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
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
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
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
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
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
Background:Developing a granulomatous liver injury preclinical model may pave the way to understanding hepatic-TB(tuberculosis)and autoimmune granulomatous liver diseases.Antitubercular(ATT)and other drugs'metabol...Background:Developing a granulomatous liver injury preclinical model may pave the way to understanding hepatic-TB(tuberculosis)and autoimmune granulomatous liver diseases.Antitubercular(ATT)and other drugs'metabolism in the presence of a specific type of liver injury is not well understood.The present study aimed to establish a preclinical model of granulomatous hepatitis by using the BCG(Bacillus CalmetteGuérin)vaccine,further studying it in the presence of ATT dosing,and analyze the pharmacokinetics of isoniazid,rifampicin,and their respective primary metabolites.Methods:We used 56 rats in seven equal groups.Group I functioned as a normal control(NC)receiving normal saline only.Groups II-IV received intravenous injections of low-,medium-,and high-dose BCG vaccine daily for 21 days.Groups V,VI,and VII received isoniazid(H)alone,rifampicin(R)alone,and isoniazid+rifampicin(HR)for a subsequent 15 days in addition to high dose BCG for the first 21 days,respectively.Liver function tests(LFT)were monitored on days 0,21,28,and 36.Rats were sacrificed later for oxidative stress and histopathological examination.Results:The study observed BCG dose-specific LFT derangements in groups II-IV compared to group I on day 21(p<0.05).Isoniazid,rifampicin,and combination intervention groups demonstrated normalization of the BCG-led LFT changes.Histology and oxidative stress parameters confirmed model development and biochemical changes.Isoniazid area under the curve(AUC)showed a reduction of 16.9%in BCG+HR group in comparison to the BCG+H group(p=0.01).Des-acetyl-rifampicin AUC and maximum-concentration value demonstrated a significant rise in BCG+HR group in comparison to the BCG+R group(p=0.001).Conclusion:A novel preclinical model of granulomatous liver injury was developed using the BCG vaccine strain and validated with ATT response.展开更多
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
BACKGROUND Primary biliary cholangitis(PBC)is a chronic autoimmune-mediated cholestatic liver disease.Nanoparticles encapsulating rapamycin(ImmTOR)suppress adaptive immune responses and induce the hepatic tolerogenic ...BACKGROUND Primary biliary cholangitis(PBC)is a chronic autoimmune-mediated cholestatic liver disease.Nanoparticles encapsulating rapamycin(ImmTOR)suppress adaptive immune responses and induce the hepatic tolerogenic immune response.AIM To investigate the effects of ImmTOR in PBC mouse models.METHODS PBC models were induced in C57BL/6 mice by two immunizations of 2-octynoic acid-coupled bovine serum albumin at two-week intervals,and polycytidylic acid every three days.The PBC mouse models were separated into the treatment group and the control group.The levels of alkaline phosphatase(ALP)and alanine aminotransferase in the mice were detected using an automatic biochemical analyzer.Liver and spleen mononuclear cells were analyzed by flow cytometry,and serum anti-mitochondrial antibodies(AMA)and the related cytokines were analyzed by enzyme-linked immunosorbent assay.Liver histopathology was examined by hematoxylin and eosin staining and scored.RESULTS After treatment with ImmTOR,the ALP level was significantly decreased(189.60 U/L±27.25 U/L vs 156.00 U/L±17.21 U/L,P<0.05),the level of AMA was reduced(1.28 ng/mL±0.27 ng/mL vs 0.56 ng/mL±0.07 ng/mL,P<0.001)and the expression levels of interferon gamma and tumor necrosis factorαwere significantly decreased(48.29 pg/mL±10.84 pg/mL vs 25.01 pg/mL±1.49 pg/mL,P<0.0001)and(84.24 pg/mL±23.47 pg/mL vs 40.66 pg/mL±14.65 pg/mL,P<0.001).The CD4+T lymphocytes,CD8+T lymphocytes and B lymphocytes in the liver were significantly reduced,with statistically significant differences(24.21%±6.55%vs 15.98%±3.03%,P<0.05;9.09%±1.91%vs 5.49%±1.00%,P<0.001;80.51%±2.96%vs 75.31%±4.34%,P<0.05).The expression of CD8+T lymphocytes and B lymphocytes in the ImmTOR treatment group also decreased(9.09%±1.91%vs 5.49%±1.00%,P<0.001;80.51%±2.96%vs 75.31%±4.34%,P<0.05).The liver pathology of PBC mice in the treatment group showed reduced inflammation and a decreased total pathology score,and the difference in the scores was statistically significant(4.50±2.88 vs 1.75±1.28,P<0.05).CONCLUSION ImmTOR can improve biochemistry and pathology of liver obvious by inhibiting the expression of CD8+T cells and B cells,and reducing the titer of AMA.展开更多
BACKGROUND Skin wounds are common injuries that affect quality of life and incur high costs.A considerable portion of healthcare resources in Western countries is allocated to wound treatment,mainly using mechanical,b...BACKGROUND Skin wounds are common injuries that affect quality of life and incur high costs.A considerable portion of healthcare resources in Western countries is allocated to wound treatment,mainly using mechanical,biological,or artificial dressings.Biological and artificial dressings,such as hydrogels,are preferred for their biocompatibility.Platelet concentrates,such as platelet-rich plasma(PRP)and platelet-rich fibrin(PRF),stand out for accelerating tissue repair and minimizing risks of allergies and rejection.This study developed PRF and PRP-based dressings to treat skin wounds in an animal model,evaluating their functionality and efficiency in accelerating the tissue repair process.AIM To develop wound dressings based on platelet concentrates and evaluating their efficiency in treating skin wounds in Wistar rats.METHODS Wistar rats,both male and female,were subjected to the creation of a skin wound,distributed into groups(n=64/group),and treated with Carbopol(negative control);PRP+Carbopol;PRF+Carbopol;or PRF+CaCl_(2)+Carbopol,on days zero(D0),D3,D7,D14,and D21.PRP and PRF were obtained only from male rats.On D3,D7,D14,and D21,the wounds were analyzed for area,contraction rate,and histopathology of the tissue repair process.RESULTS The PRF-based dressing was more effective in accelerating wound closure early in the tissue repair process(up to D7),while PRF+CaCl_(2) seemed to delay the process,as wound closure was not complete by D21.Regarding macroscopic parameters,animals treated with PRF+CaCl_(2) showed significantly more crusting(necrosis)early in the repair process(D3).In terms of histopathological parameters,the PRF group exhibited significant collagenization at the later stages of the repair process(D14 and D21).By D21,fibroblast proliferation and inflammatory infiltration were higher in the PRP group.Animals treated with PRF+CaCl_(2) experienced a more pronounced inflammatory response up to D7,which diminished from D14 onwards.CONCLUSION The PRF-based dressing was effective in accelerating the closure of cutaneous wounds in Wistar rats early in the process and in aiding tissue repair at the later stages.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
The present study aims to establish a reproducible large animal experimental unit using a minipig model to monitor cardiac function changes.A 90-min closed-chest bal-loon occlusion of the left anterior descending bran...The present study aims to establish a reproducible large animal experimental unit using a minipig model to monitor cardiac function changes.A 90-min closed-chest bal-loon occlusion of the left anterior descending branch of the coronary artery was used to induce myocardial infarction in Pannon minipigs.To monitor the cardiac function,measurements were made by cardiac magnetic resonance imaging(cMRI),invasive pressure monitoring,and a Pulse index Continuous Cardiac Output(PiCCO)hemo-dynamic system at 0,72,and 720 h during the follow-up period.End-diastolic and end-systolic volumes(EDV,ESV),left ventricular ejection fraction(LVEF)obtained by cMRI evaluation,global ejection fraction and aortic dP/dt_(max)obtained by the invasive method,were recorded and compared.The 72-and 720-h EDV data showed a signifi-cant increase(p=0.012,<0.001)compared to baseline,and the Day 30 data showed a significant increase compared to Day 3(p=0.022).The ESV 72 h after the infarction showed a significant increase(p=0.001)compared to baseline,which did not change significantly by Day 30(p=0.781)compared to Day 3.EDV and ESV were signifi-cantly negatively correlated with aortic dp_(max),and ESV was significantly correlated with LVEF.For LVEF and dP_(max),a significant(p<0.001 and p=0.002)worsening was demonstrated at Day 3 compared to baseline,which was no longer statistically de-tectable for LVEF at Day 30(p=0.141),while the difference for dP_(max)was maintained(p=0.002).The complementary use of PiCCO hemodynamic measurements in large animal models makes the previously used methodologies more robust and reliable.展开更多
Oral squamous cell carcinoma(OSCC)constitutes 90%of oral tumors.Advanced cases severely impair patients'life quality of life due to anatomical location and limited therapies.Conventional treatments often induce dr...Oral squamous cell carcinoma(OSCC)constitutes 90%of oral tumors.Advanced cases severely impair patients'life quality of life due to anatomical location and limited therapies.Conventional treatments often induce drug resistance or recurrence.Patientderived xenograft(PDX)models are widely used to simulate tumor progression and drug responses,serving as translational tools for precision medicine.This study aimed to establish drug-resistant OSCC PDX models.Human OSCC tissues were transplanted into immunodeficient mice and passaged(P1–P2).At P2(tumor volume:40–80 mm^(3)),mice received cisplatin(1 mg/kg,three times/week)with cetuximab(1 mg/kg,weekly),GSK690693(10 mg/kg,five times/week),or rapamycin(4 mg/kg,five times/week).PDX tissues from groups with less-therapeutic response(manifested as larger tumor volumes)were serially passaged to assess treatment efficacy.Tumor tissues with diminished drug sensitivity underwent histopathological analysis and identified stability of their tumor characteristics using hematoxylin–eosin(HE)and immunohistochemical staining after one additional passage and retreatment.Results demonstrated that successive passaging accelerates tumor growth.First-generation treatments showed universal sensitivity.At P2,cisplatin–cetuximab and rapamycin groups remained sensitive,whereas GSK690693 efficacy declined.Continued passaging of GSK690693-treated tumors confirmed resistance,as evidenced by exhibiting enhanced malignant characteristics at histological level.The GSK690693-resistant model was established first,whereas resistant models of other treatment groups were established according to similar protocols.These findings suggest that sequential passaging and drug exposure in PDX models recapitulated clinical tumor evolution,enabling the development of drug-resistant OSCC models.This study can offer methodological insights for precision therapy of OSCC.展开更多
Human immunodeficiency virus(HIV)infection is strongly associated with a height-ened incidence of lymphomas.To mirror the natural course of human HIV infection,animal models have been developed.These models serve as v...Human immunodeficiency virus(HIV)infection is strongly associated with a height-ened incidence of lymphomas.To mirror the natural course of human HIV infection,animal models have been developed.These models serve as valuable tools to inves-tigate disease pathobiology,assess antiretroviral and immunomodulatory drugs,ex-plore viral reservoirs,and develop eradication strategies.However,there are currently no validated in vivo models of HIV-associated lymphoma(HAL),hampering progress in this crucial domain,and scant attention has been given to developing animal models dedicated to studying HAL,despite their pivotal role in advancing knowledge.This re-view provides a comprehensive overview of the existing animal models of HAL,which may enhance our understanding of the underlying pathogenesis and approaches for malignancies linked to HIV infection.展开更多
BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)is a prevalent chronic liver disorder driven by obesity and metabolic dysfunction.MASLD progresses to metabolic dysfunction-associated steatohe...BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)is a prevalent chronic liver disorder driven by obesity and metabolic dysfunction.MASLD progresses to metabolic dysfunction-associated steatohepatitis,which is characterized by inflammation,hepatocyte injury,and fibrosis,increasing the risk of cirrhosis and liver failure.Recent studies suggest that neutrophil extracellular traps(NETs)and extracellular DNA(ecDNA)contribute to liver inflammation and fibrogenesis.However,their role in MASLD pathogenesis remains incompletely understood.AIM To investigate the dynamics of circulating NETs and ecDNA as potential biomarkers of liver injury in MASLD.METHODS Using three complementary mouse models,thioacetamide(TAA)-induced fibrosis,choline-deficient L-amino acid-defined(CDAA)diet-induced metabolic dysfunction-associated steatohepatitis,and cafeteria(CAF)diet-induced MASLD,we assessed the association between NET-related markers and liver damage.Blood samples were collected biweekly to analyze ecDNA and NET markers,including myeloperoxidase(MPO)and MPO-DNA complexes,using ELISA and real-time PCR.Liver histopathology was assessed for inflammation,fibrosis,and neutrophil infiltration.RESULTS The TAA and CDAA models exhibited significant liver injury,characterized by increased plasma alanine aminotransferase and aspartate aminotransferase levels,hepatocellular damage,and fibrosis.Elevated circulating NET markers(MPO and ecDNA)were observed in these models,with a strong correlation between NET formation and liver pathology.The CAF diet model induced steatosis but failed to elicit significant liver fibrosis or an increase in NET markers,suggesting that NETosis is associated with more severe liver damage.Notably,ecDNA and MPO levels correlated with neutrophil infiltration and fibrosis scores,indicating their potential as biomarkers of MASLD progression.CONCLUSION NETosis and ecDNA levels reflect liver injury severity in MASLD.NET markers and liver fibrosis were strongly associated in TAA and CDAA models,whereas CAF model showed minimal NET involvement.展开更多
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 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.
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 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Background:Developing a granulomatous liver injury preclinical model may pave the way to understanding hepatic-TB(tuberculosis)and autoimmune granulomatous liver diseases.Antitubercular(ATT)and other drugs'metabolism in the presence of a specific type of liver injury is not well understood.The present study aimed to establish a preclinical model of granulomatous hepatitis by using the BCG(Bacillus CalmetteGuérin)vaccine,further studying it in the presence of ATT dosing,and analyze the pharmacokinetics of isoniazid,rifampicin,and their respective primary metabolites.Methods:We used 56 rats in seven equal groups.Group I functioned as a normal control(NC)receiving normal saline only.Groups II-IV received intravenous injections of low-,medium-,and high-dose BCG vaccine daily for 21 days.Groups V,VI,and VII received isoniazid(H)alone,rifampicin(R)alone,and isoniazid+rifampicin(HR)for a subsequent 15 days in addition to high dose BCG for the first 21 days,respectively.Liver function tests(LFT)were monitored on days 0,21,28,and 36.Rats were sacrificed later for oxidative stress and histopathological examination.Results:The study observed BCG dose-specific LFT derangements in groups II-IV compared to group I on day 21(p<0.05).Isoniazid,rifampicin,and combination intervention groups demonstrated normalization of the BCG-led LFT changes.Histology and oxidative stress parameters confirmed model development and biochemical changes.Isoniazid area under the curve(AUC)showed a reduction of 16.9%in BCG+HR group in comparison to the BCG+H group(p=0.01).Des-acetyl-rifampicin AUC and maximum-concentration value demonstrated a significant rise in BCG+HR group in comparison to the BCG+R group(p=0.001).Conclusion:A novel preclinical model of granulomatous liver injury was developed using the BCG vaccine strain and validated with ATT response.
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Supported by Cultivation Project of Hebei Natural Science Foundation-Precision Medicine Joint Fund,No.H2021206239.
文摘BACKGROUND Primary biliary cholangitis(PBC)is a chronic autoimmune-mediated cholestatic liver disease.Nanoparticles encapsulating rapamycin(ImmTOR)suppress adaptive immune responses and induce the hepatic tolerogenic immune response.AIM To investigate the effects of ImmTOR in PBC mouse models.METHODS PBC models were induced in C57BL/6 mice by two immunizations of 2-octynoic acid-coupled bovine serum albumin at two-week intervals,and polycytidylic acid every three days.The PBC mouse models were separated into the treatment group and the control group.The levels of alkaline phosphatase(ALP)and alanine aminotransferase in the mice were detected using an automatic biochemical analyzer.Liver and spleen mononuclear cells were analyzed by flow cytometry,and serum anti-mitochondrial antibodies(AMA)and the related cytokines were analyzed by enzyme-linked immunosorbent assay.Liver histopathology was examined by hematoxylin and eosin staining and scored.RESULTS After treatment with ImmTOR,the ALP level was significantly decreased(189.60 U/L±27.25 U/L vs 156.00 U/L±17.21 U/L,P<0.05),the level of AMA was reduced(1.28 ng/mL±0.27 ng/mL vs 0.56 ng/mL±0.07 ng/mL,P<0.001)and the expression levels of interferon gamma and tumor necrosis factorαwere significantly decreased(48.29 pg/mL±10.84 pg/mL vs 25.01 pg/mL±1.49 pg/mL,P<0.0001)and(84.24 pg/mL±23.47 pg/mL vs 40.66 pg/mL±14.65 pg/mL,P<0.001).The CD4+T lymphocytes,CD8+T lymphocytes and B lymphocytes in the liver were significantly reduced,with statistically significant differences(24.21%±6.55%vs 15.98%±3.03%,P<0.05;9.09%±1.91%vs 5.49%±1.00%,P<0.001;80.51%±2.96%vs 75.31%±4.34%,P<0.05).The expression of CD8+T lymphocytes and B lymphocytes in the ImmTOR treatment group also decreased(9.09%±1.91%vs 5.49%±1.00%,P<0.001;80.51%±2.96%vs 75.31%±4.34%,P<0.05).The liver pathology of PBC mice in the treatment group showed reduced inflammation and a decreased total pathology score,and the difference in the scores was statistically significant(4.50±2.88 vs 1.75±1.28,P<0.05).CONCLUSION ImmTOR can improve biochemistry and pathology of liver obvious by inhibiting the expression of CD8+T cells and B cells,and reducing the titer of AMA.
文摘BACKGROUND Skin wounds are common injuries that affect quality of life and incur high costs.A considerable portion of healthcare resources in Western countries is allocated to wound treatment,mainly using mechanical,biological,or artificial dressings.Biological and artificial dressings,such as hydrogels,are preferred for their biocompatibility.Platelet concentrates,such as platelet-rich plasma(PRP)and platelet-rich fibrin(PRF),stand out for accelerating tissue repair and minimizing risks of allergies and rejection.This study developed PRF and PRP-based dressings to treat skin wounds in an animal model,evaluating their functionality and efficiency in accelerating the tissue repair process.AIM To develop wound dressings based on platelet concentrates and evaluating their efficiency in treating skin wounds in Wistar rats.METHODS Wistar rats,both male and female,were subjected to the creation of a skin wound,distributed into groups(n=64/group),and treated with Carbopol(negative control);PRP+Carbopol;PRF+Carbopol;or PRF+CaCl_(2)+Carbopol,on days zero(D0),D3,D7,D14,and D21.PRP and PRF were obtained only from male rats.On D3,D7,D14,and D21,the wounds were analyzed for area,contraction rate,and histopathology of the tissue repair process.RESULTS The PRF-based dressing was more effective in accelerating wound closure early in the tissue repair process(up to D7),while PRF+CaCl_(2) seemed to delay the process,as wound closure was not complete by D21.Regarding macroscopic parameters,animals treated with PRF+CaCl_(2) showed significantly more crusting(necrosis)early in the repair process(D3).In terms of histopathological parameters,the PRF group exhibited significant collagenization at the later stages of the repair process(D14 and D21).By D21,fibroblast proliferation and inflammatory infiltration were higher in the PRP group.Animals treated with PRF+CaCl_(2) experienced a more pronounced inflammatory response up to D7,which diminished from D14 onwards.CONCLUSION The PRF-based dressing was effective in accelerating the closure of cutaneous wounds in Wistar rats early in the process and in aiding tissue repair at the later stages.
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.
文摘The present study aims to establish a reproducible large animal experimental unit using a minipig model to monitor cardiac function changes.A 90-min closed-chest bal-loon occlusion of the left anterior descending branch of the coronary artery was used to induce myocardial infarction in Pannon minipigs.To monitor the cardiac function,measurements were made by cardiac magnetic resonance imaging(cMRI),invasive pressure monitoring,and a Pulse index Continuous Cardiac Output(PiCCO)hemo-dynamic system at 0,72,and 720 h during the follow-up period.End-diastolic and end-systolic volumes(EDV,ESV),left ventricular ejection fraction(LVEF)obtained by cMRI evaluation,global ejection fraction and aortic dP/dt_(max)obtained by the invasive method,were recorded and compared.The 72-and 720-h EDV data showed a signifi-cant increase(p=0.012,<0.001)compared to baseline,and the Day 30 data showed a significant increase compared to Day 3(p=0.022).The ESV 72 h after the infarction showed a significant increase(p=0.001)compared to baseline,which did not change significantly by Day 30(p=0.781)compared to Day 3.EDV and ESV were signifi-cantly negatively correlated with aortic dp_(max),and ESV was significantly correlated with LVEF.For LVEF and dP_(max),a significant(p<0.001 and p=0.002)worsening was demonstrated at Day 3 compared to baseline,which was no longer statistically de-tectable for LVEF at Day 30(p=0.141),while the difference for dP_(max)was maintained(p=0.002).The complementary use of PiCCO hemodynamic measurements in large animal models makes the previously used methodologies more robust and reliable.
基金National Natural Science Foundation of China,Grant/Award Number:82173399Young Elite Scientists Sponsorship Program by CAST,Grant/Award Number:2022QNRC001+2 种基金Beijing Natural Science Foundation,Grant/Award Number:7252096Beijing Natural Science Foundation-Haidian Original Innovation Joint Fund Project,Grant/Award Number:L222145CAMS&Comparative Medicine Center,PUMC (IACUC approval number:QC24002)
文摘Oral squamous cell carcinoma(OSCC)constitutes 90%of oral tumors.Advanced cases severely impair patients'life quality of life due to anatomical location and limited therapies.Conventional treatments often induce drug resistance or recurrence.Patientderived xenograft(PDX)models are widely used to simulate tumor progression and drug responses,serving as translational tools for precision medicine.This study aimed to establish drug-resistant OSCC PDX models.Human OSCC tissues were transplanted into immunodeficient mice and passaged(P1–P2).At P2(tumor volume:40–80 mm^(3)),mice received cisplatin(1 mg/kg,three times/week)with cetuximab(1 mg/kg,weekly),GSK690693(10 mg/kg,five times/week),or rapamycin(4 mg/kg,five times/week).PDX tissues from groups with less-therapeutic response(manifested as larger tumor volumes)were serially passaged to assess treatment efficacy.Tumor tissues with diminished drug sensitivity underwent histopathological analysis and identified stability of their tumor characteristics using hematoxylin–eosin(HE)and immunohistochemical staining after one additional passage and retreatment.Results demonstrated that successive passaging accelerates tumor growth.First-generation treatments showed universal sensitivity.At P2,cisplatin–cetuximab and rapamycin groups remained sensitive,whereas GSK690693 efficacy declined.Continued passaging of GSK690693-treated tumors confirmed resistance,as evidenced by exhibiting enhanced malignant characteristics at histological level.The GSK690693-resistant model was established first,whereas resistant models of other treatment groups were established according to similar protocols.These findings suggest that sequential passaging and drug exposure in PDX models recapitulated clinical tumor evolution,enabling the development of drug-resistant OSCC models.This study can offer methodological insights for precision therapy of OSCC.
基金Chongqing Professional Talents Plan,Grant/Award Number:cstc2022ycjh-bgzxm0048Fundamental Research Funds for the Central Universities,Grant/Award Number:2022CDJYGRH-001Natural Science Foundation of Chongqing,China,Grant/Award Number:CSTB2022NSCQ-MSX1150。
文摘Human immunodeficiency virus(HIV)infection is strongly associated with a height-ened incidence of lymphomas.To mirror the natural course of human HIV infection,animal models have been developed.These models serve as valuable tools to inves-tigate disease pathobiology,assess antiretroviral and immunomodulatory drugs,ex-plore viral reservoirs,and develop eradication strategies.However,there are currently no validated in vivo models of HIV-associated lymphoma(HAL),hampering progress in this crucial domain,and scant attention has been given to developing animal models dedicated to studying HAL,despite their pivotal role in advancing knowledge.This re-view provides a comprehensive overview of the existing animal models of HAL,which may enhance our understanding of the underlying pathogenesis and approaches for malignancies linked to HIV infection.
基金Supported by Slovak Research and Development Agency,No.APVV-21-0370Ministry of Education,Science,Research and Sport of the Slovak Republic,No.VEGA 1/0706/25 and No.VEGA 1/0341/23.
文摘BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)is a prevalent chronic liver disorder driven by obesity and metabolic dysfunction.MASLD progresses to metabolic dysfunction-associated steatohepatitis,which is characterized by inflammation,hepatocyte injury,and fibrosis,increasing the risk of cirrhosis and liver failure.Recent studies suggest that neutrophil extracellular traps(NETs)and extracellular DNA(ecDNA)contribute to liver inflammation and fibrogenesis.However,their role in MASLD pathogenesis remains incompletely understood.AIM To investigate the dynamics of circulating NETs and ecDNA as potential biomarkers of liver injury in MASLD.METHODS Using three complementary mouse models,thioacetamide(TAA)-induced fibrosis,choline-deficient L-amino acid-defined(CDAA)diet-induced metabolic dysfunction-associated steatohepatitis,and cafeteria(CAF)diet-induced MASLD,we assessed the association between NET-related markers and liver damage.Blood samples were collected biweekly to analyze ecDNA and NET markers,including myeloperoxidase(MPO)and MPO-DNA complexes,using ELISA and real-time PCR.Liver histopathology was assessed for inflammation,fibrosis,and neutrophil infiltration.RESULTS The TAA and CDAA models exhibited significant liver injury,characterized by increased plasma alanine aminotransferase and aspartate aminotransferase levels,hepatocellular damage,and fibrosis.Elevated circulating NET markers(MPO and ecDNA)were observed in these models,with a strong correlation between NET formation and liver pathology.The CAF diet model induced steatosis but failed to elicit significant liver fibrosis or an increase in NET markers,suggesting that NETosis is associated with more severe liver damage.Notably,ecDNA and MPO levels correlated with neutrophil infiltration and fibrosis scores,indicating their potential as biomarkers of MASLD progression.CONCLUSION NETosis and ecDNA levels reflect liver injury severity in MASLD.NET markers and liver fibrosis were strongly associated in TAA and CDAA models,whereas CAF model showed minimal NET involvement.
