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Chinese Journal of Natural Medicines 2017年第8期15卷 584-596页

作者： Chandra Sekhar Y Phani Kumar G Anilakumar K.R. Applied Nutrition Division Defence Food Research LaboratoryDRDOMysore-570011KarnatakaIndia

Stress and emotion are associated with several illnesses from headaches to heart diseases and immune deficiencies to central nervous system. Terminalia arjuna has been referred as traditional Indian medicine for several ailments. The present study aimed to elucidate the effect of T. arjuna bark extract(TA) against picrotoxin-induced anxiety. Forty two male Balb/c mice were randomly divided into six experimental groups(n = 7): control, diazepam(1.5 mg·kg^(–1)), picrotoxin(1 mg·kg^(–1)) and three TA treatemt groups(25, 50, and 100 mg/kg). Behavioral paradigms and PCR studies were performed to determine the effect of TA against picrotoxin-induced anxiety. The results showed that TA supplementation increased locomotion towards open arm(EPM) and illuminated area(light-dark box test), and increased rearing frequency(open field test) in a dose dependent manner, compared to picrotoxin(P < 0.05). Furthermore, TA increased number of licks and shocks in Vogel's conflict. PCR studies showed an up-regulation of several genes, such as BDNF, IP_3, D_2L, CREB, GABAA, SOD, GPx, and GR in TA administered groups. In conclusion, alcoholic extract of TA bark showed protective activity against picrotoxin in mice by modulation of genes related to synaptic plasticity, neurotransmitters, and antioxidant enzymes.

关键词： Anxiety Terminalia arjuna Gene expression Picrotoxin Neurotransmitters LC-MS

Andrographolide inhibits chikungunya virus infection by up-regulating host innate immune pathways

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Asian Pacific Journal of Tropical Medicine 2018年第3期11卷 214-221页

作者： Swati Gupta Kamla Prasad Mishra Paban Kumar Dash Manmohan Parida Lilly Ganju Shashi Bala Singh defence Institute of Physiology & Allied Sciences defence Research and Development Establishment

Objective: To investigate the therapeutic efficacy of andrographolide, a plant derived compound, against chikungunya virus(CHIKV) infection. Methods: Using flow cytometry and immunoblotting assay, in vitro viral protein expression was studied in THP-1 cells line. In Balb/c mouse neonates, viral RNA copy number was determined by real time PCR. Results:The results showed reduced CHIKV protein expression on andrographolide treatment in CHIKV-infected human peripheral blood mononuclear cells, Vero cells and THP-I cell *** vivo, andrographolide treatment to CHIKV-infected neonates reduced viral RNA copy number. Further. andrographolide also increased cytotoxic T lymphocytes both in vitro and in vivo. Andrographolide also activated host innate immune pathways, viz., protein kinase *** eukaryotic initiation factor 2 α, retinoic acid inducible gene-Ⅰ and interferon regulatory factor 3/7, thereby increasing IFN-a secretion. CHIKV-induced nuclear factor κlight chain enhancer of activated B cells and tumor necrosis factor-a was also reduced on andrographolide treatment. Conclusion: Andrographolide inhibits CHIKV by suppressing viral protein expression and up-regulating host innate immunity and hence could be an effective therapeutic agent against CHIKV infection.

关键词： Chikungunya virus Andrographolide Interferon α Protein kinase R Retinoic acid inducible gene-I Tumor necrosis factor α

DOCK8 regulates signal transduction events to control immunity

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Cellular & Molecular Immunology 2017年第5期14卷 406-411页

作者： Conor J Kearney Katrina L Randall Jane Oliaro immune defence laboratory Cancer Immunology Division The Peter MacCallum Cancer Centre East Melbourne Victoria 3002 Australia Sir Peter MacCallum Department of Oncology The University of Melbourne Parkville Victoria 3052 Australia Department of Immunology and Infectious Disease The John Curtin School of Medical Research Australian National University Acton Australian Capital Territory 2601 Australia Australian National University Medical School Australian National University Acton Australian Capital Territory 2605 Australia

Genetic mutations in the gene encoding DOCK8 cause an autosomal recessive form of hyper immunoglobulin E syndrome （AR-HIES）, referred to as DOCK8 deficiency. DOCK8 deficiency in humans results in the onset of combined immunodeficiency disease （CID）, clinically associated with chronic infections with diverse microbial pathogens, and a predisposition to malignancy. It is now becoming clear that DOCK8 regulates the function of diverse immune cell sub-types, particularly lymphocytes, to drive both innate and adaptive immune responses. Early studies demonstrated that DOCK8 is required for lymphocyte survival, migration and immune synapse formation, which translates to poor pathogen control in the absence of DOCK8. However, more recent advances have pointed to a crucial role for DOCK8 in regulating the signal transduction events that control transcriptional activity, cytokine production and functional polarization of immune cells. Here, we summarize recent advances in our understanding of DOCK8 function, paying particular attention to an emerging role as a signaling intermediate to promote immune responses to diverse external stimuli.

关键词： DOCK8 immunodeficiency lymphocytes NK Cells signal transduction

Dengue virus non-structural 1 protein interacts with heterogeneous nuclear ribonucleoprotein H in human monocytic cells

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Asian Pacific Journal of Tropical Medicine 2016年第2期9卷 109-114页

作者： Drishya Diwaker Mishra K P Ganju L Singh S B Immunomodulation Lab Defence Institute of Physiology & Allied Sciences

Objective: To study protein-protein interaction between heterogeneous nuclear ribonucleoprotein H(hn RNP H) and Dengue virus(DENV) proteins. Methods: DENV proteins were screened against the host hn RNP H protein, in order to identify the host-viral protein-protein interactions in DENV infected THP-1 cells by co-immunoprecipitation. The co-localization of the interacting proteins was further confirmed by immunofluorescence microscopy. Results: The host protein hn RNP H was found to interact with DENV nonstructural 1 protein and help the virus to multiply in the cell. Conclusions: The non-structural 1 glycoprotein is a key modulator of host immune response and is also involved in viral replication. Therefore, disruption of this key interaction between hn RNP H and DENV nonstructural 1 could be an important therapeutic strategy for management of DENV infection.

关键词： Dengue virus Non-structural 1 protein Heterogeneous nuclear ribonucleoprotein H Protein interactions

Altered Host Resistance to Listeria monocytogenes In Mice Exposed to 1-Chloroacetophenone (CN) Vapours

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Biomedical and Environmental Sciences 1992年第2期5卷 142-148页

作者： PRADEEP KUMAR PRAVIN KUMAR K.ZACHARIAH G.P.RAI R.VIJAYRAGHAVAN defence Research and Development Establishment Tansen RoadDefence Research and Development Establishment Tansen RoadDefence Research and Development Establishment Tansen RoadDefence Research and Development Establishment Tansen RoadDefence Research and Development Establishment Tansen Road Gwalior 474002 India Gwalior 474002 India Gwalior 474002 IndiaGwalior 474002 IndiaGwalior 474002 India

Short term repeated exposure of 1-chloroacetophenone (CN) vapours at a concentration of 0.153 mg per litre for 15 minutes daily on 10 consecuitve days in Swiss albino male mice resulted in increased mortality to Listeria monocytogenes. Significantly elevated bacterial growth was observed in the spleen and liver of the CN exposed animals. The increased bacterial count in these organs was evident within 4-6 days post challenge as compared to vehicle exposed infected and unexposed infected animals. Increased susceptibility to infection has been considered to be the function of immune alteration due to cumulative short term effects ofCN vapour inhalation. This may be attributed to immunotoxic effects of CN on Tcells mediated macrophage functions.

关键词： CN Vapours Altered Host Resistance to Listeria monocytogenes In Mice Exposed to 1-Chloroacetophenone

Co-administration of rlpaB domain of Shigella with rGroEL of s. Typhi enhances the immune responses and protective efficacy against Shigella infection

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Cellular & Molecular Immunology 2015年第6期12卷 757-767页

作者： Sekar Tamil Selvi Chitradevi Gurpreet Kaur Sivaramakrishna Uppalapati Anandprakash Yadav Dependrapratap Singh1 Anju Bansal Division of Experimental Biology Defence Institute of Physiology and Allied Sciences Delhi India Division of Microbiology Defence Food Research Laboratory Mysore India Division of Immunomodulation Defence Institute of Physiology and Allied Sciences Delhi India

Shigella species cause severe bacillary dysentery in humans and are associated with high morbidity and mortality. The Invasion plasmid antigen （IpaB） protein, which is conserved across all Shigella spp., induces macrophage cell death and is required to invade host cells. The present study evaluates the immunogenicity and protective efficacy of the recombinant （r） domain region of IpaB （rlpaB） of S. flexneri, rlpaB was administered either alone or was co-administered with the rGroEL （heat shock protein 60） protein from S. Typhi as an adjuvant in a mouse model of intranasal immunization. The IpaB domain region （37 kDa） of S. flexneriwas amplified from an invasion plasmid, cloned, expressed in BL21 Escherichia colicells and purified. Immunization with the rlpaB domain alone stimulated both humoral and cell-mediated immune responses. Furthermore, robust antibody （IgG, IgA） and T-cell responses were induced when the rlpaB domain was co-administered with rGroEL. Antibody isotyping revealed higher IgG 1 and IgG2a antibody titers and increased interferon-gamma （IFN-γ） secretion in the co-administered group. Immunization of mice with the rlpaB domain alone protected 60%-70% of the mice from lethal infection by S. flexneri, S. boydiiand S. sonnei, whereas co-administration with rGroEL increased the protective efficacy to 80%-85%. Organ burden and histopathological studies also revealed a significant reduction in lung infection in the co-immunized mice compared with mice immunized with the rlpaB domain alone. This study emphasizes that the co-administration of the rlpaB domain and rGroEL protein improves immune responses in mice and increases protective efficacy against Shigella infection. This is also the first report to evaluate the potential of the GroEL （Hsp 60） protein of S. Typhi as an adjuvant molecule, thereby overcoming the need for commercial adjuvants.

关键词： GroEL heat shock protein IpaB Shigella S. Typhi

Role of RNA secondary structure in emergence of compartment specific hepatitis B virus immune escape variants

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World Journal of Virology 2016年第4期5卷 161-169页

作者： Sibnarayan Datta Runu Chakravarty Molecular Virology laboratory Defence Research Laboratory (DRDO) Hepatitis Research laboratory ICMR Virus Unit (ICMR)

AIM To investigate the role of subgenotype specific RNA secondary structure in the compartment specific selection of hepatitis B virus(HBV)immune escape *** This study was based on the analysis of the specific observation of HBV subgenotype A1 in the serum/plasma,while subgenotype A2 with G145R mutation in the peripheral blood leukocytes(PBLs).Genetic variability found among the two subgenotypes was used for prediction and comparison of the full length pregenomic RNA(pgRNA)secondary structure and base *** secondary structures were predicted for 37℃using the Vienna RNA fold server,using default *** and detailed analysis was done using RNA shapes *** In this analysis,using similar algorithm and conditions,entirely different pgRNA secondary structures for subgenotype A1 and subgenotype A2 were predicted,suggesting different base pairing patterns within the two subgenotypes of genotype A,specifically,in the HBV genetic region encoding the major hydrophilic *** observed that for subgenotype A1 specific pgRNA,nucleotide 358U base paired with 1738A and nucleotide 587G base paired with *** in sharp contrast,in subgenotype A2 specific pgRNA,nucleotide 358U was opposite to nucleotide 588G,while 587G was opposite to 359U,hence precluding correct base pairing and thereby lesser stability of the stem *** the nucleotides at 358U and 587G were replaced with 358C and 587A respectively(as observed specifically in the PBL associated A2 sequences),these nucleotides base paired correctly with 588G and 359U,*** The results of this study show that compartment specific mutations are associated with HBV subgenotype specific alterations in base pairing of the pgRNA,leading to compartment specific selection and preponderance of specific HBV subgenotype with unique mutational pattern.

关键词： Hepatitis B Compartmentalization Peripheral blood leukocytes pgRNA RNA secondary structure G145R

Dynamic monitoring of carcinoembryonic antigen,CA19-9 and inflammation-based indices in patients with advanced colorectal cancer undergoing chemotherapy

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World Journal of Clinical Cases 2022年第3期10卷 899-918页

作者： Nebojsa Manojlovic Goran Savic Bojan Nikolic Nemanja Rancic Clinic for Gastroenterology and Hepatology Military Medical AcademyFaculty of Medicine of the Military Medical AcademyUniversity of DefenceBelgrade 11000Serbia Faculty of Medicine of the Military Medical Academy University of DefenceBelgradeSerbiaMilitary Medical AcademyBelgrade 11000Serbia Institute for Radiology Military Medical AcademyBelgrade 11000Serbia Center for Clinical Pharmacology Institute for RadiologyMilitary Medical AcademyFaculty of Medicine of the Military Medical AcademyUniversity of DefenceBelgrade 11000Serbia

BACKGROUND The roles of carcinoembryonic antigen(CEA)and carbohydrate antigen(CA19-9)in monitoring the patient response to chemotherapy for metastatic colorectal cancer(mCRC)are not clearly defined,and inflammatory indices,including the neutrophil-to-lymphocyte ratio(NLR),lymphocyte-to-monocyte ratio(LMR),platelet-to-lymphocyte ratio(PLR)and systemic immune-inflammation index(SII),have been sparsely investigated for this *** To aim of this study was to evaluate the relationship between the kinetics of CEA,CA19-9,NLR,LMR,PLR and SII in serum and patient response to chemotherapy estimated by computed tomography(CT)in patients with unresectable *** Patients with mCRC treated with a 1st-line and 2nd-line chemotherapy underwent at least 3 whole-body spiral CT scans during response monitoring according to the Response Evaluation Criteria in Solid Tumour 1.1(RECIST 1.1),and simultaneous determination of CEA,CA19-9,neutrophil,lymphocyte,platelet and monocyte levels was *** kinetics of changes in the tumour markers and inflammatory indices were calculated as the percentage change from baseline or nadir,while receiver operating characteristic curves were drawn to select the thresholds to define patients with progressive or responsive disease with the highest sensitivity(Se)and specificity(Sp).The correlation of tumour marker kinetics with inflammatory index changes and RECIST response was determined by univariate and multivariate logistic regression analysis and the clinical utility index(CUI).RESULTS A total of 102 patients with mCRC treated with chemotherapy were *** disease(PD),defined as a CEA increase of 25.52%,resulted in an Se of 80.3%,an Sp of 84%,a good CUI negative[CUI(Ve-)]value of 0.75 and a good fraction correct(FC)value of 81.2;at a CEA cut-off of-60.85%with an Se of 100%and an Sp of 35.7%for PD,CT could be avoided in 25.49%of *** 21.49%CA19-9 cut-off for PD had an Se of 66.5%,an Sp of 87.4%,an acceptable CUI(

关键词： Tumour markers Carcinoembryonic antigen Carbohydrate antigen Inflammatory-based indices Chemotherapy response Metastatic colorectal cancer

Molecular characterization and expression analysis of Lily- type lectin (SmLTL) in turbot Scophthalmus maximus, and its response to Vibrio anguillarum

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Journal of Oceanology and Limnology 2018年第2期36卷 508-518页

作者： XIA Dandan MA Aijun HUANG Zhihui SHANG Xiaomei CUI Wenxiao YANG Zhi QU Jiangbo Key laboratory of Sustainable Development of Marine Fisheries Ministry of Agriculture Qingdao Key Laboratory for Marine Fish Breeding and Biotechnology Yellow Sea Fisheries Research Institute Chinese Academy of Fishery Sciences Qingdao 266071 China Ocean University of Shanghai Shanghai 201306 China laboratory for Marine Biology and Biotechnology Qingdao National Laboratory for Marine Science and Technology Qingdao 266071 China Yantai Tianyuan Aquatic Limited Corporation Yantai 264006 China

A full-length lily-type lectin （SmLTL） was identified from turbot （Scophthalmus maximus） in this study. By searching database for protein identification and fimction prediction, SmLTL were confirmed. The full-length cDNA of SmLTL is composed of 569 bp and contains a 339 bp ORF that encodes 112 amino acid residues. The SmLTL peptide is characterized by a specific J3-prism architecture and contains three mannose binding sites in a three-fold internal repeat between amino acids 30-99; two of the repeats share the classical mannose binding domain （QxDxNxVxY） while the third binding site was similar to other fish-specific binding motifs （TxTxGxRxV）. The primary, secondary, and tertiary structures of SmLTL were predicted and analyzed, indicating that the SmLTL protein was hydrophilic, contained 5.36% a-helices, 39.29% extended strands, 16.07% [3-folds, and 39.29% random coils, and three [3-folds. Quantitative real- time polymerase chain reaction （qPCR） analysis revealed that the SmLTL mRNA was abundantly expressed in skin, gill, and intestine. Low levels of SmLTL expression were observed in other tissues. The expression of SmLTL in gill, skin and intestine increased at mRNA level after stimulation of Hbrio anguillarum, our results suggest that SmLTL serve as the first line of defence against microbial infections and play a pivotal role in the innate mucosal immune system. The current study indicates that SmLTL is a member of the lily- type lectin family and the information reported here will provide an important foundation for future research on the role of this protein.

关键词： lily-type lectin full-length of cDNA quantitative real-time polymerase chain reaction protein structure Vibrio anguillarum

Therapeutic effects of multiple sites peptide-pulsed dendritic cells vaccinations for malignant brain Tumor

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Therapeutic effects of multiple sites peptide-pulsed dendrit...