SLCO1B1 (rs4149056, 521T > C) is associated with statin-induced myotoxicity in Chinese patients with coronary artery disease. In addition, SLCO1B1 521C mutant allele increased the risk of rosuvastatin-associated myotoxicity.

Cisplatin is a first-line chemotherapy drug that is commonly used in the treatment of epithelial ovarian cancer (EOC). However, insensitivity to cisplatin markedly influences the outcomes of chemotherapy. MicroRNAs (miRNAs/miRs) have been demonstrated to modulate drug resistance in a number of types of cancer. The aim of the present study was to investigate the key miRNAs involved in modulating drug resistance in ovarian cancer cells. miR-200b and miR-200c were identified to be frequently deregulated in ovarian cancer. Upregulation of miR-200b and miR-200c promoted EOC cell death in the presence of cisplatin. Upregulation of miR-125b-5p significantly decreased tumor growth in combination with cisplatin in a mouse model. Significantly, miR-200b and miR-200c reversed cisplatin resistance by targeting DNA methyltransferases (DNMTs) (directly targeting DNMT3A/DNMT3B and indirectly targeting DNMT1 via specificity protein 1). These results indicate that miR-200b- and miR-200c-mediated regulation of DNMTs serves a crucial function in the cellular response to cisplatin. miR-200b- and miR-200c-mediated downregulation of DNMTs may improve chemotherapeutic efficacy by increasing the sensitivity of cancer cells and thus may have an impact on ovarian cancer therapy.

Porcine circovirus type 3 (PCV3) is a novel porcine circovirus species associated with several diseases such as porcine dermatitis and nephropathy syndrome (PDNS)-like clinical signs, reproductive failure, cardiac pathologies, and multisystemic inflammation in piglets and sows. Currently, many studies have focused on the interaction between microbiota composition and disease progression. However, dynamic changes in the composition of the gut microbiota following PCV3 infection are still unknown. In this study, alterations in gut microbiota in PCV3-inoculated and sham-inoculated piglets were analyzed at various time points [7, 14, 21, and 28 days post-inoculation (dpi)] using the Illumina MiSeq platform. Using principal coordinate analysis, obvious structural segregations were observed in bacterial diversity and richness between PCV3-and sham-inoculated piglets, as well as at the four different time points. The abundance of gut microbiota exhibited a remarkable time-related decrease in Clostridium_sensu_stricto_1 in PCV3-inoculated piglets. In addition, significant differences were observed in functional classification based on cluster of orthologous groups assignment, between PCV3-and sham-inoculated piglets. Our findings demonstrated that PCV3 infection caused dynamic changes in the gut microbiota community. Therefore, regulating gut microbiota community may be an effective approach for preventing PCV3 infection.

Background Accumulating evidence suggests a strong association between polycystic ovary syndrome (PCOS) and ovarian cancer (OC), but the potential molecular mechanism remains unclear. In this study, we identified previously unrecognized genes that are significantly correlated with PCOS and OC via bioinformatics. Materials and methods Multiple bioinformatic analyses, such as differential expression analysis, univariate Cox analysis, functional and pathway enrichment analysis, protein–protein interaction (PPI) network construction, survival analysis, and immune infiltration analysis, were utilized. We further evaluated the effect of OGN on FSHR expression via immunofluorescence. Results TCGA-OC, GSE140082 (for OC) and GSE34526 (for PCOS) datasets were downloaded. Twelve genes, including RNF144B, LPAR3, CRISPLD2, JCHAIN, OR7E14P, IL27RA, PTPRD, STAT1, NR4A1, OGN, GALNT6 and CXCL11, were identified as signature genes. Drug sensitivity analysis showed that OGN might represent a hub gene in the progression of PCOS and OC. Experimental analysis found that OGN could increase FSHR expression, indicating that OGN could regulate the hormonal response in PCOS and OC. Furthermore, correlation analysis indicated that OGN function might be closely related to m6A and ferroptosis. Conclusions Our study identified a 12-gene signature that might be involved in the prognostic significance of OC. Furthermore, the hub gene OGN represent a significant gene involved in OC and PCOS progression by regulating the hormonal response.

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Purpose: Tumour metabolism has become a novel factor targeted by personalized cancer drugs. This research evaluated the prognostic significance of metabolism-related genes (MRGs) in ovarian serous cystadenocarcinoma (OSC). Methods: MRGs in 379 women surviving OSC were obtained using The Cancer Genome Atlas (TCGA) database. Then, several biomedical computational algorithms were employed to identify eight hub prognostic MRGs that were significantly relevant to OSC survival. These 8 genes have important clinical significance and prognostic value in OSC. Subsequently, a prognostic index was constructed. Drug sensitivity analysis was used to screen the key genes in eight MRGs. IHC staining confirmed the expression levels of key genes and their correlations with clinical parameters and prognosis for patients. Results: A total of 701 differentially expressed MRGs were confirmed in women with OSC by the TCGA database. The random walking with restart (RWR) algorithm and the univariate Cox and lasso regression analyses indicated a prognostic signature based on eight MRGs (i.e., ENPP1, FH, CYP2E1, HPGDS, ADCY9, NDUFA5, ADH1B and PYGB), which performed moderately well in prognostic predictions. Drug sensitivity analysis indicated that PYGB played a key role in the progression of OSC. Also, IHC staining confirmed that PYGB has a close correlation with clinical parameters and poor prognosis in OSC. Conclusion: The results of this study may help to establish a foundation for future research attempting to predict the prognosis of OSC patients and to characterize OSC metabolism.

MicroRNAs (miRNAs) are a type of small noncoding RNAs that often play important roles in carcinogenesis, but the carcinogenic mechanism of miRNAs is still unclear. This study will investigate the functions and the mechanism of miR-638 in osteosarcoma (OS). The expression of miR-638 in OS and the DNA copy number of miR-638 were detected by real-time PCR. The effect of miR-638 on cell proliferation was measured by CCK8 assay. Different assays, including bioinformatics algorithms, luciferase report assay, and Western blotting, were used to identify the target gene proviral integration site for Moloney murine leukemia virus 1 (PIM1) of miR-638 in OS. The expression of PIM1 in clinical OS tissues was also validated by immunohistochemical assay. From this research, we found that miR-638 was downregulated in OS tissues compared with corresponding noncancerous tissues (NCTs), and the DNA copy number of miR-638 was lower in OS than in NCTs, which may induce the corresponding downregulation of miR-638 in OS. Ectopic expression of miR-638 inhibited OS cell growth in vitro. Subsequently, we identified that PIM1 is the downstream target gene of miR-638 in OS cells, and silencing PIM1 expression phenocopied the inhibitory effect of miR-638 on OS cell proliferation. Furthermore, we observed that PIM1 was overexpressed in OS tissues, and high expression of PIM1 in OS predicted poor overall survival. In summary, we revealed that miR-638 functions as a tumor suppressor through inhibiting PIM1 expression in OS.

Background and Purpose Non-alcoholic fatty liver disease (NAFLD) is becoming the most common liver disease in China. However, the understanding of NAFLD prevalence among Chinese mental disorder inpatients remains insufficient. We aim to investigate the prevalence of NAFLD among mental disorder inpatients in Beijing, China. Methods In this observational study, we included 66,273 mental disorder inpatients between 2014 and 2018, including inpatients with schizophrenia, bipolar disorder, depressive disorder and other mental disorders. Data were obtained from electronic health records of 19 specialized psychiatric hospitals in Beijing. NAFLD was defined by ICD-10 code, excluding other causes of liver disease. We calculated the overall and annual prevalence rates of NAFLD from 2014 to 2018, and compared NAFLD prevalence between sexes, age groups, mental disorders types, antipsychotics use, and comorbidities. Multivariable logistic regression was used to examine risk factors associated with NAFLD. Subgroup analysis was performed in different mental disorder types. Results The prevalence of NAFLD was 17.63% (95% CI 17.34–17.92%) in mental disorder inpatients, increasing from 16.88% in 2014 to 19.07% in 2018. The NAFLD prevalence in participants with schizophrenia (22.44%) was higher than that in participants with bipolar disorder (17.89%), depressive disorder (12.62%), and other mental disorders (12.99%). Women had similar or even higher NAFLD prevalence than men after 50 years. Men, 50–59 years (aOR = 1.71), schizophrenia (aOR = 1.56), bipolar disorder (aOR = 1.47), antipsychotics use (aOR = 1.46), hypertension (aOR = 1.50), diabetes (aOR = 1.83), dyslipidemia (aOR = 2.50) were risk factors for NAFLD in mental disorder inpatients. Conclusion NAFLD was common among Chinese mental disorder inpatients, and increased over years. The prevalence of NAFLD was higher among men, old women, inpatients with schizophrenia, bipolar disorder, antipsychotics, hypertension, diabetes, and dyslipidemia. Fatty liver disease among mental disorder population warrants the attention of psychiatric specialists and health policy-makers.