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Partial Fusion (F) Gene Analysis of Newcastle Disease Virus Detected in Pakistan during 2021-2022

Journal of Biosciences and Medicines 2024年第5期12卷 256-275页

作者： Muhammad Danish Mehmood Huma Anwar Ul-Haq Rauf Khalid Yasir Amin Muhammad Usman Ghani Muhammad Ismail Rabia Habib Fareeha Arshed Abdul Rasheed Shaukat Institute of Molecular Biology & Biotechnology University of Lahore Lahore Pakistan research & development Division Ottoman Pharma Lahore Pakistan Quality Assurance Department Ottoman Pharma Lahore Pakistan Veterinary research and Disease Investigation Center Abbottabad Pakistan Quality Control Department Ottoman Pharma Immuno Lahore Pakistan Production Department Ottoman Pharma Lahore Pakistan Poultry Production Department Sabir&#8217s Poultry Pvt. Ltd. Sabroso Pakistan

Newcastle disease (ND) virus is a leading threat to commercial and domestic poultry in Pakistan. The virus infects and constitutes irreversible impairment to the nervous system, damages the respiratory system, and marks severe gastrointestinal lesions leading to heavy mortality in short-living birds and substantial losses in layers and breeders. The continuous emergence and evolution of the virus made it inclined to evade the humoral response and indirectly the circumvention of artificial active immunization. Newcastle disease is caused by the orthoavula genus of the paramyxoviridae family and has shown high genetic diversity even in their genotypes while information regarding enzootic trends of the virus is scanty in Pakistan. A total of 40 tracheal samples of NDV were collected from different commercial broiler farms and 11 isolates of NDV were identified. In the current study, we determined the genetic diversity of the Newcastle disease virus based on the partial sequencing of the fusion protein gene available in the NCBI database. Genetic analysis showed that seven isolates belonged to class I genotype VII and four belonged to class II genotype II. Interestingly, two isolates had epidemiological connections with vaccine-like class II genotype II. Our findings, concerning the recent outbreaks of class I genotype VII and class II genotype II of NDV in vaccinated commercial flocks, suggest possible potential partial mutations in the fusion protein gene. Genetic diversity and formation of the new cleavage site in an important neutralizing protein of wild strain are linked with the potency of artificial active immunization and a major cause of vaccine failure.

关键词： Newcastle Disease Virus Haemagglutination Inhibition Polymerase Chain Reaction Phylogenetic Tree Mutation Analysis

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The BCL-2 inhibitor APG-2575 resets tumor-associated macrophages toward the M1 phenotype,promoting a favorable response to anti-PD-1 therapy via NLRP3 activation

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Cellular & Molecular Immunology 2024年第1期21卷 60-79页

作者： Fan Luo Han Li Wenjuan Ma Jiaxin Cao Qun Chen Feiteng Lu Miaozhen Qiu Penghui Zhou Zengfei Xia Kangmei Zeng Jianhua Zhan Ting Zhou Qiuyun Luo Wentao Pan Lin Zhang Chaozhuo Lin Yan Huang Li Zhang Dajun Yang Hongyun Zhao State Key Laboratory of Oncology in South China Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and TherapyGuangdong Provincial Clinical Research Center for CancerSun Yat-sen University Cancer CenterGuangzhouChina Ascentage pharma(Suzhou)Co Ltd 218 Xinghu StreetSuzhouJiangsu ProvinceChina

The main challenges in the use of immune checkpoint inhibitors(ICIs)are ascribed to the immunosuppressive tumor microenvironment and the lack of sufficient infiltration of activated CD8+T *** the tumor microenvironment(TME)from“cold”to“hot”and thus more likely to potentiate the effects of ICIs is a promising strategy for cancer *** found that the selective BCL-2 inhibitor APG-2575 can enhance the antitumor efficacy of anti-PD-1 therapy in syngeneic and humanized CD34+mouse *** single-cell RNA sequencing,we found that APG-2575 polarized M2-like immunosuppressive macrophages toward the M1-like immunostimulatory phenotype with increased CCL5 and CXCL10 secretion,restoring T-cell function and promoting a favorable immunotherapy ***,we demonstrated that APG-2575 directly binds to NF-κB p65 to activate NLRP3 signaling,thereby mediating macrophage repolarization and the activation of proinflammatory caspases and subsequently increasing CCL5 and CXCL10 chemokine *** a result,APG-2575-induced macrophage repolarization could remodel the tumor immune microenvironment,thus improving tumor immunosuppression and further enhancing antitumor T-cell *** immunohistochemistry confirmed that patients with better immunotherapeutic efficacy had higher CD86,p-NF-κB p65 and NLRP3 levels,accompanied by lower CD206 expression on ***,these data provide evidence that further study on APG-2575 in combination with immunotherapy for tumor treatment is required.

关键词： BCL-2 APG-2575 ICIs Macrophages NLRP3

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Biological factors driving colorectal cancer metastasis

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World Journal of Gastrointestinal Oncology 2024年第2期16卷 259-272页

作者： Shuai-Xing An Zhao-Jin Yu Chen Fu Min-Jie Wei Long-Hai Shen Department of pharmacology School of PharmacyChina Medical UniversityShenyang 110122Liaoning ProvinceChina Liaoning Key Laboratory of Molecular Targeted Antitumor Drug development and Evaluation Liaoning Cancer Immune Peptide Drug Engineering Technology Research CenterKey Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors(China Medical University)Ministry of EducationShenyang 110122Liaoning ProvinceChina BD Department Greenpine Pharma Group Co.LtdTianjin 300020China Center of Oncology Genertec Liaoyou Gem Flower HospitalPanJin 124010Liaoning ProvinceChina

Approximately 20%of colorectal cancer(CRC)patients present with metastasis at *** Stage I-III CRC patients who undergo surgical resection,18%typically suffer from distal metastasis within the first three years following initial *** median survival duration after the diagnosis of metastatic CRC(mCRC)is only 9 *** is traditionally considered to be an advanced stage malignancy or is thought to be caused by incomplete resection of tumor tissue,allowing cancer cells to spread from primary to distant organs;however,increa-sing evidence suggests that the mCRC process can begin early in tumor *** patients present with high heterogeneity and diverse cancer phenotypes that are classified on the basis of molecular and morphological *** genomic and nongenomic events can induce subclone diversity,which leads to cancer and *** the course of mCRC,metastatic cascades are associated with invasive cancer cell migration through the circulatory system,extravasation,distal seeding,dormancy,and reactivation,with each step requiring specific molecular ***,cancer cells presenting neoantigens can be recognized and eliminated by the immune *** this review,we explain the biological factors that drive CRC metastasis,namely,genomic instability,epigenetic instability,the metastatic cascade,the cancer-immunity cycle,and external lifestyle *** remarkable progress in CRC research,the role of molecular classification in therapeutic intervention remains *** review shows the driving factors of mCRC which may help in identifying potential candidate biomarkers that can improve the diagnosis and early detection of mCRC cases.

关键词： cancer Metastasis cascade Cancer immunity Genomic variation Epigenetic instability Lifestyle factor

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FTY720,Sphingosine 1-Phosphate Receptor Modulator,Ameliorates Experimental Autoimmune Encephalomyelitis by Inhibition of T Cell Infiltration

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Cellular & Molecular Immunology 2005年第6期2卷 439-448页

作者： Hirotoshi Kataoka Kunio Sugaharal Kyoko Shimano Koji Teshima Mamoru Koyama Atsyshi Fukunari Kenji Chiba research Laboratory Ⅲ(Immunology) Pharmaceutical Research UnitResearch and Development DivisionMitsubishi Pharma CorporationYokohamaJapan research Laboratory 1(CNS) Pharmaceutical Research UnitResearch and Development DivisionMitsubishi Pharma CorporationYokohamaJapan Discovery Technology Laboratory Ⅰ Pharmaceutical Research UnitResearch and Development DivisionMitsubishi Pharma CorporationYokohamaJapan research Laboratory Ⅲ(Immunology) Pharmaceutical Research UnitResearch and Development DivisionMitsubishi Pharma Corporation1000 Kamoshida-choAoba-kuYokohama 227-0033.Japan.

FTY720, a sphingosine 1-phosphate receptor modulator, induces a marked decrease in the number of peripheral blood lymphocytes and exerts immunomodulating activity in various experimental allograft and autoimmune disease models. In this study, we evaluated the effect of FTY720 and its active metabolite, （S）-enantiomer of FTY720-phosphate [（S）-FTY720-P] on experimental autoimmune encephalomyelitis （EAE） in rats and mice. Prophylactic administration of FTY720 at 0.1 to 1 mg/kg almost completely prevented the development of EAE, and therapeutic treatment with FTY720 significantly inhibited the progression of EAE and EAE-associated histological change in the spinal cords of LEW rats induced by immunization with myelin basic protein. Consistent with rat EAE, the development of proteolipid protein-induced EAE in SJL/J mice was almost completely prevented and infiltration of CD4^＋ T cells into spinal cord was decreased by prophylactic treatment with FTY720 and （S）-FTY720-P. When FTY720 or （S）-FTY720-P was given after establishment of EAE in SJL/J mice, the relapse of EAE was markedly inhibited as compared with interferon-β, and the area of demyelination and the infiltration of CD4^＋ T cells were decreased in spinal cords of EAE mice. Similar therapeutic effect by FTY720 was obtained in myelin oligodendrocyte glycoprotein-induced EAE in C57BL/6 mice. These results indicate that FTY720 exhibits not only a prophylactic but also a therapeutic effect on EAE in rats and mice, and that the effect of FTY720 on EAE appears to be due to a reduction of the infiltration of myelin antigen-specific CD4^＋ T cells into the inflammation site. Cellular ＆ Molecular Immunology. 2005;2（6）：439-448.

关键词： FTY720 S1P receptor modulator lymphopenia EAE T cell infiltration

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Role of Sphingosine 1-Phosphate Receptor Type 1 in Lymphocyte Egress from Secondary Lymphoid Tissues and Thymus

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Cellular & Molecular Immunology 2006年第1期3卷 11-19页

作者： Kenji Chiba Hirofumi Matsuyuki Yasuhiro Maeda Kunio Sugahara research Laboratory Ⅲ (Immunology) Pharmaceutical Research UnitResearch and Development DivisionMitsubishi Pharma CorporationYokohamaJapan

Circulation of mature lymphocytes between blood and secondary lymphoid tissues plays a central role in the immune system. Homing of lymphocytes from blood into secondary lymphoid tissues beyond high endothelial venules is highly dependent on the interaction between the chemokines CCL19, CCL21, CXCL12, and CXCL13, and their receptors CCR7, CXCR4 and CXCR5. However, the molecular mechanism（s） of lymphocyte egress from secondary lymphoid tissues to lymph remained unclear. We have found a new class of immunomodulator, FTY720 by chemical modification of vegetative wasp-derived natural product, ISP-I （myriocin）. FTY720 has been shown to be highly effective in experimental allograft and autoimmune disease models. A striking feature of FTY720 is the induction of a marked decrease in peripheral blood lymphocytes at doses that show immunomodulating activity in these models. The reduction of circulating lymphocytes by FTY720 is caused by sequestration of lymphocytes into secondary lymphoid tissues and thymus. FTY720 is rapidly converted to （S）-enantiomer of FTY720-phosphate [（S）-FTY720-P] by sphingosine kinase 2 in vivo. （S）-FTY720-P acting as a potent agonist of S1P receptor type 1 （S1P1）, induces long-term down-regulation of S1P1 on lymphocytes, and thereby inhibits the migration of lymphocytes toward S1P. Thus, it is presumed that FTY720-induced lymphocyte sequestration is due to the inhibition of S1P/S1P1-dependent lymphocyte egress from secondary lymphoid tissues and thymus by its active metabolite （S）-FTY720-P. Throughout the analysis of the mechanism of action of FTY720, it is clarified that S1P/S1P1 interaction plays an important role for lymphocyte egress from secondary lymphoid tissues and thymus.

关键词： FTY720 SIP S1P1 immunomodulation lymphocyte egress

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Exploring the Molecular Mechanism of Radix Astragali on Colon Cancer Based on Integrated pharmacology and Molecular Docking Technique

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World Journal of Traditional Chinese Medicine 2022年第4期8卷 502-508页

作者： Yong Jiang Yao-Dan Chang Meng Wang Yan-Ping Sun Yu-Jin Bi Zhi-Bin Wang Hai-Xue Kuang College of pharmacy Key Laboratory of Basic and Application Research of Beiyao(Heilongjiang University of Chinese Medicine)Ministry of EducationHarbinHeilongjiangChina Department of research and development SunGen Pharma LLCPrincetonNJUSA

Objective:The objective of this study was to study the mechanism of Radix Astragali on colon cancer by integrated pharmacology and molecular docking ***:Integrative pharmacology-based research platform of traditional Chinese medicine(TCMIP)V2.0 was used to obtain the chemical components and corresponding targets of Radix Astragali and the target information of colon cancer to create the main target network of drugs and *** Ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis was carried out using Hiplot website,and the interaction network of“Traditional Chinese Medicine-component-target-pathway”was established,and molecular docking with main targets was carried out for the key ***:Twenty-seven chemical constituents of Radix Astragali,their 254 corresponding targets,and 44 colon cancer-related targets were *** proteins interacting,70 nodes were obtained as core *** analysis showed that it mainly acts on lipid metabolism,nuclear receptor activity,phagocytic cup,*** pathway analysis showed that it was mainly enriched in the estrogen signaling pathway,C-type lectin receptor signaling pathway,PI3K-Akt signaling pathway,*** multidimensional network,quantitative estimate of the drug,and molecular docking showed that the main targets are AKT1,BCL2,and CDK6,and the key components involved are kumatakenin,astragaloside VIII,and ***:Kumatakenin,AstragalosideⅧ,Choline and other compounds of Radix Astragali may affect colon cancer by acting on AKT1,BCL2 and other targets,thereby regulating estrogen signaling pathway,C-type lectin receptor signaling pathway,PI3K-Akt signaling pathway and so *** will provide theoretical reference for future research on the material basis and mechanism of its pharmacodynamics.

关键词： Colon cancer integrated pharmacology mechanism Radix Astragali

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Exploring the utility of the Chasing Principle:influence of drug-free SNEDDS composition on solubilization of carvedilol, cinnarizine and R3040 in aqueous suspension

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Acta pharmaceutica Sinica B 2019年第1期9卷 194-201页

作者： Scheyla Daniela Siqueira J?rgensen Thomas Rades Huiling Mu Kirsten Graeser Anette Müllertz Department of pharmacy Faculty of Health and Medical Sciences University of Copenhagen Roche pharma research and development Therapeutic Modalities Roche Innovation Center Basel

This study assessed the influence of the composition of drug-free SNEDDS co-dosed with aqueous suspensions of carvedilol(CAR), cinnarizine(CIN) or R3040 on drug solubilization in a twocompartment in vitro lipolysis model. Correlation of drug log P or solubility in SNEDDS with drug solubilization during in vitro lipolysis in the presence of drug-free SNEDDS was assessed. SNEDDS with varying ratios of soybean oil:Maisine 35-1(1:1, w/w) and Kolliphor RH40, with ethanol at 10%(w/w) were used. SNEDDS were named F65, F55 and F20(numbers refer to the percentage of lipids) and aqueous suspensions without drug-free SNEDDS(F0) were also analyzed. While the ranking order of drug solubilization was F65? F55? F204F0 for CAR; F65? F554F204F0 for CIN and F65? F55? F204F0 for R3040-with higher CAR solubilization than for R3040 and CIN-the ranking of S_(eq)of CAR, CIN and R3040 in SNEDDS was F65 o F55o F20, F65? F554F20 and F654F554F20, respectively. Therefore, the composition of SNEDDS influenced the solubilization of CIN, but not CAR and R3040. Furthermore, high S_(eq) in SNEDDS did not reflect high drug solubilization. As CAR(log P 3.8) showed higher solubilization than CIN(log P 5.8) and R3040(log P 10.4), a correlation between drug log P and drug solubilization was observed.

关键词： Self-nanoemulsiying drug delivery system(SNEDDS) Chasing principle Two-compartment in vitro lipolysis Rat gastrointestinal conditions Drug solubilization

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development of a unilateral ureteral obstruction model in cynomolgus monkeys

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Animal Models and Experimental Medicine 2021年第4期4卷 359-368页

作者： Linghong Huang Jia Ni Tanika Duncan Zhizhan Song Timothy S.Johnson Immunology Therapeutic Area UCB PharmaSloughUK research and development Prisys BiotechnologiesPudongChina

Background:Chronic kidney disease(CKD)has a high global prevalence and large unmet *** to developing new CKD therapies are in vivo models in ***,next-generation antibody,protein,and gene therapies are highly specific,meaning some do not cross-react with rodent *** complicates preclinical development,as established in vivo rodent models cannot be utilized unless tool therapeutics are also *** compounds can be difficult to develop and,if available,typically have different epitopes,sequences,and/or altered affinity,making it unclear how efficacious the lead therapeutic may be,or what dosing regimen to *** address this,we aimed to develop a nonhuman primate model of ***:In vivo rodent unilateral ureteral obstruction(UUO)models kidney fibrosis and is commonly used due to its rapidity,consistency,and *** describe translation of this model to the cynomolgus monkey,specifically optimizing the model duration to allow adequate time for assessment of novel therapeutics prior to the fibrotic ***:We demonstrated that disease developed more slowly in cynomolgus monkeys than in rodents post-UUO,with advanced fibrosis developing by 6 *** tubulointerstitial fibrosis in cynomolgus monkeys was more consistent with human obstructive disease than in rodents,having a more aggressive tubular basement expansion and a higher fibroblast *** fibrosis was also associated with increased transglutaminase activity,consistent with that seen in patients with ***:This cynomolgus monkey UUO model can be used to test potential human-specific therapeutics in kidney fibrosis.

关键词： animal models fibrosis kidney nonhuman primates transglutaminase

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Violence on Health Professionals: Experience of the Obstetrics &Gynecology and Pediatrics Departments at the University Teaching Hospital of Bouake;, Cote d’Ivoire

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Open Journal of Pediatrics 2018年第1期8卷 8-18页

作者： Kouadio Vincent Asse Richard Azagoh-Kouadio Kouassi Christian Yao Koko Aude Aka-Tanoh Christelle Avi Kossonou Roland Yeboua John Patrick Yenan Mocket Adolphe Ehouman Yacouba Doumbia Kouie Jeannot Plo Paediatric Ward of University and Teaching Hospital of Bouake BouakeCote d’Ivoire Paediatric Ward of University and Teaching Hospital of Treichville AbidjanCote d’Ivoire olopam pharma and research&development AbidjanCote d’Ivoire Obstetrics and Gynecoology Ward of University and Teaching Hospital of Bouake BouakeCote d’Ivoire

Introduction: Violence in hospital is a major Public Health issue. In Cote d’Ivoire, acts of violence against health professionals exist and may sometimes take a dramatic turn. Objective: To research the causes of this violence for the purpose to prevent them. Materials and Methods: This is a cross-sectional, descriptive study conducted in the Obstetrics & Gynecology and Pediatrics departments at the University Teaching Hospital of Bouaké from 26 January 2016 to 24 February 2016. It included 129 health workers who gave their consent. The data collection was done through individual interviews followed by a focus group according to the socio-professional category. Results: Out of 129 health professionals included, 100 were a victim of violence i.e. a frequency of 77.5%. Most of the violence occurred during “on-call hours” (55.8%) in the emergency units (34.8%). The violence was verbal (52.5%), physical (28.6%), moral and psychological (11.6%), theft (7.3%). The aggression was mainly related to patient’s care (32.1%), visiting hours (26%) and the low level of understanding of the person (16.5%). The victim’s immediate feelings were dominated by frustration (26.7%), discouragement (21.3%) and insecurity (18.3%). The victims received a medical assistance in 9% of cases. To prevent this violence, the staff mainly offered to raise awareness about violence (27.6%) and the respect for hospital staff (25%). Conclusion: Violence against health professionals is common and has negative impacts on staff and hospital activity. Its prevention requires a holistic approach centered on awareness. Keywords: Violence, Hospital, Pediatrics, Staff, Cote d’Ivoire.

关键词： Violence Hospital Pediatrics Staff Cote d’Ivoire

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Chromatographic finger print analysis of steroids in Aerva lanata L by HPTLC technique

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Asian Pacific Journal of Tropical Biomedicine 2011年第6期1卷 428-433页

作者： Yamunadevi Mariswamy Wesely Edward Gnaraj Johnson M research&development Department Bharathiyar University Department of Botany Arignar Anna Government Arts College Department of Plant Biology and Plant Biotechnology St. Xavier's College(Autonomous)

Objective:To determine the chemical profile and steroids composition of the medicinally important plant Aerva lanata(***) ***:Preliminary phytochemicul screening was done by the method as Harborne *** studies were canied out as Harborne and Wagner et al *** Ethyl acetate-ethanol-water(8:2:1.2) was employed as mobile phase for ***:The desired aim was achieved using Chloroform-acetone(8:2) as the mobile *** methanolic extract of stem,leaves,root,flower and seeds of *** showed the presence of 30 different types of steroids with 30 different Rf values from 0.04 to 0.97. Maximum number(11) of steroids has been observed in leaves followed by root(10).Conclusions: HPTLC profile of steroids has been chosen here to reveal the diversity existing in *** finger printing is useful in differentiating the species from the adulterant and act as biochemical markers for this medicinally important plant in the pharma industry and plant systematic studies.

关键词： Steroids HPTLC profile Fingerprint Aerva lanata L.

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