Vitamin D alleviates liver fibrosis by inhibiting histidine-rich calcium binding protein (HRC).

BACKGROUND: Liver fibrosis may progress toward cirrhosis and cancer without effective therapy. Here, we investigated the underlying mechanism of Vitamin D as a therapeutic approach. METHODS: Carbon tetrachloride (CCL4)-induced mice model and transforming growth factor-ß1 (TGF-ß1) induced human hepatic stellate cell line LX-2 were used in vivo and in vitro. The fibrotic profiles, degree of liver injury and HRC expression were assessed by histology, Western blot, immunohistochemistry and Real-Time PCR. The proliferation of cells transfected with HRC +/+ and HRC-/- plasmids was detected by MTS and cell cycle methods. RESULTS: Vitamin D significantly suppressed the expression of HRC in liver fibrosis model both in vivo and in vitro (P < 0.01). The cell with overexpression of HRC significantly increased TGF-ß1/Smad3 expressions and the percentage of the S peak in cell cycle (P < 0.05). However, Vitamin D can significantly reverse the levels of TGF-ß1, Smad3 and p-smad3 caused by HRC in vitro. Furthermore, the overexpression of HRC in cell lines can attenuate the function of Vitamin D, suggesting that VD played a role by regulating HRC. Mechanically, HRC as the target of VDR is detected by CHIP method. CONCLUSIONS: Vitamin D can delay hepatic fibrosis by reducing activation of hepatic stellate cells and TGF-ß/Smad signaling through negative regulation of HRC. The findings revealed the important regulatory effect of Vitamin D in hepatic stellate cells and provided new insights into the therapeutic function of Vitamin D on liver fibrosis.

Effects of cholecalciferol cholesterol emulsion on renal fibrosis and aquaporin 2 and 4 in mice with unilateral ureteral obstruction.

There was evidence that 1,25(OH)2D3 regulated aquaporin (AQP) 2 and 4 expression while ameliorating renal fibrosis. This study investigated whether cholecalciferol cholesterol emulsion (CCE), a precursor of 1,25(OH)2D3, has similar effects. The impact of CCE on renal fibrosis and AQP2 and AQP4 expression were studied in a unilateralureteral obstruction (UUO) mouse nephropathy model. CCE reduced both the extent of fibrosis and transforming growth factor (TGF)-ß signaling compared with vehicle-treated UUO model controls. AQP2 protein expression was higher and AQP4 expression was lower in UUO-model mice treated with CCE than in vehicle-treated control mice. The results showed that CCE attenuated renal fibrosis by inhibiting TGF-ß signaling, and regulated AQP2 and AQP4 expression in this UUO mouse model.

ESR1 Gene Polymorphisms and Prostate Cancer Risk: A HuGE Review and Meta-Analysis.

BACKGROUND: Many published data on the association between single nucleotide polymorphisms (SNPs) in the ESR1 gene and prostate cancer susceptibility are inconclusive. The aim of this Human Genome Epidemiology (HuGE) review and meta-analysis is to derive a more precise estimation of this relationship. METHODS: A literature search of PubMed, Embase, Web of Science and Chinese Biomedical (CBM) databases was conducted from their inception through July 1st, 2012. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the strength of association. RESULTS: Twelve case-control studies were included with a total 2,165 prostate cancer cases and 3,361 healthy controls. When all the eligible studies were pooled into the meta-analysis, ESR1 PvuII (C>T) and XbaI (A>G) polymorphisms showed no association with the risk of prostate cancer. However, in the stratified analyses based on ethnicity and country, the results indicated that ESR1 PvuII (C>T) polymorphism was significantly associated with increased risk of prostate cancer among Asian populations, especially among Indian population; while ESR1 XbaI (A>G) polymorphism may significantly increase the risk of prostate cancer among American population. Furthermore, we also performed a pooled analysis for all eligible case-control studies to explore the role of codon 10 (T>C), codon 325 (C>G), codon 594 (G>A) and +261G>C polymorphisms in prostate cancer risk. Nevertheless, no significant associations between these polymorphisms and the risk of prostate cancer were observed. CONCLUSION: Results from the current meta-analysis indicate that ESR1 PvuII (C>T) polymorphism may be a risk factor for prostate cancer among Asian populations, especially among Indian population; while ESR1 XbaI (A>G) polymorphism may increase the risk of prostate cancer among American population.

Efficacy and tolerability of oxycodone in moderate-severe cancer-related pain: A meta-analysis of randomized controlled trials.

In order to evaluate the efficacy and tolerability of oxycodone in moderate-severe cancer-related pain, we conducted a systematic review of randomized controlled trials (RCTs). Publications addressing the efficacy and tolerability of oxycodone in moderate-severe cancer-related pain were selected from the Cochrane library, PubMed, Embase and CBM databases. Data were extracted from the studies by two independent reviewers. The meta-analysis was performed by RevMan 5.0.25 and STATA 9.2 software. From these data, odds ratios (ORs) or the standard mean difference (SMD) with 95% confidence intervals (CIs) were calculated. Finally, only seven RCTs were retrieved with a total of 613 cancer patients with moderate-severe pain. The meta-analysis results showed that oxycodone was statistically superior to other strong opioids based on pain intensity scores following intervention [weighted mean difference (WMD), 0.25; 95% CI, 0.05-0.45; P=0.01; WMD, -1.30; 95% CI, -1.55-1.05; P<0.001, respectively]. In addition, there were statistically significant differences between oxycodone and other strong opioids in cancer-related pain on the obvious effective rate and the overall effective rate (OR, 2.03; 95% CI, 1.40-2.95; P=0.0002; OR, 1.94; 95% CI, 1.09-3.44; P=0.02, respectively). Compared with other strong opioids, nausea and constipation occurred significantly less frequently with the use of oxycodone for cancer-related pain (OR=0.52, 95% CI=0.32-0.85, P=0.009; OR= 0.55, 95% CI= 0.35-0.87, P= 0.01; respectively). In conclusion, this meta-analysis confirms that the efficacy and tolerability of oxycodone are superior to those of other strong opioids, including morphine sulfate, codeine and tramadol, supporting its use as an opioid for cancer-related pain.