Infertility is a significant problem for human reproduction, with males and females equally affected. However, the molecular mechanisms underlying male infertility remain unclear. Spermatogenesis is a highly complex process involving mitotic cell division, meiosis cell division and spermiogenesis; during this period, unique and extensive chromatin and epigenetic modifications occur to bring about specific epigenetic profiles in spermatozoa. It has recently been suggested that the dysregulation of epigenetic modifications, in particular the methylation of sperm genomic DNA, may serve an important role in the development of numerous diseases. The present study is a comprehensive review on the topic of male infertility, aiming to elucidate the association between sperm genomic DNA methylation and poor semen quality in male infertility. In addition, the current status of the genetic and epigenetic determinants of spermatogenesis in humans is discussed.

Forkhead box protein A1 (FOXA1) is a pioneer factor of estrogen receptor α (ER)-chromatin binding and function, yet the role of FOXA1 in breast cancer and the underlying molecular mechanisms have not yet been elucidated. To evaluate gene expression alterations during breast carcinogenesis, FOXA1 expression was analyzed using the Serial Analysis of Gene Expression Genie suite, a gene expression profiling interactive analysis, and Oncomine analyses. The correlation between methylation and expression was analyzed using the MEXPRESS tool and UCSC Xena browser. Then, the expression and prognostic value of FOXA1 was validated by our own breast cancer samples using RT-PCR. We obtained the following important results. (1) The expression level of FOXA1 was significantly higher in breast cancer than normal tissues. (2) ER, PR, HEGR-2, and nodal status were positively correlated with FOXA1 expression. (3) Among patients with ER+ tumors, those with higher FOXA1 expression levels had better survival probabilities. (4) The major mutation type in FOXA1 in breast cancer samples was missense mutations. (5) FOXA1 expression was significantly higher in ER+ breast tumors than in ER- tumors or normal tissues. Our findings suggest that the aberrant DNA hypomethylation of promoter regions is one mechanism underlying the aberrant expression of FOXA1 in ER+ breast cancer, which might be a potential indicator of favorable prognosis.

Midkine (MK) has been reported as the potential novel diagnostic biomarker for cancer in several studies, but their results were controversial. Therefore, we performed a diagnostic meta-analysis to assess the diagnostic value of serum MK in cancer patients. A systematic electronic and manual search was performed for relevant literatures through several databases up to June 1, 2017. The quality of the studies included in the meta-analysis was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. All analyses were conducted using stata12.0 software. Ten studies collectively included 1119 cancer patients and 1441 controls met the eligible criteria. The summary estimates were: sensitivity 0.78 (95% CI = 0.68–0.85), specificity 0.83 (95% CI = 0.72–0.90), positive likelihood ratio 4,54 (95% CI = 2.64–7.80), negative likelihood 0.27 (95% CI = 0.18–0.40), diagnostic odds ratio 16.79 (95% CI = 7.17–39.33), and area under the curve 0.87 (95% CI = 0.84–0.89). Publication bias was suggested by Deeks’ funnel plot asymmetry test (P = 0.92). According to our results, serum MK has greater diagnostic value in diagnosing cancer, however, more reliable studies in larger cohort should be conducted to evaluate the diagnostic accuracy of serum MK.

Background: Homer scaffolding protein 1 (Homer1) is a postsynaptic scaffold protein that regulates the structure and function of excitatory synaptic as well as its intracellular signal transduction. However, the role of Homer1 in colorectal cancer as well as the underlying molecular mechanisms has not been elucidated. Materials and Methods: To evaluate the alternations of gene expression during colorectal cancer, Homer1 expression was analyzed using the gene expression profiling interactive analysis and Oncomine analyses. The prognostic value of Homer1 expression was validated by our own colorectal cancer specimens using RT-PCR. Then, the cell viability, migration and invasion of colorectal cancer cell lines were detected by CCK-8 and transwell assay. Results: We obtained the following important results. (1) Homer1 expression was significantly higher in colorectal cancer than normal samples. (2) Among patients with colorectal cancer, those with higher Homer1 expression had a lower survival rate. (3) The major mutation type of Homer1 in colorectal cancer samples was missense mutation. (4) Homer1 was able to promote colorectal cancer cell proliferation, migration, and invasion through up-regulating G3BP1 in vitro. Conclusion: Our findings suggest that Homer1 may play a role in malignancy of colorectal cancer mainly through the G3BP1 signaling pathway, which might be a potential indicator of poor prognosis.

Background: Inflammatory response of central nervous system is an important component mechanism in the bladder pain of interstitial cystitis/bladder pain syndrome (IC/BPS). Exosomes transfer with microRNAs (miRNA) from mesenchymal stem cell (MSCs) might inhibit inflammatory injury of the central nervous system. Herein, the purpose of our study was to explore the therapeutic effects by which extracellular vesicles （EVs） derived from miR‐9‐edreched MSCs in IC/BPS and further investigate the potential mechanism to attenuate neuroinflammation.Methods: On the basis of IC/BPS model, we used various techniques including bioinformatics, cell and molecular biology, and experimental zoology, to elucidate the role and molecular mechanism of TLR4 in regulating the activation of NLRP3 inflammasome in bladder pain of IC/BPS, and investigate the mechanism and feasibility of MSC‐EVs enriched with miR‐9 in the treatment of bladder pain of IC/BPS.Results: The inflammatory responses in systemic and central derived by TLR4 activation were closely related to the cystitis‐induced pelvic/bladder nociception in IC/BPS model. Intrathecal injection of miR‐9‐enreched MSCs derived exosomes were effective in the treatment of cystitis‐induced pelvic/bladder nociception by inhibiting TLR4/NF‑κb/NLRP3 signal pathway in central nervous system of IC/BPS mice.Conclusions: This study demonstrated that miR‐9‐enreched MSCs derived exosomes alleviate neuroinflammaiton and cystitis‐induced bladder pain by inhibiting TLR4/NF‑κb/NLRP3 signal pathway in interstitial cystitis mice, which is a promising strategy against cystitis‐induced bladder pain.