ADAM10 Alleviates Hypoxia/Reoxygenation-Induced Cardiomyocyte Injury by Activating the Notch Signaling Pathway.

The occurrence of myocardial ischemia/reperfusion injury is commonly observed during cardiac surgery; however, there remains a dearth of effective therapeutic strategies to mitigate this injury. The a disintegrin and metallopeptidase domain 10 (ADAM10) is a transmembrane protein anchored on the cell membrane surface, and its precise mechanism of action in myocardial ischemia/reperfusion injury remains incompletely understood. This study aims to investigate the impact of ADAM10 on cardiomyocyte injury induced by hypoxia/reoxygenation (H/R) and elucidate the underlying mechanisms. The ADAM10 overexpression plasmid was transfected into H9c2 cells, which were subsequently treated with the Notch signaling pathway inhibitor DAPT and cultured under H/R conditions. Cell proliferation activity was assessed using the CCK-8 assay. The levels of LDH, SOD, and MDA were quantified through colorimetric analysis. The levels of ROS and the rate of apoptosis were measured using flow cytometry. The morphological changes in the nucleus of H9c2 cells were observed by employing Hoechst 33258 staining. The mRNA expression levels of ADAM10, Notch1, NICD, and Hes1 in H9c2 cells were determined using qRT-PCR. The expressions of Notch signaling pathway and apoptosis-related proteins were analyzed by Western blot. Overexpression of ADAM10 provided protection to H9c2 cells against injury induced by H/R, leading to an increase in SOD levels and alleviation of oxidative stress caused by the accumulation of ROS and the decrease of SOD activity. Meanwhile, overexpression of ADAM10 inhibited apoptosis in H9c2 cells exposed to H/R by regulating the expression of apoptosis-related proteins, such as Bax, Bcl-2 and Cleaved-caspase-3. Additionally, overexpression of ADAM10 facilitated the activation of the Notch1 signaling pathway in H9c2 cells exposed to H/R by upregulating the protein expression of Notch1, NICD, and Hes1. However, the protective effect of ADAM10 on H/R-induced H9c2 cells was partially reversed by DAPT. Our findings demonstrate that ADAM10 exerts protective effects in H/R-induced H9c2 cells by suppressing oxidative stress and apoptosis via the activation of the Notch signaling pathway.

Mixed probiotics modulated gut microbiota to improve spermatogenesis in bisphenol A-exposed male mice.

Bisphenol A (BPA), an environmental endocrine disruptor (EDC), has been implicated in impairing intestinal and male reproductive dysfunction. The efficacy of gut microbiota modulation for BPA-exposed testicular dysfunction has yet to be verified through research. Therefore, this study explored the potential of mixed probiotics in restoring spermatogenesis damage through the gut-testis axis under BPA exposure. We selected two probiotics strains (Lactobacillus rhamnosus and Lactobacillus plantarum) with BPA removal properties in vitro and the BPA-exposed male mice model was established. The probiotics mixture effectively reduced BPA residue in the gut, serum, and testis in mice. Through 16 S rDNA-seq and metabolomics sequencing, we uncovered that vitamin D metabolism and bile acid levels in the gut was abolished under BPA exposure. This perturbation was linked to an increased abundance of Faecalibaculum and decreased abundance of Lachnospiraceae_NK4A136_group and Ligilactobacillus. The probiotics mixture restored this balance, enhancing intestinal barrier function and reducing oxidative stress. This improvement was accompanied by a restored balance of short-chain fatty acids (SCFAs). Remarkably, the probiotics ameliorated testicular dysfunction by repairing structures of seminiferous tubules and reversing arrested spermiogenesis. Further, the probiotics mixture enhanced testosterone-driven increases in spermatogonial stem cells and all stages of sperm cells. Testicular transcriptome profiling linked these improvements to fatty acid degradation and peroxisome pathways. These findings suggest a significant interplay between spermatogenesis and gut microbiota, demonstrating that probiotic intake could be a viable strategy for combating male subfertility issues caused by BPA exposure.

Effect of PFOA exposure on diminished ovarian reserve and its metabolism.

Owing to its difficulty in degrading and ease of accumulation in the body, perfluorooctanoic acid (PFOA) has a detrimental effect on reproduction. This study aimed to examine the effect of PFOA concentration in follicular fluid during ovulation stimulation on embryo quality and the impact of PFOA exposure on the metabolic components of follicular fluid. This was a single-center prospective study that included 25 patients with diminished ovarian reserve (DOR), 25 with normal ovarian reserve (NOR), and 25 with polycystic ovary syndrome (PCOS). Follicular fluid samples were analyzed using ultra-high performance liquid chromatography-tandem mass spectrometry. We demonstrated that the PFOA levels of follicular fluid in the DOR group were higher than those in the NOR group and PCOS group (P < 0.05). PFOA concentration in the PCOS group was negatively correlated with high-quality embryos (P < 0.05). To gain more insight into the impact of PFOA on the metabolic composition of follicular fluid, we classified the DOR group based on the PFOA concentration, for which metabolomic analysis was performed. In the high-concentration PFOA group, there was an increase and a decrease in three and nine metabolites, respectively, compared to that in the low-concentration group. These results suggest that PFOA may alter the metabolic composition of follicular fluid, thus, affecting ovarian reserve function.

Exposure-lag response of fine particulate matter on intrauterine fetal death: an analysis using a distributed lag non-linear model in Linxia Hui Autonomous Prefecture, China.

The results of studies on intrauterine fetal death (IUFD) caused by exposure to fine particulate matter (PM2.5) during pregnancy are inconsistent. Further exploration of the dose-response relationship and exposure window is required. We aimed to provide a reference for policy formulation by estimating the exposure-lag relationship of PM2.5 on IUFD and looking for sensitive exposure windows. IUFD data was obtained from China Children Under 5 Death Surveillance Network in Linxia Hui Autonomous Prefecture from 2016 to 2020. Air pollution data and temperature data were obtained from ambient air monitoring stations and China Meteorological Data Network, respectively. The moving average is used to describe the trend and seasonality of PM2.5 exposure; the distributed lag non-linear model (DLNM) is used to estimate the exposure-lag effect; the sandwich estimators are used to correct the variance-covariance matrix; and the model selected by Akaike's Information Criterion (AIC) finally adjusts gender, temperature, and district. About 180,622 infants were enrolled in the study, including 952 IUFDs (5.27‰). The median of PM2.5 exposure is 34.08 µg/m3. There is an exposure-lag effect of PM2.5 on IUFD approximate to a wavy shape; the concentration with effect is 40-90 µg/m3; and the sensitive lag time is 1, 2, 3, 8, 9, and 10 months. The maximum RR value of the exposure-lag effect of PM2.5 on IUFD is 1.61 [95% CI 1.19, 2.19], in which the concentration of PM2.5 is 62 µg/m3, and the lag month is 9 months. In the case of less than 6 months lag, the maximum RR value of the exposure-lag effect of PM2.5 on IUFD is 1.43 [95% CI 1.24, 1.67], in which the concentration of PM2.5 is 73 µg/m3, and the lag month is 3 months. Exposure to PM2.5 concentrations above 40 µg/m3 may increase the risk of IUFD, especially in the first and third trimesters.

The effect of intravenous lidocaine on propofol dosage in painless bronchoscopy of patients with COPD.

Background: We tested the hypothesis that intravenous (IV) lidocaine reduces propofol requirements in painless bronchoscopy in patients with chronic obstructive pulmonary disease (COPD). Methods: A total of 93 patients who underwent bronchoscopy were included in this randomized placebo-controlled study. The patients were randomly divided into two groups. After the IV doses of nalbuphine, patients were given a bolus of propofol, which was titrated if necessary until loss of consciousness. Then patients were given IV lidocaine (2 mg/kg then 4 mg/kg/h) or the same volume of saline. The primary endpoint was the propofol requirements. Secondary endpoints were the incidence of hypoxemia, the incidence of cough during glottis examination, the systolic blood pressure (SBP) and heart rate (HR) during bronchoscopy procedures, the bronchoscopist's comforts, and the time for wakefulness before recovery. Results: Lidocaine infusion resulted in a significant reduction in propofol requirements (p < .0001), and the incidence of hypoxemia (p = .001) and cough (p = .003) during examination decreased significantly in the lidocaine group. During the examination, the fluctuation of SBP and HR was significantly lower than that in the control group, and the difference was statistically significant (p < .05). Bronchoscopist's comforts were higher in the lidocaine group (p < .001), and time for wakefulness (p < .001) were significantly lower in the lidocaine group. Conclusion: In painless bronchoscopy in patients with COPD, IV infusion of lidocaine resulted in a reduction in propofol dose requirements and reduce the incidence of adverse events.

Diet and human reproductive system: Insight of omics approaches.

Nutrition and lifestyle have a great impact on reproduction and infertility in humans, as they are essential for certain processes such as implantation, placental growth, angiogenesis, and the transfer of nutrients from the mother to the fetus. The aim of this review is to provide the interconnection between nutrition and reproductive health through the insight of omics approaches (including metabolomics and nutrigenomics). The effect of various macronutrients, micronutrients, and some food-associated components on male and female reproduction was discussed. Recent research work was collected through database search from 2010 to 2020 to identify eligible studies. Alterations of metabolic pathways in pregnant women were deliberated with an emphasis on different strategies of lifestyle and dietary interventions. Several nutritional methods, which are important for embryonic and child neurological development, nutritional supplements to lactation, and improved gestational length along with birth weight have been emphasized. Considerable advances in omics strategies show potential technological development for improving human reproductive health.

Role of Exosomes in the Exchange of Spermatozoa after Leaving the Seminiferous Tubule: A Review.

BACKGROUND: Exosomes are extracellular vesicles (EVs) released from cells upon fusion of an intermediate endocytic compartment with the plasma membrane. They refer to the intraluminal vesicles released from the fusion of multivesicular bodies with the plasma membrane. The contents and number of exosomes are related to diseases such as metabolic diseases, cancer and inflammatory diseases. Exosomes have been used in neurological research as a drug delivery tool and also as biomarkers for diseases. Recently, exosomes were observed in the seminal plasma of the one who is asthenozoospermia, which can affect sperm motility and capacitation. OBJECTIVE: The main objective of this review is to deeply discuss the role of exosomes in spermatozoa after leaving the seminiferous tubule. METHODS: We conducted an extensive search of the literature available on relationships between exosomes and exosomes in spermatozoa on the bibliographic database. CONCLUSION: This review thoroughly discussed the role that exosomes play in the exchange of spermatozoa after leaving the seminiferous tubule and its potential as a drug delivery tool and biomarkers for diseases as well.