bluuebunny/crossref_metadata_2025_split huggingface dataset:
HGF Protected Against Diabetic Nephropathy via Autophagy-Lysosome Pathway in Podocyte by Modulating PI3K/Akt-GSK3β-TFEB Axis
Authors: Hou Bo , Li Yankun , Li Xue , Zhang Congying , Zhao Zhonghua , Chen Qi , Zhang Nong , Li Hui 
Published: June 2020

Abstract
Background: Podocyte loss is a detrimental feature and major cause of proteinuria in diabetic nephropathy (DN). Our previous study revealed that hepatocyte growth factor (HGF) prevented high glucose-induced podocyte injury via enhancing autophagy. In the current study, we aimed to assess the role of HGF on podocyte homeostasis in DN and clarify its mechanisms further. Methods: Streptozotocin (STZ)-induced DN mice were applied as a model to verify the impact of HGF on the prevention of type 1 diabetes. To study the mechanism involved, the autophagy flux and related signaling pathway upon HGF were examined and the relevance of lysosome acidification in cultured podocytes were investigated.Results: Diabetic mice treated with HGF had markedly reduced ratio of kidney weight to body weight, urinary albumin excretion, podocyte loss and matrix expansion compared with that in the non-treated counterpart. Simultaneously, HGF-treated diabetic mice exhibited increased autophagy activity as indicated by the decreased accumulation of sequestosome 1 (SQSTM1/ p62) and increased microtubule-associated proteins 1 light chains 3 (LC3) II/LC3I ratio. These beneficial effects of HGF were blocked by HGF/c-Met inhibitor Crizotinib or phosphatidylinositide 3-kinases (PI3K) inhibitor LY294002. Moreover, HGF treatment obviously prevented inactivation of the protein kinase B (Akt)-glycogen synthase kinase 3 beta (GSK3β)-transcription factor EB (TFEB) axis in high glucose-stimulated podocytes, which was associated with improved lysosome function and autophagy. Accordingly, adenovirus vector encoding constitutively active GSK3β (Ad-GSK3β-S9A) offset whereas small interfering RNA against GSK3β (GSK3β siRNA) recapitulated salutary effects of HGF on lysosome number and autophagy in podocytes. Conclusions: These results suggested that HGF protected against diabetic nephropathy through restoring podocyte autophagy, which at least partially involved PI3K/Akt-GSK3β-TFEB axis-mediated lysosomal function improvement.
Rsp Activates Expression of the Cnt System in Staphylococcus aureus
Authors: Vinué Laura , Hooper David C. 
Published: June 2020

Abstract
Background
The Cnt system is crucial for the optimal import of essential metals in metal-limiting conditions and contributes to virulence in S. aureus. In a screen for regulators of efflux pumps and other exporters in a phage-based ultra-high-density transposon library, we identified Rsp as a candidate regulator of the cntE exporter gene.
Results
A two-fold decrease in expression of all genes of the cnt operon was observed by RT-qPCR in the rsp mutant compared to the parental strain, indicating that Rsp acts as an activator of the cnt operon. To determine whether the Rsp activation depends on iron, we compared mutant and parent cnt expression under varying metal conditions. A 2-fold reduction in cnt gene expression was detected in the rsp mutant in TSB, and a slightly smaller decrease (1.9, 1.7, and 1.5-fold changes for cntK, cmtA, and cntE respectively) was observed after addition of dipyridyl. The greatest decrease was seen with addition of FeSO4 (4.1, 5.3 and 6.3-fold changes for cntK, cmtA and cntE respectively). These findings suggest that Rsp activates the cnt operon in both low and high iron conditions. To study the relationship between Rsp and the cnt repressors Fur and Zur, we created single and double mutants. A decrease in the expression of cntK (1.5-fold) and cntA (1.6-fold) was seen for Δfur Δrsp compared to Δfur strain. Similarly decreased expression of cntK (1.3-fold), cntA (1.6-fold) and cntE (1.6-fold) genes was seen comparing Δzur Δrsp and Δzur mutants but statistically not significant, indicating that Rsp is dependent on Fur and Zur. To determine if Rsp directly modulates expression of cnt genes, incubation of purified Rsp caused a DNA-specific band shift for both the cntK and cntA promoters.
Conclusions
Rsp activation may act to maintain basal cellular levels of staphylopine to scavenge free metals when needed, in addition to metal dependent regulation by Fur and Zur.
Revealing Oral Microbiota Composition and Functionality Associated with Heavy Cigarette Smoking.
Authors: Bataineh Mohammad Tahseen AL , Dash Nihar Ranjan , Elkhazendar Mohammed , Alnusairat Dua'a Mohammad Hasan , Darwish Islam Mohammad Ismail , Al-Hajjaj Mohamed Saleh , Hamid Qutayba 
Published: June 2020

Abstract
Background: Heavy tobacco smoking, a hallmark feature of lung cancer is drastically predominant in Middle Eastern populations. The precise links between nicotine dependence and the functional contribution of the oral microbiota remain unknown in these populations. Methods: We evaluated the functional capabilities of the oral microbiota with relation to cigarette smoking in 105 adults through shotgun metagenomics. Results: The four major enterotypes initially described in westernized cohorts were retrieved in this population. Differential relative abundance testing unveiled relative abundance of Streptobacillus hongkongensis (Log2FoldChange 4.78, P. adjusted value < 0.00004), Fusobacterium massiliense (Log2FoldChange 4.63, P. adjusted value < 0.00000004), Prevotella bivia (Log2FoldChange 2.46, P. adjusted value < 0.00024) in high nicotine dependent compared to low nicotine dependent profiles based on Fagerström test for Nicotine Dependence. Functional profiling showed marked differences between smokers and non-smokers controls with an enrichment of Tricarballylate utilization (Log2FoldChange 2.52, P. adjusted value < 0.0013) and Lactate racemization (Log2FoldChange 1.003, P. adjusted value < 0.0001) among others in smokers vs . non-smokers group. According to nicotine dependence, we detected enrichment of Xanthosine utilization (Log2FoldChange 3.38, P. adjusted value < 0.00007), p-Aminobenzoyl-Glutamate utilization (Log2FoldChange 1.33, P. adjusted value < 0.00056), and Multidrug efflux pump in Campylobacter jejuni (Log2FoldChange 1.14, P. adjusted value < 0.00007) biosynthesis modules in the high nicotine dependent group. Conclusions: These differences provide a critical insight on how variations in the oral microbiota may predispose to smoke cessation relapse, serious respiratory illnesses, and lung cancer in heavy cigarette smokers. The observed enrichment of Fusobacterium and Prevotella suggest an intriguing linkage to lung and gut cancers. This information may eventually lead to the development of screening biomarkers to predict early cancer development.
Ar-23 Derivatives With High Endosomal Disrupting Ability Enhance Poly(L-lysine)-mediated Gene Transfection
Authors: Zhang Shikun , Gong Lin , Zhang Xue , Yun Zhi-min , Li Su-Bo , Gao Hong-Wei , Dai Cong-Jie , Yuan Jian-Jun , Chen Jing-ming , Gong Feng , Tan Ying-Xia , Ji Shou-Ping 
Published: June 2020

Abstract
Background：pH-sensitive peptides are a relatively new strategy for conquering poor endosomal release of cationic polymer-mediated transfection. Modification of antimicrobial peptides (AMPs) by exchanging positively-charged residues with negatively-charged glutamic acid residues (Glu) greatly improved its lytic activity at the endosomal pH, which could improve cationic polymer-mediated transfection.Methods：In the present study, we investigate the effect of the number of Glu substituted for positively-charged residues on the endosomal escape activity of AR-23 and the ability of mutated AR-23 for enhancing cationic polymer-mediated transfection. Three analogs were synthesized by replacing the positively-charged residues in AR-23's sequence with Glu one-by-one. The pH-sensitive lysis ability of the peptides, the effect of peptides on the physicochemical characteristics, the intracellular trafficking，the transfection efficiency, and the cytotoxicity of the polyplexes were determined.Results：Increased lytic activity of peptides was observed with the increased number of Glu replacement in the AR-23 sequence at acidic pH. The number of Glu substituted for positively-charged residues of AR-23 dramatically affects its lysis ability at neutral pH. Triple-Glu substitution in AR-23's sequence greatly improved PLL-mediated gene transfection efficiency while maintaining low cytotoxicity.Conclusion：The results indicate that replacement of positively-charged residues with enough Glu residues may be considered a method for designing pH-sensitive peptides, which could be applied as potential enhancers for improving cationic polymer-mediated transfection.
Research HealthSWEDE: Costs With Sublingual Immunotherapy - A Swedish Questionnaire Study
Authors: Olsson Petter , Sköder Carl , Ahlbeck Lars , Hjalte Frida , Welin Karl-Olof , Westin Ulla , Andersson Morgan , Emanuelsson Cecilia Ahlström , Cardell Lars-Olaf 
Published: June 2020

Abstract
BackgroundThe aim of this cross-sectional survey was to compare the health-economic consequences for allergic rhinitis (AR) patients treated with sublingual Immunotherapy (SLIT) in terms of direct and indirect costs with a reference population of patients receiving standard of care pharmacological therapy. MethodsPrimary objective was to analyse the health-economic consequences of SLIT for grass pollen allergy in Sweden vs reference group waiting for subcutaneous immunotherapy (SCIT). A questionnaire was mailed to two groups of AR patients. ResultsThe questionnaire was distributed to 548 patients, 307 with SLIT and 241 in reference group (waiting for SCIT). Response rate was 53.8%. Mean annual costs were higher for reference patients than SLIT group; € 3907 (SD 4268) vs € 2084 (SD 1623) p < 0.001. Mean annual direct cost was higher for SLIT-patients, € 1191 (SD 465) than for reference, € 751 (SD 589) p< 0.001. Mean annual indirect costs for combined absenteeism and presenteeism were lower for patients treated with SLIT, € 912 (SD 1530), than for reference, € 3346 (SD 4120) p< 0.001, with presenteeism as main driver.ConclusionsSLIT seems to be a cost-beneficial way to treat seasonal AR. This information might be used to guide future recommendations.
Bigger Doesn’t Mean Bolder: Testing the Pace-of-Life Syndrome Hypothesis of Four Wild Rodent Species to Novelty and Predation Risk
Authors: Best Ian Nicholas , Shaner Pei-Jen Lee , Lo Hsuan-Yi , Pei Kurtis Jai-Chyi , Kuo Chi-Chien 
Published: June 2020

Abstract
Background: Rodents, a globally distributed and diverse taxonomic group, have been the subjects of countless studies emulating risky situations. In controlled laboratory experiments the majority of focus has been on captive-bred rodents, whereas far less attention has been paid to their wild counterparts. Understanding how wild species respond to novel situations with associated risk can provide valuable information toward the pace-of-life syndrome hypothesis; if their behaviors are associated with a fast-slow continuum of life history. Additionally, whether wild populations of rodents embody adaptive capacity and behavioral repertoires, illustrated by habituation and variation in behavioral traits, respectively. Results: In this comparative study, we examined multiple behavioral responses of three native rodent species Mus caroli, Apodemus agrarius, Rattus losea, and one invasive, Rattus exulans, exposed to an unfamiliar microenvironment and novel cue from an allopatric predator, the leopard cat (Prionailurus bengalensis). All animals were captured and tested in a laboratory setting in Hualien County, Eastern Taiwan and subject to two consecutive nights of experimental trials. Behavioral responses to a novel situation during the first trial differed between species following the predictions of the pace-of-life syndrome; smaller species investing more time in non-defensive behaviors compared to the larger species. More specifically, the smaller species M. caroli and A. agrarius allocated more time to exploration and foraging, whereas the larger rat species R. exulans and R. losea spent more time motionless or concealing. During the second trial, leopard cat cues did not elicit antipredator behaviors, but rather, rodents were found to have opposing responses with increased non-defensive behaviors, specifically foraging efforts. Conclusions: Our results suggest that these four species do largely adhere to the pace-of-life syndrome with the two smaller mice species demonstrating increased boldness in a novel context compared to the larger rat species. Also, the wild populations of rodents in Eastern Taiwan may be naïve to leopard cats. Finally, the rodents in our study demonstrated habituation to the microenvironment, indicating they possess adaptive capacity.
Residential exposure to air pollution, access to neighborhood greenspace and their association with hair cortisol concentrations in the second and third trimester of pregnancy
Authors: Verheyen Veerle Josefa , Remy Sylvie , Lambrechts Nathalie , Govarts Eva , Colles Ann , Poelmans Lien , Verachtert Els , Lefebvre Wouter , Monsieurs Pieter , Vanpoucke Charlotte , Nielsen Flemming , Eeden Lena Van den , Jacquemyn Yves , Schoeters Greet 
Published: June 2020

Abstract
Background: Exposure to air pollution during pregnancy has been associated with adverse pregnancy outcomes in studies worldwide, other studies have described beneficial effects of residential greenspace on pregnancy outcomes. The biological mechanisms that underlie these associations are incompletely understood. Recent studies have shown that a biological stress response, with release of cortisol, may underlie associations between air pollution and health effects. The available research on air pollution exposure in relation to biological stress during pregnancy is still scarce. Methods: We explored associations between residential exposure to air pollution, access to neighborhood greenspace and hair cortisol concentrations in a prospective pregnancy cohort study. We modelled participants’ residential air pollutant concentrations (particulate matter with an aerodynamic diameter ≤ 2.5 μm, nitrogen dioxide (NO2), black carbon (BC)), assessed residential distance to a major road and access to a neighborhood greenspace. Hair cortisol concentrations, reflecting cortisol secretion over a period of 3 months prior to sampling, were determined at the end of the second (n = 133) and third pregnancy trimester (n = 81). Results: Three-month mean residential NO2 and BC concentrations were positively associated with third pregnancy trimester hair cortisol concentrations. The residential distance to a major road was negatively associated with second and third trimester hair cortisol concentrations. Access to a greenspace of 10 hectares or more within 800 meters travel distance significantly moderated the association between residential proximity to a major road and second trimester hair cortisol concentrations. At an average residential distance of 304 meters from a major road, mean second trimester HCC were estimated 22% lower for mothers with access to a neighborhood greenspace (3.71 (95% CI: 3.24, 4.24) pg/mg hair) compared to mothers without access (4.22 (95% CI: 3.26, 5.47) pg/mg hair). The moderation tended towards significance in the third trimester (p < 0.10). Conclusions: Increased residential exposure to air pollution and closer proximity to a major road are associated with an increased biological stress response in the second and third trimester of pregnancy, access to neighborhood greenspace may moderate the association. Trial registration: The IPANEMA study is registered under number NCT02592005 at clinicaltrials.gov.
Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Metastasis from Breast Cancer: A Preliminary Report on 4 Cases
Authors: Yu Jun-Hui , Feng Yu , Li Xin-Bao , Zhang Cheng-Yan , Shi Feng , An Song-Lin , Liu Gang , Zhang Yan-Bin , Zhang Kai , Ji Zhong-He , Li Bing , Yan Guo-Jun , Li Yan-Ping , Li Yan 
Published: June 2020

Abstract
Background: Breast cancer (BC) has been ranked as the first malignancy most common and the fifth in mortality rate among women in China. Peritoneal metastases from BC is a rare disease and no guideline or international consensus for it. Objective: To summarise our experiences in cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) to treat breast cancer peritoneal carcinomatosis (BC PC). Methods: 4 BC PC patients underwent CRS+HIPEC were enrolled in this study. The clinic-pathologic characteristics and overall survival (OS) were collected and analysed. Result: The average age at CRS+HIPEC was 59.8 years. The average time of CRS+HIPEC was 8.8 h. The median number of resected organ areas was 7. Overall survival from CRS+HIPEC were 31, 28, 16 and 52 months. There were no serious adverse events (SAEs) during the perioperative period. Conclusions: The 4 cases provided evidence that integrated therapy with CRS+HIPEC may be a promising strategy to improve the outcome for BC PC patients.
Qualitative Analysis and Dynamical Behavior of a Lassa Haemorrhagic Fever Model with Exposed Rodents and Saturated Incidence Rate
Authors: LOYINMI ADEDAPO CHRIS , AKINFE KINGSLEY TIMILEHIN , OJO ABISOYE ABIODUN 
Published: June 2020

Abstract
We have proposed an unprecedented deterministic model of Lassa Haemorrhagic fever (LHF) model with nonlinear force of LHF infection to capture the transmission dynamics and long term effects of the disease. The Qualitative analyses we have conveyed on this model using well established methods viz: Cauchy’s differential theorem, Birkhoff & Rota’s theorem verifies and reveals the well-posedness, and carrying capacity of the model respectively. We established that a LHF-free equilibrium termed the disease-free equilibrium (DFE) exists for this model and this equilibrium however from our stability analyses, tends to be stable when the basic reproduction number computed via next generation matrix method is less than unity (one); and unstable if otherwise. Furthermore, we have carried out a sensitivity analyses to check variation effects of the model parameters when increased or decreased using the normalized forward-sensitivity index; unraveling the most sensitive parameters which requires the attention of the healthcare workers as; the effective contact rates W, and the rodents’ recruitment rate e. After which numerical simulations of the model were carried out to verify our qualitative analyses (Stability and sensitivity analysis) and to study the dynamical behavior of the model; showing that the presence of saturation instantaneously causes the system to approach a DFE/LHF-Free equilibrium.From these qualitative analyses and numerical simulation results, we recommend early intervention and early treatment of Lassa haemorrhagic virus infection (LAHV) with Ribavirin on the infected, maximum hygiene practices and periodic evacuation of rodents in households in order to curb the recruitment of wild/rodents.
Mechanism and Effect of UCMSCS on Ovarian Structure and Function in Naturally Ageing C57 Mice
Authors: PAN Xing-hua , ZHANG Xue-juan , YAO Xiang , ZHU Xiang-qing , ZHAO Jing , HE Jie , CAI Xue-min , PANG Rong-qing , Ruan Guangping 
Published: June 2020

Abstract
Background: The ovary is the core reproductive organ of a woman and is of great significance for maintaining normal functioning of the reproductive system and the stability of the endocrine system. With an increase in age, the ovaries begin to age, and ovarian ageing will cause a decline in fertility. Methods: Ageing C57 mice were used to explore the mechanism by which mouse umbilical cord mesenchymal stem cells (mUCMSCs) promote the antioxidant repair of granulocytes (mGCs). The ovarian volume in C57 mice, which were routinely reared to 18 months, decreased, and the follicles at all levels disappeared. All statistical analyses were performed using SPSS 21.0 statistical software. P <0.05 was considered to indicate a significant difference. Results: After mUCMSC transplantation, the mouse ovaries increased in size, follicles at various levels were seen in the cortex, and sinus follicle counts increased, indicating that mUCMSCs have a curative effect on ovarian ageing. Conclusions: mUCMSCs downregulated the expression of apoptosis-related genes (Bax, Caspase-3), upregulated the expression of SOD2 and the peroxidase gene PRDX IV, and reduced the granulocyte apoptosis rate and ROS level. Co-cultivation with mUCMSCs can increase antioxidative stress in mGCs and reduce mGC apoptosis.
Assessment of drivers of antimicrobial use and resistance in pig and poultry farming in the Msimbazi River Basin in Tanzania
Authors: Kimera Zuhura Idd , Frumence Gasto , Mboera Leonard E.G. , Rweyemamu Mark M , Mshana Stephen E. , Matee Mecky I.N. 
Published: June 2020

Abstract
Background Uncontrolled use of antimicrobials both in humans and animals coupled with environmental contamination by effluents, toxic chemicals, and heavy metals exacerbate the development and spread of antimicrobial resistance. This paper assessed the drivers of antimicrobial use and resistance in poultry and domestic pig farming and the environment in a densely populated area, with wide-ranging human activities in Tanzania. Methods This was a cross-sectional study conducted from June to September 2019 in the Msimbazi River basin in Eastern Tanzania, which covers an area of 271km2 and harbours a population of approximately 1.2 million. Questionnaires, in-depth interviews, and focus group discussions (FGDs) were used to collect information regarding demographic characteristics, knowledge, practices, attitudes, and perceptions of the drivers of antimicrobial use and resistance in animal farming and the environment. Descriptive statistics and the chi-square tests were used to analyse data from the survey and p<0.05 was considered as statistically significant. The FGDs and interviews were transcribed, coded into categories, and analysed manually. Results We found a higher proportion of usage of veterinary antimicrobials for prophylactic purposes (87.6%), especially tetracycline and quinolones in poultry and pigs farming, than for therapeutic purposes (80.5%). The farming experience was significantly (p<0.05) related to the knowledge on the source of antimicrobial use, methods used in disease diagnosis, access to veterinary services, stocking of antimicrobial at home, and presence of agriculture activities that involve use of manure. Additionally, a significant relationship (p<0.05) existed between the level of education and the practicing group treatment, inadequate extension officers, and inadequate knowledge on infection prevention and control of animal diseases. Uncontrolled disposal of wastes from households, uncontrolled disposal of human and veterinary drugs, and weak implementation of the legal framework was identified as the major pollutants of the environment. Conclusion The high usage of veterinary antimicrobials and environmental contamination taking place in the Msimbazi Basin requires agent multisectoral interventions, including implementation of long-term sustainable training programs aiming at reducing farmers' reliance on antimicrobials, as well as a review of government strategies, policies, and regulations on AMU.