Circular RNAs (circRNAs) are a new member of noncoding RNAs (ncRNAs) that have recently been described as key regulators of gene expression. Our previous study had identified the negative correlation between circHIPK3 and bladder cancer grade, invasion, as well as lymph node metastasis. However, the roles of circRNAs in cellular proliferation in bladder cancer remain largely unknown. We had analyzed circRNA high-throughout sequencing from human tissues and determined bladder cancer related circRNA-3 (BCRC-3, GenBank: KU921434.1) as a new candidate circRNA derived from PSMD1 gene. The expression levels of circRNAs, mRNAs and miRNAs in human tissues and cells were detected by quantitative real-time PCR (qRT-PCR). The effects of BCRC-3 on cancer cells were explored by transfecting with plasmids in vitro and in vivo. RNA pull down assay, luciferase reporter assay and fluorescence in situ hybridization were applied to verify the interaction between BCRC-3 and microRNAs. Anticancer effects of methyl jasmonate (MJ) were measured by flow cytometry assay, western blot and qRT-PCR. BCRC-3 was lowly expressed in bladder cancer tissues and cell lines. Proliferation of BC cells was suppressed by ectopic expression of BCRC-3 in vitro and in vivo. Mechanistically, overexpression of BCRC-3 induced the expression of cyclin-dependent kinase inhibitor 1B (p27). Importantly, BCRC-3 could directly interact with miR-182-5p, and subsequently act as a miRNA sponge to promote the miR-182-5p-targeted 3’UTR activity of p27. Furthermore, MJ significantly increased the expression of BCRC-3, resulting in an obvious up-regulation of p27. BCRC-3 functions as a tumor inhibitor to suppress BC cell proliferation through miR-182-5p/p27 axis, which would be a novel target for BC therapy.

Background: A series of novel inflammation-related indexes has been confirmed to be efficient indicators of human immune and inflammatory status, with great potential as predictors for a variety of diseases. However, the association between inflammation-related indexes and sex hormones in the general population remained uncertain.Methods: We incorporated data from the NHANES 2013-2016 survey of American adults. On the basis of distribution and comparison analysis, we chose to undertake separate analyses of men and women (including premenopausal and postmenopausal groups). Multivariable weighted linear regression models, eXtreme Gradient Boosting (XGBoost) models, generalized linear analysis, stratified models, logistic regression models and sensitivity analysis were utilized to assess the relationships between inflammation-related indexes and sex hormones.Results: Total 9372 participants out of 20146 were fitted into our research. We conducted separate gender analysis due to different distribution. Multivariable weighted linear regression indicated every component of the inflammation-related index was negatively correlated with at least one component of the male hormone indexes. However, SII, NLR, PPN, and NC were associated positively with female estradiol. XGBoost identify SII, PLR and NLR were the critical indexes on sex hormones. Inflammation-related indexes was associated with Testosterone deficiency in male and postmenstrual group and associated with Excessive Estradiol in premenstrual group. Finally, the subgroup analysis revealed that the association between sex hormones and inflammatory indicators was prominent in American adults over the age of 60 or those with BMI (>28 kg/m²).Conclusion: In all, inflammation-related indexes act as independent risks associated with sex hormone alterations and metabolic disorder in both genders. Using multiple models, we revealed the relative importance of inflammation-related indexes. Subgroup analysis also identified the high-risk population. More prospective and experimental research should be conducted to validate the results.

Kidney stone disease is a multifactorial disease with increasing incidence worldwide. Trans-ancestry GWAS has become a popular strategy to dissect genetic structure of complex traits. Here, we conduct a large trans-ancestry GWAS meta-analysis on kidney stone disease with 31,715 cases and 943,655 controls in European and East Asian populations. We identify 59 kidney stone disease susceptibility loci, including 13 novel loci and show similar effects across populations. Using fine-mapping, we detect 1612 variants at these loci, and pinpoint 25 causal signals with a posterior inclusion probability >0.5 among them. At a novel locus, we pinpoint TRIOBP gene and discuss its potential link to kidney stone disease. We show that a cross-population polygenic risk score, PRS-CSx_EAS&EUR, exhibits superior predictive performance for kidney stone disease than other polygenic risk scores constructed in our study. Relative to individuals in the third quintile of PRS-CSx_EAS&EUR, those in the lowest and highest quintiles exhibit distinct kidney stone disease risks with odds ratios of 0.57 (0.51–0.63) and 1.83 (1.68–1.98), respectively. Our results suggest that kidney stone disease patients with higher polygenic risk scores are younger at onset. In summary, our study advances the understanding of kidney stone disease genetic architecture and improves its genetic predictability.

The adverse effects of early-life tobacco smoke exposure on chronic kidney disease (CKD) risk remain unclear. This study aimed to investigate the associations of early-life tobacco smoke exposure with CKD incidence in adulthood, and further explore the modification effects of physical activity (PA). A total of 352,883 participants were included from the UK Biobank. The information on early-life tobacco smoke exposure was assessed by employing in utero tobacco smoke exposure and age of smoking initiation. Weekly moderate-to-vigorous physical activity (MVPA) was calculated for each individual. Cox proportional hazard regression was fitted to estimate the hazard ratio (HR) and 95% confidence interval (CI) of CKD risk, and to investigate the modification effects of MVPA. CKD incidence significantly increased in participants with in utero tobacco smoke exposure (HR: 1.08, 95% CI: 1.04, 1.12). Compared with never-smokers, we found a monotonic increase in the risk of CKD with smoking initiation across adulthood (HR: 1.21, 95% CI: 1.16, 1.27), adolescence (HR: 1.29, 95% CI: 1.24, 1.35), and childhood (HR: 1.34, 95% CI: 1.25, 1.43) (P trend < 0.001). Additionally, we identified joint cumulative effects of MVPA and early-life tobacco smoke exposure on incident CKD. Compared with never-smokers with recommended MVPA, prenatal or childhood tobacco smokers without recommended MVPA had the highest CKD risk, and the HRs (95% CIs) were 1.17 (1.10, 1.24) and 1.51 (1.36, 1.68), respectively. Early-life tobacco smoke exposure may contribute to CKD incidence in adulthood, and the observed associations could be modified by MVPA. These findings provide important information on CKD prevention in the participant’s early life while urging a more rapid and powerful need for tobacco control among pregnant couples, children, and adolescents.

To investigate the association between blood calcium concentration and incident kidney stone as well as to assess the role played by genetic susceptibility. We performed a population-based cohort study based on participants from the UK Biobank. A multivariable Cox proportional hazards regression model was used to estimate hazard ratios (HRs) and 95% CIs of incident kidney stone for blood calcium level and polygenic risk score (PRS). In addition, the potential interaction was explored. The study was conducted from January 28, 2023, through June 4, 2023. During the follow-up of 423,301 participants with a total of 5,490,332 person-years (median follow-up of 13.4 years), 4502 cases of kidney stone were recorded. Compared with the low blood calcium concentration group (first tertile), individuals in the high (third tertile) and moderate (second tertile) concentration groups had higher risks of kidney stone with HRs of 1.24 (95% CI, 1.15 to 1.33) and 1.11 (1.04 to 1.20), respectively. The PRS for kidney stone contained 40 independent single-nucleotide polymorphisms and was used to assign individuals to 3 groups according to the quintile. Participants with high (Q5) and moderate (Q2 to Q4) genetic risks had increased risks of kidney stone compared with low (Q1) genetic risk with HRs of 1.70 (1.53 to 1.89) and 1.31 (1.20 to 1.44), respectively. There was a joint cumulative risk of incident kidney stone between blood calcium concentration and genetic susceptibility. Blood calcium concentration and PRS are significantly associated with incident kidney stone risk. Excessive blood calcium concentration might bring additional stone risk in populations at high genetic risk. A nonlinear correlation between blood calcium concentration and kidney stone risk was indicated.

Background: Zinner syndrome is a rare congenital malformation of the male genitourinary system, characterized by a triad: seminal vesicle cyst, unilateral renal agenesis, and ipsilateral ejaculatory duct obstruction. The etiology of this uncommon disease remains largely elusive; however, genetic mutations may contribute to its development. In this report, we present a case of symptomatic Zinner syndrome that was surgically treated, alongside an investigation into the potential genetic basis of the syndrome via whole exome sequencing. Case presentation: We report the case of an 18-year-old male presenting with urinary pain and was diagnosed with right renal agenesis and a left seminal vesicle cyst following comprehensive imaging. The patient also experienced perineal pain and urgency, without symptoms of frequent urination, dysuria, or hematuria, and no familial history of genitourinary anomalies was documented. He successfully underwent laparoscopic resection of a pelvic mass, with pathological examination confirming a seminal vesicle cyst. Postoperative recovery was uneventful. Whole exome sequencing of blood and tissue samples highlighted myeloma overexpressed gene (MYEOV), B melanoma antigen family member (BAGE), and N-acetylated-alpha-linked acidic dipeptidase 2 (NAALAD2) as potential mutated genes related to Zinner syndrome. Additionally, two predisposing genetic variants were identified. Conclusions: Zinner syndrome is a rare condition commonly diagnosed via various imaging modalities. Surgical resection remains the most effective treatment for symptomatic cases. Gene sequencing provides valuable insights into the genetic etiology of Zinner syndrome, enhancing our understanding and potentially guiding future diagnostic approaches.