Macrophages are widely distributed innate immune cells that play indispensable roles in the innate and adaptive immune response to pathogens and in-tissue homeostasis. Macrophages can be activated by a variety of stimuli and polarized to functionally different phenotypes. Two distinct subsets of macrophages have been proposed, including classically activated (M1) and alternatively activated (M2) macrophages. M1 macrophages express a series of proinflammatory cytokines, chemokines, and effector molecules, such as IL-12, IL-23, TNF-α, iNOS and MHCI/II. In contrast, M2 macrophages express a wide array of anti-inflammatory molecules, such as IL-10, TGF-β, and arginase1. In most tumors, the infiltrated macrophages are considered to be of the M2 phenotype, which provides an immunosuppressive microenvironment for tumor growth. Furthermore, tumor-associated macrophages secrete many cytokines, chemokines, and proteases, which promote tumor angiogenesis, growth, metastasis, and immunosuppression. Recently, it was also found that tumor-associated macrophages interact with cancer stem cells. This interaction leads to tumorigenesis, metastasis, and drug resistance. So mediating macrophage to resist tumors is considered to be potential therapy.
Following a previous genome-wide association study (GWAS 1) including 744 cases and 895 controls, we analyzed genome-wide association data from a new cohort of Han Chinese (GWAS 2) with 1,510 polycystic ovary syndrome (PCOS) cases and 2,016 controls. We followed up significantly associated signals identified in the combined results of GWAS 1 and 2 in a total of 8,226 cases and 7,578 controls. In addition to confirming the three loci we previously reported, we identify eight new PCOS association signals at P < 5 × 10(-8): 9q22.32, 11q22.1, 12q13.2, 12q14.3, 16q12.1, 19p13.3, 20q13.2 and a second independent signal at 2p16.3 (the FSHR gene). These PCOS association signals show evidence of enrichment for candidate genes related to insulin signaling, sexual hormone function and type 2 diabetes (T2D). Other candidate genes were related to calcium signaling and endocytosis. Our findings provide new insight and direction for discovering the biological mechanisms of PCOS.
Background In the past few months, the coronavirus disease (COVID-19) pandemic has caused extensive economic and social damage. Objective The purpose of this study was to assess the impact of COVID-19–related measures on partner relationships and sexual and reproductive health in China. Methods From May 1 to 5, 2020, 3500 young Chinese individuals were recruited through WeChat or Weibo to participate in a survey to obtain information on sexual and reproductive health (eg, sexual desire, frequency of sexual intercourse, sexual satisfaction, etc). The questionnaire also collected demographic data (eg, age, race, education, current financial status, sexual orientation, relationship status, etc). Results In total, 967 participants were included in the sexual health analysis. Due to the COVID-19 pandemic and related containment measures, 22% of participants (n=212) reported a decrease in sexual desire; 41% (n=396) experienced a decrease in the sexual intercourse frequency; 30% (n=291) reported an increase in the frequency of masturbation; 20% (n=192) reported a decrease in alcohol consumption before or during sexual activities, and 31% (n=298) reported a deterioration in partner relationships during the pandemic. The logistic regression analysis indicated that the following influenced partner relationships: accommodations during the pandemic (P=.046; odds ratio [OR] 0.59; 95% CI 0.30-0.86); exclusive relationship status (yes or no) (P<.001; OR 0.44; 95 % CI 0.27-0.73); sexual desire (P=.02; OR 2.01; 95% CI 1.38-2.97); and sexual satisfaction (P<.001; OR 1.92; 95% CI 1.54-2.50). COVID-19 also caused disruptions in reproductive health services such as prenatal and postnatal care, childbirth and abortion services, contraception availability, and the management of sexually transmitted infections. Conclusions Our results show that many young people have wide-ranging issues affecting their sexual and reproductive health due to the COVID-19 pandemic and related containment measures. Strategies and guidelines are needed to safeguard the sexual and reproductive health of young people during this pandemic.
Male infertility is a major health concern. Among its different causes, multiple morphological abnormalities of the flagella (MMAF) induces asthenozoospermia and is one of the most severe forms of qualitative sperm defects. Sperm of affected men display short, coiled, absent, and/or irregular flagella. To date, six genes (DNAH1, CFAP43, CFAP44, CFAP69, FSIP2, and WDR66) have been found to be recurrently associated with MMAF, but more than half of the cases analyzed remain unresolved, suggesting that many yet-uncharacterized gene defects account for this phenotype. Here, whole-exome sequencing (WES) was performed on 168 infertile men who had a typical MMAF phenotype. Five unrelated affected individuals carried a homozygous deleterious mutation in ARMC2, a gene not previously linked to the MMAF phenotype. Using the CRISPR-Cas9 technique, we generated homozygous Armc2 mutant mice, which also presented an MMAF phenotype, thus confirming the involvement of ARMC2 in human MMAF. Immunostaining experiments in AMRC2-mutated individuals and mutant mice evidenced the absence of the axonemal central pair complex (CPC) proteins SPAG6 and SPEF2, whereas the other tested axonemal and peri-axonemal components were present, suggesting that ARMC2 is involved in CPC assembly and/or stability. Overall, we showed that bi-allelic mutations in ARMC2 cause male infertility in humans and mice by inducing a typical MMAF phenotype, indicating that this gene is necessary for sperm flagellum structure and assembly.
Background High-grade serous ovarian cancer (HGSOC) is one of the most common ovarian epithelial malignancies. tRNA-derived fragments (tRFs) have been identified as novel potential biomarkers and targets for cancer therapy. Nevertheless, the influence of tRFs on HGSOC remains unknown. This study aimed to identify HGSOC-associated tRFs and to investigate the function and mechanism of key tRFs in SK-OV-3 ovarian cancer cells. Methods The tRF profiles in HGSOC patients and controls were investigated using small RNA sequencing. Differentially expressed tRFs were verified by real-time PCR, and a key tRF was evaluated in a function study. Results A total of 27 tRFs were differentially expressed between HGSOC patients and controls. Differentially expressed tRFs were mainly involved in the functions of protein phosphorylation, transcription and cell migration and the pathway of cancer, and the MAPK and Wnt signaling pathways. Real-time PCR verified that tRF-03357 and tRF-03358 were significantly increased in the HGSOC serum samples and SK-OV-3 cells compared to their expression levels in the controls. Importantly, tRF-03357 promoted SK-OV-3 cell proliferation, migration and invasion. Moreover, tRF-03357 was predictively targeted, and significantly downregulated HMBOX1. Conclusion This study suggests that tRF-03357 might promote cell proliferation, migration and invasion, partly by modulating HMBOX1 in HGSOC.
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