Overexpression of decoy receptor 3 in hepatocellular carcinoma and its association with resistance to Fas ligand-mediated apoptosis

AIM： To characterize the expression and genomic amplification of decoy receptor 3 （DcR3） in hepatocellular carcinoma （HCC） and to evaluate the role of DcR3 in apoptosis.METHODS： We examined 48 cases of HCC for DcR3 expression by RT-PCR and DcR3 gene amplification by quantitative genomic PCR. DcR3 protein was detected by immunohistochemistry. Terminal deoxynucleotidyl transferase-mediated dUTP digoxigenin nick and labeling （TUNEL） was used to identify the apoptosis cells in tissues. Primary hepatoma cell culture and MTT test were used to evaluate the protection against FasL- and chemicalinduced apoptosis by DcR3 expression. RESULTS： DcR3 mRNA overexpression was detected in 60% HCC （29/48） patients. The occurrence of HCC was not associated with amplification of the gene. One sample base substitution was found in three sites as a sequence in Genbank. The expression of DcR3 in HCC was associated with the apoptotic index （0.067±0.04 vs 0.209±0.12, P〈0. 01）, size of mass, stage, and infiltration or metastasis （41.2% vs71.0%, 40% vs75%, 51.8% vs84.6%, P〈0. 05）. DcR3 expression could protect hepatoma cells against apoptosis induced by FasL, but not by chemicals. CONCLUSION： These data suggest that in addition to gene amplification there may be another mechanism underlying DcR3 overexpression. The effect of overexpression of DcR3 on the apoptosis of cancer cells may have direct therapeutic implications for the management of HCC.

Aluminium tolerance in barley (Hordeum vulgare L.): physiological mechanisms, genetics and screening methods

Aluminium (Al) toxicity is one of the major limiting factors for barley production on acid soils. It inhibits root cell division and elongation, thus reducing water and nutrient uptake, consequently resulting in poor plant growth and yield. Plants tolerate Al either through external resistance mechanisms, by which Al is excluded from plant tissues or internal tolerance mechanisms, conferring the ability of plants to tolerate Al ion in the plant symplasm where Al that has permeated the plas- malemma is sequestered or converted into an innocuous form. Barley is considered to be most sensitive to Al toxicity among cereal species. Al tolerance in barley has been assessed by several methods, such as nutrient solution culture, soil bioassay and field screening. Genetic and molecular mapping research has shown that Al tolerance in barley is controlled by a single locus which is located on chromosome 4H. Molecular markers linked with Al tolerance loci have been identified and validated in a range of diverse populations. This paper reviews the (1) screening methods for evaluating Al tolerance, (2) genetics and (3) mechanisms underlying Al tolerance in barley.

青海省人民政府办公厅关于印发进一步加强行政复议工作若干意见的通知

青政办[2009]131号西宁市、各自治州人民政府,海东行署,省政府各委、办、厅、局:《关于进一步加强行政复议工作的若干意见》已经省人民政府同意,现印发给你们,请认真组织实施。

海南省政府信息公开办法

海南省人民政府令第194号《海南省政府信息公开办法》已经2005年8月15日海南省人民政府第70次常务会议审议通过,现予公布,自2005年10月1日起施行。

Significance of endothelial dysfunction in the pathogenesis of early and delayed radiation enteropathy

This review summarizes the current state of knowledge regarding the role of endothelial dysfunction in the pathogenesis of early and delayed intestinal radiation toxicity and discusses various endothelial-oriented interventions aimed at reducing the risk of radiation enteropathy. Studies published in the biomedical literature during the past four decades and cited in PubMed, as well as clinical and laboratory data from our own research program are reviewed. The risk of injury to normal tissues limits the cancer cure rates that can be achieved with radiation therapy. During treatment of abdominal and pelvic tumors, the intestine is frequently a major close-limiting factor. Microvascular injury is a prominent feature of both early （inflammatory）, as well as delayed （fibroproliferative） radiation injuries in the intestine and in many other normal tissues. Evidence from our and other laboratories suggests that endothelial dysfunction, notably a deficiency of endothelial thrombomodulin, plays a key role in the pathogenesis of these radiation responses. Deficient levels of thrombomodulin cause loss of vascular thromboresistance, excessive activation of cellular thrombin receptors by thrombin, and insufficient activation of protein C, a plasma protein with anticoagulant, anti-inflammatory, and cytoprotective properties. These changes are presumed to be critically involved in many aspects of early intestinal radiation toxicity and may sustain the fibroproliferative processes that lead to delayed intestinal dysfunction, fibrosis, and clinical complications. In conclusion, injury of vascular endothelium is important in the pathogenesis of the intestinal radiation response. Endothelial-oriented interventions are appealing strategies to prevent or treat normal tissue toxicity associated with radiation treatment of cancer.

Food intolerance and skin prick test in treated and untreated irritable bowel syndrome

AIM： To correlate the clinical features of treated and untreated patients with irritable bowel syndrome （IBS） to the results of skin prick test （SPT） for food and inhalant allergens. METHODS： We recruited 105 subjects to form three different target groups： treated group （n=44） undergoing treatment for IBS, untreated group （n =31） meeting the Rome Ⅱ criteria without treatment for IBS, control group （n = 30） with no IBS symptoms. RESULTS： SPT results were different among the three groups in which SPT was positive in 17 （38.6%） treated patients, in 5 （16.1%） untreated patients and in 1 （3.3%） control （P〈0.01）. The number of positive SPTs was greater in the IBS group than in the control group （P〈 0.001）. The number of positive food SPTs was higher in the treated IBS group than in the untreated IBS group （P= 0.03）. CONCLUSION： Positive food SPT is higher in IBS patients than in controls.

Toll-like receptors in inflammatory bowel disease-stepping into uncharted territory

Ulcerative colitis and Crohn's disease are chronic relapsing-remitting inflammatory processes of the intestinal tract. The etiology of these diseases is currently unknown. However, inflammation is hypothesized to result from inappropriate activation of mucosal immunity by luminal antigens in genetically susceptible individuals. Toll-like receptors (TLRs) are a family of transmembrane proteins that act as microbial pattern recognition receptors. They are crucial initiators of innate immune responses. The role of TLRs in the pathogenesis of inflammatory bowel disease (IBD) has not been fully elucidated. In this review, we aim to analyze the available data connecting individual TLRs to intestinal inflammation and IBD.

Cyclin Dl antisense oligodexoyneucleotides inhibits growth and enhances chemosensitivity in gastric carcinoma cells

AIM： To examine the effects of cyclin D1 antisense oligodexoyneucleotides （ASODN） on growth and chemosensitivity of gastric carcinoma cell lines SGC7901 and its mechanism. METHODS： Phosphorothioate modified cyclin D1 ASODN was encapsulated by LipofectAMINE2000 （LF2000） and transfected into cells, the dose-effect curves and growth curves were observed. 5-FU, MTX, CDDP of different concentrations were given after transfecting cells with cyclin D1 ASODN for 24 h, the dose-effect responses were observed and IC50s were calculated. The mRNA expression of cyclin D1, thymidylate synthase （TS）, thymidine phosphorylase （TP） and dihydrofolate reductase （DHFR） was detected by reverse transcription-PCR （RTPCR） at 24 h and 48 h after transfection. RESULTS： Dose-dependent inhibitory effect was caused by cyclin D1 ASODN in SGC7901 cells. Transfecting gastric carcinoma cells with 0.2 μmol/L cyclin D1 ASODN for 24 h could inhibit growth significantly and reduce expression of cyclin D1 mRNA. Cyclin D1 ASODN could increase the chemosensitivity to 5-FU, MTX, CDDP in cells, The IC50s of different chemotherapeutic agents in ASODN plus chemotherapy groups were significantly lower than those in controls. Transfection with cyclin D1 ASODN leaded to an increase in TS and DHFR mRNA and a decrease in TP mRNA as determined by RT-PCR at 24 h, the alterations were more significant at 48 h. CONCLUSIONS： Cyclin D1 ASODN can decrease mRNA expression of cyclin D1, inhibit growth and enhance the chemosensitivity by changing the expression of enzymes related to metabolism of chemotherapeutic agents in SGC7901 gastric carcinoma cells.

Role of Toll-like receptors in health and diseases of gastrointestinal tract

The human gastrointestinal （GI） tract is colonized by non-pathogenic commensal microflora and frequently exposed to many pathogenic organisms. For the maintenance of GI homeostasis, the host must discriminate between pathogenic and non-pathogenic organisms and initiate effective and appropriate immune and inflammatory responses. Mammalian tolllike receptors （TLRs） are members of the patternrecognition receptor （PRR） family that plays a central role in the initiation of innate cellular immune responses and the subsequent adaptive immune responses to microbial pathogens. Recent studies have shown that gastrointestinal epithelial cells express almost all TLR subtypes characterized to date and that the expression and activation of TLRs in the GI tract are tightly and coordinately regulated. This review summarizes the current understanding of the crucial dual roles of TLRs in the development of host innate and adaptive immune responses to GI infections and the maintenance of the immune tolerance to commensal bacteria through downregulation of surface expression of TLRs in intestinal epithelial cells.

Role of nuclear receptor CAR in carbon tetrachloride-induced hepatotoxicity

AIM： To investigate the precise roles of CAR in CCI4- induced acute hepatotoxicity. METHODS： To prepare an acute liver injury model, CCI4 was intraperitoneally injected in CAR＋/＋ and CAR-/- mice. RESULTS： Elevation of serum alanine aminotransferase and extension of centrilobular necrosis were slightly inhibited in CAR-/- mice compared to CAR＋/＋ mice without PB. Administration of a CAR inducer, PB, revealed that CCl4-induced liver toxicity was partially inhibited in CAR-/- mice compared with CAR＋/＋ mice. On the other hand, androstanol, an inverse agonist ligand, inhibited hepatotoxicity in CAR＋/＋ but not in CAR./. mice. Thus, CAR activation caused CCl4 hepatotoxicity while CAR inhibition resulted in partial protection against CCl4-induced hepatotoxicity.There were no differences in the expression of CYP2E1, the main metabolizing enzyme for CCl4, between CAR＋/＋ and CAR./. mice. However, the expression of other CCI4-metabolizing enzymes, such as CYP2B10 and 3All, was induced by PB in CAR＋/＋ but not in CAR-/- mice. Although the main pathway of CCl4-induced acute liver injury is mediated by CYP2E1, CAR modulates its pathway via induction of CYP2B10 and 3All in the presence of activator or inhibitor. CONCLUSION： The nuclear receptor CAR modulates CCl4- induced liver injury via induction of CCl4-metabolizing enzymes in the presence of an activator. Our results suggest that drugs interacting with nuclear receptors such as PB might play critical roles in drug-induced liver injury or drug- drug interaction even though such drugs themselves are not hepatotoxic.

Role of the intracellular receptor domain of gp130 (exon 17) in human inflammatory bowel disease

AIM: To study the role of the intracellular receptor domain of gp130 in human inflammatory bowel disease (IBD).METHODS: We amplified and sequenced the complete exon 17 of the human gp130 gene in 146 patients with IBD. According to clinical and histopathological signs,the 146 patients with IBD were classified as having Crohn's disease (n = 73) or ulcerative colitis (n = 63),or as indeterminate status (n = 10).RESULTS: No mutations in exon 17 of the gp130 gene could be detected in any of the 146 patients with IBD examined.CONCLUSION: There is no evidence that mutations in exon 17 of the gp130 gene are involved in the pathogenesis of human IBD.

Enhanced Photocatalytic Properties of Silver Oxide Loaded Bismuth Vanadate

In this work, BiV04 powders were synthesized by a sol-gel method, and the BiV04 gels with different calcination temperature were investigated by X-ray diffraction （XRD）. Absorption range and band gap energy, which are respon- sible for the observed photocatalyst behavior, were investigated by UV/vis diffuse reflectance spectroscopy （DRS） for pure and silver oxide loaded BiV04. Pbotocatalytic properties of the prepared samples were examined by studying the degradation of the methyl orange. When using NaCI02 as an electron acceptor, the possible photocatalytic mech- anism has been discussed by photocatalytic reactions. With the help of electron acceptor, the results show clearly that the BiV04 loaded silver oxide exhibited superior photocatalytic activity in simulated dye wastewater treatment.

Systematic Pharmacological Strategies to Explore the Regulatory Mechanism of Ma Xing Shi Gan Decoction on COVID-19

Objective To use systematic pharmacological strategies to explore the regulatory mechanisms of Ma Xing Shi Gan Decoction(MXSGD)against the coronavirus disease 2019(COVID-19).Methods Data on the compounds and targets of MXSGD were collected from the Traditional Chinese Medicene Systems Parmacology Database and Analysis Platform(TCMSP)and TCM Databases@Taiwan.Data on ACE2-related targets and the protein-protein interaction(PPI)were collected from the String database.The Cytoscape 3.7.2 was used to construct and analyze the networks.The DAVID platform was used for Gene Ontology(GO)and pathway enrichment analyses.Results Data on 272 MXSGD targets and 21 SARS-CoV-2 potential targets were collected.Four networks were constructed and analyzed based on the data:(1)compound-target network of MXSGD;(2)MXSGD-SARS-CoV-2-PPI network;(3)cluster of MXSGD-SARS-CoV-2-PPI network;(4)Herb-Pathway-Target network.The core targets included AKT1,MAPK3,IL-6,TP53,VEGFA,TNF,CASP3,EGFR,EGF and MAPK1.The antiviral biological processes were inflammatory responses(inflammatory cells,inflammatory cytokines and their signaling pathways),immune responses(T cells,monocytes,B cells and other immune cells),immune factors(IFN-γ,TNF-αand so on),virus defense,humoral immunity and mucosal innate immune response.The antivirus-related signaling pathways included TNF,NOD-like receptor,FoxO,PI3K-AKT and Toll-like receptor signaling pathways.Conclusions MXSGD can control disease progression by regulating multiple compounds and targets;it can reduce inflammation and balance immunity by regulating several proteins that interact with ACE2 and signaling pathways closely related to disease development.

Bitter gourd (Momordica charantia): A potential mechanism in anti-carcinogenesis of colon

TO THE EDITOR Bitter gourd （Momordica charantia）, has received widespread attention in the scientific community due to its beneficial effects, including anti-diabetic, anti-cancer and anti- inflammatory effects in laboratory studies. However, a well-defined mechanism by which this important plant food exerts its beneficial effects has not been elucidated. We present some of the latest findings on the plant＇s effects against colon cancer.

INTRACELLULAR REDISTRIBUTION OF CARDIAC ENDOTHELIN- 1 RECEPTOR IN RAT DURING MYOCARDIAL HYPERTROPHY

Objective. In a model of rat cardiac hypertrophy, the changes in the distribution of ET- 1 receptors in two subcellular fractions, the sarcolemma and the light vesicles during myocardial hypertrophy were studied. Methods. Cardiac hypertrophy was produced by placing a constricting clip around the suprarenal abdominal aorta of rats, and ET- 1 receptor was assayed with radioactive analysis method. Results. It was found that plasma and ventricular ET- 1 levels increased significantly on week 2 and week 4 of pressure overload. ET- 1 binding studies showed that during myocardial hypertrophy, the maximum binding capacity (Bmax) was increased by 41％ (P< 0.01) and 65％ (P< 0.01) in sarcolemma in H- 2 week and H- 4 week groups, but was decreased by 24％ (P< 0.01) and 21％ (P< 0.01) in light vesicles. The sum of Bmax of sarcolemmal and light vesicle fractions was increased by 33％ (P< 0.01) and 57％ (P< 0.01) in group H- 2 week and H- 4 week, respectively. Conclusion. ET- 1 receptors in rat heart were externalized from light vesicles to sarcolemma, which may contribute to the development of myocardial hypertrophy.

The Mechanism of Henipavirus Fusion:Examining the Relationships between the Attachment and Fusion Glycoproteins

The henipaviruses,represented by Nipah virus and Hendra virus,are emerging zoonotic viral pathogens responsible for repeated outbreaks associated with high morbidity and mortality in Australia,Southeast Asia,India and Bangladesh. These viruses enter host cells via a class I viral fusion mechanism mediated by their attachment and fusion envelope glycoproteins;efficient membrane fusion requires both these glycoproteins in conjunction with specific virus receptors present on susceptible host cells. The henipavirus attachment glycoprotein interacts with a cellular B class ephrin protein receptor triggering conformational alterations leading to the activation of the viral fusion(F) glycoprotein. The analysis of monoclonal antibody(mAb) reactivity with G has revealed measurable alterations in the antigenic structure of the glycoprotein following its binding interaction with receptor. These observations only appear to occur with full-length native G glycoprotein,which is a tetrameric oligomer,and not with soluble forms of G(sG) ,which are disulfide-linked dimers. Single amino acid mutations in a heptad repeat-like structure within the stalk domain of G can disrupt its association with F and subsequent membrane fusion promotion activity. Notably,these mutants of G also appear to confer a post-receptor bound conformation implicating the stalk domain as an important element in the G glycoprotein's structure and functional relationship with F. Together,these observations suggest fusion is dependent on a specific interaction between the F and G glycoproteins of the henipaviruses. Further,receptor binding induces measurable changes in the G glycoprotein that appear to be greatest in respect to the interactions between the pairs of dimers comprising its native tetrameric structure. These receptor-induced conformational changes may be associated with the G glycoprotein's promotion of the fusion activity of F.

Individual aortic baroreceptors are sensitive to different ranges of blood pressures

Many receptors,including thermal receptors and mechanical receptors,are only activated by stimuli within a clearly defined range of intensities.Differences in the receptive ranges enable individual receptors and their sensory centers to precisely detect the intensity of the stimulus and changes in intensity.Baroreceptors are the sensory terminals of the baroreflex.It is well understood that an increasing number of baroreceptors are recruited to produce afferent action potentials as the blood pressure increases,indicating that individual baroreceptors have different pressure thresholds.The present study revealed that individual baroreceptors could stop their afferent signals when the blood pressure exceeds a certain level,indicating that individual baroreceptors are sensitive to a specific range of blood pressure.The receptive ranges of individual baroreceptors differ in terms of the total range,the lower threshold,and the upper threshold.Of 85 baroreceptors examined in this study,the upper thresholds for about half were within the physiological blood pressure range.These results indicate that supraphysiological blood pressure is unlikely to be encoded by the recruitment of more baroreceptors.Instead,supraphysiological blood pressure levels might be signaled by an increase in the frequency of action potentials or by other mechanisms.In conclusion,our results indicate that rabbit baroreceptors are activated by blood pressure levels within specific receptive ranges.These findings should encourage further studies to examine the role of population coding of blood pressure by baroreceptors in the baroreflex.

In Situ Dissimilatory Nitrate Reduction to Ammonium in a Paddy Soil Fertilized with Liquid Cattle Waste

Most studies on dissimilatory nitrate reduction to ammonium （DNRA） in paddy soils were conducted in the laboratory and in situ studies are in need for better understanding of the DNRA process. In this study, in situ incubations of soil DNRA using ^15N tracer were carried out in paddy fields under conventional water （CW） and low water （LW） managements to explore the potential of soil DNRA after liquid cattle waste （LCW） application and to investigate the impacts of soil redox potential （Eh） and labile carbon on DNRA. DNRA rates ranged from 3.06 to 10.40 mg N kg 1 dry soil d-1, which accounted for 8.55%-12.36% and 3.88% 25.44% of consumption of added NO3-^15N when Eh at 5 cm soil depth ranged from 230 to 414 mV and -225 to -65 mV, respectively. DNRA rates showed no significant difference in paddy soils under two water managements although soil Eh and/or dissolved organic carbon （DOC） were more favorable for DNRA in the paddy soil under CW management 1 d before, or 5 and 7 d after LCW application. Soil DNRA rates were negatively correlated with soil Eh （P 〈 0.05, n = 5） but positively correlated with soil DOC （P 〈 0.05, n - 5） in the paddy soil under LW management, while no significant correlations were shown in the paddy soil under CW management. The potential of DNRA measured in situ was consistent with previous laboratory studies; and the controlling factors of DNRA in paddy soils might be different under different water managements, probably due to the presence of different microfioras of DNRA.