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Single-cell RNA sequencing to understand host-virus interactions

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Virologica Sinica 2024年第1期39卷 1-8页

作者： Jia-Tong Chang Li-Bo Liu Pei-Gang Wang Jing An department of Microbiology School of Basic Medical SciencesCapital Medical UniversityBeijing 100069China

Single-cell RNA sequencing(scRNA-seq)has allowed for the profiling of host and virus transcripts and host-virus interactions at single-cell resolution.This review summarizes the existing scRNA-seq technologies together with their strengths and weaknesses.The applications of scRNA-seq in various virological studies are discussed in depth,which broaden the understanding of the immune atlas,host-virus interactions,and immune repertoire.scRNA-seq can be widely used for virology in the near future to better understand the pathogenic mechanisms and discover more effective therapeutic strategies.

关键词： Single-cell RNA sequencing(scRNA-seq) Host-virus interaction COVID-19 Flavivirus

Prevalence of Anemia in Patients with Diabetes Mellitus:A Systematic Review and Meta-Analysis

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Biomedical and Environmental sciences 2024年第1期37卷 96-107页

作者： Monireh Faghir-Ganji Narjes Abdolmohammadi Maryam Nikbina Alireza Amanollahi Alireza Ansari-Moghaddam Rozhan Khezri Hamidreza Baradaran Student Research Committee Iran University of Medical SciencesTehranIran department of Epidemiology School of Public HealthIran University of Medical SciencesTehranIran department of Epidemiology School of Public HealthTehran University of Medical SciencesTehranIran department of Midwifery Shoushtar Faculty of Medical SciencesShoushtarIran department of Epidemiology School of Public Health and SafetyShahid Beheshti University of Medical SciencesTehranIran Trauma and Injury Research Center Iran University of Medical SciencesTehranIran Health Promotion Research Center Zahedan University of Medical SciencesZahedanIran Endocrine Research Center Institute of Endocrinology and MetabolismIran University of Medical SciencesTehranIran

Objective Anemia is a common public health concern in patients with type 2 diabetes worldwide.This study aimed to identify the prevalence of anemia among patients with diabetes.Methods Electronic databases,including PubMed,Scopus,Web of sciences,and Google Scholar,were searched systematically for studies published between 2010 and 2021.After removing duplicates and inappropriate reports,the remaining manuscripts were reviewed and appraised using theNewcastleOttawa Scale(NOS)tool.A random-effects model was used to calculate the pooled estimates of the extracted data using Stata version 17.Heterogeneity of the studies was assessed using the Q statistic.Results A total of 51 articles containing information on 26,485 patients with diabetes were included in this study.The articles were mainly from Asia(58.82%)and Africa(35.29%).The overall prevalence of anemia was 35.45%(95%CI:30.30–40.76),with no evidence of heterogeneity by sex.Among the two continents with the highest number of studies,the prevalence of anemia in patients with diabetes was significantly higher in Asia[40.02;95%CI:32.72–47.54]compared to Africa[28.46;95%CI:21.90–35.50](P for heterogeneity=0.029).Moreover,there has been an increasing trend in the prevalence of anemia in patients with diabetes over time,from[15.28;95%CI:9.83–22.21]in 2012 to[40.70;95%CI:10.21–75.93]in 2022.Conclusion Globally,approximately 4 in 10 patients with diabetes suffer from anemia.Therefore,routine anemia screening and control programs every 3 months might be useful in improving the quality of life of these patients.

关键词： Prevalence Diabetic foot Anemia Diabetes mellitus

Combinational therapy with Myc decoy oligodeoxynucleotides encapsulated in nanocarrier and X-irradiation on breast cancer cells

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Oncology Research 2024年第2期32卷 309-323页

作者： BEHROOZ JOHARI MILAD PARVINZAD LEILAN MAHMOUD GHARBAVI YOUSEF MORTAZAVI ALI SHARAFI HAMED REZAEEJAM department of medical Biotechnology School of MedicineZanjan University of Medical SciencesZanjanIran Zanjan Pharmaceutical Biotechnology Research Center Zanjan University of Medical SciencesZanjanIran Nanotechnology Research Center Ahvaz Jundishapur University of Medical SciencesAhvazIran department of Radiology Technology School of Allied Medical SciencesZanjan University of Medical SciencesZanjanIran

The Myc gene is the essential oncogene in triple-negative breast cancer(TNBC).This study investigates the synergistic effects of combining Myc decoy oligodeoxynucleotides-encapsulated niosomes-selenium hybrid nanocarriers with X-irradiation exposure on the MDA-MB-468 cell line.Decoy and scramble ODNs for Myc transcription factor were designed and synthesized based on promoter sequences of the Bcl2 gene.The nanocarriers were synthesized by loading Myc ODNs and selenium into chitosan(Chi-Se-DEC),which was then encapsulated in niosome-nanocarriers(NISM@Chi-Se-DEC).FT-IR,DLS,FESEM,and hemolysis tests were applied to confirm its characterization and physicochemical properties.Moreover,cellular uptake,cellular toxicity,apoptosis,cell cycle,and scratch repair assays were performed to evaluate its anticancer effects on cancer cells.All anticancer assessments were repeated under X-ray irradiation conditions(fractionated 2Gy).Physicochemical characteristics of niosomes containing SeNPs and ODNs showed that it is synthesized appropriately.It revealed that the anticancer effect of NISM@Chi-Se-DEC can be significantly improved in combination with X-ray irradiation treatment.It can be concluded that NISM@Chi-Se-DEC nanocarriers have the potential as a therapeutic agent for cancer treatment,particularly in combination with radiation therapy and in-vivo experiments are necessary to confirm the efficacy of this nano-drug.

关键词： Combinational therapy Antisense therapy Myc signaling pathway Niosomes Radiation therapy SeNPs

Progress in the generation of spinal cord organoids over the past decade and future perspectives

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Neural Regeneration Research 2024年第5期19卷 1013-1019页

作者： Gang Zhou Siyuan Pang Yongning Li Jun Gao department of Neurosurgery Peking Union Medical College HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijingChina department of International medical Service Peking Union Medical College HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijingChina

Spinal cord organoids are three-dimensional tissues derived from stem cells that recapitulate the primary morphological and functional characteristics of the spinal cord in vivo.As emerging bioengineering methods have led to the optimization of cell culture protocols,spinal cord organoids technology has made remarkable advancements in the past decade.Our literature search found that current spinal cord organoids do not only dynamically simulate neural tube formation but also exhibit diverse cytoarchitecture along the dorsal-ventral and rostral-caudal axes.Moreover,fused organoids that integrate motor neurons and other regionally specific organoids exhibit intricate neural circuits that allows for functional assessment.These qualities make spinal cord organoids valuable tools for disease modeling,drug screening,and tissue regeneration.By utilizing this emergent technology,researchers have made significant progress in investigating the pathogenesis and potential therapeutic targets of spinal cord diseases.However,at present,spinal cord organoid technology remains in its infancy and has not been widely applied in translational medicine.Establishment of the next generation of spinal cord organoids will depend on good manufacturing practice standards and needs to focus on diverse cell phenotypes and electrophysiological functionality evaluation.

关键词： development organoid-on-a-chip pluripotent stem cells progress spinal cord diseases spinal cord organoids vascularization

TRAIL and Celastrol Combinational Treatment Suppresses Proliferation, Migration, and Invasion of Human Glioblastoma Cells via Targeting Wnt/β-catenin Signaling Pathway

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Chinese Journal of Integrative Medicine 2024年第4期30卷 322-329页

作者： QIN Jing-jing NIU Meng-da CHA Zhe GENG Qing-hua LI Yu-lin REN Chun-guang David P.Molloy YU Hua-rong Research Center of Neuroscience School of Basic Medical SciencesChongqing Medical UniversityChongqing(400016)China Laboratory of Developmental Biology Department of Cell Biology and GeneticsSchool of Basic Medical SciencesChongqing Medical UniversityChongqing(400016)China department of Biochemistry and Molecular Biology School of Basic Medical SciencesChongqing Medical UniversityChongqing(400016)China

Objective To investigate the mechanistic basis for the anti-proliferation and anti-invasion effect of tumor necrosis factor-related apoptosis-induced ligand(TRAIL)and celastrol combination treatment(TCCT)in glioblastoma cells.Methods Cell counting kit-8 was used to detect the effects of different concentrations of celastrol(0-16µmol/L)and TRAIL(0-500 ng/mL)on the cell viability of glioblastoma cells.U87 cells were randomly divided into 4 groups,namely control,TRAIL(TRAIL 100 ng/mL),Cel(celastrol 0.5µmol/L)and TCCT(TRAIL 100 ng/mL+celastrol 0.5µmol/L).Cell proliferation,migration,and invasion were detected by colony formation,wound healing,and Transwell assays,respectively.Quantitative reverse transcription polymerase chain reaction and Western blotting were performed to assess the levels of epithelial-mesenchymal transition(EMT)markers(zona occludens,N-cadherin,vimentin,zinc finger E-box-binding homeobox,Slug,and β-catenin).Wnt pathway was activated by lithium chloride(LiCl,20 mol/L)and the mechanism for action of TCCT was explored.Results Celastrol and TRAIL synergistically inhibited the proliferation,migration,invasion,and EMT of U87 cells(P<0.01).TCCT up-regulated the expression of GSK-3β and down-regulated the expression of β-catenin and its associated proteins(P<0.05 or P<0.01),including c-Myc,Cyclin-D1,and matrix metalloproteinase(MMP)-2.In addition,LiCl,an activator of the Wnt signaling pathway,restored the inhibitory effects of TCCT on the expression of β-catenin and its downstream genes,as well as the migration and invasion of glioblastoma cells(P<0.05 or P<0.01).Conclusions Celastrol and TRAIL can synergistically suppress glioblastoma cell migration,invasion,and EMT,potentially through inhibition of Wnt/β-catenin pathway.This underlies a novel mechanism of action for TCCT as an effective therapy for glioblastoma.

关键词： celastrol Chinese medicine tumor necrosis factor-related apoptosis-induced ligand glioblastoma β-catenin Tripterygium wilfordii

Pancreatic ductal adenocarcinoma chemoresistance:From metabolism reprogramming to novel treatment

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Chinese medical Journal 2024年第4期137卷 408-420页

作者： Jingcheng Zhang Yutong Wang Lejunzi Wang Lei You Taiping Zhang department of General Surgery Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China Peking Union medical College Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China department of Anaesthesia Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China Clinical Immunology Centre Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China

As pancreatic cancer(PC)is highly malignant,its patients tend to develop metastasis at an early stage and show a poor response to conventional chemotherapies.First-line chemotherapies for PC,according to current guidelines,include fluoropyrimidine-and gemcitabine-based regimens.Accumulating research on drug resistance has shown that biochemical metabolic aberrations in PC,especially those involving glycolysis and glutamine metabolism,are highly associated with chemoresistance.Additionally,lipid metabolism is a major factor in chemoresistance.However,emerging compounds that target these key metabolic pathways have the potential to overcome chemoresistance.This review summarizes how PC develops chemoresistance through aberrations in biochemical metabolism and discusses novel critical targets and pathways within cancer metabolism for new drug research.

关键词： Pancreatic cancer Drug resistance Drug development Signal transduction

Targeting the RAS/RAF/MAPK pathway for cancer therapy: from mechanism to clinical studies

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Signal Transduction and Targeted Therapy 2024年第1期9卷 173-210页

作者： Md Entaz Bahar Hyun Joon Kim Deok Ryong Kim department of Biochemistry and Convergence medical sciences and Institute of medical Science Gyeongsang National UniversityCollege of MedicineJinjuSouth Korea department of Anatomy and Convergence medical sciences and Institute of medical Science Gyeongsang National UniversityCollege of MedicineJinjuSouth Korea

Metastatic dissemination of solid tumors,a leading cause of cancer-related mortality,underscores the urgent need for enhanced insights into the molecular and cellular mechanisms underlying metastasis,chemoresistance,and the mechanistic backgrounds of individuals whose cancers are prone to migration.The most prevalent signaling cascade governed by multi-kinase inhibitors is the mitogen-activated protein kinase(MAPK)pathway,encompassing the RAS–RAF–MAPK kinase(MEK)–extracellular signal-related kinase(ERK)pathway.RAF kinase is a primary mediator of the MAPK pathway,responsible for the sequential activation of downstream targets,such as MEK and the transcription factor ERK,which control numerous cellular and physiological processes,including organism development,cell cycle control,cell proliferation and differentiation,cell survival,and death.Defects in this signaling cascade are associated with diseases such as cancer.RAF inhibitors(RAFi)combined with MEK blockers represent an FDAapproved therapeutic strategy for numerous RAF-mutant cancers,including melanoma,non-small cell lung carcinoma,and thyroid cancer.However,the development of therapy resistance by cancer cells remains an important barrier.Autophagy,an intracellular lysosome-dependent catabolic recycling process,plays a critical role in the development of RAFi resistance in cancer.Thus,targeting RAF and autophagy could be novel treatment strategies for RAF-mutant cancers.In this review,we delve deeper into the mechanistic insights surrounding RAF kinase signaling in tumorigenesis and RAFi-resistance.Furthermore,we explore and discuss the ongoing development of next-generation RAF inhibitors with enhanced therapeutic profiles.Additionally,this review sheds light on the functional interplay between RAF-targeted therapies and autophagy in cancer.

关键词： RAF insight mechanism

Long-term prognosis and its associated predictive factors in patients with eosinophilic gastroenteritis

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World Journal of Gastroenterology 2024年第2期30卷 146-157页

作者： Kai-Wen Li Ge-Chong Ruan Shuang Liu Tian-Ming Xu Ye Ma Wei-Xun Zhou Wei Liu Peng-Yu Zhao Zhi-Rong Du Ji Li Jing-Nan Li department of Gastroenterology Chinese Academy of Medical Sciences and Peking Union Medical College HospitalBeijing 100730China department of Allergy Chinese Academy of Medical Sciences and Peking Union Medical College HospitalBeijing 100730China department of Pathology Chinese Academy of Medical Sciences and Peking Union Medical College HospitalBeijing 100730China department of Radiology Chinese Academy of Medical Sciences and Peking Union Medical College HospitalBeijing 100730China Affairs Office Chinese Academy of Medical Sciences and Peking Union Medical College Hospital(West campus)Beijing 100032China

BACKGROUND Eosinophilic gastroenteritis(EGE)is a chronic recurrent disease with abnormal eosinophilic infiltration in the gastrointestinal tract.Glucocorticoids remain the most common treatment method.However,disease relapse and glucocorticoid dependence remain notable problems.To date,few studies have illuminated the prognosis of EGE and risk factors for disease relapse.AIM To describe the clinical characteristics of EGE and possible predictive factors for disease relapse based on long-term follow-up.METHODS This was a retrospective cohort study of 55 patients diagnosed with EGE admitted to one medical center between 2013 and 2022.Clinical records were collected and analyzed.Kaplan-Meier curves and log-rank tests were conducted to reveal the risk factors for long-term relapse-free survival(RFS).RESULTS EGE showed a median onset age of 38 years and a slight female predominance(56.4%).The main clinical symptoms were abdominal pain(89.1%),diarrhea(61.8%),nausea(52.7%),distension(49.1%)and vomiting(47.3%).Forty-three(78.2%)patients received glucocorticoid treatment,and compared with patients without glucocorticoid treatments,they were more likely to have elevated serum immunoglobin E(IgE)(86.8%vs 50.0%,P=0.022)and descending duodenal involvement(62.8%vs 27.3%,P=0.046)at diagnosis.With a median follow-up of 67 mo,all patients survived,and 56.4%had at least one relapse.Six variables at baseline might have been associated with the overall RFS rate,including age at diagnosis24 kg/m^(2)(HR 0.3922,95%CI:0.1916-0.8027,P=0.014),disease duration from symptom onset to diagnosis>3.5 mo(HR 2.4725,95%CI:1.220-5.0110,P=0.011),vomiting(HR 3.1259,95%CI:1.5246-6.4093,P=0.001),total serum IgE>300 KU/L at diagnosis(HR 0.2773,95%CI:0.1204-0.6384,P=0.022)and glucocorticoid treatment(HR 6.1434,95%CI:2.8446-13.2676,P=0.003).CONCLUSION In patients with EGE,younger onset age,longer disease course,vomiting and glucocorticoid treatment were

关键词： Eosinophilic gastroenteritis Prognosis Relapse Glucocorticoid Glucocorticoid dependence

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 investigated.Epithelial-mesenchymal transition(EMT)process is a characteristic of PF.We 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 determined.To investigate the toxicity of SPM,an MTT test was performed to detect cell viability.Next,A549cells were exposed to selected concentrations of SPM(20 and 40μg/mL)for single and repeated exposures.The 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 supernatant.Western blot was used to detect the expression of proteins associated with EMT and the SMAD3-dependent pathway.Results of western blot demonstrated that E-cadherin was reduced,whereas p-SMAD3,vimentin,andα-smooth muscle actin were elevated.Our 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