bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of SDF-1/CXCR7 on the Migration, Invasion and Epithelial-Mesenchymal Transition of Gastric Cancer Cells
Authors: Shi Ameng , Wang Ting , Jia Miao , Dong Lei , Shi Haitao
Published: August 2021

We found that SDF-1/CXCR7 axis plays an important role in the growth and proliferation of gastric cancer in previous studies. The objectives of this study were to explore the effects of SDF-1/CXCR7 on the metastatic ability of gastric cancer cells and the possible mechanisms. SGC-7901 gastric cancer cells were cultured in vitro, CXCR7 expression was stably knocked down via lentiviral vectors. The cell migration and invasion abilities were detected by transwell migration and invasion assays. The expression of matrix metalloproteinase 2 (MMP-2), MMP-9, vascular endothelial growth factor (VEGF), epithelial-mesenchymal transition (EMT) markers and Akt phosphorylation were detected with western blot. We found that SDF-1 markedly enhanced the migration and invasion abilities of SGC-7901 gastric cancer cells; CXCR7 knockdown by lentiviral infection inhibited these effects. SDF-1/CXCR7 increased the expression of MMP-2, MMP-9 and VEGF. SDF-1/CXCR7 also downregulated E-cadherin expression but upregulated N-cadherin, vimentin and Snail expression, suggesting that SDF-1/CXCR7 could promote the development of EMT in gastric cancer cells. Furthermore, SDF-1/CXCR7 could promote Akt phosphorylation. Our results indicated that SDF-1/CXCR7 promoted the migration, invasion and EMT of gastric cancer cells and thus CXCR7 inhibition may be a strategy for inhibiting gastric cancer metastasis.
FGFR1 Promotes Tumor Immune Evasion via YAP-Mediated PD-L1 Expression Upregulation in Lung Squamous Cell Carcinoma
Authors: Lu Min , Wang Kaixuan , Ji Wenxiang , Yu Yongfeng , Li Ziming , Xia Weiliang , Lu Shun
Published: August 2021

Background: Variations in fibroblast growth factor receptor 1 (FGFR1), which occur frequently, are common driver mutations of lung squamous cell carcinoma. Immune checkpoint inhibitors targeting programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) are powerful anticancer weapons. Activation of FGFR1 leads to tumorigenesis through multiple downstream molecules, including Yes-associated protein (YAP), but whether and how FGFR1 regulates tumor immune evasion remain largely unclear. Methods: H520 and HCC95 cells were treated with siRNA and plasmids to increase or decrease the expression of FGFR1, YAP and PD-L1, as assessed by molecular assays of protein and mRNA expression. The interaction between YAP and PD-L1 was verified by chromatin immunoprecipitation. After FGFR1 knockdown by shRNA, cancer cells were cocultured with Jurkat T cells, and then cell proliferation and activity were assessed. In C57BL/6 mice, the tumor immune microenvironment was analyzed by flow cytometry, immunofluorescence and immunohistochemistry after FGFR1 knockdown. The effect of the combination of FGFR1 knockdown and PD-1 blockade was explored both in vitro and in vivo. Results: In H520 and HCC95 cells, FGFR1 upregulated PD-L1 expression via YAP, and YAP initiated the transcription of PD-L1 after binding to its promoter region. Both in vitro and in vivo, FGFR1 knockdown decreased tumor growth and reduced immune escape and reactivation of T cells. The combination of FGFR1 knockdown and PD-1 blockade synergistically exerted antitumor effects. In human LSQCC, the expression of fibroblast growth factor 2 (FGF2), the activator of FGFR1, was positively correlated with that of PD-L1 at the mRNA level. Conclusions: The FGFR1/YAP/PD-L1 regulatory axis mediates tumor-associated immune suppression in lung squamous cell carcinoma, and FGFR1 knockdown reactivates T cells in the tumor microenvironment. Synergistic inhibition of both FGFR1 and PD-1/PD-L1 may be a possible treatment for lung cancer patients.
Genetic Variants Associated mRNA Stability in Lung
Authors: Li Jian-Rong , Tang Mabel , Li Yafang , Amos Christopher I , Cheng Chao
Published: August 2021

Background: Expression quantitative trait loci (eQTLs) analyses have been widely used to identify genetic variants associated with gene expression levels to understand what molecular mechanisms underlie genetic traits. The resultant eQTLs might affect the expression of associated genes through transcriptional or post-transcriptional regulation. In this study, we attempt to distinguish these two types of regulation by identifying genetic variants associated with mRNA stability of genes (stQTLs).Results: Here, we presented a computational framework that take the advantage of recently developed methods to infer the mRNA stability of genes based on RNA-seq data and performed association analysis to identify stQTLs. Using the Genotype-Tissue Expression (GTEx) lung RNA-Seq data, we identified a total of 142,801 stQTLs for 3,942 genes and 186,132 eQTLs for 4,751 genes from 15,122,700 genetic variants for 13,476 genes, respectively. Interesting, our results indicated that stQTLs were enriched in the CDS and 3’UTR regions, while eQTLs are enriched in the CDS, 3’UTR, 5’UTR, and upstream regions. We also found that stQTLs are more likely than eQTLs to overlap with RNA binding protein (RBP) and microRNA (miRNA) binding sites. Our analyses demonstrate that simultaneous identification of stQTLs and eQTLs can provide more mechanistic insight on the association between genetic variants and gene expression levels.
Usability and Acceptability of Oral-Based HCV Self-Testing Among Key Populations: A Mixed-Methods Evaluation in Tbilisi, Georgia
Authors: Fajardo Emmanuel , Watson Victoria , Kumwenda Moses , Usharidze Dali , Gogochashvili Sophiko , Kakhaberi David , Giguashvili Ana , Johnson Cheryl C , Jamil Muhammad S , Dacombe Russell , Stvilia Ketevan , Easterbrook Philippa , Reipold Elena Ivanova
Published: August 2021

Background: Hepatitis C virus self-testing (HCVST) is an additional approach that may expand access to HCV testing. We conducted a mixed-methods cross-sectional observational study to assess the usability and acceptability of HCVST among people who inject drugs (PWID), men who have sex with men (MSM) and transgender (TG) people in Tbilisi, Georgia. Methods: The study was conducted from December 2019 to June 2020 among PWID at one harm reduction site and among MSM/TG at one community-based organization. We used a convergent parallel mixed-methods design. Usability was assessed by observing errors made and difficulties faced by participants. Acceptability was assessed using an interviewer-administered semi-structured questionnaire. A subset of participants participated in cognitive and in-depth interviews.Results: A total of 90 PWID, 84 MSM and 6 TG were observed performing HCVST. PWID were older (median age 35 vs 24) and had a lower level of education compared to MSM/TG (27% vs 59%). The proportion of participants who completed all steps successfully without assistance was 60% among PWID and 80% among MSM/TG. The most common error was in sample collection and this was observed more often among PWID than MSM/TG (21.1% vs 5.5%; p=0.002). More PWID requested assistance during HCVST compared to MSM/TG (22.2% vs 7.8%; p=0.011). Acceptability was high in both groups (98% vs 96%; p=0.407). Inter-reader agreement was 96.7% among PWID and 98.9% among MSM/TG. Qualitative data from cognitive (n=20) and in-depth interviews (n=20) was consistent with the quantitative data confirming a high usability and acceptability. Conclusions: HCVST was highly acceptable among key populations in Georgia of relatively high educational level, and most participants performed HCVST correctly. A significant difference in usability was observed among PWID compared to MSM/TG, indicating that PWID may benefit from improved messaging and education as well as options to receive direct assistance when self-testing for HCV.
Inflammatory Myofibroblastic Tumor of the Sigmoid Colon in an Infant: A Case Report
Authors: wu luyao , meng xinyao , sun xiaoyi , zhu tianqi , yu donghai , feng jiexiong
Published: August 2021

Background: Inflammatory myofibroblastic tumor (IMT), an infrequent mesenchymal lesion composed of myofibroblastic and fibroblastic spindle cells with inflammatory infiltration, mostly occurred in pediatric patients. IMT has been reported in a number of locations throughout the body. However, the cases occurred in the gastrointestinal tract, especially those involving the sigmoid colon in pediatric patients, are very rare and even have not been reported. Here we present a case of a large IMT originating from the sigmoid colon and invading the omentum and the surrounding tissues in an 11-month-old boy. Case presentation: The patient is an 11-month-old boy initially presenting with symptoms of fever and vomiting. Abdominal ultrasound revealed an inhomogeneous echo with a size of 9.9*4.6 cm in the left lower abdomen. Abdomen computed tomography (CT) scanning confirmed that a mass with a size of 10*8*6 cm located in the left middle and lower abdomen. Post-operative pathological examination confirmed the histopathologic diagnosis of IMT. Complete resection of the tumor along with the involved colon segments were performed and followed by end-to-end colon anastomosis. The boy recovered well without postoperative complications or recurrence during one-year follow-up. Conclusions: Colon IMT is extremely rare; its etiology and pathogeny are unclear. Imaging examination may provide reliable evidence for determining IMT. However, postoperative histopathologic examination is also important for the final diagnosis. Complete tumor excision, accompanied by rare recurrence and satisfying survival, is the best therapeutic approach at present. This case report may complete the clinical presentation of IMT by reminding physicians not to ignore the possibility of IMT in the colon.
PM2.5 Induced Airway Remodeling via Wnt5a/β-catenin Pathway in Chronic Obstructive Pulmonary Diseases
Authors: Zou Weifeng , Wang Xiaoqian , Sun Ruiting , Hu Jinxing , Ye Dong , Liu Sha , Guo Meihua , Ran Pixin
Published: August 2021

Background: PM2.5-associated airway remodeling has recently been recognized as a central feature of COPD. The activation of Wnt/β-catenin pathway is closely related to the occurrence of airway remodeling. Accordingly, the goal of this study was to determine whether Wnt5a/β-Catenin is involved in PM2.5-induced smooth muscle proliferation in vivo and vitro, which promoted the development of airway remodeling in COPD.Methods: The effect of Wnt5a on β-Catenin-mediated airway remodeling was assessed by using an in vivo model of PM2.5-induced COPD and PM2.5-exposed human bronchial smooth muscle cell (HBSMC) in vitro. Small animal spirometry to measure lung function in mice. H&E staining and immunohistological inspection of emphysema and airway remodeling indexes. qPCR to detect Wnt5a, β-Catenin, TGF-β1, CyclinD1 and c-myc mRNA expression. CCK8 assay for cellular activity. Western blotting for PCNA, α-SMA, Wnt5a, β-Catenin, PDGFRβ and TenascinC protein expression. Detection of β-Catenin expression by cellular immunofluorescence.Results: The exposure to PM2.5 led to emphysema, airway wall thickening, increased smooth muscle layer thickness, decreased lung function and induced the expression of Wnt5a, β-Catenin, PDGFRβ and Tenascin C protein expression in lung tissue of mice. BOX5 alleviated PM2.5-induced these outcomes in mice. Moreover, PM2.5 induced the mRNA expression of Wnt5a, β-Catenin, TGF-β1, CyclinD1 and c-myc in HBSMC. BOX5 also inhibited PM2.5-induced the increase of PCNA, α-SMA, Wnt5a, β-Catenin, PDGFRβ and Tenascin C protein expression in HBSMC. Conclusions: Our findings suggest that PM2.5 exposure induce HBSMC proliferation, contributing to airway remodeling via Wnt5a/β-Catenin signaling pathway in vivo and in vitro, which could be a target of treatment of COPD.
Bixin Protects Mice Against Bronchial Asthma Though Modulating PI3K/Akt Pathway
Authors: Zhu Yingjie , Sun Dong , Liu Han , Sun Linzi , Jie Jing , Luo Jingjing , Peng Liping , Song Lei
Published: August 2021

Background: Accumulating evidence has implicated the potential of natural compounds in treatment of asthma. Bixin is a natural food coloring isolated from the seeds of Bixa Orellana, which possesses anti-tumor, anti-inflammatory and antioxidative properties. Nevertheless, its therapeutic effect in asthma has not been elucidated. Methods: Acute and chronic asthma models of Balb/c mice were established by ovalbumin (OVA) sensitization. For the establishment of a glucocorticoids (GCs) resistant asthma model, Freund’s Adjuvant (CFA) was injected intraperitoneally with OVA. After Bixin treatment, cells in Bronchoalveolar lavage fluid (BALF) were stained with Diff Quick staining and the levels of cytokines were measured by enzyme linked immunosorbent assay (ELISA). The levels of protein in cells and tissues were determined by immunoblotting and/or immunostaining with specific antibodies. The histological changes were determined by Hematoxylin and eosin (H&E), PAS and MASSON staining. Results: Our present study demonstrated that administration of Bixin suppressed allergic airway inflammation and reversed GCs resistance, as well as alleviated airway remodeling and airway hyperresponsiveness (AHR) in asthmatic mice. In vitro studies showed that Bixin treatment could inhibit the development of epithelial-mesenchymal transition (EMT) mediated by transforming growth factor beta (TGF-β) signaling. Importantly, Bixin antagonized activation of phosphatidylinositol 3‑kinase/protein kinase B (PI3K/Akt) pathway both in vitro and in vivo. Conclusions: Above all, our findings reveal that Bixin functions as a potent antagonist of PI3K/Akt signaling to protect against allergic asthma, highlighting a novel strategy for asthma treatment based on natural products.
Occupation And Occurrence of Respiratory Infections Among Adults With Newly Diagnosed Asthma
Authors: Jaakkola Maritta S. , Lajunen Taina K. , Rantala Aino K. , Nadif Rachel , Jaakkola Jouni J.K.
Published: August 2021

Background: Work environments are potential areas for spreading respiratory infections. We hypothesized that certain occupations increase susceptibility to respiratory infections among adults with asthma. Our objective was to compare the occurrence of respiratory infections among different occupations in adults with newly diagnosed asthma.Methods: We analysed a study population of 492 working-age adults with newly diagnosed asthma who were living in the geographically defined Pirkanmaa Area in Southern Finland during a population-based Finnish Environment and Asthma Study (FEAS). The determinant of interest was occupation at the time of diagnosis of asthma. We assessed potential relations between occupation and occurrence of both upper respiratory tract infections and lower respiratory tract infections during the past 12 months. The measures of effect were incidence rate ratio (IRR) and risk ratio (RR) adjusted for age, gender, and smoking habits. Professionals, clerks, and administrative personnel formed the reference group. Results: The mean number of common colds in the study population was 1.85 (95% CI 1.70, 2.00) infections in the last 12 months. The following occupational groups showed increased risk of common colds: forestry and related workers (aIRR 2.20, 95% CI 1.15-4.23) and construction and mining (aIRR 1.67, 95% CI 1.14-2.44). The risk of lower respiratory tract infections was increased in the following groups: glass, ceramic, and mineral workers (aRR 3.82, 95% CI 2.54-5.74), fur and leather workers (aRR 2.06, 95% CI 1.01-4.20) and metal workers (aRR 1.80, 95% CI 1.04-3.10).Conclusions: We provide evidence that the occurrence of respiratory infections is related to certain occupations.
Controlling friction and wear with anisotropic microstructures in MoN coated surfaces
Authors: Schulz Wadim , Köhn Florian , Kolb David , Balzer Martin , Riegel Harald , Albrecht Joachim
Published: August 2021

Steel surfaces have been patterned by laser surface texturing (LST) to create anisotropic microstructures with typical dimensions of a few 10 micrometers. The subsequent deposition of thin molybdenum nitride coatings by high power impulse magnetron sputtering (HiPIMS) leads to surfaces that conserve the surface microstructures and exhibit an extraordinarily large resistance against mechanical wear. Tribological experiments with steel counter bodies show a substantial influence of the relative orientation of structures and wear track on friction and wear. It is pointed out that the main effect is the removal of abrasion particles from the mechanical contact. Analogue experiments with alumina counter bodies that hardly provide wear particles show that the orientation effect is absent.
Greenland's thaw pushes the biodiversity crisis
Authors: Ureta Carolina , Ramírez-Barahona Santiago , Calderón-Bustamante Óscar , Cruz-Santiago Pedro , Gay Carlos , Swingedouw Didier , DeFrance Dimitri , Cuervo-Robayo Ángela P.
Published: August 2021

Global warming1, is reshaping the distribution of biodiversity across the world and can lead to the occurrence of large-scale singular events, such as the melting of polar ice sheets2,3. The potential impacts of such a melting event on species persistence across taxonomic groups – in terms of magnitude and geographic extent – remain unexplored. Here we assess impacts on biodiversity of global warming and melting of Greenland’s ice sheet on the distribution of 21,146 species of vascular plants and tetrapods across twelve megadiverse countries. We show that high global warming would lead to widespread reductions in species’ geographic ranges (median range loss, 35–78%), which are magnified (median range loss, 95–99%) with the added contribution of Greenland’s melting and its potentially large impact on oceanic circulation and regional climate changes. Our models project a decline in the geographical extent of species hotspots across countries (median reduction, 48–95%) and a substantial alteration of species composition in the near future (mean temporal dissimilarity, 0.26–0.89). These results imply that, in addition to global warming, the influence of Greenland’s melting can lead to the collapse of biodiversity across the globe, providing an added domino in its cascading effects.
Acoustically Manipulating Internal Structure of Disk-in-Sphere Endoskeletal Droplets
Authors: Shakya Gazendra , Yang Tao , Gao Yu , Fajrial Apresio , Li Baowen , Ruzzene Massimo , Borden Mark , Ding Xiaoyun
Published: August 2021

Manipulation of micro/nano particles has been well studied and demonstrated by optical, electromagnetic, and acoustic approaches, or their combinations. Manipulation of internal structure of droplet/particle is rarely explored and remains challenging due to its complicated nature. Here we demonstrated the manipulation of internal structure of disk-in-sphere endoskeletal droplets using acoustic wave for the first time. We developed a model to investigate the physical mechanisms behind this novel phenomenon. Theoretical analysis of the acoustic interactions indicated that these assembly dynamics arise from a balance of the primary and secondary radiation forces. Additionally, the disk orientation was found to change with acoustic driving frequency, which allowed on-demand, reversible adjusting disk orientations with respect to the substrate. This novel dynamic behavior leads to unique reversible arrangements of the endoskeletal droplets and their internal architecture, which may provide a new avenue for directed assembly of novel hierarchical colloidal architectures and intracellular organelles or intra-organoid structures.
Galaxy lacking dark matter in the standard cosmological paradigm
Authors: Moreno Jorge , Danieli Shany , Bullock James , Feldmann Robert , Hopkins Philip , Catmabacak Onur , Gurvich Alexander , Lazar Alexandres , Klein Courtney , Hummels Cameron , Hafen Zachary , Mercado Francisco , Yu Sijie , Jiang Fangzhou , Wheeler Coral , Wetzel Andrew , Angles-Alcazar Daniel , Boylan-Kolchin Michael , Eliot Quataert , Faucher-Giguere Claude-Andre , Keres Dusan
Published: August 2021

The standard cold dark matter plus cosmological constant model predicts that galaxies form within dark matter halos and that low-mass galaxies are more dark-matter dominated than massive ones. The unexpected discovery of two low-mass galaxies lacking dark matter immediately provoked concerns about the standard cosmology and ignited explorations of alternatives, including self-interacting dark matter and modified gravity. Apprehension grew after several simulations using the conventional cosmology failed to adequately form numerical analogs. Here we show that the standard paradigm naturally produces galaxies lacking dark matter, with characteristics largely in agreement with observations. Using a state-of-the-art cosmological simulation and a meticulous galaxy-identification technique, we find that extreme close-encounters with massive neighbors can transform regular galaxies into dark-matter deficient ones. We predict that ∼30% of massive central galaxies (with at least 1e11 solar masses in stars) harbor at least one dark-matter deficient satellite (with 1e8−1e9 solar masses in stars). This distinctive class of galaxies opens an additional layer to our understanding of the role of interactions in shaping galactic properties. Future observations surveying galaxies in the aforementioned regime will provide a crucial test of this scenario.
Investigation of Pharmacological Mechanisms of Schisandrin a for the Treatment of Asthma Determined by Network Pharmacology and Experimental Validation
Authors: Qiu Qing , Huang Fangfang , Su Jiating , Lin Qianwen , Huang Yuge , luo lianxiang
Published: August 2021

Traditional Chinese medicines (TCM) are increasingly applied and accepted in asthma prevention and treatment. In the present investigation, we aimed to evaluate the effects of schisandrin A against asthma and examine its underlying mechanism. Here, 68 intersection targets between schisandrin A and asthma were identified by network pharmacology. Further enrichment analysis demonstrated that the nuclear factor-kappaB (NF-κB) signaling pathway may be a major signaling pathway and cyclooxygenase 2 (COX-2/PTGS2) may be a key target in the anti-asthmatic mechanism of schisandrin A. Then, the relevant mechanisms were verified. In vitro, we found that schisandrin A knock down the expression of COX-2 and iNOS (inducible nitric oxide synthase) in 16 HBE cells and RAW264.7 cells in a dose-dependent manner. While, it ameliorated the epithelial barrier function injury, and reduced the activation of NF-κB signaling pathway effectively. Additionally, OVA-induced asthma mice model showed that inflammatory cell infiltration, mucus secretion as well as airway remodeling could be availably suppressed by schisandrin A treatment. In conclusion, our data suggested that schisandrin A can reduce asthma symptoms by inhibiting inflammation production, including lowering the Th2 cell ratio, which provides a basis for further understanding of the treatment of asthma with schisandrin A.
Mediation Effect of Obesity on the Association Between Triglyceride-glucose Index and Hyperuricemia in Chinese Hypertension Adults.
Authors: Sun Jin , Su Yongkang , Li Man , Ma Shouyuan , Zhang Yan , Zhang Anhang , Cai Shuang , Cheng Bokai , Bao Qiligeer , Wang Shuxia , Zhu Ping
Published: August 2021

Background: The triglyceride glucose (TyG) index was regarded as a simple surrogate marker of insulin resistance (IR). It is confirmed that IR was significantly associated with hyperuricemia, and obesity was the risk factor for IR and hyperuricemia. However, the relationship of TyG index and hyperuricemia and the potential role of obesity in Han Chinese hypertension are not entirely elucidated.Method：A community-based cross-sectional study was conducted in 4551 hypertension patients aged 40-75 years with clinical and biochemical data. The TyG index was calculated as ln [fasting triglyceride (mg/dl) × fasting blood glucose (mg/dl)/2]. Hyperuricemia was determined as serum uric acid ≥357μmol/L (6 mg/dl) for females and ≥417μmol/L (7 mg/dl) for males. Body mass index (BMI), waist (WC) and hip circumference (HC) were regarded as obesity indexes, to evaluate the mediation effect of the association between TyG index and hyperuricemia.Result：The TyG index was higher in patients with hyperuricemia than in those without (8.99±0.61, 8.70±0.59, P<0.001). The prevalence of hyperuricemia in patients with the lowest (≤8.32), second (8.33-8.66), the third (8.67-9.07) and the highest quartile (≥9.08) of TyG index was 6.0%, 10.4%, 15.4%, 21.4%, respectively. Logistic regression analysis suggested that the higher quartile of TyG index were associated with increased hyperuricemia risk whether in crude or adjusted models (P<0.05). Mediation analysis showed that all of our obesity indexes partially mediated the association between TyG index and hyperuricemia to some extent.Conclusion：TyG index is significantly associated with hyperuricemia in hypertension patients among Han Chinese, obesity plays a partial mediation role in this relationship.
Impact of Targeted Antibiotic Therapy and Infectious Diseases Specialist Input in the Management of Cystic Neutrophilic Granulomatous Mastitis
Authors: Lever Robert Andrew , Ryan Rebecca , Rathbone Victoria , Mahadeva Ula , Franks Joanna , Morris-Jones Stephen , Khiroya Reena , Brown Michael
Published: August 2021

Objectives: Cystic neutrophilic granulomatous mastitis (CNGM) is a rare cause of destructive inflammatory breast disease which has been linked to the presence of lipophilic Corynebacteria which often show broad resistance to antibiotics. Antibiotic therapy is frequently utilised as an adjunct to surgical management however there is a lack of reported data on optimal antimicrobial strategies and recovery is often prolonged. Methods: We developed a management strategy in a tertiary infectious diseases unit to identify potential Corynebacteria-related CNGM pathology and took a targeted antibiotic-led approach to treatment. Clinical, laboratory, imaging, and therapeutic data were collected retrospectively from patients seen in our clinic between 2016-2020. Results: Thirteen patients were identified who met criteria for the diagnosis of CNGM. The mean age was 42.6 years and all patients were female. All had bacteriological evidence of Corynebacteria infection or granulomatous findings on histology. Microbiological evidence of Corynebacteria was present in 76.9%. Antibiotics were used as first line therapy in 92.6%, with a variety of agents used. Steroids were used as an adjunctive therapy in 53.8%. Most patients underwent surgical drainage or clinic-based aspiration of an abscess as part of their treatment. Eleven of thirteen patients (84.6%) experienced complete resolution of symptoms however recovery was protracted with a median time to resolution of >6 months. Conclusions: We present a case series of a rare clinical entity, CNGM, and highlight the outcomes of implementation of an antibiotic and infection service-led clinical approach in these patients.
Letrozole Protects Against Cadmium-induced Inhibition of Spermatogenesis via LHCGR and Hsd3b6 to Activate Testosterone Synthesis in Mice
Authors: Yao Yao , Wan Yangyang , Shi Xiaoyun , Guo Lan , Jiang Hui , Zhang Xiansheng , Xu Bo , Hua Juan
Published: August 2021

The heavy metal cadmium is believed to be one of the environmental endocrine disruptors of spermatogenesis. Cadmium-induced inhibition of spermatogenesis is associated with hormone secretion disorder. Letrozole is an aromatase inhibitor that can raise peripheral androgen levels and stimulate spermatogenesis. However, the potential protective effects of letrozole against cadmium-induced reproductive toxicity remain to be elucidated. In this study, male mice were administered CdCl2 (4 mg/kg BW) orally by gavage alone or in combination with letrozole (0.25 mg/kg BW) for 30 days. Cd exposure caused a significant decrease in body weight, sperm count, motility, vitality and plasma testosterone levels. Histopathological changes revealed extensive vacuolization and decreased spermatozoa in the lumen. However, in the Cd+letrozole group, letrozole treatment compensated for deficits in sperm parameters (count, motility, and vitality) induced by Cd. Letrozole treatment significantly increased serum testosterone levels, which were reduced by Cd. Histopathological studies revealed a systematic array of all germ cells, a preserved basement membrane and relatively less vacuolization. For mechanistic exploration, RNA-seq was used to profile alterations in gene expression in response to letrozole. Compared with that in the Cd-treated group, RNA-Seq analysis showed that 214 genes were differentially expressed in the presence of letrozole. Gene ontology (GO) enrichment analysis and KEGG signaling pathway analysis showed that steroid biosynthetic processes were the processes most affected by letrozole treatment. Furthermore, we found that the expression of the testosterone synthesis-related genes LHCGR (luteinizing hormone/choriogonadotropin receptor) and Hsd3b6 (3 beta- and steroid delta-isomerase 6) was significantly downregulated in Cd‐induced testes, but in letrozole-treated testes, these genes maintained similar expression levels as the control group. However, the transcription levels of inflammatory cytokines, such as IL-1β and IL-6, and oxidative stress-related genes (Nrf2, Nqo1, and Ho-1) showed no changes. The present study suggests that the protective potential of letrozole against Cd-induced reproductive toxicity might be due to upregulation of LHCGR and Hsd3b6, which could beneficially increase testosterone synthesis to achieve optimum protection in sperm quality and spermatogenesis.
Tissue-engineered Collagenous Fibrous Cap Models to Systematically Elucidate Atherosclerotic Plaque Rupture.
Authors: Wissing T.B. , Heiden K. Van der , Serra S.M. , Smits A.I.P.M. , Bouten C.V.C. , Gijsen F.J.H.
Published: August 2021

A significant amount of vascular thrombotic events is associated with rupture of the fibrous cap that overlie atherosclerotic plaques. Cap rupture is however difficult to predict due to the heterogenous composition of the plaque, unknown material properties, and the stochastic nature of the event. Here, we aim to create tissue engineered human fibrous cap models with a variable but controllable collagen composition, suitable for mechanical testing, to scrutinize the reciprocal relationships between composition and mechanical properties. Myofibroblasts were cultured in 1 x 1.5 cm-sized fibrin-based constrained gels for 21 days according to established (dynamic) culture protocols (i.e. static, intermittent or continuous loading) to vary collagen composition (e.g. amount, type and organization). At day 7, a soft 2 mm ∅ fibrin inclusion was introduced in the centre of each tissue to mimic the soft lipid core, simulating the heterogeneity of a plaque. Results demonstrate reproducible collagenous tissues, that mimic the bulk mechanical properties of human caps and vary in collagen composition due to the presence of an successfully integrated soft inclusion and the culture protocol applied. The models can be deployed to assess tissue mechanics, evolution and failure of fibrous caps or complex heterogeneous tissues in general.
Using Satellite Data to Estimate Risk of Mercury Exposure in the Amazonian Wayana Language Territory between Suriname, French Guiana, and Brazil
Authors: Peplow Daniel
Published: August 2021

BackgroundThere is a need for methods that measure the public and environmental health risks of mercury from small-scale gold mines (SSGMs) at a regional scale in tropical forests. Mercury is poisonous, with mercury toxicity in humans most commonly affecting the neurologic, gastrointestinal and renal organ systems at the individual, community and population scale. Economic development policies and projects responsible for SSGM in regions held by indigenous people are developed at the regional scale.MethodsThe synoptic regional-scale perspective of overhead remote imaging technology was used to supplement previous ground-level community risk and health assessment studies. The objective was to evaluate the usefulness of remote sensing as a method for measuring mercury impacts over large areas and test whether regional-level vegetation index values are lower in a test area where mercury contamination from SSGMs are known to impact human health compared to index values in a pristine reference area.ResultsLow vegetation index values were obtained in the test area compared to the high index values at the pristine reference location where vegetation stress is low. Public policy solutions to system-level causes of indigenous health issues caused by natural resource extraction projects are limited in this region where policymakers and economists perform cost-benefit analyses, ostensibly to develop rational economic development policies, that are built on the legal principle terra nullius codified in Western civil law as the Doctrine of Discovery. This principle designates the land and resources held by indigenous people as vacant and empty thus rendering the value of the lives of indigenous people equal to zero. Conclusions﻿ Vegetation index values were lower in the test area where there was mercury contamination from SSGMs when compared to a pristine reference area. These results suggest that remote sensing methods can be useful for measuring mercury contamination at scales that support the supranational policy development processes and address health issues caused by factors that lie outside the health sector and are economically formed. At this scale, the ratio comparing the cost of prevention to the benefits is revealed to be an irrational number when the benefit value of the lives saved is set at zero.
Potentially Probiotic Lactiplantibacillus Plantarum Strains From Indian Foods: Isolation, Characterization and Comparative Genomics
Authors: Surve Sarvesh , Shinde Dasharath , Kulkarni Ram
Published: August 2021

L. plantarum is one of the most diverse species of lactic acid bacteria found in various habitats. Here we report the isolation of two distinct strains of L. plantarum from Indian foods, one each from dhokla batter and jaggery, and analysis of their probiotic potential, technical properties, and genomic features. Both the strains were bile and acid tolerant, utilized various sugars, adhered to intestinal epithelial cells, produced exopolysaccharides, were susceptible for tetracycline, erythromycin, and chloramphenicol, did not cause hemolysis, and exhibited antimicrobial activity against a few pathogenic bacteria. The genetic determinants of bile tolerance, cell-adhesion, bacteriocins production, riboflavin and folate biosynthesis, plant polyphenols utilization, and exopolysaccharide production were found in both the strains. One of the strains contained a large number of unique genes while the other had a simultaneous presence of glucansucrase and fructansucrase genes which is a rare trait in L. plantarum. Comparative genome analysis of 149 L. plantarum strains highlighted high variation in the cell-adhesion and sugar metabolism genes while the genomic regions for some other properties were relatively conserved. This work highlights the unique properties of our strains along with the probiotic and technically important genomic features of a large number of L. plantarum strains.
The Gut Microbiome as Mediator Between Diet and its Impact on Immune Function
Authors: Shi Huiqing , Horst Rob ter , Nielen Suzanne , Bloemendaal Mirjam , Jaeger Martin , Joosten Irma , Koenen Hans , Joosten Leo A.B. , Schweren Lizanne JS , Vasquez Alejandro Arias , Netea Mihai G. , Buitelaar Jan
Published: August 2021

Background. Dietary habits may influence chronic low-grade inflammation in humans. Here we explore this interaction as well as the potential mediating role of the gut microbiome (GM), given that the GM is both involved in processing of dietary components and influences the immune system. Methods. A cross-sectional analysis of a sample of 482 healthy participants (207 males and 275 females) was performed. Dietary intake was assessed by a semiquantitative food questionnaire. Adipokines and soluble inflammatory mediators were assayed with multiple immunoassays and ELISA. Microbial DNA was extracted from frozen stool samples of the 471 participants. Polychoric correlation analysis was used to establish dietary patterns, and joint multivariate associations between these dietary patterns and immune biomarkers were studied using regression analyses with adjustment for sex, age, BMI, smoking, education levels and physical exercise and other dietary patterns. Non-parametric entropy mediation (NPEM) was applied to investigate whether diet-immune relationships are mediated by abundance of microbial species. Results. We identified 3 dietary patterns, characterized as “high-meat” (meat and sweetened drink), “prudent diet” (fish, fruit, legumes and vegetables) and “high alcohol” (higher alcohol consumption). Higher adherence to prudent diet was associated with a higher adiponectin level. The high alcohol pattern was associated with high concentrations of circulating concentrations of pro-inflammatory markers (CRP, IL-6, VEGF). Dialister invisus was found to mediate the relationship between a prudent dietary pattern and adiponectin, AAT, CRP, IL-6, and VEGF. Conclusion. A meat-based diet and a diet with high alcohol consumption were associated with high concentrations of biomarkers of chronic low-grade inflammation, and conversely, a prudent diet was associated with anti-inflammatory biomarkers. Diet-inflammation regulation may differ between sexes. Mediation analyses revealed that the association between prudent diet and immune function was partially mediated by the GM. Our study adds to our understanding of the associations between diet, the immune system and the GM in a healthy population.
Dose-dependent Effects of Perfluorocarbon Based Blood Substitute Perftoran on Cardyodinamics in Animal Model of Ischemia-reperfusion Injury
Authors: Jakovljevic Vladimir , Vorobyev Sergey , Bolevich Sergey , Morozova Elena , Bolevich Stefani , Saltykov Alexander , Litvickiy Peter , Fisenko Vladimir , Tsymbal Alexander , Orlova Alexandra , Sinelnikova Tatiana , Kruglova Maria , Silina Ekaterina , Mikhaleva Anastasia , Milosavljevic Isidora , Jeremic Jovana , Turnic Tamara Nikolic
Published: August 2021

The main goal of this study was to investigate the cardioprotective properties in terms of effects on cardiodynamics of perfluorocarbon emulsion in ex vivo-induced ischemic-reperfusion injury of an isolated rat heart. The first part of the study aims to determine the dose of 10% perfluoroemulsion (PFT) that will show the best cardioprotective effect in rats on ex vivo-induced ischemic / reperfusion injury of an isolated rat heart. Depending on whether the animals received saline or PFT, the animals were divided into a control or experimental group, and depending on the application of a dose (8, 12, 16 ml / kg body weight) of saline or PFT. At a dose of 8 ml / kg, the results indicate statistically significantly lower values ​​of the maximum pressure growth rate in the group treated with 10% PFT compared to the control group treated with saline at R5 and R25 points. At a dose of 12 ml / kg, the maximum left ventricular pressure growth rate differed statistically significantly in the PFT group, ie there was an increase in this parameter at points R25 and R30, and the minimum left ventricular pressure growth rate in R15-R30 compared to saline-treated group. At a dose of 16 ml / kg, PFT also had a statistically significant effect on the change in cardiodynamic parameters in an isolated rat heart organ. Based on all the above, we can conclude that Peftoran administered immediately before ischemia (1 hour) has less positive effects on myocardial function in a model of an isolated rat heart compared to earlier administration (10 and 20 hours). Also, the effects of 10% peftoran solution are more pronounced if there is a longer period of time from application to ischemia, ie immediate application of peftoran before ischemia (1 hour) gave the weakest effects on the change of cardiodynamics of isolated rat heart.
The Role of Sirtuin 1 in Palmitic-acid-induced Endoplasmic-reticulum Stress in Cardiac Myoblasts
Authors: Yang Hsiang-Yu , Chen Jhao-Ying , Huo Yen-Nien , Yu Pei-Ling , Lin Pei-Zhen , Hsu Shih-Che , Huang Shih-Ming , Tsai Chien-Sung , Lin Chih-Yuan
Published: August 2021

Background: Lipotoxicity causes endoplasmic reticulum (ER) stress, leading to cell apoptosis. Sirtuin 1 (Sirt1) regulates gene transcription and cellular metabolism. In this study, we investigated the role of Sirt1 in palmitate-induced ER stress. Methods: H9c2 myoblasts and heart-specific Sirt1 knockout mice fed a palmitate-enriched high-fat diet were used. Results: The high-fat diet induced C/EBP homologous protein (CHOP) and activating transcription factor 4 (ATF4) expression in both Sirt1 knockout mice and controls. Sirt1 knockout mice showed higher CHOP and ATF4 expression compared to those in control. Palmitic acid (PA) induced ATF4 and CHOP expression in H9c2 cells. PA-treated H9c2 cells showed decreased cytosolic NAD+/NADH alongside reduced Sirt1’s activity. H9c2 cells showed increased ATF4 and CHOP expression when transfected with plasmid encoding dominant negative mutant Sirt1. Sirt1 activator SRT1720 did not affect CHOP and ATF4 expression. Although SRT1720 enhanced nuclear translocation of ATF4, the extent of the binding of ATF4 to the CHOP promoter did not increase further in PA treated-H9c2 cells.Conclusion: PA-induced ER stress is mediated through upregulation of ATF4 and CHOP. Cytosolic NAD+ concentration is diminished by PA-induced ER stress, leading to decreased Sirt1 activity. The Sirt1 activator SRT1720 promotes nuclear translocation of ATF4 in PA-treated H9c2 cells.
Invasion and escalation of Aleurodicus rugioperculatus (Hemiptera: Aleyrodidae): An alarming pest in east coast region of India
Authors: SINGH SATYAPRIYA , Samant Deepa , Sahoo Manas Ranjan , Kishore Kundan , Acharya Gobinda Chandra
Published: August 2021

Invasive species causes serious threat to the natural ecosystem. Severe and up surging phenomenon of exotic rugose spiraling whitefly (RSW), Aleurodicus rugioperculatus Martin became a major concern in global crop production. The present study aimed to document and assesses the host range, nature, and intensity of damage caused by this cryptic species. The roving survey was conducted to study the occurrence of RSW in the fruit orchards, vegetable gardens, ornamental crops, and avenues trees plantation in the east-coast region of India. Hierarchical clustering was performed based on its incidence on different host plants and correlated with the dissimilarity index. The RSW was identified based on morphological characteristics and the nature of the damage. RSW infested a total of twenty-seven crops was noticed. Four host plants viz., Cocos nucifera L., Musa sp., Psidium guajava L., and Syzygium cumini L. Skeels showed severe levels of infestation. An important implication from the current study is the occurrence of its incidence on the two new host crops viz., Amaranthus tricolor L. and Solanum torvum that was envisaged firstly to the scientific world. This study provides baseline information about RSW among various stakeholders and helps to develop a sustainable management strategy for timely mitigation of RSW menace.
The Relationship Between Depression and Constipation: Results From a Large Cross-sectional Study in Adults
Authors: Adibi Peyman , Abdoli Maryam , Daghaghzadeh Hamed , Keshteli Ammar Hassanzadeh , Afshar Hamid , Roohafza Hamidreza , Esmaillzadeh Ahmad , Feizi Awat
Published: August 2021

Background and objective: accumulating evidence based on scarce studies suggests that the relation between depression and functional constipation is possible. However, more studies in order to provide more reliable evidence are needed. About one-third of depressed people experience constipation and, it has a key role in reducing the perceived quality of life of the affected individuals. In the current study, therefore, we aimed to evaluate whether depression is associated with higher risk of functional constipation and whether it is gender specific.Methods: This cross-sectional study was carried out among 3362 adults aged 18–55 years. In this study, functional gastrointestinal symptoms were determined using a Iranian reliable and valid version of the modified Rome III questionnaire. The Iranian validated version of Hospital Depression Scale (HADS) was used to evaluate psychological health. Scores of 8 or more on depression subscale in the questionnaire were considered to indicate the presence of depression. Self-administered questionnaires have been used to collect information regarding age, sex, marital status, education level, anthropometric measures, smoking, physical activity, antipsychotic medications use, dietary intakes. History of any predisposing chronic diseases including diabetes mellitus and cardiovascular diseases was also asked. Simple and binary logistic regression were used for data analysis. Results: mean ± SD age of participants was 36.29 ± 7.87 years and 58.5% were female. The prevalence of depression and constipation in our study sample was 28.6% and 33.6%, respectively. In crude model, in total sample depressed people showed higher significant risk of constipation OR=1.97 (95%CI:1.66-2.33). Although, we observed a significant association between depression and constipation in both genders, however the association was stronger in men than women (OR: 2.64; 95%CI: 1.91, 3.64 vs. OR: 1.52; 95%CI: 1.24, 1.86).In the full adjusted model, in total sample depressed people showed higher significant risk of constipation Adjusted OR=1.69 (95%CI:1.37-2.09). Although, we observed a significant association between depression and constipation in both genders, however the association was stronger in men than women (AOR: 2.28; 95%CI: 1.50, 3.63 vs. AOR: 1.55; 95%CI: 1.21, 1.99).Conclusion: Our study showed depressed people are at higher significant risk affecting by constipation. Our study findings justify mental health evaluation in all patients with functional gastrointestinal disorders particularly among constipated individuals.
Mislocalisation of Pax7 and Its Interaction with Importin-α1 (KPNA2) in Dystrophin-Deficient Myoblasts
Authors: Yazid Muhammad Dain , Sulaiman Nadiah , Lam Chung-Liang , Chen Hung-Chih
Published: August 2021

Background: Pax 7 is one of the key factors in the development of tissues and organs during embryogenesis. It has been suggested that Pax7 may play a major role during myogenesis. Our previous study has shown that Pax7 cell is attenuated in the mdx embryo during gestation as well as in dystrophic muscle indicating that an absence of dystrophin in muscle affects pax7 regulation in Duchene Muscular Dystrophy (DMD). Therefore, we aimed to investigate the Pax7 expression pattern as well as their specific transport protein in dystrophin-deficient myoblasts at postnatal/juvenile stage. Methods: In this study, dfd13 (dystrophin-deficient) and C2C12 (non-dystrophic) myoblasts were cultured under normal conditions prior to further analyse its expression pattern at proliferating stage via western blot and immunofluorescence analysis. Protein prediction and protein interaction study was done via in silico and co-immunoprecipitation analyses, respectively.Results: It was found that Pax7 localised in the cytoplasm of dystrophin-deficient myoblasts and high expression retained during differentiation. Co-localisation analysis of Pax7 with subcellular markers indicated that Pax7 is highly synthesised at their proliferative state. Interestingly, it is shown that Pax7 possess a nuclear location signal and KPNA2 was suggested as an escort protein for Pax7 translocation into the nucleus. Conclusion: For the first time, our study showed that Pax7 is mislocalised in dystrophin-deficient myoblasts and it is postulated that KPNA2 is the karyopherin-α which might be responsible for Pax7 translocation into the nucleus.