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Targeting TrkB–PSD-95 coupling to mitigate neurological disorders

Neural Regeneration research 2025年第3期20卷 715-724页

作者： Xin Yang Yu-Wen Alvin Huang John Marshall department of Molecular Biology Cell Biology and BiochemistryBrown UniversityProvidenceRIUSA department of Neurology Warren Alpert Medical School of Brown UniversityProvidenceRIUSA Center for Translational Neuroscience Robert J.and Nancy D.Carney Institute for Brain Science and Brown Institute for Translational ScienceBrown UniversityProvidenceRIUSA

Tropomyosin receptor kinase B(TrkB)signaling plays a pivotal role in dendritic growth and dendritic spine formation to promote learning and *** activity-dependent release of brain-derived neurotrophic factor at synapses binds to pre-or postsynaptic TrkB resulting in the strengthening of synapses,reflected by long-term ***,the association of postsynaptic density protein-95 with TrkB enhances phospholipase Cγ-Ca^(2+)/calmodulin-dependent protein kinaseⅡand phosphatidylinositol 3-kinase-mechanistic target of rapamycin signaling required for long-term *** this review,we discuss TrkB-postsynaptic density protein-95 coupling as a promising strategy to magnify brain-derived neurotrophic factor signaling towards the development of novel therapeutics for specific neurological disorders.A reduction of TrkB signaling has been observed in neurodegenerative disorders,such as Alzheimer's disease and Huntington's disease,and enhancement of postsynaptic density protein-95 association with TrkB signaling could mitigate the observed deficiency of neuronal connectivity in schizophrenia and *** with brain-derived neurotrophic factor is problematic,due to poor pharmacokinetics,low brain penetration,and side effects resulting from activation of the p75 neurotrophin receptor or the truncated TrkB.T1 *** TrkB agonists and antibodies that activate TrkB are being intensively investigated,they cannot distinguish the multiple human TrkB splicing isoforms or cell type-specific *** TrkB–postsynaptic density protein-95 coupling provides an alternative approach to specifically boost TrkB signaling at localized synaptic sites versus global stimulation that risks many adverse side effects.

关键词： Angelman syndrome autism brain-derived neurotrophic factor depression neurodegenerative disorder neurodevelopmental disorder postsynaptic density protein-95 synaptic plasticity TrkB

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Prospects for inhibiting the post-transcriptional regulation of gene expression in hepatitis B virus

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World Journal of Gastroenterology 2014年第25期20卷 7993-8004页

作者： Augustine Chen Nattanan Panjaworayan T-Thienprasert Chris M Brown centre for Translational cancer research Department of BiochemistryUniversity of Otago710 Cumber-land StDunedin 9054New Zealand department of Bio-chemistry Faculty of ScienceKasetsart UniversityLadyaow ChatuchakBangkok 10900Thailand department of biochemistry and Webster centre for Infectious diseases University of Otago710 Cum-berland StDunedin 9054New Zealand

There is a continuing need for novel antivirals to treat hepatitis B virus (HBV) infection, as it remains a major health problem worldwide. Ideally new classes of antivirals would target multiple steps in the viral lifecycle. In this review, we consider the steps in which HBV RNAs are processed, exported from the nucleus and translated. These are often overlooked steps in the HBV life-cycle. HBV, like retroviruses, incorporates a number of unusual steps in these processes, which use a combination of viral and host cellular machinery. Some of these unusual steps deserve a closer scrutiny. They may provide alternative targets to existing antiviral therapies, which are associated with increasing drug resistance. The RNA post-transcriptional regulatory element identified 20 years ago promotes nucleocytoplasmic export of all unspliced HBV RNAs. There is evidence that inhibition of this step is part of the antiviral action of interferon. Similarly, the structured RNA epsilon element situated at the 5’ end of the polycistronic HBV pregenomic RNA also performs key roles during HBV replication. The pregenomic RNA, which is the template for translation of both the viral core and polymerase proteins, is also encapsidated and used in replication. This complex process, regulated at the epsilon element, also presents an attractive antiviral target. These RNA elements that mediate and regulate gene expression are highly conserved and could be targeted using novel strategies employing RNAi, miRNAs or aptamers. Such approaches targeting these functionally constrained genomic regions should avoid escape mutations. Therefore understanding these regulatory elements, along with providing potential targets, may also facilitate the development of other new classes of antiviral drugs.

关键词： Hepatitis B virus Translational control Antiviral Nuclear export Post-transcriptional control Nucleocytoplasmic export

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Amplifying colorectal cancer progression: impact of a PDIA4/SP1 positive feedback loop by circPDIA4 sponging miR-9-5p

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cancer Biology & Medicine 2024年第10期21卷 916-933页

作者： Yan Zhuang Yiding Ai Peng Li Xin Yue Yue Li Luling Shan Tongtong Wang Peng Zhao Xun Jin department of Colorectal Oncology Tianjin Medical University Cancer Institute&HospitalNational Clinical Research Center for CancerTianjin's Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin 300060China department of biochemistry and Molecular Biology Tianjin Medical University Cancer Institute&HospitalNational Clinical Research Center for CancerTianjin's Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin 300060China department of Neurosurgery and Neuro-Oncology Tianjin Medical University Cancer Institute&HospitalNational Clinical Research Center for CancerTianjin's Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin 300060China department of Gastro Colorectal Oncology Tianjin Cancer Hospital Airport HospitalTianjin 300308China

Objective:Colorectal cancer(CRC)is a prevalent malignant tumor with a high fatality ***4 has been shown to have a vital role in cancer development by acting as a ***,the impact of the circPDIA4/miR-9-5p/SP1 axis on development of CRC has not been ***:Western blot,immunohistochemistry,and reverse transcription-quantitative polymerase chain reaction assays were used to analyze gene *** CCK-8 assay was used to assess cell *** Transwell assay was used to detect invasion and migration of *** luciferase reporter and RNA immunoprecipitation tests were used to determine if miR-9-5p and circPDIA4(or SP1)bind to one *** in vivo assay was used to measure tumor ***:It was shown that circPDIA4 expression was greater in CRC cell lines and tissues than healthy cell lines and ***4 knockdown prevented the invasion,migration,and proliferation of cells in ***,the combination of circPDIA4 and miR-9-5p was confirmed,as well as miR-9-5p binding to *** experiments also showed that the circPDIA4/miR-9-5p/SP1 axis accelerated the development of *** addition,SP1 combined with the promoter region of circPDIA4 and induced circPDIA4 ***4 was shown to facilitate tumor growth in an in vivo ***:The circPDIA4/miR-9-5p/SP1 feedback loop was shown to aggravate CRC *** finding suggests that the ceRNA axis may be a promising biomarker for CRC patient treatment.

关键词： CircRNA positive feedback loop colorectal cancer PDIA4 SP1

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Metabolic reprogramming in tumors:Contributions of the tumor microenvironment

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Genes & Diseases 2020年第2期7卷 185-198页

作者： Andrew N.Lane Richard M.Higashi Teresa W-M.Fan Center for Environmental and Systems biochemistry Markey Cancer CenterDepartment of Toxicology and Cancer BiologyUniversity of KentuckyUSA

The genetic alterations associated with cell transformation are in large measure expressed in the metabolic phenotype as cancer cells proliferate and change their local environment,and prepare for ***,the fundamental biochemistry of cancer cells is generally the same as in the untransformed cells,but the cancer cells produce a local environment,the TME,that is hostile to the stromal cells,and compete for *** order to proliferate,cells need sufficient nutrients,either those that cannot be made by the cells themselves,or must be made from simpler ***,in solid tumors,the nutrient supply is often limiting given the potential for rapid proliferation,and the poor quality of the ***,cancer cells may employ a variety of strategies to obtain nutrients for survival,growth and *** much has been learned using established cell lines in standard culture conditions,it is becoming clear from in vivo metabolic studies that this can also be misleading,and which nutrients are used for energy production versus building blocks for synthesis of macromolecules can vary greatly from tumor to tumor,and even within the same *** we review the operation of metabolic networks,and how recent understanding of nutrient supply in the TME and utilization are being revealed using stable isotope tracers in vivo as well as in vitro.

关键词： cancer metabolism Nutrient supply Stable isotope resolved metabolomics Tumor microenvironment Metabolic flux

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Serum homocysteine,lipid profile and BMI as atherosclerotic risk factors in children with numerical chromosomal aberrations

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World Journal of Pediatrics 2022年第6期18卷 443-448页

作者： Eman R.Youness Sherien MEl-Daly Hanaa Reyad Abdallah Hala T.El-Bassyouni Hisham Megahed Azzah A.Khedr Marwa Elhady Walaa Alsharany Abuelhamd Medical biochemistry department Medical Research DivisionNational Research CentreGizaEgypt Biological Anthropology department Medical Research DivisionNational Research CentreGizaEgypt Clinical Genetics department Human Genetics and Genome Research DivisionNational Research CentreEl-Tahrir StreetPO:12622GizaEgypt Human Cytogenetics department Human Genetics and Genome Research DivisionNational Research CentreGizaEgypt Pediatric department Faculty of Medicine for GirlsAl-Azhar UniversityCairoEgypt department of Pediatrics Faculty of MedicineCairo UniversityCairoEgypt

Down syndrome,Turner syndrome,and Klinefelter syndrome are the most common chromosomal disorders *** syndrome is caused by an extra copy of the 21st chromosome and has an incidence of 1 in 800 to 1000 live *** syndrom... 详细信息

关键词： chromosomal Turner Serum

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Schistosomiasis:progress and problems

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World Journal of Gastroenterology 2000年第1期6卷 12-19页

作者： Wu GY Halim MH department of Medicine Division of Gastroenterology-Hepatology-University of Connecticut Health CenterFarmingtonCT USA department of biochemistry National Research CentreCairoDokkiEgypt

INTRODUCTIONSchistosomiasis,also commonly known asbilharziasis,is one of the most significant parasiticdiseases of humans.A report of World HealthOrganization in 1996 estimated that over 200 millionpeople were infeste... 详细信息

关键词： Subject headings schistosomiasis development immune response diagnosis treatment

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Prospective study of SEVA TB peroxidase assay for cocktail antigen and antibody in the diagnosis of Tuberculosis in suspected patients attending a tertiary care hospital located in rural area

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Asian Pacific Journal of Tropical Medicine 2010年第5期3卷 356-359页

作者： Anindita Majumdar Pranita D Kamble CM Badole BC Harinath Jamnalal Bajaj Tropical Disease research centre department of biochemistry MGIMSSevagramIndia department of Orthopaedics MGIMSSevagramIndia

Objective:To evaluate inhouse developed SEVA TB peroxidase enzyme immunoassay using cocktail of mycobacterial excretory-secretory antigens(ES-31,ES-43 & EST-6) for antibody detection and their affinity purified antibodies for antigen detection in tuberculosis suspected ***:Inhouse developed SEVA TB peroxidase enzyme immunoassay was evaluated prospectively in 73 suspected pulmonary and 46 extra-pulmonary tuberculosis patients during November 2008~March 2009 in a tertiary hospital located in rural ***:Assay on prospective analysis showed 100% correlation of pulmonary tuberculosis(PTB) and extrapulmonary tuberculosis(EPTB) acid fast bacilli positivity and antitubercular treatment in 11 *** nine PTB and 12 EPTB cases showed negative for EUSA test and were also not given antitubercular *** 30 PTB and 27 EPTB cases showing ELISA positivity were neither acid fast bacilli positive nor antitubercular therapy *** cases may possibly have dormant infection and need further *** EPTB cases ELISA was observed to be more useful than AFB smear ***:This inhouse developed user-friendly peroxidase ELISA can be used as an adjunct test of smear microscopy or culture techniques for routine screening of patients suspected of PTB or EPTB.

关键词： Excretory secretory antigen Cocktail antigen SEVA TB ELISA Pulmonary tuberculosis Extra-pulmonary tuberculosis

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Morphological phylogeny among 15 accessions of bamboos growing in Kokrajhar district of the Bodoland Territorial Area Districts,Assam

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Journal of Forestry research 2018年第5期29卷 1379-1386页

作者： Anusriti Basumatary Sushil Kumar Middha Talambedu Usha Samik Bhattacharya Birendra Kumar Brahma Arvind Kumar Goyal centre for Bamboo Studies and department of Biotechnology Bodoland University DBT-BIF centre Department of BiotechnologyPG Research CentreMaharani Lakshmi Ammanni College for Women department of biochemistry Maharani Lakshmi Ammanni College for Women department of Molecular Ecology Max Planck Institute of Chemical Ecology

Bamboo is nature＇s wonderful gift historically associated with the rural population of the Bodoland Territorial Area ***,indiscriminate use of the resource and the ambiguity in the identification of bamboos in the absence of flowering characters pose a potential risk to the bamboo ***,we considered revising the taxonomic positions and phylogenetic relationships among 15 tropical bamboo species using 35 key morphological descriptors（MD） to assess the reliability of vegetative characters in identifying *** phylogenetic tree constructed from the similarity matrix,derived from an unweighted pair group method of analysis（UPGMA） of the 35 MDs,marginally deviated from the conventional taxonomic positions of the bamboo *** the two varieties,one forma of Bambusa vulgaris（***,***,***） and two species of the genus Dendrocalamus（*** and ***）clustered together in a single clade,and *** was distantly placed from their *** discrepancy with the conventional classification might have ensued since only vegetative characters such as culm anatomy,culm sheath,leaf,and leaf sheath were considered in the present *** the phylogenetic relationship among the 15 tropical bamboos（computed from exhaustive MDs）grossly corroborate the conventional taxonomic grouping,a molecular-marker-based multidisciplinary approach should resolve the remaining conflicts in bamboo identification.

关键词： Bamboo Bodoland Culm Culm-sheath Leaf-sheath Phylogenetic relationship conflict

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Novel drug designing rationale against Brugia malayi microfilariae using herbal extracts

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Asian Pacific Journal of Tropical Medicine 2010年第11期3卷 846-850页

作者： Sharma RD Petare S Shinde GB Kalyan Goswami Reddy MVR JB Tropical Disease research centre & department of biochemistry Mahatma Gandhi Institute of Medical Sciences Sevagram- 442102India Post Graduate Teaching department of biochemistry RTM Nagpur UniversityNagpurM.S.India JB Tropical Disease research centre & department of biochemistry Mahatma Gandhi Institute of Medical SciencesSevagram- 442102India

Objective:To explore the effect of herbal polyphenolics on filariasis in ***:Two herbal extracts,methanolic extracts of roots of Vitex negundo Linn.（Nirgundi） and leaves of Aegle marmelos Juss.（Beal） in different concentrations ranging from 40-80 ng/mL were tested for their antifilarial activity either alone or in combination with diethyl carbonate（DEC）（300μg/mL） and/or H2O2（0.5 mM）.Results:Combination of DEC and each extract had significant anti-filarial *** fractions of both extracts were not effective as crude herbal ***: Such unique pharmacodynamics reported in this study might provide new drug development stratagem against filariasis.

关键词： Herbal extracts Polyphenolics Apoptosis Brugia malayi

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Restoration of dysregulated CC chemokine signaling for monocyte/macrophage chemotaxis in head and neck squamous cell carcinoma patients by neem leaf glycoprotein maximizes tumor cell cytotoxicity

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Cellular & Molecular Immunology 2010年第5期7卷 396-408页

作者： Krishnendu Chakraborty Anamika Bose Tathagata Chakraborty Koustav Sarkar Shyamal Goswami Smarajit Pal Rathindranath Baral department of Immunoregulation and Immunodiagnostics Chittaranjan National Cancer InstituteKolkataIndia Unit of Clinical biochemistry Chittaranjan National Cancer InstituteKolkataIndia

Previous studies have shown that the CC chemokine receptor CCR5 is downregulated on monocyte/macrophage(MO/Mw)surfaces in head and neck squamous cell carcinoma(HNSCC)patients(stage IIIB).Ligands(RANTES,MIP-1a and MIP-1b)of this chemokine receptor were also secreted in lesser quantity from MO/Mw of HNSCC patients in comparison with healthy *** an aim to restore this dysregulated receptor–ligand signaling,we have used neem leaf glycoprotein(NLGP),a novel immunomodulator reported from our *** upregulated CCR5 expression,as evidenced from studies on MO/Mw of peripheral blood from HNSCC patients as well as healthy *** of RANTES,MIP-1a and MIP-1b was also upregulated following NLGP treatment of these cells in ***,NLGP has little effect on the expression of CCR5 and the ligand RANTES in oral cancer *** restored CCR5 receptor–ligand signaling seen in MO/Mw was reflected in improved CCR5-dependent,p38 mitogen-activated protein kinase(MAPK)-mediated migration of MO/Mw after NLGP treatment to a standard *** also induces better antigen presentation and simultaneous costimulation to effector T cells by MO/Mw by upregulating human leucocyte antigen(HLA)-ABC,CD80 and *** addition,NLGP-treated MO/Mw-primed T cells can effectively lyse tumor cells in *** effects of NLGP on monocyte migration and T cell-mediated oral tumor cell killing were further demonstrated in transwell assays with or without CCR5 *** results suggest a new approach in cancer immunotherapy by modulating dysregulated CCR5 signals from MO/Mw.

关键词： CCR5 chemokine head and neck squamous cell carcinoma monocytes neem leaf glycoprotein

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