Simultaneous downregulation of uPAR and MMP-9 induces overexpression of the FADD-associated protein RIP and activates caspase 9-mediated apoptosis in gliomas

We have previously demonstrated the effectiveness of simultaneous RNA interference (RNAi)-mediated downregulation of urokinase-type plasminogen activator receptor (uPAR) and matrix metalloproteinase-9 (MMP-9) in inhibiting tumor invasion in vitro and in vivo. In particular, we have shown that the downregulation of uPAR and MMP-9 inhibits intracranial tumor growth. The mechanism of the inhibition of tumor growth has not yet been determined. In this study, we have attempted to explain the mechanisms involved in the inhibition of invasiveness and tumor growth in vitro. SNB19 glioma cells were transfected with scrambled vector plasmid (pSV) and a siRNA-expressing plasmid targeting either uPAR (pU) or MMP-9 (pM) singly or in combination (pUM). Untransfected cells were also used as a control. Western blotting and RT-PCR analyses showed the downregulation of uPAR in pU-transfected cells and MMP-9 in pM-transfected cells. In cells transfected with pUM, we observed down-regulation of both uPAR and MMP-9, thereby indicating the specificity of the siRNA-expressing plasmids. An increase in caspase 9 expression was observed in cells transfected with pUM whereas no change in the level of caspase 9 was observed in pU or pM-transfected cells. Additionally, no change in the expression level of caspase 8 was observed. However, an increase in the expression level of cleaved PARP was observed in the case of cells transfected with pU, pM and pUM. Cells transfected with pUM showed the highest levels of cleaved PARP expression. Expression levels of APAF-1 were also higher in pUM-transfected cells with no change in expression levels of controls and in pU and pM-transfected cells. Total CAD expression levels did not change under any of the transfection conditions. However, immunohistochemical studies demonstrated that CAD was translocated to the nucleus, thereby indicating DNA damage. As determined by Western blot analysis of subcellular fractions, cytoplasmic levels of cytochrome c were also increased. We determined the extent of DNA damage using the TUNEL assay (poly-A termination of free -OH ends of degraded nuclear DNA). Based on our results we conclude that the simultaneous downregulation of uPAR and MMP-9 induces apoptosome-mediated apoptosis.     

Pre-S2 deletion mutants of hepatitis B virus could have an important role in hepatocarcinogenesis in Asian children

Although many studies on the risk factors and their carcinogenesis in adult hepatocellular carcinoma (HCC) have been reported, they remain poorly understood in childhood HCC. A retrospective study of 42 HCC cases in Asian children was conducted. Hepatitis B virus (HBV)-DNA in HCC tissues was detected in 36 of 42 (86%) cases tested, while no hepatitis C virus (HCV)-RNA was detectable in any of HCCs. Twenty of 36 (56%) HCC cases were accompanied by cirrhosis. Surprisingly, very high prevalence of the HBV pre-S deletion mutant was recognized in 27 of 30 (90%) HCCs examined. They occurred most frequently in pre-S2 (20/27, 74%) followed by pre-S1 (5/27, 18.5%), and both pre-S1/S2 (2/27, 7.4%). Interestingly, the pre-S2 mutant consistently appeared with deletion at nt 4-57 in all of the 20 cases with the pre-S2 mutant (100%) and within this locus in the two cases with both pre-S-1/S2 mutants. Type II ground-glass hepatocytes in non-tumorous livers were seen in 15 of the 22 HCCs with the pre-S2 deletion mutant (68%). This hotspot mutation in the pre-S2 was further confirmed by complete genomic sequence of HBV in a Japanese boy who eventually developed HCC. Our result strongly suggests that HBV is a major contributor to the development of HCC in Asian children. The HBV pre-S2 deletion mutant at nt 4-57 which has a CD8 T-cell epitope could be responsible for the emergence and aggressive outcome of childhood HCC. Determination of this hotspot mutation in the pre-S2 region could be a useful index for predicting the clinical outcome of HCC development. ( Cancer Sci 2009; 100: 2249–2254)     

UV法测定双氯芬酸钠凝胶剂的含量

目的：建立双氯芬酸钠凝胶剂的含量测定方法。方法：采用紫外分光光度法于276nm波长外测定其吸收度并计算含量。结果：线性范围在5－30μg/ml,回归方程：A＝0．03185c－0．01323;r＝0．9999(n＝6）,平均回收率为100．42％,RSD=0．88％。结论：方法简便,准确,适合双氯芬酸钠凝胶剂的含量测定。     

CSF-1受体/c-fms与肝癌

肝癌的致癌机制是一个多步骤、多因素、多基因协同或单独作用不同阶段的复杂过程.正常情况下原癌基因参与细胞的生长、分化及信号传递调节,部分原癌基因的编码产物就是生长因子和(或)受体.原癌基因的突变或转录活化在不适当时期的表达或过量表达,在肝癌的发生机制中具有重要意义[1-15].集落刺激因子1受体(CSF-1R)是c-fms原癌基因的编码产物,具有酪氨酸激酶活性.CSF-1R在肝癌及癌旁肝组织中过量表达与肝癌的发生、发展、生长相关.CSF-1/CSF-1R可能是肝癌发生、发展中的一对自泌/邻泌系统.因此,阐明CSF-1R在肝癌发生、发展机制中的作用具有药物开发和临床诊治的意义.     

The burden of rotavirus diarrhea in Khanh Hoa Province, Vietnam: baseline assessment for a rotavirus vaccine trial

BACKGROUND: In Vietnam, rotavirus is seen as a priority disease because studies have demonstrated that >50% of children hospitalized for treatment of diarrhea have rotavirus as the pathogen. To anticipate the availability of new vaccines, we have examined our field area in Nha Trang, Khanh Hoa Province, Vietnam, as a potential site to conduct a field trial of a future rotavirus vaccine. METHODS: Data from a population census, incidence rates of diarrhea from a previous cholera vaccine trial and hospitalization rates from computerized records collected from the 2 main hospitals in the province were reviewed to estimate the burden of rotavirus-related diarrhea that might be expected during a field trial of a rotavirus vaccine. RESULTS: For a birth cohort of approximately 5000 children, we would expect approximately 2500 clinic visits and 650-850 hospitalizations for treatment of diarrhea, of which approximately 375-425 would be attributable to rotavirus. For the Vietnamese birth cohort of 1,639,000 children, these numbers translate into approximately 820,000 clinic visits, 122,000-140,000 hospitalizations and 2900-5400 deaths annually attributable to rotavirus-related diarrhea. CONCLUSIONS: Vietnam is an early adaptor of new vaccines, has high national coverage rates (>85%) for childhood immunization and receives international donor support for the introduction of new vaccines. We found the epidemiologic features of rotavirus in rural Vietnam to be more similar to those of rotavirus in a developed country than to those of rotavirus in India or Bangladesh.     

Inhibition of dentate granule cell neurogenesis with brain irradiation does not prevent seizure-induced mossy fiber synaptic reorganization in the rat

Aberrant reorganization of dentate granule cell axons, the mossy fibers, occurs in human temporal lobe epilepsy and rodent epilepsy models. Whether this plasticity results from the remodeling of preexisting mossy fibers or instead reflects an abnormality of developing dentate granule cells is unknown. Because these neurons continue to be generated in the adult rodent and their production increases after seizures, mossy fibers that arise from either developing or mature granule cells are potential substrates for this network plasticity. Therefore, to determine whether seizure-induced, mossy fiber synaptic reorganization arises from either developing or mature granule cell populations, we used low-dose, whole-brain x-irradiation to eliminate proliferating dentate granule cell progenitors in adult rats. A single dose of 5 Gy irradiation blocked cell proliferation and eliminated putative progenitor cells in the dentate subgranular proliferative zone. Irradiation 1 d before pilocarpine-induced status epilepticus significantly attenuated dentate granule cell neurogenesis after seizures. Two irradiations, 1 d before and 4 d after status epilepticus, essentially abolished dentate granule cell neurogenesis but failed to prevent mossy fiber reorganization in the dentate molecular layer. These results indicate that dentate granule cell neurogenesis in the mature hippocampal formation is vulnerable to the effects of low-dose ionizing irradiation. Furthermore, the development of aberrant mossy fiber remodeling in the absence of neurogenesis suggests that mature dentate granule cells contribute substantially to seizure-induced network reorganization.     

External benchmarking of trauma services in New South Wales: Risk-adjusted mortality after moderate to severe injury from 2012 to 2016

Background

Trauma centres and systems have been associated with improved morbidity and mortality after injury. However, variability in outcomes across centres within a given system have been demonstrated. Performance improvement initiatives, that utilize external benchmarking as the backbone, have demonstrated system-wide improvements in outcomes. This data driven approach has been lacking in Australia to date. Recent improvement in local data quality may provide the opportunity to engage in data driven performance improvement. Our objective was to generate risk-adjusted outcomes for the purpose of external benchmarking of trauma services in New South Wales (NSW) based on existing data standards.

Human health risk of mercury in street dust: A case study of children in the vicinity of compact fluorescence lamp factory,Hanoi, Vietnam

Urban dust has been contaminated with toxic heavy metals from various diffused sources. On August 28, 2019, the compact fluorescence lamp (CFL) factory that generates light for Rang Dong Light Source and Vacuum Flask in Hanoi City in Vietnam was accidentally fired. The assessment for Hg contamination and its human health impact 2 months after the incident was conducted in autumn 2019. The heavy Hg pollution is still found near CFL. Additionally, localized Hg pollution by air and wind direction was identified at sites in the northeast direction from CFL. Namely, in the area located downstream of the southwest monsoon wind, Hg had a trend higher than other directions. The hazard quotient (HQ) and the hazard index (HI) were evaluated by four routes of Hg exposure pathways. The HI values for children and adults in the most polluted site (Site 15) were 0.968 and 0.468, respectively. This meant that children who lived around this site and commuted to schools were the most at risk regarding the potential adverse health effects of Hg in street dust around the polluted areas. This study also showed that Hg levels were affected by wind direction and that the higher Hg levels in the most polluted sites resulted from the wind flow to the sites. This study revealed that street dust may be a useful tool for the assessment of human and environmental health.