RIG-I-like receptors (RLRs) belong to pattern recognition receptors, which perform significant roles in antiviral responses. RLRs can initiate a cascade of signaling transduction that induces the production of type I interferon and activates the interferon signaling pathway, ultimately resulting in antiviral responses. In the course of evolution, viruses have been constantly counteracting host immune systems to facilitate their own survival and replication, and have developed a set of antagonistic strategies. These mainly comprise elusion, disguise and attack strategies to eliminate the activation of RLRs. In virus-infected cells, RLRs recognize viral RNA and then induce antiviral responses. A better understanding of viral antagonistic strategies against RLRs will provide insights into the development of new antiviral medicines. This mini-review concludes that there are three main antagonistic strategies by which RNA viruses can counteract the activation of the RLRs pathway. It aims to provide references and insights for similar studies on viral antagonism in an array of RNA viruses.
DEAD Box Protein 58 ; DEAD-box RNA Helicases ; genetics ; immunology ; Host-Pathogen Interactions ; Humans ; RNA Viruses ; genetics ; immunology ; physiology ; RNA, Double-Stranded ; genetics ; immunology ; RNA, Viral ; genetics ; immunology ; Virus Diseases ; genetics ; immunology ; virology

OBJECTIVETo explore the antitumoral effect of indirubin on androgen-independent prostate cancer PC-3 cells and its possible mechanisms.

METHODSWe measured the inhibitory effect of indirubin on the proliferation of prostate cancer PC-3 cells using MTT assay, detected their cell cycles by flow cytometry, and determined the expressions of the cell cycle regulatory protein cyclin D1 and its related downstream gene c-myc by Western blot.

RESULTSThe viability of the PC-3 cells was significantly decreased by indirubin in a concentration-dependent manner, reduced to 52. 2% and 13. 6% at 5 and 10 µmol/L, respectively. The cell cycle of the PC-3 cells was markedly inhibited by indirubin at 5 µmol/L, with the cells remarkably increased in the G0 and G1 phases and decreased in the S and G2/M phases. Meanwhile, indirubin also inhibited the expressions of cyclin D1 and c-myc in the Wnt signaling pathway.

CONCLUSIONIndirubin can suppress the proliferation of androgen-independent prostate cancer PC-3 cells, which may be associated with its inhibitory effect on the cell cycle and Wnt signaling pathway.

Antibiotics, Antineoplastic ; administration & dosage ; pharmacology ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cell Survival ; drug effects ; Coloring Agents ; Cyclin D1 ; metabolism ; Dose-Response Relationship, Drug ; Genes, myc ; Humans ; Indoles ; administration & dosage ; pharmacology ; Male ; Prostatic Neoplasms, Castration-Resistant ; drug therapy ; pathology ; Proto-Oncogene Proteins c-myc ; metabolism ; Tetrazolium Salts ; Thiazoles

Objective To explore the effect of the open and closed endotracheal suction on the infection prevention and control among adults after cardiac surgery.Methods Totals of 159 patients after cardiac surgery with mechanical ventilation were randomly divided into the closed suction group (n =77 ) and the open suction group (n =82).There was no significantly difference in the average ages,gender composition,disease composition between two groups.The white blood cell (WBC) count of two groups in the day and the first,second and third days after surgery,the positive rate of sputum culture before extubation,and total duration time of mechanical ventilation of two groups were observed and compared,respectively.Results The WBC count of closed suction group in the day and the first day was ( 10.42 ± 3.81 ) × 109/L,( 12.03 ± 3.87 ) × 109/L and that of the open suction group was (9.44 ± 3.36) × 109/L,( 11.32 ± 3.59) × 109/L,and the difference was no statistically significant( P ＞0.05 ).There was significantly difference in the WBC between closed suction group and open suction group in second and third days after surgery[ (16.14±5.78) × 109/L vs (14.81 ±3.68) × 109/L),( 15.09 ± 5.91 ) × 109/L vs ( 12.65 ± 3.18 ) × 109/L;t =- 2.044,- 2.409,respectively; P ＜ 0.05 ) ].The positive rate of sputum culture showed no difference between closed suction group and open suction group ( 12.2％ vs 10.4％ ; x2 =0.129,P ＞ 0.05 ),and the total mechanical ventilation time of the closed suction group was significantly longer than that of the open suction group [ ( 14.48 ± 4.71 ) h vs ( 12.15 ± 4.47 ) h ;t =2.994,P ＜ 0.05 ) ].Conclusions The effect of open endotracheal suction is better than closed suction in the mechanical ventilation patients after cardiac surgery,and it is not expensive than closed suction for the patients with short period mechanical ventilation.

Adult ; Female ; Hepatitis ; pathology ; Humans ; Liver ; pathology ; physiopathology ; Male ; Shock ; mortality ; pathology ; physiopathology ; Survival Rate

OBJECTIVETo express the domain III of DENV II envelop protein in Escherichia coli, obtain the purified recombinant protein and identify its immunoreactivity.

METHODSSuckling mice were inoculated with live DENV II in the brain. The total RNA was extracted from the brain of the infected mice, and the envelope protein DNA fragment was amplified by RT-PCR and ligated into pMD 18-T to construct pMD 18-T-DV2-E. The domain III DNA fragment of the envelope protein was amplified by PCR with pMD 18-T-DV2-E as the template and cloned into pET-32a(+) to construct the expression plasmid pET-32a(+)-DV2-E-DIII. The recombinant plasmid was transformed into E.coli BL21(DE3) and induced by IPTG, and the expressed products were analyzed by SDS-PAGE and Western blotting.

RESULTSAfter RT-PCR amplification, a specific DNA fragment of about 1.5 kb was obtained and ligated into pMD 18-T to construct pMD 18-T-DV2-E. With pMD 18-T-DV2-E as the template, the domain III DNA fragment about 320 bp in length was amplified and the expression plasmid pET-32a(+)-DV2-E-DIII was successfully constructed. After induction with IPTG, a specific soluble protein with a relative molecular mass of 29000 was obtained and the expression product accounted for 52.50 percent; of the total protein of the cell lysate. Western blotting demonstrated reactivity of the recombinant protein with His-Tag McAb and DENV (Type I-IV) McAb.

CONCLUSIONThe recombinant plasmid can be highly expressed in E.coli BL21(DE3) in a soluble form and the recombinant protein can react with DENV (Type I-IV) McAb.

Animals ; Dengue Virus ; genetics ; isolation & purification ; Escherichia coli ; metabolism ; Genetic Vectors ; Mice ; Mice, Inbred Strains ; Plasmids ; Protein Interaction Domains and Motifs ; Viral Envelope Proteins ; genetics ; isolation & purification

Objective To describe the trend of overall mortality and major causes of death in Shandong population from 1970 to 2005,and to quantitatively estimate the influential factors.Methods Trends of overall mortality and major causes of death were described using indicators such as mortality rates and age-adjusted death rates by comparing three large-scale mortality surveys in Shandong province.Difference decomposing method was applied to estimate the contribution of demographic and nondemographic factors for the change of mortality.Results The total mortality had had a slight change since 1970s,but had increased since 1990s.However,both the mortality rates of age-adjusted and age-specific decreased significantly.The mortality of Group Ⅰ diseases including infectious diseases as well maternal and perinatal diseases decreased drastically.By contrast,the mortality of non-communicable chronic diseases (NCDs)including cardiovascular diseases(CVDs),cancer and injuries increased.The sustentation of recent overall mortality was caused by the interaction of demographic and non-demographic factors which worked oppositely.Non-demographic factors were responsible for the decrease of Group Ⅰ disease and the increase of injuries.With respect to the increase of NCDs as a whole.demographic factors might take the full responsibility and the non-demographic factors were the opposite force to reduce the mortality.Nevertheless,for the increase of some leading NCD diseases as CVDs and cancer,the increase was mainly due to non-demographic rather than demographic factors.Conclusion Through the interaction of the aggravation of ageing population and the enhancement of non-demographic effect,the overall mortality in Shandong would maintain a balance or slightly rise in the coming years.Group Ⅰ diseases in Shandong had been effectively under control.Strategies focusing on disease control and prevention should be transferred to chronic diseases,especially leading NCDs,such as CVDs and cancer.

Objective:To summarize and analyze the practice of the local practice on covering drugstore bills by pooled funds of basic medical insurance,and provide a reference for improving relevant policies.Methods:The medical insurance policies from various provinces,municipalities,autonomous regions,and coordination areas were systematically retrieved.ROST CM6 software was applied to analyze the high-frequency words and semantic network of the policy text,and combined with the interview and field investigation resultss,the key dimensions of the policy practice were identified and summarized.Then the regional differences,existing problems,and their causes were analyzed to put forward policy recommendations.Result:The selection of pharmacies covered in the payment system with outpatient expenses reimbursed by the pooled fund,the formulation of drug reimbursement list,the design of benefit plans,the management of drug prices and payments,and the supervision of hospital outflow prescriptions were five key dimensions of policy practice.There were significant differences in practice among different regions,and the problems mainly included the overall arrangement of covering pharmacies in the payment system,the mechanism of drug prices in pharmacies,and the coordination with other medical insurance policies.Conclusion:To improve the convenience of buying drugs for the insured,it is necessary to make full use of the advantages of pharmacies to meet the demand for outpatient medicine,promote the transparency of drug prices in pharmacies,coordinate the relevant medical insurance policies,strengthen the collaborative management between the healthcare security administration and relevant departments such as the health commission and the medical products administration,analyze and evaluate the potential effects of policy measures,and adjust policy measures promptly according to local conditions.

Objective To investigate the characteristics of radiation-induced optic neuropathy (RON) in patients with nasopharypgeal carcinoma after radiotherapy,and explore its risk factors.Methods A retrospective study was performed on the clinical data of 22 RON patients with nasopharyngeal carcinoma after radiotherapy,admitted to our hospital from January 1997 to January 2011.Their clinical manifestations,eye examinations and cranial MRI data were concluded.Results Visual deterioration,or even,blindness,was the most common manifestation.RON occurred after the initial radiotherapy in 18 cases,and during the initial radiotherapy in 2 cases.And 2 cases developed RON in re-irradiation for recurrences.Blindness developed in 8 eyes,and decreased vision occurred in 27 eyes; 14 patients displayed retinal optic nerve atrophy in the eye examinations.Typical radiological imaging of the skull showed optic nerve enlargement in 30 eyes,optic nerve atrophy in 5 eyes; and the incidence of optic neuropathy was high when radiation dose was over 70 Gy.Conclusion RON may occur in nasopharyngeal carcinoma patients following radiotherapy,having vision disorders,visual field changes,abnormal visual evoked potential and typical cranial imaging performances; the occurrence of RON may be correlated with radiation field and radiation dose; routine eye and imaging examination is of great significance.

OBJECTIVE: In order to improve accuracy and reliability of forensic diagnosis of sudden cardiac death, pathogenesis and relationship between the viral myocarditis (VMC) and dilated cardiomyopathy (DCM) were investigated. METHODS: Improved immunohistochemical technique was used to detect the expression of the CAR in myocardium samples, including 22 deceased with VMC, 20 deceased with DCM and 16 control deceased. RESULTS: The brown staining on the cell membrane of myocardium showed positive result. There was a prominent CAR expression in VMC group and DCM group, which were statistically significant difference compared with control group (P < 0.05). CONCLUSION The CAR expression showed significantly higher in VMC and DCM groups. The viral infection can result in myocardial necrosis and impaired cardiac functions. These abnormalities can trigger a cascade of events that contributed to the progress of VMC to DCM.
Cardiomyopathy, Dilated/pathology* ; Case-Control Studies ; Coxsackie and Adenovirus Receptor-Like Membrane Protein ; Coxsackievirus Infections/complications* ; Death, Sudden, Cardiac ; Female ; Forensic Pathology ; Humans ; Immunohistochemistry ; Male ; Myocarditis/virology* ; Myocardium/pathology* ; Receptors, Virus/metabolism* ; Staining and Labeling

Objective To investigate the impact of 5-fluorouracil (5-FU) on miR-22 expression in human hepato-cellular carcinoma (HCC) cell lines and to elucidate the molecular mechanism of 5-fluorouracil for HCC chemo-therapy. Methods Real-time PCR analysis was conducted to determine the expression levels of miR-22 in HCC tissue specimens and HCC cell lines. The expression of miR-22 and pri-miR-22 (primary miR-22) was evaluated in HepG2 and Huh7 cells with 5-FU treatment by using real-time PCR and we also performed Western blot analysis to detect the protein level of HDAC4 in HCC cells with the same treatment. A rescue assay was employed by using 5-FU treatment in combination with miR-22 inhibitor(Anti-22) to further investigate the correlation among 5-FU, miR-22,and HCC cell growth. Results miR-22 expression depicted a significant downregulation in HCC tissues and cell lines (P<0.01). 5-FU treatment led to an augment of miR-22 expression in HepG2 and Huh7 cells(P<0.001) and resulted in a decrease of HDAC4 protein levels, which was verified as a direct target of miR-22 in HCC cells (P<0.01). Conclusions 5-FU has suppressive effect on HCC growth which could be potentially ex-plained by miR-22-mediated HDAC4 axis.