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Promising use of metformin in treating neurological disorders:biomarker-guided therapies

Neural Regeneration Research 2024年第5期19卷 1045-1055页

作者： Allison Loan Charvi Syal Margarita Lui Ling He Jing Wang regenerative medicine Program Ottawa Hospital Research InstituteOttawaONCanada department of Biology Faculty of ScienceUniversity of OttawaOttawaONCanada department of Pediatrics and medicine Johns Hopkins Medical SchoolBaltimoreMDUSA department of Cellular and Molecular medicine Faculty of MedicineUniversity of OttawaOttawaONCanada University of Ottawa Brain and Mind Research Institute OttawaONCanada

Neurological disorders are a diverse group of conditions that affect the nervous system and include neurodegenerative diseases(Alzheimer’s disease,multiple sclerosis,Parkinson’s disease,Huntington’s disease),cerebrovascular conditions(stroke),and neurodevelopmental disorders(autism spectrum disorder).Although they affect millions of individuals around the world,only a limited number of effective treatment options are available *** most neurological disorders express mitochondria-related metabolic perturbations,metformin,a biguanide type II antidiabetic drug,has attracted a lot of attention to be repurposed to treat neurological disorders by correcting their perturbed energy ***,controversial research emerges regarding the beneficial/detrimental effects of metformin on these neurological *** that most neurological disorders have complex etiology in their pathophysiology and are influenced by various risk factors such as aging,lifestyle,genetics,and environment,it is important to identify perturbed molecular functions that can be targeted by metformin in these neurological *** molecules can then be used as biomarkers to stratify subpopulations of patients who show distinct molecular/pathological properties and can respond to metformin treatment,ultimately developing targeted *** this review,we will discuss mitochondria-related metabolic perturbations and impaired molecular pathways in these neurological disorders and how these can be used as biomarkers to guide metformin-responsive treatment for the targeted therapy to treat neurological disorders.

关键词： Alzheimer’s disease Huntington’s disease metformin mitochondrial perturbation multiple sclerosis neural degenerative diseases Parkinson’s disease stroke targeted therapy

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CircZFR promotes colorectal cancer progression via stabilizing BCLAF1 and regulating the miR-3127-5p/RTKN2 axis

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Science China(Life Sciences) 2024年第9期67卷 1881-1898页

作者： Jiaxin Chen Huijuan Wang Jianbin Xu Engeng Chen Qing Meng Jiawei Wang Haoyi Xiang Wei Zhou Ge Shan Zhenyu Ju Zhangfa Song department of Colorectal Surgery Sir Run Run Shaw HospitalZhejiang University School of MedicineHangzhou 310016China Key Laboratory of Biological Treatment of Zhejiang Province Hangzhou 310016China department of Pulmonary and Critical Care medicine Regional medical center for National Institute of Respiratory DiseaseSir Run Run Shaw HospitalZhejiang University School of MedicineHangzhou 310016China Key Laboratory of regenerative medicine of Ministry of Education Institute of Aging and Regenerative MedicineJinan UniversityGuangzhou 510632China department of Breast Surgery the Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310009China department of Orthopedic Surgery the Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310009China

Aberrant expression of circular RNAs(circ RNAs)is frequently linked to colorectal cancer(CRC).Here,we identified circ ZFR as a promising biomarker for CRC diagnosis and *** ZFR was upregulated in CRC tissues and serum exosomes and its level was linked to cancer incidence,advanced-stages,and *** both in vitro and in vivo settings,circ ZFR promoted the growth and spread while suppressing apoptosis of *** with circ ZFR overexpression promoted the proliferation and migration of cocultured CRC ***,epithelial splicing regulatory protein 1(ESRP1)in CRC cells may enhance the production of circ ***2-associated transcription factor 1(BCLAF1)bound to circ ZFR,which prevented its ubiquitinated ***,circ ZFR sponged mi R-3127-5p to boost rhotekin 2(RTKN2)*** TCP1-CD-QDs nanocarrier was able to carry and deliver circ ZFR si RNA(si-circ ZFR)to the vasculature of CRC tissues and cells,which inhibited the growth of tumors in patient-derived xenograft(PDX)*** together,our results show that circ ZFR is an oncogenic circ RNA,which promotes the development and spread of CRC in a BCLAF1 and mi R-3127-5p-dependent *** ZFR is a possible serum biopsy marker for the diagnosis and a desirable target for further treatment of CRC.

关键词： circZFR exosome ESRP1 BCLAF1 miR-3127-5p nanoparticle(NP)

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Placenta-derived mesenchymal stem cells attenuate secondary brain injury after controlled cortical impact in rats by inhibiting matrix metalloproteinases

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BIOCELL 2024年第1期48卷 149-162页

作者： PING YANG YUANXIANG LAN ZHONG ZENG YAN WANG HECHUN XIA department of Neurosurgery School of Clinical MedicineNingxia Medical UniversityYinchuanChina Key Laboratory of Ningxia Stem Cell and regenerative medicine General Hospital of Ningxia Medical UniversityYinchuanChina department of Neurosurgery Xi’an International Medical Center HospitalXi’anChina

Background:As a form of biological therapy,placenta-derived mesenchymal stem cells(PDMSCs)exhibit considerable promise in addressing the complex pathological processes of traumaticbrain injury(TBI)due to their multi-target and multi-pathway mode of ***&Methods:This study investigates the protective mechanisms and benefits of PDMSCs in mitigating the effects of controlled cortical impact(CCI)in rats and glutamate-induced oxidative stress injury in HT22 cells in *** primary objective is to provide evidence supporting the clinical application of ***:In the in vivo arm of our investigation,we observed a swift elevation of matrix metalloproteinase-9(MMP-9)in the proximal cortex of injured brain tissues after ***,distinguished by their heightened expression of metalloproteinase tissue inhibitors-1 and-2(TIMP-1 and TIMP-2):were intravenously administered via the caudal *** intervention yielded significant reductions in the permeability of the blood-brain barrier(BBB):the extent of brain edema,the levels of inflammatory cytokines IL-1βand TNF-αin damaged brain tissue,and the activation status of microglia in CCI-afflicted *** the realm of in vitro experiments,PDMSC-conditioned media demonstrated substantial reductions in mortality rates and cleaved caspase-3 levels in glutamate-induced HT22 cells compared with conventional ***,this advantage was negated upon the introduction of neutralizing antibodies targeting TIMP-1 and ***:Collectively,our findings underscore the potential of PDMSCs in alleviating oxidative stress injury and secondary brain injury in the pathological process of TBI.

关键词： Traumatic brain injury Mesenchymal stem cells Oxidative stress Matrix metalloproteinases

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Therapeutic advances in atrial fibrillation based on animal models

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第2期25卷 135-152页

作者： Qian GONG Xuan LE Pengcheng YU Lenan ZHUANG Institute of Genetics and Reproduction College of Animal SciencesZhejiang UniversityHangzhou310058China Key Laboratory of Cardiovascular Intervention and regenerative medicine of Zhejiang Province Department of CardiologySir Run Run Shaw HospitalSchool of MedicineZhejiang UniversityHangzhou310016China

Atrial fibrillation(AF)is the most prevalent sustained cardiac arrhythmia among humans,with its incidence increasing significantly with *** the high frequency of AF in clinical practice,its etiology and management remain *** develop effective treatment strategies,it is imperative to comprehend the underlying mechanisms of AF;therefore,the establishment of animal models of AF is vital to explore its *** spontaneous AF is rare in most animal species,several large animal models,particularly those of pigs,dogs,and horses,have proven as invaluable in recent years in advancing our knowledge of AF pathogenesis and developing novel therapeutic *** review aims to provide a comprehensive discussion of various animal models of AF,with an emphasis on the unique features of each model and its utility in AF research and *** data summarized in this review provide valuable insights into the mechanisms of AF and can be used to evaluate the efficacy and safety of novel therapeutic interventions.

关键词： Atrial fibrillation Animal model Therapeutic

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Validation and performance of three scoring systems for predicting primary non-function and early allograft failure after liver transplantation

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Hepatobiliary & Pancreatic Diseases International 2024年第5期23卷 463-471页

作者： Yu Nie Jin-Bo Huang Shu-Jiao He Hua-Di Chen Jun-Jun Jia Jing-Jing Li Xiao-Shun He Qiang Zhao General Surgery Center Department of Hepatobiliary Surgery IIResearch Center for Artificial Organ and Tissue EngineeringGuangzhou Clinical Research and Transformation Center for Artificial LiverInstitute of Regenerative MedicineZhujiang HospitalSouthern Medical UniversityGuangzhou 510515China Organ Transplant Center the First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510080China Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology Guangzhou 510080China Guangdong Provincial International Cooperation Base of Science and Technology Guangzhou 510080China Division of Hepatobiliary Pancreatic Surgery the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China

Background: Primary non-function(PNF) and early allograft failure(EAF) after liver transplantation(LT) seriously affect patient outcomes. In clinical practice, effective prognostic tools for early identifying recipients at high risk of PNF and EAF were urgently needed. Recently, the Model for Early Allograft Function(MEAF), PNF score by King's College(King-PNF) and Balance-and-Risk-Lactate(BAR-Lac) score were developed to assess the risks of PNF and EAF. This study aimed to externally validate and compare the prognostic performance of these three scores for predicting PNF and EAF. Methods: A retrospective study included 720 patients with primary LT between January 2015 and December 2020. MEAF, King-PNF and BAR-Lac scores were compared using receiver operating characteristic(ROC) and the net reclassification improvement(NRI) and integrated discrimination improvement(IDI) analyses. Results: Of all 720 patients, 28(3.9%) developed PNF and 67(9.3%) developed EAF in 3 months. The overall early allograft dysfunction(EAD) rate was 39.0%. The 3-month patient mortality was 8.6% while 1-year graft-failure-free survival was 89.2%. The median MEAF, King-PNF and BAR-Lac scores were 5.0(3.5–6.3),-2.1(-2.6 to-1.2), and 5.0(2.0–11.0), respectively. For predicting PNF, MEAF and King-PNF scores had excellent area under curves(AUCs) of 0.872 and 0.891, superior to BAR-Lac(AUC = 0.830). The NRI and IDI analyses confirmed that King-PNF score had the best performance in predicting PNF while MEAF served as a better predictor of EAD. The EAF risk curve and 1-year graft-failure-free survival curve showed that King-PNF was superior to MEAF and BAR-Lac scores for stratifying the risk of EAF. Conclusions: MEAF, King-PNF and BAR-Lac were validated as practical and effective risk assessment tools of PNF. King-PNF score outperformed MEAF and BAR-Lac in predicting PNF and EAF within 6 months. BAR-Lac score had a huge advantage in the prediction for PNF without post-transplant variables. Proper use

关键词： Primary non-function Early allograft failure Risk predicting model Liver transplantation

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New evidence for the epigenetic regulation of skeletal stem cells

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Science Bulletin 2024年第13期69卷 2004-2006页

作者： Liming Zhao Jun Xiao Charles K.F.Chan Institute for Stem Cell Biology and regenerative medicine Stanford University School of MedicineStanford CA 94305USA department of Surgery Division of Plastic and Reconstructive SurgeryStanford University School of MedicineStanford CA 94305USA department of Orthopaedic Surgery Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China

Skeletal stem cells(SSCs)are crucial for skeletal development and regeneration,yet the epigenetic regulation of these cells remains poorly *** studies have delineated the epigenetic landscape across the developmental trajectory of SSCs,highlighting the involvement of Ptip in regulating SSC *** skeletal system undergoes dynamic remodeling throughout *** stem cells(SSCs),residing within the skeleton and lineage-restricted,serve as a cellular reserve to foster development and maintain skeletal *** categorized within the broader mesenchymal stromal/stem cells(MSCs).

关键词： skeletal involvement maintain

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The Effect of Spironolactone Loading on the Properties of 3D-Printed Polycaprolactone/Gold Nanoparticles Composite Scaffolds for Myocardial Tissue Engineering

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Journal of Bionic Engineering 2024年第2期21卷 924-937页

作者： Sharareh Ghaziof Shahrokh Shojaei Mehdi Mehdikhani Mohammad Khodaei Milad Jafari Nodoushan department of Biomedical Engineering Central Tehran BranchIslamic Azad UniversityTehran***Iran Stem Cells Research Center Tissue Engineering and Regenerative Medicine InstituteCentral Tehran BranchIslamic Azad UniversityTehran***Iran department of Biomedical Engineering Faculty of EngineeringUniversity of IsfahanIsfahan***Iran Materials Engineering Group Golpayegan College of EngineeringIsfahan University of TechnologyGolpayegan87717-67498Iran Hard Tissue Engineering Research Center Tissue Engineering and Regenerative Medicine InstituteCentral Tehran BranchIslamic Azad UniversityTehran***Iran

Engineered cardiac constructs(ECC)aid in the progression of regenerative medicine,disease modeling and targeted drug delivery to adjust and aim the release of remedial combination as well as decrease the side effects of *** this research,polycaprolactone/gold nanoparticles(PCL/GNPs)three-dimensional(3D)composite scaffolds were manufactured by 3D printing using the fused deposition modeling(FDM)method and then coated with gelatin/spironolactone(GEL/SPL).Scanning electron microscopy(SEM)and Fourier transform-infrared spectroscopy(FTIR–ATR)were applied to characterize the ***,drug release,biodegradation,behavior of the myoblasts(H9C2)cell line,and cytotoxicity of the 3D scaffolds were *** microstructural observation of the scaffolds reported interconnected pores with 150–300µm in *** 3D scaffolds were degraded significantly after 28 days of immersion in stimulated body fluid(SBF),with the maximum rate of GEL-coated 3D *** release from cross-linked GEL coating demonstrated the excess of drug release over time,and according to the control release systems,the drug delivery systems(DDS)went into balance after the 14th *** addition,cell culture study showed that with the addition of GNPs,the proliferation of(H9C2)was enhanced,and with GEL/SPL coating the cell attachment and viability were improved *** findings suggested that PCL/GNPs 3D scaffolds coated with GEL/SPL can be an appropriate choice for myocardial tissue engineering.

关键词： Polycaprolactone Gold nanoparticles Drug delivery systems Spironolactone Cell behavior Myoblasts

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Efficacy of stromal vascular fraction for knee osteoarthritis:A prospective,single-centre,non-randomized study with 2 years follow-up

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World Journal of Orthopedics 2024年第5期15卷 457-468页

作者： Madhan Jeyaraman Naveen Jeyaraman Tarun Jayakumar Swaminathan Ramasubramanian Rajni Ranjan Saurabh Kumar Jha Ashim Gupta department of Orthopaedics ACS Medical College and HospitalDr MGR Educational and Research InstituteChennaiTamil Nadu 600077India department of Biotechnology School of Engineering and TechnologySharda UniversityGreater NoidaUttar Pradesh 201310India department of Orthopaedics and regenerative medicine South Texas Orthopaedic Research InstituteLaredoTX 78045United States department of Orthopaedics KIMS-Sunshine HospitalHyderabadTelangana 500032India department of Orthopaedics Government Medical CollegeOmandurar Government EstateChennaiTamil Nadu 600002India department of Orthopaedics School of Medical Sciences and ResearchSharda UniversityGreater NoidaUttar Pradesh 201306India department of Zoology Kalindi CollegeUniversity of DelhiNew Delhi 110008India department of Orthopaedics and regenerative medicine Regenerative OrthopaedicsNoida 201301Uttar PradeshIndia department of Orthopaedics and regenerative medicine Future BiologicsLawrencevilleGA 30043United States department of Orthopaedics and regenerative medicine BioIntegrateLawrencevilleGA 30043United States

BACKGROUND Current osteoarthritis(OA)treatments focus on symptom relief without addressing the underlying disease *** regenerative medicine,current treatments have *** regenerative medicine,more research is needed for intra-articular stromal vascular fraction(SVF)injections in OA,including dosage optimization,long-term efficacy,safety,comparisons with other treatments,and mechanism *** To compare the efficacy of intra-articular SVF with corticosteroid(ICS)injections in patients with primary knee *** The study included 50 patients with Kellgren-Lawrence grades II and III *** were randomly assigned(1:1)to receive either a single intra-articular SVF injection(group A)or a single intra-articular ICS(triamcinolone)(group B)*** were followed up at 1,3,6,12,and 24 *** analog score(VAS)and International Knee Documentation Committee(IKDC)scores were administered before the procedure and at all *** safety of SVF in terms of adverse and severe adverse events was *** analysis was performed with SPSS Version 26.0,IBM Corp,Chicago,IL,United *** Both groups had similar demographics and baseline clinical ***-up showed minor patient loss,resulting in 23 and 24 in groups A and B *** A experienced a notable reduction in pain,with VAS scores decreasing from 7.7 to 2.4 over 24 months,compared to a minor reduction from 7.8 to 6.2 in Group *** difference in pain reduction in group A was statistically significant from the third month ***,Group A showed significant improvements in knee functionality,with IKDC scores rising from 33.4 to 83.10,whereas Group B saw a modest increase from 36.7 to *** improvement in Group A was statistically significant from 6 months and maintained through 24 *** Our study demonstrated that intra-articular administration of SVF can lead to reduced pain and improved knee function in pa

关键词： Knee osteoarthritis Adipose tissue Stromal vascular fraction regenerative medicine Orthobiologics

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MAP4K inhibition as a potential therapy for amyotrophic lateral sclerosis

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Neural Regeneration Research 2024年第8期19卷 1639-1640页

作者： Shuaipeng Ma Chun-Li Zhang department of Molecular Biology University of Texas Southwestern Medical CenterDallasTXUSA Hamon Center for regenerative Science and medicine University of Texas Southwestern Medical CenterDallasTXUSA

Amyotrophic lateral sclerosis(ALS)is a rare neurological disease,featuring gradual loss of muscle controls due to degeneration of motor ***,there is currently no cure for *** available therapies only offer a limited e... 详细信息

关键词： degeneration sclerosis MAP4

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A pathological joint-liver axis mediated by matrikine-activated CD4^(+)T cells

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2679-2693页

作者： Junzhi Yi Hui Zhang Fangyuan Bao Zhichu Chen Yuliang Zhong Tianning Ye Xuri Chen Jingyi Qian Mengya Tian Min Zhu Zhi Peng Zongyou Pan Jianyou Li Zihao Hu Weiliang Shen Jiaqi Xu Xianzhu Zhang Youzhi Cai Mengjie Wu Hua Liu Jing Zhou Hongwei Ouyang department of Sports medicine of the Second Affiliated Hospital and Liangzhu LaboratoryZhejiang University School of MedicineHangzhouChina Dr.Li Dak Sum&Yip Yio Chin Center for Stem Cells and regenerative medicine Zhejiang University School of MedicineHangzhouChina Stomatology Hospital School of StomatologyZhejiang University School of MedicineZhejiang Provincial Clinical Research Center for Oral DiseasesHangzhouChina The MOE Key Laboratory of Biosystems Homeostasis&Protection The Key Laboratory of Cancer Molecular Cell Biology of Zhejiang ProvinceLife Sciences InstituteZhejiang UniversityHangzhouChina department of Orthopedics Huzhou Central HospitalAffiliated Huzhou HospitalZhejiang University School of MedicineHuzhouChina China Orthopedic regenerative medicine Group(CORMed) HangzhouChina department of Orthopedics The First Affiliated HospitalZhejiang University School of MedicineHangzhouChina

The knee joint has long been considered a closed *** pathological effects of joint diseases on distant organs have not been ***,our clinical data showed that post-traumatic joint damage,combined with joint bleeding(hemarthrosis),exhibits a worse liver function compared with healthy *** mouse model,hemarthrosis induces both cartilage degeneration and remote liver ***,we found that hemarthrosis induces the upregulation in ratio and differentiation towards Th17 cells of CD4^(+)T cells in peripheral blood and *** of CD4^(+)T cells reverses hemarthrosis-induced liver *** of cartilage matrix induced by hemarthrosis upregulates serological type Ⅱ collagen(COL Ⅱ),which activates CD4^(+)T *** application of a COL Ⅱ antibody blocks the ***,bulk RNAseq and single-cell qPCR analysis revealed that the cartilage Akt pathway is inhibited by blood ***-articular application of Akt activator blocks the cartilage degeneration and thus protects against the liver impairment in mouse and pig *** together,our study revealed a pathological joint-liver axis mediated by matrikine-activated CD4^(+)T cells,which refreshes the organ-crosstalk axis and provides a new treatment target for hemarthrosis-related disease.

关键词： degeneration damage inhibited

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