcomes. In adjusted models, forgone medical care was a statistically significant predictor of nonrestorative sleep (average marginal effect 0.16), as was employment instability (average marginal effect 0.12). The probability of sleep problems and nonrestorative sleep increased with a greater number of hardships overall (average marginal effects of .02 and .05, respectively). We found marginally statistically significant positive associations between food insecurity and short sleep and sleep problems.CONCLUSIONS: This study finds that, except when considering foregone medical care, employment instability, and total count of material hardships, associations between material hardship and negative sleep outcomes are not statistically significant after adjusting for a robust set of sociodemographic and health characteristics. | [
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] |
BACKGROUND: All-trans retinoic acid (ATRA) potentiates TGF--dependent regulatory T cells (Treg) induction, while it inhibits pro-inflammatory interleukin-17-producing T helper cells (Th17) differentiation. Combined application of ATRA and TGF- may shift Treg-Th17 balance towards Treg.OBJECTIVE: To investigates the effect of ATRA on the regulation of Th17-Treg balance through ERK and p38 signaling pathway.METHODS: Mice naive CD4+T cells were isolated and co-cultured with 100 nmol/ml ATRA and 5 ng/ml TGF-. The effect of ATRA on the phosphorylation of ERK and P38 was evaluated. The induction of Treg and Th17 was investigated before and after the application of the inhibitor of ERK and P38.RESULTS: The expression of p-ERK1 and p-ERK2 increased significantly when the cells were incubated for 3 days with both TGF- and ATRA. The upregulated expression of p38 was found after incubation for 1 day. The inhibition of ERK prohibited Treg induction and promoted Th17 development. However, the inhibition of p38 only had inhibitory effect on Treg induction.CONCLUSIONS: ERK and p38 pathways participated in ATRA-activated Treg-Th17 balance adjustment. | [
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BACKGROUND: Stimulated dendritic cells (DCs) have been shown to be effective in the induction of specific immune cells. Also, the CMV pp65 plays an important role in CMV life cycle and immune recognition.OBJECTIVE: To assess the effect of CMV pp65 on the maturity and function of dendritic cells.METHODS: Splenic DCs were treated with non-cytotoxic concentrations of the pp65 and analyzed for MHC II, CD86, and CD40 expression by flow cytometry. Then, ROR-, GATA3, T-bet, and FOXP3 gene expression levels were evaluated in T cells co-cultured with DCs using Real time-PCR. Finally, the effects of pp65 on allogenic T-cell responses in mixed lymphocyte culture (MLR), and the release of cytokines were investigated by ELISA and flow cytometry.RESULTS: The phagocytosis rate was significantly lower in the pp65-treated DCs than the non-stimulated DCs. There were significant differences in the raised level of CD40, CD86, and CCR7 in DCs as maturation markers. Furthermore, ROR-, and T-bet overexpression in T cells of the pp65-treated group compared with the non-stimulated group was observed. Significant differences were observed in the levels of IL-2, IL-6, IL-17, IL-22, TNF-, and IFN- in pp65-stimulated groups compared with the non-stimulated DCs.CONCLUSIONS: The pp65-treated DCs can induce differentiation and functional activity of the cellular immune system, including Th17, and Th1, but not other major T-cell subsets such as Tregs, and Th2 population. | [
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BACKGROUND: We have recently produced an inhibitory mouse anti-human HER2 mAb (2A8) which displayed potent anti-tumor activity in combination with trastuzumab.OBJECTIVE: To describe chimerization and functional characterization of 2A8 mAb.METHODS: The VH and VL genes of 2A8 mAb were amplified from cDNA of the mouse hybridoma, ligated to constant regions of human immunoglobulin, and expressed in CHO cell line. Reactivity with four members of human HER family, the inhibitory effects and antibody-dependent cell cytotoxicity (ADCC) of purified chimeric mAb (c2A8) were assessed by ELISA, XTT, H3-tymidine incorporation and lactate dehydrogenase assays. Inhibition of ERK and AKT downstream signaling pathways by the chimeric antibody were analyzed by Western blotting.RESULTS: Chimeric 2A8 mAb bound to recombinant human HER2 and did not cross-react with the other members of HER family. Moreover, c2A8 was able to recognize HER2-overexpressing cancer cell line and inhibited growth and proliferation of these cells. The binding affinity of c2A8 was comparable to the mouse parental mAb. ADCC and Western blotting results showed that the mouse 2A8 mAb was successfully chimerized and could significantly inhibit phosphorylation of AKT in combination with trastuzumab.CONCLUSION: The c2A8 mAb is potentially a valuable tool for targeted immunotherapy of HER2 positive cancers. | [
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BACKGROUND: Members of B7 family are reported to regulate lymphocytes activation, transmit both costimulatory and co-inhibitory signals, control T cell-mediated immune responses and tolerance. Among which B7-H4 is reported to regulate the immune response negatively.OBJECTIVE: To investigate the plasma concentration of soluble B7-H4 (sB7-H4) and its clinical significance in systemic lupus erythematosus (SLE).METHODS: Fifty-six SLE patients with or without active SLE (ASLE) and 29 age- and gender-matched healthy volunteers were recruited. Plasma concentration of sB7-H4 was measured using sandwich ELISA kits.RESULTS: Compared with healthy subjects, the concentration of sB7-H4 was significantly higher in patients with SLE (p=0.006). Plasma sB7-H4 concentration in patients with lupus nephritis (LN) were also significantly higher than healthy subjects (p=0.008), but no difference was found between LN and SLE patients without LN (non-LN). Additionally, the sB7-H4 concentration in patients was negatively correlated with the SLE disease activity index score (SLEDAI) (r=-0.3055, p=0.022). Compared with inactive disease, the concentration of sB7-H4 in ASLE patients was significantly lower (p=0.002). There were statistical significances between the positive and negative groups with decreased leukocytes or thrombocytes (p=0.012; p=0.033; respectively), but no statistically significant difference was found in other positive and negative serum laboratory indicators.CONCLUSIONS: The increased level of sB7-H4 in patients suggests that this pathway might be involved in the pathogenesis of SLE. However, the exact mechanism or physiological role of sB7-H4 in SLE pathogenesis remains to be investigated. | [
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BACKGROUND: Interleukin 17 (IL-17) is a pro-inflammatory cytokine that plays an important role in cancer pathogenesis.OBJECTIVE: To investigate the association of two IL-17 gene polymorphisms (rs2275913 and rs763780), as well as IL-17 serum levels with susceptibility to Basal Cell Carcinoma (BCC) of skin.METHODS: Two hundred subjects with BCC and 200 healthy controls were recruited. DNA was extracted from peripheral blood leukocytes and genotypes were determined using PCR-RFLP methods. Serum levels were assessed by ELISA.RESULTS: At position rs2275913 in IL-17A, the frequencies of GG, AG and AA genotypes were 99 (49.5%), 76 (38%) and 25 (12.5%) in patients and 97 (48.5%), 84 (42%) and 19 (9.5%) in the control group. The distribution of AA, GA and GG genotypes at position rs763780 in IL-17F were 166 (83%), 34 (17%) and 0 (0%) in patients and 158 (79%), 40 (20%) and 2 (1%) in the control group. Haplotype analysis by Arlequin software package revealed that GA haplotype was the most frequent haplotype in both groups. No significant differences were found in alleles, genotypes, and haplotypes frequencies between study groups at both positions (P>0.05). While no difference in IL-17 serum levels was observed between individuals with different genotypes, statistical analysis showed higher IL-17A serum levels, but not IL-17F, in patients compared to controls (0.65 0.11 and 0.03 0.02 pg/ml), respectively, (P<0.001).CONCLUSION: Our findings do not support the association of rs763780 and rs2275913 gene polymorphisms in IL-17gene with susceptibility of Iranians with BCC. Increased IL-17A serum levels may still play a role in pathogenesis of BCC. | [
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BACKGROUND: Ulcerative colitis (UC) and Crohn's disease (CD) are the two forms of inflammatory bowel disease (IBD). Adaptive immune responses involving helper T cells play an important role in developing IBDs. Programmed death (PD)-1 and its ligands namely PD-L1 and PD-L2 are negative costimulatory molecules that control T cell motility and formation of an immune synapse between T cells and antigen-presenting cells (APCs).OBJECTIVE: To investigate the role of PD-L1 and PD-L2 in patients with UC to clarify the mechanism of IBD development.METHODS: Biopsy specimens were obtained from 50 UC patients and 45 sex- and age-matched control subjects. Total RNA was extracted from all samples and applied for cDNA synthesis. Relative expression of PD-L1 and PD-L2 mRNA was determined using Taqman qRT-PCR.RESULTS: Relative gene expression levels of both PD-L1 and PD-L2 were higher in UC patients than the control groups (p<0.05 and p<0.01, respectively). Furthermore, both PD-L1 and PD-L2 expressions were positively correlated in all study subjects (r=0.339, p<0.001). However, among the groups with disease severity, the relative gene expression levels of PD-L1 and PD-L2 showed no significant difference.CONCLUSIONS: During IBD, the occurrence of PD-L1 and PD-L2 up-regulation may modulate the chronic inflammation of colonic mucosa. | [
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