Mechanisms of Dihydroartemisinin and Dihydroartemisinin/Holotransferrin Cytotoxicity in T-Cell Lymphoma Cells

The validated therapeutic effects of dihydroartemisinin (DHA) in solid tumors have encouraged us to explore its potential in treating T-cell lymphoma. We found that Jurkat cells (a T-cell lyphoma cell line) were sensitive to DHA treatment with a IC50 of dihydroartemisinin. The cytotoxic effect of DHA in Jurkat cells showed a dose- and time- dependent manner. Interestingly, the cytotoxic effect of DHA was further enhanced by holotransferrin (HTF) due to the high expression of transferrin receptors in T-cell lymphoma. Mechanistically, DHA significantly increased the production of intracellular reactive oxygen species, which led to cell cycle arrest and apoptosis. The DHA treatment also inhibited the expression of protumorgenic factors including VEGF and telomerase catalytic subunit. Our results have proved the therapeutic effect of DHA in T-cell lymphoma. Especially in combination with HTF, DHA may provide a novel efficient approach in combating the deadly disease.     

松花江干流大型底栖动物群落结构与水质生物评价

于2010年春季（4-5月）、夏季（7-8月）和秋季（9-11月）,对松花江干流大型底栖动物群落结构进行调查研究,并利用生物指数对松花江干流水质进行评价.共采集到大型底栖动物16目36科116种,其中水生昆虫种类最多,为74种,属6目21科,占总数63.8%,年平均密度为66.80 ind·m^-2、生物量为24.30 g·m^-2.春、夏、秋季的平均密度以春季最高 (90.52 ind·m^-2),秋季(61.26 ind·m^-2)次之,夏季(48.63 ind·m^-2)最低;平均生物量以秋季最高(35.35 g·m^-2),夏季(23.12 g·m^-2)次之,春季(14.41 g·m^-2)最低.Shannon指数、Pielou均匀度指数、Simpson指数均以春季最高,夏季与秋季相近.各断面微生境共有种不多, 物种相似性不高,最大仅为60%;功能摄食群种类数相近,共有撕食者26种,收集者32种,刮食者28种,捕食者30种.采用BI生物指数和FBI生物指数对松花江干流水质的评价结果基本一致,并与化学监测结果基本吻合.松花江干流哈尔滨断面以上水质一般,哈尔滨以下断面水质在不同时期处于污染或严重污染状态.推测大顶子山航电枢纽的修建已对大型底栖动物的物种组成、群落结构造成了较大影响.     

Colonization study of gfp-tagged Achromobacter marplatensis strain in sugar beet

This study details the introduction of a gfp marker into an endophytic bacterial strain (Achromobacter marplatensis strain 17, isolated from sugar beet) to monitor its colonization of sugar beet (Beta. vulgaris L.). Stability of the plasmid encoding the gfp was confirmed in vitro for at least 72 h of bacterial growth and after the colonization of tissues, under nonselective conditions. The colonization was observed using fluorescence microscopy and enumeration of culturable endophytes in inoculated sugar beet plants that grew for 10 or 20 days. gfp-Expressing strains were re-isolated from the inner tissues of surface-sterilized roots and stems of inoculated plants, and the survival of the Achromobacter marplatensis 17:gfp strain in plants 20 days after inoculation, even in the absence of selective pressure, suggests that it is good colonizer. These results also suggest that this strain could be a useful tool for the delivery of enzymes or other proteins into plants. In addition, the study highlights that sugar beet plants can be used effectively for detailed in vitro studies on the interactions between A. marplatensis strain 17 and its host, particularly if a gfp-tagged strain of the pathogen is used.     

How Human Household Size Affects the Habitat of Black-and-White Snub-Nosed Monkeys (<Emphasis Type="Italic">Rhinopithecus bieti</Emphasis>) in Hongla Snow Mountain Nature Reserve in Tibet,China

Human impacts on the environment at local or regional scales largely depend on intrinsic characteristics of the population, such as household size, household number, and human population growth. These demographic factors can vary considerably among ethnic groups sharing similar ecological landscapes, yet the role of traditional cultural practices in shaping local environmental impacts is not well known for many parts of the world. We here quantify land-cover changes and their relation to the habitat of the endangered Rhinopithecus bieti in Tibet, in 2 areas populated by different ethnic groups (polyandrous Tibetans and monogamous Naxi) from 1986 to 2006. Results indicate that habitat of the monkey decreased greatly within our study area over the 20-yr period. Polyandrous and monogamous ethnic communities differed in household size, household number, population growth, and per capita and per household land use. The practice of polyandry by ethnic Tibetan appears to have reduced per capita resource consumption by reducing the growth of overall household number and increasing household size, which can mitigate the negative effects of higher human density and population growth on the environment. Ethnic Tibetan may also reduce land impacts by adhering to Buddhist customs and alternative, more sustainable means of livelihood. Accordingly, the protection of traditional cultural resources, such as polyandry and Buddhist beliefs, could be an effective way to aid biodiversity and environmental conservation efforts in this key ecosystem.     

The Influence of Hepatitis B Viral Load and Pre-S Deletion Mutations on Post-Operative Recurrence of Hepatocellular Carcinoma and the Tertiary Preventive Effects by Anti-Viral Therapy

Background

Whether or not hepatitis B virus (HBV) genotypes, mutations, and viral loads determine outcomes for patients with HBV-induced hepatocellular carcinoma (HCC) remains controversial.

Aims

To study the influence of HBV viral factors on prognoses for patients with HBV-induced HCC after resection surgery and investigate if antiviral therapy could counteract the adverse effects of viral factors.

Methods

A total of 333 HBV-related HCC patients who underwent tumor resection were enrolled retrospectively. Serum HBV DNA levels, mutations, anti-viral therapy, and other clinical variables were analyzed for their association with post-operative recurrence.

Results

After a median follow-up of 45.9 months, 208 patients had HCC recurrence after resection. The 5-year overall survival and recurrence-free survival rates were 55.4% and 35.3%, respectively. Multivariate analysis showed indocyanine green retention rate at 15 minutes >10%, gamma-glutamyltransferase (GGT) level >60 U/L, macroscopic and microscopic venous invasion, and the absence of anti-viral therapy were significant risk factors for recurrence. Anti-viral therapy could decrease recurrence in patients with early stage HCC, but the effect was less apparent in those with the Barcelona-Clinic Liver Cancer stage C HCC. For patients without antiviral therapy after resection, serum HBV DNA levels >10⁶ copies/mL, GGT >60 U/L, and macroscopic and microscopic venous invasion were significant risk factors predicting recurrence. Among the 216 patients without anti-viral therapy but with complete HBV surface gene mapping data, 73 were with pre-S deletion mutants. Among patients with higher serum HBV DNA levels, those with pre-S deletion had significantly higher rates of recurrence. Moreover, multivariate analysis showed multi-nodularity, macroscopic venous invasion, cirrhosis, advanced tumor cell differentiation, and pre-S deletion were significant risk factors predictive of recurrence.

Conclusions

Ongoing HBV viral replication and pre-S deletion are crucial for determining post-operative tumor recurrence. Anti-viral therapy can help reduce recurrence and improve prognosis, especially for those with early stage HCC.     

Cyr61 induces IL-6 production by fibroblast-like synoviocytes promoting Th17 differentiation in rheumatoid arthritis

Cysteine-rich protein 61 (Cyr61)/CCN1 is a product of an immediate early gene and functions in mediating cell adhesion and inducing cell migration. We previously showed that increased production of Cyr61 by fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA) promotes FLS proliferation and participates in RA pathogenesis with the IL-17-dependent pathway. However, whether Cyr61 in turn regulates Th17 cell differentiation and further enhances inflammation of RA remained unknown. In the current study, we explored the potential role of Cyr61 as a proinflammatory factor in RA pathogenesis. We found that Cyr61 treatment dramatically induced IL-6 production in FLS isolated from RA patients. Moreover, IL-6 production was attenuated by Cyr61 knockdown in FLS. Mechanistically, we showed that Cyr61 activated IL-6 production via the αvβ5/Akt/NF-κB signaling pathway. Further, using a coculture system consisting of purified CD4(+) T cells and RA FLS, we found that RA FLS stimulated Th17 differentiation, and the pro-Th17 differentiation effect of RA FLS can be attenuated or stimulated by Cyr61 RNA interference or addition of exogenous Cyr61, respectively. Finally, using the collagen-induced arthritis animal model, we showed that treatment with the anti-Cyr61 mAb led to reduction of IL-6 levels, decrease of Th17 response, and attenuation of inflammation and disease progression in vivo. Taken together, our results reveal a novel role of Cyr61 in promoting Th17 development in RA via upregulation of IL-6 production by FLS, thus adding a new layer into the functional interplay between FLS and Th17 in RA pathogenesis. Our study also suggests that targeting of Cyr61 may represent a novel strategy in RA treatment.