Search

Problem: Anti‐Ro/SSA and/or anti‐La/SSB (anti‐SSA/SSB) antibodies impair pregnancy outcomes, including embryo implantation and pregnancy maintenance. Optimal endometrial immune status is essential for successful pregnancy. However, whether these antibodies affect endometrial immune status is still unclear. Menstrual blood can be collected non‐invasively, differs from peripheral blood, and can reflect the endometrial immune status. We herein focused on changes in subsets of natural killer (NK) cells and T cells in menstrual blood. Methods of study: Menstrual blood samples from anti‐SSA/SSB antibody–positive (n = 18) and anti‐SSA/SSB antibody–negative control (n = 8) women were collected, and the profile of lymphocyte subsets was analyzed. The phenotypes of menstrual blood CD49a− and CD49a+ NK cells were compared, and the abundance of NK and CD49a+ NK cells in menstrual blood of the two groups was assessed. Additionally, CD4+T and CD8+T cells were investigated for their ability to secret functional cytokines. Results: Menstrual blood contains a large number of (mostly CD49a+) NK cells, which exhibited a more exhausted phenotype with greater expression of the immune checkpoint molecules programmed cell death protein 1 and Tim‐3 compared to CD49a− conventional NK cells. CD8+T cells in menstrual blood from anti‐SSA/SSB antibody–positive women produced a stronger response after stimulation, accompanied by increased interferon‐γ, tumor necrosis factor–α, and granzyme B secretion (P < 0.05, separately). Conclusion: Menstrual blood cell composition differs between anti‐SSA/SSB antibody–positive women and normal controls, especially in terms of CD49a+ NK cells and CD8+T cells, unbalancing the immune cell composition and inflammatory uterine microenvironment and possibly contributing to adverse pregnancy outcomes. [ABSTRACT FROM AUTHOR]

To conduct a meta-analysis to determine the association between two single nucleotide polymorphisms (SNPs) miRNA146a rs2910164 (G > C) and miRNA-499 rs3746444 (T > C) and asthma risk. PubMed and Embase (updated May 17, 2019). (microRNA OR microRNAs) AND (polymorphism OR polymorphisms) AND (Asthmas OR Bronchial Asthma OR Asthma, Bronchial). Six eligible case-control studies (2441 asthma cases and 3044 controls) met our inclusion criteria. A trend of increased asthma risk was indicated by the heterozygote model (miR-499: TC versus TT, OR = 1.38, 95% CI = 1.06–1.79, P < 0.01) and the dominant model (miR-499: TC + CC versus TT, OR = 1.60, 95% CI = 1.07–2.39, P < 0.01) of miRNA-499 rs3746444. Polymorphisms rs2910164 in miRNA-146a of the allele model (miR-146a: C versus G, OR = 0.84, 95% CI = 0.74–0.96, P = 0.238), homozygote model (miR-146a: CC versus GG, OR = 0.68, 95% CI = 0.51–0.91, P = 0.213), recessive model (miR-146a: CC versus GC + GG, OR = 0.75, 95% CI = 0.60–0.94, P = 0.149) indicated a decreased risk of asthma. The miR-499 rs3746444 (T > C) polymorphism is associated with asthma susceptibility and miRNA-146a rs2910164 (G > C) polymorphism has a protective role against susceptibility to asthma. [ABSTRACT FROM AUTHOR]

Background: Mitochondrial dysfunction plays a crucial role in Type 2 Diabetes Mellitus (T2DM) and its complications. However, the genetic pathophysiology remains under investigation. Through multi-omics Mendelian Randomization (MR) and colocalization analyses, we identified mitochondrial-related genes causally linked with T2DM and its complications., Methods: Summary-level quantitative trait loci data at methylation, RNA, and protein levels were retrieved from European cohort studies. GWAS summary statistics for T2DM and its complications were collected from the DIAGRAM and FinnGen consortiums, respectively. Summary-data-based MR was utilized to estimate the causal effects. The heterogeneity in dependent instrument test assessed horizontal pleiotropy, while colocalization analysis determined whether genes and diseases share the same causal variant. Enrichment analysis, drug target analysis, and phenome-wide MR were conducted to further explore the biological functions, potential drugs, and causal associations with other diseases., Results: Integrating evidence from multi-omics, we identified 18 causal mitochondrial-related genes. Enrichment analysis revealed they were not only related to nutrient metabolisms but also to the processes like mitophagy, autophagy, and apoptosis. Among these genes, Tu translation elongation factor mitochondrial ( TUFM ), 3-hydroxyisobutyryl-CoA hydrolase ( HIBCH ), and iron-sulfur cluster assembly 2 ( ISCA2 ) were identified as Tier 1 genes, showing causal links with T2DM and strong colocalization evidence. TUFM and ISCA2 were causally associated with an increased risk of T2DM, while HIBCH showed an inverse causal relationship. The causal associations and colocalization effects for TUFM and HIBCH were validated in specific tissues. TUFM was also found to be a risk factor for microvascular complications in T2DM patients including retinopathy, nephropathy, and neuropathy. Furthermore, drug target analysis and phenome-wide MR underscored their significance as potential therapeutic targets., Conclusions: This study identified 18 mitochondrial-related genes causally associated with T2DM at multi-omics levels, enhancing the understanding of mitochondrial dysfunction in T2DM and its complications. TUFM , HIBCH , and ISCA2 emerge as potential therapeutic targets for T2DM and its complications., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Miao, Feng, Zhu, Chen, Kang, Wang, Lu and Zhang.)

Human autologous sperm freezing involves ejaculated sperm, and testicular or epididymal puncture sperm freezing, and autologous sperm freezing is widely used in assisted reproductive technology. In previous studies, researchers have tried to cryopreserve sperm from mammals (rats, dogs, etc.) using a -80°C freezer and have achieved success. It is common to use liquid nitrogen vapor rapid freezing to cryopreserve human autologous sperm. However, the operation of this cooling method is complicated, and the temperature drop is unstable. In this study, we compared the quality of human ejaculation and testicular sperm after liquid nitrogen vapor rapid freezing and -80°C freezing for the first time. By analyzing sperm quality parameters of 93 ejaculated sperm and 10 testicular sperm after liquid nitrogen vapor rapid freezing and -80°C freezing, we found reactive oxygen species (ROS) of sperm of the -80°C freezer was significantly lower than liquid nitrogen vapor rapid freezing. Regression analysis showed that progressive motility, ROS, and DNA fragmentation index (DFI) in post-thaw spermatozoa were correlated with sperm progressive motility, ROS, and DFI before freezing. For the freezing method, the -80°C freezer was positively correlated with the sperm progressive motility. Among the factors of freezing time, long-term freezing was negatively correlated with sperm progressive motility and ROS. Although freezing directly at -80°C freezer had a slower temperature drop than liquid nitrogen vapor rapid freezing over the same period, the curves of the temperature drop were similar, and slight differences in the freezing point were observed. Furthermore, there were no statistically significant differences between the two methods for freezing testicular sperm. The method of direct -80°C freezing could be considered a simplified alternative to vapor freezing for short-term human sperm storage. It could be used for cryopreservation of autologous sperm (especially testicular sperm) by in vitro fertilization centers. Clinical Trial Registration: (website), identifier (ChiCTR2100050190)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Lu, Bai, Wu, Huang, Zhou, Xu, Wan, Jin, Jiang and Tong.)