Aged, 80 and over ; Antibodies, Monoclonal ; metabolism ; Carcinoma, Squamous Cell ; metabolism ; pathology ; Diagnosis, Differential ; Granuloma ; metabolism ; pathology ; Humans ; Keratins ; immunology ; Male ; Mucin-1 ; metabolism ; Skin Neoplasms ; metabolism ; pathology

Currently, clinically used drugs for the treatment of gout inflammation, such as colchicine, nonsteroidal anti-inflammatory drugs, and glucocorticoids, can only relieve the pain of joint inflammation and have severe hepatorenal toxicity and multiple organ adverse reactions. The NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome is a key complex that induces the onset of gout inflammation and has become a crucial target in the development of anti-gout drugs. This article reviews the research progress of anti-gout small molecules targeting the NLRP3 inflammasome and their bioactivity evaluation methods in the past five years, in order to provide information for the development of specific drugs for the treatment of gout inflammation.

OBJECTIVETo observe the effect of Feiyanning Granule (FYN) on tumor growth and cell cycle distribution in mice with Lewis lung cancer, as well as its influence on G1/S cell cycle checkpoint dominating signaling RB-E2F1 bio-axis.

METHODSModeled C57BL/6 mice were randomly divided into 6 groups: the model group (A), the DDP treated group (B) peritoneally injected with cisplatin 0.1 mg on d1, d3 and d5 after modeling, and the 4 FYN treated groups (C-F), administered via gastrogavage with FYN Decoction, and FYN Granule in small-, median- and high- dose respectively for 14 days. The tumour inhibiting rate, tumour weight, and body weight of mice were observed after treatment; cell cycle distribution was detected by flow cytometry (FCM), RB-E2F1mRNA expressions in tumour tissue were analyzed by RT-PCR, and their protein expressions by Western blot.

RESULTSTumour weight in the 5 treated groups was lower than that in the model group (P < 0.05, P < 0.01). Body weight in group E was significantly higher than that in group A and B (P < 0.05, P < 0.01). FCM analysis showed the proportion of G0/G1 phase was higher in group E than in group A, B and C (P < 0.01), and cancer cell proliferation index (PI) in group E was lower than in group B (P < 0.05, P < 0.01). RT-PCR showed mRNA level of E2F1 was lower, but that of RB was significantly higher in group E than those in group A, B and C respectively (P < 0.01). Westem blot analysis showed the protein expression of E2F1 was lower in group E and B than that in group A (P < 0.05), while the protein expression of Rb in group E was higher than that in group A, B and C (P < 0.05).

CONCLUSIONThe effect of FYN in inhibiting Lewis lung cancer growth was related to its intervention on cancer cell cycle distribution which blocks most tumor cells in G0/G1 phase. Moreover, FYN can reduce MDM2 expression, enhance P53 expression to influence cell cycle G1/S checkpoint dominating signaling, so as to achieve the effect of antagonizing lung cancer cell proliferation.

Animals ; Carcinoma, Lewis Lung ; metabolism ; pathology ; Cell Cycle Checkpoints ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Male ; Mice ; Mice, Inbred C57BL ; Signal Transduction ; drug effects

BACKGROUNDTo determine the antigenicity of recombinant hepatitis E virus ORF2 (rHEV ORF2) protein expressed in Pichia pastoris (P. pastoris).

METHODSBy using the rHEV ORF2 protein from E.coli as control, an indirect ELISA was adopted to identify the sensitivity, specificity and stability of rHEV ORF2 protein from P. pastoris in detection of HEV IgM and IgG antibody in sera from patients with hepatitis E. The reactivity of the rHEV ORF2 against 5 HEV ORF2 monoclonal antibodies (McAbs) was also tested.

RESULTSThe minimum concentration of coated antigen with which HEV IgG could be detected was 12.5 ng/ml, while the highest serum dilution to detect both IgM and IgG antibodies against HEV was 1:5 120. No cross-reaction was found with sera from patients with any other types of hepatitis. The 37 degree C acceleration test showed that the rORF2 was highly stable within 12 months at 4 degrees C. The 5 HEV ORF2 McAbs showed better reaction with the rORF2 from P. pastoris, especially that 4B2, 2E2, whose reaction against the rORF2 were 125 and 25 times respectively higher than that of rORF2 from E.Coli.

CONCLUSIONThere may be more extensive conformational epitopes in the rHEV ORF2 from P. pastoris. The excellent antigenicity, sensitivity and stability suggest that it can be served as a new candidate antigen for the development of diagnostic reagents of hepatitis E.

Gene Expression ; Hepatitis Antibodies ; blood ; Hepatitis Antigens ; genetics ; immunology ; Hepatitis E ; immunology ; Hepatitis E virus ; genetics ; immunology ; Humans ; Pichia ; genetics ; metabolism ; Recombinant Proteins ; genetics ; immunology ; Viral Proteins ; genetics ; immunology

Human immunodeficiency virus type 1 (HIV-1) viral infectivity factor (Vif), one of the accessory proteins, which is a small basic phosphoprotein, is essential for viral replication and pathogenesis. The best well-characterized function of Vif is its ability to neutralize the host cell antiviral factor, apolipoprotein B mRNA editing enzyme catalytic polypeptide like 3G (APOBEC3G), which makes the viral particles more infective. In addition, Vif can regulate the reverse transcription and the advanced stage of replication of the virus particle, as well as induce the termination of cell cycle at G2 stage and so on. The designed drug aimed directly at Vif can efficiently block the maturation and infectivity of HIV-1. In this review, the structure, function and especially the related inhibitors of Vif are reviewed.
APOBEC-3G Deaminase ; Amino Acid Sequence ; Anti-HIV Agents ; pharmacology ; Cytidine Deaminase ; metabolism ; Ethylenediamines ; pharmacology ; HIV-1 ; physiology ; Humans ; Reverse Transcription ; Virus Replication ; vif Gene Products, Human Immunodeficiency Virus ; antagonists & inhibitors ; genetics ; metabolism ; physiology

This study is to investigate the effect of rhein lysinate on inducing human breast cancer cell line SK-Br-3 apoptosis and the role of HER-2 signal pathway in the apoptosis. MTT assay was used to detect SK-Br-3 cell proliferation. Cell cycle and apoptosis were analyzed by flow cytometry. The protein expression and the protein phosphorylation of HER-2 signal pathway were detected by Western blotting. The level of HER-2 mRNA was detected by RT-PCR and the level of HER-2 expression was also detected by immunofluorescence cytochemical methods. The results showed that rhein lysinate remarkably inhibited breast cancer SK-Br-3 cell proliferation. The IC50 value for 48 h treatment was 85 micromol x L(-1). Apoptosis in SK-Br-3 cells was induced by rhein lysinate in a dose dependent manner. The protein expressions of HER-2, NF-KB, and the protein phosphorylation of HER-2 were downregulated, however the protein expression of p53 and p21 was upregulated after rhein lysinate treatment. The level of HER-2 mRNA decreased by using RT-PCR assay and the level of HER-2 expression was also decreased by using immunofluorescence cytochemical assay after rhein lysinate treatment. It can be concluded that rhein lysinate could inhibit SK-Br-3 cell proliferation and induce apoptosis. HER-2/NF-kappaB/p53/p21 signal pathway might be involved in this process. Rhein lysinate has a good prospect to be an adjuvant chemotherapeutic drug.
Anthraquinones ; pharmacology ; Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Breast Neoplasms ; metabolism ; pathology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cyclin-Dependent Kinase Inhibitor p21 ; metabolism ; Female ; Humans ; Inhibitory Concentration 50 ; Lysine ; pharmacology ; NF-kappa B ; metabolism ; RNA, Messenger ; metabolism ; Receptor, ErbB-2 ; genetics ; metabolism ; Signal Transduction ; Tumor Suppressor Protein p53 ; metabolism

OBJECTIVETo evaluate the influence of glucose-insulin-potassium treatment (GIK) on the levels of inflammatory cytokines in the scalded rats with MODS.

METHODSOne hundred and twenty Sprague Dawley rats were inflicted with 30% TBSA full-thickness scalding, and MODS model was reproduced with intraperitoneal injection of endotoxin following burn injury. Then the rats were randomly divided into GIK, glucose (G) and control (C) groups, with 40 rats in each group. The serum contents of glucose, lactate acid, TNF-alpha, NO and IL-6 of the rats in the three groups were determined during 1 to 7 PSD, and the mortality rate within 7 PSD was observed.

RESULTSThe serum contents of glucose, lactate acid, TNF-alpha, NO and IL-6 of the rats in the GIK group were obviously lower than those in the other two groups during 1 to 7 PSD (P < 0.01), and reached the lowest level at 6 to 7 PSD (TNF-alpha: 2.37 +/- 0.54 microg/L; IL-6: 0.28 +/- 0.17 microg/L; NO: 29 +/- 9 micromol/L). The content of glucose and lactate acid in G group were obviously higher than those in control group (P < 0.01), but the contents of TNF-alpha, IL-6 and NO content were similar between these two groups (P > 0.05). The mortality in GIK group within 7 PSD was 20.0%, which was evidently lower than that in G (37.5%) and C (47.5%) groups (P < 0.05), while that between G and C groups was similar (P > 0.05).

CONCLUSIONThe administration of GIK might ameliorate sepsis by reducing the levels of inflammatory cytokine after burns and endotoxin challenge.

Animals ; Blood Glucose ; metabolism ; Burns ; complications ; diagnosis ; metabolism ; Cytokines ; metabolism ; Disease Models, Animal ; Glucose ; therapeutic use ; Insulin ; therapeutic use ; Lactic Acid ; blood ; Multiple Organ Failure ; diagnosis ; etiology ; metabolism ; Potassium ; therapeutic use ; Prognosis ; Rats ; Rats, Sprague-Dawley

[Objective]To investigate the effect of GRACE scores on prediction of 30-day cardiovascular adverse events in acute chest pain patients.[Methods]A prospective,observational analysis was conducted in the patients with acute chest pain in Emergency Department(ED)from January 1,2016 through April 1,2016.Data including characteris-tics and GRACE scores were collected.All causes leading to MACE were followed up at 30th day after the onset of acute chest pain.[Results]Among a total of 209 patients presenting with acute chest pain enrolled in this study,110 were male (52.63%)and 99 were female(47.37%).The range of age was 20-98years old,and mean age was(65.28±16.85)years old.During follow-up period,12 patients had MACE,2 patients died in ED,3 patients died in hospital,6 patients died out of hospital,and 1 person was diagnosed with myocardial infarction. When compared with non-MACE group,factors including age,BMI,hospitalized patient number,and number of patients admitted in CCU as well as GRACE scores, were significantly higher in MACE group(P<0.05). The predictive ROC curve area of GRACE scores in 30-day MACE was 0.819(0.735 to 0.902). The optimal sensitivity and specificity were 0.92 and 0.65,respectively. The probability of 30-day cardiovascular adverse events in various GRACE score risk stratification was 0.95%(low-risk),6.67%(medi-um-risk),and 18.92%(high-risk),respectively.[Conclusion]The GRACE score was a useful predictor to the occur-rence of 30-day cardiovascular adverse events in acute chest pain patients.

A 47-year-old man presented with a scrotal swelling. Ultrasonography of the testes showed that it was an extratesticular swelling. However, the swelling was intraoperatively found to be intratesticular. Histology showed an intratesticular leiomyoma, which is extremely rare.
Diagnosis, Differential ; Humans ; Leiomyoma ; diagnosis ; diagnostic imaging ; surgery ; Male ; Middle Aged ; Scrotum ; pathology ; Testicular Neoplasms ; diagnosis ; diagnostic imaging ; surgery ; Treatment Outcome ; Ultrasonography

To construct gene vaccine of PPV and to investigate the effects of interleukin 2 (IL-2) as an adjuvant on immune responses in mouse, the recombinant expression plasmid of pCIneo-IL2-VP2 was constructed and transfected into PK-15 cells by lipofectamine, the expressed product was detected by immunofluore assay. To study the immune effects of DNA vaccine in vitro and in vivo, mice were used as the animal model. The recombinant plasmid pCIneo-IL2-VP2, the control plasmid pCI-neo and the PPV live vaccine were immunized by intramuscular injection. Anti-PPV antibodies were measured by ELISA, lymphocyte proliferation activity was detected using MTT method, and the specific killing activities of CTL were assayed too. The results show that the immunized mice produced PPV antibody after one week, and reached to highest after four weeks. Compared with the control group, the pCIneo-IL2-VP2 immunized group produced significant differences in the antibody titers, the lymphocyte proliferation activity and the specific killing activities of CTL. The pCIneo-IL2-VP2 induced humoral and cellular immunity responses similarly to that the live vaccine induced. These results manifested that the PPV DNA vaccine successfully induced humoral and cellular immunity response in mice with the IL-2 gene as an adjuvant.
Adjuvants, Immunologic ; genetics ; Animals ; Antibodies, Viral ; blood ; Antigens, Viral ; genetics ; immunology ; Capsid Proteins ; genetics ; immunology ; Escherichia coli ; genetics ; metabolism ; Genetic Vectors ; Immunization ; Interleukin-2 ; genetics ; immunology ; Mice ; Parvovirus, Porcine ; genetics ; immunology ; Random Allocation ; Recombinant Fusion Proteins ; genetics ; immunology ; T-Lymphocytes, Cytotoxic ; immunology ; Transfection ; Vaccines, DNA ; immunology ; Viral Vaccines ; immunology