Myasthenia gravis is a chronic autoimmune disorder that affects the neuromuscular junction leading to fluctuating skeletal muscle fatigability. The majority of myasthenia gravis patients have detectable antibodies in ...Myasthenia gravis is a chronic autoimmune disorder that affects the neuromuscular junction leading to fluctuating skeletal muscle fatigability. The majority of myasthenia gravis patients have detectable antibodies in their serum, targeting acetylcholine receptor, muscle-specific kinase, or related proteins. Current treatment for myasthenia gravis involves symptomatic therapy, immunosuppressive drugs such as corticosteroids, azathioprine, and mycophenolate mofetil, and thymectomy, which is primarily indicated in patients with thymoma or thymic hyperplasia. However, this condition continues to pose significant challenges including an unpredictable and variable disease progression, differing response to individual therapies, and substantial longterm side effects associated with standard treatments(including an increased risk of infections, osteoporosis, and diabetes), underscoring the necessity for a more personalized approach to treatment. Furthermore, about fifteen percent of patients, called “refractory myasthenia gravis patients”, do not respond adequately to standard therapies. In this context, the introduction of molecular therapies has marked a significant advance in myasthenia gravis management. Advances in understanding myasthenia gravis pathogenesis, especially the role of pathogenic antibodies, have driven the development of these biological drugs, which offer more selective, rapid, and safer alternatives to traditional immunosuppressants. This review aims to provide a comprehensive overview of emerging therapeutic strategies targeting specific immune pathways in myasthenia gravis, with a particular focus on preclinical evidence, therapeutic rationale, and clinical translation of B-cell depletion therapies, neonatal Fc receptor inhibitors, and complement inhibitors.展开更多
Lung cancer has one of the highest rates of incidence and mortality worldwide,mak-ing research on its mechanisms and treatments crucial.Animal models are essential in lung cancer research as they accurately replicate ...Lung cancer has one of the highest rates of incidence and mortality worldwide,mak-ing research on its mechanisms and treatments crucial.Animal models are essential in lung cancer research as they accurately replicate the biological characteristics and treatment outcomes seen in human diseases.Currently,various lung cancer models have been established,including chemical induction models,orthotopic transplan-tation models,ectopic transplantation models,metastasis models,and gene editing mouse models.Additionally,lung cancer grafts can be categorized into two types:tissue-based and cell-based grafts.This paper summarizes the phenotypes,advan-tages,and disadvantages of various induction methods based on their modeling tech-niques.The goal is to enhance the simulation of clinical lung cancer characteristics and to establish a solid foundation for future clinical research.展开更多
Depressive disorder is a chronic,recurring,and potentially life-endangering neuropsychiatric disease.According to a report by the World Health Organization,the global population suffering from depression is experienci...Depressive disorder is a chronic,recurring,and potentially life-endangering neuropsychiatric disease.According to a report by the World Health Organization,the global population suffering from depression is experiencing a significant annual increase.Despite its prevalence and considerable impact on people,little is known about its pathogenesis.One major reason is the scarcity of reliable animal models due to the absence of consensus on the pathology and etiology of depression.Furthermore,the neural circuit mechanism of depression induced by various factors is particularly complex.Considering the variability in depressive behavior patterns and neurobiological mechanisms among different animal models of depression,a comparison between the neural circuits of depression induced by various factors is essential for its treatment.In this review,we mainly summarize the most widely used behavioral animal models and neural circuits under different triggers of depression,aiming to provide a theoretical basis for depression prevention.展开更多
Noninvasive brain stimulation techniques offer promising therapeutic and regenerative prospects in neurological diseases by modulating brain activity and improving cognitive and motor functions.Given the paucity of kn...Noninvasive brain stimulation techniques offer promising therapeutic and regenerative prospects in neurological diseases by modulating brain activity and improving cognitive and motor functions.Given the paucity of knowledge about the underlying modes of action and optimal treatment modalities,a thorough translational investigation of noninvasive brain stimulation in preclinical animal models is urgently needed.Thus,we reviewed the current literature on the mechanistic underpinnings of noninvasive brain stimulation in models of central nervous system impairment,with a particular emphasis on traumatic brain injury and stroke.Due to the lack of translational models in most noninvasive brain stimulation techniques proposed,we found this review to the most relevant techniques used in humans,i.e.,transcranial magnetic stimulation and transcranial direct current stimulation.We searched the literature in Pub Med,encompassing the MEDLINE and PMC databases,for studies published between January 1,2020 and September 30,2024.Thirty-five studies were eligible.Transcranial magnetic stimulation and transcranial direct current stimulation demonstrated distinct strengths in augmenting rehabilitation post-stroke and traumatic brain injury,with emerging mechanistic evidence.Overall,we identified neuronal,inflammatory,microvascular,and apoptotic pathways highlighted in the literature.This review also highlights a lack of translational surrogate parameters to bridge the gap between preclinical findings and their clinical translation.展开更多
Human herpesvirus,a specific group within the herpesvirus family,is responsible for a variety of human diseases.These viruses can infect humans and other vertebrates,primarily targeting the skin,mucous membranes,and n...Human herpesvirus,a specific group within the herpesvirus family,is responsible for a variety of human diseases.These viruses can infect humans and other vertebrates,primarily targeting the skin,mucous membranes,and neural tissues,thereby signifi-cantly impacting the health of both humans and animals.Animal models are crucial for studying virus pathogenesis,vaccine development,and drug testing.Despite several vaccine candidates being in preclinical and clinical stages,no vaccines are current available to prevent lifelong infections caused by these human herpesviruses,except for varicella-zoster virus(VZV)vaccine.However,the strict host tropism of herpes-viruses and other limitations mean that no single animal model can fully replicate all key features of human herpesvirus-associated diseases.This makes it challeng-ing to evaluate vaccines and antivirals against human herpesvirus comprehensively.Herein,we summarize the current animal models used to study the human herpesvi-ruses includingα-herpesviruses(herpes simplex virus type 1(HSV-1),HSV-2,VZV),β-herpesviruses(human cytomegalovirus(HCMV),γ-herpesviruses(Epstein-Barr virus(EBV))and Kaposi's sarcoma herpesvirus(KSHV)).By providing concise information and detailed analysis of the potential,limitations and applications of various models,such as non-human primates,mice,rabbits,guinea pigs,and tree shrews,this sum-mary aims to help researchers efficiently select the most appropriate animal model,offering practical guidance for studying human herpesvirus.展开更多
Photodynamic therapy(PDT)is an emerging minimally invasive therapeutic modality that relies on the activation of a photosensitizing agent by light of a specific wavelength in the presence of molecular oxygen,leading t...Photodynamic therapy(PDT)is an emerging minimally invasive therapeutic modality that relies on the activation of a photosensitizing agent by light of a specific wavelength in the presence of molecular oxygen,leading to the generation of reactive oxygen species(ROS).This mechanism facilitates selective cytotoxic effects within pathological tissues and has demonstrated therapeutic potential across diverse disease contexts.However,the broader clinical applications remain limited by photosensitizer selectivity,shallow light penetration,and the risk of off-target cytotoxicity.Recent advancements in PDT have focused on the development of next-generation photosensitizers,the integration of nanotechnology for enhanced delivery and targeting,and the strategic combination of PDT with complementary therapeutic approaches.Experimental animal models play a crucial role in validating the efficacy and safety of PDT,optimizing its therapeutic parameters,and determining its mechanisms of action.This review provides a comprehensive overview of PDT applications in various disease models,including oncological,infectious,and nonconventional indications.Special emphasis is placed on the importance of large animal models in PDT research,such as rabbits,pigs,dogs,and non-human primates,which provide experimental platforms that more closely resemble human physiological and pathological states.The use of these models for understanding the mechanisms of PDT,optimizing therapeutic regimens,and evaluating clinical outcomes is also discussed.This review aims to inform future directions in PDT research and emphasizes the importance of selecting appropriate preclinical animal models to facilitate successful clinical translation.展开更多
Background:Colocasia esculenta(L.)Schott,known as the taro vegetable,possesses various beneficial effects and is traditionally used in folk medicine.This study explores the ameliorative antioxidant and hepatoprotectiv...Background:Colocasia esculenta(L.)Schott,known as the taro vegetable,possesses various beneficial effects and is traditionally used in folk medicine.This study explores the ameliorative antioxidant and hepatoprotective effect of a methanolic extract of the C.esculenta flower(ME-CEF)against oxidative damage and hepatotoxicity in mice.Methods:The antioxidant efficacy of ME-CEF was assessed using 2,2′-azino-bis-(3-ethylbenzothiazoline-6-sulfonic)(ABTS)and 2,2-diphenyl-1-picrylhydrazyl(DPPH)scavenging assay.The hepatoprotective effect was investigated by an assessment of liver injury indicators(amino transferase[ALT],aspartate amino transferase[AST],alkaline phosphatase[ALP],bilirubin,creatinine)and normalizing lipid profiles(cho-lesterol[CHO],triglyceride[TG],high-density lipoprotein[HDL],and low-density li-poprotein[LDL])along with histopathological study and antioxidant enzymes(CAT).A phytochemical analysis,both qualitative and quantitative,was conducted,including gas chromatography-tandem mass spectrometry(GC-MS/MS)analysis and an in silico molecular docking study.Results:The Result Showed that ME-CEF Possesses Moderate ABTS and DPPH Scavenging Activity with IC_(50) Values of 117.18 and 160.41μg/mL.As Illustrated by Reducing Liver Enzymes(ALT,AST,ALP,Bilirubin,Creatinine)and Lipid Profile(CHO,TG,LDL)and Raising HDL Levels(p<0.01),ME-CEF Dose Dependently Mitigated CCl_(4)-Induced Acute Liver Injury.Furthermore,ME-CEF Blocked Hepatic Oxidative Stress by Boosting Antioxidant Enzymes(CAT)and Preventing Liver Tissue Damage and Apoptosis.In Silico Investigations Also Showed a Promising Binding Affinity with Tumor Necrosis Factor α(TNF-α),Interleukin 6(IL-6),PRAP-1,and Xanthin Oxidoreductase,which Displayed Antioxidant and Hepatoprotective Candidacy while Notable Safety and Efficacy Profile Was Also Documented through ADME/T Studies.Histopathological Analysis Showed Reduced Hepatocellular Necrosis and Vascular Congestion in Silymarin and Extract Groups.Conclusion:Based on these results,our findings strongly recommend the medicinal use of the plant,highlighting its antioxidant and hepatoprotective potentials.展开更多
Cisplatin chemotherapy has been used as the main treatment for different types of cancer.However,cisplatin chemotherapy-induced peripheral neuropathic pain(CIPNP)seriously affects the treatment process and quality of ...Cisplatin chemotherapy has been used as the main treatment for different types of cancer.However,cisplatin chemotherapy-induced peripheral neuropathic pain(CIPNP)seriously affects the treatment process and quality of life of patients.In addition,it impacts the underlying mechanism and prevention and treatment strategies,indicating that drug selection and efficacy evaluation need to be further investigated.Furthermore,an animal model that is more consistent with the pathological mechanism needs to be developed.In this study,we describe and discuss the methods of developing and detecting CIPNP models in rats and mice induced by cisplatin chemotherapy.The aim was to improve the modeling rate and develop animal models that are more consistent with the developmental pattern of the disease.In addition,the study provides ideal reference animal models for clinical research and drug discovery and development.展开更多
Post-stroke depression(PSD) is a common psychiatric complication affecting nearly one-third of stroke survivors, leading to increased disability, mortality, and cognitive decline. Traditional Chinese Medicine(TCM) has...Post-stroke depression(PSD) is a common psychiatric complication affecting nearly one-third of stroke survivors, leading to increased disability, mortality, and cognitive decline. Traditional Chinese Medicine(TCM) has proven effective in treating PSD through syndrome differentiation, yet existing animal models primarily reflect Western medical concepts and fail to incorporate the TCM principle of “同病异治”( treating the same disease with different methods). This paper provides a review of the current methods for constructing animal models of post-stroke depression(PSD) from the perspective of Traditional Chinese Medicine(TCM) syndrome differentiation and proposes multi-dimensional assessment indicators. By integrating TCM theories with modern biomedical techniques, this study offers a comprehensive framework for deepening the understanding of the pathogenesis and therapeutic evaluation of PSD. This approach not only contributes to advancing PSD research but also paves the way for innovative treatment strategies that combine traditional and modern medicine.展开更多
Animal models are necessary to investigate the pathogenic features underlying motor neuron degeneration and for therapeutic development in amyotrophic lateral sclerosis（ALS）. Measures of model validity allow for a c...Animal models are necessary to investigate the pathogenic features underlying motor neuron degeneration and for therapeutic development in amyotrophic lateral sclerosis（ALS）. Measures of model validity allow for a critical interpretation of results from each model and caution from over-interpretation of experimental models. Face and construct validity refer to the similarity in phenotype and the proposed causal factor to the human disease, respectively. More recently developed models are restricted by limited phenotype characterization, yet new models hold promise for novel disease insights, thus highlighting their importance. In this article, we evaluate the features of face and construct validity of our new zebrafish model of environmentally-induced motor neuron degeneration and discuss this in the context of current environmental and genetic ALS models, including C9 orf72, mutant Cu/Zn superoxide dismutase 1 and TAR DNA-binding protein 43 mouse and zebrafish models. In this mini-review, we discuss the pros and cons to validity criteria in each model. Our zebrafish model of environmentally-induced motor neuron degeneration displays convincing features of face validity with many hallmarks of ALS-like features, and weakness in construct validity. However, the value of this model may lie in its potential to be more representative of the pathogenic features underlying sporadic ALS cases, where environmental factors may be more likely to be involved in disease etiology than single dominant gene mutations. It may be necessary to compare findings between different strains and species modeling specific genes or environmental factors to confirm findings from ALS animal models and tease out arbitrary strain-and overexpression-specific effects.展开更多
Lung cancer is the leading cause of cancer mortality worldwide.Even with the applications of excision, radiotherapy, chemotherapy, and gene therapy, the 5 year survival rate is only 15% in the USA. Clinically relevant...Lung cancer is the leading cause of cancer mortality worldwide.Even with the applications of excision, radiotherapy, chemotherapy, and gene therapy, the 5 year survival rate is only 15% in the USA. Clinically relevant laboratory animal models of the disease could greatly facilitate understanding of the pathogenesis of lung cancer, its progression, invasion and metastasis. Transplanted lung cancer models are of special interest and are widely used today. Such models are essential tools in accelerating development of new therapies for lung cancer. In this communication we will present a brief overview of the hosts, sites and pathways used to establish transplanted animal lung tumor models.展开更多
Background:Due to the widespread use of cell phone devices today,numerous re-search studies have focused on the adverse effects of electromagnetic radiation on human neuropsychological and reproductive systems.In most...Background:Due to the widespread use of cell phone devices today,numerous re-search studies have focused on the adverse effects of electromagnetic radiation on human neuropsychological and reproductive systems.In most studies,oxidative stress has been identified as the primary pathophysiological mechanism underlying the harmful effects of electromagnetic waves.This paper aims to provide a holistic review of the protective effects of melatonin against cell phone-induced electromag-netic waves on various organs.Methods:This study is a systematic review of articles chosen by searching Google Scholar,PubMed,Embase,Scopus,Web of Science,and Science Direct using the key-words‘melatonin’,‘cell phone radiation’,and‘animal model’.The search focused on articles written in English,which were reviewed and evaluated.The PRISMA process was used to review the articles chosen for the study,and the JBI checklist was used to check the quality of the reviewed articles.Results:In the final review of 11 valid quality-checked articles,the effects of me-latonin in the intervention group,the effects of electromagnetic waves in the case group,and the amount of melatonin in the chosen organ,i.e.brain,skin,eyes,testis and the kidney were thoroughly examined.The review showed that electromagnetic waves increase cellular anti-oxidative activity in different tissues such as the brain,the skin,the eyes,the testis,and the kidneys.Melatonin can considerably augment the anti-oxidative system of cells and protect tissues;these measurements were sig-nificantly increased in control groups.Electromagnetic waves can induce tissue atro-phy and cell death in various organs including the brain and the skin and this effect was highly decreased by melatonin.Conclusion:Our review confirms that melatonin effectively protects the organs of an-imal models against electromagnetic waves.In light of this conclusion and the current world-wide use of melatonin,future studies should advance to the stages of human clinical trials.We also recommend that more research in the field of melatonin physi-ology is conducted in order to protect exposed cells from dying and that melatonin should be considered as a pharmaceutical option for treating the complications result-ing from electromagnetic waves in humans.展开更多
Cardiac arrest(CA)is a critical condition in the field of cardiovascular medicine.Despite successful resuscitation,patients continue to have a high mortality rate,largely due to post CA syndrome(PCAS).However,the inju...Cardiac arrest(CA)is a critical condition in the field of cardiovascular medicine.Despite successful resuscitation,patients continue to have a high mortality rate,largely due to post CA syndrome(PCAS).However,the injury and pathophysiological mechanisms underlying PCAS remain unclear.Experimental animal models are valuable tools for exploring the etiology,pathogenesis,and potential interventions for CA and PCAS.Current CA animal models include electrical induction of ventricular fibrillation(VF),myocardial infarction,high potassium,asphyxia,and hemorrhagic shock.Although these models do not fully replicate the complexity of clinical CA,the mechanistic insights they provide remain highly relevant,including post-CA brain injury(PCABI),post-CA myocardial dysfunction(PAMD),systemic ischaemia/reperfusion injury(IRI),and the persistent precipitating pathology.Summarizing the methods of establishing CA models,the challenges encountered in the modeling process,and the mechanisms of PCAS can provide a foundation for developing standardized CA modeling protocols.展开更多
Depression is a chronic,recurring and potentially life-threatening illness that affects up to 20%of the population across the world.Despite its prevalence and considerable impact on human,little is known about its pat...Depression is a chronic,recurring and potentially life-threatening illness that affects up to 20%of the population across the world.Despite its prevalence and considerable impact on human,little is known about its pathogenesis.One of the major reasons is the restricted availability of validated animal models due to the absence of consensus on the pathology and etiology of depression.Besides,some core symptoms such as depressed mood,feeling of worthlessness,and recurring thoughts of death or suicide,are impossible to be modeled on laboratory animals.Currently,the criteria for identifying animal models of depression rely on either of the 2 principles：actions of known antidepressants and responses to stress.This review mainly focuses on the most widely used animal models of depression,including learned helplessness,chronic mild stress,and social defeat paradigms.Also,the behavioral tests for screening antidepressants,such as forced swimming test and tail suspension test,are also discussed.The advantages and major drawbacks of each model are evaluated.In prospective,new techniques that will be beneficial for developing novel animal models or detecting depression are discussed.展开更多
Although hypertension is a frequently seen chronic condition across the world,its exact cause remains unclear.Animal models are beneficial for clarifying the pathogenic mechanism of hypertension and examining new trea...Although hypertension is a frequently seen chronic condition across the world,its exact cause remains unclear.Animal models are beneficial for clarifying the pathogenic mechanism of hypertension and examining new treatments.An optimal animal model for studies on hypertension must well mimic human-like hemodynamics and pathophysiological structural modification,showing human disease features and complications timely or even ahead of time.A review of the most frequently used hypertensive animal models available,including small and large animals,induced and genetic models,would provide an insight into the appropriate targets to be addressed in the development of different hypertensive animal models.Another focus of the review are the processes of target-organs injury caused by high blood pressure,which mainly influences human health.展开更多
Rotator cuff tears are highly prevalent,and there is an urgent need to understand their healing mechanisms to improve treatment outcomes for patients.This editorial aims to summarize the roles and limitations of commo...Rotator cuff tears are highly prevalent,and there is an urgent need to understand their healing mechanisms to improve treatment outcomes for patients.This editorial aims to summarize the roles and limitations of common animal models(including rodents,rabbits,sheep,dogs,and primates)and second-look arthroscopy in rotator cuff healing research.Different animal models offer distinct advantages and disadvantages.For example,rodent models are cost-effective and suitable for genetic studies but have anatomical differences from humans.Rabbit models are favored for their relatively large tendon size and ease of surgical manipulation,yet they still deviate from human shoulder anatomy in some aspects.Larger animals like sheep and dogs have more similar shoulder structures to humans but come with high costs and challenges in maintaining consistent experimental conditions.Second-look arthroscopic studies have provided evidence for the effectiveness of current surgical techniques.Animal models will continue to play a crucial role in further exploring the local microenvironment of the rotator cuff,which is expected to help develop more effective strategies to promote healing.展开更多
Severe combined immunodeficiency disease(SCID),characterized by profound immune system dysfunction,can lead to life-threatening infections and death.Animal models play a pivotal role in elucidating biological processe...Severe combined immunodeficiency disease(SCID),characterized by profound immune system dysfunction,can lead to life-threatening infections and death.Animal models play a pivotal role in elucidating biological processes and advancing therapeutic strategies.Recent advances in gene-editing technologies,including zincfinger nucleases(ZFNs),transcription activator-like effector nucleases(TALENs),CRISPR/Cas9,and base editing,have significantly enhanced the generation of SCID models.These models have not only deepened our understanding of disease pathophysiology but have also driven progress in cancer therapy,stem cell transplantation,organ transplantation,and infectious diseasemanagement.Thisreviewprovidesa comprehensive overview of current SCID models generated using novel gene-editing approaches,highlighting their potential applications in translational medicine and their role in advancing biomedical research.展开更多
The mortality rate of patients with abdominal aortic aneurysm(AAA) after rupture is extremely high,and this disease has become an important disease endangering the health of the Chinese population.Methods used to mode...The mortality rate of patients with abdominal aortic aneurysm(AAA) after rupture is extremely high,and this disease has become an important disease endangering the health of the Chinese population.Methods used to model AAA include intraluminal pressurized elastase infusion,chronic infusion of angiotensin Ⅱ(Ang Ⅱ) via an osmotic pump,periarterial application of calcium chloride,vascular grafting,and gene modification.AAA models induced by elastase and Ang Ⅱ are the two most widely used animal models.In the elastase-induced model,because intraluminal infusion is transient,with the cessation of initial stimulation,the aneurysm lesion tends to be stable and rarely ruptures.The model induced by Ang Ⅱ infusion often presents with a typical aortic dissection with a false lumen,whereas clinical AAA patients do not necessarily have dissection.Currently,the treatment of AAA in clinical practice remains endovascular,and there is a lack of pharmacological therapy,which is also related to the fact that the pathogenic mechanism has not been fully elucidated.Smoking,old age,male sex,and hypertension are the main risk factors for AAA,but these risk factors have not been fully investigated in the current modeling methods,which may affect the clinical translational application of research results based on animal models.Therefore,this article reviews the most commonly used AAA modeling methods,comments on their applications and limitations,and provides a perspective on the development of novel animal models.展开更多
Parkinson’s disease is chara cterized by the loss of dopaminergic neurons in the substantia nigra pars com pacta,and although restoring striatal dopamine levels may improve symptoms,no treatment can cure or reve rse ...Parkinson’s disease is chara cterized by the loss of dopaminergic neurons in the substantia nigra pars com pacta,and although restoring striatal dopamine levels may improve symptoms,no treatment can cure or reve rse the disease itself.Stem cell therapy has a regenerative effect and is being actively studied as a candidate for the treatment of Parkinson’s disease.Mesenchymal stem cells are considered a promising option due to fewer ethical concerns,a lower risk of immune rejection,and a lower risk of teratogenicity.We performed a meta-analysis to evaluate the therapeutic effects of mesenchymal stem cells and their derivatives on motor function,memory,and preservation of dopamine rgic neurons in a Parkinson’s disease animal model.We searched bibliographic databases(PubMed/MEDLINE,Embase,CENTRAL,Scopus,and Web of Science)to identify articles and included only pee r-reviewed in vivo interve ntional animal studies published in any language through J une 28,2023.The study utilized the random-effect model to estimate the 95%confidence intervals(CI)of the standard mean differences(SMD)between the treatment and control groups.We use the systematic review center for laboratory animal expe rimentation’s risk of bias tool and the collaborative approach to meta-analysis and review of animal studies checklist for study quality assessment.A total of 33studies with data from 840 Parkinson’s disease model animals were included in the meta-analysis.Treatment with mesenchymal stem cells significantly improved motor function as assessed by the amphetamine-induced rotational test.Among the stem cell types,the bone marrow MSCs with neurotrophic factor group showed la rgest effect size(SMD[95%CI]=-6.21[-9.50 to-2.93],P=0.0001,I^(2)=0.0%).The stem cell treatment group had significantly more tyrosine hydroxylase positive dopamine rgic neurons in the striatum([95%CI]=1.04[0.59 to 1.49],P=0.0001,I^(2)=65.1%)and substantia nigra(SMD[95%CI]=1.38[0.89 to 1.87],P=0.0001,I^(2)=75.3%),indicating a protective effect on dopaminergic neurons.Subgroup analysis of the amphetamine-induced rotation test showed a significant reduction only in the intracranial-striatum route(SMD[95%CI]=-2.59[-3.25 to-1.94],P=0.0001,I^(2)=74.4%).The memory test showed significant improvement only in the intravenous route(SMD[95%CI]=4.80[1.84 to 7.76],P=0.027,I^(2)=79.6%).Mesenchymal stem cells have been shown to positively impact motor function and memory function and protect dopaminergic neurons in preclinical models of Parkinson’s disease.Further research is required to determine the optimal stem cell types,modifications,transplanted cell numbe rs,and delivery methods for these protocols.展开更多
Acute hepatic failure (AHF) is a severe liver injury accompanied by hepatic encephalopathy which causes multiorgan failure with an extremely high mortality rate, even if intensive care is provided. Management of sever...Acute hepatic failure (AHF) is a severe liver injury accompanied by hepatic encephalopathy which causes multiorgan failure with an extremely high mortality rate, even if intensive care is provided. Management of severe AHF continues to be one of the most challenging problems in clinical medicine. Liver transplantation has been shown to be the most effective therapy, but the procedure is limited by shortage of donor organs. Although a number of clinical trials testing different liver assist devices are under way, these systems alone have no significant effect on patient survival and are only regarded as a useful approach to bridge patients with AHF to liver transplantation. As a result, reproducible experimental animal models resembling the clinical conditions are still needed. The three main approaches used to create an animal model for AHF are: surgical procedures, toxic liver injury and infective procedures. Most common models are based on surgical techniques (total/partial hepatectomy, complete/transient devascularization) or the use of hepatotoxic drugs (acetaminophen, galactosamine, thioacetamide, and others), and very few satisfactory viral models are available. We have recently developed a viral model of AHF by means of the inoculation of rabbits with the virus of rabbit hemorrhagic disease. This model displays biochemical and histological characteristics, and clinical features that resemble those in human AHF. In the present article an overview is given of the most widely used animal models of AHF, and their main advantages and disadvantages are reviewed.展开更多
文摘Myasthenia gravis is a chronic autoimmune disorder that affects the neuromuscular junction leading to fluctuating skeletal muscle fatigability. The majority of myasthenia gravis patients have detectable antibodies in their serum, targeting acetylcholine receptor, muscle-specific kinase, or related proteins. Current treatment for myasthenia gravis involves symptomatic therapy, immunosuppressive drugs such as corticosteroids, azathioprine, and mycophenolate mofetil, and thymectomy, which is primarily indicated in patients with thymoma or thymic hyperplasia. However, this condition continues to pose significant challenges including an unpredictable and variable disease progression, differing response to individual therapies, and substantial longterm side effects associated with standard treatments(including an increased risk of infections, osteoporosis, and diabetes), underscoring the necessity for a more personalized approach to treatment. Furthermore, about fifteen percent of patients, called “refractory myasthenia gravis patients”, do not respond adequately to standard therapies. In this context, the introduction of molecular therapies has marked a significant advance in myasthenia gravis management. Advances in understanding myasthenia gravis pathogenesis, especially the role of pathogenic antibodies, have driven the development of these biological drugs, which offer more selective, rapid, and safer alternatives to traditional immunosuppressants. This review aims to provide a comprehensive overview of emerging therapeutic strategies targeting specific immune pathways in myasthenia gravis, with a particular focus on preclinical evidence, therapeutic rationale, and clinical translation of B-cell depletion therapies, neonatal Fc receptor inhibitors, and complement inhibitors.
基金Sichuan Provincial Administration of Traditional Chinese Medicine,Grant/Award Number:2023MS564National Natural Science Foundation of China,Grant/Award Number:82474436。
文摘Lung cancer has one of the highest rates of incidence and mortality worldwide,mak-ing research on its mechanisms and treatments crucial.Animal models are essential in lung cancer research as they accurately replicate the biological characteristics and treatment outcomes seen in human diseases.Currently,various lung cancer models have been established,including chemical induction models,orthotopic transplan-tation models,ectopic transplantation models,metastasis models,and gene editing mouse models.Additionally,lung cancer grafts can be categorized into two types:tissue-based and cell-based grafts.This paper summarizes the phenotypes,advan-tages,and disadvantages of various induction methods based on their modeling tech-niques.The goal is to enhance the simulation of clinical lung cancer characteristics and to establish a solid foundation for future clinical research.
基金supported by the Brain&Behavior Research Foundation(30233).
文摘Depressive disorder is a chronic,recurring,and potentially life-endangering neuropsychiatric disease.According to a report by the World Health Organization,the global population suffering from depression is experiencing a significant annual increase.Despite its prevalence and considerable impact on people,little is known about its pathogenesis.One major reason is the scarcity of reliable animal models due to the absence of consensus on the pathology and etiology of depression.Furthermore,the neural circuit mechanism of depression induced by various factors is particularly complex.Considering the variability in depressive behavior patterns and neurobiological mechanisms among different animal models of depression,a comparison between the neural circuits of depression induced by various factors is essential for its treatment.In this review,we mainly summarize the most widely used behavioral animal models and neural circuits under different triggers of depression,aiming to provide a theoretical basis for depression prevention.
基金funded by the Deutsche Forschungsgemeinschaft(DFG,German Research Foundation):project ID 431549029-SFB 1451the Marga-und-Walter-Boll-Stiftung(#210-10-15)(to MAR)a stipend from the'Gerok Program'(Faculty of Medicine,University of Cologne,Germany)。
文摘Noninvasive brain stimulation techniques offer promising therapeutic and regenerative prospects in neurological diseases by modulating brain activity and improving cognitive and motor functions.Given the paucity of knowledge about the underlying modes of action and optimal treatment modalities,a thorough translational investigation of noninvasive brain stimulation in preclinical animal models is urgently needed.Thus,we reviewed the current literature on the mechanistic underpinnings of noninvasive brain stimulation in models of central nervous system impairment,with a particular emphasis on traumatic brain injury and stroke.Due to the lack of translational models in most noninvasive brain stimulation techniques proposed,we found this review to the most relevant techniques used in humans,i.e.,transcranial magnetic stimulation and transcranial direct current stimulation.We searched the literature in Pub Med,encompassing the MEDLINE and PMC databases,for studies published between January 1,2020 and September 30,2024.Thirty-five studies were eligible.Transcranial magnetic stimulation and transcranial direct current stimulation demonstrated distinct strengths in augmenting rehabilitation post-stroke and traumatic brain injury,with emerging mechanistic evidence.Overall,we identified neuronal,inflammatory,microvascular,and apoptotic pathways highlighted in the literature.This review also highlights a lack of translational surrogate parameters to bridge the gap between preclinical findings and their clinical translation.
基金National Natural Science Foundation of China,Grant/Award Number:82222041 and 82241068CAMS Innovation Fund for Medical Sciences,Grant/Award Number:2021-I2M-1-037 and 2023-I2M-2-001+1 种基金National Key Research and Development Project of China,Grant/Award Number:2023YFC2309000Beijing Natural Science Foundation,Grant/Award Number:Z220018。
文摘Human herpesvirus,a specific group within the herpesvirus family,is responsible for a variety of human diseases.These viruses can infect humans and other vertebrates,primarily targeting the skin,mucous membranes,and neural tissues,thereby signifi-cantly impacting the health of both humans and animals.Animal models are crucial for studying virus pathogenesis,vaccine development,and drug testing.Despite several vaccine candidates being in preclinical and clinical stages,no vaccines are current available to prevent lifelong infections caused by these human herpesviruses,except for varicella-zoster virus(VZV)vaccine.However,the strict host tropism of herpes-viruses and other limitations mean that no single animal model can fully replicate all key features of human herpesvirus-associated diseases.This makes it challeng-ing to evaluate vaccines and antivirals against human herpesvirus comprehensively.Herein,we summarize the current animal models used to study the human herpesvi-ruses includingα-herpesviruses(herpes simplex virus type 1(HSV-1),HSV-2,VZV),β-herpesviruses(human cytomegalovirus(HCMV),γ-herpesviruses(Epstein-Barr virus(EBV))and Kaposi's sarcoma herpesvirus(KSHV)).By providing concise information and detailed analysis of the potential,limitations and applications of various models,such as non-human primates,mice,rabbits,guinea pigs,and tree shrews,this sum-mary aims to help researchers efficiently select the most appropriate animal model,offering practical guidance for studying human herpesvirus.
基金supported by the China Postdoctoral Science Foundation(2024M751098,2024M761134)Jilin Province Development and Reform Commission Program(ZKJCFGW2023015)+1 种基金Wenzhou Science&Technology Bureau Basic Public Welfare Research Program(Y20240006)Jilin University Young Teachers and Students Cross-disciplinary Training Project(2023-JCXK-08)。
文摘Photodynamic therapy(PDT)is an emerging minimally invasive therapeutic modality that relies on the activation of a photosensitizing agent by light of a specific wavelength in the presence of molecular oxygen,leading to the generation of reactive oxygen species(ROS).This mechanism facilitates selective cytotoxic effects within pathological tissues and has demonstrated therapeutic potential across diverse disease contexts.However,the broader clinical applications remain limited by photosensitizer selectivity,shallow light penetration,and the risk of off-target cytotoxicity.Recent advancements in PDT have focused on the development of next-generation photosensitizers,the integration of nanotechnology for enhanced delivery and targeting,and the strategic combination of PDT with complementary therapeutic approaches.Experimental animal models play a crucial role in validating the efficacy and safety of PDT,optimizing its therapeutic parameters,and determining its mechanisms of action.This review provides a comprehensive overview of PDT applications in various disease models,including oncological,infectious,and nonconventional indications.Special emphasis is placed on the importance of large animal models in PDT research,such as rabbits,pigs,dogs,and non-human primates,which provide experimental platforms that more closely resemble human physiological and pathological states.The use of these models for understanding the mechanisms of PDT,optimizing therapeutic regimens,and evaluating clinical outcomes is also discussed.This review aims to inform future directions in PDT research and emphasizes the importance of selecting appropriate preclinical animal models to facilitate successful clinical translation.
基金partially funded by the Bangladesh Council of Scientific and Industrial Research (BCSIR) as an R&D project work of the 2022–2023 fiscal year,reference no.:39.02.0000.011.14.157.2022/172 (Date:10.11.2022).
文摘Background:Colocasia esculenta(L.)Schott,known as the taro vegetable,possesses various beneficial effects and is traditionally used in folk medicine.This study explores the ameliorative antioxidant and hepatoprotective effect of a methanolic extract of the C.esculenta flower(ME-CEF)against oxidative damage and hepatotoxicity in mice.Methods:The antioxidant efficacy of ME-CEF was assessed using 2,2′-azino-bis-(3-ethylbenzothiazoline-6-sulfonic)(ABTS)and 2,2-diphenyl-1-picrylhydrazyl(DPPH)scavenging assay.The hepatoprotective effect was investigated by an assessment of liver injury indicators(amino transferase[ALT],aspartate amino transferase[AST],alkaline phosphatase[ALP],bilirubin,creatinine)and normalizing lipid profiles(cho-lesterol[CHO],triglyceride[TG],high-density lipoprotein[HDL],and low-density li-poprotein[LDL])along with histopathological study and antioxidant enzymes(CAT).A phytochemical analysis,both qualitative and quantitative,was conducted,including gas chromatography-tandem mass spectrometry(GC-MS/MS)analysis and an in silico molecular docking study.Results:The Result Showed that ME-CEF Possesses Moderate ABTS and DPPH Scavenging Activity with IC_(50) Values of 117.18 and 160.41μg/mL.As Illustrated by Reducing Liver Enzymes(ALT,AST,ALP,Bilirubin,Creatinine)and Lipid Profile(CHO,TG,LDL)and Raising HDL Levels(p<0.01),ME-CEF Dose Dependently Mitigated CCl_(4)-Induced Acute Liver Injury.Furthermore,ME-CEF Blocked Hepatic Oxidative Stress by Boosting Antioxidant Enzymes(CAT)and Preventing Liver Tissue Damage and Apoptosis.In Silico Investigations Also Showed a Promising Binding Affinity with Tumor Necrosis Factor α(TNF-α),Interleukin 6(IL-6),PRAP-1,and Xanthin Oxidoreductase,which Displayed Antioxidant and Hepatoprotective Candidacy while Notable Safety and Efficacy Profile Was Also Documented through ADME/T Studies.Histopathological Analysis Showed Reduced Hepatocellular Necrosis and Vascular Congestion in Silymarin and Extract Groups.Conclusion:Based on these results,our findings strongly recommend the medicinal use of the plant,highlighting its antioxidant and hepatoprotective potentials.
基金Liaoning Provincial Key Research and Development Program,Grant/Award Number:2024JH2/102500062China Health Promotion Foundation Spark Program,Grant/Award Number:XH-D001National Natural Science Foundation of China,Grant/Award Number:82104838。
文摘Cisplatin chemotherapy has been used as the main treatment for different types of cancer.However,cisplatin chemotherapy-induced peripheral neuropathic pain(CIPNP)seriously affects the treatment process and quality of life of patients.In addition,it impacts the underlying mechanism and prevention and treatment strategies,indicating that drug selection and efficacy evaluation need to be further investigated.Furthermore,an animal model that is more consistent with the pathological mechanism needs to be developed.In this study,we describe and discuss the methods of developing and detecting CIPNP models in rats and mice induced by cisplatin chemotherapy.The aim was to improve the modeling rate and develop animal models that are more consistent with the developmental pattern of the disease.In addition,the study provides ideal reference animal models for clinical research and drug discovery and development.
基金Jilin Provincial Department of Education,Grant/Award Number:JJKH20230958KJJilin Scientific and Technological Development Program,Grant/Award Number:YDZJ202401092ZYTS。
文摘Post-stroke depression(PSD) is a common psychiatric complication affecting nearly one-third of stroke survivors, leading to increased disability, mortality, and cognitive decline. Traditional Chinese Medicine(TCM) has proven effective in treating PSD through syndrome differentiation, yet existing animal models primarily reflect Western medical concepts and fail to incorporate the TCM principle of “同病异治”( treating the same disease with different methods). This paper provides a review of the current methods for constructing animal models of post-stroke depression(PSD) from the perspective of Traditional Chinese Medicine(TCM) syndrome differentiation and proposes multi-dimensional assessment indicators. By integrating TCM theories with modern biomedical techniques, this study offers a comprehensive framework for deepening the understanding of the pathogenesis and therapeutic evaluation of PSD. This approach not only contributes to advancing PSD research but also paves the way for innovative treatment strategies that combine traditional and modern medicine.
基金supported by a grant from Estate of Luther Allyn Shourds Dean,No.20R17162(to CAS)
文摘Animal models are necessary to investigate the pathogenic features underlying motor neuron degeneration and for therapeutic development in amyotrophic lateral sclerosis（ALS）. Measures of model validity allow for a critical interpretation of results from each model and caution from over-interpretation of experimental models. Face and construct validity refer to the similarity in phenotype and the proposed causal factor to the human disease, respectively. More recently developed models are restricted by limited phenotype characterization, yet new models hold promise for novel disease insights, thus highlighting their importance. In this article, we evaluate the features of face and construct validity of our new zebrafish model of environmentally-induced motor neuron degeneration and discuss this in the context of current environmental and genetic ALS models, including C9 orf72, mutant Cu/Zn superoxide dismutase 1 and TAR DNA-binding protein 43 mouse and zebrafish models. In this mini-review, we discuss the pros and cons to validity criteria in each model. Our zebrafish model of environmentally-induced motor neuron degeneration displays convincing features of face validity with many hallmarks of ALS-like features, and weakness in construct validity. However, the value of this model may lie in its potential to be more representative of the pathogenic features underlying sporadic ALS cases, where environmental factors may be more likely to be involved in disease etiology than single dominant gene mutations. It may be necessary to compare findings between different strains and species modeling specific genes or environmental factors to confirm findings from ALS animal models and tease out arbitrary strain-and overexpression-specific effects.
文摘Lung cancer is the leading cause of cancer mortality worldwide.Even with the applications of excision, radiotherapy, chemotherapy, and gene therapy, the 5 year survival rate is only 15% in the USA. Clinically relevant laboratory animal models of the disease could greatly facilitate understanding of the pathogenesis of lung cancer, its progression, invasion and metastasis. Transplanted lung cancer models are of special interest and are widely used today. Such models are essential tools in accelerating development of new therapies for lung cancer. In this communication we will present a brief overview of the hosts, sites and pathways used to establish transplanted animal lung tumor models.
基金Deputy for Research and Technology,Kermanshah University of Medical Sciences,Grant/Award Number:4030031。
文摘Background:Due to the widespread use of cell phone devices today,numerous re-search studies have focused on the adverse effects of electromagnetic radiation on human neuropsychological and reproductive systems.In most studies,oxidative stress has been identified as the primary pathophysiological mechanism underlying the harmful effects of electromagnetic waves.This paper aims to provide a holistic review of the protective effects of melatonin against cell phone-induced electromag-netic waves on various organs.Methods:This study is a systematic review of articles chosen by searching Google Scholar,PubMed,Embase,Scopus,Web of Science,and Science Direct using the key-words‘melatonin’,‘cell phone radiation’,and‘animal model’.The search focused on articles written in English,which were reviewed and evaluated.The PRISMA process was used to review the articles chosen for the study,and the JBI checklist was used to check the quality of the reviewed articles.Results:In the final review of 11 valid quality-checked articles,the effects of me-latonin in the intervention group,the effects of electromagnetic waves in the case group,and the amount of melatonin in the chosen organ,i.e.brain,skin,eyes,testis and the kidney were thoroughly examined.The review showed that electromagnetic waves increase cellular anti-oxidative activity in different tissues such as the brain,the skin,the eyes,the testis,and the kidneys.Melatonin can considerably augment the anti-oxidative system of cells and protect tissues;these measurements were sig-nificantly increased in control groups.Electromagnetic waves can induce tissue atro-phy and cell death in various organs including the brain and the skin and this effect was highly decreased by melatonin.Conclusion:Our review confirms that melatonin effectively protects the organs of an-imal models against electromagnetic waves.In light of this conclusion and the current world-wide use of melatonin,future studies should advance to the stages of human clinical trials.We also recommend that more research in the field of melatonin physi-ology is conducted in order to protect exposed cells from dying and that melatonin should be considered as a pharmaceutical option for treating the complications result-ing from electromagnetic waves in humans.
基金supported by the National Key Research and Development Program(2021YFC3002205)the Postgraduate Research and Innovation Program of Tianjin Municipal Education Commission(2022BKY113),China.
文摘Cardiac arrest(CA)is a critical condition in the field of cardiovascular medicine.Despite successful resuscitation,patients continue to have a high mortality rate,largely due to post CA syndrome(PCAS).However,the injury and pathophysiological mechanisms underlying PCAS remain unclear.Experimental animal models are valuable tools for exploring the etiology,pathogenesis,and potential interventions for CA and PCAS.Current CA animal models include electrical induction of ventricular fibrillation(VF),myocardial infarction,high potassium,asphyxia,and hemorrhagic shock.Although these models do not fully replicate the complexity of clinical CA,the mechanistic insights they provide remain highly relevant,including post-CA brain injury(PCABI),post-CA myocardial dysfunction(PAMD),systemic ischaemia/reperfusion injury(IRI),and the persistent precipitating pathology.Summarizing the methods of establishing CA models,the challenges encountered in the modeling process,and the mechanisms of PCAS can provide a foundation for developing standardized CA modeling protocols.
文摘Depression is a chronic,recurring and potentially life-threatening illness that affects up to 20%of the population across the world.Despite its prevalence and considerable impact on human,little is known about its pathogenesis.One of the major reasons is the restricted availability of validated animal models due to the absence of consensus on the pathology and etiology of depression.Besides,some core symptoms such as depressed mood,feeling of worthlessness,and recurring thoughts of death or suicide,are impossible to be modeled on laboratory animals.Currently,the criteria for identifying animal models of depression rely on either of the 2 principles：actions of known antidepressants and responses to stress.This review mainly focuses on the most widely used animal models of depression,including learned helplessness,chronic mild stress,and social defeat paradigms.Also,the behavioral tests for screening antidepressants,such as forced swimming test and tail suspension test,are also discussed.The advantages and major drawbacks of each model are evaluated.In prospective,new techniques that will be beneficial for developing novel animal models or detecting depression are discussed.
基金National Natural Science Foundation of China,Grant/Award Number:82270289Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(CAMS),Grant/Award Number:2021-I2M-1-035the National key research and development program,Grant/Award Number:2022YFF0710600。
文摘Although hypertension is a frequently seen chronic condition across the world,its exact cause remains unclear.Animal models are beneficial for clarifying the pathogenic mechanism of hypertension and examining new treatments.An optimal animal model for studies on hypertension must well mimic human-like hemodynamics and pathophysiological structural modification,showing human disease features and complications timely or even ahead of time.A review of the most frequently used hypertensive animal models available,including small and large animals,induced and genetic models,would provide an insight into the appropriate targets to be addressed in the development of different hypertensive animal models.Another focus of the review are the processes of target-organs injury caused by high blood pressure,which mainly influences human health.
文摘Rotator cuff tears are highly prevalent,and there is an urgent need to understand their healing mechanisms to improve treatment outcomes for patients.This editorial aims to summarize the roles and limitations of common animal models(including rodents,rabbits,sheep,dogs,and primates)and second-look arthroscopy in rotator cuff healing research.Different animal models offer distinct advantages and disadvantages.For example,rodent models are cost-effective and suitable for genetic studies but have anatomical differences from humans.Rabbit models are favored for their relatively large tendon size and ease of surgical manipulation,yet they still deviate from human shoulder anatomy in some aspects.Larger animals like sheep and dogs have more similar shoulder structures to humans but come with high costs and challenges in maintaining consistent experimental conditions.Second-look arthroscopic studies have provided evidence for the effectiveness of current surgical techniques.Animal models will continue to play a crucial role in further exploring the local microenvironment of the rotator cuff,which is expected to help develop more effective strategies to promote healing.
基金supported by the Postdoctoral Fellowship Program of CPSF (GZC20231064)China Postdoctoral Science Foundation (2024M761345)+3 种基金Guangzhou Basic and Applied Basic Research Foundation (2024A04J6615)Scientific Research Project of Southern Medical University Stomatological Hospital (PY2023004)National Key Research and Development Program of China (2021YFA0805300)National Natural Science Foundation of China (82171244,32470564)。
文摘Severe combined immunodeficiency disease(SCID),characterized by profound immune system dysfunction,can lead to life-threatening infections and death.Animal models play a pivotal role in elucidating biological processes and advancing therapeutic strategies.Recent advances in gene-editing technologies,including zincfinger nucleases(ZFNs),transcription activator-like effector nucleases(TALENs),CRISPR/Cas9,and base editing,have significantly enhanced the generation of SCID models.These models have not only deepened our understanding of disease pathophysiology but have also driven progress in cancer therapy,stem cell transplantation,organ transplantation,and infectious diseasemanagement.Thisreviewprovidesa comprehensive overview of current SCID models generated using novel gene-editing approaches,highlighting their potential applications in translational medicine and their role in advancing biomedical research.
基金Natural Science Foundation of Shaanxi Province,Grant/Award Number:2023-CX-PT-17General Project of Natural Science Research in Luoyang Polytechnic College,Grant/Award Number:2024B01。
文摘The mortality rate of patients with abdominal aortic aneurysm(AAA) after rupture is extremely high,and this disease has become an important disease endangering the health of the Chinese population.Methods used to model AAA include intraluminal pressurized elastase infusion,chronic infusion of angiotensin Ⅱ(Ang Ⅱ) via an osmotic pump,periarterial application of calcium chloride,vascular grafting,and gene modification.AAA models induced by elastase and Ang Ⅱ are the two most widely used animal models.In the elastase-induced model,because intraluminal infusion is transient,with the cessation of initial stimulation,the aneurysm lesion tends to be stable and rarely ruptures.The model induced by Ang Ⅱ infusion often presents with a typical aortic dissection with a false lumen,whereas clinical AAA patients do not necessarily have dissection.Currently,the treatment of AAA in clinical practice remains endovascular,and there is a lack of pharmacological therapy,which is also related to the fact that the pathogenic mechanism has not been fully elucidated.Smoking,old age,male sex,and hypertension are the main risk factors for AAA,but these risk factors have not been fully investigated in the current modeling methods,which may affect the clinical translational application of research results based on animal models.Therefore,this article reviews the most commonly used AAA modeling methods,comments on their applications and limitations,and provides a perspective on the development of novel animal models.
文摘Parkinson’s disease is chara cterized by the loss of dopaminergic neurons in the substantia nigra pars com pacta,and although restoring striatal dopamine levels may improve symptoms,no treatment can cure or reve rse the disease itself.Stem cell therapy has a regenerative effect and is being actively studied as a candidate for the treatment of Parkinson’s disease.Mesenchymal stem cells are considered a promising option due to fewer ethical concerns,a lower risk of immune rejection,and a lower risk of teratogenicity.We performed a meta-analysis to evaluate the therapeutic effects of mesenchymal stem cells and their derivatives on motor function,memory,and preservation of dopamine rgic neurons in a Parkinson’s disease animal model.We searched bibliographic databases(PubMed/MEDLINE,Embase,CENTRAL,Scopus,and Web of Science)to identify articles and included only pee r-reviewed in vivo interve ntional animal studies published in any language through J une 28,2023.The study utilized the random-effect model to estimate the 95%confidence intervals(CI)of the standard mean differences(SMD)between the treatment and control groups.We use the systematic review center for laboratory animal expe rimentation’s risk of bias tool and the collaborative approach to meta-analysis and review of animal studies checklist for study quality assessment.A total of 33studies with data from 840 Parkinson’s disease model animals were included in the meta-analysis.Treatment with mesenchymal stem cells significantly improved motor function as assessed by the amphetamine-induced rotational test.Among the stem cell types,the bone marrow MSCs with neurotrophic factor group showed la rgest effect size(SMD[95%CI]=-6.21[-9.50 to-2.93],P=0.0001,I^(2)=0.0%).The stem cell treatment group had significantly more tyrosine hydroxylase positive dopamine rgic neurons in the striatum([95%CI]=1.04[0.59 to 1.49],P=0.0001,I^(2)=65.1%)and substantia nigra(SMD[95%CI]=1.38[0.89 to 1.87],P=0.0001,I^(2)=75.3%),indicating a protective effect on dopaminergic neurons.Subgroup analysis of the amphetamine-induced rotation test showed a significant reduction only in the intracranial-striatum route(SMD[95%CI]=-2.59[-3.25 to-1.94],P=0.0001,I^(2)=74.4%).The memory test showed significant improvement only in the intravenous route(SMD[95%CI]=4.80[1.84 to 7.76],P=0.027,I^(2)=79.6%).Mesenchymal stem cells have been shown to positively impact motor function and memory function and protect dopaminergic neurons in preclinical models of Parkinson’s disease.Further research is required to determine the optimal stem cell types,modifications,transplanted cell numbe rs,and delivery methods for these protocols.
基金Supported by Fondo de Investigación Sanitaria,Spain (Grant PI070788)CIBERehd is funded by Instituto de la Salud Carlos Ⅲ,Spain
文摘Acute hepatic failure (AHF) is a severe liver injury accompanied by hepatic encephalopathy which causes multiorgan failure with an extremely high mortality rate, even if intensive care is provided. Management of severe AHF continues to be one of the most challenging problems in clinical medicine. Liver transplantation has been shown to be the most effective therapy, but the procedure is limited by shortage of donor organs. Although a number of clinical trials testing different liver assist devices are under way, these systems alone have no significant effect on patient survival and are only regarded as a useful approach to bridge patients with AHF to liver transplantation. As a result, reproducible experimental animal models resembling the clinical conditions are still needed. The three main approaches used to create an animal model for AHF are: surgical procedures, toxic liver injury and infective procedures. Most common models are based on surgical techniques (total/partial hepatectomy, complete/transient devascularization) or the use of hepatotoxic drugs (acetaminophen, galactosamine, thioacetamide, and others), and very few satisfactory viral models are available. We have recently developed a viral model of AHF by means of the inoculation of rabbits with the virus of rabbit hemorrhagic disease. This model displays biochemical and histological characteristics, and clinical features that resemble those in human AHF. In the present article an overview is given of the most widely used animal models of AHF, and their main advantages and disadvantages are reviewed.
