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Liver transplantation and resection in patients with hepatocellular cancer and portal vein tumor thrombosis: Feasible and effective?

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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 them.In 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 them.This 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 disease.Downstaging therapies have helped make curative resection or LT a reality in selected patients.This review emphasizes on the key points to focus on when considering surgery in these patients,who are usually relegated to palliative systemic therapy alone.Meticulous 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

Epithelial stem cells and niches in lung alveolar regeneration and diseases

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Chinese Medical Journal Pulmonary and Critical Care medicine 2024年第1期2卷 17-26页

作者： Jilei Zhang Yuru Liu Department of Pharmacology and regenerative medicine University of Illinois College of MedicineChicagoIL 60612USA University of Illinois Cancer center ChicagoIL 60612USA

Alveoli serve as the functional units of the lungs,responsible for the critical task of blood-gas ***-prising type I(AT1)and type II(AT2)cells,the alveolar epithelium is continuously subject to external aggressors like pathogens and airborne particles.As such,preserving lung function requires both the homeostatic renewal and reparative regeneration of this epithelial layer.Dysfunctions in these processes contribute to various lung diseases.Recent research has pinpointed specific cell subgroups that act as potential stem or progenitor cells for the alveolar epithelium during both homeostasis and regeneration.Additionally,endothelial cells,fibroblasts,and immune cells synergistically establish a nurturing microenvironment-or“niche”-that modulates these ep-ithelial stem cells.This review aims to consolidate the latest findings on the identities of these stem cells and the components of their niche,as well as the molecular mechanisms that govern them.Additionally,this article highlights diseases that arise due to perturbations in stem cell-niche interactions.We also discuss recent technical innovations that have catalyzed these discoveries.Specifically,this review underscores the heterogeneity,plastic-ity,and dynamic regulation of these stem cell-niche systems.It is our aspiration that a deeper understanding of the fundamental cellular and molecular mechanisms underlying alveolar homeostasis and regeneration will open avenues for identifying novel therapeutic targets for conditions such as chronic obstructive pulmonary disease(COPD),fibrosis,coronavirus disease 2019(COVID-19),and lung cancer.

关键词： Alveoli Epithelium Type II cell(AT2) Stem cell Niche

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 neurons.Unfortunately,there is currently no cure for ALS.The available therapies ... 详细信息

关键词： degeneration sclerosis MAP4

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 clear disparities between model organisms and brain

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 functions.The field of genome modification in rabbits has progressed slowly.However,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 pathologies.These models hold great promise in advancing biomedical research due to their closer physiological and biochemical resemblance to humans compared to mice.This 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

Angiotensin-converting enzyme 2 and AMPK/mTOR pathway in the treatment of liver fibrosis:Should we consider further implications?

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World Journal of Gastroenterology 2024年第18期30卷 2391-2396页

作者： Michele Barone Section of Gastroenterology Department of Precision and Regenerative Medicine-Jonian Area-University of BariBari 70124Italy

This editorial contains comments on the article by Zhao et al in print in the World Journal of Gastroenterology.The mechanisms responsible for hepatic fibrosis are also involved in cancerogenesis.Here,we recapitulated the complexity of the renin-angiotensin system,discussed the role of hepatic stellate cell(HSC)autophagy in liver fibrogenesis,and analyzed the possible implications in the development of hepatocarcinoma(HCC).Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers definitively contribute to reducing hepatic fibrogenesis,whereas their involvement in HCC is more evident in experimental conditions than in human studies.Angiotensin-converting enzyme 2(ACE2),and its product Angiotensin(Ang)1-7,not only regulate HSC autophagy and liver fibrosis,but they also represent potential targets for unexplored applications in the field of HCC.Finally,ACE2 overexpression inhibits HSC autophagy through the AMP-activated protein kinase(AMPK)/mammalian target of rapamycin(mTOR)pathway.In this case,Ang 1-7 acts binding to the MasR,and its agonists could modulate this pathway.However,since AMPK utilizes different targets to suppress the mTOR downstream complex mTOR complex 1 effectively,we still need to unravel the entire pathway to identify other potential targets for the therapy of fibrosis and liver cancer.

关键词： Renin-angiotensin system Liver fibrosis Hepatic stellate cells Autophagy Hepatocellular carcinoma

Clinical applications of stem cell-derived exosomes

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Signal Transduction and Targeted Therapy 2024年第2期9卷 621-651页

作者： Fei Tan Xuran Li Zhao Wang Jiaojiao Li Khawar Shahzad Jialin Zheng Department of ORL-HNS Shanghai Fourth People’s Hospitaland School of MedicineTongji UniversityShanghaiChina Plasma medicine and Surgical Implants center Tongji UniversityShanghaiChina The Royal College of Surgeons in Ireland DublinIreland The Royal College of Surgeons of England LondonUK center for Translational Neurodegeneration and regenerative Therapy Tongji Hospital affiliated to Tongji University School of MedicineShanghaiChina Shanghai Frontiers Science center of Nanocatalytic medicine Tongji UniversityShanghaiChina

Although stem cell-based therapy has demonstrated considerable potential to manage certain diseases more successfully than conventional surgery,it nevertheless comes with inescapable drawbacks that might limit its clinical translation.Compared to stem cells,stem cell-derived exosomes possess numerous advantages,such as non-immunogenicity,non-infusion toxicity,easy access,effortless preservation,and freedom from tumorigenic potential and ethical issues.Exosomes can inherit similar therapeutic effects from their parental cells such as embryonic stem cells and adult stem cells through vertical delivery of their pluripotency or multipotency.After a thorough search and meticulous dissection of relevant literature from the last five years,we present this comprehensive,up-to-date,specialty-specific and disease-oriented review to highlight the surgical application and potential of stem cell-derived exosomes.Exosomes derived from stem cells(e.g.,embryonic,induced pluripotent,hematopoietic,mesenchymal,neural,and endothelial stem cells)are capable of treating numerous diseases encountered in orthopedic surgery,neurosurgery,plastic surgery,general surgery,cardiothoracic surgery,urology,head and neck surgery,ophthalmology,and obstetrics and gynecology.The diverse therapeutic effects of stem cells-derived exosomes are a hierarchical translation through tissue-specific responses,and cell-specific molecular signaling pathways.In this review,we highlight stem cell-derived exosomes as a viable and potent alternative to stem cell-based therapy in managing various surgical conditions.We recommend that future research combines wisdoms from surgeons,nanomedicine practitioners,and stem cell researchers in this relevant and intriguing research area.

关键词： viable stem capable

Glial progenitor heterogeneity and plasticity in the adult spinal cord

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Neural Regeneration Research 2024年第12期19卷 2567-2568页

作者： Haichao Wei Jia Qian Wu Department of Neurosurgery McGovern Medical SchoolThe University of Texas Health Science Center at HoustonHoustonTXUSA center for Stem Cell and regenerative medicine UT Brown Foundation Institute of Molecular MedicineHoustonTXUSA MD Anderson Cancer center UTHealth Graduate School of Biomedical Sciences HoustonTXUSA

Glial progenitor cells were reported to have the capacity to generate various types of cells in both the central nervous system(CNS)and peripheral nervous system.Glial progenitor cells can respond to diverse environmental signals and transform into distinct populations,each serving specific functions.Notably,the adult spinal cord hosts various populations of glial progenitors,a region integral to the central nervous system.During development,glial progenitors express glial fibrillary acidic protein(GFAP;Dimou and Gotz,2014).However,the specific identities of GFAP-expressing progenitors in the adult spinal cord were not thoroughly investigated.

关键词： functions plasticity thoroughly

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 disorders.We 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