Flavonoids and stilbenoids as a promising arsenal for the management of chronic arsenic toxicity

Rapid industrial and technological development has impacted ecosystem homeostasis strongly. Arsenic is one of the most detrimental environmental toxins and its management with chelating agents remains a matter of concern due to associated adverse effects. Thus, safer and more effective alternative therapy is required to manage arsenic toxicity. Based on existing evidence, native and indigenous plant-based active biomolecules appear as a promising strategy to mitigate arsenic-induced toxicity with an acceptable safety profile. In this regard, various phytochemicals (flavonoids and stilbenoids) are considered important classes of polyphenolic compounds with antioxidant and chelation effects, which may facilitate the removal of arsenic from the body more effectively and safely with regard to conventional approaches. This review presents an overview of conventional chelating agents and the potential role of flavonoids and stilbenoids in ameliorating arsenic toxicity. This report may provide a roadmap for identifying novel prophylactic/therapeutic strategies for managing arsenic toxicity.     

消癌平分散片的研制

目的优选消癌平分散片的成型工艺。方法以崩解时间为考察指标,考察不同种类的辅料及其用量,设计确定最佳处方。结果最佳处方组成为乌骨藤1 500 g、甘露醇100 g、微晶纤维素100 g、低取代羟丙基纤维素125 g、交联聚乙烯吡咯烷酮45 g、阿斯帕坦2.5 g、硬脂酸镁5 g。按该处方压片,崩解时间小于3 min,崩解迅速且完全。对三批中试样品按质量标准进行检验,结果均符合要求。结论所选处方合理,工艺可行。     

The organochlorine p,p′-dichlorodiphenyltrichloroethane induces colorectal cancer growth through Wnt/β-catenin signaling

Dichlorodiphenyltrichloroethane (DDT), an organochlorine pollutant, is associated with several types of cancer. However, the relationship between DDT and colorectal cancer is uncertain. In this study, the impact of p,p′-DDT on colorectal cancer growth was evaluated using both in vitro and in vivo models. Our results indicated that the proliferation of human colorectal adenocarcinoma DLD1 cells was significantly promoted after exposed to low concentrations of p,p′-DDT ranging from 10⁻¹² to 10⁻⁷ M for 96 h. Exposure to p,p′-DDT from 10⁻¹⁰ to 10⁻⁸ M led to upregulation of phospho-GSK3β (Ser9), β-catenin, c-Myc and cyclin D1 in DLD1 cells. RNA interference of β-catenin inhibited the proliferation of DLD1 cells stimulated by p,p′-DDT. Inhibiting of estrogen receptors (ERs) had no significant effect on the action of p,p′-DDT. Treatment with p,p′-DDT induced production of intracellular reactive oxygen species (ROS) and inhibited superoxide dismutase (SOD) activity in DLD1 cells. Treatment with N-acetyl-L-cysteine (NAC), a ROS inhibitor, suppressed the induction of Wnt/β-catenin signaling and DLD1 cell proliferation by p,p′-DDT. Moreover, in a mouse xenograft model, 5 nmol/kg p,p′-DDT resulted in increased tumor size, oxidative stress and Wnt/β-catenin signaling. These results indicated that low concentrations of p,p′-DDT promoted colorectal cancer growth through Wnt/β-catenin signaling, which was mediated by oxidative stress. The finding suggests an association between low concentrations of p,p′-DDT exposure and colorectal cancer progression.     

Aprepitant exerts anti-fibrotic effect via inhibition of TGF-β/Smad3 pathway in bleomycin-induced pulmonary fibrosis in rats

Bleomycin is a well-recognized antineoplastic drug. However, pulmonary fibrosis (PF) is considered to be the principal drawback that greatly limits its use. Here, we sought to investigate ability of the neurokinin receptor 1 blocker, aprepitant, to prevent PF caused by bleomycin. Male adult Wistar rat groups were given a single intratracheal injection of bleomycin, either alone or in combination with aprepitant therapy for 3 or 14 days. Collagen deposition and a rise in transforming growth factor beta (TGF-β) immunoreactivity in lung tissue serve as evidence of bleomycin-induced PF. The serum levels of lactate dehydrogenase, alkaline phosphatase, and total antioxidant improved after aprepitant therapy.Additionally, it reduced the protein expressions of interferon alpha, tumor necrosis factor alpha, and lung lipid peroxidation. Moreover, aprepitant treatment led to an increase in the antioxidant indices glutathione, glutathione peroxidase, and catalase. Aprepitant is postulated to protect against bleomycin-induced PF by decreasing TGF-β, phosphorylating Smad3, and increasing interleukin 37, an anti-fibrotic cytokine, and G Protein-coupled Receptor Kinase 2. Aprepitant for 14 days considerably exceeded aprepitant for 3 days in terms of improving lung damage and having an anti-fibrotic impact. In conclusion, aprepitant treatment for 14 days may be used as an adjuvant to bleomycin therapy to prevent PF, mostly through inhibiting the TGF-/p-Smad3 fibrotic pathway.     

Ochratoxin A induced differentiation nephrotoxicity in renal tubule and glomeruli via autophagy differential regulation

Ochratoxin A (OTA) is a mycotoxin that mainly causes nephrotoxicity. The single nephrotoxicity of OTA exposure on glomeruli or renal tubule had been well documented, however, the comparison toxicity between it is still unclear. Here, C57BL/6 mice and two types of nephrocyte were treated with concentration-gradient OTA to explore its differentiation nephrotoxicity. Results showed that OTA induced nephrotoxicity in vivo and in vitro, manifested as the deteriorative kidney function in mice and the cut-down cell viability in nephrocyte. Besides, results of murine kidney pathological section and IC₅₀ of two types nephrocyte indicated that OTA-induced toxicity in renal tubule was higher than its in glomeruli. In addition, OTA exposure induced autophagy signaling differentiation expression. It revealed that autophagy was implicated in OTA-induced differential nephrotoxicity in glomeruli and renal tubule. Altogether, we proved that OTA induces a differentiation nephrotoxicity in glomeruli and renal tubule, and it is related to autophagy differential regulation.     

腺病毒载体RNAi技术抑制血吸虫病小鼠肝细胞Fas表达

目的探讨RNAi技术对血吸虫病肝组织中Fas表达的作用。方法采用尾静脉注射腺病毒载体,在小鼠体内表达Fas-shRNA抑制血吸虫病小鼠肝细胞Fas的表达。冰冻切片荧光显微镜检查腺病毒载体对肝细胞的转染率,免疫组化和Western Blot方法检测肝组织Fas表达情况,RT-PCR方法检测肝组织Fas mRNA表达情况。结果免疫组化和Western Blot方法检测均表明RNAi组Fas表达受到抑制(t=29.799,P<0.01),模型组和HK对照组Fas表达增强。对Fas mRNA表达的RT-PCR方法检测也与上述结果一致。腺病毒载体对肝细胞的转染率达78.5%。结论腺病毒载体Fas-shRNA能够有效抑制血吸虫病小鼠肝细胞Fas的表达,尾静脉注射腺病毒载体能高效率感染肝细胞。     

Self-rated health status transition and long-term care need,of the oldest Chinese

ObjectivesThe objectives of this paper are: (1) to estimate the transition probabilities among self-rated health status for the oldest Chinese aged 80 and above; (2) to project the future need of long-term care due to changes in demography and health status among the oldest Chinese.MethodsSelf-rated health data collected in Chinese Longitudinal Healthy Longevity Survey conducted in 1998, 2000 and 2002 were used to estimate the self-rated health status transition probabilities, and to project future long-term care need by calculating the number of unhealthy person-years.ResultsThe majority of the oldest Chinese's health status remains unchanged or worsens within 2 years. The number of unhealthy person-years rises regardless of gender, and the absolute number and increase rate of females are higher than those of males. Under the assumption that average care expenditure is 15 US dollars per hour in 2010, the long-term care expenditure will increase from 8352 million dollars in 2010 to 42,530 million dollars in 2050, a growth of more than 400% over the next 40 years.ConclusionsLong-term care need for the oldest Chinese will rise rapidly in the next decades, which should stimulate increased governmental and public awareness of their need.