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Transcription tipping points for T follicular helper cell and T-helper 1 cell fate commitment

Cellular & Molecular Immunology 2021年第3期18卷 528-538页

作者： amania a.sheikh Joanna R.Groom Divisions of Immunology and Molecular Immunology Walter and Eliza Hall Institute of Medical ResearchParkvilleVIC 3052Australia Department of Medical Biology University of MelbourneParkvilleVIC 3010Australia

During viral infection,immune cells coordinate the induction of inflammatory responses that clear infection and humoral responses that promote protection.CD4^(+)T-cell differentiation sits at the center of this axis.Differentiation toward T-helper 1(Th1)cells mediates inflammation and pathogen clearance,while T follicular helper(Tfh)cells facilitate germinal center(GC)reactions for the generation of high-affinity antibodies and immune memory.While Th1 and Tfh differentiation occurs in parallel,these CD4^(+)T-cell identities are mutually exclusive,and progression toward these ends is determined via the upregulation of T-bet and Bcl6,respectively.These lineage-defining transcription factors act in concert with multiple networks of transcriptional regulators that tip the T-bet and Bd6 axis in CD4^(+)T-cell progenitors to either a Th1 or Tfh fate.It is now clear that these transcriptional networks are guided by cytokine cues that are not only varied between distinct viral infections but also dynamically altered throughout the duration of infection.Thus,multiple intrinsic and extrinsic factors combine to specify the fate,plasticity,and function of Th1 and Tfh cells during infection.Here,we review the current information on the mode of action of the lineage-defining transcription factors Bcl6 and T-bet and how they act individually and in complex to govern CD4^(+)T-cell ontogeny.Furthermore,we outline the multifaceted transcriptional regulatory networks that act upstream and downstream of Bcl6 and T-bet to tip the differentiation equilibrium toward either a Tfh or Th1 fate and how these are impacted by dynamic inflammatory cues.

关键词： Cytokines Infection T follicular helper cells T-helper 1 cells Transcription factors

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Blockade of Rho-associated kinase prevents inhibition of axon regeneration of peripheral nerves induced by anti-ganglioside antibodies

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Neural Regeneration Research 2024年第4期19卷 895-899页

作者： Andrés Berardo Cristian R.Bacaglio Bárbara B.Báez Rubén Sambuelli Kazim a.sheikh Pablo H.H.Lopez Laboratorio de Neurobiología Instituto de Investigación Médica Mercedes y Martin Ferreyra(INIMEC)-Consejo Nacional de Investigaciones Cientificas y Técnicas(CONICET)Universidad Nacional de Córdoba Departamento de Química Biológica-Centro de Investigaciones en Química Biológica de Córdoba(CIQUIBIC)-Consejo Nacional de Investigaciones Cientificas y Técnicas(CONICET) Facultad de Cs.QuímicasUniversidad Nacional de Córdoba Servicio de Anatomía Patológica Clínica Universitaria Reina FabiolaUniversidad Católica de Córdoba Department of Neurology University of Texas Medical School at Houston

Anti-ganglioside antibodies are associated with delayed/poor clinical recovery in Guillain-Barrèsyndrome,mostly related to halted axon regeneration.Cross-linking of cell surface gangliosides by anti-ganglioside antibodies triggers inhibition of nerve repair in in vitro and in vivo paradigms of axon regeneration.These effects involve the activation of the small GTPase Rho A/ROCK signaling pathways,which negatively modulate growth cone cytoskeleton,similarly to well stablished inhibitors of axon regeneration described so far.The aim of this work was to perform a proof of concept study to demonstrate the effectiveness of Y-27632,a selective pharmacological inhibitor of ROCK,in a mouse model of axon regeneration of peripheral nerves,where the passive immunization with a monoclonal antibody targeting gangliosides GD1a and GT1b was previously reported to exert a potent inhibitory effect on regeneration of both myelinated and unmyelinated fibers.Our results demonstrate a differential sensitivity of myelinated and unmyelinated axons to the pro-regenerative effect of Y-27632.Treatment with a total dosage of 9 mg/kg of Y-27632 resulted in a complete prevention of anti-GD1a/GT1b monoclonal antibody-mediated inhibition of axon regeneration of unmyelinated fibers to skin and the functional recovery of mechanical cutaneous sensitivity.In contrast,the same dose showed toxic effects on the regeneration of myelinated fibers.Interestingly,scale down of the dosage of Y-27632 to 5 mg/kg resulted in a significant although not complete recovery of regenerated myelinated axons exposed to anti-GD1a/GT1b monoclonal antibody in the absence of toxicity in animals exposed to only Y-27632.Overall,these findings confirm the in vivo participation of Rho A/ROCK signaling pathways in the molecular mechanisms associated with the inhibition of axon regeneration induced by anti-GD1a/GT1b monoclonal antibody.Our findings open the possibility of therapeutic pharmacological intervention targeting Rho A/Rock pathway in immune neuropathies associated wi

关键词： anti-ganglioside antibodies anti-glycan antibodies axon regeneration ganglioside Guillain-Barrésyndrome nerve repair ROCK Y-27632

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Potential role of tubulin glutamylation in neurodegenerative diseases

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Neural Regeneration Research 2024年第6期19卷 1191-1192页

作者： Abdullah Md.sheikh Shatera Tabassum Department of Laboratory Medicine Shimane University Faculty of Medicine

The differentiation of neuronal stem cells into mature neurons is a complex process that involves both structural and functional changes. As cells undergo differentiation, there are notable functional changes, including the expression of various transcription factors, cytokines, and neurotransmitiers. Additionally, structural changes occur as the cells develop various processes from the cell body and establish synaptic contacts with other cells.

关键词： POLARITY

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Disease clearance in ulcerative colitis:A new therapeutic target for the future

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World Journal of Gastroenterology 2024年第13期30卷 1801-1809页

作者： Syed Adeel Hassan Neeraj Kapur Fahad sheikh Anam Fahad Somia Jamal Division of Digestive Disease and Nutrition University of KentuckyLexingtonKY 40536United States Department of Pathology and Laboratory Medicine Montefiore Medical CenterAlbert Einstein College of MedicineNew YorkNY 10461United States Division of Primary Care Essen HealthcareNew YorkNY 10457United States Department of Internal Medicine Karachi Medical and Dental CollegeKarachi 74700SindhPakistan

Advancements in murine modeling systems for ulcerative colitis have diversified our understanding of the pathophysiological factors involved in disease onset and progression.This has fueled the identification of molecular targets,resulting in a rapidly expanding therapeutic armamentarium.Subsequently,management strategies have evolved from symptomatic resolution to well-defined objective endpoints,including clinical remission,endoscopic remission and mucosal healing.While the incorporation of these assessment modalities has permitted targeted intervention in the context of a natural disease history and the prevention of complications,studies have consistently depicted discrepancies associated with ascertaining disease status through clinical and endoscopic measures.Current recommendations lack consideration of histological healing.The simultaneous achievement of clinical,endoscopic,and histologic remission has not been fully investigated.This has laid the groundwork for a novel therapeutic outcome termed disease clearance(DC).This article summarizes the concept of DC and its current evidence.

关键词： Inflammatory bowel disease Ulcerative colitis Clinical remission Endoscopic remission Histological remission Mucosal healing Disease clearance

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Garg incontinence scores: New scoring system on the horizon to evaluate fecal incontinence. Will it make a difference?

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World Journal of Gastroenterology 2024年第3期30卷 204-210页

作者： Petr Tsarkov Inna Tulina Parvez sheikh Darya D Shlyk Pankaj Garg Department of Colorectal Surgery Sechenov First Moscow State Medical UniversityMoscow 119991Russia Department of Oncologic Colorectal Surgery Sechenov First Moscow State Medical UniversityMoscow 119991Russia Department of Colorectal Surgery Saifee HospitalMumbai 400004MaharashtraIndia Department of Colorectal Surgery Garg Fistula Research InstitutePanchkula 134113HaryanaIndia

The main aim of this opinion review is to comment on the recent article published by Garg et al in the World Journal of Gastroenterology 2023;29:4593–4603.The authors in the published article developed a new scoring system,Garg incon-tinence scores(GIS),for fecal incontinence(FI).FI is a chronic debilitating disease that has a severe negative impact on the quality of life of the patients.Rome IV criteria define FI as multiple episodes of solid or liquid stool passed into the clothes at least twice a month.The associated social stigmatization often leads to significant under-reporting of the condition,which further impairs management.An important point is that the complexity and vagueness of the disease make it difficult for the patients to properly define and report the magnitude of the problem to their physicians.Due to this,the management becomes even more difficult.This issue is resolved up to a considerable extent by a scoring ques-tionnaire.There were several scoring systems in use for the last three decades.The prominent of them were the Cleveland Clinic scoring system or the Wexner scoring system,St.Marks Hospital or Vaizey’s scores,and the FI severity index.However,there were several shortcomings in these scoring systems.In the opinion review,we tried to analyze the strength of GIS and compare it to the existing scoring systems.The main pitfalls in the existing scoring systems were that most of them gave equal weightage to different types of FI(solid,liquid,flatus,etc.),were not comprehensive,and took only the surgeon’s perception of FI into view.In GIS,almost all shortcomings of previous scoring systems had been addressed:different weights were assigned to different types of FI by a robust statistical methodology;the scoring system was made comprehensive by including all types of FI that were previously omitted(urge,stress and mucus FI)and gave priority to patients’rather than the physicians’perceptions while developing the scoring system.Due to this,GIS indeed looked like a paradigm shift in the evaluat

关键词： Fecal incontinence Scoring system Urge Stress Flatus

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Niosome-encapsulated auraptene reduced the mRNA expression of VEGF-A and PDGFs genes in human retinaderived RPE cell line

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International Journal of Ophthalmology(English edition) 2024年第6期17卷 1028-1035页

作者： Akram Vahidi Teymoor Khosravi Farzad Dastaviz Mehdi sheikh Arabi Ayyoob Khosravi Morteza Oladnabi Student Research Committee Golestan University of Medical SciencesGorgan ***Iran Department of Medical Nanotechnology Faculty of Advanced Medical TechnologiesGolestan University of Medical SciencesGorgan ***Iran Stem Cell Research Center Golestan University of Medical SciencesGorgan ***Iran Department of Molecular Medicine Faculty of Advanced Medical TechnologiesGolestan University of Medical SciencesGorgan ***Iran Gorgan Congenital Malformations Research Center Golestan University of Medical SciencesGorgan ***Iran

AIM:To evaluate the effect of auraptene(AUR)treatment in forms of free and encapsulated in niosome nanoparticles by investigating the mRNA expression level of vascular endothelium growth factor(VEGF)-A and platelet-derived growth factors(PDGFs)in human retinal pigment epithelium(RPE)cell line.METHODS:Niosome nanocarriers were produced using two surfactants Span 60 and Tween 80.RPE cell line was treated with both free AUR and niosome-encapsulated.Optimum dosage of treatments was calculated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)assay.Expression of VEGF-A and PDGF-A,PDGF-B,PDGF-C,PDGF-D genes was measured after total RNA extraction and cDNA synthesis,using real-time polymerase chain reaction(RT-PCR).RESULTS:The highest entrapment efficiency(EE)was achieved by Span 60:cholesterol(1:1)with 64.3%.The half maximal inhibitory concentration(IC50)of free and niosome-encapsulated AUR were 38.5 and 27.78µg/mL,respectively.Release study revealed that niosomal AUR had more gradual delivery to the cells.RT-PCR results showed reduced expression levels of VEGF-A,PDGF-A,PDGF-B,PDGF-C,and PDGF-D after treatment with both free and niosomal AUR.CONCLUSION:Niosomal formulation of Span 60:cholesterol(1:1)is an effective drug delivery approach to transfer AUR to RPE cells.VEGF-A,PDGF-A,PDGF-B,PDGF-C,and PDGF-D are four angiogenic factors,inhibiting which by niosomal AUR may be effective in age-related macular degeneration.

关键词： auraptene niosome age-related macular degeneration angiogenesis nanocarrier

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Unveiling health rights:A call to action for sex workers'HIV care in the Philippines

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Asian Pacific Journal of Tropical Medicine 2024年第1期17卷 45-46页

作者： sheikh Mohd Saleem Shah Sumaya Jan Health Section International NGONew DelhiIndia Department of Anatomy Govt.Medical CollegeSrinagarIndia

We are writing in response to the article titled“Addressing the needs and rights of sex workers for HIV healthcare services in the Philippines”[1].The article calls for attention on the significant challenges faced by sex workers in the Philippines in accessing HIV healthcare.We appreciate the article’s effort to examine these issues in depth.We would like to present a constant flow of thoughts in this letter while highlighting the positive aspects,potential obstacles,and additional points that contribute to this ongoing discussion.

关键词： workers action letter

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Navigating the future of malaria control:Insights from India's pioneering malaria slide bank

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Asian Pacific Journal of Tropical Medicine 2024年第3期17卷 139-140页

作者： sheikh Mohd Saleem Shah Sumaya Jan Public Health Expert Health SectionInternational Non-Government OrganisationNew DelhiIndia Department of Anatomy Government.Medical CollegeSrinagarIndia

We applaud the authors for their illuminating perspective on India's malaria slide bank(MSB),featured in the recent publication in your esteemed journal[1].The article provides a comprehensive overview of the establishment,challenges,and future potential of MSBs,offering valuable insights into the complexities and opportunities inherent in this critical asset for India's malaria elimination program.

关键词： malaria journal offering

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Integrating artificial intelligence and high-throughput phenotyping for crop improvement

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Journal of Integrative Agriculture 2024年第6期23卷 1787-1802页

作者： Mansoor sheikh Farooq Iqra Hamadani Ambreen Kumar A Pravin Manzoor Ikra Yong Suk Chung Phenomics Laboratory Department of Plant Resources and EnvironmentJeju National UniversityJeju 63234Republic of Korea Council of Scientific&Industrial Research Indian Institute of Integrative MedicinePulwamaJ&K 192301India Animal and Dairy Science University of WisconsinMadisonWI 530706United States of America Division of Fruit Science Faculty of HorticultureSher-e-Kashmir University of Agricultural Sciences and Technology of KashmirSrinagar 190025India

Crop improvement is crucial for addressing the global challenges of food security and sustainable agriculture.Recent advancements in high-throughput phenotyping(HTP)technologies and artificial intelligence(AI)have revolutionized the field,enabling rapid and accurate assessment of crop traits on a large scale.The integration of AI and machine learning algorithms with HTP data has unlocked new opportunities for crop improvement.AI algorithms can analyze and interpret large datasets,and extract meaningful patterns and correlations between phenotypic traits and genetic factors.These technologies have the potential to revolutionize plant breeding programs by providing breeders with efficient and accurate tools for trait selection,thereby reducing the time and cost required for variety development.However,further research and collaboration are needed to overcome the existing challenges and fully unlock the power of HTP and AI in crop improvement.By leveraging AI algorithms,researchers can efficiently analyze phenotypic data,uncover complex patterns,and establish predictive models that enable precise trait selection and crop breeding.The aim of this review is to explore the transformative potential of integrating HTP and AI in crop improvement.This review will encompass an in-depth analysis of recent advances and applications,highlighting the numerous benefits and challenges associated with HTP and AI.

关键词： artificial intelligence crop improvement data analysis high-throughput phenotyping machine learning precision agriculture trait selection

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Understanding the Novel Approach of Nanoferroptosis for Cancer Therapy

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Nano-Micro Letters 2024年第9期16卷 501-556页

作者： Afsana.sheikh Prashant Kesharwani Waleed H.Almalki Salem Salman Almujri Linxin Dai Zhe‑Sheng Chen Amirhossein Sahebkar Fei Gao Department of Pharmaceutics School of Pharmaceutical Education and ResearchJamia HamdardNew Delhi 110062India Department of Pharmacology and Toxicology Faculty of PharmacyUmm Al-Qura UniversityMakkahSaudi Arabia Department of Pharmacology College of PharmacyKing Khalid University61421 Asir‑AbhaSaudi Arabia State Key Laboratory of Southwestern Chinese Medicine Resources Pharmacy SchoolChengdu University of Traditional Chinese MedicineChengdu 611130People’s Republic of China Department of Pharmaceutical Sciences College of Pharmacy and Health SciencesSt.John’s UniversityNew York 11439USA Biotechnology Research Center Pharmaceutical Technology InstituteMashhad University of Medical SciencesMashhadIran Applied Biomedical Research Center Mashhad University of Medical SciencesMashhadIran

As a new form of regulated cell death,ferroptosis has unraveled the unsolicited theory of intrinsic apoptosis resistance by cancer cells.The molecular mechanism of ferroptosis depends on the induction of oxidative stress through excessive reactive oxygen species accumulation and glutathione depletion to damage the structural integrity of cells.Due to their high loading and structural tunability,nanocarriers can escort the delivery of ferro-therapeutics to the desired site through enhanced permeation or retention effect or by active targeting.This review shed light on the necessity of iron in cancer cell growth and the fascinating features of ferroptosis in regulating the cell cycle and metastasis.Additionally,we discussed the effect of ferroptosis-mediated therapy using nanoplatforms and their chemical basis in overcoming the barriers to cancer therapy.

关键词： Ferroptosis Nanoparticles Ferrotherapy Cancer Genes Nanotechnology Toxicity Reactive oxygen species

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