Traditional Herbal Medicine Use Associated with Liver Fibrosis in Rural Rakai,Uganda

Background

Traditional herbal medicines are commonly used in sub-Saharan Africa and some herbs are known to be hepatotoxic. However little is known about the effect of herbal medicines on liver disease in sub-Saharan Africa.

Methods

500 HIV-infected participants in a rural HIV care program in Rakai, Uganda, were frequency matched to 500 HIV-uninfected participants. Participants were asked about traditional herbal medicine use and assessed for other potential risk factors for liver disease. All participants underwent transient elastography (FibroScan®) to quantify liver fibrosis. The association between herb use and significant liver fibrosis was measured with adjusted prevalence risk ratios (adjPRR) and 95% confidence intervals (CI) using modified Poisson multivariable logistic regression.

Results

19 unique herbs from 13 plant families were used by 42/1000 of all participants, including 9/500 HIV-infected participants. The three most-used plant families were Asteraceae, Fabaceae, and Lamiaceae. Among all participants, use of any herb (adjPRR = 2.2, 95% CI 1.3–3.5, p = 0.002), herbs from the Asteraceae family (adjPRR = 5.0, 95% CI 2.9–8.7, p<0.001), and herbs from the Lamiaceae family (adjPRR = 3.4, 95% CI 1.2–9.2, p = 0.017) were associated with significant liver fibrosis. Among HIV infected participants, use of any herb (adjPRR = 2.3, 95% CI 1.0–5.0, p = 0.044) and use of herbs from the Asteraceae family (adjPRR = 5.0, 95% CI 1.7–14.7, p = 0.004) were associated with increased liver fibrosis.

Conclusions

Traditional herbal medicine use was independently associated with a substantial increase in significant liver fibrosis in both HIV-infected and HIV-uninfected study participants. Pharmacokinetic and prospective clinical studies are needed to inform herb safety recommendations in sub-Saharan Africa. Counseling about herb use should be part of routine health counseling and counseling of HIV-infected persons in Uganda.     

Effects of Genetic Variants Previously Associated with Fasting Glucose and Insulin in the Diabetes Prevention Program

Common genetic variants have been recently associated with fasting glucose and insulin levels in white populations. Whether these associations replicate in pre-diabetes is not known. We extended these findings to the Diabetes Prevention Program, a clinical trial in which participants at high risk for diabetes were randomized to placebo, lifestyle modification or metformin for diabetes prevention. We genotyped previously reported polymorphisms (or their proxies) in/near G6PC2, MTNR1B, GCK, DGKB, GCKR, ADCY5, MADD, CRY2, ADRA2A, FADS1, PROX1, SLC2A2, GLIS3, C2CD4B, IGF1, and IRS1 in 3,548 Diabetes Prevention Program participants. We analyzed variants for association with baseline glycemic traits, incident diabetes and their interaction with response to metformin or lifestyle intervention. We replicated associations with fasting glucose at MTNR1B (P<0.001), G6PC2 (P = 0.002) and GCKR (P = 0.001). We noted impaired β-cell function in carriers of glucose-raising alleles at MTNR1B (P<0.001), and an increase in the insulinogenic index for the glucose-raising allele at G6PC2 (P<0.001). The association of MTNR1B with fasting glucose and impaired β-cell function persisted at 1 year despite adjustment for the baseline trait, indicating a sustained deleterious effect at this locus. We also replicated the association of MADD with fasting proinsulin levels (P<0.001). We detected no significant impact of these variants on diabetes incidence or interaction with preventive interventions. The association of several polymorphisms with quantitative glycemic traits is replicated in a cohort of high-risk persons. These variants do not have a detectable impact on diabetes incidence or response to metformin or lifestyle modification in the Diabetes Prevention Program.     

鳞片状细胞癌抗原Ⅰ与乙型肝炎病毒的结合受反应位点环域疏水性的影响

鳞片状细胞癌抗原Ⅰ (SCCA1)是丝氨酸蛋白酶抑制剂 (serpin)超家族的成员 ,具有多种变异体。有报道其中的两种(BP和AJ515706 )能通过乙型肝炎病毒 (HBV)的前S1抗原促进表达SCCA1的细胞与HBV的结合。本研究从HepG2细胞中扩增出的一株SCCA1(A1)却不具备HBV结合能力。将A1的C末端与BP的C末端互换 ,获得的A1-BP能够结合HBV ,而BP-A1却不能。A1与BP的C末端仅有 3个氨基酸的差异 ,其中 2个位于反应位点环域。一级结构分析发现在该区域内 ,A1的疏水性较弱 ,而BP和AJ515706的疏水性较强。将A1的aa349位的弱疏水性的谷氨酸突变为强疏水性的缬氨酸 ,则可获得HBV结合能力。反之 ,将BP同一位点的缬氨酸突变为谷氨酸 ,则会丧失HBV结合能力。这些结果提示SCCA1与HBV的结合受反应位点环域的疏水性的影响。     

siRNA, miRNA and HIV: promises and challenges

INTRODUCTION The recent discovery of small interfering RNA (siRNA) revealed an important role for small RNAs in regulating gene expression. First described in plants, as “post- trancriptional gene silencing” (PTGS) [1], RNA interfer- ence (RNAi) is a nucleic-acid based immune defense against viruses, transgenes and transposons [2]. Triggered by double-stranded RNA (dsRNA), RNAi leads to the se- quence specific degradation of a target mRNA [3]. In eukaryotic cells, long dsRN…     

中国新纪录属--兜小叶蝉属并记三新种(同翅目,叶蝉科,小叶蝉亚科,小绿叶蝉族)

报道中国小叶蝉亚科小绿叶蝉族1新纪录属--兜小叶蝉属Velu Ghauri,1963,记述3新种:叉突兜小叶蝉 V.furcatum sp.nov.,长突兜小叶蝉V.longiprojectum sp.nov.及侧突兜小叶蝉V.pleuroprominens sp.nov,编制了分种检索表,绘制了鉴别特征图.模式标本保存于西北农林科技大学昆虫博物馆(NWSUAF).     

中国跗雄管蓟马属一新种记述(缨翅目,管蓟马科)

记述中国跗雄管蓟马属1新种,即钝鬃跗雄管蓟马Hoplandrothrips trucatoapicus sp. nov.,新种与H.bidens近似,并与其进行了比较.模式标本保存于包头市园林科技研究所(BLRI).     

Mortality among patients with hypertension from 1995 to 2005: a population-based study

Background

We have reported that the prevalence of diagnosed hypertension increased by 60% from 1995 to 2005 in Ontario. In the present study, we asked whether this increase is explained by a decrease in the mortality rate.

Methods

We performed a population-based cohort study using linked administrative data for Ontario, a Canadian province with over 12 million residents. We identified prevalent cases of hypertension using a validated case-definition algorithm for hypertension, and we examined trends in mortality from 1995 to 2005 among adults aged 20 years and older with hypertension.

Results

The age-and sex-adjusted mortality among patients with hypertension decreased from 11.3 per 1000 people in 1995 to 9.6 per 1000 in 2005 (p < 0.001), which is a relative reduction of 15.5%. We found that the relative decrease in age-adjusted mortality was higher among men than among women (–22.2% v. –7.3%, p < 0.001).

Interpretation

Mortality rates among patients with hypertension have decreased. Along with an increasing incidence, decreased mortality rates may contribute to the increased prevalence of diagnosed hypertension. Sex-related discrepancies in the reduction of mortality warrant further investigation.High blood pressure is the leading risk factor for mortality around the world.^1,2 Over a decade ago, the Canadian Heart Health Survey reported that 42% of Canadian adults with hypertension were unaware that they had the condition and that only 16% of cases were treated and controlled.³ More recent studies in the United States⁴ and England⁵ have reported improved awareness, treatment and control among adults with hypertension. In addition, increased initiation of hypertensive medications among elderly patients⁶ and increased use of polytherapy for treating hypertension have been reported.⁷ Given that blood pressure control has been shown to reduce mortality, one might expect that enhanced awareness and treatment of hypertension has led to improvements in mortality among patients with this condition. Greater survival of patients with hypertension would contribute to an overall increase in the prevalence of hypertension.In another article in this issue of CMAJ, we report that the prevalence of diagnosed hypertension among adults increased by 60% from 1995 to 2005, which greatly surpassed prior projections for the developed world.⁸ Previous projections may have underestimated prevalence⁹ because researchers did not adequately account for the contribution of increased survival. Indeed, the increased prevalence cannot be explained by increased incidence alone, because the incidence of hypertension increased by 25.7% between 1997 and 2004 whereas prevalence increased by 35.5% during that same period. In the present study, our objective was to examine the mortality rates among patients with hypertension to determine whether declining mortality also contributed to the rising prevalence of hypertension.     

Senescence-like changes induced by expression of p21~(Waf1/Cip1) in NIH3T3 cell line

P21Waf1/Cip1 is a potent cyclin-dependent kinase inhibitor. As a downstream mediator of p53, p21Waf1/Cip1 involves in cell cycle arrest, differentiation and apoptosis. Previous studies in human cells provided evidence for a link between p21Waf1/Cip1 and cellular senescence. While in murine cells, the role of p21Waf1/Cip1 is indefinite. We explored this issue using NIH3T3 cells with inducible p21Waf1/Cip1 expression. Induction of p21Waf1/Cip1 triggered G1 growth arrest, and NIH3T3-p21 cells exhibited morphologic features, such as enlarged and flattened cellular shape, specific to the senescence phenotype. We also showed that p21Waf1/Cip1-transduced NIH3T3 cells expressed β-galactosidase activity at pH 6.0, which is known to be a marker of senescence. Our results suggest that p21Waf1/Cip1 can also induce senescence-like changes in murine cells.     

PKCα translocation from mitochondria to nucleus is closely related to induction of apoptosis in gastric cancer cells

PKCs have been implicated in the regulation of cellular differentiation, proliferation, apoptosis and signal transduction. It was demonstrated in this study that PKCa was located both at mitochondria and in cytosol in gastric cancer cell line BGC-823. Treatment of cells with 12-O-tetradecanoylphorbol-13-acetate (TPA) resulted in the translocation of PKCa from both mitochondria and cytosol to nucleus as clearly shown by laser-scanning-confocal microscopy, while the protein level of PKCa was not changed by TPA treatment as detected by Western blot. The results also revealed that TPA-induced translocation of PKCa was in close association with apoptosis induction, and such association was further affirmed by other experiments where various apoptotic stimuli and specific inhibitors of PKC were used. Taken together, these findings indicate that translocation of PKCa from both mitochondria and cytosol to nucleus in gastric cancer cell is accompanied by induction of apoptosis, and may imply a new mechanism of th