Transcriptomic and proteomic features of a mouse model of sperm DNA damage induced by benzo(a)pyrene.

This study replicated a mouse model of sperm DNA damage induced by benzo(a)pyrene (BaP), and the transcriptomic and proteomic features of the model were examined to clarify the pathways related to BaP-induced damage to sperm DNA. Male mice in the BaP group were subjected to BaP at a dosage of 100 mg/kg/d or an equivalent quantity of saline solution in the control group for 60 days. Subsequently, the DNA fragmentation index (DFI) in sperm was assessed using a sperm chromatin structure assay (SCSA). RNA-seq and data-independent acquisition (DIA) were used to identify the mRNA and protein expression patterns in the testis. The sperm DFI significantly increased in the BaP group. Compared to the control group, the BaP group exhibited differential expression of 240 genes (referred to as DEGs) and 616 proteins (referred to as DEPs). These molecules included Aldh1a1, Cyb5r3, Fads1, Oxsm, Rcn3, and Prss45. Pathways in cancer, the PI3K-Akt signaling pathway, metabolic pathways, and the MAPK signaling pathway were the primary areas where these genes showed enrichment. BaP can damage the DNA of sperm and affect metabolism, the PI3K-Akt pathway, and pathways associated with cancer signaling.

Causal relationship between worry, tension, insomnia, sensitivity to environmental stress and adversity, and erectile dysfunction: a study using Mendelian randomization.

BACKGROUND: This study aims to investigate the causal relationship between erectile dysfunction (ED) and psychological states including worry, tension, insomnia, sensitivity to environmental stress and adversity (SESA). METHOD: This study the used two-sample bi-directional Mendelian randomization (MR) method. The study data was obtained from a pooled dataset of genome-wide association studies (GWAS). The bi-directional MR analysis was performed using inverse variance weighting, weighted median method, and MR-Egger regression analysis to assess the causality between ED and psychological states including worry, tension, insomnia, SESA in terms of odd ratios (OR). The study tested for heterogeneity using the Cochran Q method and for multiple validity using the MR-Egger and MR-PRESSO methods. RESULTS: In forward MR analysis correlating worry, tension, insomnia, and SESA as exposures, no causal relationship was found between worry or tension and ED (p < 0.05). However, insomnia (p = 0.001, OR = 3.441, 95%CI = 1.593-7.435) and SESA (p = 0.004, OR = 1.804, 95%CI = 1.203-2.701) were found to have a significant causal effect on ED risk. The reverse MR analysis with ED as the exposure did not show any significant correlation (all p > 0.05). CONCLUSION: Individuals with insomnia and SESA are at higher risk for developing ED. Clinical evaluation should be more thorough for these individuals. Insomnia can be treated simultaneously with psychological counseling to reduce the risk of ED. In addition, there is no evidence to suggest that worry and tension increase the risk of ED.

Repair mechanism of Yishen Tongluo formula on mouse sperm DNA fragmentation caused by polystyrene microplastics.

CONTEXT: Plastics can break down into millions of microplastic (MPs, < 5 mm) particles in the soil and ocean. These MPs can then affect the function of the reproductive system. There is currently no effective solution to this problem aside from traditional Chinese medicine. We have previously used Yishen Tongluo formula (YSTL) to treat sperm DNA damage caused by some toxic substances. OBJECTIVE: To investigate the mechanism underlying the repair of mouse sperm DNA fragmentation caused by polystyrene microplastics by YSTL. MATERIALS AND METHODS: An animal model of polystyrene microplastic (PS-MP)-induced sperm DNA damage was replicated by gavage of SPF ICR (CD1) mice PS-MPs at 1 mg/d and treated with YSTL at 11.89, 23.78 and 47.56 g/kg, respectively, for 60 days. The Sperm DNA fragmentation index (DFI) of each group was detected and compared. The target genes of YSTL identified by transcriptomic and proteomic analyses were validated by qRT-PCR and western blotting. RESULTS: The DFI of the PS group (20.66%) was significantly higher than that of the control group (4.23%). The medium and high doses of the YSTL group (12.8% and 11.31%) exhibited a significant repairing effect. The most enriched pathway was PI3K/Akt. TBL1X, SPARC, hnRNP0, Map7D1, Eps8 and Mrpl27 were screened and SPARC was validated. DISCUSSION AND CONCLUSIONS: The precise mechanism by which YSTL inhibits PD-MPs DNA damage may be associated with the PI3K/Akt pathway and SPARC. It provides a new direction for using traditional Chinese medicine to prevent and repair reproductive system injury caused by MPs.

[The causal relationship between gut microbiota and male reproductive and sexual health].

OBJECTIVE: The purpose of this study was to use the MR method to explore the causal relationship between 211 gut microbiota and male reproductive and sexual health. METHODS: The MiBioGen alliance published genome-wide association study (GWAS) related genetic variation data was used as instrumental variables (IVs) for gut microbiota, and the Finngen biobank GWAS related genetic variation data was used as IVs for male infertility, abnormal sperm, sexual dysfunction, erectile dysfunction, and testicular dysfunction. The inverse variance-weighted (IVW) method was used as the MR analysis method, the results were evaluated according to the odds ratio and 95% confidence interval of the effect measures, and data sensitivity analysis was performed. RESULTS: The results showed that 6 types of gut microbiota were related to male infertility, 12 types were related to abnormal sperm, 5 types were related to sexual dysfunction, 4 types were related to erectile dysfunction, and 4 types were related to testicular dysfunction. And there was no abnormality in the data sensitivity analysis. CONCLUSION: The intestinal microbiota is closely related to male reproductive and sexual health.

Transcriptomic and proteomic characteristics of the di(2-ethylhexyl) phthalate-induced sperm dna damage mouse model.

Di(2-ethylhexyl) phthalate (DEHP) is one of the most common organic pollutants and is added to various plastic products as a plasticizer. DEHP oxidative metabolite content in the human body is associated with DNA damage in sperm and decreased testosterone levels in blood. In this study, a DEHP-induced sperm DNA damage mouse model was replicated and improved, and the transcriptomic and proteomic characteristics of the model were observed. Male mice in the two groups were exposed to DEHP 1 g/kg/d or the same amount of normal saline for 60 days, and the sperm DNA fragmentation index (DFI) was detected by a sperm chromatin structure assay (SCSA). The mRNA and protein expression profiles of the testis were detected by RNA-seq and data-independent acquisition (DIA). The sperm DFI of the DEHP group was significantly increased. Compared with the control group, 111 differentially expressed genes (DEGs) and 2147 differentially expressed proteins (DEPs), such as Lamb2, Ahnak, Tkt, Dnah8 and Tbl2, were found in the DEHP group. These genes were mainly enriched in metabolic pathways, pathways in cancer and the PI3K-Akt signaling pathway. Our results showed that DEHP 1 g/kg/d can induce sperm DNA damage in a male mouse model after 60 days of intragastric administration. The reproductive toxicity of DEHP may be related to metabolic pathways in cancer and the PI3K-Akt signaling pathway.

Transcriptomics and proteomics analysis to explore the mechanism of Yishen Tongluo formula repairing sperm DNA damage in rats.

The sperm DNA fragmentation index (DFI) is an objective indicator of male fertility. Currently, effective treatments for high sperm DFI are limited and traditional Chinese medicine (TCM) has certain advantages in this aspect. Yishen Tongluo formula (YSTL), a TCM formula, has been found to reduce DFI in patients. To better understand the mechanisms underlying its activity, we used transcriptomics and proteomics to analyse the potential target gene YSTL repairing tripterygium glycosides (TGs)-mediated sperm DNA damage in rats, followed by validation analyses using RT-qPCR and western blotting, which showed that relative to the control group, DFI was markedly elevated in the TGs group, but markedly lower in the YSTL group relative to the TGs group. KEGG pathway analysis of 119 differentially expressed genes and 158 DEPs identified using trend analysis revealed that they were enriched for apoptosis and base excision repair at the transcriptomic level and for microRNAs in cancer and complement and coagulation cascades at the proteomic level. Ttr and Pnpla2 were identified as potential target genes for YSTL. Our data show that YSTL can protect rat sperm DNA from TGs-induced damage, which may be related to apoptosis, DNA repair and other pathways, and the possible target genes are Ttr and Pnpla2.

Methylation status of TK1 correlated with immune infiltrates in prostate cancer.

TK1 is overexpressed in numerous cancers and is associated with to a poor prognosis. However, the relationship between methylation status of TK1 and Immune Infiltrates in Prostate Cancer (PCa) is unknown. The goal of this study was to use comprehensive bioinformatic analyses to elucidate the involvement relationship between methylation status of TK1 and Immune Infiltrates in PCa. TK1 mRNA expression and methylation data in PCa were investigated via GEPIA, TIMER, and UALCAN coupled with MEXPRESS data resources. We employed the LinkedOmics data resource to determine the signaling cascades linked to TK1 expression. Single-cell analysis was performed using the CancerSEA data resource. GeneMANIA and CancerSEA were used to analyze the correlation between TK1 and TK1 coexpressed genes. In addition, TIMER and TISIDB were adopted to assess tumor-invading immune cells and immunomodulators. CTD was utilized to detect the drugs acting on TK1. This study found that TK1 was overexpressed in PCa, and its contents were linked to tumor stage and prognosis. Genes co-expressed with TK1 were enriched in cascades involved in the ribosome, cell cycle, oxidative phosphorylation, DNA replication, oocyte meiosis, and the proteasome. The expression of TK1 along with its methylation status was found to be linked to tumor-invading immune cells, as well as PCa immunomodulators. We also examined the prospect of employing TK1 as a possible target for PCa therapy. This work provides the clinical value of TK1 hypermethylation in PCa and highlights new insights into its novel immunomodulatory functions.

Repair mechanism of Wuwei Fuzheng Yijing formula in di-2-ethylhexyl phthalate-induced sperm DNA fragmentation in mice.

CONTEXT: Di-2-ethylhexyl phthalate (DEHP), a known persistent organic pollutant, can increase the sperm DNA fragmentation index (DFI). OBJECTIVE: To investigate the mechanism underlying the repair of DEHP-induced sperm DNA damage in mice by Wuwei Fuzheng Yijing (WFY) formula. MATERIALS AND METHODS: The potential targets of WFY and sperm DNA fragment (SDF) were obtained from the TCMSP, BATMAN-TCM, OMIM and GeneCards. The protein-protein interaction (PPI) network, GO and KEGG pathway analyses of WFY-SDF were constructed. An animal model of DEHP-induced sperm DNA damage was replicated by gavage of SPF ICR (CD1) mice DEHP at 1 g/kg/d and treated with WFY at 8.92, 17.84 and 35.67 g/kg, respectively, for 60 d. Sperm DFI of each group was detected and compared. The target genes of WFY identified by transcriptomic and proteomic analyses were validated by qRT-PCR and Western blotting. RESULTS: Network pharmacology pathway analysis indicated that PI3K/Akt was the potential target of WFY on SDF. The DFI of the DEHP group (25.48%) was significantly higher than that of the control group (4.02%). The high-dose WFY group (19.05%) exhibited the most significant repairing effect. The related pathways were PI3K/Akt and metabolic. Aass, Aldh1a7, GSTA3, betaine homocysteine S-methyltransferase (Bhmt), Mug2 and Svs1 were screened and Bhmt was validated. DISCUSSION AND CONCLUSIONS: WFY can repair sperm DNA damage caused by DEHP, and the mechanism may be related to PI3K/Akt and metabolic pathways, and Bhmt. This provides a new direction for using traditional Chinese medicine to prevent and repair reproductive system injury caused by pollutants.

Synthesis of nitrogen-rich magnetic hypercrosslinked polymer as robust adsorbent for the detection of neonicotinoids in honey, tomatoes, lettuce and Chinese cabbage.

In this study, a novel nitrogen-rich magnetic hypercrosslinked polymer (Fe3O4@Ph-HCP) was fabricated via a facile one-pot reaction of 1,3,5-triphenylbenzene, 2,4-dichloropyrimidine and phenyl-functionalized magnetic Fe3O4 nanoparticles. The Fe3O4@Ph-HCP possessed high specific surface, abundant nanopores and good stability. Especially, Fe3O4@Ph-HCP exhibited excellent adsorption capability with fast adsorption rate to neonicotinoid insecticides. It was applied as a superior magnetic adsorbent for rapid enrichment and isolation of four neonicotinoid insecticides (thiamethoxam, imidacloprid, acetamiprid and thiacloprid) from honey, tomato, lettuce and Chinese cabbage samples prior to high performance liquid chromatography-diode array detection. Under the optimized conditions, the good linearity was obtained in the range of 1-1000 ng g-1 for honey, tomato, lettuce and Chinese cabbage samples, and the detection limits (S/N = 3) were 0.30-0.67 ng g-1 for honey, 1-1.5 ng g-1 for tomato, lettuce and Chinese cabbage. The spiked recoveries were 80.1-111%, and relative standard deviations were less than 10.0%. These results demonstrate that the developed method can be used as a good alternative method for sensitive determination of neonicotinoid insecticides in complex samples.

Microplastics May Be a Significant Cause of Male Infertility.

Due to the problematic degradation properties of plastics, the decomposition of plastic results in the formation of numerous microplastics (MPs), less than 5 mm in diameter. These MPs enter the soil and the ocean, eventually passing through the air, water, or food chain back to the human body and harming human health. In the last 80 years, male semen analysis parameters have shown a significant decline for unknown reasons, speculated to be caused by pollutants. No studies examined the relationship between human MP exposure and male infertility. In this article, we reviewed the relevant animal experimental research literature in recent years and calculated that the minimum human equivalent dose of MPs leading to abnormal male semen quality is 0.016 mg/kg/d. The literature comparison found that MP exposure in Japan and South Korea was close to this value. These results suggest that MPs can affect male semen quality and that MPs may significantly impact male fertility.

Gender differences in the efficacy of pioglitazone treatment in nonalcoholic fatty liver disease patients with abnormal glucose metabolism.

BACKGROUND: Pioglitazone is a promising therapeutic method for nonalcoholic fatty liver disease (NAFLD) patients with or without type 2 diabetes. However, there is remarkable variability in treatment response. We analyzed our previous randomized controlled trial to examine the effects of gender and other factors on the efficacy of pioglitazone in treating Chinese nonalcoholic fatty liver disease (NAFLD) patients with abnormal glucose metabolism. METHODS: This is a post hoc analysis of a previous randomized, parallel controlled, open-label clinical trial (RCT) with an original purpose of evaluating the efficacy of berberine and pioglitazone on NAFLD. The total population (n = 185) was randomly divided into three groups: lifestyle intervention (LSI), LSI + pioglitazone (PGZ) 15 mg qd, and LSI + berberine (BBR) 0.5 g tid, respectively, for 16 weeks. The study used proton magnetic resonance spectroscopy (1H-MRS) to assess liver fat content. RESULTS: As compared with LSI, PGZ + LSI treatment further decreased liver fat content in women (- 15.24% ± 14.54% vs. - 8.76% ± 13.49%, p = 0.025), but less decreased liver fat content in men (- 9.95% ± 15.18% vs. - 12.64% ± 17.78%, p = 0.046). There was a significant interaction between gender and efficacy of pioglitazone before and after adjustment for age, smoking, drinking, baseline BMI, BMI change, treatment adherence, baseline liver fat content, and glucose metabolism. CONCLUSION: The study recommends pioglitazone plus lifestyle intervention for Chinese NAFLD female patients with abnormal glucose metabolism. TRIAL REGISTRATION: Role of Pioglitazone and Berberine in Treatment of Non-Alcoholic Fatty Liver Disease, NCT00633282 . Registered on 3 March 2008, https://register.clinicaltrials.gov .