Molecular Mechanism of "Transmission Between Lung and Brain" of Influenza and Intervention Effect of Maxing Shigantang Based on JAK1/STAT1 Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo explore the molecular mechanism of "transmission between the lung and brain" of influenza based on Janus kinase 1/signal transducer and activator of transcription 1（JAK1/STAT1） signaling pathway and further investigate the intervention effect of Maxing Shigantang （MXSGT）. MethodA total of 100 SPF BALB/c mice were randomly divided into a normal group，a model group，an oseltamivir group （21.63 mg·kg-1·d-1），an antiviral granules group（3.9 g·kg-1·d-1）， and an MXSGT group（6.05 g·kg-1·d-1）， with 20 mice in each group. The pneumonia model was induced in mice except for those in the normal group by intranasal infection of influenza A virus（IAV）. Twenty-four hours after modeling，mice were treated with corresponding drugs， while those in the normal group and the model group received the same amount of normal saline by gavage， once a day for 3 and 7 days. The pathological changes in the lung and brain were observed by hematoxylin-eosin（HE）staining. The mRNA expression of IAV nucleoprotein（NP），JAK1， and STAT1 in the lung and brain was detected by real-time quantitative polymerase chain reaction（Real-time PCR）， and the protein expression of JAK1 and STAT1 in the lung and brain was detected by Western blot. Immunohistochemical method was used to detect the expression of phosphorylated（p）-STAT1 in the lung and brain tissues， and enzyme-linked immunosorbent assay（ELISA） was used to detect the serum levels of interleukin-1β（IL-1β） and interleukin-10（IL-10）. ResultCompared with the normal group， the model group showed obvious pathological changes in the lung tissues and cerebral cortex， increased relative mRNA expression of IAV NP in the lung （P<0.01）， elevated mRNA and protein expression of JAK1 and STAT1 in the lung and brain tissues （P<0.05，P<0.01），up-regulated expression level of p-STAT1 in lung tissues and cerebral cortex （P<0.05，P<0.01）， and increased serum level of IL-1β （P<0.05）. Compared with the model group， the MXSGT group showed alleviated pathological damage to lung tissues and cerebral cortex， decreased relative mRNA expression of IAV NP in lung tissues（P<0.01），reduced mRNA and protein expression levels of JAK1 and STAT1 in lung tissues and brain tissues（P<0.05，P<0.01）， and increased serum level of IL-10（P<0.01）. ConclusionThe abnormal activation of the JAK1-STAT1 signaling pathway may be one of the molecular mechanisms of "transmission between the lung and brain" of influenza. As an effective compound prescription against the influenza virus，MXSGT can alleviate the pathological damage of brain tissues in mice infected with IAV by regulating the level of cytokines mediated by this pathway.

Effect mechanism of Ma Xing Gan Shi Decoction against influenza virus from JAK2/STAT3 signaling pathway by combining network pharmacology / 中国药理学通报

Aim To explore the effect of JAK2/STAT3 signaling pathway on lung tissue injury induced by influenza A virus in combination with network pharmacology and to further explore the intervention effect of Ma Xing Gan Shi Decoction.Methods Network pharmacological method was used to screen the signal pathway enriched by Ma Xing Gan Shi Decoction on the potential target of influenza virus.BLAB/c mice were intranasally infected with influenza A virus.The mice were divided into normal control group, model control group, oseltamivir group, antiviral granule group and Ma Xing Shigan decoction group.The animals were treated with corresponding drugs for 3 and 7 days.Body weight and lung index were detected by HE for observation of the pathological changes of lung tissues.Real-time PCR(RT-PCR)was used to detect the mRNA expression levels of JAK2, STAT3, IL-1β and IL-4 in lung tissues.Western blot and ELISA were used to detect the protein expression levels of JAK2, STAT3, IL-1β and IL-4 in lung tissues.AutoDock Vina software was used to conduct molecular docking between STAT3 and target compounds.Results The main active components of Ma Xing Gan Shi Decoction had 110 intersection targets with influenza virus and were enriched in 170 signaling pathways.Ma Xing Shigan decoction could up-regulate the body weight of mice infected with influenza A virus, improve the pathological injury of lung tissues, down-regulate the lung index and the expression levels of JAK2, STAT3, IL-1β mRNA and protein in lung tissues, and up-regulate the expression levels of IL-4 mRNA and protein.STAT3 had better binding activity with glycyrrhiza chalcone A, an active compound in Ma Xing Gan Shi Decoction.Conclusions Ma Xing Gan Shi Decoction, as an effective compound prescription of traditional Chinese medicine against influenza virus, can effectively reduce pulmonary inflammation and regulate the balance of cytokines.The possible mechanism is to alleviate the lung injury caused by influenza A virus infection in mice by inhibiting the activation of JAK2/STAT3 signal pathway.

Theoretic analysis on twirling acupuncture manipulation for reinforcing and reducing in treatment of hypertension by academician / 中国针灸

The paper explains academician

Study on material base of Ligusticum wallichii for treating brain ischemia and its molecular mechanism based on molecular docking / 中国中药杂志

To explore the effective ingredients and mechanism of Ligusticum wallichii in treating brain ischemia. Four brain ischemia-related target proteins were selected in the joint screening for the 45 component in L. wallichii reported in literatures based on molecular docking by reference to the corresponding drugs in the market. According to the docking results, multiple components in L. wallichii, such as phthalides, were superior to the corresponding drugs in the market, suggesting that they may be the major effective components in L. wallichii for treating brain ischemia. The method can be used to study the material base and molecular mechanism of traditional Chinese medicines.

Study on action mechanism and material base of compound Danshen dripping pills in treatment of carotid atherosclerosis based on techniques of gene expression profile and molecular fingerprint / 中国中药杂志

Action mechanism and material base of compound Danshen dripping pills in treatment of carotid atherosclerosis were discussed based on gene expression profile and molecular fingerprint in this paper. First, gene expression profiles of atherosclerotic carotid artery tissues and histologically normal tissues in human body were collected, and were screened using significance analysis of microarray (SAM) to screen out differential gene expressions; then differential genes were analyzed by Gene Ontology (GO) analysis and KEGG pathway analysis; to avoid some genes with non-outstanding differential expression but biologically importance, Gene Set Enrichment Analysis (GSEA) were performed, and 7 chemical ingredients with higher negative enrichment score were obtained by Cmap method, implying that they could reversely regulate the gene expression profiles of pathological tissues; and last, based on the hypotheses that similar structures have similar activities, 336 ingredients of compound Danshen dripping pills were compared with 7 drug molecules in 2D molecular fingerprints method. The results showed that 147 differential genes including 60 up-regulated genes and 87 down regulated genes were screened out by SAM. And in GO analysis, Biological Process ( BP) is mainly concerned with biological adhesion, response to wounding and inflammatory response; Cellular Component (CC) is mainly concerned with extracellular region, extracellular space and plasma membrane; while Molecular Function (MF) is mainly concerned with antigen binding, metalloendopeptidase activity and peptide binding. KEGG pathway analysis is mainly concerned with JAK-STAT, RIG-I like receptor and PPAR signaling pathway. There were 10 compounds, such as hexadecane, with Tanimoto coefficients greater than 0.85, which implied that they may be the active ingredients (AIs) of compound Danshen dripping pills in treatment of carotid atherosclerosis (CAs). The present method can be applied to the research on material base and molecular action mechanism of TCM.

Study on prediction of compound-target-disease network of chuanxiong rhizoma based on random forest algorithm / 中国中药杂志

To collect small molecule drugs and their drug target data such as enzymes, ion channels, G-protein-coupled receptors and nuclear receptors from KEGG database as the training sets, in order to establish drug-target interaction models based on the random forest algorithm. The accuracies of the models were evaluated by the 10-fold cross-validation test, showing that the predicted success rates of the four drug target models were 71.34%, 67.08%, 73.17% and 67.83%, respectively. The models were adopted to predict the targets of 26 chemical components and establish the compound-target-disease network. The results were well verified by literatures. The models established in this paper are highly accurate, and can be used to discover potential targets in other traditional Chinese medicine ingredients.

Optimized Ultrasonic-Assisted Extraction of Polysaccharides from Chinese Traditional Medicinal Plant Paris fargesii Using Orthogonal Design.

Paris fargesii is a famous Chinese traditional medicinal plant used as antipyretic, antidotal, antiphlogistic and analgesic. This research aimed at the determination of the total polysaccharides contents in P. fargesii, which were collected from Baoxing country of Sichuan Province in order to get the optimized extraction technology. Ultrasonic method was adopted in the extraction of total polysaccharides from P. fargesii. Through single factor experiment and orthogonal test, the effects of ultrasonic extraction conditions on the total polysaccharides extraction were measured, including solid-liquid ratio, ultrasonic temperature, ultrasonic power and ultrasonic time. Then colorimetric method was applied for the assaying. The optimized extraction conditions of total polysaccharides from P. fargesii were as follows: ultrasonic power: 600w, solid-liquid ratio: 1:20, ultrasonic extraction time: 1.5h and ultrasonic temperature: 90℃. Under the optimum parameters, the total polysaccharides extraction efficiency was 0.0715%.

Effect of GBV-C/HIV coinfection on HIV/AIDS disease progression and HIV replication / 病毒学报

Several research groups have recently reported that persistent GB virus C (GBV-C) co-infected with human immunodeficiency virus (HIV) leads to slower AIDSs disease progression than HIV-1 infection alone. However, these findings were not confirmed by several other studies. To investigate the association between GBV-C replication and plasma HIV loads and CD4+ T cell counts, 203 HIV-1 positive former blood/plasma donors(FBDs) were enrolled from Fuyang city of Anhui Province in China. Plasma specimens were collected from them and were tested for GBV-C using RT-PCR and ELISA. Out of 203 specimens, 52 (25.6%) cases were positive for GBV-C, including 35 male (67.3%) and 17 female (32.7%) cases. No significant association was identified between GBV-C infection and CD4+ T-cell counts or between GBV-C infection and HIV viral loads. Since all the subjects studied were naive to ART, the influence of therapy on AIDS disease progression was ruled out in this study. Overall, our data indicated that HIV-1 positive male FBDs were prone to be infected, GBV-C coinfection with HIV-1 does not significantly influence HIV/AIDS disease progression during the late stage of chronic HIV-1 infection.

HIV-specific T cell immunity across the entire HIV genome in Chinese men who have sex with men / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Man who has sex with man (MSM) is one of the high risk groups for spreading HIV/AIDS. It was reported that the most prevalent human immunodeficiency virus type 1 (HIV-1) strain among MSM is subtype B; however, T cell immunity remains unknown across the HIV-1 B genome in this population.</p><p><b>METHODS</b>Using Elispot assay with synthetic peptides spanning the sequence of HIV-1 consensus B, HIV-1-specific cytotoxic T-cell lymphocyte responses were quantified among 3 treated and 19 untreated HIV-1 infected MSM from Beijing, China. Cross-sectional association between viral loads and cellular immune responses were analyzed.</p><p><b>RESULTS</b>Peptide pools corresponding to each HIV-1 protein were used for Env, Gag, Pol, Nef, Tat/Rev, Vpr/Vpu and Vif. The results showed that the magnitude of T cell responses in the 3 treated HIV(+) MSM group [median, 770 spot forming cells (SFCs) per 10(6) peripheral blood mononuclear cells (PBMCs)] might be significantly lower than that in the 19 untreated HIV(+) MSM group (median, 6175 SFCs per 10(6) PBMCs). Nef, Gag and Pol are the most frequently targeted HIV-1 antigens; and 16 subjects (73%) were identified with vigorous T cell immunity against each of these three proteins. The overall magnitude of T cell immunity closely related to its breadth (r = 0.72, P < 0.05) and was inversely but weakly associated with viral loads (r = -0.15). Further analysis showed that both Gag (r = -0.24) and Pol specific T cells (r = -0.12) contributed to this inverse association whereas Nef specific T cells showed no association with viral loads.</p><p><b>CONCLUSIONS</b>The magnitude of HIV-1 specific T cells is inversely but weakly associated with viral loads among MSM; HIV-specific T cell responses against conservative sequences (Gag and Pol) are the main contributors to this association among Chinese HIV(+) MSM. These findings have important implications for vaccine design.</p>