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Male infertility has evolved from a common reproductive system disease to a major social issue. Youjing granule (YG) is a Chinese medicinal material used as a therapy method for tonifying the kidneys and removing dampness due to its pathogenic characteristics. YG has been shown to regulate sperm quality in clinical trials, but the underlying mechanism is not fully understood. The present study was aimed to explore the protective effects and mechanism of action of YG on male reproductive system damage caused by methyl methane sulfonate (MMS). We first established an infertility model of rats through oral administration of MMS and then treated with YG. To determine the effect of YG, spermatogenesis, microvascular density, and secretory function of Leydig cells and Sertoli cells in rats were assessed. Spermatogonial stem cells (SSCs) were co-cultured with mouse embryo fibroblast (MEF) cells as an in vitro cell model before exposure to serum containing YG. Furthermore, the proliferation and apoptosis of SSCs were measured. Results indicated that YG increased the expression of self-renewal and proliferation-related molecules such as glial cell line derived neurotrophic factor (GDNF) and fibroblast growth factor-2 (FGF2), and improved the quality of sperm and the proliferation of SSCs. In conclusion, YG may protect spermatogenetic function of rats through regulating the proliferation and self-renewal of SSCs.

Background Metallothionein 1M (MT1M) functions to regulate cell proliferation and cancer metastasis. This study assessed the effects of MT1M overexpression and mouse double minute 2 homolog (MDM2) knockdown on the regulation of non-small cell lung cancer A549 cell viability, migration, and protein expression in vitro and explored the underlying molecular events. Methods A549 cells were stably infected with lentivirus carrying MT1M cDNA or transiently transfected MDM2 siRNA and/or treated with the p53 inhibitor for the assessment of changes in cell viability, wound healing, Transwell migration, and qRT-PCR and Western blot assays. Luciferase reporter assay was performed to investigate p53 binding to the MT1M promoter. Results The data showed that MT1M overexpression inhibited A549 cell viability and migration capacity in vitro, whereas the p53 inhibitor reversed the inhibition of A549 cell viability and migration caused by MT1M overexpression as well as the expression of MMP2, MMP9, and MMP14. Furthermore, knockdown of MDM2, an upstream inhibitor of p53 activity, was able to reduce A549 cell viability, migration, and protein expression. Thus, MDM2 knockdown had synergistic effects with MT1M overexpression on the suppression of A549 cell viability, migration, and protein expression. Conclusions In conclusion, MDM2 can bind to and phosphorylate p53 protein to inactivate the protein, thereby reducing MT1M expression and leading to tumor cell proliferation and migration.

Diabetic foot ulcer has become a worldwide clinical medical challenge as traditional treatments are not effective enough to reduce the amputation rate. Therefore, it is of great social significance to deeply study the pathogenesis and biological characteristics of the diabetic foot, explore new treatment strategies and promote their application. Stem cell-based therapy holds tremendous promise in the field of regenerative medicine, and its mechanisms include promoting angiogenesis, ameliorating neuroischemia and inflammation, and promoting collagen deposition. Studying the specific molecular mechanisms of stem cell therapy for diabetic foot has an important role and practical clinical significance in maximizing the repair properties of stem cells. In addition, effective application modalities are also crucial in order to improve the survival and viability of stem cells at the wound site. In this paper, we reviewed the specific molecular mechanisms of stem cell therapy for diabetic foot and the extended applications of stem cells in recent years, with the aim of contributing to the development of stem cell-based therapy in the repair of diabetic foot ulcers.

To investigate the effect and action mechanism of Yu Si Granules (YSG) in the treatment methyl methanesulphonate (MMS)-induced oligoasthenozoospermia (OAZ) in mice.Thirty adult male mice were randomly divided into three groups of equal number, normal control, OAZ model control and YSG intervention. The OAZ model was established by oral administration of MMS and the model mice in the YSG intervention group were treated intragastrically with YSG suspension at 0.144 g/100 g of the body weight per day for 48 successive days. Then, all the mice were sacrificed and their epididymides harvested for detection of the sperm count and motility, observation of the morphology of the seminiferous tubules by HE staining, determination of the expressions of the germ cell-, sperm cell-, spermatocyte-, Sertoli cell- and blood-testis barrier-related genes by RT-PCR, and measurement of the levels of oxidative stress in the blood.Compared with the normal control, the OAZ model mice showed significantly decreased sperm count (［49.2 ± 0.7］ vs ［23.6 ± 0.4］ ×107/ml/g, P0.05) and sperm motility (［76.3 ± 0.7］% vs ［5.0 ± 5.8］%, P0.05), which were both remarkably increased after YSG intervention (［38.4 ± 0.5］ ×107/ml/g and ［71.5 ± 0.5］%) (P0.05). The OAZ model mice also exhibited degenerated and atrophic seminiferous tubules, thinner seminiferous epithelia, disorderly arranged cells at different levels, reduced number of sperm in the lumen and unclear layers of germ cells in the epididymis, while those after YSG intervention manifested regularly organized seminiferous tubules with orderly arrangement and clear layers. The expressions of the Vasa, Dazl and Snd1 genes were significantly decreased (P0.05), but not those of Gfra, Plzf, Stra8, Spo11, Sycp3, Sox9 and Vim (P0.05) in the OAZ model and YSG intervention groups as compared with those in the normal control group. The superoxide dismutase (SOD) activity in the serum was markedly reduced in the OAZ model mice as compared with that in the normal controls (P0.05) and increased again after YSP intervention (P0.05), but the opposite was the case with the expression of the superoxide anion.YSG can significantly reduce MMS-induced OAZ in mice, which may be associated with oxidative stress.

To investigate the effect of decitabine (DAC) alone or in combination with arsenic trioxide (AsThe inhibitory effect of DAC and AsThe inhibitory effect of DAC or AsDAC or As

CYP3A5 genetic polymorphisms have been reported to be strongly associated with the tacrolimus pharmacokinetics in adult kidney transplantation. However, there is no published meta-analysis in the influence of CYP3A5 variants on the requirements of the tacrolimus dose in pediatric renal-transplant recipients (RTRs). We wished to determine the effects of CYP3A5 polymorphisms on tacrolimus pharmacokinetics in pediatric RTRs. A literature search was conducted to include relevant articles by searching PubMed, EMBASE and the Cochrane Central Register of Controlled Trials. Pharmacokinetic-associated parameters such as dose administration, as well as concentrations and dose-adjusted concentrations of tacrolimus were extracted and the meta-analysis undertaken. The meta-analysis involved four studies and one study series involving 268 pediatric RTRs. A significant difference was observed in the mean trough concentration/dose of tacrolimus between recipients carrying CYP3A5* 3/*3 variants (referred to as "non-expressers") and those carrying CYP3A5*1 (referred to as "expressers") [standard mean difference (SMD)=-1.09, 95% confidence interval (CI): -1.92 to -0.25, P=0.011]. Moreover, significance was observed in the mean daily dose of tacrolimus between non-expressers and expressers in pediatric RTRs (SMD=0.44, 95% CI: 0.20 to 0.68, P