BackgroundChronic hypoxia contributes to progressive tubulointerstitial injury and, consequently, renal failure. However, the effect of hypoxia on glomerular podocytes, which are integral to the slit diaphragm complex and responsible for selectivity of the glomerular filtration barrier, has not been completely determined.MethodsConditionally immortalized mouse podocyte cells were exposed to hypoxic (1% O2) or normoxic (room air) conditions for 24, 48, or 72 hours, after which cell viability was determined by MTT assay. Cells were stained with podocin and phalloidin to determine podocin and intracellular actin distribution. Expression of synaptopodin, CD2-associated protein (CD2AP), NcK, transforming growth factor-β1 (TGF-β1), hypoxia-inducible factor (HIF-1α) were evaluated by real-time polymerase chain reaction.ResultsPodocytes exposed to hypoxia had significantly reduced viability at 48 (87%) and 72 hours (66%). There was disarrangement of intracellular filament actin by phalloidin staining, a 30% weaker fluorescence intensity by podocin staining, significantly reduced expression of synaptopodin (12%), CD2AP (42%), NcK (38%), and increased expression of TGF-β1 and P-ERK after hypoxia treatment.ConclusionPodocyte exposure to hypoxia leads to reduced viability and SD protein expression, which may explain persistent and/or increasing proteinuria in patients with progressive renal failure. Increased expression of TGF-β1 and P-ERK is associated with apoptosis and fibrosis, which could be the link between hypoxia and glomerular injury.

Tuberculosis is a deadly communicable disease caused by the bacillus Mycobacterium tuberculosis (MTB), and pulmonary tuberculosis accounts for over 80% of the total cases. The 1,2,4-triazole is a privileged structure in the discovery of new drugs, and its derivatives act on various targets in MTB. In particular, 1,2,4-triazole hybrids can not only exert dual or multiple antitubercular mechanisms of action but also have the potential to enhance efficacy and reduce side effects. The present work aims to summarize the current status of 1,2,4-triazole hybrids as potential antitubercular agents, covering articles published between 2010 and 2020, to aid the further rational design of novel potential drug candidates endowed with higher efficacy, better compliance and fewer side effects.

Apoptosis is well documented to be a common feature of many pathological processes of the heart. Exogenous endothelin-1 (ET-1) has been shown to be proapoptotic or antiapoptotic, depending on ET-1 concentration, cell type, and the ratio of ET A /ET B receptor subtypes. The role of endogenous ET-1 in cardiomyocyte apoptosis, however, is not clarified. This study observed the effects of the ET A -receptor antagonists BQ610 and BQ123 and the ET B -receptor antagonist BQ788 on hypoxia-induced apoptosis in primary cultured neonatal rat cardiomyocytes. Hypoxic apoptosis was induced by incubating cardiomyocytes in serum-free medium under 3% O2 and 5% CO2 for 24 h and evaluated by TUNEL analysis and flow cytometry. TUNEL analysis showed that the apoptotic cardiomyocytes constituted 24.2% ± 2.2% of the total cells under hypoxic conditions. Treatment with BQ610 (5 mmol/L) significantly reduced the apoptosis rate to 13.2% ± 3.7% (data from 4 independent experiments, p < 0.01 vs. hypoxia). Flow cytometry showed that the percentage of apoptotic cells positively stained with annexin V and propidium iodide was 42.76% ± 4.44% (n = 12) in cultures subjected to hypoxia. BQ123 at 0.04, 0.2, and 1.0 mmol/L dose-dependently reduced the apoptosis rate to 34.00% ± 10.35% (n = 6, p < 0.05), 30.38% ± 8.28% (n = 6, p < 0.01), and 22.89% ± 4.19% (n = 6, p < 0.01), respectively. In contrast, BQ788 did not affect hypoxic apoptosis. These findings suggested that endogenous ET-1 contributed to hypoxia-induced apoptosis in cultured cardiomyocytes, which was mediated by ETA receptors, but not by ETB receptors.Key words: endothelin-1, cardiomyocytes, apoptosis, hypoxia. Résumé :On sait que l'apoptose est une caractéristique commune de nombreuses pathologies du coeur. De plus, des travaux ont montré que l'endothéline-1 exogène est proapoptotique ou antiapoptotique selon la concentration d'ET-1, le type de cellules et le rapport des récepteurs ET A /ET B . Toutefois, le rôle de l'ET-1 endogène dans l'apoptose des cardiomyocytes n'est pas clair. La présente étude a observé les effets des antagonistes des récepteurs ET A , BQ610 et BQ123, et de l'antagoniste des récepteurs ET B , BQ788, sur l'apoptose induite par l'hypoxie dans des cardiomyocytes de rats néonatals en culture primaire. L'apoptose hypoxique a été induite en incubant les cardiomyocytes dans un milieu sans sérum, sous 3 % d'O 2 -5 % de CO 2 pendant 24 h, et évaluée par analyse TUNEL et cytométrie en flux. L'analyse TUNEL a montré un taux de cardiomyocytes apoptotiques de 24,2 % ± 2,2 % sous hypoxie. Un traitement par BQ610 (5 mmol/L) a réduit le taux d'apoptose à 13,2 % ± 3,7 % (calculé à partir de quatre expériences indépendantes, p < 0,01 vs. hypoxie). Le cytomé-trie en flux a indiqué que le pourcentage de cellules apoptotiques positivement marquées par l'annexine V et l'iodure de propidium a été de 42,76 % ± 4,44 % (n = 12) dans les cultures soumises à l'hypoxie. Des doses de 0,04, 0,2 et 1,0 mmol/L de BQ123 ont réduit le taux d'apoptose, en fonction de la dose, à 34,00 % ±...

A positive experience of nature triggers beneficial mental and physical responses. Today, we live in a rapidly urbanizing world where access to nature is often limited. Against this backdrop, this systematic review investigated studies on the effectiveness of small-scale greenery for stress reduction. We searched EMBASE, Cochrane, Web of Science, Scopus, PubMed, and Science Direct, searching databases from inception to April 2022. Studies were screened against predetermined criteria, and the risk of bias was assessed using the Cochrane Handbook for Systematic Reviews of Interventions for RCTs and The Risk of Bias in Non-Randomized Studies of Interventions (ROBINS-I) tool. Of the 2500 records identified, we screened 1817 citations for eligibility, which included 13 RCT studies and 6 non-RCT studies. The studies were conducted in eight different countries. The study populations included office workers, students, senior citizens, and patients with specific diseases. Research has mainly focused on indoor greening, with relatively little research on small-scale outdoor greening. All included studies assessed the impact of the intervention on various stress reduction-related outcomes, with the most common stress measures being blood pressure and the State Trait Anxiety Inventory (STAI). Various beneficial effects of the interventions on human health were reported in all 19 studies, 15 of which reported positive effects on stress reduction. All included studies were at high risk of bias. It is recommended that future studies in this area take appropriate measures to reduce bias and improve quality in order to build a strong evidence-based medical foundation. According to our findings, even very small-scale greening, including indoor green walls and potted plants, may provide effective help for stress relief. Understanding the physiological and psychological benefits of small-scale greenery can help better provide more opportunities for urban residents to engage with nature in the context of dense urban trends, as well as provide some reference for urban design planning.