Miracle-dz/UniFAR-FTUs huggingface dataset:
The effect of ambroxol on chloride transport, CFTR and ENaC in cystic fibrosis airway epithelial cells

Ambroxol, a mucokinetic anti‐inflammatory drug, has been used for treatment of cystic fibrosis (CF). The respiratory epithelium is covered by the airway surface liquid (ASL), the thickness and composition of which is determined by Cl− efflux via the cystic fibrosis transmembrane conductance regulator (CFTR) and Na+ influx via the epithelial Na+ channel (ENaC). In cells expressing wt‐CFTR, ambroxol increased the Cl‐ conductance, but not the bicarbonate conductance of the CFTR channels. We investigated whether treatment with ambroxol enhances chloride transport and/or CFTR and ENaC expression in CF airway epithelial cells (CFBE) cells. CFBE cells were treated with 100 µM ambroxol for 2, 4 or 8 h. mRNA expression for CFTR and ENaC subunits was analysed by real‐time polymerase chain reaction (RT‐PCR); protein expression was measured by Western blot. The effect of ambroxol on Cl− transport was measured by Cl− efflux measurements with a fluorescent chloride probe. Ambroxol significantly stimulated Cl− efflux from CFBE cells (a sixfold increase after 8 h treatment), and enhanced the expression of the mRNA of CFTR and α‐ENaC, and of the CFTR protein. No significant difference was observed in β‐ENaC after exposure to ambroxol, whereas mRNA expression of γ‐ENaC was reduced. No significant effects of ambroxol on the ENaC subunits were observed by Western blot. Ambroxol did not significantly affect the intracellular Ca2+ concentration. Upregulation of CFTR and enhanced Cl− efflux after ambroxol treatment should promote transepithelial ion and water transport, which may improve hydration of the mucus, and therefore be beneficial to CF‐patients.
Home environments, physical activity, and energy expenditure among low-income overweight and obese women

ABSTRACT Ecologic models of physical activity identify multiple environmental domains that influence activity levels, including the home. This study examined aspects of the home environment associated with objective measures of physical activity in overweight and obese women. Study participants were recruited through three federally qualified health centers in rural southwest Georgia as part of a randomized controlled trial of a home-environment-focused weight gain prevention intervention. Data collected from February 2011 to December 2012 were from 301 participants who completed baseline interviews and wore accelerometers for 7 days. Most were African American (83.4%) and obese (50.5%) or morbidly obese with body mass index ≥40 (35.6%). Mean age was 50.6 years. Participants were highly sedentary, with 7.9 hours of non-sedentary time per week, primarily in light activity. In a multivariate model, exercise equipment (p = .03), family support (p = .02), and full-time employment (p = .03) were positively associated with non-sedentary time, whereas age (p = .003), living in a more rural area (p = .03), and having an exercise space (p = .01) were negatively associated. Home environments may be promising targets for programs aimed at increasing activity levels among overweight and obese women.
SLC26 anion exchangers in uterine epithelial cells and spermatozoa: clues from the past and hints to the future

The solute carrier 26 (SLC26) family emerges as a distinct class of anion transporters with its members SLC26A3 (Slc26a3) and SLC26A6 (Slc26a6) reported to be electrogenic Cl−/HCO3− exchangers. While it is known that uterine fluid has high HCO3− content and that HCO3− is essential for sperm capacitation, the molecular mechanisms underlying the transport of HCO3− across uterine epithelial cells and sperm have not been fully investigated. The present review re‐examines the results from early reports studying anion transport, finding clues for the involvement of Cl−/HCO3− anion exchangers in electrogenic HCO3− transport across endometrial epithelium. We also summarise recent work on Slc26a3 and Slc26a6 in uterine epithelial cells and sperm, revealing their functional role in working closely with the cystic fibrosis transmembrane conductance regulator (CFTR) for HCO3− transport in these cells. The possible involvement of these anion exchangers in other HCO3− dependent reproductive processes and their implications for infertility are also discussed.
Role of microRNA‐27a in myoblast differentiation

MicroRNAs (miRNAs) are a class of endogenous non‐coding RNAs that are critically involved in roles in various aspects of skeletal myogenesis. microRNA miR‐27a promotes myoblast proliferation by targeting myostatin, a critical inhibitor of skeletal muscle development, but its mode of action in myoblast differentiation remains unclear. We have found that expression of miR‐27a and myostatin were upregulated and downregulated, respectively, during myoblast differentiation. Overexpression of miR‐27a increased the number of myosin heavy chain (MHC)‐positive cells and upregulated mRNA and protein of MyoD and myogenin. These findings indicate that miR‐27a plays a role in enhancing myoblast differentiation.
Identification of microRNAs involved in the radioresistance of esophageal cancer cells

Radioresistance is considered as the most important reason for local tumour recurrence. This study investigates the role of miRNAs in radioresistant human esophageal cancer cells. Human miRNA microarray has been used to detect the differential expressed microRNAs between radioresistant esophageal cell line KYSE‐150R and the parental cell line KYSE‐150. The relative expression of some candidate miRNAs was measured by quantitative real‐time PCR (qRT‐PCR). Potential mRNA targets were analysed bioinformatically. Significant upregulation of 10 microRNAs and downregulation of 25 microRNAs were detected. The statistical significance of downregulation in hsa‐miR‐301a, hsa‐miR‐141 and hsa‐miR‐18b expression (P < 0.05) were confirmed by qRT‐PCR. The correlation of the predicted microRNA target genes to apoptosis (63 genes), cell cycle (67 genes), DNA damage and repair (18 genes) were confirmed by functional annotation. The downregulation of hsa‐miR‐301a promoted radioresistance in KYSE‐150R through the upregulation of wnt1, indicating that wnt/β‐catenin signal pathway might be important in radioresistance. In conclusion, a unique set of miRNAs and their expression profiles in radiation resistance have been identified, providing a solid basis for future studies to investigate the target genes of these miRNAs and their function.
Obesity pandemic, correlated factors and guidelines to define, screen and manage obesity in Taiwan

The prevalence of obesity and associated chronic diseases has increased rapidly in Taiwan. Data from three consecutive Nutrition and Health surveys in Taiwan show that obesity prevalence has tripled for elementary school boys and doubled for girls since 1993–1996. About one‐third of boys (15.5% and 14.7% for overweight and obesity, respectively) and one‐quarter of girls were either overweight (14.4%) or obese (9.1%) in 2001–2002. For adults, obesity prevalence rates defined by body mass index ≥27 kg m−2 increased from 10.5% in men and 13.2% in women in the 1993–1996 survey, to around 17% in 2005. Prevalence of overweight was around 20% in 1993–1996 for both men or women, and increased to 30% in 2005 for men. No change was found in women. The underprivileged regions usually had higher prevalence of obesity and associated diseases. Scientific bases for Taiwan obesity definition are set out together with the screening and management plans. High‐calorie intake was associated with obesity in young children (grades 1–2), but not in older children and adults. Physical inactivity and sedentary lifestyle‐related variables were associated with obesity in men and older boys. In addition, good dietary quality was associated with a lower risk of obesity independent of energy intake in elderly Taiwanese. More research is needed to find effective determinants and public health measures for obesity, and concerted efforts are required to combat this rising health problem.
Health-related quality-of-life and receipt of women-centered HIV care among women living with HIV in Canada

ABSTRACT We measured health-related quality of life (HRQOL) using the SF-12 among women living with HIV (WLWH) in Canada between August 2013 and May 2015. We investigated differences by perceived receipt of women-centered HIV care (WCHC), assessed using an evidence-based definition with a 5-point Likert item: “Overall, I think that the care I have received from my HIV clinic in the last year has been women-centered” (dichotomized into agree vs. disagree/neutral). Of 1308 participants, 26.3 percent were from British Columbia, 48.2 percent from Ontario, and 25.5 percent from Québec. The median age was 43 years (interquartile range = 36–51). Most (42.2 percent) were White, 29.4 percent African/Caribbean/Black, and 21.0 percent Indigenous. Overall, 53.4 percent perceived having received WCHC. Mean physical and mental HRQOL scores were 43.8 (standard deviation [SD] = 14.4) and 41.7 (SD = 14.2), respectively. Women perceiving having received WCHC had higher mean physical (44.7; SD = 14.0) and mental (43.7; SD = 14.1) HRQOL scores than those not perceiving having received WCHC (42.9; SD = 14.8 and 39.5; SD = 14.0, respectively; p < .001). In multivariable linear regression, perceived WCHC was associated with higher mental (β = 3.48; 95 percent confidence interval: 1.90, 5.06) but not physical HRQOL. Improving HRQOL among Canadian WLWH, which was lower than general population estimates, is needed, including examining the potential of WCHC as an effective model of clinical care.
Comparative study of directional differentiation of human and mouse embryonic stem cells into cardiomyocytes

This comparative study investigates the method, efficiency, and anti‐hypoxic ability of cardiomyocytes, directionally induced from human (h) and mouse (m) embryonic stem cells (ESCs). hESCs were induced into cardiomyocytes by suspension culture, without inducers, or adherent culture using the inducers activin A and BMP4. mESCs were induced into cardiomyocytes by hanging‐drop method, without inducers or induced with vitamin C. All four methods successfully induced ESCs to differentiate into cardiomyocytes. There was a significant difference between groups with and without inducers. A significant difference was found between mESC and hESC groups with inducers. The average beating frequency of cardiomyocytes differentiated from hESC was lower than cardiomyocytes differentiated from mESC, while the average beating frequency of cardiomyocytes differentiated from the same cell line, despite different culture methods, did not differ. Beating cardiomyocytes of each group were positive for cTnT staining. Spontaneous action potentials of beating cardiomyocytes were detected by patch‐clamp experiments in each group. Different apoptotic ratios were detected in beating cardiomyocytes in each group and the difference between cardiomyocytes induced from mESCs and hESCs was statistically significant. The differentiation efficiencies in the groups without inducers were significantly higher than those without inducers. The induction of mESCs was more simple and efficient compared with hESCs. Without the presence of other protective factors, the anti‐hypoxic ability of cardiomyocytes induced from hESCs was stronger and the beating times were longer in vitro compared with mESCs.
Chronic disease trends due to excess body weight in Australia

Trends in chronic diseases provide insights into strategies required to improve population health. The authors determined prevalence and multiple‐adjusted population attributable risk (PAR) estimates of chronic diseases because of lifestyle factors among Australian adults between 1989–90 and 2004–5, accounting for demographic factors. Between 1989–90 and 2004–5, prevalence increased for diabetes (3.8–6.0%, P < 0.001) and high cholesterol (11.3–13.9%, P < 0.001), but decreased for high blood pressure (21.4–20.4%, P = 0.003) and cardiovascular disease (CVD, 6.2–5.4%, P < 0.001). Prevalence increased for body mass index (BMI) 25–29.9 (30.3–34.9%, P < 0.001), BMI 30–34.9 (7.4–13.5%, P < 0.001) and BMI 35+ (2.1–5.4%, P < 0.001), but decreased for metabolic equivalent‐hours per week (MET‐hr/week) 0 (36.8–33.1%, P < 0.001) and current smokers (27.6–24.4%, P < 0.001). Diabetes, high cholesterol and high blood pressure burden increased mostly for 60+ years, lowest income quintiles and high BMI (30–34.9 and 35+). Diabetes and CVD burden increased mostly for MET‐hr/week 0. Many chronic disease cases would have been theoretically prevented if adults had no prior exposure to BMI 25–29.9 (PAR 9–17%), BMI 30+ (PAR 1–14%) and MET‐hr/week 0 (PAR 6–14%). Reducing exposure to lifestyle hazards across the lifespan is required for reversing the rising burden of chronic diseases. Decreases in CVD and high blood pressure prevalence were likely due to targeted improvements in health care, indicating that more can and should be done.
The Diet, Obesity and Genes (Diogenes) Dietary Study in eight European countries – a comprehensive design for long‐term intervention

Diogenes is a Pan‐European, randomized, controlled dietary intervention study investigating the effects of dietary protein and glycaemic index on weight (re)gain, metabolic and cardiovascular risk factors in obese and overweight families in eight European centres. The article is methodological in character, and the presentation of ‘results’ will be limited to baseline characteristics of the study populations included. A total of 891 families with at least one overweight/obese parent underwent screening. The parents started an initial 8‐week low‐calorie diet and families with minimum one parent attaining a weight loss of ≥8%, were randomized to one of five energy ad libitum, low‐fat (25–30 E%) diets for 6 or 12 months: low protein/low glycaemic index, low protein/high glycaemic index, high protein/low glycaemic index, high protein/high glycaemic index or control (national dietary guidelines). At two centres the families were provided dietary instruction plus free foods for 6 months followed by 6‐month dietary instruction only. At the remaining six centres the families received dietary instruction only for 6 months. The median weight loss during the low‐calorie diet was 10.3 kg (inter‐quartile range: 8.7–12.8 kg, n = 775). A total of 773 adults and 784 children were randomized to the 6‐month weight (re)gain prevention phase. Despite major cultural and dietary regional differences in Europe, interventions addressing effects of dietary factors are feasible with a reasonable attrition.
Mini-percutaneous nephrolithotomy versus retrograde intrarenal surgery for renal stones larger than 10 mm : a prospective randomized controlled trial

OBJECTIVES: To compare mini-percutaneous nephrolithotomy (mini-PCNL) and retrograde intrarenal surgery (RIRS) in the management of renal stones larger than 10 mm in a single session. METHODS: Seventy patients presenting with renal stones >10 mm were randomized to a mini-PCNL or a RIRS group in a ratio of 1:1. Randomization was performed by a biostatistician and opened to the surgeon at the time of the patient’s admission on the day before surgery. Patient and stone characteristics, perioperative outcomes, and complications were compared between the two groups. The primary end point of “stone-free” which was defined as no residual stone or stones <2 mm on computed tomography within 3 months postoperatively. RESULTS: Thirty-five patients (Mini-PCNL) and 33 (RIRS) were included in the final analysis. Mini-PCNL and RIRS had a stone free rate of 85.7% and 97.0%, respectively (P=0.199). Operation time (P=0.148), hemoglobin decline (P=0.323), and hospital stay (P=0.728) were similar between the two groups. Pain visual analogue score at 1 hour postoperatively (P=0.029) and analgesic requirement (P=0.050) were higher in the RIRS group. Two patients in the mini-PCNL group and one in the RIRS group had minor pelvic or ureter perforation. One patient in each of the two groups had hypertension and urinary tract infection. CONCLUSIONS: Mini-PCNL and RIRS are safe and feasible surgical options to manage renal stones larger than 10 mm. RIRS produced a slightly higher stone free rate, but more immediate postoperative pain and higher analgesic requirement M AN US CR IP T AC CE PT ED ACCEPTED MANUSCRIPT
Inhibition of Gli/hedgehog signaling in prostate cancer cells by “cancer bush” Sutherlandia frutescens extract

Sutherlandia frutescens is a medicinal plant, traditionally used to treat various types of human diseases, including cancer. Previous studies of several botanicals link suppression of prostate cancer growth with inhibition of the Gli/hedgehog (Gli/Hh) signaling pathway. Here we hypothesized the anti‐cancer effect of S. frutescens was linked to its inhibition of the Gli/Hh signaling in prostate cancer. We found a dose‐ and time‐dependent growth inhibition in human prostate cancer cells, PC3 and LNCaP, and mouse prostate cancer cell, TRAMP‐C2, treated with S. frutescens methanol extract (SLE). We also observed a dose‐dependent inhibition of the Gli‐reporter activity in Shh Light II and TRAMP‐C2QGli cells treated with SLE. In addition, SLE can inhibit Gli/Hh signaling by blocking Gli1 and Ptched1 gene expression in the presence of a Gli/Hh signaling agonist (SAG). A diet supplemented with S. frutescens suppressed the formation of poorly differentiated carcinoma in prostates of TRAMP mice. Finally, we found Sutherlandioside D was the most potent compound in the crude extract that could suppress Gli‐reporter in Shh Light II cells. Together, this suggests that the S. frutescens extract may exert anti‐cancer effect by targeting Gli/Hh signaling, and Sutherlandioside D is one of the active compounds.
A systematic review of environmental factors and obesogenic dietary intakes among adults: are we getting closer to understanding obesogenic environments?

This study examined whether physical, social, cultural and economical environmental factors are associated with obesogenic dietary behaviours and overweight/obesity among adults. Literature searches of databases (i.e. PubMed, CSA Illumina, Web of Science, PsychInfo) identified studies examining environmental factors and the consumption of energy, fat, fibre, fruit, vegetables, sugar‐sweetened drinks, meal patterns and weight status. Twenty‐eight studies were in‐scope, the majority (n= 16) were conducted in the USA. Weight status was consistently associated with the food environment; greater accessibility to supermarkets or less access to takeaway outlets were associated with a lower BMI or prevalence of overweight/obesity. However, obesogenic dietary behaviours did not mirror these associations; mixed associations were found between the environment and obesogenic dietary behaviours. Living in a socioeconomically‐deprived area was the only environmental factor consistently associated with a number of obesogenic dietary behaviours. Associations between the environment and weight status are more consistent than that seen between the environment and dietary behaviours. The environment may play an important role in the development of overweight/obesity, however the dietary mechanisms that contribute to this remain unclear and the physical activity environment may also play an important role in weight gain, overweight and obesity.
Autophagy regulates the apoptosis of bone marrow‐derived mesenchymal stem cells under hypoxic condition via AMP‐activated protein kinase/mammalian target of rapamycin pathway

Bone marrow‐derived mesenchymal stem cells (BM‐MSCs) have been demonstrated as an ideal autologous stem cells source for cell‐based therapy for myocardial infarction (MI). However, poor viability of donor stem cells after transplantation limits their therapeutic efficiency, whereas the underlying mechanism is still poorly understood. Autophagy, a highly conserved process of cellular degradation, is required for maintaining homeostasis and normal function. Here, we investigated the potential role of autophagy on apoptosis in BM‐MSCs induced by hypoxic injury. BM‐MSCs, isolated from male C57BL/6 mice, were subjected to hypoxia and serum deprivation (H/SD) injury for 6, 12, and 24 h, respectively. The autophagy state was regulated by 3‐methyladenine (3MA) and rapamycin administration. Furthermore, compound C was administrated to inhibit AMPK. The apoptosis induced by H/SD was determined by TUNEL assays. Meanwhile, autophagy was measured by GFP‐LC3 plasmids transfection and transmission electron microscope. Moreover, protein expressions were evaluated by Western blot assay. In the present study, we found that hypoxic stress increased autophagy and apoptosis in BM‐MSCs time dependently. Meanwhile, hypoxia increased the activity of AMPK/mTOR signal pathway. Moreover, increased apoptosis in BM‐MSCs under hypoxia was abolished by 3‐MA, whereas was aggravated by rapamycin. Furthermore, the increased autophagy and apoptosis in BM‐MSCs induced by hypoxia were abolished by AMPK inhibitor compound C. These data provide evidence that hypoxia induced AMPK/mTOR signal pathway activation which regulated the apoptosis and autophagy in BM‐MSCs. Furthermore, the apoptosis of BM‐MSCs under hypoxic condition was regulated by autophagy via AMPK/mTOR pathway.
Bovine endometrial cells: a source of mesenchymal stem/progenitor cells

Endometrial mesenchymal stem/progenitor cells (eMSCs) are multipotent cells known to modulate the immune system and have clinical application for human and animal health. This makes these bovines cells attractive for dual use as cellular therapy and experimental model. The aim of this study was to isolate, evaluate the differentiation potential, immunophenotypic and immunocytochemistry characteristics, chromosomal stability, cloning efficiency, and cryopreservation response of bovine eMSCs collected in two phases of the estrous cycle. For this, cells were isolated and submitted to differentiation for adipogenic and osteogenic lineage. The cells were then characterized by flow cytometer (FC) (vimentin, CD29, CD44, MHC‐II, CD34) and immunocytochemistry (vimentin, pan‐cytokeratin, CD44) and submitted to cytogenetic and cloning efficiency assay. The cells were also cryopreserved using two different medium of cryopreservation and analyzed by FC for viability, necrosis, late‐apoptosis + necrosis, and initial apoptosis rates before and after cryopreservation. We obtained homogeneous cell populations which have fibroblastic morphology and adherence to plastic. These cells expressed high levels of markers CD29, CD44, and vimentin, low expression levels for CD34 and no MHC‐II. The cells were chromosomally stable (2n = 60) with high cloning efficiency and no difference (P > 0.05) between medium of cryopreservation or phase was observed after thawing. We showed the presence and differentiation potential of bovine eMSCs, with chromosomal stability and great response to cryopreservation with both medium, which has implications for build biobanks or development of new therapeutic approaches to combat uterine diseases or to study.