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Constructing a biofunctionalized 3D-printed gelatin/sodium alginate/chitosan tri-polymer complex scaffold with improvised biological andmechanical properties for bone-tissue engineering

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Bio-Design and Manufacturing 2024年第1期7卷 57-73页

作者： Amit Kumar Singh Krishna Pramanik Amit Biswas Centre of Excellence in Tissue Engineering Department of Biotechnology and Medical EngineeringNational Institute of TechnologyRourkela 769008India

Sodium alginate(SA)/chitosan(CH)polyelectrolyte scaffold is a suitable substrate for tissue-engineering *** present study deals with further improvement in the tensile strength and biological properties of this type of scaffold to make it a potential template for bone-tissue *** experimented with adding 0%–15%(volume fraction)gelatin(GE),a protein-based biopolymer known to promote cell adhesion,proliferation,and *** resulting tri-polymer complex was used as bioink to fabricate SA/CH/GEmatrices by three-dimensional(3D)*** studies using scanning electron microscopy revealed the microfibrous porous architecture of all the structures,which had a pore size range of 383–419μm.X-ray diffraction and Fourier-transform infrared spectroscopy analyses revealed the amorphous nature of the scaffold and the strong electrostatic interactions among the functional groups of the polymers,thereby forming polyelectrolyte complexes which were found to improve mechanical properties and structural *** scaffolds exhibited a desirable degradation rate,controlled swelling,and hydrophilic characteristics which are favorable for bone-tissue *** tensile strength improved from(386±15)to(693±15)kPa due to the increased stiffness of SA/CH scaffolds upon addition of *** enhanced protein adsorption and in vitro bioactivity(forming an apatite layer)confirmed the ability of the SA/CH/GE scaffold to offer higher cellular adhesion and a bone-like environment to cells during the process of tissue *** vitro biological evaluation including the MTT assay,confocal microscopy analysis,and alizarin red S assay showed a significant increase in cell attachment,cell viability,and cell proliferation,which further improved biomineralization over the scaffold *** addition,SA/CH containing 15%gelatin designated as SA/CH/GE15 showed superior performance to the other fabricated 3D structures,demonstrating its pote

关键词： Scaffold Biomaterial Sodium alginate Chitosan Gelatin 3D printing Tissue engineering

γδT cells:Major advances in basic and clinical research in tumor immunotherapy

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Chinese medical Journal 2024年第1期137卷 21-33页

作者： Yueqi Zhao Peng Dong Wei He Jianmin Zhang Hui Chen Department of Immunology CAMS Key Laboratory for T Cell and ImmunotherapyState Key Laboratory of Medical Molecular BiologyInstitute of Basic Medical SciencesChinese Academy of Medical Sciences and School of Basic MedicinePeking Union Medical CollegeBeijing 100005China Changzhou Xitaihu institute for Frontier Technology of Cell Therapy ChangzhouJiangsu 213000China Haihe Laboratory of Cell Ecosystem Chinese Academy of Medical Sciences and Peking Union Medical CollegeTianjin 300020China

γδT cells are a kind of innate immune T *** have not attracted sufficient attention because they account for only a small proportion of all immune cells,and many basic factors related to these cells remain ***,in recent years,with the rapid development of tumor immunotherapy,γδT cells have attracted increasing attention because of their ability to exert cytotoxic effects on most tumor cells without major histocompatibility complex(MHC)*** increasing number of basic studies have focused on the development,antigen recognition,activation,and antitumor immune response ofγδT ***,γδT cell-based immunotherapeutic strategies are being developed,and the number of clinical trials investigating such strategies is *** review mainly summarizes the progress of basic research and the clinical application ofγδT cells in tumor immunotherapy to provide a theoretical basis for further the development ofγδT cell-based strategies in the future.

关键词： Gamma-delta T-cells T cell receptor CD1a Tumor immunotherapy Receptors,chimeric antigen Vδ1 cells αβT cells

Strategies and opportunities of micro/nano delivery systems for targeted therapy of ulcerative colitis:Focus on underlying mechanisms and future perspectives

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Chinese Chemical Letters 2024年第2期35卷 118-130页

作者： Zihan Liu Han Liu Jialing Cheng Hongliang Wang Yanfang Yang Jun Ye Yuling Liu State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences & Peking Union Medical CollegeBeijing 100050China Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation Institute of Materia MedicaChinese Academy of Medical Sciences & Peking Union Medical CollegeBeijing 100050China

Ulcerative colitis(UC)is a common progressive inflammatory disease whose incidence has increased rapidly in recent years,and can develop into colorectal cancer in severe *** are currently no adequate or effective treatments for UC due to the fact that some patients have found suboptimal results after repeated administration,while others have experienced adverse *** the rapid development of nanotechnology,developing innovative colon-targeting platforms is essential to improving efficacy,reducing side effects,and improving patient *** this review,we summarize the pathophysiological characteristics of UC and the most recent status of numerous nanodrug delivery systems based on different targeting mechanisms in treating ***,intravenous,and rectal drug delivery nanoparticles targeting the colon are discussed,which can provide ideas for the design of colon-targeting nanoparticles for the treatment of colon diseases,especially for the treatment of *** but not least,we provide a glimpse into the future of colon-targeted delivery systems,as well as future advancements in the field.

关键词： Ulcerative colitis Physiological characteristics Colon-specific drug delivery Mechanisms of action Targeted therapy of UC

Suspended particulate matter promotes epithelial-to-mesenchymal transition in alveolar epithelial cells via TGF-β1-mediated ROS/IL-8/SMAD3 axis

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Journal of Environmental Sciences 2024年第7期141卷 139-150页

作者： Shahrzad Molavinia Dian Dayer Mohammad Javad Khodayar Gholamreza Goudarzi Maryam Salehcheh Cellular and Molecular Research Center Medical Basic Sciences Research InstituteAhvaz Jundishapur University of Medical SciencesAhvazIran Department of Toxicology School of PharmacyAhvaz Jundishapur University of Medical SciencesAhvazIran Student Research Committee Ahvaz Jundishapur University of Medical SciencesAhvazIran Toxicology Research Center Medical Basic Sciences Research InstituteAhvaz Jundishapur University of Medical SciencesAhvazIran Air Pollution and Respiratory Diseases Research Center Ahvaz Jundishapur University of Medical SciencesAhvazIran Iranian Scientific Association of Clean Air TehranIran

Epidemiological evidence presents that dust storms are related to respiratory diseases,such as pulmonary fibrosis(PF).However,the precise underlying mechanisms of SPM-elicited adverse effects still need to be ***-mesenchymal transition(EMT)process is a characteristic of *** discussed whether suspended particulate matter(SPM)is involved in EMT induction via transforming growth factor-β1(TGF-β1).In this study,a detailed elemental analysis(55 elements),particle size,and morphology were *** investigate the toxicity of SPM,an MTT test was performed to detect cell ***,A549cells were exposed to selected concentrations of SPM(20 and 40μg/mL)for single and repeated *** DCFH-DA assay showed that exposure to SPM could produce reactive oxygen species(ROS).The ELISA assay demonstrated increased levels of interleukin-8(IL-8)and TGF-β1 in the *** blot was used to detect the expression of proteins associated with EMT and the SMAD3-dependent *** of western blot demonstrated that E-cadherin was reduced,whereas p-SMAD3,vimentin,andα-smooth muscle actin were *** findings indicated that SPM triggered EMT by induction of oxidative stress,inflammation,and the TGF-β1/SMAD3 pathway activation.

关键词： Particulate matter TGF-β1 Oxidative stress Epithelial-mesenchymal transition Pulmonary fibrosis Cells

Targeted metabolomics reveals the aberrant energy status in diabetic peripheral neuropathy and the neuroprotective mechanism of traditional Chinese medicine JinMaiTong

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Journal of Pharmaceutical Analysis 2024年第2期14卷 225-243页

作者： Bingjia Zhao Qian Zhang Yiqian He Weifang Cao Wei Song Xiaochun Liang Department of Traditional Chinese Medicine Peking Union Medical College HospitalPeking Union Medical CollegeChinese Academy of Medical SciencesBeijing100730China institute of Basic Medicine Sciences Chinese Academy of Medical SciencesBeijing100005China medical Research Center Peking Union Medical College HospitalPeking Union Medical CollegeChinese Academy of Medical SciencesBeijing100730China

Diabetic peripheral neuropathy (DPN) is a common and devastating complication of diabetes, for which effective therapies are currently lacking. Disturbed energy status plays a crucial role in DPN pathogenesis. However, the integrated profile of energy metabolism, especially the central carbohydrate metabolism, remains unclear in DPN. Here, we developed a metabolomics approach by targeting 56 metabolites using high-performance ion chromatography-tandem mass spectrometry (HPIC-MS/MS) to illustrate the integrative characteristics of central carbohydrate metabolism in patients with DPN and streptozotocin-induced DPN rats. Furthermore, JinMaiTong (JMT), a traditional Chinese medicine (TCM) formula, was found to be effective for DPN, improving the peripheral neurological function and alleviating the neuropathology of DPN rats even after demyelination and axonal degeneration. JMT ameliorated DPN by regulating the aberrant energy balance and mitochondrial functions, including excessive glycolysis restoration, tricarboxylic acid cycle improvement, and increased adenosine triphosphate (ATP) generation. Bioenergetic profile was aberrant in cultured rat Schwann cells under high-glucose conditions, which was remarkably corrected by JMT treatment. In-vivo and in-vitro studies revealed that these effects of JMT were mainly attributed to the activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK) and downstream peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). Our results expand the therapeutic framework for DPN and suggest the integrative modulation of energy metabolism using TCMs, such as JMT, as an effective strategy for its treatment.

关键词： Diabetic peripheral neuropathy JinMaiTong Energy metabolism Targeted metabolomics Adenosine monophosphate-activated protein kinase

Chemical construction and anti-HCoV-OC43 evaluation of novel 10,12-disubstituted aloperine derivatives as dual cofactor inhibitors of TMPRSS2 and SR-B1

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Chinese Chemical Letters 2024年第5期35卷 201-206页

作者： Yulong Shi Fenbei Chen Mengyuan Wu Xin Zhang Runze Meng Kun Wang Yan Wang Yuheng Mei Qionglu Duan Yinghong Li Rongmei Gao Yuhuan Li Hongbin Deng Jiandong Jiang Yanxiang Wang Danqing Song Beijing Key Laboratory of Antimicrobial Agents Institute of Medicinal BiotechnologyChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China Department of Pharmacy Affiliated Hospital of Jining Medical UniversityJining Medical UniversityJining 272000China

Thirty-one new 10,12-disubstituted aloperine derivatives were subtly constructed through a selective oxidation on the 10-α-C-H induced by sulfonyl and a nucleophilic substitution with the stereoselectivity and *** them,compound 6b displayed a moderate anti-human coronavirus OC43(HCoV-OC43)potency and blocked the viral entry stage through a host mechanism of *** chemoproteomic techniques,both transmembrane serine protease 2(TMPRSS2)and scavenger receptor class B type 1(SR-B1)proteins,which act as host cofactors of viral entry,were identified to be the direct targets of 6b against ***,6b may deactivate the TMPRSS2 by inducing a change in protein conformation,rather than binding to its catalytic center,thus suppressing the viral membrane ***,our study provided key scientific data for the development of aloperine derivatives into a new class of antiviral candidates against humanβ-coronavirus,including severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).

关键词： Aloperine SARS-CoV-2 TMPRSS2 SR-B1 Synthesis

Inhibiting HMGCR represses stemness and metastasis of hepatocellular carcinoma via Hedgehog signaling

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Genes & Diseases 2024年第5期11卷 470-483页

作者： Zhirong Zhang Jiayao Yang Rui Liu Jing Ma Kai Wang Xiaojun Wang Ni Tang Key Laboratory of Molecular Biology for Infectious Diseases(Ministry of Education) Institute for Viral HepatitisDepartment of Infectious DiseasesThe Second Affiliated HospitalChongqing Medical UniversityChongqing 400016China institute of Hepatobiliary Surgery Southwest HospitalThird Military Medical University(Army Medical University)Chongqing 400038China

Cancer stem cells(CSCs)play a crucial role in tumor initiation,recurrence,metastasis,and drug ***,the current understanding of CSCs in hepatocellular carcinoma(HCC)remains *** a comprehensive analysis of the database,it has been observed that 3-hydroxy-3-methylglutaryl-coenzyme A reductase(HMGCR),a critical enzyme involved in cholesterol synthesis,is up-regulated in HCC tissues and liver ***,high expression of HMGCR is associated with a poor prognosis in patients with ***,HMGCR promotes the stemness and metastasis of HCC both in vitro and in *** screening various signaling pathway inhibitors,we have determined that HMGCR regulates stemness and metastasis by activating the Hedgehog signaling in ***,HMGCR positively correlates with the expression of the Smoothened receptor and facilitates the nuclear translocation of the transcriptional activator GLI family zinc finger *** of the Hedgehog pathway can reverse the stimulatory effects of HMGCR on stemness and metastasis in ***,simvastatin,an FDA-approved cholesterol-lowering drug,has been shown to inhibit stemness and metastasis of HCC by targeting *** together,our findings suggest that HMGCR promotes the regeneration and metastasis of HCC through the activation of Hedgehog signaling,and simvastatin holds the potential for clinical suppression of HCC metastasis.

关键词： Cancer stem cells Hedgehog Hepatocellular carcinoma Metastasis Statin

Signaling pathways governing the behaviors of leukemia stem cells

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Genes & Diseases 2024年第2期11卷 830-846页

作者： Shirin Azizidoost Ava Nasrolahi Mohadeseh Sheykhi-Sabzehpoush Amir Anbiyaiee Seyed Esmaeil Khoshnam Maryam Farzaneh Shahab Uddin Atherosclerosis Research Center Ahvaz Jundishapur University of Medical SciencesAhvaz ***Iran Infectious Ophthalmologic Research Center Ahvaz Jundishapur University of Medical SciencesAhvaz ***Iran Department of Laboratory Imam Khomeini Hospital ComplexTehran University of Medical SciencesTehran ***Iran Department of Surgery School of MedicineAhvaz Jundishapur University of Medical SciencesAhvaz ***Iran Persian Gulf Physiology Research Center Medical Basic Sciences Research InstituteAhvaz Jundishapur University of Medical SciencesAhvaz ***Iran Fertility Infertility and Perinatology Research CenterAhvaz Jundishapur University of Medical SciencesAhvaz ***Iran Translational Research institute and Dermatology institute Academic Health SystemHamad Medical CorporationDoha 3050Qatar

Leukemia is a malignancy in the blood that develops from the lymphatic system and bone *** various treatment options have been used for different types of leukemia,understanding the molecular pathways involved in the development and progression of leukemia is *** studies showed that leukemia stem cells(LSCs)play essential roles in the pathogenesis of leukemia by targeting several signaling pathways,including Notch,Wnt,Hedgehog,and *** are highly proliferative cells that stimulate tumor initiation,migration,EMT,and drug *** review summarizes cellular pathways that stimulate and prevent LSCs'self-renewal,metastasis,and tumorigenesis.

关键词： Leukemia Leukemia stem cells Pathogenesis Signaling pathways Stem cells

Internal m^(6)A and m^(7)G RNA modifications in hematopoietic system and acute myeloid leukemia

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Chinese medical Journal 2024年第9期137卷 1033-1043页

作者： Xiaoxu Zhang Yanni Ma Jia Yu Rui Su Xiaoshuang Wang State Key Laboratory of Common Mechanism Research for Major Diseases State Key Laboratory for ComplexSevereand Rare DiseasesInstitute of Basic Medical SciencesChinese Academy of Medical Sciences/Peking Union Medical CollegeBeijing 100005China Department of Systems Biology Beckman Research Institute of City of HopeMonroviaCA 91016USA The institute of Blood Transfusion Chinese Academy of Medical Sciences/Peking Union Medical CollegeChengduSichuan 610052China Key Laboratory of RNA and Hematopoietic Regulation Chinese Academy of Medical SciencesBeijing 100005China Department of Biochemistry and Molecular Biology Chinese Academy of Medical SciencesSchool of Basic Medicine Peking Union Medical CollegeBeijing 100005China

Epitranscriptomics focuses on the RNA-modification-mediated post-transcriptional regulation of gene *** past decade has witnessed tremendous progress in our understanding of the landscapes and biological functions of RNA modifications,as prompted by the emergence of potent analytical *** hematopoietic system provides a lifelong supply of blood cells,and gene expression is tightly controlled during the differentiation of hematopoietic stem cells(HSCs).The dysregulation of gene expression during hematopoiesis may lead to severe disorders,including acute myeloid leukemia(AML).Emerging evidence supports the involvement of the mRNA modification system in normal hematopoiesis and AML pathogenesis,which has led to the development of small-molecule inhibitors that target N6-methyladenosine(m^(6)A)modification machinery as ***,we summarize the latest findings and our most up-to-date information on the roles of m^(6)A and N7-methylguanine in both physiological and pathological conditions in the hematopoietic ***,we will discuss the therapeutic potential and limitations of cancer treatments targeting m^(6)A.

关键词： N6-methyladenosine N7-methylguanine Hematopoiesis Acute myeloid leukemia Therapeutic target RNA modifications