The aim of this study was to investigate the effects of IcarisideII(ICAII) on the prevention of streptozotocin (STZ) induced spermatogenic dysfunction. Forty male Sprague-Dawley rats received intraperitoneal injection of STZ (55 mg/kg) and were equally randomized to gavage feeding of vehicle (the vehicle group) or ICAII (0.5, 1.5 or 4.5 mg/kg/day, respectively). Ten normal rats received vehicle and served as control. Four weeks later, sperm parameters, histopathological changes, testicular lipid peroxidation, antioxidant enzyme activities, and apoptosis index (AI) were evaluated. Results showed that ICAII treatment resulted in a significant recovery of sperm parameters and histopathological changes relative to the vehicle group (p < 0.05). In the vehicle group, antioxidant enzyme activities and the expression of Sertoli cell Vimentin filaments obviously decreased, while lipid peroxidation and AI significantly increased as compared with the control group (p < 0.05). Following ICAII treatment, corrective effects on these items towards normal levels were observed. The results suggested that ICAII has beneficial effect on the preservation of spermatogenic function in the STZ-induced diabetic rats. The mechanisms might be related to its improvement of antioxidant enzyme activities, preservation of the protein expression and apical extensions of Vimentin filaments, and anti-apoptosis capability.

Diabetic erectile dysfunction is associated with penile dorsal nerve bundle neuropathy in the corpus cavernosum and the mechanism is not well understood. We investigated the neuropathy changes in the corpus cavernosum of rats with streptozotocin-induced diabetes and the effects of Icariside II (ICA II) on improving neuropathy. Thirty-six 8-week-old Sprague-Dawley rats were randomly distributed into normal control group, diabetic group and ICA-II treated group. Diabetes was induced by a one-time intraperitoneal injection of streptozotocin (60 mg/kg). Three days later, the diabetic rats were randomly divided into 2 groups including a saline treated placebo group and an ICA II-treated group (5 mg/kg/day, by intragastric administration daily). Twelve weeks later, erectile function was measured by cavernous nerve electrostimulation with real time intracorporal pressure assessment. The penis was harvested for the histological examination (immunofluorescence and immunohistochemical staining) and transmission electron microscopy detecting. Diabetic animals exhibited a decreased density of dorsal nerve bundle in penis. The neurofilament of the dorsal nerve bundle was fragmented in the diabetic rats. There was a decreased expression of nNOS and NGF in the diabetic group. The ICA II group had higher density of dorsal nerve bundle, higher expression of NGF and nNOS in the penis. The pathological change of major pelvic nerve ganglion (including the microstructure by transmission electron microscope and the neurite outgrowth length of major pelvic nerve ganglion tissue cultured in vitro) was greatly attenuated in the ICA II-treated group (p < 0.01). ICA II treatment attenuates the diabetes-related impairment of corpus cavernosum and major pelvic ganglion neuropathy in rats with Streptozotocin-Induced Diabetes.

Background: Kidney transplantation is an optimal method for treatment of end-stage kidney failure. However, kidney transplant rejection (KTR) is commonly observed to have negative effects on allograft function. MicroRNAs (miRNAs) are small non-coding RNAs with regulatory role in KTR genesis, the identification of miRNA biomarkers for accurate diagnosis and subtyping of KTR is therefore of clinical significance for active intervention and personalized therapy. Methods: In this study, an integrative bioinformatics model was developed based on multi-omics network characterization for miRNA biomarker discovery in KTR. Compared with existed methods, the topological importance of miRNA targets was prioritized based on cross-level miRNA-mRNA and protein–protein interaction network analyses. The biomarker potential of identified miRNAs was computationally validated and explored by receiver-operating characteristic (ROC) evaluation and integrated “miRNA-gene-pathway” pathogenic survey. Results: Three miRNAs, i.e., miR-145-5p, miR-155-5p, and miR-23b-3p, were screened as putative biomarkers for KTR monitoring. Among them, miR-155-5p was a previously reported signature in KTR, whereas the remaining two were novel candidates both for KTR diagnosis and subtyping. The ROC analysis convinced the power of identified miRNAs as single and combined biomarkers for KTR prediction in kidney tissue and blood samples. Functional analyses, including the latent crosstalk among HLA-related genes, immune signaling pathways and identified miRNAs, provided new insights of these miRNAs in KTR pathogenesis. Conclusions: A network-based bioinformatics approach was proposed and applied to identify candidate miRNA biomarkers for KTR study. Biological and clinical validations are further needed for translational applications of the findings.