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Dynamic gut microbiome-metabolome in cationic bovine serum albumin induced experimental immune-complex glomerulonephritis and effect of losartan and mycophenolate mofetil on microbiota modulation

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Journal of Pharmaceutical Analysis 2024年第4期14卷 562-577页

作者： Wenying Shi Zhaojun Li Weida Wang Xikun Liu Haijie Wu Xiaoguang Chen Xunrong Zhou Sen Zhang State Key Laboratory of Bioactive Substances and Functions of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing100050China State Key Laboratory of Functions and Applications of Medicinal Plants College of PharmacyGuizhou Provincial Engineering Technology Research Center for Chemical Drug R&DGuizhou Medical UniversityGuiyang550004China Department of Medicine Solna Center for Molecular MedicineKarolinska University Hospital and Karolinska InstituteStockholm17176Sweden Department of Pharmacy The Second Affiliated Hospital of Guizhou University of Traditional Chinese MedicineGuiyang550001China

Dynamic changes in gut dysbiosis and metabolomic dysregulation are associated with immune-complex glomerulonephritis(ICGN).However,an in-depth study on this topic is currently ***,we report an ICGN model to address this *** was induced via the intravenous injection of cationized bovine serum albumin(c-BSA)into Sprague-Dawley(SD)rats for two weeks,after which mycophenolate mofetil(MMF)and losartan were administered *** and six weeks after ICGN establishment,fecal samples were collected and 16S ribosomal DNA(rDNA)sequencing and untargeted metabolomic were *** microbiota transplantation(FMT)was conducted to determine whether gut normali-zation caused by MMF and losartan contributed to their renal protective effects.A gradual decline in microbial diversity and richness was accompanied by a loss of renal *** 18 genera were found to have significantly different relative abundances between the early and later stages,and Marvinbryantia and Allobaculum were markedly upregulated in both *** metabolomics indicated that the tryptophan metabolism was enhanced in ICGN,characterized by the overproduction of indole and kynurenic acid,while the serotonin pathway was *** of losartan and MMF ameliorated microbial dysbiosis and reduced the accumulation of indoxyl conjugates in *** using feces from animals administered MMF and losartan improved gut dysbiosis by decreasing the Firmicutes/Bacteroidetes(F/B)ratio but did not improve renal *** findings indicate that ICGN induces serous gut dysbiosis,wherein an altered tryptophan metabolism may contribute to its *** and losartan significantly reversed the gut microbial and metabolomic dysbiosis,which partially contributed to their renoprotective effects.

关键词： Immune-complex glomerulonephritis Gut microbiome Metabolomics Fecal microbiota transplant Tryptophan metabolism

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Is convenience really king? Comparative evaluation of catastrophic costs due to tuberculosis in the public and private healthcare sectors of Viet Nam: a longitudinal patient cost study

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贫困所致传染病(英文) 2024年第2期13卷 17-28页

作者： Nguyen Hoa Binh Quang Vo Luan Nguyen Forse Rachel Jeanette Wiemers Anja Maria Christine Huynh Huy Ba Dong Thuy Thi Thu Phan Yen Thi Hoang Creswell Jacob Dang Thi Minh Ha Nguyen Lan Huu Shedrawy Jad L?nnroth Knut Nguyen Tuan Dinh Van Dinh Luong Annerstedt Kristi Sidney Codlin Andrew James National Lung hospital Ha Noi Viet Nam Friends for International TB Relief Ha Noi Viet Nam Department of Global Public Health WHO Collaboration Centre On Tuberculosis and Social Medicine Karolinska Institute Stockholm Sweden Stop TB Partnership Geneva Switzerland Pham Ngoc Thach hospital Ho Chi Minh City Viet Nam

Background In Viet Nam, tuberculosis (TB) represents a devastating life-event with an exorbitant price tag, partly due to lost income from daily directly observed therapy in public sector care. Thus, persons with TB may seek care in the private sector for its flexibility, convenience, and privacy. Our study aimed to measure income changes, costs and catastrophic cost incurrence among TB-affected households in the public and private *** Between October 2020 and March 2022, we conducted 110 longitudinal patient cost interviews, among 50 patients privately treated for TB and 60 TB patients treated by the National TB Program (NTP) in Ha Noi, Hai Phong and Ho Chi Minh City, Viet Nam. Using a local adaptation of the WHO TB patient cost survey tool, participants were interviewed during the intensive phase, continuation phase and post-treatment. We compared income levels, direct and indirect treatment costs, catastrophic costs using Wilcoxon rank-sum and chi-squared tests and associated risk factors between the two cohorts using multivariate *** The pre-treatment median monthly household income was significantly higher in the private sector versus NTP cohort (USD 868 vs USD 578;P=0.010). However, private sector treatment was also significantly costlier (USD 2075 vs USD 1313;P=0.005), driven by direct medical costs which were 4.6 times higher than costs reported by NTP participants (USD 754 vs USD 164;P<0.001). This resulted in no significant difference in catastrophic costs between the two cohorts (Private: 55% vs NTP: 52%;P=0.675). Factors associated with catastrophic cost included being a single-person household [adjusted odds ratio [(aOR=13.71; 95% confidence interval (CI): 1.36–138.14;P=0.026], unemployment during treatment (aOR=10.86; 95%CI: 2.64–44.60;P<0.001) and experiencing TB-related stigma (aOR=37.90; 95%CI: 1.72–831.73;P=0.021).Conclusions Persons with TB in Viet Nam face similarly high risk of catastrophic costs whether treated in the

关键词： Tuberculosis Patient cost Catastrophic cost Private sector Comparative analysis Viet Nam

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Microwave ablation of hepatocellular carcinomas in octogenarians

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Hepatoma Research 2020年第3期6卷 24-30页

作者： Jacob Freedman Department of Surgery and Urology Danderyd University HospitalStockholm 18288Sweden Department of clinical sciences Karolinska InstitutetStockholm 18288Sweden

Aim:To evaluate wether it is safe and meaningful to treat octogenarians with microwave ablation for hepatocellular *** an ageing population being healthier than previous generations,old limits for treating disease founded on patient age need to be *** of the most common tumour related death causes is hepatocellular carcinoma(HCC).With the development of minimally invasive therapies with curative potential,new ground is being broken offering treatments to older patients in the hope of achieving prolongation and better quality of ***:In this retrospective single centre study of patients having a first microwave ablation therapy for HCC in a national referral centre for ablative liver treatments,septuagenarians(n=161,age 70-80)were compared with octogenarians(n=32,age 80-90).Results:Octogenarians selected for microwave ablation of HCC at a regional multidisciplinary team conference have similar outcomes as their younger control ***,complications and length of stay are not ***:Octogenarians who are fit for ablative treatment of HCC should not be disqualified on grounds of age,recognising that this group has an obvious immortality,or lead-time,bias as well as a probable selection bias in part explaining their good results.

关键词： Microwave ablation hepatocellular carcinoma octogenarians survival complications

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Distinct molecular targets of ProEGCG from EGCG and superior inhibition of angiogenesis signaling pathways for treatment of endometriosis

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Journal of Pharmaceutical Analysis 2024年第1期14卷 100-114页

作者： Sze Wan Hung Massimiliano Gaetani Yiran Li Zhouyurong Tan Xu Zheng Ruizhe Zhang Yang Ding Gene Chi Wai Man Tao Zhang Yi Song Yao Wang Jacqueline Pui Wah Chung Tak Hang Chan Roman A.Zubarev Chi Chiu Wang Department of Obstetrics&Gynaecology The Chinese University of Hong KongHong KongChina Division of Physiological Chemistry I Department of Medical Biochemistry and BiophysicsKarolinska InstitutetStockholmSE 17177Sweden Chemical Proteomics Core Facility Department of Medical Biochemistry and BiophysicsKarolinska InstitutetStockholmSE 17177Sweden Unit of Chemical Proteomics Science for Life Laboratory(SciLifeLab)StockholmSE 17177Sweden Center for Reproductive Medicine Henan Key Laboratory of Reproduction and GeneticsThe First Affiliated Hospital of Zhengzhou UniversityZhengzhou450003China Department of Chemistry McGill UniversityMontrealH3A2K6Canada Department of Pharmacological&Technological Chemistry I.M.Sechenov First Moscow State Medical UniversityMoscow119146Russia Reproduction and Development Li Ka Shing Institute of Health SciencesThe Chinese University of Hong KongHong KongChina School of Biomedical Sciences The Chinese University of Hong KongHong KongChina Chinese University of Hong Kong-Sichuan University Joint Laboratory in Reproductive Medicine The Chinese University of Hong KongHong KongChina

Endometriosis is a common chronic gynecological disease with endometrial cell implantation outside the *** is a major pathophysiology in *** previous studies have demonstrated that the prodrug of epigallocatechin gallate(ProEGCG)exhibits superior anti-endometriotic and anti-angiogenic effects compared to epigallocatechin gallate(EGCG).However,their direct binding targets and underlying mechanisms for the differential effects remain *** this study,we demonstrated that oral ProEGCG can be effective in preventing and treating ***,1D and 2D Proteome Integral Solubility Alteration assay-based chemical proteomics identified metadherin(MTDH)and PX domain containing serine/threonine kinase-like(PXK)as novel binding targets of EGCG and ProEGCG,*** simulation and BioLayer interferometry were used to confirm their binding *** results showed that MTDH-EGCG inhibited protein kinase B(Akt)-mediated angiogenesis,while PXK-ProEGCG inhibited epidermal growth factor(EGF)-mediated angiogenesis via the EGF/hypoxia-inducible factor(HIF-1a)/vascular endothelial growth factor(VEGF)*** vitro and in vivo knockdown assays and microvascular network imaging further confirmed the involvement of these signaling ***,our study demonstrated that ProEGCG has superior therapeutic effects than EGCG by targeting distinct signal transduction pathways and may act as a novel antiangiogenic therapy for endometriosis.

关键词： Molecular targets ProEGCG EGCG Angiogenesis Treatment Endometriosis

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Reduced efficacy of single-dose albendazole against Ascaris lumbricoides, and Trichuris trichiura, and high reinfection rate after cure among school children in southern Ethiopia: a prospective cohort study

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Infectious Diseases of Poverty 2024年第1期13卷 95-96页

作者： Tigist Dires Gebreyesus Eyasu Makonnen Tafesse Tadele Kalkidan Mekete Habtamu Gashaw Heran Gerba Eleni Aklillu Department of Global Public Health Karolinska Institutet Karolinska University Hospital Stockholm Sweden Ethiopian Food and Drug Authority Addis Ababa Ethiopia Center for Innovative Drug Development and Therapeutic Trials for Africa College of Health Sciences Addis Ababa University Addis Ababa Ethiopia Departments of Pharmacology and Clinical Pharmacy College of Health Sciences Addis Ababa University Addis Ababa Ethiopia College of Medicine and Health Sciences Hawassa University Hawassa Ethiopia Ethiopian Public Health Institute Addis Ababa Ethiopia

Background Mass drug administration(MDA)program of albendazole to at-risk populations as preventive chemo-therapy is the core public health intervention to control soil-transmitted helminths(STHs).Achieving this goal relies on drug effectiveness in reducing the parasite reservoirs in the community and preventing *** assessed the effcacy of albendazole against STH parasite infection and reinfection status after *** A total of 984 schoolchildren infected with at least one type of STH parasite(hookworm,Ascaris lumbri-coides,Trichuris trichiura)in southern Ethiopia were enrolled and received albendazole and praziquantel in MDA campaign conducted from January to March *** exams at week-4 and at week-8 of post-MDA were done using Kato Katz *** primary outcome was effcacy assessed by cure rate(CR)and fecal egg reduction rates(ERRs)at four weeks of *** secondary outcome was reinfection status defined as parasite egg positivity at eight weeks among those who were cured at 4 weeks of *** comparisons in CR and related factors were assessed with chi-square or Fisher's exact *** of CR were examined through univariate and multi-variate regression *** The overall CR and ERR for hookworm infection were 97.2%(95%CI:94.6-99.4)and 97.02%,*** overall CR and ERR for *** were 71.5%(95%CI:68.3-74.6)and 84.5% *** overall CR and ERR and for *** were 49.5%(95%CI:44.8-54.2)and 68.3%,*** CR among moderate *** infec-tion intensity was 28.6%.Among children cured of hookworm,*** and *** at week 4 post-MDA,4.6%,18.3% and 52.4% became reinfected at week-8 post-MDA,*** lower CR(36.6%)and higher reinfection after cure(60.6%)among *** and *** coinfected children than *** only(CR=69.6%,reinfection rate=15.1%)or *** only infected children(CR=55.6%,reinfection rate=47.1%)was obse

关键词： Soil transmitted helminths Neglected tropical diseases Preventive chemotherapy Albendazole School age children Ethiopia

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Variability of platelet aggregation in patients with clopidogrel treatment and hip fracture: A retrospective case-control study on 112 patients

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World Journal of Orthopedics 2015年第5期6卷 439-445页

作者： Anna Clareus Inga Fredriksson Hkan Wallén Max Gordon André Stark Olof Skldenberg Division of Orthopaedics Department of Clinical Sciences at Danderyd Hospital Karolinska Institutet Division of Anesthesiology Department of Clinical Sciences at Danderyd Hospital Karolinska Institutet Division of Cardiology Department of Clinical Sciences at Danderyd Hospital Karolinska Institute

AIM: To identify the rate of non-responders to clopidogrel treatment in hip fracture patients and study how non-responders differ from ***: In a retrospective case-control study we included 28 cases of acute proximal femoral fracture with clopidogrel treatment 2011 to 2013. Eighty-four controls from the same time period were included. Data collected included response to clopidogrel measured with multiple electrode aggregometry(MEA), intraoperative bleeding, erythrocyte transfusion, time to surgery and the incidence of adverse events up to 3 mo after surgery. RESULTS: Eight(29%) of the 28 cases were nonresponders. The median intraoperative bleeding was 300 mL(range, 0-1500), and was lower for non-responders(50 m L) but did not reach statistical significance. Erythrocyte transfusions did not differ between responders, non-responders and controls. Forty-five(40%) of 112 patients had adverse events postoperatively but the rate did not differ between patients with and without clopidogrel ***: Almost one-third of patients withclopidogrel treatment and an acute proximal femoral fracture are non-responders to antiplatelet therapy and can be operated without delay.

关键词： Proximal femoral fracture Clopidogrel Variability Bleeding Adverse events

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The role of corneal endothelium in macular corneal dystrophy development and recurrence

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Science China(Life Sciences) 2024年第2期67卷 332-344页

作者： Bi-Ning Zhang Benxiang Qi Chunxiao Dong Bin Zhang Jun Cheng Xin Wang Suxia Li Xiaoyun Zhuang Shijiu Chen Haoyun Duan Dewei Li Sujie Zhu Guoyun Li Yihai Cao Qingjun Zhou Lixin Xie Eye Institute of Shandong First Medical University Qingdao Eye Hospital of Shandong First Medical UniversityQingdao 266071China State Key Laboratory Cultivation Base Shandong Provincial Key Laboratory of OphthalmologyQingdao 266071China School of Ophthalmology Shandong First Medical UniversityQingdao 250021China Department of Medicine Qingdao UniversityQingdao 266071China Eye Institute of Shandong First Medical University Eye Hospital of Shandong First Medical University(Shandong Eye Hospital)Jinan 250021China Department of Ophthalmology School of Clinical MedicineWeifang Medical UniversityWeifang 261072China Institute of Translational Medicine College of MedicineQingdao UniversityQingdao 266071China Key Laboratory of Marine Drugs of Ministry of Education Shandong Provincial Key Laboratory of Glycoscience and GlycotechnologySchool of Medicine and PharmacyOcean University of ChinaQingdao 266071China Laboratory for Marine Drugs and Bioproducts Pilot National Laboratory for Marine Science and Technology(Qingdao)Qingdao 266071China Department of Microbiology Tumor and Cell BiologyBiomedicumKarolinska InstitutetStockholm 17177Sweden

Macular corneal dystrophy(MCD)is a progressive,bilateral stromal dystrophic disease that arises from mutations in carbohydrate sulfotransferase 6(CHST6).Corneal transplantation is the ultimate therapeutic solution for MCD ***,postoperative recurrence remains a significant *** conducted a retrospective review of a clinical cohort comprising 102 MCD patients with 124 eyes that underwent either penetrating keratoplasty(PKP)or deep anterior lamellar keratoplasty(DALK).Our results revealed that the recurrence rate was nearly three times higher in the DALK group(39.13%,9/23 eyes)compared with the PKP group(10.89%,11/101 eyes),suggesting that surgical replacement of the corneal endothelium for treating MCD is advisable to prevent postoperative *** experimental data confirmed the robust m RNA and protein expression of CHST6 in human corneal endothelium and the rodent homolog CHST5 in mouse *** knockdown of wild-type Chst5 in mouse corneal endothelium(AC^(siChst5)),but not in the corneal stroma,induced experimental MCD with similar extracellular matrix synthesis impairments and corneal thinning as observed in MCD *** carrying Chst5 point mutation also recapitulated clinical phenotypes of MCD,along with corneal endothelial *** injection of wild-type Chst5 rescued the corneal impairments in AC^(siChst5)mice and retarded the disease progression in Chst5 mutant ***,our study provides new mechanistic insights and therapeutic approaches for MCD treatment by highlighting the role of corneal endothelium in MCD development.

关键词： macular corneal dystrophy recurrence corneal endothelium keratan sulfate penetrating keratoplasty

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An Update on the Clinical Pipelines of New Antibacterial Drugs Developed in China

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Engineering 2024年第7期38卷 52-68页

作者： Xinyi Yang Congran Li Xiukun Wang Zhonghui Zheng Peiyi Sun Chunjie Xu Luni Chen Jiandong Jiang Staffan Normark Birgitta Henriques-Normark Xuefu You Beijing Key Laboratory of Antimicrobial Agents/Laboratory of Pharmacology Institute of Medicinal BiotechnologyChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China Division for Medicinal Microorganism-Related Strains CAMS Collection Center of Pathogenic MicroorganismsChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China State Key Laboratory of Bioactive Substances and Functions of Natural Medicines Institute of Medicinal BiotechnologyChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China Shandong Xinhua Pharmaceutical Co. Ltd.Zibo 255005China Department of Microbiology Tumor and Cell BiologyKarolinska InstitutetStockholm SE-17177Sweden State Key Laboratory of Bioactive Substances and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China Institute of Medicinal Biotechnology Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China Clinical Microbiology Karolinska University HospitalBioclinicumStockholm SE-17176Sweden

Antibacterial resistance is a global health threat that requires further concrete action on the part of all *** this context,one of the biggest concerns is whether enough new antibacterial drugs are being discovered and *** several high-quality reviews on clinical antibacterial drug pipelines from a global perspective were published recently,none provides comprehensive information on original antibacterial drugs at clinical stages in *** this review,we summarize the latest progress of novel antibacterial drugs approved for marketing and under clinical evaluation in China since *** was obtained by consulting official websites,searching commercial databases,retrieving literature,asking personnel from institutions or companies,and other means,and a considerable part of the data covered here has not been included in other *** of June 30,2023,a total of 20 antibacterial projects from 17 Chinese pharmaceutical companies or developers were identified and *** them,two new antibacterial drugs that belong to traditional antibiotic classes were approved by the National Medical Products Administration(NMPA)in China in 2019 and 2021,respectively,and 18 antibacterial agents are in clinical development,with one under regulatory evaluation,five in phase-3,six in phase-2,and six in *** of the clinical candidates are new analogs or monocomponents of traditional antibacterial pharmacophore types,including two dual-acting hybrid antibiotics and a recombinant antibacterial ***,despite there being 17 antibacterial clinical candidates,our analysis indicates that there are still relatively few clinically differentiated antibacterial agents in stages of clinical development in ***,Chinese pharmaceutical companies and institutions will develop more innovative and clinically differentiated candidates with good market potential in the future research and development(R&D)of original antibacterial drugs.

关键词： Antimicrobial resistance New antibiotics Clinical pipelines WHO priority pathogens National Mega-Project for Innovative Drugs

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High level of deoxycholic acid in human bile does not promote cholesterol gallstone formation

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World Journal of Gastroenterology 2003年第7期9卷 1576-1579页

作者： Ulf Gustafsson Staffan Sahlin Curt Einarsson Department of Surgery Danderyd HospitalStockholmSweden Division of Gastroenterology and Hepatology Department of MedicineHuddinge University HospitalKarolinska InstitutetStockholmSweden

AIM:To study whether patients with excess deoxycholic acid (DCA) differ from those with normal percentage of DCA with respect to biliary lipid composition and cholesterol saturation of gallbladder bile. METHODS:Bile was collected during operation through puncturing into the gallbladder from 122 cholesterol gallstone patients and 46 gallstone-free subjects undergoing *** data,biliary lipids,bile add composition, presence of crystals and nucleation time were analyzed. RESULTS:A subgroup of gallstone patients displayed a higher proportion of DCA in bile than gallstone free subjects. By choosing a cut-off level of the 90th percentile,a group of 13 gallstone patients with high DCA levels (mean 50 percent of total bile acids) and a large group of 109 patients with normal DCA levels (mean 21 percent of total bile acids) were *** mean age of the patients with high DCA levels was higher than that of the group with normal levels (mean age:62 years vs45 years) and so was the mean BMI (28.3 vs.24.7).Plasma levels of cholesterol and triglycerides were slightly higher in the DCA excess groups compared with those in the normal DCA *** was no difference in biliary lipid composition,cholesterol saturation,nucleation time or occurrence of cholesterol crystals in bile between patients with high and normal levels of DCA. CONCLUSION:Gallstone patients with excess DCA were of older age and had higher BMI than patients with normal *** two groups of patients did not differ with respect to biliary lipid composition,cholesterol saturation,nucleation time or occurrence of cholesterol *** is concluded that DCA in bile does not seem to contribute to gallstone formation in cholesterol gallstone patients.

关键词： Adolescent Adult Aged Aged, 80 and over Bile Body Mass Index Cholesterol Crystallization Deoxycholic Acid Female Gallstones Humans Lipids Male Middle Aged Research Support, Non-U.S. Gov't

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Current perspectives on mesenchymal stromal cell therapy for graft versus host disease

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Cellular & Molecular Immunology 2023年第6期20卷 613-625页

作者： Nadir Kadri Syivie Amu llen lacobaeus Erik Boberg Katarina Le Blanc Department of Laboratory Medicine Karolinska InstitutetStockholmSweden Department of Clinical Neuroscience Division of NeurologyKarolinska Institute and Karolinska University HospitalStockholmSweden Department of Haematology Karolinska University HospitalStockholmSweden Department of Cell Therapies and Allogeneic Stem Cell Transplantation Karolinska University hospital StockholmSweden

Graft versus host disease(GvHD)is the clinical condition in which bone marrow-derived mesenchymal stromal cells(MsCs)have been most frequently *** this review,we summarize the experience from clinical trials that have paved the way to *** MsC-based therapy has shown an exceptional safety profile,identifying potency assays and disease biomarkers that reliably predict the capacity of a specific MSC batch to alleviate GvHD has been *** GvHD diagnosis and staging are based solely on clinical criteria,individual patients recruited in the same clinical trial may have vastly different underlying biology,obscuring trial outcomes and making it difficult to determine the benefit of MsCs in subgroups of *** accumulating body of evidence indicates the importance of considering not only the cell product but also patient-specific biomarkers and/or immune characteristics in determining MSC responsiveness.A mode of action where intravascular MSC destruction is followed by monocyte-efferocytosis-mediated skewing of the immune repertoire in a permissive inflammatory environment would both explain why cell engraftment is irrelevant for MsC efficacy and stress the importance of biologic differences between responding and nonresponding *** recommend a combined analysis of clinical outcomes and both biomarkers of disease activity and MSC potency assays to identify patients with GvHD who are likely to benefit from MSC therapy.

关键词： MSC GVHD Hematological malignancies acute GVHD chronic GVHD

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