Association between organophosphorus insecticides exposure and osteoarthritis in patients with arteriosclerotic cardiovascular disease.

BACKGROUND: Organic phosphorus insecticides (OPPs) are a class of environmental pollutants widely used worldwide with potential human health risks. We aimed to assess the association between exposure to OPPs and osteoarthritis (OA) particularly in participants with atherosclerotic cardiovascular disease (ASCVD). METHODS: Participants' information was obtained from data in the National Health and Nutrition Examination (NHANES). Weighted logistic regression models were utilized to detect associations between OPPs metabolites and OA. Restricted cubic spline plots (RCS) were drawn to visualize the dose-response relationship between each metabolite and OA prevalence. Weighted quantile sum (WQS) regression and Bayesian kernel-machine regression (BKMR), were applied to investigate the joint effect of mixtures of OPPs on OA. RESULTS: A total of 6871 samples were included in our study, no significant associations between OPPs exposure and OA incidence were found in whole population. However, in a subset of 475 individuals with ASCVD, significant associations between DMP (odds ratio [OR] as a continuous variable = 1.22, 95% confidence interval [CI]: 1.07,1.28), DEP ((odds ratio [OR] of the highest tertile compared to the lowest = 2.43, 95% confidence interval [CI]: 1.21,4.86), and OA were observed. DMP and DEP showed an increasing dose-response relationship to the prevalence of OA, while DMTP, DETP, DMDTP and DEDTP showed a nonlinear relationship. Multi-contamination modeling revealed a 1.34-fold (95% confidence intervals:0.80, 2.26) higher prevalence of OA in participants with high co-exposure to OPPs compared to those with low co-exposure, with a preponderant weighting (0.87) for the dimethyl dialkyl phosphate metabolites (DMAPs). The BKMR also showed that co-exposure of mixed OPPs was associated with an increased prevalence of OA, with DMP showing a significant dose-response relationship. CONCLUSION: High levels of urine dialkyl phosphate metabolites (DAP) of multiple OPPs are associated with an increased prevalence of OA in patients with ASCVD, suggesting the need to prevent exposure to OPPs in ASCVD patients to avoid triggering OA and further avoid the occurrence of cardiovascular events caused by OA.

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.

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.

RUNX1/miR-582-5p Pathway Regulates the Tumor Progression in Clear Cell Renal Cell Carcinoma by Targeting COL5A1.

Recent evidences indicated that miRNAs played core role in the progression of clear cell renal cell carcinoma (ccRCC). However, its molecular mechanism in ccRCC is still remained unclear. The study was designed to identify the role and regulatory mechanism of miR-582-5p in ccRCC. In this study, the low expression level of miR-582-5p were detected by qRT-PCR in ccRCC patient tumor samples and ccRCC cell lines, respectively. The expression level of miR-582-5p was associated with tumor stage and metastasis. In vivo and in vitro experiments found miR-582-5p inhibit tumor growth via suppressing COL5A1 expression. Additionally, RUNX1 was identified as the negative regulator of miR-582-5p through database prediction and chromatin immunoprecipitation. Finally, the negative relation of RUNX1 and miR-582-5p was verified through rescue experiment both in vitro and in vivo. In summary, miR-582-5p, which was regulated by RUNX1, inhibited tumor growth and invasion by targeting COL5A1, indicating that miR-582-5p may act as a biomarker and that the RUNX1/miR-582-5p/COL5A1 axis could be a potential therapeutic target for ccRCC.

Meta-analysis and experimental validation identified atrazine as a toxicant in the male reproductive system.

Atrazine (ATZ), as a widely used triazine herbicide, is an environmental endocrine disruptor (EDC) that can cause many health problems. Therefore, we conducted this study based on the evidence of rats and mice to figure out the characteristics of ATZ damage to the reproductive system and further evaluate its health effects on the human. PRISMA's guidelines were followed according to the principles recommended by the Cochrane Handbook for Systematic Review. Health assessment was performed using the OHAT approach. Our new data were obtained from randomized controlled trials in rats designed in accordance with toxicological guidelines. Exposure to ATZ was significantly associated with decreased testosterone production (SMD = - 0.90, 95% CI - 1.27 to - 0.53), and reduced absolute weights of testis (SMD = - 0.41, 95% CI - 0.61 to - 0.22) and other reproductive organs. The damaging effect of sperm quality was also observed clearly, which included reduction of sperm count both in epididymis (SMD = - 2.32, 95% CI - 2.83 to - 1.81) and testis (SMD = - 1.01, 95% CI - 1.37 to - 0.64), decrease in sperm motility (SMD = - 8.86, 95% CI - 10.88 to - 6.83), and increase in sperm abnormality. Subgroup analysis revealed consistency across different species, life stage, and dosage. In addition, we found that ATZ exposure at a daily dose of 120 mg/kg during adolescence could cause decrease in weight gain and histological damage to the testis. The gene expression levels of Nrf2/HO-1 and Bcl-2/caspase signaling pathways in testis tissues were changed significantly. The results of this SR indicated that exposure to ATZ was associated with impairment of male reproductive system in rodents regardless of species, exposure life stage, and dosage. It is believed that ATZ exposure may have similar effects on male reproductive system of human beings. Pathways related to oxidative stress and apoptosis may be the mechanism leading to testicular damage in rats treated with ATZ.

Promoting cell proliferation, cell cycle progression, and glycolysis: Glycometabolism-related genes act as prognostic signatures for prostate cancer.

BACKGROUND: The Warburg effect seen in most solid tumors occurs only in the late stages of prostate cancer (PCa). Currently, the management of patients with low-risk localized PCa and patients after radical therapy remains a challenge. Our objective here was to evaluate glycometabolism-related genes as prognostic signatures for PCa. METHODS: The International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA) databases and glycometabolism-related gene sets were obtained online. Glycometabolic prognostic signatures were identified and validated in a TCGA cohort and tested in an ICGC cohort. We used the gene set enrichment analysis to reveal biological processes associated with the glycometabolism-related signatures. Novel glycometabolism-related genes were selected for verifying their oncogenic phenotypes in vitro. RESULTS: Two glycometabolic prognostic signatures were applied respectively to construct risk score formulas for PCa. Survival and receiver operating characteristic curve analyses were performed to detect the value of these prognostic signatures. We performed univariate and multivariate Cox regression analyses in the TCGA cohort, demonstrating the independence of the prognostic signatures. Three glycometabolism-related genes were found to be novel PCa-associated genes. These were shown to affect proliferation, cell cycle progression, and glycolysis of DU145 and PC3 cells in different degrees. CONCLUSION: The present research represents the first glycometabolic and high-throughput investigation on PCa, revealing potential biomarkers and treatment targets. We confirm the vital role of glycometabolism in PCa and provide essential resources for future exploration of metabolism in PCa.

lncRNA MIR4435-2HG promoted clear cell renal cell carcinoma malignant progression via miR-513a-5p/KLF6 axis.

Long non-coding RNAs (lncRNAs) take various biological effects in clear cell renal cell carcinoma (ccRCC) mostly through sponging with microRNAs (miRNAs). lncRNA MIR4435-2HG is found to promote tumour progression in gastric cancer, glioblastoma and hepatocellular carcinoma. However, the role of lncRNA MIR4435-2HG in ccRCC progression remains unknown. The purpose of this research was to investigate the potential molecular mechanism of lncRNA MIR4435-2HG regarding the regulation of ccRCC initiation and progression. In this study, we found the up-regulation of MIR4435-2HG in ccRCC tissues and cell lines. Functionally, overexpression of MIR4435-2HG promoted the proliferation as well as the metastasis in ccRCC cell lines, whereas knockdown of MIR4435-2HG inhibited the above changes. Then, bioinformatic analysis and luciferase reporter assays confirmed the negative regulation effect of MIR4435-2HG on miR-513a-5p. And further investigations showed that KLF6, which collected from the intersection of databases, was the potential conjugated mRNAs of miR-513a-5p. Finally, the rescue experiments revealed the relation among MIR4435-2HG and KLF6, which showed that KLF6 could reverse the promoting effect of MIR4435-2HG on ccRCC in vitro and in vivo. Therefore, our findings provided insight into the mechanisms of MIR4435-2HG in ccRCC and revealed an alternative target for the clinical diagnosis and treatment of ccRCC.

Comparison of prostate cancer detection rates between magnetic resonance imaging-targeted biopsy and transrectal ultrasound-guided biopsy according to Prostate Imaging Reporting and Data System in patients with PSA ≥4 ng/mL: a systematic review and meta-analysis.

BACKGROUND: Previous studies have investigated magnetic resonance imaging-targeted biopsy (MRI-TBx) on the detection for prostate cancer (PCa). Prostate Imaging Reporting and Data System (PI-RADS), as a standardized MRI reporting system, has widely been used in the management of PCa. However, basing the PI-RADS score, the comparability between MRI-TBx and transrectal ultrasound-guided biopsy (TRUS-Bx) in diagnosing PCa remained inconsistent or even controversial. Thus, this systematic meta-analysis aimed to assess the value of PI-RADS in sifting better prostate biopsy method. METHODS: A meta-analysis including 10 articles was performed. In these included studies, biopsy-naive subjects with concerning PSA levels and/or an abnormal digital rectal examination (DRE) were consecutively enrolled by referral from urologists. All subjects underwent multiparameter MRI (mpMRI) prostate and the results were scored independently by PI-RADS. Subjects with equivocal (PI-RADS 3) and intermediate/high-risk (PI-RADS 4/5) lesions underwent MRI-TBx and followed by TRUS-Bx performed by a urologist. The online databases PubMed, Embase and Web of Science were searched to find all correlated articles until October 1st, 2019. Data were pooled by odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the associations. Subgroup analyses were conducted based on Gleason score. RESULTS: Overall, 10 studies were included in this meta-analysis from January, 2015 to June, 2019. In the comparison of the detection of MRI-TBx and TRUS-Bx in PCa patients, TRUS-Bx had a significant advantage in overall PCa detection compared with MRI-TBx (OR =0.78, 95% CI: 0.62-0.98) in PI-RADS 3. Basing subgroup analysis of Gleason score (csPCa: Gleason score ≥7; non-csPCa: Gleason score <7), a summary analysis of the detection rate of csPCa showed that no significant difference was found (OR =0.82, 95% CI: 0.58-1.16); Meanwhile, no significant difference in non-csPCa patients was also detected (OR =0.83, 95% CI: 0.53-1.28). In PI-RADS 4 or 5, no significant results were detected between MRI-TBx and TRUS-Bx (OR =0.96, 95% CI: 0.87-1.06) for overall PCa detection. The stratification analyses by Gleason score found that TRUS-Bx had an advantage over MRI-TBx in non-csPCa patients (OR =0.76, 95% CI: 0.60-0.98); However, there was no significant difference in the detection rate of csPCa (OR =1.05, 95% CI: 0.93-1.20). CONCLUSIONS: This meta-analysis indicated that using TRUS-Bx was better than MRI-TBx for the diagnosis of PCa in PI-RADS 3; Besides, TRUS-Bx have an advantage over MRI-TBx in the detection for non-csPCa in PI-RADS 4 or 5. Therefore, PI-RADS could be used as a MRI evaluation system in the selection of prostate biopsy.