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Hepatobiliary & Pancreatic Diseases International 2024年第2期23卷 123-128页

作者： Prashant Bhangui institute of Liver Transplantation and regenerative medicine Medanta–The MedicitySector 38GurgaonDelhi NCR 122001India

Patients with locally advanced hepatocellular cancer(HCC)and portal vein tumor thrombosis(PVTT)have a dismal prognosis since limited treatment options are available for *** recent years,effective systemic therapy,and advances in the understanding of technicalities and effectiveness of ablative therapies especially radiotherapy,have given some hope to prolong survival in *** review summarized recent evidence in literature regarding the possible role of liver resection(LR)and liver transplantation(LT)in patients with locally advanced HCC and PVTT with no extrahepatic *** therapies have helped make curative resection or LT a reality in selected *** review emphasizes on the key points to focus on when considering surgery in these patients,who are usually relegated to palliative systemic therapy *** patient selection based on tumor biology,documented downstaging based on imaging and decrease in tumor marker levels,and an adequate waiting period to demonstrate stable disease,may help obtain satisfactory long-term outcomes post LR or LT in an intention to treat strategy in patients with HCC and PVTT.

关键词： Hepatocellular carcinoma Portal vein tumour thrombosis Downstaging therapies Living donor liver transplantation and resection Outcomes

How do neurons age?A focused review on the aging of the microtubular cytoskeleton

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Neural Regeneration Research 2024年第9期19卷 1899-1907页

作者： Brad Richardson Thomas Goedert Shmma Quraishe Katrin Deinhardt Amritpal Mudher School of Biological Sciences University of SouthamptonSouthamptonUK institute of Developmental and regenerative medicine University of OxfordOxfordUK

Aging is the leading risk factor for Alzheimer’s disease and other neurodegenerative diseases. We now understand that a breakdown in the neuronal cytoskeleton, mainly underpinned by protein modifications leading to the destabilization of microtubules, is central to the pathogenesis of Alzheimer’s disease. This is accompanied by morphological defects across the somatodendritic compartment, axon, and synapse. However, knowledge of what occurs to the microtubule cytoskeleton and morphology of the neuron during physiological aging is comparatively poor. Several recent studies have suggested that there is an age-related increase in the phosphorylation of the key microtubule stabilizing protein tau, a modification, which is known to destabilize the cytoskeleton in Alzheimer’s disease. This indicates that the cytoskeleton and potentially other neuronal structures reliant on the cytoskeleton become functionally compromised during normal physiological aging. The current literature shows age-related reductions in synaptic spine density and shifts in synaptic spine conformation which might explain age-related synaptic functional deficits. However, knowledge of what occurs to the microtubular and actin cytoskeleton, with increasing age is extremely limited. When considering the somatodendritic compartment, a regression in dendrites and loss of dendritic length and volume is reported whilst a reduction in soma volume/size is often seen. However, research into cytoskeletal change is limited to a handful of studies demonstrating reductions in and mislocalizations of microtubule-associated proteins with just one study directly exploring the integrity of the microtubules. In the axon, an increase in axonal diameter and age-related appearance of swellings is reported but like the dendrites, just one study investigates the microtubules directly with others reporting loss or mislocalization of microtubule-associated proteins. Though these are the general trends reported, there are clea

关键词： age-related changes aging cytoskeleton microtubules neuronal morphology

Genome-edited rabbits:Unleashing the potential of a promising experimental animal model across diverse diseases

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Zoological Research 2024年第2期45卷 253-262页

作者： Yang Han Jiale Zhou Renquan Zhang Yuru Liang Liangxue Lai Zhanjun Li Key Laboratory of Zoonosis Research Ministry of EducationCollege of Animal ScienceJilin UniversityChangchunJilin 130062China CAS Key Laboratory of regenerative Biology Guangdong Provincial Key Laboratory of Stem Cell and Regenerative MedicineSouth China Institute for Stem Cell Biology and Regenerative MedicineGuangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhouGuangdong 510530China Guangzhou regenerative medicine and Health Guang Dong Laboratory(GRMH-GDL) GuangzhouGuangdong 510005China institute for Stem Cell and Regeneration Chinese Academy of SciencesBeijing 100101China

Animal models are extensively used in all aspects of biomedical research,with substantial contributions to our understanding of diseases,the development of pharmaceuticals,and the exploration of gene *** field of genome modification in rabbits has progressed ***,recent advancements,particularly in CRISPR/Cas9-related technologies,have catalyzed the successful development of various genome-edited rabbit models to mimic diverse diseases,including cardiovascular disorders,immunodeficiencies,agingrelated ailments,neurological diseases,and ophthalmic *** models hold great promise in advancing biomedical research due to their closer physiological and biochemical resemblance to humans compared to *** review aims to summarize the novel gene-editing approaches currently available for rabbits and present the applications and prospects of such models in biomedicine,underscoring their impact and future potential in translational medicine.

关键词： Genome editing Animal model Rabbit CRISPR/Cas9 Genetic diseases

Programmable synthetic receptors:the next-generation of cell and gene therapies

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Signal Transduction and Targeted Therapy 2024年第2期9卷 376-400页

作者： Fei Teng Tongtong Cui Li Zhou Qingqin Gao Qi Zhou Wei Li University of Chinese Academy of Sciences Beijing 101408China State Key Laboratory of Stem Cell and regenerative Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China institute for Stem Cell and Regeneration Chinese Academy of SciencesBeijing 100101China Beijing institute for Stem Cell and regenerative medicine Beijing 100101China

Cell and gene therapies hold tremendous promise for treating a range of difficult-to-treat ***,concerns over the safety and efficacy require to be further addressed in order to realize their full *** receptors,a synthetic biology tool that can precisely control the function of therapeutic cells and genetic modules,have been rapidly developed and applied as a powerful *** designed and engineered,they can be applied to finetune the therapeutic activities,i.e.,to regulate production of dosed,bioactive payloads by sensing and processing user-defined signals or *** review provides an overview of diverse synthetic receptor systems being used to reprogram therapeutic cells and their wide applications in biomedical *** a special focus on four synthetic receptor systems at the forefront,including chimeric antigen receptors(CARs)and synthetic Notch(synNotch)receptors,we address the generalized strategies to design,construct and improve synthetic ***,we also highlight the expanding landscape of therapeutic applications of the synthetic receptor systems as well as current challenges in their clinical translation.

关键词： synthetic landscape payload

Bioceramic scaffolds with two-step internal/external modification of copper-containing polydopamine enhance antibacterial and alveolar bone regeneration capability

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第1期25卷 65-82页

作者： Xiaojian JIANG Lihong LEI Weilian SUN Yingming WEI Jiayin HAN Shuaiqi ZHONG Xianyan YANG Zhongru GOU Lili CHEN Department of Oral medicine the Second Affiliated HospitalZhejiang University School of MedicineHangzhou310009China Bio-nanomaterials and regenerative medicine Research Division Zhejiang–California International Nanosystem InstituteZhejiang UniversityHangzhou310058China

Magnesium-doped calcium silicate(CS)bioceramic scaffolds have unique advantages in mandibular defect repair;however,they lack antibacterial properties to cope with the complex oral ***,for the first time,the CS scaffold was functionally modified with a novel copper-containing polydopamine(PDA(Cu^(2+)))rapid deposition method,to construct internally modified(*P),externally modified(@PDA),and dually modified(*P@PDA)*** morphology,degradation behavior,and mechanical properties of the obtained scaffolds were evaluated in *** results showed that the CS*P@PDA had a unique micro-/nano-structural surface and appreciable mechanical *** the prolonged immersion stage,the release of copper ions from the CS*P@PDA scaffolds was rapid in the early stage and exhibited long-term sustained *** in vitro evaluation revealed that the release behavior of copper ions ascribed an excellent antibacterial effect to the CS*P@PDA,while the scaffolds retained good cytocompatibility with improved osteogenesis and angiogenesis ***,the PDA(Cu^(2+))-modified scaffolds showed effective early bone regeneration in a critical-size rabbit mandibular defect ***,it was indicated that considerable antibacterial property along with the enhancement of alveolar bone regeneration can be imparted to the scaffold by the two-step PDA(Cu^(2+))modification,and the convenience and wide applicability of this technique make it a promising strategy to avoid bacterial infections on implants.

关键词： Copper-containing polydopamine Modification Antibacterial property Bone regeneration Angiogenesis Bioceramic scaffold

One-step cell biomanufacturing platform:porous gelatin microcarrier beads promote human embryonic stem cell-derived midbrain dopaminergic progenitor cell differentiation in vitro and survival after transplantation in vivo

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Neural Regeneration Research 2024年第2期19卷 458-464页

作者： Lin Feng Da Li Yao Tian Chengshun Zhao Yun Sun Xiaolong Kou Jun Wu Liu Wang Qi Gu Wei Li Jie Hao Baoyang Hu Yukai Wang State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijingChina institute for Stem Cell and regenerative medicine Chinese Academy of SciencesBeijingChina National Stem Cell Resource Center Chinese Academy of SciencesBeijingChina Savaid Medical School University of Chinese Academy of SciencesBeijingChina Beijing institute for Stem Cell and regenerative medicine BeijingChina State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijingChina

Numerous studies have shown that cell replacement therapy can replenish lost cells and rebuild neural circuitry in animal models of Parkinson’s *** of midbrain dopaminergic progenitor cells is a promising treatment for Parkinson’s ***,transplanted cells can be injured by mechanical damage during handling and by changes in the transplantation ***,we developed a one-step biomanufacturing platform that uses small-aperture gelatin microcarriers to produce beads carrying midbrain dopaminergic progenitor *** beads allow midbrain dopaminergic progenitor cell differentiation and cryopreservation without digestion,effectively maintaining axonal integrity in ***,midbrain dopaminergic progenitor cell bead grafts showed increased survival and only mild immunoreactivity in vivo compared with suspended midbrain dopaminergic progenitor cell ***,our findings show that these midbrain dopaminergic progenitor cell beads enhance the effectiveness of neuronal cell transplantation.

关键词： axonal integrity cell cryopreservation cellular environment cellular niche cell replacement therapy dopaminergic progenitors human pluripotent stem cell mechanical damage neuronal cell delivery Parkinson’s disease small-aperture gelatin microcarriers

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

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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

Multifunctional glycolipids as multi-targeting therapeutics for neural regeneration

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Neural Regeneration Research 2024年第4期19卷 707-708页

作者： Yutaka Itokazu Department of Neuroscience and regenerative medicine Medical College of GeorgiaAugusta UniversityAugustaGAUSA

Many patients with neurodegenerative diseases,such as Alzheimer’s(AD)and Parkinson’s(PD)diseases suffer from disease progression without any satisfying clinical intervention,likely due to our lack of knowledge on how normal aging impacts the pathogenic mechanisms of these debilitating diseases.A growing body of literature has emerged in recent years that clearly demonstrates the involvement of glycolipids in the protein-oligomerization of neurodegenerative *** hypothesize that changes in glycolipids composition are a common mechanism underlying the shift from healthy brain aging to the neuropathological processes of neurodegenerative diseases.

关键词： lipids involvement diseases

Effect of weight-adjusted antimicrobial antibiotic prophylaxis on postoperative dosage and surgical site infection incidence in total joint arthroplasty

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World Journal of Orthopedics 2024年第4期15卷 318-320页

作者： Ashim Gupta Vijay Kumar Jain Department of Orthopaedics and regenerative medicine Future BiologicsLawrencevilleGA 30043United States Department of Orthopaedics South Texas Orthopaedic Research Institute(STORI Inc.)LaredoTX 78045United States Department of regenerative medicine BioIntegrateLawrencevilleGA 30043United States Department of Orthopaedics and regenerative medicine Regenerative OrthopaedicsNoida 201301India Department of Orthopaedics Atal Bihari Vajpayee Institute of Medical SciencesDr Ram Manohar Lohia HospitalNew Delhi 110001India

Surgical site infections(SSI)following total joint arthroplasty pose a significant concern for both providers and patients across the ***,administration of antimicrobial antibiotic prophylaxis is used throughout the world to reduce the incidence of ***,the correct dosage and frequency of administration remains *** this editorial,we emphasized the determination of the effect of administration of weight-adjusted antimicrobial antibiotic prophylaxis regime on the incidence of SSI and postoperative dosage reduction compared to the conventionally used regime during total joint *** results demonstrated similar efficacy between both regimes with respect to the incidence of *** addition,weight-adjustment led to reduced postoperative dosage and has the potential to reduce chances of achieving lower therapeutic concentration,drug resistance,drug toxicity,and costs.

关键词： Antibiotics Antimicrobial prophylaxis Weight-adjusted Surgical site infections Total joint arthroplasty Knee arthroplasty Hip arthroplasty

Autologous peripheral blood-derived orthobiologics:Different types and their effectiveness in managing knee osteoarthritis

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World Journal of Orthopedics 2024年第5期15卷 400-403页

Knees are the most commonly impacted weight-bearing joints in osteoarthritis(OA),affecting millions of people *** increasing life spans and obesity rates,the incidence of knee OA will further increase,leading to a significant increase in the economic *** treatment modalities utilized to manage knee OA have *** the last decade,the role of various autologous peripheral blood-derived orthobiologics(APBOs)for the treatment of knee OA has been extensively *** editorial provided an overview and focused on defining and shedding light on the current state of evidence based on the most recent published clinical studies concerning the use of APBO for the management of knee *** numerous studies have demonstrated promising results for these preparations,a notable gap exists in the comparative analysis of these diverse *** absence of head-to-head studies poses a considerable challenge for physicians/surgeons in determining the optimal preparation for managing knee OA and achieving sustained longterm ***,more adequately powered,multicenter,prospective,doubleblind,randomized controlled trials with longer follow-ups are needed to establish the long-term efficacy and to aid physicians/surgeons in determining the optimal APBO for the management of knee OA.

关键词： Knee osteoarthritis Platelet-rich plasma Platelet lysate Autologous conditioned serum Gold-induced cytokine Plasma rich in growth factors Growth factor concentrate Autologous protein solution Platelet-rich fibrin Hyperacute serum