Sepsis-associated myocardial injury, an invertible myocardial depression, is a common complication of sepsis. Neogambogic acid is an active compound in garcinia and exerts anthelmintic, anti-inflammatory, and detoxification properties.The role of neogambogic acid in sepsis-associated myocardial injury was assessed.Firstly, mice were pretreated with neogambogic acid and then subjected to lipopolysaccharide treatment to induce sepsis. Results showed that lipopolysaccharide treatment induced up-regulation of biomarkers involved in cardiac injury, including lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), and troponin I (cTnI).However, pretreatment with neogambogic acid reduced levels of LDH, CK-MB, and cTnI, and ameliorated histopathological changes in the heart tissues of septic mice.Secondly, neogambogic acid also improved cardiac function in septic mice through reduction in left ventricular end-diastolic pressure, and enhancement of ejection fraction, fractional shortening, and left ventricular systolic mean pressure. Moreover, neogambogic acid suppressed cardiac apoptosis and inflammation in septic mice and reduced cardiac fibrosis. Lastly, protein expression of p-p38, p-JNK, and p-NFκB in septic mice was decreased by neogambogic acid. In conclusion, neogambogic acid exerted anti-apoptotic, anti-fibrotic, and anti-inflammatory effects in septic mice through the inactivation of MAPK/NF-κB pathway.

A new coronavirus (SARS-CoV-2) has been identified as the etiologic agent for the COVID-19 outbreak. Currently, effective treatment options remain very limited for this disease; therefore, there is an urgent need to identify new anti-COVID-19 agents. In this study, we screened over 6,000 compounds that included approved drugs, drug candidates in clinical trials, and pharmacologically active compounds to identify leads that target the SARS-CoV-2 papain-like protease (PLpro). Together with main protease (M
Antiviral Agents/therapeutic use* ; Binding Sites ; COVID-19/virology* ; Coronavirus Papain-Like Proteases/metabolism* ; Crystallography, X-Ray ; Drug Evaluation, Preclinical ; Drug Repositioning ; High-Throughput Screening Assays/methods* ; Humans ; Imidazoles/therapeutic use* ; Inhibitory Concentration 50 ; Molecular Dynamics Simulation ; Mutagenesis, Site-Directed ; Naphthoquinones/therapeutic use* ; Protease Inhibitors/therapeutic use* ; Protein Structure, Tertiary ; Recombinant Proteins/isolation & purification* ; SARS-CoV-2/isolation & purification*

Objective:To investigate the effectiveness of scanning glucose monitoring system in dawn phenomenon of patients with type 2 diabetes mellitus (T2DM) based on continuous glucose monitoring system (CGMS) .Methods:A total of 45 patients with T2DM hospitalized in the Endocrine Department of Xinxiang Central Hospital from June 2019 to June 2020 were selected as the research subjects by convenience sampling method. All selected patients were asked to wear the scanning glucose monitoring system after admission, and then the CGMS for continuous glucose monitoring after 48 hours. The scanning glucose monitoring system and the CGMS were taken off at the same time after 72 hours. The blood glucose analysis report of the same period was checked to determine whether the dawn phenomenon occurred. The consistency to determine dawn phenomenon was analyzed between CGMS and scanning blood glucose monitoring by Kappa test. According to the CGMS judgment results, the receiver operating characteristic curve (ROC) of the scanning blood glucose monitoring system was drawn to evaluate the optimal tangent value of the night blood glucose for predicting dawn phenomenon and the next day fasting blood glucose for evaluating dawn phenomenon.Results:Among the 45 study subjects, there was no statistical difference in determining the incidence of dawn phenomena between CGMS and scanning glucose monitoring system [55.56% (25/45) vs. 46.67% (21/45) , χ 2=0.711, P>0.05]. Consistency analysis showed that Kappa value was 0.895, and the consistency of CGMS and scanning glucose monitoring system in judging dawn phenomenon was good (Kappa=0.895, 95% CI 1.130-4.883, P<0.01) . The optimal tangent value of night blood glucose for predicting dawn phenomenon was 8.31 mmol/L, and the optimal tangent value of the next day fasting blood glucose for evaluating dawn phenomenon was 7.25 mmol/L. The value of the area under the ROC curve were 0.729 and 0.803 respectively. Conclusions:Scanning blood glucose monitoring can accurately judge the dawn phenomenon. When the night blood glucose value is 8.31 mmol/L, it indicates that the dawn phenomenon may occur. When the next day's fasting blood glucose value is 7.25 mmol/L, it indicates that the dawn phenomenon may already occur.

Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide, such as the on-going outbreak of the novel coronavirus SARS-CoV-2. Herein, we identified two potent inhibitors of human DHODH, S312 and S416, with favorable drug-likeness and pharmacokinetic profiles, which all showed broad-spectrum antiviral effects against various RNA viruses, including influenza A virus, Zika virus, Ebola virus, and particularly against SARS-CoV-2. Notably, S416 is reported to be the most potent inhibitor so far with an EC of 17 nmol/L and an SI value of 10,505.88 in infected cells. Our results are the first to validate that DHODH is an attractive host target through high antiviral efficacy in vivo and low virus replication in DHODH knock-out cells. This work demonstrates that both S312/S416 and old drugs (Leflunomide/Teriflunomide) with dual actions of antiviral and immuno-regulation may have clinical potentials to cure SARS-CoV-2 or other RNA viruses circulating worldwide, no matter such viruses are mutated or not.
Animals ; Antiviral Agents ; pharmacology ; therapeutic use ; Betacoronavirus ; drug effects ; physiology ; Binding Sites ; drug effects ; Cell Line ; Coronavirus Infections ; drug therapy ; virology ; Crotonates ; pharmacology ; Cytokine Release Syndrome ; drug therapy ; Drug Evaluation, Preclinical ; Gene Knockout Techniques ; Humans ; Influenza A virus ; drug effects ; Leflunomide ; pharmacology ; Mice ; Mice, Inbred BALB C ; Orthomyxoviridae Infections ; drug therapy ; Oseltamivir ; therapeutic use ; Oxidoreductases ; antagonists & inhibitors ; metabolism ; Pandemics ; Pneumonia, Viral ; drug therapy ; virology ; Protein Binding ; drug effects ; Pyrimidines ; biosynthesis ; RNA Viruses ; drug effects ; physiology ; Structure-Activity Relationship ; Toluidines ; pharmacology ; Ubiquinone ; metabolism ; Virus Replication ; drug effects

Objective To analyze the effect of angiopoietin-like protein 4(ANGPTL4) on M2 macrophage differentiation.Methods The frequency of M2 macrophages in spleen of ANGPTL 4-/-mice and the controls was detected by flow cytometry.And the changes of M2 macrophages was measured by LPS stimulation.F4/80 + macrophages was separated by flow cytometry and treated with LPS or recombinant ANGPTL 4 protein.The secretion of IL-4 in CD4 + T cells was observed after purified macrophages after co-culture with CD4 + T cells by the flow-cytometric intracellular staining method.Results There was no significant difference in the frequency of M2 macrophages in ANGPTL 4-/-mice and controls.LPS stimulation did not affect the expression of M2 macrophages from ANGPTL 4-/-mice.The macrophages from ANGPTL 4/-mice did not promote differentiation of CD4 + T cells into Th2 cells.After co-culturing of macrophages and CD4 + T cells for 48 h in vitro,IL-4 secretion of CD4 + T cells was not changed.Conclusions ANGPTL4 has no effects on M2 macrophage differentiation.

Objective To analyze the effect of angiopoietin-like protein 4(ANGPTL4) on M2 macrophage differentiation.Methods The frequency of M2 macrophages in spleen of ANGPTL 4-/-mice and the controls was detected by flow cytometry.And the changes of M2 macrophages was measured by LPS stimulation.F4/80 + macrophages was separated by flow cytometry and treated with LPS or recombinant ANGPTL 4 protein.The secretion of IL-4 in CD4 + T cells was observed after purified macrophages after co-culture with CD4 + T cells by the flow-cytometric intracellular staining method.Results There was no significant difference in the frequency of M2 macrophages in ANGPTL 4-/-mice and controls.LPS stimulation did not affect the expression of M2 macrophages from ANGPTL 4-/-mice.The macrophages from ANGPTL 4/-mice did not promote differentiation of CD4 + T cells into Th2 cells.After co-culturing of macrophages and CD4 + T cells for 48 h in vitro,IL-4 secretion of CD4 + T cells was not changed.Conclusions ANGPTL4 has no effects on M2 macrophage differentiation.

Theandhave been the state-compiled textbooks of acupuncture-moxibustion in colleges and universities of TCM for nearly more than half a century, which play a regulating and guiding role for acupuncture education and to a certain extent represent the development status of this discipline. The indications included infrom 1th edition to 7th edition andfrom 1th edition to 3rd edition were analyzed in this study, which was aimed to basically reflect the current situation of acupuncture indications. As a result, it was found the inheritance and innovation of indications were both reflected in each edition of textbooks, 1/3 of which occurred repeatedly in more than half of the textbooks, and 1/3 of which occurred only once. The indications were classified by internal medicine, surgery, gynecology, dermatology, orthopedics, etc., which were not consistent with system classification of modern medicine such as digestive system, respiratory system, etc. The indications were mainly named after TCM disease names, involving only several names of western medicine diseases, which were contradicted to the names adopted from journals and literature. This inconformity of classification method and naming method between TCM and western medicine was not only a difficulty for modern acupuncture and moxibustion, but also an essential factor to hinder the development of acupuncture, therefore comparative study was needed in the future.

[ ABSTRACT] AIM:To investigate the relationship between morphological changes of autophagy and apoptosis in the PC12 cells induced by oxygen-glucose deprivation and reoxygenation .METHODS:The PC12 cells were randomly di-vided into normal control group , oxygen-glucose deprivation and reoxygenation group , autophagy inhibitor group and auto-phagy activator group .The cells in oxygen-glucose deprivation and reoxygenation group , autophagy inhibitor group and au-tophagy activator group were exposed to reoxygenation (12 h) after 3 h of oxygen-glucose deprivation, and autophagy inhib-itor 3-methyladenine and autophagy activator rapamycin were added into the cells at the same time .Using transmission elec-tron microscope and monodansylcadaverine fluorescence staining , the morphological changes of autophagosome were ob-served.The apoptosis of the PC12 cells were analyzed by flow cytometry with Annexin V-FITC/PI staining and TUNEL method.RESULTS: Compared with normal control group , the numbers of autophagosomes and the apoptotic rates in-creased in oxygen-glucose deprivation and reoxygenation group (P<0.05).Compared with oxygen-glucose deprivation and reoxygenation group , the numbers of autophagosomes decreased obviously ( P<0.05 ) and the apoptotic rates increased markedly in autophagy inhibitor group (P<0.05).The numbers of autophagosomes increased obviously (P<0.05), the apoptotic rates decreased markedly ( P<0.05 ) , the autophagosomes became bigger in size , and autolysosomes was also found in autophagy activator group .CONCLUSION: Oxygen-glucose deprivation and reoxygenation induce autophagy in PC12 cells, and autophagy inhibits cell apoptosis to play a protective role .