bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Paecilomyces tenuipes Extract on Testosterone-Induced Benign Prostatic Hyperplasia in Sprague–Dawley Rats
Authors: Choi Young-Jin , Kim Eun-Kyung , Fan Meiqi , Tang Yujiao , Hwang Young Joung , Sung Si-Heung
Published: October 2019

Benign prostatic hyperplasia (BPH) is one of the major public health concerns, which has a high prevalence rate and causes significant decline in men’s quality of life. BPH is highly related to sexual hormone metabolism and aging. In particular, dihydrotestosterone (DHT), to which testosterone is modified by 5α-reductase (5AR), has a significant effect on BPH development. DHT binds to an androgen receptor (AR) and steroid receptor coactivator 1 (SRC-1); then, it induces the proliferation of a prostate cell and expression of prostate specific antigen (PSA). Paecilomyces tenuipes (P. tenuipes) is a mushroom that has been popularized by the artificial cultivation of fruiting bodies based on silkworms by researchers from the Republic of Korea. In a previous study, we identified the effect of PE on PSA mRNA expression in LNCaP cells. This suggests that PE may have an inhibitory effect on androgen signaling. Therefore, we confirmed the expression of androgen signaling-related factors, such as AR, SRC-1, and PSA in LNCaP. Furthermore, we confirmed the androgen signaling inhibitory effect of PE using the testosterone propionate (TP)-induced BPH rat model. A BPH rat model was established with a four-week treatment of daily subcutaneous injections of testosterone propionate (TP, 3 mg/kg) dissolved in corn oil after castration. The rats in the treatment group were orally gavaged P. tenuipes extract (PE), finasteride (Fi), or saw palmetto extract (Saw) with TP injection. DHT induced an increase in the expression levels of AR, SRC-1, and PSA proteins in LNCaP cells. On the contrary, the PE treatment reduced the expression levels. In vivo, the BPH group showed an increase in prostate size compared with the control group. The PE gavaged group showed a decrease in prostate size compared with the BPH group. In addition, the protein expressions of AR, 5AR2, and PSA were significantly lower in the PE gavaged group than BPH group in prostate tissue. These results suggest the beneficial effects of PE on BPH via the modulation of AR signaling pathway.
Long-Term Monitoring of Extremely Low Frequency Magnetic Fields in Electric Vehicles
Authors: Yang Lei , Lu Meng , Lin Jun , Li Congsheng , Zhang Chen , Lai Zhijing , Wu Tongning
Published: October 2019

Extremely low frequency (ELF) magnetic field (MF) exposure in electric vehicles (EVs) has raised public concern for human health. There have been many studies evaluating magnetic field values in these vehicles. However, there has been no report on the temporal variation of the magnetic field in the cabin. This is the first study on the long-term monitoring of actual MFs in EVs. In the study, we measured the magnetic flux density (B) in three shared vehicles over a period of two years. The measurements were performed at the front and rear seats during acceleration and constant-speed driving modes. We found that the B amplitudes and the spectral components could be modified by replacing the components and the hubs, while regular checks or maintenance did not influence the B values in the vehicle. This observation highlights the necessity of regularly monitoring ELF MF in EVs, especially after major repairs or accidents, to protect car users from potentially excessive ELF MF exposure. These results should be considered in updates of the measurement standards. The ELF MF effect should also be taken into consideration in relevant epidemiological studies.
Exposure to Ambient Air Pollution and Cognitive Impairment in Community-Dwelling Older Adults: The Korean Frailty and Aging Cohort Study
Authors: Shin Jinyoung , Han Seol-Heui , Choi Jaekyung
Published: October 2019

The aim of this study was to investigate the associations between ambient air pollutants and cognitive impairment in Korean older adults. The cognitive function of 2,896 participants aged 70 to 84 years was measured using the Korean version of the mini-mental state examination, the digit span test, the word list learning test, and the frontal assessment battery. After matching the average concentrations of particulate matter (PM) <10 μm in size (PM10) and <2.5 μm (PM2.5), NO2, CO, SO2, and O3 between 2013 and 2017, the association between air pollutants and cognitive scales was analyzed using a linear mixed regression and a multiple logistic regression analysis (after adjusting for age, sex, health related behaviors, socioeconomic status, comorbidity, and meteorological data). Exposure to PM2.5, PM10, NO2, SO2, and CO was associated with cognitive impairment above and beyond age or education level effects. Specifically, PM2.5 was negatively associated with most components of the cognitive scales (interquartile range for PM2.5: 2.0 μg/m3, odds ratio for poor global cognition: 2.28, 95% confidence interval: 1.60–3.26). These associations may be affected by sex, residence area, or alcohol intake. Conclusively, air pollutants, especially PM2.5, were associated with cognitive impairment, including global cognition, attention, memory, and executive function in Korean older adults aged ≥70 years.
Does Income Inequality Explain the Geography of Residential Burglaries? The Case of Belo Horizonte, Brazil
Authors: Ramos Rafael G.
Published: October 2019

The relationship between crime and income inequality is a complex and controversial issue. While there is some consensus that a relationship exists, the nature of it is still the subject of much debate. In this paper, this relationship is investigated in the context of urban geography and whether income inequality can explain the geography of crime within cities. This question is examined for the specific case of residential burglaries in the city of Belo Horizonte, Brazil, where I tested how much burglary rates are affected by local average household income and by local exposure to poverty, while I controlled for other variables relevant to criminological theory, such as land-use type, density and accessibility. Different scales were considered for testing the effect of exposure to poverty. This study reveals that, in Belo Horizonte, the rate of burglaries per single family house is significantly and positively related to income level, but a higher exposure to poverty has no significant independent effect on these rates at any scale tested. The rate of burglaries per apartment, on the other hand, is not significantly affected by either average household income or exposure to poverty. These results seem consistent with a description where burglaries follow a geographical distribution based on opportunity, rather than being a product of localized income disparity and higher exposure between different economic groups.
From Osteoclast Differentiation to Osteonecrosis of the Jaw: Molecular and Clinical Insights
Authors: Anesi Alexandre , Generali Luigi , Sandoni Laura , Pozzi Samantha , Grande Alexis
Published: October 2019

Bone physiology relies on the delicate balance between resorption and formation of its tissue. Bone resorption depends on a process called osteoclastogenesis in which bone-resorbing cells, i.e., osteoclasts, are produced by the differentiation of more undifferentiated progenitors and precursors. This process is governed by two main factors, monocyte-colony stimulating factor (M-CSF) and receptor activator of NFκB ligand (RANKL). While the former exerts a proliferating effect on progenitors/precursors, the latter triggers a differentiation effect on more mature cells of the same lineage. Bone homeostasis requires a perfect space–time coordination of the involved signals. When osteoclastogenesis is poorly balanced with the differentiation of the bone forming counterparts, i.e., osteoblasts, physiological bone remodelling can turn into a pathological state, causing the systematic disruption of bone tissue which results in osteopenia or osteolysis. Examples of these conditions are represented by osteoporosis, Paget’s disease, bone metastasis, and multiple myeloma. Therefore, drugs targeting osteoclastogenesis, such as bisphosphonates and an anti-RANKL monoclonal antibody, have been developed and are currently used in the treatment of such diseases. Despite their demonstrated therapeutic efficacy, these agents are unfortunately not devoid of side effects. In this regard, a condition called osteonecrosis of the jaw (ONJ) has been recently correlated with anti-resorptive therapy. In this review we will address the involvement of osteoclasts and osteoclast-related factors in the pathogenesis of ONJ. It is to be hoped that a better understanding of the biological mechanisms underlying bone remodelling will help in the design a medical therapeutic approach for ONJ as an alternative to surgical procedures.
Metabolomic Perspectives in Antiblastic Cardiotoxicity and Cardioprotection
Authors: Deidda Martino , Mercurio Valentina , Cuomo Alessandra , Noto Antonio , Mercuro Giuseppe , Cadeddu Dessalvi Christian
Published: October 2019

Despite advances in supportive and protective therapy for myocardial function, cardiovascular diseases due to antineoplastic therapy—primarily cardiomyopathy associated with contractile dysfunction—remain a major cause of morbidity and mortality. Because of the limitations associated with current therapies, investigators are searching for alternative strategies that can timely recognise cardiovascular damage—thus permitting a quick therapeutic approach—or prevent the development of the disease. Damage to the heart can result from both traditional chemotherapeutic agents, such as anthracyclines, and new targeted therapies, such as tyrosine kinase inhibitors. In recent years, metabolomics has proved to be a practical tool to highlight fundamental changes in the metabolic state in several pathological conditions. In this article, we present the state-of-the-art technology with regard to the metabolic mechanisms underlying cardiotoxicity and cardioprotection.
Pyruvate Substitutions on Glycoconjugates
Authors: Hager Fiona F. , Sützl Leander , Stefanović Cordula , Blaukopf Markus , Schäffer Christina
Published: October 2019

Glycoconjugates are the most diverse biomolecules of life. Mostly located at the cell surface, they translate into cell-specific “barcodes” and offer a vast repertoire of functions, including support of cellular physiology, lifestyle, and pathogenicity. Functions can be fine-tuned by non-carbohydrate modifications on the constituting monosaccharides. Among these modifications is pyruvylation, which is present either in enol or ketal form. The most commonly best-understood example of pyruvylation is enol-pyruvylation of N-acetylglucosamine, which occurs at an early stage in the biosynthesis of the bacterial cell wall component peptidoglycan. Ketal-pyruvylation, in contrast, is present in diverse classes of glycoconjugates, from bacteria to algae to yeast—but not in humans. Mild purification strategies preventing the loss of the acid-labile ketal-pyruvyl group have led to a collection of elucidated pyruvylated glycan structures. However, knowledge of involved pyruvyltransferases creating a ring structure on various monosaccharides is scarce, mainly due to the lack of knowledge of fingerprint motifs of these enzymes and the unavailability of genome sequences of the organisms undergoing pyruvylation. This review compiles the current information on the widespread but under-investigated ketal-pyruvylation of monosaccharides, starting with different classes of pyruvylated glycoconjugates and associated functions, leading to pyruvyltransferases, their specificity and sequence space, and insight into pyruvate analytics.
KRIT1 Deficiency Promotes Aortic Endothelial Dysfunction
Authors: Vieceli Dalla Sega Francesco , Mastrocola Raffaella , Aquila Giorgio , Fortini Francesca , Fornelli Claudia , Zotta Alessia , Cento Alessia S. , Perrelli Andrea , Boda Enrica , Pannuti Antonio , Marchi Saverio , Pinton Paolo , Ferrari Roberto , Rizzo Paola , Retta Saverio Francesco
Published: October 2019

Loss-of-function mutations of the gene encoding Krev interaction trapped protein 1 (KRIT1) are associated with the pathogenesis of Cerebral Cavernous Malformation (CCM), a major cerebrovascular disease characterized by abnormally enlarged and leaky capillaries and affecting 0.5% of the human population. However, growing evidence demonstrates that KRIT1 is implicated in the modulation of major redox-sensitive signaling pathways and mechanisms involved in adaptive responses to oxidative stress and inflammation, suggesting that its loss-of-function mutations may have pathological effects not limited to CCM disease. The aim of this study was to address whether KRIT1 loss-of-function predisposes to the development of pathological conditions associated with enhanced endothelial cell susceptibility to oxidative stress and inflammation, such as arterial endothelial dysfunction (ED) and atherosclerosis. Silencing of KRIT1 in human aortic endothelial cells (HAECs), coronary artery endothelial cells (HCAECs), and umbilical vein endothelial cells (HUVECs) resulted in increased expression of endothelial proinflammatory adhesion molecules vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1) and in enhanced susceptibility to tumor necrosis factor alpha (TNF-α)-induced apoptosis. These effects were associated with a downregulation of Notch1 activation that could be rescued by antioxidant treatment, suggesting that they are consequent to altered intracellular redox homeostasis induced by KRIT1 loss-of-function. Furthermore, analysis of the aorta of heterozygous KRIT1+/− mice fed a high-fructose diet to induce systemic oxidative stress and inflammation demonstrated a 1.6-fold increased expression of VCAM-1 and an approximately 2-fold enhanced fat accumulation (7.5% vs 3.6%) in atherosclerosis-prone regions, including the aortic arch and aortic root, as compared to corresponding wild-type littermates. In conclusion, we found that KRIT1 deficiency promotes ED, suggesting that, besides CCM, KRIT1 may be implicated in genetic susceptibility to the development of atherosclerotic lesions.
Cloning, Expression and Effects of P. americana Thymosin on Wound Healing
Authors: Jing Jie , Sun Xiaohong , Zhou Chuang , Zhang Yifan , Shen Yongmei , Zeng Xiaomao , Yue Bisong , Zhang Xiuyue
Published: October 2019

The American cockroach (Periplaneta americana) is a medicinal insect. Its extract is used clinically to promote wound healing and tissue regeneration, but the effective medicinal components and mechanisms are not yet clear. It has been reported that human thymosin beta 4 (Tβ4) may accelerate skin wound healing, however, the role of P. americana thymosin (Pa-THYs) is still poorly understood. In the present study, we identify and analyze the DNA sequences of Pa-THYs by bioinformatics analysis. Then we clone, express, and purify the Pa-THYs proteins and evaluate the activity of recombinant Pa-THYs proteins by cell migration and proliferation assays in NIH/3T3 cells. To elucidate the role of Pa-THYs in wound healing, a mouse model is established, and we evaluate wound contraction, histopathological parameters, and the expressions of several key growth factors after Pa-THYs treatment. Our results showed that three THY variants were formed by skipping splicing of exons. Pa-THYs could promote fibroblast migration, but have no effect on fibroblast proliferation. In wound repair, Pa-THYs proteins could effectively promote wound healing through stimulating dermal tissue regeneration, angiogenesis, and collagen deposition. On the molecular mechanism, Pa-THYs also stimulated the expression of several key growth factors to promote wound healing. The data suggest that Pa-THYs could be a potential drug for promoting wound repair.
Low-Energy Extracorporeal Shock Wave Ameliorates Streptozotocin Induced Diabetes and Promotes Pancreatic Beta Cells Regeneration in a Rat Model
Authors: Hsiao Chang-Chun , Lin Cheng-Chan , Hou You-Syuan , Ko Jih-Yang , Wang Ching-Jen
Published: October 2019

Traditional therapy for diabetes mellitus has focused on supportive treatment, and is not significant in the promotion of pancreatic beta cells regeneration. We investigated the effect of low- energy extracorporeal shock wave (SW) on a streptozotocin induced diabetes (DM) rat model. Methods: The DM rats were treated with ten sessions of low-energy SW therapy (weekly for ten consecutive weeks) or left untreated. We assessed blood glucose, hemoglobin A1c (HbA1c), urine volume, pancreatic islets area, c-peptide, glucagon-like peptide 1 (GLP-1) and insulin production, beta cells number, pancreatic tissue inflammation, oxidative stress, apoptosis, angiogenesis, and stromal cell derived factor 1 (SDF-1) ten weeks after the completion of treatment. Results: The ten- week low-energy SW therapy regimen significantly reduced blood glucose, HbA1c, and urine volume as well as significantly enhancing pancreatic islets area, c-peptide, GLP-1, and insulin production in the rat model of DM. Moreover, low-energy SW therapy increased the beta cells number in DM rats. This was likely primarily attributed to the fact that low-energy SW therapy reduced pancreatic tissue inflammation, apoptosis, and oxidative stress as well as increasing angiogenesis, cell proliferation, and tissue repair potency. Conclusions: Low-energy SW therapy preserved pancreatic islets function in streptozotocin-induced DM. Low-energy SW therapy may serve as a novel noninvasive and effective treatment of DM.
Possible Phenotypic Consequences of Structural Differences in Idic(15) in a Small Cohort of Patients
Authors: Czakó Márta , Till Ágnes , Szabó András , Ripszám Réka , Melegh Béla , Hadzsiev Kinga
Published: October 2019

Among human supernumerary marker chromosomes, the occurrence of isodicentric form of 15 origin is relatively well known due to its high frequency, both in terms of gene content and associated clinical symptoms. The associated epilepsy and autism are typically more severe than in cases with interstitial 15q duplication, despite copy number gain of approximately the same genomic region. Other mechanisms besides segmental aneuploidy and epigenetic changes may also cause this difference. Among the factors influencing the expression of members of the GABAA gene cluster, the imprinting effect and copy number differences has been debated. Limited numbers of studies investigate factors influencing the interaction of GABAA cluster homologues. Five isodicentric (15) patients are reported with heterogeneous symptoms, and structural differences of their isodicentric chromosomes based on array comparative genomic hybridization results. Relations between the structure and the heterogeneous clinical picture are discussed, raising the possibility that the structure of the isodicentric (15), which has an asymmetric breakpoint and consequently a lower copy number segment, would be the basis of the imbalance of the GABAA homologues. Studies of trans interaction and regulation of GABAA cluster homologues are needed to resolve this issue, considering copy number differences within the isodicentric chromosome 15.
Ginsenoside Rb1 Attenuates High Glucose-Induced Oxidative Injury via the NAD-PARP-SIRT Axis in Rat Retinal Capillary Endothelial Cells
Authors: Fan Chunlan , Ma Qing , Xu Meng , Qiao Yuan , Zhang Yi , Li Pin , Bi Yucong , Tang Minke
Published: October 2019

(1) Aims: The present study aimed to observe the effects of Ginsenoside Rb1 on high glucose-induced endothelial damage in rat retinal capillary endothelial cells (RCECs) and to investigate the underlying mechanism. (2) Methods: Cultured RCECs were treated with normal glucose (5.5 mM), high glucose (30 mM glucose), or high glucose plus Rb1 (20 μM). Cell viability, lactate dehydrogenase (LDH) levels, the mitochondrial DNA copy number, and the intracellular ROS content were measured to evaluate the cytotoxicity. Superoxide dismutase (SOD), catalase (CAT), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX), poly(ADP-ribose) polymerase (PARP), and sirtuin (SIRT) activity was studied in cell extracts. Nicotinamide adenine dinucleotide (NAD+)/NADH, NADPH/NADP+, and glutathione (GSH)/GSSG levels were measured to evaluate the redox state. The expression of nicotinamide mononucleotide adenylyltransferase 1 (NMNAT1), SIRT1, and SIRT3 was also evaluated after Rb1 treatment. (3) Results: Treatment with Rb1 significantly increased the cell viability and mtDNA copy number, and inhibited ROS generation. Rb1 treatment increased the activity of SOD and CAT and reduced the activity of NOX and PARP. Moreover, Rb1 enhanced both SIRT activity and SIRT1/SIRT3 expression. Additionally, Rb1 was able to re-establish the cellular redox balance in RCECs. However, Rb1 showed no effect on NMNAT1 expression in RCECs exposed to high glucose. (4) Conclusion: Under high glucose conditions, decreases in the reducing power may be linked to DNA oxidative damage and apoptosis via activation of the NMNAT-NAD-PARP-SIRT axis. Rb1 provides an advantage during high glucose-induced cell damage by targeting the NAD-PARP-SIRT signaling pathway and modulating the redox state in RCECs.
A2A Receptor Homodimer-Disrupting Sequence Efficiently Delivered by a Protease-Resistant, Cyclic CPP Vector
Authors: Gallo Maria , Navarro Gemma , Franco Rafael , Andreu David
Published: October 2019

G-protein-coupled receptors associate into dimers/oligomers whose function is not well understood. One approach to investigate this issue is to challenge oligomerization by peptides replicating transmembrane domains and to study their effect on receptor functionality. The disruptor peptides are typically delivered by means of cell-penetrating vectors such as the human immunodeficiency virus (HIV) transcription trans-activation protein Tat. In this paper we report a cyclic, Tat-like peptide that significantly improves its linear analogue in targeting interreceptor sequences in the transmembrane space. The same cyclic Tat-like vector fused to a transmembrane region not involved in receptor oligomerization was totally ineffective. Besides higher efficacy, the cyclic version has enhanced proteolytic stability, as shown by trypsin digestion experiments.
An Improved Prediction Model for Ovarian Cancer Using Urinary Biomarkers and a Novel Validation Strategy
Authors: Lee Shin-Wha , Lee Ha-Young , Bang Hyo Joo , Song Hye-Jeong , Kong Sek Won , Kim Yong-Man
Published: October 2019

This study was designed to analyze urinary proteins associated with ovarian cancer (OC) and investigate the potential urinary biomarker panel to predict malignancy in women with pelvic masses. We analyzed 23 biomarkers in urine samples obtained from 295 patients with pelvic masses scheduled for surgery. The concentration of urinary biomarkers was quantitatively assessed by the xMAP bead-based multiplexed immunoassay. To identify the performance of each biomarker in predicting cancer over benign tumors, we used a repeated leave-group-out cross-validation strategy. The prediction models using multimarkers were evaluated to develop a urinary ovarian cancer panel. After the exclusion of 12 borderline tumors, the urinary concentration of 17 biomarkers exhibited significant differences between 158 OCs and 125 benign tumors. Human epididymis protein 4 (HE4), vascular cell adhesion molecule (VCAM), and transthyretin (TTR) were the top three biomarkers representing a higher concentration in OC. HE4 demonstrated the highest performance in all samples withOC(mean area under the receiver operating characteristic curve (AUC) 0.822, 95% CI: 0.772–0.869), whereas TTR showed the highest efficacy in early-stage OC (AUC 0.789, 95% CI: 0.714–0.856). Overall, HE4 was the most informative biomarker, followed by creatinine, carcinoembryonic antigen (CEA), neural cell adhesion molecule (NCAM), and TTR using the least absolute shrinkage and selection operator (LASSO) regression models. A multimarker panel consisting of HE4, creatinine, CEA, and TTR presented the best performance with 93.7% sensitivity (SN) at 70.6% specificity (SP) to predict OC over the benign tumor. This panel performed well regardless of disease status and demonstrated an improved performance by including menopausal status. In conclusion, the urinary biomarker panel with HE4, creatinine, CEA, and TTR provided promising efficacy in predicting OC over benign tumors in women with pelvic masses. It was also a non-invasive and easily available diagnostic tool.
The Regulatory Role of MicroRNAs in Breast Cancer
Authors: Loh Hui-Yi , Norman Brendan P. , Lai Kok-Song , Rahman Nik Mohd Afizan Nik Abd. , Alitheen Noorjahan Banu Mohamed , Osman Mohd Azuraidi
Published: October 2019

MicroRNAs (miRNAs) are small non-coding RNA molecules which function as critical post-transcriptional gene regulators of various biological functions. Generally, miRNAs negatively regulate gene expression by binding to their selective messenger RNAs (mRNAs), thereby leading to either mRNA degradation or translational repression, depending on the degree of complementarity with target mRNA sequences. Aberrant expression of these miRNAs has been linked etiologically with various human diseases including breast cancer. Different cellular pathways of breast cancer development such as cell proliferation, apoptotic response, metastasis, cancer recurrence and chemoresistance are regulated by either the oncogenic miRNA (oncomiR) or tumor suppressor miRNA (tsmiR). In this review, we highlight the current state of research into miRNA involved in breast cancer, with particular attention to articles published between the years 2000 to 2019, using detailed searches of the databases PubMed, Google Scholar, and Scopus. The post-transcriptional gene regulatory roles of various dysregulated miRNAs in breast cancer and their potential as therapeutic targets are also discussed.
Cyclin D1 is Associated with Radiosensitivity of Triple-Negative Breast Cancer Cells to Proton Beam Irradiation
Authors: Choi Changhoon , Park Sohee , Cho Won Kyung , Choi Doo Ho
Published: October 2019

Proton therapy offers a distinct physical advantage over conventional X-ray therapy, but its biological advantages remain understudied. In this study, we aimed to identify genetic factors that contribute to proton sensitivity in breast cancer (BC). Therefore, we screened relative biological effectiveness (RBE) of 230 MeV protons, compared to 6 MV X-rays, in ten human BC cell lines, including five triple-negative breast cancer (TNBC) cell lines. Clonogenic survival assays revealed a wide range of proton RBE across the BC cell lines, with one out of ten BC cell lines having an RBE significantly different from the traditional generic RBE of 1.1. An abundance of cyclin D1 was associated with proton RBE. Downregulation of RB1 by siRNA or a CDK4/6 inhibitor increased proton sensitivity but not proton RBE. Instead, the depletion of cyclin D1 increased proton RBE in two TNBC cell lines, including MDA-MB-231 and Hs578T cells. Conversely, overexpression of cyclin D1 decreased the proton RBE in cyclin D1-deficient BT-549 cells. The depletion of cyclin D1 impaired proton-induced RAD51 foci formation in MDA-MB-231 cells. Taken together, this study provides important clues about the cyclin D1-CDK4-RB1 pathway as a potential target for proton beam therapy in TNBC.
The Neuropeptide Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) Is Protective in Inflammation and Oxidative Stress-Induced Damage in the Kidney
Authors: Horvath Gabriella , Opper Balazs , Reglodi Dora
Published: October 2019

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a pleiotropic neuropeptide with a widespread distribution throughout the entire body including the urinary system. PACAP exerts protective actions in different injury models related to several organ systems. Its protective effect is mainly based on its antiapoptotic, anti-inflammatory and antioxidant effects. The present review aims to summarize the effects of PACAP in pathologies associated with inflammation and oxidative stress-induced damage in the kidney. Both in vitro and in vivo data are available proving its protective actions against oxidative stress, hypoxia, renal ischemia/reperfusion, diabetic nephropathy, myeloma kidney injury, amyloidosis and different types of drug-induced nephropathies. Data showing the nephroprotection by PACAP emphasize the potential of PACAP’s therapeutic use in various renal pathologies.
Sirtuins and SIRT6 in Carcinogenesis and in Diet
Authors: de Céu Teixeira Maria , Sanchez-Lopez Elena , Espina Marta , Garcia Maria Luisa , Durazzo Alessandra , Lucarini Massimo , Novellino Ettore , Souto Selma B. , Santini Antonello , Souto Eliana B.
Published: October 2019

Sirtuins are a highly conserved family of nicotinamide adenine dinucleotide (NAD)-dependent protein lysine modifying enzymes. They are key regulators for a wide variety of cellular and physiological processes such as cell proliferation, differentiation, DNA damage and stress response, genome stability, cell survival, metabolism, energy homeostasis, organ development and aging. Aging is one of the major risk factors of cancer, as many of the physiological mechanisms and pathologies associated with the aging process also contribute to tumor initiation, growth and/or metastasis. This review focuses on one the mammalian sirtuins, SIRT6, which has emerged as an important regulator of longevity and appears to have multiple biochemical functions that interfere with tumor development and may be useful in cancer prevention and for site-specific treatment. The recent evidence of the role of SIRT6 in carcinogenesis is also discussed, focusing on the potential use of SIRT6 modulators in cancer nanomedicine.
Transgelin, a p53 and PTEN-Upregulated Gene, Inhibits the Cell Proliferation and Invasion of Human Bladder Carcinoma Cells In Vitro and In Vivo
Authors: Tsui Ke-Hung , Lin Yu-Hsiang , Chang Kang-Shuo , Hou Chen-Pang , Chen Pin-Jung , Feng Tsui-Hsia , Juang Horng-Heng
Published: October 2019

Transgelin (TAGLN/SM22-α) is a regulator of the actin cytoskeleton, affecting the survival, migration, and apoptosis of various cancer cells divergently; however, the roles of TAGLN in bladder carcinoma cells remain inconclusive. We compared expressions of TAGLN in human bladder carcinoma cells to the normal human bladder tissues to determine the potential biological functions and regulatory mechanisms of TAGLN in bladder carcinoma cells. Results of RT-qPCR and immunoblot assays indicated that TAGLN expressions were higher in bladder smooth muscle cells, fibroblast cells, and normal epithelial cells than in carcinoma cells (RT-4, HT1376, TSGH-8301, and T24) in vitro. Besides, the results of RT-qPCR revealed that TAGLN expressions were higher in normal tissues than the paired tumor tissues. In vitro, TAGLN knockdown enhanced cell proliferation and invasion, while overexpression of TAGLN had the inverse effects in bladder carcinoma cells. Meanwhile, ectopic overexpression of TAGLN attenuated tumorigenesis in vivo. Immunofluorescence and immunoblot assays showed that TAGLN was predominantly in the cytosol and colocalized with F-actin. Ectopic overexpression of either p53 or PTEN induced TAGLN expression, while p53 knockdown downregulated TAGLN expression in bladder carcinoma cells. Our results indicate that TAGLN is a p53 and PTEN-upregulated gene, expressing higher levels in normal bladder epithelial cells than carcinoma cells. Further, TAGLN inhibited cell proliferation and invasion in vitro and blocked tumorigenesis in vivo. Collectively, it can be concluded that TAGLN is an antitumor gene in the human bladder.
Carbonation Resistance Performance and Micro-Structure Analysis of Glazed Hollow Bead Insulation Concrete
Authors: Huang Xin , Yao Weijing , Pang Jianyong
Published: October 2019

In this paper, the carbonation depths of glazed hollow bead insulation concrete (GHBC) and normal concrete (NC) at different carbonation ages are tested. The microstructure of GHBC and NC before and after carbonation were observed and compared by mercury intrusion porosimetry (MIP), energy dispersive spectrometer (EDS), and X-ray diffraction (XRD). The results showed that NC had better carbonation resistance than GHBC, and GHBC had a carbonation depth of 1.61 times than that of NC at 28 days accelerated carbonation experiment. The microstructural analysis showed that with the decrease of porosity of the samples, the carbon content and CaCO3 content increased after carbonation. The porosity of NC decreased from 14.36% to 13.53%, the carbon content increased from 4.42% to 5.94%, and the CaCO3 content increased from 18.5% to 56.0%. The porosity of GHBC decreased from 22.94% to 20.71%, the carbon content increased from 4.97% to 5.31%, and the CaCO3 content increased from 70.0% to 82.0%. The above results showed that carbon reacts with hydration products 3CaO·SiO2, 2CaO·SiO2, and Ca(OH)2 to produce a large amount of CaCO3 which causes a large amount of pores to be filled and refined hence the porosity and pore size were reduced leading to increase in the compactness of the material. From the results obtained, the carbonation depth prediction formula of glazed hollow bead insulation concrete was developed, and carbonation life was predicted.
Effectiveness between Dry Needling and Ischemic Compression in the Triceps Surae Latent Myofascial Trigger Points of Triathletes on Pressure Pain Threshold and Thermography: A Single Blinded Randomized Clinical Trial
Authors: Benito-de-Pedro María , Becerro-de-Bengoa-Vallejo Ricardo , Losa-Iglesias Marta Elena , Rodríguez-Sanz David , López-López Daniel , Cosín-Matamoros Julia , Martínez-Jiménez Eva María , Calvo-Lobo César
Published: October 2019

Background: Deep dry needling (DDN) and ischemic compression technic (ICT) may be considered as interventions used for the treatment of Myofascial Pain Syndrome (MPS) in latent myofascial trigger points (MTrPs). The immediate effectiveness of both DDN and ICT on pressure pain threshold (PPT) and skin temperature of the latent MTrPs of the triceps surae has not yet been determined, especially in athletes due to their treatment requirements during training and competition. Objective: To compare the immediate efficacy between DDN and ICT in the latent MTrPs of triathletes considering PPT and thermography measurements. Method: A total sample of 34 triathletes was divided into two groups: DDN and ICT. The triathletes only received a treatment session of DDN (n = 17) or ICT (n = 17). PPT and skin temperature of the selected latent MTrPs were assessed before and after treatment. Results: Statistically significant differences between both groups were shown after treatment, showing a PPT reduction (p < 0.05) in the DDN group, while PPT values were maintained in the ICT group. There were not statistically significant differences (p > 0.05) for thermographic values before and treatment for both interventions. Conclusions: Findings of this study suggested that ICT could be more advisable than DDN regarding latent MTrPs local mechanosensitivity immediately after treatment due to the requirements of training and competition in athletes’ population. Nevertheless, further studies comparing both interventions in the long term should be carried out in this specific population due to the possible influence of delayed onset muscle soreness and muscle damage on PPT and thermography values secondary to the high level of training and competition.
Alternations of Circadian Clock Genes Expression and Oscillation in Obstructive Sleep Apnea
Authors: Yang Ming-Yu , Lin Pei-Wen , Lin Hsin-Ching , Lin Pai-Mei , Chen I-Ya , Friedman Michael , Hung Chi-Fa , Salapatas Anna M. , Lin Meng-Chih , Lin Sheng-Fung
Published: October 2019

Circadian misalignment plays an important role in disease processes and can affect disease severity, treatment outcomes, and even survivorship. In this study, we aim to investigate whether expression and daily oscillation patterns of core circadian clock genes were disturbed in patients with obstructive sleep apnea/hypopnea (OSA) syndrome. We performed real-time quantitative reverse transcriptase-polymerase chain reactions to examine the expression of the nine core circadian clock genes in leukocytes of peripheral blood collected at 12 AM, 6 AM, 12 PM, and 6 PM from 133 patients with OSA and 11 normal controls. Daily expression patterns of the nine circadian clock genes were observed in normal controls, but three of these genes (BMAL1, CLOCK, CRY2) were disrupted in patients with OSA. The expressions of eight circadian clock genes (except PER1) at midnight were significantly downregulated in patients with severe OSA. Binary logistic regression analysis selected CRY1 and PER3 as independent factors for severe OSA and showed that the combined expressions of CRY1 and PER3 enhanced the capability of predicting severe OSA (Odds ratio, 5.800; 95% CI, 1.978 to 17.004; p = 0.001). Our results show that combined expressions of CRY1 and PER3 at midnight could be a potential predictor for severe OSA.
Papillary Vessel Density Changes after Intravitreal Anti-VEGF Injections in Hypertensive Patients with Central Retinal Vein Occlusion: An Angio-OCT Study
Authors: Nicolai Michele , Franceschi Alessandro , De Turris Serena , Rosati Alessandro , Pirani Vittorio , Mariotti Cesare
Published: October 2019

Purpose: To investigate papillary microvascular changes in patients affected by macular edema due to Central Retinal Vein Occlusions (CRVO) after anti-Vascular Endothelial Growth Factor (VEGF) therapy. Methods: Prospective analysis of papillary and peripapillary vessel density (VD) changes in 18 eyes of 18 hypertensive patients affected by CRVO before and after the loading-phase of intravitreal Ranibizumab (IVR) injections. Data were quantitatively measured by optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) before as well as 1 month and 4 months after injections. The correlation between post-treatment best-corrected visual acuity (BCVA) and changes in the retinal microvasculature evaluated by OCTA was assessed. Results: 18 eyes of 18 consecutive patients with a known history of arterial hypertension and affected by an acute CRVO episode were enrolled. Central macular thickness (CMT) was significantly reduced after IVR injections (p < 0.001), while mean BCVA improved from 0.70 ± 0.26 logarithm of the minimal angle of resolution (logMAR) units at baseline to 0.25 ± 0.18 logMAR units after 4 months (p < 0.001). VD inside disc and peripapillary significantly increased (p < 0.001 and p = 0.01, respectively) after treatment. Conclusions: OCTA showed VD increase in the papillary area in patients affected by CRVO after anti-VEGF therapy. This area could represent a new region of interest to study microvasculature changes concomitant with severe macular edema.
Effects of rAAV-Mediated sox9 Overexpression on the Biological Activities of Human Osteoarthritic Articular Chondrocytes in Their Intrinsic Three-Dimensional Environment
Authors: Daniels Oliver , Frisch Janina , Venkatesan Jagadeesh K. , Rey-Rico Ana , Schmitt Gertrud , Cucchiarini Magali
Published: October 2019

Gene therapy for osteoarthritis offers powerful, long-lasting tools that are well adapted to treat such a slow, progressive disorder, especially those therapies based on the clinically adapted recombinant adeno-associated viral (rAAV) vectors. Here, we examined the ability of an rAAV construct carrying a therapeutic sequence for the cartilage-specific SOX9 transcription factor to modulate the phenotype of human osteoarthritic articular chondrocytes compared with normal chondrocytes in a three-dimensional environment where the cells are embedded in their extracellular matrix. Successful sox9 overexpression via rAAV was noted for at least 21 days, leading to the significant production of major matrix components (proteoglycans, type-II collagen) without affecting the proliferation of the cells, while the cells contained premature hypertrophic processes relative to control conditions (reporter rAAV-lacZ application, absence of vector treatment). These findings show the value of using rAAV to adjust the osteoarthritic phenotype when the chondrocytes are confined in their inherently altered environment and the possibility of impacting key cellular processes via gene therapy to remodel human osteoarthritic cartilage lesions.
A Systematic Review and Meta-Analysis of the Impact of Mindfulness Based Interventions on Heart Rate Variability and Inflammatory Markers
Authors: Rådmark Lina , Sidorchuk Anna , Osika Walter , Niemi Maria
Published: October 2019

Mindfulness Based Interventions (MBIs) have recently been increasingly used in clinical settings, and research regarding their effects on health has grown rapidly. However, with regard to the physiological effects of mindfulness practices, studies have reported associations that vary in strength and direction. Therefore, in this systematic review and meta-analysis, we aimed to systematically identify, appraise, and summarize the existing data from randomized and non-randomized controlled trials that examine physiological effects of the standardized MBIs by focusing on pro-inflammatory cytokines and C-reactive protein, and commonly used heart rate variability parameters. The following electronic databases were searched: MEDLINE (via Ovid), PsychINFO (via Ovid), PubMed, Web of Science, EMBASE, CINAHL, ProQuest (Dissertations and Theses), and Centre for Reviews and Dissemination. The systematic review identified 10 studies to be included in the meta-analysis, comprising in total 607 participants. The meta-analysis ended up with mixed and inconclusive results. This was assumedly due to the small number of the original studies and, in particular, to the lack of large, rigorously conducted RCTs. Therefore, the current meta-analysis highlights the necessity of larger, more rigorously conducted RCTs on physiological outcomes with standardized MBIs being compared to various forms of active controls, and with more long-term follow-ups.
The Role of Physical Fitness in Cognitive-Related Biomarkers in Persons at Genetic Risk of Familial Alzheimer’s Disease
Authors: Tsai Chia-Liang , Sun H.-Sunny , Kuo Yu-Min , Pai Ming-Chyi
Published: October 2019

Introduction: Nondemented people with a family history of Alzheimer’s disease (ADFH) and the ApoE-4 allele have been demonstrated to show a trend for a higher probability of cognitive decline and aberrant levels of cognitive-related biomarkers. However, the potential interactive effects on physical fitness have not been investigated. Purpose: The primary purpose of this study was to determine whether ADFH individuals with the ApoE-4 genotype show deviant brain event-related neural oscillatory performance and cognitively-related molecular indices. A secondary purpose was to examine the interactive effects on physical fitness. Methods: Blood samples were provided from 110 individuals with ADFH to assess molecular biomarkers and the ApoE genotype for the purpose of dividing them into an ApoE-4 group (n = 16) and a non-ApoE-4 group (n = 16) in order for them to complete a visuospatial working memory task while simultaneously recording electroencephalographic signals. They also performed a senior functional physical fitness (SFPF) test. Results: While performing the cognitive task, the ApoE-4 relative to non-ApoE-4 group showed worse accuracy rates (ARs) and brain neural oscillatory performance. There were no significant between-group differences with regard to any molecular biomarkers (e.g., IL-1β, IL-6, IL-8, BDNF, Aβ1-40, Aβ1-42). VO2max was significantly correlated with the neuropsychological performance (i.e., ARs and RTs) in the 2-item and 4-item conditions in the ApoE-4 group and across the two groups. However, the electroencephalogram (EEG) oscillations during visuospatial working memory processing in the two conditions were not correlated with any SFPF scores or cardiorespiratory tests in the two groups. Conclusions: ADFH individuals with the ApoE-4 genotype only showed deviant neuropsychological (e.g., ARs) and neural oscillatory performance when performing the cognitive task with a higher visuospatial working memory load. Cardiorespiratory fitness potentially played an important role in neuropsychological impairment in this group.
The Effect of Disc Surface Topography on the Dry Gross Fretting Wear of an Equal-Hardness Steel Pair
Authors: Lenart Agnieszka , Pawlus Pawel , Dzierwa Andrzej
Published: October 2019

Experimental investigations were carried out with an Optimol SRV5 tribological tester in a flat-on-sphere scheme. The balls co-acted with the discs in a gross sliding fretting regime. The balls and discs were made from the same steel with a very similar hardness. Tests were conducted at 25–35% relative humidity, 30 °C, and a constant normal load and number of cycles (18,000). The discs had different textures after various machining treatments. It was found that the total wear level of the tribological assembly was proportional to the disc surface amplitude. The influence of the disc roughness on the coefficient of friction was evident only for the smallest stroke of 0.1 mm, and the frequency of oscillation affected this dependency.
Influence of Thermal Parameters Related to Destabilization Treatments on Erosive Wear Resistance and Microstructural Variation of White Cast Iron Containing 18% Cr. Application of Design of Experiments and Rietveld Structural Analysis
Authors: Gonzalez-Pociño Alejandro , Alvarez-Antolin Florentino , Asensio-Lozano Juan
Published: October 2019

High-Cr hypo-eutectic white cast irons are used in very demanding environments that require high resistance to erosive wear. The influence on the microstructural variation and erosive wear resistance of several fundamental factors related to the thermal treatments of these cast irons was analysed by means of a fractional Design of Experiments (DoE). These factors included the ones related to the destabilization of austenite. The precipitated phases were identified by X-ray diffraction (XRD), while the Rietveld structural refinement method was used to determine their percentages by weight. Erosion wear resistance was calculated using the test defined by ASTM G76. It was concluded that the quench cooling medium does not significantly influence either erosive wear resistance or the proportion of martensite or retained austenite. The destabilization temperature is a key factor with respect to the percentage of retained austenite. In order to increase the amount of martensite and decrease the amount of retained austenite, temperatures not exceeding 1000 °C are required. An increase of 100 °C in the destabilization temperature can lead to a 25% increase in retained austenite. Moreover, tempering temperatures of around 500 °C favour an additional increase in the percentage of martensite. Erosive wear commences on the matrix constituent without initially affecting the eutectic carbides. Once the deterioration of the matrix constituent surrounding these carbides occurs, they are released. High tempering times provide an increase in resistance to erosive wear due to a second destabilization of austenite during the said tempering.