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Context Plant microRNAs (miRNAs) present in Yishen Tongluo formula (YSTL, a traditional Chinese herbal medicine formula) are considered as potential therapeutic drugs for reducing the sperm DNA fragmentation index (DFI).Objective To study the effectiveness of plant miRNAs in YSTL for repairing mouse sperm DNA damage caused by benzo(a)pyrene (BaP).Methods and materials Twenty-four male SPF ICR (CD1) mice were divided into control, BaP and YSTL groups. A BaP-induced (100 mg/kg) sperm DNA damage model was established in the BaP and YSTL groups, and the mice in the YSTL group were treated with YSTL (23.78 g/kg) for 8 weeks. Sperm DFI was determined via a sperm chromatin structure assay (SCSA). MicroRNAs in the testes of the mice were analysed via RNA-seq, and the top four plant miRNAs were screened, identified and overexpressed in GC cells. The effects of plant miRNAs on the viability and DNA integrity of GC cells exposed to benzo(a)pyrene diol epoxide (BPDE) (1 μM) were tested using CCK8 and comet assays.Results Compared with that of the BaP group, the DFI of the YSTL group decreased (9.57% vs. 18.54%, F = 18.645, p = 0.0236). miR166-y, miR894-x, miR822-x and miR396-x were screened. The CCK8 and comet assays revealed that the DFI of the mimic group was significantly lower than that of the BPDE (IC50 = 1.006 μM) group, with the most significant difference in the miR396-x group.Discussion and Conclusions Plant miRNAs such as miR396-x can penetrate the blood–testis barrier through the digestive system to repair sperm DNA.

AbstractContext 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.

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.

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.

Oligoasthenozoospermia is a complex disease caused by a variety of factors, and its incidence is increasing yearly worldwide. Yishen Tongluo formula (YSTLF), created by Professor Sun Zixue, has been used to treat oligoasthenozoospermia in clinical practice for several decades with a good therapeutic effect. However, the chemical and pharmacological profiles of YSTLF remain unclear and need to be elucidated. In this study, a network pharmacology approach was applied to explore the potential mechanisms of YSTLF in oligoasthenozoospermia treatment. All of the compounds in YSTLF were retrieved from the corresponding databases, and the bioactive ingredients were screened according to their oral bioavailability (OB) and drug-likeness (DL). The potential proteins of YSTLF were obtained from the traditional Chinese medicine systems pharmacology (TCMSP) database and the Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM) database, while the potential genes of oligoasthenozoospermia were obtained from the GeneCards database and the DisGeNET database. The STRING database was used to construct an interaction network according to the common targets identified by the online tool Venny for YSTLF and oligoasthenozoospermia. The topological characteristics of nodes were visualized and analyzed through Cytoscape. Biological functions and significant pathways were determined and analyzed using the Gene Ontology (GO) knowledgebase, the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Metascape. Finally, the disease-formula-compound-target-pathway network was constructed by Cytoscape. A total of 106 bioactive ingredients and 134 potential targets from YSTLF were associated with oligoasthenozoospermia or considered to be therapeutically relevant. Pathway analysis indicated that the PI3K/Akt, MAPK and apoptosis signaling pathways were significant pathways involved in oligoasthenozoospermia. In conclusion, the current study expounded the pharmacological actions and molecular mechanisms of YSTLF in treating oligoasthenozoospermia from a holistic viewpoint. The potential molecular mechanisms were closely related to antioxidative stress, antiapoptosis and anti-inflammation, with TNF, CCND1, ESR1, NFKBIA, NR3C1, MAPK8, and IL6 being possible targets. This network pharmacology prediction may offer a helpful tool to illustrate the molecular mechanisms of the Chinese herbal compound YSTLF in oligoasthenozoospermia treatment.

Abstract Background Both multimorbidity and activities of daily living (ADL) disability and instrument activities of daily living (IADL) disability are common among elderly individuals. ADL/IADL disability may reduce individuals’ capacities for independent living and quality of life. This study aimed to examine the association between multimorbidity and ADL/IADL disability. Methods A multi-stage cluster sample of 2058 residents aged 80 or older was investigated in Shanghai, China. Multimorbidity was defined as the simultaneous presence of two or more chronic diseases with ten common chronic conditions under consideration. Subjects who responded that they “need partial or full assistance” to any ADL/IADL items were defined as having ADL/IADL disability. We examined the association of multimorbidity with ADL/IADL disability, adjusted for socio-demographic characteristics by using logistic regression. Results Of respondents, 23.23 % had ADL disability, 37.90 % had IADL disability, and 49.17 % had multimorbidity. After adjusted socio-demographic characteristics, a graded association was showed between ADL disability and the quantity of chronic conditions: odds ratio (OR) for 1 condition, 1.53(95 % confidence interval [CI], 1.04-2.24); OR for 2 conditions, 2.06(95 % CI, 1.43-2.96); OR for 3 conditions, 3.23(95 % CI, 2.14-4.86); OR for 4 or more conditions, 5.61(95 % CI, 3.26-9.66). Similar associations were also observed between the quantity of chronic conditions and IADL disability. Conclusions The quantity of chronic conditions had relatively strong association with both ADL and IADL disability. Initiating prevention of additional chronic conditions and interventions on clusters of diseases may decrease the potential risk of ADL/IADL disability. Additionally, more attention should been given to the older low-income women living with relatives/non-relatives with multimorbidity.