Associations between Urinary Concentrations of Polycyclic Aromatic Hydrocarbons and Overactive Bladder in US Adults: Data from the National Health and Nutrition Examination Survey 2005-2016.

INTRODUCTION: Polycyclic aromatic hydrocarbons (PAHs) are a group of chemicals that can induce oxidative stress and related cytotoxicity. Whether urinary concentrations of PAHs have effects on overactive bladder (OAB) in the general population is still unclear. This study investigated the associations between urinary PAHs and OAB. METHODS: 7,146 adults aged over 20 who participated in the US National Health and Nutrition Examination Survey 2005-2016 were studied. The impact of the six PAHs on OAB was evaluated by multivariate logistic regression, and percent changes related to different quartiles of those six PAH levels were calculated. Confounders including age, logarithmic urinary creatinine, gender, race, body mass index, educational level, marriage, poverty income ratio, diabetes, hypertension, and metabolic syndrome were controlled. RESULTS: There is a significant positive correlation between urinary concentrations of the six PAHs we include in the study and the occurrence of OAB. Furthermore, individuals with higher PAH levels also reported a more severe OAB symptom score (OABSS). CONCLUSIONS: Our findings revealed that adult men in the USA with higher urinary PAHs had a higher risk of OAB incidence. These findings suggest the importance of strong environmental regulation of PAHs to protect population health. However, the underlying mechanisms still need further exploration.

Comprehensive analysis of the impact of emerging flame retardants on prostate cancer progression: The potential molecular mechanisms and immune infiltration landscape.

Emerging flame retardants have been used to replace traditional flame retardants, but their potential impact on cancer, especially prostate cancer, is not well understood. Our study aimed to explore the link between flame retardants and prostate cancer, and identify potential carcinogenic mechanisms among populations exposed to emerging flame retardants. We screened flame retardant interacting genes differentially expressed in prostate cancer patients and identified hub genes by protein-protein interaction (PPI) analysis based on the STRING database. Univariate and multivariate Cox regression analyses were performed to construct risk models and identify flame retardant-related prognostic genes. We calculated the proportion of immune cell infiltration to explore the potential mechanism of the prognostic gene, and verified the target cell population of the prognostic gene in the single-cell transcriptome dataset. Our study revealed a significant link between emerging flame retardants and prostate cancer. We constructed a risk model with good predictive ability for prostate cancer prognosis using TCGA dataset, and identified six flame retardant-related prognostic genes validated in the GSE70769 dataset. We found that the expression of M2 macrophages was up-regulated in patients with high expression of prognostic genes, and the single-cell dataset confirmed the expression of prognostic genes in macrophages. Our study confirms the link between emerging flame retardants and prostate cancer, and highlights the role of immune-related pathways in the high-risk population exposed to these flame retardants.

Exploring the potential mechanisms of impairment on genitourinary system associated with coronavirus disease 2019 infection: Bioinformatics and molecular simulation analyses.

Objective: The novel coronavirus (severe acute respiratory syndrome coronavirus 2) has been spreading worldwide since December 2019, posing a serious danger to human health and socioeconomic development. A large number of clinical trials have revealed that coronavirus disease 2019 (COVID-19) results in multi-organ damage including the urogenital system. This study aimed to explore the potential mechanisms of genitourinary damage associated with COVID-19 infection through bioinformatics and molecular simulation analysis. Methods: We used multiple publicly available databases to explore the expression patterns of ACE2, TMPRSS2, and CD147 (Basigin [BSG]) in major organs in the healthy and disease-specific populations, particularly the genitourinary organs. Single-cell RNA sequencing was used to analyze the cell-specific expression patterns of ACE2, TMPRSS2, CD147, cytokine receptors, and cytokine interacting proteins in genitourinary organs, such as the bladder, kidney, prostate, and testis. Additionally, gene set enrichment analysis was used to investigate the relationship between testosterone levels and COVID-19 vulnerability in patients with prostate cancer. Results: The results revealed that ACE2, TMPRSS2, and CD147 were highly expressed in normal urogenital organs. Then, they were also highly expressed in multiple tumors and chronic kidney diseases. Additionally, ACE2, TMPRSS2, and CD147 were significantly expressed in a range of cells in urogenital organs according to single-cell RNA sequencing. Cytokine receptors and cytokine interacting proteins, especially CCL2, JUN, and TIMP1, were commonly highly expressed in urogenital organs. Finally, gene set enrichment analysis results showed that high testosterone levels in prostate cancer patients were significantly related to the JAK/STAT signaling pathway and the Toll-like receptor signaling pathway which were associated with COVID-19. Conclusion: Our study provides new insights into the potential mechanisms of severe acute respiratory syndrome coronavirus 2 damage to urogenital organs from multiple perspectives, which may draw the attention of urologists to COVID-19 and contribute to the development of targeted drugs.

Exposure to bisphenol A alternatives bisphenol AF and fluorene-9-bisphenol induces gonadal injuries in male zebrafish.

Bisphenol A (BPA), present in many household products, can damage the male reproductive system. Accordingly, we summarized urine samples from 6921 human in National Health and Nutrition Examination Survey and found urinary BPA levels were inversely linked with blood testosterone in the children group. Currently, BPA replacements, such as fluorene-9-bisphenol (BHPF) and Bisphenol AF (BPAF), have been introduced to produce "BPA-free" products. Here we demonstrated that BPAF and BHPF could induce delayed gonadal migration and reduce the number of progenitors of germ cell lineage in zebrafish larvae. A close receptor analysis study reveals that BHPF and BPAF can strongly bind to androgen receptors, leading to the downregulation of meiosis-related genes and the overexpression of inflammatory markers. Furthermore, BPAF and BPHF can induce activation of the gonadal axis via negative feedback, leading to the hypersecretion of some upstream hormones and an increase in the expression of upstream hormone receptors. Our findings call for further research on the toxicological effects of BHPF and BPAF on human health and recommend that BPA replacements be investigated for anti-estrogenic action.

Relationship Between Marijuana Use and Overactive Bladder (OAB): A Cross-Sectional Research of NHANES 2005 to 2018.

BACKGROUND: Current research is starting to focus on the medical value of marijuana and the possible health problems it can cause. Previous studies have shown that marijuana can relieve lower urinary tract symptoms, which can pose a significant public health burden. In this study, we assessed the association between regular marijuana use and overactive bladder as part of low urinary tract symptoms. METHODS: Data from the National Health and Nutrition Examination Survey 2005-2018 were obtained for analysis. The Overactive Bladder Symptom Score scale was used to define the presence of overactive bladder for each participant. Multivariate logistic regression and ordinal logistic regression were used to analyze the association of marijuana use with the onset and severity of overactive bladder, respectively. RESULTS: We found that approximately 24% of the US population reported regular marijuana use. Compared with nonregular users, regular marijuana users were younger, thinner, more likely to be male, smokers, low-income, less educated, unmarried, and non-Hispanic White/Black. Multivariate logistic regression revealed that marijuana exposure may be an independent risk factor for overactive bladder (odds ratio 1.39; 95% confidence interval, 1.16-1.66). Ordinal logistic regression results showed that marijuana exposure was associated with the severity of overactive bladder (odds ratio 1.45; 95% confidence interval, 1.30-1.60). Moreover, all frequencies of regular use showed almost consistent effects on the onset and severity of overactive bladder. CONCLUSION: Regular marijuana use may increase the risk of overactive bladder. Our data do not support the evidence for the use of cannabinoids in the medical treatment of patients with overactive bladder, especially given the thorny health problems caused by marijuana.

The landscape of micron-scale particles including microplastics in human enclosed body fluids.

Exogenous microparticles including microplastics are novel pollutants that could persist in the environment with potential health effects, while crucial data on their exposure in humans are still lacking. To understand the panorama of microparticles including microplastics exposure and distribution characteristics in different kinds of body fluids. A non-targeted microparticle internal exposure landscape analysis was done in thirteen kinds of human enclosed body fluids covering eight body systems. Totally 104 patients aged 24-96 years with an average age of 56 years were included in this study. After sample digestion, non-soluble microparticles were detected and identified with one Raman Microspectroscope under a strict quality control-particle detection system. Totally 702 microparticles with size ranging from 2.15 to 103.27 µm were detected in samples. Microparticles were identified into 84 substances or 66 molecules, most of which were firstly reported inside human body. Nine kinds of microplastics were originally reported in human body fluids with their size ranging from 19.66 to 103.27 µm. Microparticles exposure was unexpectedly high inside the human body despite the protection of biological barriers and membranes, raising awareness of the impact of particle pollution on sustainable development.

Prognostic Role of DNA Damage Response Genes Mutations and their Association With the Sensitivity of Olaparib in Prostate Cancer Patients.

OBJECTIVE: Evidence shows that gene mutation is a significant proportion of genetic factors associated with prostate cancer. The DNA damage response (DDR) is a signal cascade network that aims to maintain genomic integrity in cells. This comprehensive study was performed to determine the link between different DNA damage response gene mutations and prostate cancer. MATERIALS AND METHODS: A systematic literature search was performed using PubMed, Web of Science, and Embase. Papers published up to February 1, 2022 were retrieved. The DDR gene mutations associated with prostate cancer were identified by referring to relevant research and review articles. Data of prostate cancer patients from multiple PCa cohorts were obtained from cBioPortal. The OR or HR and 95% CIs were calculated using both fixed-effects models (FEMs) and random-effects models (REMs). RESULTS: Seventy-four studies were included in this research, and the frequency of 13 DDR genes was examined. Through the analysis of 33 articles that focused on the risk estimates of DDR genes between normal people and PCa patients, DDR genes were found to be more common in prostate cancer patients (OR = 3.6293 95% CI [2.4992; 5.2705]). Also, patients in the mutated group had a worse OS and DFS outcome than those in the unmutated group (P < .05). Of the 13 DDR genes, the frequency of 9 DDR genes in prostate cancer was less than 1%, and despite differences in race, BRCA2 was the potential gene with the highest frequency (REM Frequency = .0400, 95% CI .0324 - .0541). The findings suggest that mutations in genes such as ATR, BLM, and MLH1 in PCa patients may increase the sensitivity of Olaparib, a PARP inhibitor. CONCLUSION: These results demonstrate that mutation in any DDR pathway results in a poor prognosis for PCa patients. Furthermore, mutations in ATR, BLM, and MLH1 or the expression of POLR2L, PMS1, FANCE, and other genes significantly influence Olaparib sensitivity, which may be underlying therapeutic targets in the future.

Associations between benzophenone-3 and sex steroid hormones among United States adult men.

It has been demonstrated that benzophenone-3 is one of the endocrine-disrupting compounds which are considered as potential risk factors of adverse health effects. However, whether benzophenone-3 exposure can influence the sex steroid hormones levels remains unknown. We used data from the National Health and Nutrition Examination Survey, which is a cross-sectional dataset, from 2013 to 2016. A total of 1690 male US participants aged 18 or above were included. Urinary benzophenone-3, serum total testosterone, serum estradiol, serum sex hormone-binding globulin were measured. Confounders including age, body mass index, race, education level, urinary creatinine, ratio of family income to poverty, alcohol use, time of venipuncture, cardiac arterial diabetic score, energy intake, bisphenol A, triclosan and total parabens were controlled. After full adjustment (Model III), the upper benzophenone-3 quintiles had odds ratios (95 % confidence intervals) of testosterone deficiency of 1.75 (1.03, 2.99), 2.47 (1.53, 3.98), 2.08 (1.13, 3.84) and 1.74 (0.94, 3.23) compared with quintile 1. Compared with quintile 1, percent changes (95 % confidence intervals) in testosterone were - 12 % (-19 %, -5 %) and - 9 % (-17 %, -1 %) for quintile 3 and quintile 5 in Model III. Estradiol and sex hormone-binding globulin were generally similar to total testosterone in the associations with benzophenone-3. In conclusion, our results demonstrated that adult men in the US with higher urinary benzophenone-3 had a higher risk of testosterone deficiency and had inverse associations with total testosterone, estradiol and sex hormone-binding globulin. To confirm the causal links between benzophenone-3 and sex steroid hormones, prospective studies are needed.

Association of urinary phthalate metabolites with renal function among 9989 US adults.

PURPOSE: This study aimed to investigate the relationship between phthalate metabolites and renal function. METHODS: We analyzed data from 9989 participants who took part in the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018. Renal function was reflected by estimated glomerular filtration rate (eGFR), urinary albumin-to-creatinine ratio (UACR), and hypertension. We used generalized linear regression to estimate the correlation between covariate-adjusted creatinine-normalized phthalate metabolites and renal function. In addition, subgroup analysis was used to further compare the effect differences between various populations. RESULTS: In the adjusted model, we found differential associations between phthalates and plasticizers metabolites and renal function. We found that Mono-benzyl phthalate, Mono-(3-carboxypropyl) phthalate, and Mono-(2-ethyl-5-oxohexyl) phthalate were positively associated with lower eGFR with odds ratios (95% confidence intervals) of 1.38 (1.14, 1.67), 1.30 (1.09, 1.57), and 1.27 (1.04, 1.53). While Mono-ethyl phthalate, Mono-(2-ethyl)-hexyl phthalate, Mono-isononyl phthalate and Mono-isobutyl phthalate were negatively associated with lower eGFR with OR values of 0.79 (0.69, 0.90), 0.64 (0.52, 0.78), 0.65 (0.51, 0.82) and 0.80 (0.63, 1.00), respectively. In addition, we found that Mono(carboxyoctyl) phthalate and Mono-isobutyl phthalate were negatively associated with hypertension with ORs of 0.86 (0.78, 0.96) and 0.84 (0.72, 0.98). But phthalates and plasticizers metabolites were not associated with UACR. CONCLUSION: This study found differences in the effects of phthalates and plasticizers metabolites on kidney function, which may raise concerns about possible changes in kidney function resulting from exposure to current levels of plasticizers.

Lineage plasticity in prostate cancer depends on JAK/STAT inflammatory signaling.

Drug resistance in cancer is often linked to changes in tumor cell state or lineage, but the molecular mechanisms driving this plasticity remain unclear. Using murine organoid and genetically engineered mouse models, we investigated the causes of lineage plasticity in prostate cancer and its relationship to antiandrogen resistance. We found that plasticity initiates in an epithelial population defined by mixed luminal-basal phenotype and that it depends on increased Janus kinase (JAK) and fibroblast growth factor receptor (FGFR) activity. Organoid cultures from patients with castration-resistant disease harboring mixed-lineage cells reproduce the dependency observed in mice by up-regulating luminal gene expression upon JAK and FGFR inhibitor treatment. Single-cell analysis confirms the presence of mixed-lineage cells with increased JAK/STAT (signal transducer and activator of transcription) and FGFR signaling in a subset of patients with metastatic disease, with implications for stratifying patients for clinical trials.

Erectile dysfunction in hypospadiac male adult rats induced by maternal exposure to di-n-butyl phthalate.

For the treatment of hypospadias, a significant number of studies focus on penile reconstruction. However, scant attention is given to sexual behavior of hypospadiac patients and underlying mechanisms. A rat model of hypospadias was constructed by maternal di-n-butyl phthalate (DBP) exposure (800 mg/kg/day by gavage during gestational days 14-18). Ten-week-old male rats with hypospadias undertook significantly decreased penis/body weight ratio, reduced testis/body weight ratio, lower serum testosterone level and thinner myelin sheath thickness of cavernosum nerves. Meanwhile, erectile dysfunction (ED) was found in hypospadiac rats, which showed significant increases in transforming growth factor-ß1 (TGF-ß1) protein expression and decreases in the expression of alpha smooth muscle actin (α-SMA) protein, neuronal and endothelial nitric oxide synthase protein (nNOS and eNOS). In addition, phosphorylated protein kinase B/protein kinase B (pAkt/Akt) ratios were remarkably lower, but the Bcl-2-associated X protein (Bax)/Bcl-2 ratios, caspase-3 protein expression, nuclear factor erythroid 2-related factor 2/ Kelch-like ECH-associated protein 1 (Nrf2/Keap-1) ratios, NAD(P)H dehydrogenase quinone 1(NQO1) protein expression and heme oxygenase-1 (HO-1) protein expression were higher in the hypospadias groups than the control group. Notably, ED is comorbid with hypospadias in cases. Penile fibrosis, testosterone deficiency, and endothelial dysfunction lead to ED in hypospadias induced by DBP eventually, which might be explained by activating Akt/Bad/Bax/caspase-3 pathway, Nrf2/Keap-1 pathway and suppressing NOS/cGMP pathway in penis.

Chromatin profiles classify castration-resistant prostate cancers suggesting therapeutic targets.

In castration-resistant prostate cancer (CRPC), the loss of androgen receptor (AR) dependence leads to clinically aggressive tumors with few therapeutic options. We used ATAC-seq (assay for transposase-accessible chromatin sequencing), RNA-seq, and DNA sequencing to investigate 22 organoids, six patient-derived xenografts, and 12 cell lines. We identified the well-characterized AR-dependent and neuroendocrine subtypes, as well as two AR-negative/low groups: a Wnt-dependent subtype, and a stem cell-like (SCL) subtype driven by activator protein-1 (AP-1) transcription factors. We used transcriptomic signatures to classify 366 patients, which showed that SCL is the second most common subtype of CRPC after AR-dependent. Our data suggest that AP-1 interacts with the YAP/TAZ and TEAD proteins to maintain subtype-specific chromatin accessibility and transcriptomic landscapes in this group. Together, this molecular classification reveals drug targets and can potentially guide therapeutic decisions.

Clinical characteristics and prognosis of patients with Castleman disease in a Chinese hospital: paraneoplastic pemphigus is an independent risk factor.

OBJECTIVE: Castleman disease (CD) is a rare lymphoproliferative disorder with limited clinical research data. This study aimed to investigate the clinical manifestations, pathologic features, and prognostic factors of CD. METHODS: The clinicopathological data of 54 patients with CD hospitalized in the First Affiliated Hospital of Nanjing Medical University were retrospectively analyzed. Univariate analysis and multivariate analysis were performed by Cox regression model to determine independent prognostic factors for patients' survival. RESULTS: According to clinical classification, 30 cases (55.6%) had unicentric CD (UCD) and 24 cases (44.4%) had multicentric CD (MCD). Moreover, pathologic classification revealed 32 cases (59.3%) with hyaline vascular variant, 3 (5.6%) with mixed cellular variant, and 19 (35.2%) with plasmacytic variant. Patients with MCD commonly presented with clinical signs and symptoms, including fever, splenomegaly, and pleural effusion and/or ascites. Clinical complications, such as liver injury, anemia, and polyradiculoneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder, skin changes (POEMS) syndrome were more common in patients with MCD. Univariate analysis showed that the presence of paraneoplastic pemphigus (PNP) and the elevation of C-reactive protein were unfavorable prognosticators of survival in patients with CD. By multivariate analysis PNP was an independent prognostic factor in patients with CD. CONCLUSIONS: This study provided a panoramic elaboration of CD cases and showed that the presence of PNP was an independent unfavorable factor.

Gut microbiota may contribute to the postnatal male reproductive abnormalities induced by prenatal dibutyl phthalate exposure.

Phthalate is an environmental endocrine disruptor that causes direct and intergenerational male reproductive damage. However, its mechanisms require further investigation. The role of gut microbiota in male reproductive function has been gradually revealed in the past. To explore the intergenerational testicular injury and the influence on offspring gut microbiota of the widely used phthalate dibutyl phthalate (DBP), we conducted a prenatal DBP exposure experiment with microbiota sequencing. We finally explained the gestational DBP exposure-induced gut dysbacteriosis, which is one of the mechanisms of testicular injury in the offspring. The occurrence of seminiferous atrophy and spermatogenic cells apoptosis showed a slight increase. Our study partially supported the results of previous research works on the characteristics of gut dysbacteriosis, which featured the increased relative abundance of Bacteroidetes, Prevotella and P. copri. Focusing on the role of gut microbiota in reproductive function is important. Future studies need to investigate the relationship between environmental pollution and human health.

Immune Microenvironment and Response in Prostate Cancer Using Large Population Cohorts.

Immune microenvironment of prostate cancer (PCa) is implicated in disease progression. However, previous studies have not fully explored PCa immune microenvironment. This study used ssGSEA algorithm to explore expression levels of 53 immune terms in a combined PCa cohort (eight cohorts; 1,597 samples). The top 10 immune terms were selected based on the random forest analysis and used for immune-related risk score (IRS) calculation. Furthermore, we explored differences in clinical and genomic features between high and low IRS groups. An IRS signature based on the 10 immune terms showed high prediction potential for PCa prognosis. Patients in the high IRS group showed significantly higher percentage of immunotherapy response factors, implying that IRS is effective in predicting immunotherapy response rate. Furthermore, consensus clustering was performed to separate the population into three IRSclusters with different clinical outcomes. Patients in IRScluster3 showed the worst prognosis and highest immunotherapy response rate. On the other hand, patients in IRScluster2 showed better prognosis and low immunotherapy response rate. In addition, VGLL3, ANPEP, CD38, CCK, DPYS, CST2, COMP, CRISP3, NKAIN1, and F5 genes were differentially expressed in the three IRSclusters. Furthermore, CMap analysis showed that five compounds targeted IRS signature, thioridazine, trifluoperazine, 0175029-0000, trichostatin A, and fluphenazine. In summary, immune characteristics of PCa tumor microenvironment was explored and an IRS signature was constructed based on 10 immune terms. Analysis showed that this signature is a useful tool for prognosis and prediction of immunotherapy response rate of PCa.

Animal Toxicology Studies on the Male Reproductive Effects of 2,3,7,8-Tetrachlorodibenzo-p-Dioxin: Data Analysis and Health Effects Evaluation.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a well-known environmental poison that exist in the environment for many years. However, its effect on the male reproductive system has not been clearly stated. We conducted a meta-analysis of the effect of TCDD on the male reproductive system of rodents about TCDD. Results showed that that TCDD exposure reduced the testis weight (weighted mean difference [WMD]: -0.035, 95% confidence interval [CI]: -0.046 to -0.025), sperm count (WMD: -35, 95% CI: -42.980 to -27.019), and blood testosterone concentration (WMD: -0.171, 95% CI: -0.269 to -0.073). According to our research results, TCDD can cause damage to the male reproductive system of rodents through direct or indirect exposure. In order to further explore the potential hazards of TCDD to humans, more human-related research needs to be carried out.

Genetic comprehension of organophosphate flame retardants, an emerging threat to prostate cancer.

In recent years, organophosphate ester flame retardants (OPFRs), which have been regarded as alternatives for brominated flame retardants (BFRs), have become widely used in building materials, textiles, and electric equipment. Elucidating the relationship between OPFRs and tumors holds great significance for the treatment and prevention of diseases. In this work, we found a new method for predicting the correlation between the interactive genes of OPFRs and tumors. Transcriptome profiles and OPFR information were obtained from The Cancer Genome Atlas and the Genotype-Tissue Expression, Comparative Toxicogenomics, and PharmMapper databases. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis showed that interactive genes were mainly enriched in prostate cancer, steroid metabolic process, and steroid hormone regulation. Furthermore, protein-protein interaction network analysis revealed 33 biological hub genes. The operating characteristic curves and survival analysis showed the role of key genes in predicting the prognosis of prostate cancer. Gene target prediction and gene set variation analysis proved that OPFRs and their metabolites exert potential effects on prostate cancer. Colony formation assay showed that the cells with AR, mTOR and DDIT3 knockdown could remarkably mitigate the cell proliferation ability in both PC-3 and LNCap cells. Transwell assay demonstrated that the silencing of AR, mTOR and DDIT3 could significantly inhibit the cell invasion capacity of prostate cells. Triphenyl phosphate (TPP) significantly increase the cell proliferation ability and promote cell invasion capacity. AR, mTOR and DDIT3 in the PC-3 and LNCap cells were significantly upregulated with 10-6 M TPP treated.

Pyrethroids Toxicity to Male Reproductive System and Offspring as a Function of Oxidative Stress Induction: Rodent Studies.

Pyrethroids may be related to male reproductive system damage. However, the results of many previous studies are contradictory and uncertain. Therefore, a systematic review and a meta-analysis were performed to assess the relationship between pyrethroid exposure and male reproductive system damage. A total of 72 articles were identified, among which 57 were selected for meta-analysis, and 15 were selected for qualitative analysis. Pyrethroid exposure affected sperm count (SMD= -2.0424; 95% CI, -2.4699 to -1.6149), sperm motility (SMD=-3.606; 95% CI, -4.5172 to -2.6948), sperm morphology (SMD=2.686; 95% CI, 1.9744 to 3.3976), testis weight (SMD=-1.1591; 95% CI, -1.6145 to -0.7038), epididymal weight (SMD=-1.1576; 95% CI, -1.7455 to -0.5697), and serum testosterone level (SMD=-1.9194; 95% CI, -2.4589 to -1.3798) in the studies of rats. We found that gestational and lactational exposure to pyrethroids can reduce sperm count (SMD=1.8469; 95% CI, -2.9010 to -0.7927), sperm motility (SMD=-2.7151; 95% CI, -3.9574 to -1.4728), testis weight (SMD=-1.4361; 95% CI, -1.8873 to -0.9848), and epididymal weight (SMD=-0.6639; 95% CI, -0.9544 to -0.3733) of F1 offspring. Exposure to pyrethroids can increase malondialdehyde (SMD=3.3451; 95% CI 1.9914 to 4.6988) oxide in testes and can reduce the activities of glutathione (SMD=-2.075; 95% CI -3.0651 to -1.0848), superoxide dismutase (SMD=-2.4856; 95% CI -3.9612 to -1.0100), and catalase (SMD=-2.7564; 95% CI -3.9788 to -1.5340). Pyrethroid exposure and oxidative stress could damage male sperm quality. Gestational and lactational pyrethroid exposure affects the reproductive system of F1 offspring.

TRIM37 orchestrates renal cell carcinoma progression via histone H2A ubiquitination-dependent manner.

BACKGROUND: Ubiquitylation modification is one of the multiple post-transcriptional process to regulate cellular physiology, including cell signaling, cycle regulation, DNA repair and transcriptional regulation. Members of TRIM family proteins could be defined as E3 ubiquitin ligases as they contain a RING-finger domain, and alterations of TRIM proteins are involved into a broad range of diverse disorders including cancer. TRIM37 is a novel discovered E3 ubiquitin ligase and acts as a oncoprotein in multiple human neoplasms, however its biological role in RCC still remains elusive. METHODS: RCC microarray chips and public datasets were screened to identify novel TRIMs member as TRIM37, which was dysregulated in RCC. Gain or loss of functional cancer cell models were constructed, and in vitro and in vivo assays were performed to elucidate its tumorigenic phenotypes. Interactive network analyses were utilized to define intrinsic mechanism. RESULTS: We identified TRIM37 was upregulated in RCC tumors, and its aberrant function predicted aggressive neoplastic phenotypes, poorer survival endings. TRIM37 promoted RCC cells EMT and malignant progression via TGF-ß1 signaling activation, as a consequence of directly mediated by ubiquitinating-H2A modifications. CONCLUSIONS: Our findings identified a previously unappreciated role of TRIM37 in RCC progression and prognostic prediction. Importantly, we declared a novel ubiquitination-dependent link between TRIM ubiquitin ligases and TGF-ß1 signaling in regulating cancerous malignancies.