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Effect of ginsenoside Rg1 on hematopoietic stem cells in treating aplastic anemia in mice via MAPK pathway

World Journal of Stem Cells 2024年第5期16卷 591-603页

作者： Jin-Bo Wang Ming-Wei Du Yan Zheng Internal medicine of Traditional Chinese medicine Tongde Hospital of Zhejiang ProvinceHangzhou 310012Zhejiang ProvinceChina Institute of Cardiovascular Disease Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghai 201203China Shanghai Key laboratory of molecular Medical Mycology Second Affiliated Hospital of Naval Medical UniversityShanghai 200003China Shanghai Key laboratory of Traditional Chinese Clinical medicine Shanghai 201203China department of Hepatic The Xixi Hospital of Hangzhou Affiliated to Zhejiang University of Traditional Chinese MedicineHangzhou 310023Zhejiang ProvinceChina

BACKGROUND Aplastic anemia(AA)presents a significant clinical challenge as a life-threatening condition due to failure to produce essential blood cells,with the current the-rapeutic options being notably *** To assess the therapeutic potential of ginsenoside Rg1 on AA,specifically its protective effects,while elucidating the mechanism at *** We employed a model of myelosuppression induced by cyclophosphamide(CTX)in C57 mice,followed by administration of ginsenoside Rg1 over 13 *** invest-igation included examining the bone marrow,thymus and spleen for pathological changes via hematoxylin-eosin ***,orbital blood of mice was collected for blood routine *** cytometry was employed to identify the impact of ginsenoside Rg1 on cell apoptosis and cycle in the bone marrow of AA ***,the study further evaluated cytokine levels with enzyme-linked immunosorbent assay and analyzed the expression of key proteins in the MAPK signaling pathway via western *** Administration of CTX led to significant damage to the bone marrow’s structural integrity and a reduction in hematopoietic cells,establishing a model of *** Rg1 successfully reversed hematopoietic dysfunction in AA *** comparison to the AA group,ginsenoside Rg1 provided relief by reducing the induction of cell apoptosis and inflammation factors caused by ***,it helped alleviate the blockade in the cell *** with ginsenoside Rg1 significantly alleviated myelosuppression in mice by inhibiting the MAPK signaling *** This study suggested that ginsenoside Rg1 addresses AA by alleviating myelosuppression,primarily through modulating the MAPK signaling pathway,which paves the way for a novel therapeutic strategy in treating AA,highlighting the potential of ginsenoside Rg1 as a beneficial intervention.

关键词： Aplastic anemia Ginsenoside Rg1 Myelosuppression MAPK signaling pathway Bone marrow Hematopoietic stem cells

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molecular Engineering of Aptamer to Solubilize Hydrophobic Near-Infrared Photosensitizer for Enhanced Cancer Photodynamic Therapy

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CCS Chemistry 2024年第5期6卷 1240-1254页

作者： Rongjun Zhang Ding-Kun Ji Defan Yao Zeyu Xiao Weihong Tan Institute of molecular medicine(IMM) Renji HospitalState Key Laboratory of Oncogenes and Related GenesShanghai Jiao Tong University School of MedicineShanghai 200240 department of Radiology Xinhua HospitalShanghai Jiao Tong University School of MedicineShanghai 200092 department of Pharmacology and Chemical Biology School of MedicineShanghai Jiao Tong UniversityShanghai 200025 Zhejiang Cancer Hospital Hangzhou Institute of Medicine(HIM)The Chinese Academy of SciencesHangzhouZhejiang 310022 molecular Science and Biomedicine laboratory(MBL) State Key Laboratory of Chemo/Biosensing and ChemometricsCollege of Chemistry and Chemical EngineeringCollege of BiologyAptamer Engineering Center of Hunan ProvinceHunan UniversityChangshaHunan 410082

Photodynamic therapy(PDT)is a clinically representative treatment strategy for ***,conventional photosensitizers(PSs)are usually hampered by poor water solubility and low targeting ***,we report the precise molecular engineering of aptamer oligonucleotides to solubilize hydrophobic near-infrared(NIR)PSs for enhanced cancer *** pyropheophorbide A(PA)is precisely conjugated to aptamer oligonucleotides by combing DNA solid-phase synthesis technology and Cu-free click *** coupling of insoluble PA to hydrophilic aptamer oligonucleotides vastly improves its solubility to as high as 750μM in water without any cosolvent,resulting in an enhanced NIR fluorescence property(quantum yield=23%)and ***,the targeting ability of aptamer oligonucleotides is not affected by our molecular engineering *** reactive oxygen species(ROS)are produced intracellularly with 660 nm laser irradiation,eliciting mitochondria damage and cell *** growth is effectively inhibited with a single dose of aptamer-PA conjugates without in vivo *** therapeutic effect is more than 20-fold higher than that of *** with traditional formulation,using aptamer oligonucleotides as functional carriers to solubilize hydrophobic NIR PSs is more precise and *** DNA molecular engineering strategy paves a way for the rational design of molecularly targeted medicine for future clinical cancer therapy.

关键词： aptamer aptamer-drug conjugates photosensitive drugs targeted photodynamic therapy cancer theranostics

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Effects of acupuncture on hypothalamic–pituitary–adrenal axis:Current status and future perspectives

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Journal of Integrative medicine 2024年第4期22卷 445-458页

作者： Jia-yuan Zheng Jing Zhu Yu Wang Zhan-zhuang Tian department of Integrative medicine and Neurobiology School of Basic Medical SciencesState Key Laboratory of Medical Neurobiology and Ministry of Education Frontiers Center for Brain ScienceInstitutes of Brain ScienceInstitute of Acupuncture ResearchAcademy of Integrative MedicineShanghai Key Laboratory for Acupuncture Mechanism and Acupoint FunctionShanghai Medical CollegeFudan UniversityShanghai 200032China department of Human Anatomy School of Integrative MedicineShanghai University of Traditional Chinese MedicineShanghai 201203China

The hypothalamic–pituitary–adrenal(HPA) axis is a critical component of the neuroendocrine system,playing a central role in regulating the body's stress response and modulating various physiological processes. Dysregulation of HPA axis function disrupts the neuroendocrine equilibrium, resulting in impaired physiological functions. Acupuncture is recognized as a non-pharmacological type of therapy which has been confirmed to play an important role in modulating the HPA axis and thus favorably targets diseases with abnormal activation of the HPA axis. With numerous studies reporting the promising efficacy of acupuncture for neuroendocrine disorders, a comprehensive review in terms of the underlying molecular mechanism for acupuncture, especially in regulating the HPA axis, is currently in need. This review fills the need and summarizes recent breakthroughs, from the basic principles and the pathological changes of HPA axis dysfunction, to the molecular mechanisms by which acupuncture regulates the HPA axis. These mechanisms include the modulation of multiple neurotransmitters and their receptors, neuropeptides and their receptors, and microRNAs in the paraventricular nucleus,hippocampus, amygdala and pituitary gland, which alleviate the hyperfunctioning of the HPA *** review comprehensively summarizes the mechanism of acupuncture in regulating HPA axis dysfunction for the first time, providing new targets and prospects for further exploration of acupuncture.

关键词： Acupuncture Electroacupuncture Hypothalamic-pituitary-adrenal axis Mechanism Neurotransmitter microRNA

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Id2 epigenetically controls CD8^(+)T-cell exhaustion by disrupting the assembly of the Tcf3-LSD1 complex

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Cellular & molecular Immunology 2024年第3期21卷 292-308页

作者： Yiming Li Mingwei Han Haolin Wei Wan Huang Zhinan Chen Tianjiao Zhang Meirui Qian Lin Jing Gang Nan Xiuxuan Sun Shuhui Dai Kun Wang Jianli Jiang Ping Zhu Liang Chen department of Cell Biology of National Translational Science Center for molecular medicine and department of Clinical Immunology of Xijing Hospital Fourth Military Medical UniversityXi’anShaanxi 710032China State Key laboratory of New Targets Discovery and Drug Development for Major Diseases GanzhouJiangxi341000Xi’anShaanxi 710032China School of medicine Shanghai UniversityShanghai 200444China

CD8^(+)T-cell exhaustion is a state of dysfunction that promotes tumor progression and is marked by the generation of Slamf6^(+)progenitor exhausted(Tex^(prog))and Tim-^(3+)terminally exhausted(Tex^(term))*** of DNA binding protein 2(Id2)has been shown to play important roles in T-cell development and CD8^(+)T-cell ***,the role of Id2 in CD8^(+)T-cell exhaustion is ***,we found that Id2 transcriptionally and epigenetically regulates the generation of Texprog cells and their conversion to Texterm *** deletion of Id2 dampens CD8^(+)T-cell-mediated immune responses and the maintenance of stem-like CD8^(+)T-cell subpopulations,suppresses PD-1 blockade and increases tumor ***,through its HLH domain,Id2 binds and disrupts the assembly of the Tcf3-Tal1 transcriptional regulatory complex,and thus modulates chromatin accessibility at the Slamf6 promoter by preventing the interaction of Tcf3 with the histone lysine demethylase ***,Id2 increases the abundance of the permissive H3K4me2 mark on the Tcf3-occupied E-boxes in the Slamf6 promoter,modulates chromatin accessibility at the Slamf6 promoter and epigenetically regulates the generation of Slamf6+Texprog *** LSD1 inhibitor GSK2879552 can rescue the Id2 knockout phenotype in tumor-bearing *** of LSD1 increases the abundance of Slamf6^(+)Tim-3^(−)Tex^(prog) cells in tumors and the expression level of Tcf1 in Id2-deleted CD8+T *** study demonstrates that Id2-mediated transcriptional and epigenetic modification drives hierarchical CD8^(+)T-cell exhaustion,and the mechanistic insights gained may have implications for therapeutic intervention with tumor immune evasion.

关键词： Id2 T-cell exhaustion Epigenetic modification Immune evasion

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Beyond functional MRI signals:molecular and cellular modifiers of the functional connectome and cognition

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Neural Regeneration Research 2024年第5期19卷 937-938页

作者： Lorenzo Pini Alessandro Salvalaggio Maurizio Corbetta Padova Neuroscience Center University of PadovaItaly Veneto Institute of molecular medicine VIMMPadovaItaly department of Neuroscience University of PadovaItaly

Our brain is constantly *** at rest,the brain carries out essential functions such as maintenance of resting potentials,subthreshold synaptic activity,and spiking activity related to information *** resting activity can be assessed with several in vivo tools,such as resting-state functional magnetic resonance *** technique measures subtle changes in blood flow,volume,and oxygenation that occur over *** vascular in nature,resting-state functional magnetic resonance imaging is considered a reliable proxy of neural activity and several studies have shown that the brain is functionally divided into interacting neural networks called the“functional connectome”.

关键词： functional neural measures

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Immunology demystified: A guide for transplant hepatologists

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World Journal of Transplantation 2024年第1期14卷 48-61页

作者： Iva Kosuta Tomislav Kelava Ana Ostojic Vibor Sesa Anna Mrzljak Hrvoje Lalic department of Intensive Care medicine University Hospital Centre ZagrebZagreb 10000Croatia department of Physiology School of MedicineUniveristy of ZagrebZagreb 10000Croatia laboratory for molecular Immunology Croatian Institute for Brain ResearchZagreb 10000Croatia department of Gastroenterology and Hepatology Liver Transplant CenterUniversity Hospital Centre ZagrebZagreb 10000Croatia department of medicine School of MedicineUniversity of ZagrebZagreb 10000Croatia department of Physiology University of Zagreb School of MedicineZagreb 10000Croatia laboratory for Cell Biology Croatian Institute for Brain ResearchUniversity of Zagreb School of MedicineZagreb 10000Croatia department of laboratory Immunology Clinical Department of Laboratory DiagnosticsUniversity Hospital Center ZagrebZagreb 10000Croatia

Liver transplantation has become standard practice for treating end-stage liver *** success of the procedure relies on effective immunosuppressive medications to control the host's immune *** the liver's inherent capacity to foster tolerance,the early post-transplant period is marked by significant immune *** ensure favorable outcomes,it is imperative to identify and manage various rejection types,encompassing T-cell-mediated,antibody-mediated,and chronic ***,the approach to prescribing immunosuppressants relies heavily on clinical judgment rather than evidencebased *** that the majority of patients will require lifelong immunosuppression as the mechanisms underlying operational tolerance are still being investigated,healthcare providers must possess an understanding of immune responses,rejection mechanisms,and the pathways targeted by immunosuppressive *** knowledge enables customization of treatments and improved patient care,even though a consensus on an optimal immunosuppressive regimen remains elusive.

关键词： Liver transplantation Allograft rejection Operational immune tolerance Immune reaction Immunosuppression

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Characteristics of cell motility during cell collision

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Chinese Physics B 2024年第2期33卷 72-77页

作者：马一凯李娜陈唯 State Key laboratory of Surface Physics and department of Physics Fudan UniversityShanghai 200438China China National Center for Bioinformation Beijing 100101China National genomics Data Center Beijing Institute of GenomicsChinese Academy of SciencesBeijing 100101China

Quantitative examination of cellular motion and intercellullar interactions possesses substantial relevance for both biology and ***,the effects of intercellular interactions during cellular locomotion remain under-explored in experimental *** such,this study seeks to bridge this research gap,adopting Dictyostelium discoideum(Dicty)cells as a paradigm to investigate variations in cellular motion during reciprocal *** aim to attain a comprehensive understanding of how cell interactions influence cell *** observing and processing the motion trajectories of colliding cells under diverse chemical environments,we calculated the diffusion coefficient(D)and the persistence time(τ),using mean square *** analysis of the relationship dynamics between D andτprior to the collisions reveals intricate and non-monotonic alterations in cell movements during *** quantitatively scrutinizing theτtrend,we were able to categorize the cellular responses to interactions under different ***,we ascertained that the effect of cell interactions during collisions in Dicty cells emulates a classical sigmoid *** discovery suggests that cellular responses might comply with a pattern akin to the Weber–Fechner law.

关键词： cell migration random walk cell-cell interaction

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The dysfunctional Wnt pathway down-regulates MLH1/SET expression and promotes microsatellite instability and immunotherapy response in colorectal cancer

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Genes & Diseases 2024年第2期11卷 542-545页

作者： Jiyan Wang Tao He Qingle Gao Hongkai Chang Xintong Dai Juze Yang Shuangping Liu Shuai Zhang Changliang Shan Chunze Zhang State Key laboratory of Medicinal Chemical Biology College of Pharmacy and Tianjin Key Laboratory of Molecular Drug ResearchNankai UniversityTianjin 300350China departments of Pathology Characteristic Medical Center of The Chinese People's Armed Police ForceTianjin 300162China department of Respiratory medicine Sir Run Run Shaw Hospital and Institute of Translational MedicineZhejiang University School of MedicineHangzhouZhejiang 310016China department of Pathology Medical SchoolDalian UniversityDalianLiaoning 116622China School of Integrative medicine Tianjin University of Traditional Chinese MedicineTianjin 301617China department of Colorectal Surgery Tianjin Union Medical CenterNankai UniversityTianjin 300121China

The tumor heterogeneity results in different clinical characteristics of tumor patients,so precise therapy is a popular treatment strategy *** instability(MSI)is found in 10%-15%of colorectal cancer(CRC)patients and exhibits different clinical outcomes than microsatellite stable(MSS)***,MSI patients have a better prognosis than patients with stable *** patients exhibit clinical features that are not responsive to chemotherapy,however,Msl patients showed excellent responses to immunotherapy.'Although the subtype classification of MSI is beneficial to the clinical treatment of CRC patients,the mechanism of MSl remains unclear.

关键词： immunotherapy colorectal clinical

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Acupoint catgut-embedding therapy ameliorates DNCB-induced atopic dermatitis in BALB/c mice by regulating Th2 type immune response and reducing infiltration of CD4^(+)and CD8^(+)cells

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Traditional medicine Research 2024年第9期9卷 14-20页

作者： Cheng Qin Xiang-Yi Kong Fang Wang Jin Xu Zhuo Zhang Xue-Song Yang Jian-Zhou Ye College of First Clinical medicine Yunnan University of Traditional Chinese MedicineKunming 650500China Yunnan Key laboratory of Dai and Yi medicines Yunnan University of Chinese MedicineKunming 650500China Yunnan Provincial Key laboratory of molecular Biology for Sinomedicine Yunnan University of Chinese MedicineKunming 650500China department of Dermatology The First Affiliated Hospital of Yunnan University of Traditional Chinese MedicineKunming 650021China

Background:This study aimed to assess how acupoint catgut-embedding therapy influences Th2-type immune response and the infiltration of CD4^(+)and CD8^(+)cells in DNCB-induced atopic dermatitis in BALB/c *** also conducted an initial examination of the underlying molecular ***:Seventy-two mice were randomly divided into four groups:normal control,DNCB-induced atopic dermatitis model(AD),AD with acupoint catgut-embedding treatment(ADA),and AD with sham-acupoint catgut-embedding *** DNCB challenge to induce AD,the ADA group received acupoint catgut-embedding therapy treatment at Zusanli(ST 36)and Quchi(LI 11)acupoints every other week from day *** in the AD with sham-acupoint catgut-embedding treatment group underwent the same procedure as the ADA group but without catgut *** was assessed using SCORAD on treatment days 1,10,and *** day 18,nine mice per group were euthanized,and the remaining on day *** changes were observed using hematoxylin-eosin and immunohistochemistry ***-α,IL-4,IL-6,and IL-13 levels were analyzed by ELISA,and GATA3 and STAT6 protein levels by western ***:After 20 days of acupoint catgut-embedding therapy treatment,mice showed reduced dermatitis scores compared to DNCB-induced AD-like *** decreases occurred in serum IL-4,IL-6,IL-13,and TNF-α*** analysis revealed marked reductions in CD4^(+)and CD8^(+)cell infiltration,as well as GATA3 and STAT6 protein ***:Acupoint catgut-embedding therapy may effectively alleviate atopic dermatitis by suppressing Th2 immune responses via the STAT6-GATA3 pathway and reducing CD4^(+)and CD8^(+)T cell infiltration in skin lesions.

关键词： atopic dermatitis acupoint catgut-embedding therapy Th2 type immune response

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Phosphodiesterase 9 localization in cytoplasm and nucleus:the gateway to selective targeting in neuroprotection?

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Neural Regeneration Research 2025年第6期20卷 1701-1702页

作者： Giovanni Ribaudo Matteo Giannangeli Margrate Anyanwu Alessandra Gianoncelli department of molecular and Translational medicine University of BresciaBresciaItaly

The umbrella term"neurodege ne rative disorders"(NDDs) refers to several conditions characterized by a progressive loss of structure and function of cells belonging to the nervous *** diseases affect more than 50million people *** disorders are characterized by sundry factors and pathophysiological mechanisms that a re challenging to be fully *** of these rely on cell signaling pathways to preserve homeostasis,involving second messengers such as cyclic adenosine monophosphate (cAMP)and cyclic guanosine 3',5'-monophosphate(cGMP).Their ability to control the duration and amplitude of the signaling cascade is given by the presence of several common and uncommon *** kinases A and G (PKA and PKG),phosphodiesterases (PDEs),and scaffold proteins are among them.

关键词： gateway homeostasis preserve

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