[Research progress in the relationship of hypoxia-inducible factor 1 with prostate diseases in hypoxic environment].

The relationship between male prostate diseases and the hypoxic microenvironment has drawn increasing attention from the medical world. The role of hypoxia-inducible factor 1 (HIF-1), a typical factor for the hypoxic microenvironment, in prostate diseases is one of the hotspots in recent studies. HIF-1 plays an important role in different prostate diseases by participating in metabolic reprogramming, angiogenesis, tissue remodeling, immune regulation and other life activities. This review focuses on the action mechanisms of HIF-1 in prostatitis, prostatic hyperplasia and prostate cancer.

Integrated 16S rRNA sequencing and metabolomics analysis to investigate the antidepressant role of Yang-Xin-Jie-Yu decoction on microbe-gut-metabolite in chronic unpredictable mild stress-induced depression rat model.

Objectives: Our goals were to evaluate the antidepressant efficacy of Yang-Xin-Jie-Yu Decoction (YXJYD) in Chronic Unpredictable Mild Stress (CUMS)-induced depression rat model and to investigate the underlying mechanisms. Design: We used CUMS-induced depression rat model to evaluate whether oral administration of YXJYD with different doses (2.1 g/kg, 1.05 g/kg and 0.525 g/kg, respectively) improve the depressive-like symptoms, and then performed UHPLC-Q-TOF-MS to explore the active ingredients of YXJYD. Subsequently, rat's cecal contents, serum, and urine were collected from the control group, CUMS model group, and YXJYD high-dose (2.1 g/kg) treatment group. The 16S rRNA sequencing was performed on the cecal contents, based on Illumina MiSeq platform, and ANOVA analysis were used to analyze the composition variety and screen differential expression of gut bacteria in the three groups. 1H Nuclear Magnetic Resonance (NMR) analysis was used for analyzing the metabolites obtained from cecal contents, serum, and urine, and KEGG enrichment analysis was used to identify pathways of differential metabolites. An integrated 16S rRNA sequencing and metabolomic data were conducted to characterize the underlying mechanisms of YXJYD Results: The gut microbial communities, and serum, cecal content, urine metabolic compositions were significantly significantly altered in CUMS-induced depressive rats, while YXJYD effectively ameliorated the CUMS-associated gut microbiota dysbiosis, especially of Monoglobus, and alleviated the disturbance of serum, cecal content, urine metabolome and reversed the changes of key depressive and gut microbiota-related metabolites, such as succinic acid, taurine, hippuric acid, melatonin. With an integrated study of the gut microbiota and metabolomes, we identified the pathway of tricarboxylic acid cycle (TCA cycle) and propanoate metabolism as the regulated target of YXJYD on host-microbiome interaction. Conclusion: Our findings further confirmed the imbalance of metabolism and intestinal microbial is closely related to CUMS-induced depression. YXJYD regulates gut microbiome to affect body metabolomes and then produce antidepressant-like effect in CUMS-induced depressive rats while its molecular mechanism possibly be increased Monoglobus abundance in gut microbiota and regulated the TCA cycle pathway and propanoate metabolism in host.

[Antagonistic effect of modified Dahuang Zhechong Granule against the apoptosis of epididymal spermatogenic cells in varicocele rats based on Nrf2/HO-1 pathways].

OBJECTIVE: To investigate the effects of modified Dahuang Zhechong Granule (DZG) on the epididymal tissue of varicocele (VC) rats and the expressions of the nuclear factor erythroid 2 (NF-E2)-related factor (Nrf2) and heme oxygenase-1 (HO-1) protein. METHODS: Sixty SD rats were randomly divided into six groups of an equal number: sham operation, VC model control, aescuven forte (AF) and low-, medium- and high-dose DZG. The VC model was established by ligation of the left renal vein with the Turner's method, followed by intragastrical administration of normal saline to the rats in the sham operation and VC model control groups, AF Tablets at 54 mg/kg to those in the AF group, and modified DZG at 0.6, 1.2 and 2.4 g/ml to those in the low-, medium- and high-dose DZG groups respectively, all once daily for 8 weeks. Then, all the animals were sacrificed and their left epididymides harvested for examination of semen quality, observation of local ultrastructural changes, measurement of the apoptosis of spermatogenic cells by Annexin V-FITC, and determination of the expressions of Nrf2 and HO-1 in the epididymal tissue by immunohistochemistry. RESULTS: Evident pathological damage was observed in the left epididymal tissue of the VC model controls, with significantly reduced numbers of spermatogenic cells and sperm at all levels, partially destroyed cellular structure, and disappearance of some subcellular structures such as the lysosome, mitochondrion, endoplasmic reticulum, nucleus and cell membrane, which were all improved to some extent in the DZG and AF group. Sperm concentration and motility in the left epididymis were significantly higher in the medium- and high-dose DZG and AF groups than in the VC model controls (P < 0.05), even more significantly in the high-dose DZG than in the AF group (P < 0.05). The apoptosis rate of spermatogenic cells was markedly higher in the VC model control than in the sham operation group (P < 0.05), but lower in the medium- and high-dose DZG and AF groups than in the VC model controls (P < 0.05). Immunohistochemistry showed positive expressions of Nrf2 and HO-1 proteins, brown, scattered and with a low luminance of the cells, in the left epididymis tissue of the VC model control rats, but with a significantly higher cell luminance in the high-dose DZG and AF groups. CONCLUSIONS: Modified Dahuang Zhechong Granule can effectively repair pathological damage to the epididymis of varicocele rats, increase the expressions of Nrf2 and HO-1 proteins, antagonize the apoptosis of spermatogenic cells and provide a favorable condition for sperm maturation.

[Impacts of the expressions of Fas and FasL mRNA and proteins on sperm concentration and motility].

Objective: To investigate the influence of the expressions of apoptosis-related Fas and FasL mRNA and proteins on sperm concentration and motility. METHODS: We collected semen samples from 80 adult males and divided them into four groups of an equal number according to sperm concentration and the percentage of progressively motile sperm (PMS): normal, asthenospermia (AS), oligozoospermia (OS) and oligoasthenospermia (OAS). We examined the routine semen parameters, the levels of Fas and FasL proteins and the expressions of Fas and FasL genes in different groups. RESULTS: The sperm concentrations in the normal, AS, OS and OAS groups were (68.11 ± 35.49), (92.21 ± 60.96), (8.55 ± 2.82) and (5.96 ± 3.80) ×106/ml, respectively, and the percentages of PMS were (49.40 ± 13.86)%, (22.12 ± 7.13)%, (40.77 ± 8.41)% and (14.53 ± 9.74), respectively. The Fas protein level was significantly higher in the AS, OS and OAS than in the normal group (ï¼»425.03 ± 50.56ï¼½, ï¼»442.32 ± 84.88ï¼½ and ï¼»448.42 ± 84.79ï¼½ vs ï¼»381.07 ± 52.37ï¼½ pg/ml, P < 0.05), correlated negatively with sperm concentration (r = －0.377, P < 0.01) and PMS (r = －0.350, P < 0.01), but exhibited no statistically significant differences between the former three and latter group (ï¼»166.98 ± 27.39ï¼½, ï¼»169.51 ± 32.62ï¼½ and ï¼»171.46 ± 32.61ï¼½ vs ï¼»167.49 ± 29.91ï¼½ pg/ml, P > 0.05). The relative levels of the Fas gene in the normal, AS, OS and OAS groups were 1, (0.88 ± 1.17), (2.55 ± 2.11) and (0.69 ± 0.90) respectively, lower in the AS and OAS than in the normal group, and positively correlated with sperm motility; those of the FasL gene were 1, (1.99 ± 1.81), (2.08 ± 2.06) and (2.03 ± 2.23) respectively, higher in the OS and OAS than in the normal group, and negatively correlated with sperm motility. Compared with the normal group, the expressions of Fas and FasL were down-regulated in the AS but up-regulated in the OS group; the expression of Fas, however, was down-regulated and that of FasL up-regulated in the OAS group. The expression of Fas mRNA was positively correlated with the percentage of PMS (r = 0.355, P = 0.01) and total sperm motility (r = 0.358, P < 0.01), while sperm concentration negatively correlated with the expression FasL mRNA (r = －0.305, P < 0.05). There was no significant correlation between the other parameters. CONCLUSIONS: Fas and FasL are differentially expressed in normal, asthenospermia, oligozoospermia and oligoasthenospermia males. Their up-regulated expressions may promote the apoptosis of spermatogenic and sperm cells and induce oligozoospermia, while their down-regulated expressions may indicate the failure of abnormal spermatogenic and sperm cells to immediately undergo programmed death, which can be one of the causes of asthenospermia.

[Regulatory effect of Qianliexiao Decoction on TGF-ß1, Smad4 and Smad 7 signaling pathways and the proliferation and apoptosis of prostate fibroblasts in mice with experimental autoimmune prostatitis].

OBJECTIVE: To study the effect of intervening in the signal transduction pathways of TGF-ß1, Smad4 and Smad7 with Qianliexiao Decoction (QLX) on the proliferation and apoptosis of prostate fibroblasts (PrF) in mice with experimental autoimmune prostatitis (EAP). METHODS: A model of EAP with damp-heat syndrome was established in C57BL/6 mice by immunization induction combined with the TCM modeling method. The prostate tissue of the mice was harvested for isolation, culturing and purification of PrFs and detection of their purity. After modeling by stimulation with a medium containing >90%-purity or 5 ng/ml TGF-ß1, the PrFs in the logarithmic growth phase were obtained and randomly divided into a blank control (serum-free medium), a model control, a positive control (medium containing 5 ng/ml TGF-ß1), a low-dose QLX (serum containing 5% QLX), a medium-dose QLX (serum containing 10% QLX), and a high-dose QLX group (serum containing 20% QLX). After 24 hours of intervention, the proliferation of the PrFs was measured, the protein expressions of TGF-ß1, Smad4, Smad7, p-Smad4 and p-Smad7 detected by Western blot, their mRNA expressions determined by qPCR, and the apoptosis of the PrFs examined by flow cytometry. RESULTS: After induction with TGF-ß1, the proliferation of the PrFs was significantly increased in the positive control (P < 0.05), but inhibited in the medium- and low-dose QLX groups (P < 0.05) and even more significantly in the high-dose QLX group as compared with that in the model control (P < 0.01). The expressions of Smad4, p-Samd7 and TGF-ß1 proteins in the PrFs were remarkably higher in the positive control than in the model control group (P < 0.05), while those of p-Smad4 and TGF-ß1 markedly lower (P < 0.01) and that of p-Smad7 dramatically higher in the QLX intervention groups than in the positive control (P < 0.01), in an evident dose-dependent manner. In comparison with the model control group, the high-dose QLX group exhibited a significant decrease in the mRNA expression of Smad4 (P < 0.05) but all the three QLX groups showed a dramatic increase in those of Smad7 (P < 0.05) and TGF-ß1 (P < 0.01). The mRNA expression of Smad4 was markedly down-regulated in the high-dose QLX group compared with that in the positive control (P < 0.05), that of Smad7 up-regulated in the model control and QLX groups (P < 0.01), and that of TGF-ß1 down-regulated in the three QLX groups (P < 0.01). The apoptosis rate of the PrFs was significantly higher in the QLX groups than in the model control (P < 0.05) in a dose-dependent manner, but showed no statistically significant difference between the model control and the positive control groups (P > 0.05). CONCLUSIONS: TGF-ß1 can stimulate the proliferation of PrFs, up-regulate the expressions of TGF-ß1 and p-Smad4, and down-regulate that of p-Smad7, while QLX can inhibit the proliferation of PrFs in a dose-dependent manner by decreasing the expressions of TGF-ß1 and p-Smad4, increasing that of p-Smad7, and thereby suppressing TGF-ß1-induced proliferation of PrFs.