Sex-dependent effects of subacute mercuric chloride exposure on histology, antioxidant status and immune-related gene expression in the liver of adult zebrafish (Danio rerio).

Mercury (Hg) is a global pollutant that causes negative health effects. In order to assess Hg-induced hepatotoxicity in fish and examine whether gender differences existed in response to Hg exposure, adult zebrafish were exposed to 0, 15 and 30 µg L-1 Hg2+ for 30 days, and histology, antioxidant status and the transcription levels of several immune-related genes were examined in the liver. Hg2+ exposure caused a dose-dependent increase in histopathological lesions of the liver, including vacuolization, parenchyma disorganization and pyknotic nucleus, and these lesions were more severe in males than in females. In females, Hg2+ exposure decreased CAT activity and its mRNA levels, while increased GSH content and the expressions of sod1, gpx1a, gstr and keap1. In males, the decrease in cat1 expression and the increase in GST activity, GSH and MDA contents as well as gpx1a, gstr, nrf2 and keap1 mRNA levels were observed in Hg2+-exposed groups, but the activities of CAT, SOD and GPX were only stimulated in the 15 µg L-1 Hg2+ group. Moreover, both in females and males, Hg2+ exposure down-regulated il-8 expression while up-regulated il-10 and lyz mRNAs. However, the down-regulation of il-1ß and tnfα was detected only in males under Hg2+ treatments. Thus, our results indicated that HgCl2 exposure induced histopathological damage, oxidative stress and immunotoxicity in the liver of zebrafish. Different response patterns of histology, antioxidant status and immune defenses to Hg2+ between females and males suggested sex-dependent effects of Hg, and males showed more vulnerable to Hg2+ exposure than females.

Short hairpin rna targeting insulin-like growth fator binding protein-3 restores the bioavailability of insulin-like growth factor-1 in diabetic rats.

PURPOSE: To investigate whether intracavernosal injection of short hairpin RNA for IGFBP-3 could improve erectile function in streptozotocin-induced diabetic rats. MATERIALS AND METHODS: After 12 weeks of IGFBP-3 short hairpin RNA injection treatment, intracavernous pressure responses to electrical stimulation of cavernous nerves were evaluated. The expression of IGFBP-3 and IGF-1 at mRNA and protein levels were detected by quantitative real-time PCR analysis and Western blot, respectively. The concentration of cavernous cyclic guanosine monophosphate was detected by enzyme-linked immunosorbent assay. RESULTS: At 12 weeks after intracavernous administration of IGFBP-3 shRNA, the cavernosal pressure was significantly increased in response to the cavernous nerves stimulation compared to the diabetic group (P<0.05). Cavernous IGFBP-3 expression at both mRNA and protein levels was significantly inhibited. At the same time, cavernous IGF-1 expression was significantly increased in the IGFBP-3 shRNA treatment group compared to the diabetic group (P<0.01). Cavernous cyclic guanosine monophosphate concentration was significantly increased in the IGFBP-3 shRNA treatment group compared to the diabetic group (P<0.01). CONCLUSIONS: Gene transfer of IGFBP-3 shRNA could improve erectile function via the restoration of cavernous IGF-1 bioavailability and an increase of cavernous cGMP concentration in the pathogenesis of erectile dysfunction in streptozotocin-induced diabetic rats.

Short hairpin RNA targeting insulin-like growth factor binding protein-3 restores the bioavailability of insulin-like growth factor-1 in diabetic rats

ABSTRACT Purpose To investigate whether intracavernosal injection of short hairpin RNA for IGFBP-3 could improve erectile function in streptozotocin-induced diabetic rats. Materials and methods After 12 weeks of IGFBP-3 short hairpin RNA injection treatment, intracavernous pressure responses to electrical stimulation of cavernous nerves were evaluated. The expression of IGFBP-3 and IGF-1 at mRNA and protein levels were detected by quantitative real-time PCR analysis and Western blot, respectively. The concentration of cavernous cyclic guanosine monophosphate was detected by enzyme-linked immunosorbent assay. Results At 12 weeks after intracavernous administration of IGFBP-3 shRNA, the cavernosal pressure was significantly increased in response to the cavernous nerves stimulation compared to the diabetic group (P<0.05). Cavernous IGFBP-3 expression at both mRNA and protein levels was significantly inhibited. At the same time, cavernous IGF-1 expression was significantly increased in the IGFBP-3 shRNA treatment group compared to the diabetic group (P<0.01). Cavernous cyclic guanosine monophosphate concentration was significantly increased in the IGFBP-3 shRNA treatment group compared to the diabetic group (P<0.01). Conclusions Gene transfer of IGFBP-3 shRNA could improve erectile function via the restoration of cavernous IGF-1 bioavailability and an increase of cavernous cGMP concentration in the pathogenesis of erectile dysfunction in streptozotocin-induced diabetic rats.

Rapid Onset of the Effects of Combined Selective Serotonin Reuptake Inhibitors and Electroacupuncture on Primary Depression: A Meta-Analysis.

OBJECTIVES: To evaluate the efficacy and safety of combined selective serotonin reuptake inhibitors (SSRIs) and electroacupuncture therapies for the early treatment of primary depression. METHODS: Randomized controlled trials (RCTs) were analyzed to compare therapy combining SSRIs and electroacupuncture to SSRI therapy alone. The RCTs were identified by searching, among others, PubMed, the Cochrane Library, the Chinese National Knowledge Infrastructure, the Chongqing VIP database for Chinese Technical Periodicals, WANFANG DATA, and the Chinese Biological Medical Literature Database. Scores from Self-Rated Depression Scale (SDS), the Hamilton Depression Scale (HAMD), the Side Effect Rating Scale (SERS), and the Treatment Emergent Symptom Scale (TESS) were analyzed and coded by two independent investigators and used to evaluate the safety and efficacy of treatment. Statistical analyses were performed using RevMan 5.2 software. RESULTS: Six RCTs were analyzed. The meta-analysis revealed that the combined therapy of SSRIs and electroacupuncture were associated with superior scores on the HAMD, SDS, and SERS measures compared with SSRIs alone after 1-4 weeks of treatment: HAMD scores, mean difference (MD)(1 week), 2.32 (95% confidence interval [CI](1 week), 1.47-3.16, p(1 week)<0.00001); MD(2 weeks), 2.65 (95% CI(2 weeks), 1.81- 3.50, p(2 weeks)<0.00001); MD(4 weeks), 2.70 (95% CI(4 weeks), 1.90-3.51, p(4 weeks)<0.00001); SDS scores: MD(1 week), 3.13 (95% CI(1 week), 1.22-5.03, p(1 week) = 0.001); MD(2 weeks), 4.05 (95% CI(2 weeks), 0.22-7.87, p(2 weeks) = 0.04); MD(4 weeks), 5.02 (95% CI(4 weeks), 1.61-8.43, p(4 weeks) = 0.004); SERS scores: MD(2 weeks), 2.20 (95% CI(2 weeks), 1.43-2.96, p(2 weeks)<0.00001); MD(4 weeks), 2.12 (95% CI(4 weeks), 1.42-2.83, p(4 weeks)<0.00001). However, two of the aforementioned outcomes were rated as medium quality because of heterogeneity, as assessed using the Grading of Recommendations Assessment, Development and Evaluation system. CONCLUSIONS: The available evidence suggests that the early treatment of primary depression using both SSRI and electroacupuncture therapies is more efficient than treatments with SSRIs alone and leads to a better and earlier control of depressive symptoms.

Short hairpin ribonucleic acid constructs targeting insulin-like growth factor binding protein-3 rehabilitated decreased testosterone concentrations in diabetic rats.

BACKGROUND: The aim of this study was to determine if shRNA constructs targeting insulin-like growth factor binding protein-3 can rehabilitate decreased serum testosterone concentrations in streptozotocin-induced diabetic rats. MATERIAL/METHODS: After 12 weeks of intracavernous administration of IGFBP-3 shRNA, intracavernous pressure responses to electrical stimulation of cavernous nerves were evaluated. The expression of IGFBP-3 at mRNA and protein levels was detected by quantitative real-time PCR analysis and Western blot, respectively. The concentrations of serum testosterone and cavernous cyclic guanosine monophosphate were detected by enzyme-linked immunosorbent assay. RESULTS: After 12 weeks of intracavernous administration of IGFBP-3 shRNA, the cavernosal pressure was significantly increased in response to the cavernous nerves stimulation compared to the diabetic control group (p<0.01). Cavernous IGFBP-3 expression at both mRNA and protein levels was significantly inhibited. Both serum testosterone and cavernous cyclic guanosine monophosphate concentrations were significantly increased in the IGFBP-3 shRNA treatment group compared to the diabetic control group (p<0.01). CONCLUSIONS: These results suggest that IGFBP-3 shRNA may rehabilitate erectile function via increases of concentrations of serum testosterone and cavernous cyclic guanosine monophosphate in streptozotocin-induced diabetic rats.