Profiling the urinary microbiome in men with calcium-based kidney stones.

BACKGROUND: The dogma that urine is sterile in healthy individuals has been overturned by recent studies applying molecular-based methods. Mounting evidences indicate that dysbiosis of the urinary microbiota is associated with several urological diseases. In this study, we aimed to investigate the urinary microbiome of male patients with calcium-based kidney stones and compare it with those of healthy individuals. RESULTS: The diversity of the urinary microbiota in kidney stone patients was significantly lower than that of healthy controls based on the Shannon and Simpson index (P < 0.001 for both indices). The urinary microbiota structure also significantly differed between kidney stone patients and healthy controls (ANOSIM, R = 0.11, P < 0.001). Differential representation of inflammation associated bacteria (e.g., Acinetobacter) and several enriched functional pathways were identified in the urine of kidney stones patients. Meanwhile, we found the species diversity, overall composition of microbiota and predicted functional pathways were similar between bladder urine and renal pelvis urine in kidney stone patients. CONCLUSIONS: A marked dysbiosis of urinary microbiota in male patients with calcium-based kidney stones was observed, which may be helpful to interpret the association between bacteria and calcium-based kidney stones.

Knocking down glycoprotein nonmetastatic melanoma protein B suppresses the proliferation, migration, and invasion in bladder cancer cells.

Glycoprotein nonmetastatic melanoma protein B is a type 1 transmembrane protein that has been recently found to play a role in cancer cell proliferation, angiogenesis, and invasion. Due to its potential responsibility in cancer aggressiveness, the main objective of this work was to investigate its expression in bladder cancer and the biological functions in bladder cancer cells. Using immunohistochemistry, western blot, and reverse transcription polymerase chain reaction, we analyzed the expression of glycoprotein nonmetastatic melanoma protein B in bladder cancer tissues and bladder cancer cell lines. The effects of glycoprotein nonmetastatic melanoma protein B on proliferation, migration, and invasion were tested after knocking down the glycoprotein nonmetastatic melanoma protein B in bladder cancer cells with small interfering RNAs by CCK-8, Transwell, and Matrigel assays. Our results showed that glycoprotein nonmetastatic melanoma protein B protein was highly expressed in the bladder cancer tissues and cell lines. Downregulating glycoprotein nonmetastatic melanoma protein B could suppress the proliferation, migration, and invasion in bladder cancer cells. Glycoprotein nonmetastatic melanoma protein B expression was related to the poor differentiation and recurrence by immunohistochemistry analysis. The survival analysis also showed that glycoprotein nonmetastatic melanoma protein B was related to the patient prognosis. In conclusion, Glycoprotein nonmetastatic melanoma protein B protein was highly expressed in the bladder cancer, which was related to the poor prognosis in bladder cancer patients. Glycoprotein nonmetastatic melanoma protein B promoted the proliferation, migration, and invasion in bladder cancer cells.

Psychological burden, sexual satisfaction and erectile function in men whose partners experience recurrent pregnancy loss in China: a cross-sectional study.

BACKGROUND: The aim of this study was to elucidate recurrent pregnancy loss (RPL)-associated psychosocial effects and sexual functions of Chinese men whose partners experience a history of RPL. METHODS: Questionnaire data from a total of 236 men whose partners experience RPL(RPL group) and another 236 non-RPL male volunteers(control group) were analyzed. The self-administered questionnaires included anxiety and depression measures (SAS & SDS), the Index of Sexual Satisfaction (ISS) and the International Index of Erectile Function (IIEF-5) for evaluating psychological burden, sexual satisfaction and erectile function, respectively. RESULTS: The mean age of the RPL group and control group was 29.8 ± 8.6 and 28.2 ± 7.3, respectively. The incidence of erectile dysfunction was significantly higher in the RPL group than in the control group (19.07 % vs. 7.63 %, P < 0.001). Anxiety and depression were also more prevalent in RPL group than in the control group (anxiety: 36.90 % vs. 19.08 %, P < 0.001; depression: 26.30 % vs. 7.63 %, P < 0.001). Furthermore, after adjusting for age in the RPL group, negative relationships were observed between the IIEF-5 score and anxiety and depression (P < 0.001), and a positive correlation was found between the ISS and anxiety and depression (P < 0.001). In addition, history of RPL, anxiety and depressive symptoms were significantly associated with a higher risk of ED. CONCLUSIONS: Psychological functioning, sexual satisfaction and erectile function are impaired in infertile men with RPL partners. These men should be targeted for psychological consultation.

[Expression and significance of CMTM5 and epidermal growth factor receptor in prostate cancer].

OBJECTIVE: To investigate the expression patterns of CKLF-like MARVEL transmembrane domain containing 5 (CMTM5), a novel tumor suppressor, and epidermal growth factor receptor (EGFR) in prostate cancer (PCa) tissues and cells and to analyze the relationship between CMTM5 and EGFR in PCa. METHODS: The expression patterns of CMTM5 and EGFR in PCa tissues and cells were detected by immunohistochemistry and Western blot, respectively. RESULTS: CMTM5 was highly expressed in 75% (27/36) of benigh prostatic hyperplasia (BPH) tissues but 35.9% (23/64) of PCa tissues (P<0.001). There was a significant difference of CMTM5 expression between the two groups of PCa tissues with different Gleason scores (P=0.003), though its expression was not related to the age, clinical stage, and metastatic situation (P>0.05). EGFR was highly expressed in 57.8% (37/64) of PCa tissues, it had statistical significance between EGFR and CMTM5 expressions in PCa tissues. Furthermore, 23 cases (35.9%) had low CMTM5 expression and high EGFR expression. Western blot showed that CMTM5 was undetectable in PCa cells, in which the EGFR expression was upregulated. CONCLUSION: The loss of CMTM5 may participate in the progression of PCa resulting from deregulated EGFR.

The urinary microbiota composition and functionality of calcium oxalate stone formers.

Background: Accumulated evidences indicate that dysbiosis of the urinary microbiota is associated with kidney stone formation. In the present study, we aimed to investigate the urinary microbiota composition and functionality of patients with calcium oxalate stones and compare it with those of healthy individuals. Method: We collected bladder urine samples from 68 adult patients with calcium oxalate stones and 54 age-matched healthy controls by transurethral catheterization. 16S rRNA gene and shotgun sequencing were utilized to characterize the urinary microbiota and functionality associated with calcium oxalate stones. Results: After further exclusion, a total of 100 subjects was finally included and analyzed. The diversity of the urinary microbiota in calcium oxalate stone patients was not significantly different from that of healthy controls. However, the urinary microbiota structure of calcium oxalate stone formers significantly differed from that of healthy controls (PERMANOVA, r = 0.026, P = 0.019). Differential representation of bacteria (e.g., Bifidobacterium) and several enriched functional pathways (e.g., threonine biosynthesis) were identified in the urine of calcium oxalate stone patients. Conclusion: Our results showed significantly different urinary microbiota structure and several enriched functional pathways in calcium oxalate stone patients, which provide new insight into the pathogenesis of calcium oxalate stones.

[Expression and clinical significance of glycoprotein non-metastatic melanoma protein B in human renal cell carcinoma].

OBJECTIVE: To investigate the role of glycoprotein non-metastatic melanoma protein B (GPNMB) in renal cell carcinoma (RCC). METHODS: The method of immunohistochemistry (IHC) and Western blot were utilized to examine the expression of GPNMB in RCC and the normal adjacent tissues matched. RESULTS: The expression of GPNMB was lower in RCC than in the matched normal adjacent tissues (P=0.022). CONCLUSION: The abnormal expression of GPNMB may play an important role in the development of RCC and the detection of GPNMB may be useful for the early diagnosis of tumor and its development.

[Free fatty acids induce proliferation of human renal carcinoma 786-O cell line via integrin-linked kinase].

OBJECTIVE: To investigate the effects of free fatty acids on cell proliferation and integrin-linked kinase (ILK) expression in human renal carcinoma 786-O cell line. METHODS: The 786-O cells were exposed to normal medium and different concentrations of oleic acid (OA) carried by de-fatty bovine serum albumin (d-BSA). The MTT assay and the flow cytometry assay were performed respectively for cell proliferation and apoptosis after the treatment with OA for 48 h. The expressions of ILK, Akt and p-Akt were detected by Western blot. RESULTS: The MTT assay showed that the cell viabilities of 0.05 mmol/L, 0.1 mmol/L and 0.2 mmol/L OA groups were increased gradually, as compared with the blank control (absorbance: 0.657 ± 0.056, 0.682 ± 0.028, 0.718 ± 0.042 vs. 0.495 ± 0.034; all P<0.001). The effects of OA on cells apoptosis were not significant (apoptotic rates: 2.42% ± 0.25% vs. 2.33% ± 0.87% vs. 2.25%± 0.51%, P=0.082). After being treated with OA, the expressions of ILK and p-Akt were increased in 786-O cells. CONCLUSION: The results suggested that free fatty acids could promote the development of renal cell carcinoma via up-regulating ILK/Akt pathway, which may reveal the relations between metabolic disturbance and renal carcinoma to a certain extent.

[CMTM2 antagonizes cyclophosphamide-induced reproductive toxicity and regulates StAR expression in a transgenic mouse model].

OBJECTIVE: To observe the effects of CMTM2 on cyclophosphamide (CP)-induced reproductive toxicity and the expression of steroidogenic acute regulatory (StAR) protein in the transgenic mouse model. METHODS: Twenty CMTM2 transgenic mice were equally divided into a CMTM2 + CP and a CMTM2 + NS group, the former intraperitoneally injected with CP at 50 mg per kg per d, while the latter with the equivalent dose of normal saline, both for 7 days. Another 20 wild C57BL/6J mice were randomly assigned to a WT + CP and a WT + NS group, treated the same way above. After 30 days, all the mice were sacrificed and their epididymides and testes removed for measurement of the serum testosterone level by radioimmunoassay, determination of sperm concentration and motility by light microscopy and detection of the expression of StAR by Western blot. RESULTS: The levels of serum testosterone, sperm concentration and sperm motility were significantly decreased in the CMTM2 + CP group as compared with the CMTM2 + NS group ([42.98 +/- 3.25] nmol/L vs [46.74 +/- 3.38] nmol/L, [16.89 +/- 1.17 ] x 10(6)/ml vs [24.68 +/- 0.95 ] x 10(6)/ml, [72.75 +/- 1.25]% vs [85.14 +/- 1.12]%, P < 0.05), but remarkably less than in the WT + CP group ([37.97 +/- 4.17] nmol/L, [12.75 +/- 1.02] x 10(6)/ml, [50.52 +/- 1.37] %) (P < 0.05). However, the expression of StAR was significantly higher in the CMTM2 + CP than in the WT + CP group (1.16 +/- 0.07 vs 0.69 +/- 0.08, P < 0.05). CONCLUSION: CMTM2 antagonizes cyclophosphamide-induced reproductive toxicity via regulating the expression of StAR, and hence plays a protective role in the reproductive system.

[Research advances in CKLF-like MARVEL transmembrane domain containing member 5].

CKLF-like MARVEL transmembrane domain containing member(CMTM)is a novel generic family firstly reported by Peking University Center for Human Disease Genomics. CMTM5 belongs to this family and has exhibited tumor-inhibiting activities. It can encode proteins approaching to the transmembrane 4 superfamily(TM4SF). CMTM5 is broadly expressed in normal adult and fetal human tissues, but is undetectable or down-regulated in most carcinoma cell lines and tissues. Restoration of CMTM5 may inhibit the proliferation, migration, and invasion of carcinoma cells. Although the exact mechanism of its anti-tumor activity remains unclear, CMTM5 may be involved in various signaling pathways governing the occurrence and development of tumors. CMTM5 may be a new target in the gene therapies for tumors, while further studies on CMTM5 and its anti-tumor mechanisms are warranted.

HMGB1-mediated autophagy confers resistance to gemcitabine in hormone-independent prostate cancer cells.

As a main treatment of prostate cancer, castration therapy has been widely applied in the clinic. However, the therapeutic strategy for hormone-independent prostate cancer (HIPC) was not satisfied. Gemcitabine is an important chemotherapeutic agent that has been approved for the treatment of numerous human solid tumors, including HIPC, whereas the gemcitabine resistance has become a serious problem in clinical chemotherapy. In the present study, the mechanisms of resistance to gemcitabine were investigated in HIPC cell lines. The results demonstrated that the autophagy markers were induced significantly in HIPC cells subsequent to gemcitabine treatment. Meanwhile, administration of gemcitabine to HIPC cells increased the expression of high mobility group box1 (HMGB1). Furthermore, the gemcitabine-induced autophagy response was attenuated in stable HIPC cells harboring HMGB1 shRNA. Notably, the HIPC cells stably transfected with HMGB1 shRNA or treated with autophagy inhibitors were more sensitive to gemcitabine compared with the control group. These data suggested that inhibition of HMGB1 increased the sensitivity to gemcitabine by decreasing autophagy response in HIPC cells. Overall, the present findings demonstrate a new mechanism for the resistance to gemcitabine in HIPC cell lines.

Androgen replacement therapy improves psychological distress and health-related quality of life in late onset hypogonadism patients in Chinese population.

BACKGROUND: Late onset hypogonadism negatively impacts on men's psychological well-being. This study was conducted to examine the interrelationship among symptoms of testosterone deficiency, psychological well-being, and quality of life. METHODS: Eligible subjects were randomized into active treatment and control groups, and were asked to complete the following questionnaires at baseline and month 6: aging male's symptoms (AMS) rating scale, hospital anxiety and depression scale (HADS), perceived stress scale (PSS) and the short form health survey-12 (SF-12). In this study, men were treated and monitored for 6 months with oral testosterone undecanoate (TU) capsules or vitamin E/C capsules in a single-blinded fashion. All in the active treatment group were administered a total of 120 - 160 mg TU orally on a daily basis. Total and free T levels between baseline and month 6 were compared. RESULTS: One hundred and sixty eligible subjects were recruited and followed up. In the active treatment group, total serum testosterone concentrations before and after intervention were (7.98 ± 0.73) nmol/L and (13.7 ± 1.18) nmol/L. The mean HADS anxiety subscale scores for the subjects at baseline and at month 6 were 3.47 ± 0.4 and 1.72 ± 0.2, respectively (t = 1.526, P < 0.05). Additionally, the mean HADS depression subscale scores were 4.91 ± 0.6 and 2.39 ± 0.3, respectively (t = 3.466, P < 0.05). The mean scores on PSS for the subjects at baseline and at month 6 were 12.88 ± 2.1 and 9.83 ± 1.7, respectively (t = 4.009, P < 0.05). Significantly improved SF-12 could be observed (t = 1.433 and 1.118, respectively; both P < 0.05). No significant changes were observed in the control group at month 6. CONCLUSION: Androgen replacement not only improves androgen deficiency associated symptoms, but also enhances comprehensive improvement in psychological issues.