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Recent advances in promising drugs for primary prevention of gastroesophageal variceal bleeding with cirrhotic portal hypertension

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Hepatobiliary & Pancreatic Diseases International 2024年第1期23卷 4-13页

作者： Ji-Yao Sheng Zi-Fan Meng Qiao Li Yong-Sheng Yang department of Hepatobiliary and Pancreatic surgery the Second Hospital of Jilin UniversityChangchun 130041China Jilin Engineering Laboratory for translational medicine of Hepatobiliary and Pancreatic Diseases the Second Hospital of Jilin UniversityChangchun 130041China

Background:Gastroesophageal variceal bleeding is one of the most severe complications of patients with *** primary prevention drugs,including non-selectiveβ-blockers,have effectively reduced the incidence of bleeding,their efficacy is limited due to side effects and related *** recent advances in precision medicine,precise drug treatment provides better treatment *** sources:Literature search was conducted in PubMed,MEDLINE and Web of Science for relevant articles published up to May *** on clinical trials was obtained from https://***/and http://***/.Results:The in-depth understanding of the pathogenesis and advances of portal hypertension has enabled the discovery of multiple molecular targets for promising *** to the site of action,these drugs could be classified into four classes:intrahepatic,extrahepatic,both intrahepatic and extrahepatic targets and *** these classes of drugs offer advantages over traditional treatments in prevention of gastroesophageal variceal bleeding in patients with cirrhotic portal ***:This review classified and summarized the promising drugs,which prevent gastroesophageal variceal bleeding by targeting specific markers of pathogenesis of portal hypertension,demonstrating the significance of using the precision medicine strategy to discover and develop promising drugs for the primary prevention of gastroesophageal variceal bleeding in patients with cirrhotic portal hypertension.

关键词： Cirrhotic portal hypertension Target drug Primary prevention Bleeding

Regenerative medicine strategies for chronic complete spinal cord injury

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Neural Regeneration Research 2024年第4期19卷 818-824页

作者： Shogo Hashimoto Narihito Nagoshi Masaya Nakamura Hideyuki Okano department of Orthopedic surgery Keio University School of Medicine department of Physiology Keio University School of Medicine

Spinal cord injury is a condition in which the parenchyma of the spinal cord is damaged by trauma or various *** rapid progress has been made in regenerative medicine for spinal cord injury that was previously untreatable,most research in this field has focused on the early phase of incomplete ***,the majority of patients have chronic severe injuries;therefore,treatments for these situations are of fundamental *** reason why the treatment of complete spinal cord injury has not been studied is that,unlike in the early stage of incomplete spinal cord injury,there are various inhibitors of neural ***,we assumed that it is difficult to address all conditions with a single treatment in chronic complete spinal cord injury and that a combination of several treatments is essential to target severe ***,we established a combination therapy of cell transplantation and drug-releasing scaffolds,which contributes to functional recovery after chronic complete transection spinal cord injury,but we found that functional recovery was limited and still needs further ***,for the further development of the treatment of chronic complete spinal cord injury,we review the necessary approaches to the different pathologies based on our findings and the many studies that have been accumulated to date and discuss,with reference to the literature,which combination of treatments is most effective in achieving functional recovery.

关键词： cell transplantation chronic phase complete transection regenerative medicine spinal cord injury

Thiamine-modified metabolic reprogramming of human pluripotent stem cell-derived cardiomyocyte under space microgravity

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2132-2142页

作者： Xinglong Han Lina Qu Miao Yu Lingqun Ye Liujia Shi Guangfu Ye Jingsi Yang Yaning Wang Hao Fan Yong Wang Yingjun Tan Chunyan Wang Qi Li Wei Lei Jianghai Chen Zhaoxia Liu Zhenya Shen Yinghui Li Shijun Hu department of Cardiovascular surgery of the First Affiliated Hospital&Institute for Cardiovascular Science State Key Laboratory of Radiation Medicine and ProtectionSuzhou Medical CollegeSoochow UniversitySuzhouChina State Key Laboratory of Space medicine China Astronaut Research and Training CenterBeijingChina department of hand surgery Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina

During spaceflight,the cardiovascular system undergoes remarkable adaptation to microgravity and faces the risk of cardiac ***,the effects and mechanisms of microgravity on cardiac morphology,physiology,metabolism,and cellular biology need to be further *** China started constructing the China Space Station(CSS)in 2021,we have taken advantage of the Shenzhou-13 capsule to send human pluripotent stem cell-derived cardiomyocytes(hPSC-CMs)to the Tianhe core module of the *** this study,hPSC-CMs subjected to space microgravity showed decreased beating rate and abnormal intracellular calcium *** and transcriptomic analyses revealed a battery of metabolic remodeling of hPSC-CMs in spaceflight,especially thiamine *** microgravity condition blocked the thiamine intake in *** decline of thiamine utilization under microgravity or by its antagonistic analog amprolium affected the process of the tricarboxylic acid *** decreased ATP production,which led to cytoskeletal remodeling and calcium homeostasis imbalance in *** importantly,in vitro and in vivo studies suggest that thiamine supplementation could reverse the adaptive changes induced by simulated *** study represents the first astrobiological study on the China Space Station and lays a solid foundation for further aerospace biomedical *** data indicate that intervention of thiamine-modified metabolic reprogramming in human cardiomyocytes during spaceflight might be a feasible countermeasure against microgravity.

关键词： programming battery modified

Engineered plant extracellular vesicles for autoimmune diseases therapy

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Nano Research 2024年第4期17卷 2857-2873页

作者： Ruina Han Yan Wu Yafei Han Xiangfei Liu Han Liu Jiacan Su Institute of translational medicine Shanghai UniversityShanghai 200444China Organoid Research Center Shanghai UniversityShanghai 200444China National Center for translational medicine(Shanghai)SHU Branch Shanghai UniversityShanghai 200444China department of Orthopedics Shanghai Zhongye HospitalShanghai 200941China department of Orthopedics Xinhua HospitalShanghai Jiao Tong University School of MedicineShanghai 200092China

Autoimmune diseases(AID)encompass a diverse array of conditions characterized by immune system dysregulation,resulting in aberrant responses of B cells and T cells against the body’s own healthy *** extracellular vesicles(PEVs)are nanoscale particles enclosed by phospholipid bilayers,secreted by plant cells,which facilitate intercellular communication by transporting various bioactive *** to their nanoscale structure,safety,abundant sources,low immunogenicity,high yield,biocompatibility,and effective targeting of the colon and liver,PEVs are regarded as a promising platform for the treatment of *** review provides a comprehensive summary of PEV biogenesis,physicochemical and biological properties,internalization mechanisms,isolation methods,and their applications in various diseases,with a specific focus on their potential roles in ***,we propose engineering approaches and administration methods for ***,we present an overview of the advantages and challenges associated with utilizing PEVs for the treatment of *** gaining a comprehensive understanding of PEVs,we anticipate the development of innovative therapeutic strategies for *** and engineered PEVs hold substantial promise as a valuable resource for innovative technologies in AID treatment.

关键词： autoimmune diseases plant extracellular vesicles extracellular vesicles engineering modification

SETDB1-mediated CD147-K71 di-methylation promotes cell apoptosis in non-small cell lung cancer

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Genes & Diseases 2024年第2期11卷 978-992页

作者： Ming-Yan Shi Yarong Wang Ying Shi Ruofei Tian Xiaohong Chen Hai Zhang Ke Wang Zhinan Chen Ruo Chen National translational Science Center for Molecular medicine & department of Cell Biology Fourth Military Medical UniversityXi'anShaanxi 710032China

Protein post-translational modifications(PTMs)are at the heart status of cellular signaling events and broadly involved in tumor ***147 is a tumor biomarker with various PTMs,promoting tumor metastasis and metabolism ***,the relationship between the PTMs of CD147 and apoptosis has not been *** our study,we produced a specific anti-CD147-K71 di-methylation(CD147-K71me2)antibody by immunizing with a di-methylated peptide and observed that the level of CD147-K71me2 in non-small cell lung cancer(NSCLC)tissues were lower than that in NSCLC adjacent ***1 was identified as the methyltransferase catalyzing CD147 to generate ***-seq showed that FOSB was the most significant differentially expressed gene(DEG)between wild-type CD147(CD147-WT)and K71-mutant CD147(CD147-K71R)***,we found that CD147-K71me2 promoted the expression of FOSB by enhancing the phosphorylation of p38,leading to tumor cell *** vivo experiments showed that CD147-K71me2 significantly inhibited tumor progression by promoting cell *** together,our findings indicate the inhibitory role of CD147-K71me2 in tumor progression from the perspective of post-translational modification,which is distinct from the pro-cancer function of CD147 itself,broadening our perspective on tumor-associated antigen CD147.

关键词： CD147 di-methylation Cell apoptosis FOSB Non-small cell lung cancer SETDB1

Paeoniflorin,the Main Monomer Component of Paeonia lactiflora,Exhibits Anti-inflammatory Properties in Osteoarthritis Synovial Inflammation

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Chinese Journal of Integrative medicine 2024年第5期30卷 433-442页

作者： CHEN Pu ZHOU Jun RUAN An-min MA Yu-feng WANG Qing-fu department of Orthopaedic surgery Beijing University of Chinese Medicine Third Affiliated HospitalBeijing 100029China department of Orthopaedic surgery Guangdong Provincial Hospital of Chinese MedicineGuangzhou 510120China department of Orthopaedic surgery Beijing Longfu HospitalBeijing 100010China

Objective:To explore the mechanism of paeoniflorin(PF)on osteoarthritis(OA)synovial inflammation from network pharmacology to experimental ***:Targets of OA were constructed by detecting the database of network database platforms(Therapeutic Target database,Drug Bank and Gene Cards),and the targets of PF were constructed by Pub Chem and Herbal Ingredients'Targets *** Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis of these co-targeted genes were conducted via Database for Annotation,Visualization,and Integrated Discovery(DAVID)database,and protein-protein interaction(PPI)networks were conducted via the search tool for the retrieval of interacting genes(STRING)*** counting kit-8(CCK-8)assay was performed to assess the potential toxicity of PF on human OA fibroblast-like synoviocytes(FLS),quantitative real-time polymerase chain reaction(q PCR),enzyme-linked immunosorbent assay(ELISA)and Western blot were used to verify the potential mechanism of PF in synovial ***:Twenty-six co-targeted genes were *** enrichment results showed that these co-targeted genes were most likely localized in the cytoplasm,and the biological processes mainly involved'cellular response to hypoxia''lipopolysaccharide(LPS)-mediated signaling pathway'and'positive regulation of gene expression'.KEGG pathway analysis indicated that these co-targeted genes may function through pathways associated with'hypoxia-inducible factor-1(HIF-1)signaling pathway'and'tumornecrosis factor(TNF)signaling pathway'.The PPI network showed that the top 3 hub genes were TP53,TNF,and *** docking results showed that PF was well docking with ***-8 showed no potential toxicity of 10,20 and 50μmol/L PF on human OA *** PF significantly decreased the expression levels of interleukin-1β,interleukin-6,TNF-αmatrix metalloproteinase 13(MMP13),and a disintegrin and metalloproteinase with thrombospondin motifs 5(ADAMTS5)and TNF

关键词： paeoniflorin osteoarthritis synovial inflammation tumor necrosis factor-α network pharmacology Paeonia lactiflora

Periplaneta americana extract promotes infectious diabetic ulcers wound healing by downregulation of LINC01133/SLAMF9

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Chinese Journal of Natural medicines 2024年第7期22卷 608-618页

作者： YANG Yuhang HUANG Jun LI Xintian LIN Renjing WANG Xiaoyan XIAO Ge ZENG Juanni WANG Zhenquan department of Anorectal Disease 1 The Second Affiliated Hospital of Hunan University of Traditional Chinese MedicineChangsha 410005China department of Anorectal Disease 3 The Second Affiliated Hospital of Hunan University of Traditional Chinese MedicineChangsha 410005China Laboratory of Vascular Biology and translational medicine Medical SchoolHunan University of Chinese Medicine/Hunan Provincial Key Laboratory of Vascular Biology and Translational MedicineChangsha 410208China

Wound healing in diabetic ulcers remains a significant clinical challenge,primarily due to bacterial infection and impaired *** americana extract(PAE)has been widely used to treat diabetic wounds,yet its underlying mechanisms are not fully *** study aimed to elucidate these mechanisms by analyzing long non-coding RNA(lncRNA)expressions in the wound tissues from diabetic anal fistula patients treated with or without PAE,using high-throughput *** blood monocytes from patients were differentiated into M0 macrophages with human macrophage colony-stimulating factor(hMCSF)and subsequently polarized into M1 macrophages with *** results indicated that LINC01133 and SLAMF9 were downregulated in wound tissues of patients treated with ***,PAE suppressed M1 macrophage polarization and enhanced human umbilical vein endothelial cell(HUVEC)proliferation,migration,and *** effects were diminished when LINC01133 or SLAMF9 were ***,LINC01133 was shown to upregulate SLAMF9 through interaction with *** of SLAMF9 reversed the effects of LINC01133 silencing on macrophage polarization and HUVEC *** conclusion,PAE facilitates the healing of infected diabetic ulcers by downregulating the LINC01133/SLAMF9 pathway.

关键词： Periplaneta americana extract Infectious diabetic ulcers M1 macrophage polarization LINC01133 SLAMF9

Dexamethasone and N-acetylcysteine before transarterial chemoembolization in hepatocellular carcinoma:A Western perspective

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World Journal of Gastroenterology 2024年第31期30卷 3635-3639页

作者： Marco Biolato Maurizio Pompili department of Medical and Surgical Sciences CEMAD Digestive Disease CenterFondazione Policlinico Universitario Agostino Gemelli IRCCSRome 00168Italy department of translational medicine and surgery Catholic University of Sacred HeartRome 00168LazioItaly

Post-embolization syndrome(PES)is the most common complication in patients with hepatocellular carcinoma treated with transarterial *** strategies have been evaluated to reduce the incidence of PES,but no standard prevention guidelines currently *** a single-center,placebo-controlled trial,Simasingha et al evaluated the prophylactic administration of a combination of dexamethasone and N-acetylcysteine and documented a significant reduction in the incidence of PES(from 80%to 6%),of post-procedural liver decompensation(from 14%to 0%),and a shorter hospital stay(4 days vs 6 days),alongside an acceptable safety *** results of this study raise several controversial points regarding their applicability in the Western *** the West,there is a greater and increasing prevalence of metabolic and alcoholic etiologies of liver cirrhosis,so a not negligible number of patients with type II diabetes or hypertension would be excluded from high-dosage dexamethasone ***,in the West,there is a preferred use of drug-eluting beads loaded with doxorubicin,which are associated with a lower incidence of PES.A study on prophylaxis with dexamethasone and/or N-acetylcysteine in a Western population is hopefully awaited.

关键词： Chemotherapeutic drugs Lipiodol Post-embolization syndrome Prevention Prophylaxis

Long-term outcome of stem cell transplantation with and without anti-tumor necrotic factor therapy in perianal fistula with Crohn’s disease

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World Journal of Stem Cells 2024年第3期16卷 257-266页

作者： Min Young Park Yong Sik Yoon Jae Ha Park Jong Lyul Lee Chang Sik Yu Division of Colon and Rectal surgery Department of SurgeryYonsei University College of MedicineSeoul 03722South Korea Division of Colon and Rectal surgery Department of SurgeryUniversity of Ulsan College of MedicineAsan Medical CenterSeoul 05505South Korea

BACKGROUND Stem cell transplantation is a promising therapeutic option for curing perianal fistula in Crohn’s disease(CD).Anti-tumor necrotic factor(TNF)therapy combined with drainage procedure is effective as ***,previous studies are limited to proving whether the combination treatment of biologics and stem cell transplantation improves the effect of fistula *** This study aimed to evaluate the long-term outcomes of stem cell transplantation and compare Crohn’s perianal fistula(CPF)closure rates after stem cell transplantation with and without anti-TNF therapy,and to identify the factors affecting CPF closure and *** The patients with CD who underwent stem cell transplantation for treating perianal fistula in our institution between Jun 2014 and December 2022 were *** data were compared according to anti-TNF therapy and CPF *** A total of 65 patients were *** median age of females was 26 years(range:21-31)and that of males was 29(44.6%).The mean follow-up duration was 65.88±32.65 months,and complete closure was observed in 50(76.9%)*** closure rates were similar after stem cell transplantation with and without anti-TNF therapy(66.7%vs 81.6%at 3 year,P=0.098).The patients with fistula closure had short fistulous tract and infrequent proctitis and anorectal stricture(P=0.027,0.002,and 0.008,respectively).Clinical factors such as complexity,number of fistulas,presence of concurrent abscess,and medication were not significant for *** cumulative 1-,2-,and 3-year closure rates were 66.2%,73.8%,and 75.4%,*** Anti-TNF therapy does not increase CPF closure rates in patients with stem cell ***,both refractory and non-refractory CPF have similar closure rates after additional anti-TNF *** tract length,proctitis,and anal stricture are risk factors for non-closure in patients with CPF after stem cell transplantation.

关键词： Crohn’s disease Anus Fistula Stem cell transplantation Tumor necrosis factor-alpha inhibitors Infliximab