USP30 promotes the progression of breast cancer by stabilising Snail.

Breast cancer (BC) is the most prevalent tumour in women worldwide. USP30 is a deubiquitinase that has been previously reported to promote tumour progression and lipid synthesis in hepatocellular carcinoma. However, the role of USP30 in breast cancer remains unclear. Therefore, we investigated its biological action and corresponding mechanisms in vitro and in vivo. In our study, we found that USP30 was highly expressed in breast cancer samples and correlated with a poor patient prognosis. Knockdown of USP30 significantly suppressed the proliferation, invasion and migration abilities of BC cells in vitro and tumour growth in vivo, whereas overexpression of USP30 exhibited the opposite effect. Mechanistically, we verified that USP30 interacts with and stabilises Snail to promote its protein expression through deubiquitination by K48-linked polyubiquitin chains and then accelerates the EMT program. More importantly, USP30 reduced the chemosensitivity of BC cells to paclitaxel (PTX). Collectively, these data demonstrate that USP30 promotes the BC cell EMT program by stabilising Snail and attenuating chemosensitivity to PTX and may be a potential therapeutic target in BC.

Gut Microbiota-Derived Short Chain Fatty Acids Are Associated with Clinical Pregnancy Outcome in Women Undergoing IVF/ICSI-ET: A Retrospective Study.

Gut microbiota and its metabolites are related to the female reproductive system. Animal experiments have demonstrated the relationship between gut microbiota-derived short chain fatty acids (SCFAs) and embryo quality. However, few studies have linked SCFAs to clinical pregnancy outcomes in humans. This retrospective cross-sectional study recruited 147 patients undergoing in vitro fertilization or intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET) (70 with no pregnancies and 77 with clinical pregnancies). The association between SCFAs levels and clinical pregnancy outcomes was evaluated using univariate and multivariate logistic regression analyses. The association between SCFAs and metabolic parameters was analyzed using a linear regression model. Receiver operating characteristic (ROC) curve analysis was used for assessing the efficiency of SCFAs to evaluate the clinical pregnancy outcomes. Fecal propionate levels were significantly higher in the no pregnancy group than in the clinical pregnancy group (p < 0.01). Fecal acetate and butyrate levels were not significantly different between females with and without clinical pregnancies (p > 0.05). There were positive relationships between fecal propionate levels and fasting serum insulin (FSI) (r = 0.245, p = 0.003), Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) (r = 0.276, p = 0.001), and triglycerides (TG) (r = 0.254, p = 0.002). Multivariate analyses determined that fecal propionate (OR, 1.103; 95% CI, 1.045-1.164; p < 0.001) was an independent risk factor for no pregnancies. The area under the ROC curve (AUC) of fecal propionate was 0.702 (p < 0.001), with a sensitivity of 57.1% and a specificity of 79.2%. High fecal propionate concentration has a negative association on clinical pregnancy outcomes and is positively correlated with FSI, TG, and HOMA-IR.

Ferritinophagy, a form of autophagic ferroptosis: New insights into cancer treatment.

Ferritinophagy, a form of autophagy, is also an important part of ferroptosis, a type of regulated cell death resulting from abnormal iron metabolism involving the production of reactive oxygen species. As ferroptosis, autophagy and cancer have been revealed, ferritinophagy has attracted increasing attention in cancer development. In this review, we discuss the latest research progress on ferroptosis, autophagy-associated ferroptosis led by ferritinophagy, the regulators of ferritinophagy and promising cancer treatments that target ferritinophagy. Ferritinophagy is at the intersection of ferroptosis and autophagy and plays a significant role in cancer development. The discussed studies provide new insights into the mechanisms of ferritinophagy and promising related treatments for cancer.

Enterotypes in asthenospermia patients with obesity.

The essence of enterotypes is stratifying the entire human gut microbiome, which modulates the association between diet and disease risk. A study was designed at the Center of Reproductive Medicine, Shengjing Hospital of China Medical University and Jinghua Hospital of Shenyang. Prevotella and Bacteroides were analyzed in 407 samples of stool, including 178 men with enterotype B (61 normal, 117 overweight/obese) and 229 men with enterotype P (74 normal, 155 overweight/obese). The ratio between Prevotella and Bacteroides abundance, P/B, was used as a simplified way to distinguish the predominant enterotype. In enterotype P group (P/B ≥ 0.01), obesity was a risk factor for a reduced rate of forward progressive sperm motility (odds ratio [OR] 3.350; 95% confidence interval [CI] 1.881-5.966; P < 0.001), and a reduced rate of total sperm motility (OR 4.298; 95% CI 2.365-7.809; P < 0.001). Obesity was also an independent risk factor (OR 3.131; 95% CI 1.749-5.607; P < 0.001) after adjusting follicle-stimulating hormone. In enterotype P, body mass index, as a diagnostic indicator of a reduced rate of forward progressive sperm motility and a decreased rate of decreased total sperm motility, had AUC values of 0.627 (P = 0.001) and 0.675 (P < 0.0001), respectively, which were significantly higher than the predicted values in all patients. However, in enterotype B group (P < 0.01), obesity was not a risk factor for asthenospermia, where no significant difference between obesity and sperm quality parameters was observed. This study is tried to introduce enterotypes as a population-based individualized classification index to investigate the correlation between BMI and asthenospermia. In our study, overweight/obese men with enterotype P were found to have poorer sperm quality. however, sperm quality was not associated with overweight/obese in men with enterotype B. Thereof, BMI is a risk factor for asthenospermia only in men with enterotype P, but not in men with enterotype B.

Bioinformatics searching of diagnostic markers and immune infiltration in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is one of the most common endocrine diseases in reproductive-aged women, and it affects numerous women worldwide. This study aimed to identify potential diagnostic markers and explore the infiltration of immune cells in PCOS, contributing to the development of potential therapeutic drugs for this disease. We identified five key genes: CBLN1 (AUC = 0.924), DNAH5 (AUC = 0.867), HMOX1 (AUC = 0.971), SLC26A8 (AUC = 0,933), and LOC100507250 (AUC = 0.848) as diagnostic markers of PCOS. Compared with paired normal group, naïve B cells, gamma delta T cells, resting CD4 memory T cells, and activated CD4 memory T cells were significantly decreased in PCOS while M2 macrophages were significantly increased. Significant correlations were presented between the five key genes and the components of immune infiltrate. The results of CMap suggest that four drugs, ISOX, apicidin, scriptaid, and NSC-94258, have the potential to reverse PCOS. The present study helps provide novel insights for the prevention and treatment of PCOS, and immune cell infiltration plays a role that cannot be ignored in the occurrence and progression of the disease.

Association of Gut Microbiota Enterotypes with Blood Trace Elements in Women with Infertility.

Infertility is defined as failure to achieve pregnancy within 12 months of unprotected intercourse in women. Trace elements, a kind of micronutrient that is very important to female reproductive function, are affected by intestinal absorption, which is regulated by gut microbiota. Enterotype is the classification of an intestinal microbiome based on its characteristics. Whether or not Prevotella-enterotype and Bacteroides-enterotype are associated with blood trace elements among infertile women remains unclear. The study aimed to explore the relationship between five main whole blood trace elements and these two enterotypes in women with infertility. This retrospective cross-sectional study recruited 651 Chinese women. Whole blood copper, zinc, calcium, magnesium, and iron levels were measured. Quantitative real-time PCR was performed on all fecal samples. Patients were categorized according to whole blood trace elements (low levels group, <5th percentile; normal levels group, 5th‒95th percentile; high levels group, >95th percentile). There were no significant differences in trace elements between the two enterotypes within the control population, while in infertile participants, copper (P = 0.033), zinc (P < 0.001), magnesium (P < 0.001), and iron (P < 0.001) in Prevotella-enterotype was significantly lower than in Bacteroides-enterotype. The Chi-square test showed that only the iron group had a significant difference in the two enterotypes (P = 0.001). Among infertile patients, Prevotella-enterotype (Log(P/B) > −0.27) predicted the low levels of whole blood iron in the obesity population (AUC = 0.894; P = 0.042). For the high levels of iron, Bacteroides-enterotype (Log(P/B) <−2.76) had a predictive power in the lean/normal group (AUC = 0.648; P = 0.041) and Log(P/B) <−3.99 in the overweight group (AUC = 0.863; P = 0.013). We can infer that these two enterotypes may have an effect on the iron metabolism in patients with infertility, highlighting the importance of further research into the interaction between enterotypes and trace elements in reproductive function.