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 Non-erosive reflux disease(NERD),the main gastroesophageal reflux subtype,features reflux symptoms without mucosal damage.Anxiety links to visceral hypersensitivity in NERD,yet mechanisms and animal models ...BACKGROUND Non-erosive reflux disease(NERD),the main gastroesophageal reflux subtype,features reflux symptoms without mucosal damage.Anxiety links to visceral hypersensitivity in NERD,yet mechanisms and animal models are unclear.AIM To establish a translational NERD rat model with anxiety comorbidity via tail clamping and study corticotropin-releasing hormone(CRH)-mediated neuroimmune pathways in visceral hypersensitivity and esophageal injury.METHODS Sprague-Dawley(SD)and Wistar rats were grouped into sham,model,and modified groups(n=10 each).The treatments for the modified groups were as follows:SD rats received ovalbumin/aluminum hydroxide suspension+acid perfusion±tail clamping(40 minutes/day for 7 days),while Wistar rats received fructose water+tail clamping.Esophageal pathology,visceral sensitivity,and behavior were assessed.Serum CRH,calcitonin gene-related peptide(CGRP),5-hydroxytryptamine(5-HT),and mast cell tryptase(MCT)and central amygdala(CeA)CRH mRNA were measured via ELISA and qRT-PCR.RESULTS Tail clamping induced anxiety,worsening visceral hypersensitivity(lower abdominal withdrawal reflex thresholds,P<0.05)and esophageal injury(dilated intercellular spaces and mitochondrial edema).Both models showed raised serum CRH,CGRP,5-HT,and MCT(P<0.01)and CeA CRH mRNA expression(P<0.01).Behavioral tests confirmed anxiety-like phenotypes.NERD-anxiety rats showed clinical-like symptom severity without erosion.CONCLUSION Tail clamping induces anxiety in NERD models,worsening visceral hypersensitivity via CRH neuroimmune dysregulation,offering a translational model and highlighting CRH as a treatment target.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 Tuberculosis is among the most devastating infectious diseases worldwide.Spinal tuberculosis is not easy to detect at an early stage,which without effective treatment often leads to spinal deformity and spi...BACKGROUND Tuberculosis is among the most devastating infectious diseases worldwide.Spinal tuberculosis is not easy to detect at an early stage,which without effective treatment often leads to spinal deformity and spinal cord damage which in turn cause complications such as paraplegia and quadriplegia.In this study,we established a model using three concentrations of bacteria and carried out a comprehensive evaluation of the model by imaging,general observations,and histopathological and bacteriological studies.AIM To establish a rabbit model of spinal tuberculosis and examine the effect on the model’s efficacy using different concentrations of Mycobacterium tuberculosis(M.tuberculosis)inoculum.METHODS New Zealand rabbits were randomly divided into experimental,control and blank groups.The experimental and control animals were sensitized with complete Freund′s adjuvant,a hole was drilled beneath the upper endplate of the L6 vertebral body and filled with gelfoam sponge.The experimental group was divided into three subgroups(experimental 1,experimental 2,experimental 3)and infused with M.tuberculosis suspension at various concentrations.The control group was inoculated with saline and the blank group received no treatment.The 12-week post-operative survival rates were 100%,80%and 30%in the experimental groups inoculated with concentrations of 106,107 and 108 CFU/mL bacteria,respectively.RESULTS The survival rate of the control and blank groups was 100%.Vertebral body destruction at 8 weeks in the three experimental groups as determined by X-ray analysis was 33.3%,62.5%and 66.7%,and by computed tomography(CT)and 3-dimensional CT 44.4%,75%and 100%,respectively.At 12 weeks,the figures were 44.4%,75%and 100%by X-ray analysis and 44.4%,100%and 100%by CT and 3-dimensional CT,respectively.All surviving rabbits of the experimental groups had vertebral destruction.The positive bacterial culture rates were 22.2%,75%and 66.7%,respectively,in the experimental groups.After being sensitized with complete Freund's adjuvant,large differences were observed in the extent of spinal tuberculosis after inoculation of the rabbits with different concentrations of H37RV standard M.tuberculosis.CONCLUSION The experimental 1 had a low success rate at establishing an infection.The experimental 3 resulted in high mortality and complication rates.The experimental 2 was optimum for establishing a spinal tuberculosis model based on the high level of symptoms observed and the low rabbit mortality.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
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
Despite the well-established functions of neurotransmitters and their receptors in depression studies,the aetiology of depression remains unknown.Further research into the field of animal studies is required in order ...Despite the well-established functions of neurotransmitters and their receptors in depression studies,the aetiology of depression remains unknown.Further research into the field of animal studies is required in order to facilitate a more comprehensive understanding of the underlying mechanisms that contribute to the development of depression.While the potential of animal behaviour to elucidate the molecular underpinnings of depression remains to be elucidated,the establishment of animal models can facilitate the identification of analogous pathogenic pathways through the application of rigorous methodologies.Animal models that are suitable for simulating the illness state of human depression can be utilised to investigate the pathophysiology of depression and the development of novel antidepressant medications.Currently,there is an absence of an optimal animal model that can fully replicate the pathogenic pathways of human depression,which limits future research in this field.It is evident that stress constitutes the primary catalyst for the onset of depressive states,a phenomenon that has been observed in both human and animal subjects.From this standpoint,animal models of stress-induced depression should be better equipped to simulate the onset process of human depression.This study offers a comprehensive summary and analysis of the most frequently employed rodent models of depression,with a view to providing a more diverse range of models and resources for animal studies in the field of depression research.展开更多
Background:Aortic atherosclerosis increases the risk of embolic events under extracorporeal circulation(ECC).To evaluate the hemodynamic impact of ECC on atheromatous plaques,an atherosclerosis animal model,which is a...Background:Aortic atherosclerosis increases the risk of embolic events under extracorporeal circulation(ECC).To evaluate the hemodynamic impact of ECC on atheromatous plaques,an atherosclerosis animal model,which is also eligible for ECC,is required.Methods:Twenty-nine New Zealand White rabbits received a pro-atherosclerotic diet(group diet,n=10),a pro-atherosclerotic diet and additional intraaortic balloon insufflation injury(group BI,n=9),or served as controls(n=10).After 3 or 6 months,aortic explants were analyzed by(immuno-)histology and RT-PCR.Results:Blood serum analyses revealed increased cholesterol-levels in groups diet and BI compared to controls(3 months:p=0.03 each,6 months:p<0.0001 each).Aortic inflammatory infiltration was significantly enhanced in groups diet(CD3 at 3 months:p<0.0001,6 months:p=0.02;CD68 at 3 months:p=0.01)and BI(CD3 at 3 months:p<0.0001,6 months:p=0.03;CD68 at 3 months:p=0.04,6 months:p=0.02).Increased intima hyperplasia occurred in both groups(p<0.0001 each).Macroscopic analyses after 3 and 6 months showed ubiquitous lumen-narrowing aortic plaques.Calcification of the intima and media was increased in groups diet(intima:p<0.0001 at 3 and 6 months;media at 3 months:p<0.0001,6 months:p=0.01)and BI(intima:p<0.0001 at 3 and 6 months;media at 3 months:p<0.0001,6 months:p=0.02).Extensive lipid accumulation was found in the intima in both treatment groups(p<0.0001 each).Conclusions:A rabbit model with high aortic calcific plaque burden—diet-induced with no implicit need of an additional intimal injury by an intraaortic balloon insufflation due to comparable outcome—exhibiting multiple pathophysiological aspects of human atherosclerosis has been designed and thoroughly characterized.It is suitable for use in future studies on the interaction between atherosclerotic plaques and the arterial blood flow under ECC.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
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
Robust preclinical models of transgender male(TGM) gender-affirming hormone therapy(GAHT) can inform clinicians of the isolated effects of GAHT;however existing models vary significantly in approach. We aimed to asses...Robust preclinical models of transgender male(TGM) gender-affirming hormone therapy(GAHT) can inform clinicians of the isolated effects of GAHT;however existing models vary significantly in approach. We aimed to assess existing methodology and how it influences circulating sex-hormone levels in rodent models of TGM GAHT to provide recommendations of best practise. Pub Med, Embase, and Scopus databases were systematically searched for studies that investigated GAHT in rodent models and were published from inception to the 1st of August 2024. Study characteristics and methodology were extracted and compared. Post-intervention circulating sex hormone concentrations were the primary outcome used to determine whether successful gender affirming hormone therapy had been achieved. Sixteen experimental rodent studies were included. Studies were performed on mice( n = 11) and rats( n = 5). Subcutaneous(SC) pellets and SC silastic implants were featured in some studies but weekly SC injections of testosterone enanthate was the preferred method. Sesame oil was the preferred solvent for injected testosterone formulations. Weekly doses of ~ 450 μg(mice) and ~ 420–900 μg(rats) consistently induced the testosterone levels of the male counterpart. Similarly, 10 mg of unesterified testosterone in a SC silastic implant in mice or 10 mg/100 g in rats were also successful methods. Most studies administered hormones for 6–8 weeks before performing post-treatment assessments. This review demonstrates that methods largely varied across studies and successfully identifies the effective methodological approaches that improve the reproducibility and accuracy of preclinical models. Representing an integral step forward to bridging gaps in preclinical transgender healthcare 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
Backgroud:Thoracic Trauma and Limb Fractures Are the Two most Common Injuries in Multiple Trauma.However,there Is Still a Lack of Mouse Models of Trauma Combining Tibial Shaft Fracture(TSF)and Thoracic Trauma.In this ...Backgroud:Thoracic Trauma and Limb Fractures Are the Two most Common Injuries in Multiple Trauma.However,there Is Still a Lack of Mouse Models of Trauma Combining Tibial Shaft Fracture(TSF)and Thoracic Trauma.In this Study,we Attempted to Develop a Novel Mouse Model of TSF Combined with Blunt Chest Trauma(BCT).Methods:A total of 84 C57BL/6J male mice were used as the multiple trauma model.BCT was induced by hitting the chests of mice with heavy objects,and TSF was in-duced by hitting the tibia of mice with heavy objects after intramedullary fixation.Serum specimens of mice were received by cardiac puncture at defined time points of 0,6,12,24,48,and 72 h.Results:Body weight and body temperature tended to decrease within 24 h after mul-tiple trauma.Hemoglobin analyses revealed a decrease during the first 24 h after mul-tiple trauma.Some animals died by cardiac puncture immediately after chest trauma.These animals exhibited the most severe pulmonary contusion and hemorrhage.The level of lung damage varied in diverse mice but was apparent in all animals.Classic he-matoxylin and eosin(H&E)-stained paraffin pulmonary sections of mice with multiple trauma displayed hemorrhage and an immunoinflammatory reaction.Bronchoalveolar lavage fluid(BALF)and serum samples of mice with multiple trauma showed an upreg-ulation of interleukin-1β(IL-1β),IL-6,and tumor necrosis factor-1α(TNF-1α)compared with the control group.Microimaging confirmed the presence of a tibia fracture and pulmonary contusion.Conclusions:The novel mouse multiple trauma model established in this study is a common trauma model that shows similar pathological mechanisms and imaging characteristics in patients with multiple injuries.This study is useful for determining whether blockade or intervention of the cytokine response is beneficial for the treat-ment of patients with multiple trauma.Further research is needed in the future.展开更多
Background:The mechanisms underlying cardiac remodeling in aortic valvular(AoV)disease remain poorly understood,partially due to the insufficiency of appropriate preclinical animal models.Here,we present a novel murin...Background:The mechanisms underlying cardiac remodeling in aortic valvular(AoV)disease remain poorly understood,partially due to the insufficiency of appropriate preclinical animal models.Here,we present a novel murine model of aortic regurgitation(AR)generated by transapical wire destruction of the AoV.Methods:Directed by echocardiography,apical puncture of the left ventricle(LV)was performed in adult male C57BL/6 mice,and a metal guidewire was used to induce AoV destruction.Echocardiography,invasive LV hemodynamic and histological examination were conducted to assess the degree of AR,LV function and remodeling.Results:AR mice exhibited rapid aortic regurgitation velocity(424±15.22 mm/s)immediately following successful surgery.Four weeks post-surgery,echocardiography revealed a 54.6%increase in LV diastolic diameter and a 55.1%decrease in LV ejection fraction in AR mice compared to sham mice.Pressure-volume catheterization indicated that AR mice had significantly larger LV end-diastolic volumes(66.2±1.5μL vs.41.8±3.4μL),reduced LV contractility(lower dP/dt max and Ees),and diminished LV compliance(smaller dP/dt min and longer Tau)compared to sham mice.Histological examination demonstrated that AR mice had significantly larger cardiomyocyte area and more myocardial fibrosis in LV tissue,as well as a 107%and a 122%increase of heart weight/tibial length and lung weight/tibial length,respectively,relative to sham mice.Conclusions:The trans-apex wire-induced destruction of the AoV establishes a novel and efficient murine model to develop AR,characterized by significant eccentric LV hypertrophy,heart failure,and pulmonary congestion.展开更多
Background:Hemorrhagic expansion into the fourth ventricle is an independent risk factor for poor outcomes in intraventricular hemorrhage(IVH)patients.However,to date,available animal models of IVH are limited to mode...Background:Hemorrhagic expansion into the fourth ventricle is an independent risk factor for poor outcomes in intraventricular hemorrhage(IVH)patients.However,to date,available animal models of IVH are limited to models of supratentorial ventricular hemorrhage,and there are no specific models of fourth ventricle hemorrhage.This limitation hinders comprehensive basic research and the understanding of the pathophysiological changes that occur following fourth ventricle hemorrhage.Therefore,the development of an animal model of fourth ventricle hemorrhage is highly important.Methods:In this study,a novel rat model of fourth ventricle hemorrhage was established via autologous blood injection through the foramen of Magendie.Anesthetized rats were positioned in a stereotaxic apparatus with their heads tilted downward at an angle of approximately 20°relative to the vertical axis.A needle was inserted through the foramen,and autologous blood obtained from the rat's heart was injected into the fourth ventricle via a microinfusion pump.Systematic evaluations of the model were conducted using small-animal magnetic resonance imaging,histopathological analysis,and neurological function assessment.Results:The rats developed stable and reproducible fourth ventricle hematomas and ventricular dilation.They also exhibited acute-phase hydrocephalus and pathological features of perilesional brain tissue injury,with observed neurological deficits comparable to patients with fourth ventricle hemorrhage.Conclusion:This model successfully recapitulates the clinicopathological and pathophysiological characteristics of patients with fourth ventricle hemorrhage and can be utilized for further investigation into the pathophysiological mechanisms underlying posthemorrhagic hydrocephalus and perilesional brainstem tissue injury.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
Background:SARS-CoV-2,first identified in late 2019,has given rise to numerous variants of concern(VOCs),posing a significant threat to human health.The emer-gence of Omicron BA.1.1 towards the end of 2021 led to a pa...Background:SARS-CoV-2,first identified in late 2019,has given rise to numerous variants of concern(VOCs),posing a significant threat to human health.The emer-gence of Omicron BA.1.1 towards the end of 2021 led to a pandemic in early 2022.At present,the lethal mouse model for the study of SARS-CoV-2 needs supplementation,and the alterations in neutrophils and monocytes caused by different strains remain to be elucidated.Methods:Human ACE2 transgenic mice were inoculated with the SARS-CoV-2 proto-type and Omicron BA.1,respectively.The pathogenicity of the two strains was evalu-ated by observing clinical symptoms,viral load and pathology.Complete blood count,immunohistochemistry and flow cytometry were performed to detect the alterations of neutrophils and monocytes caused by the two strains.Results:Our findings revealed that Omicron BA.1 exhibited significantly lower vir-ulence compared to the SARS-CoV-2 prototype in the mouse model.Additionally,we observed a significant increase in the proportion of neutrophils late in infection with the SARS-CoV-2 prototype and Omicron BA.1.We found that the proportion of monocytes increased at first and then decreased.The trends in the changes in the proportions of neutrophils and monocytes induced by the two strains were similar.Conclusion:Our study provides valuable insights into the utility of mouse models for simulating the severe disease of SARS-CoV-2 prototype infection and the milder manifestation associated with Omicron BA.1.SARS-CoV-2 prototype and Omicron BA.1 resulted in similar trends in the changes in neutrophils and monocytes.展开更多
Psychoneuroimmunology is a scientific discipline exploring the interconnectedness of the nervous system,emotion state,and immune system.The current review examines the distinct mechanisms through which the mind and bo...Psychoneuroimmunology is a scientific discipline exploring the interconnectedness of the nervous system,emotion state,and immune system.The current review examines the distinct mechanisms through which the mind and body interact when subjected to stress.Manifestations of psychoneuroimmunological stress encompass symptoms such as depression,aggression,fear,and social withdrawal,which can exert a profound impact on physiological well-being.Some observations suggest that humans and nonhuman animals exhibit similar stress-related symptoms,aiding in the identification of pharmacological pathways and potential clinical implications of therapeutic interventions.Animal stress models are predicated on varying approaches aimed at eliciting a motivational state to navigate and confront aversive circumstances.The current review describes the diverse stress induction models that have been investigated internationally,incorporating an ethological perspective that involves evaluating innate and unpunished behaviors through methodologies like the elevated plus maze,elevated zero maze,light-dark box,and open field test.Additionally,conditioned operant conflict tests,such as the Vogel conflict test,fall under the purview of learning and punishment models.This category encompasses classic conditioning models like fear conditioning,psychosocial models such as social defeat,and physical and chronic unpredictable stress paradigms.In this review,we critically evaluate existing cognitive and behavioral frameworks underpinning the development and perpetuation of stress-related disorders,while also elucidating the impact of immune system responses on the mental and physical health of animals.The primary objective of this review is to elucidate the array of animal models employed in previous research and the testing protocols used to assess animal performance in stress induction scenarios,with the ultimate aim of reducing mortality rates among research animals.展开更多
Background:In view of the ever-increasing representation of Staphylococcus spp.strains resistant to various antibiotics,the development of in vivo models for evaluation of novel antimicrobials is of utmost importance....Background:In view of the ever-increasing representation of Staphylococcus spp.strains resistant to various antibiotics,the development of in vivo models for evaluation of novel antimicrobials is of utmost importance.Methods:In this article,we describe the development of a fully immunocompetent porcine model of extensive skin and soft tissue damage suitable for testing topical anti-microbial agents that matches the real clinical situation.The model was developed in three consecutive stages with protocols for each stage amended based on the results of the previous one.Results:In the final model,10 excisions of the skin and underlying soft tissue were created in each pig under general anesthesia,with additional incisions to the fascia performed at the base of the defects and immediately inoculated with Staphylococcus aureus suspension.One pig was not inoculated and used as the negative control.Subsequently,the bandages were changed on Days 4,8,11,and 15.At these time points,a filter paper imprint technique(FPIT)was made from each wound for semi-quantitative microbiological evaluation.Tissue samples from the base of the wound together with the adjacent intact tissue of three randomly selected defects of each pig were taken for microbiological,histopathological,and molecular-biological examination.The infection with the inoculated S.aureus strains was sufficient during the whole experiment as confirmed by both FPIT and from tissue samples.The dynamics of the inflammatory markers and clinical signs of infection are also described.Conclusions:A successfully developed porcine model is suitable for in vivo testing of novel short-acting topical antimicrobial agents.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Supported by the National Key Specialty of Traditional Chinese Medicine(Spleen and Stomach Diseases),No.0500004National Natural Science Foundation of China,No.82205104 and No.82104850+1 种基金Hospital Capability Enhancement Project of Xiyuan Hospital,CACMS,No.XYZX0303-07the Fundamental Research Funds for the Central Public Welfare Research Institutes,Excellent Young Scientists Training Program of China Academy of Chinese Medical Sciences,No.ZZ16-YQ-002.
文摘BACKGROUND Non-erosive reflux disease(NERD),the main gastroesophageal reflux subtype,features reflux symptoms without mucosal damage.Anxiety links to visceral hypersensitivity in NERD,yet mechanisms and animal models are unclear.AIM To establish a translational NERD rat model with anxiety comorbidity via tail clamping and study corticotropin-releasing hormone(CRH)-mediated neuroimmune pathways in visceral hypersensitivity and esophageal injury.METHODS Sprague-Dawley(SD)and Wistar rats were grouped into sham,model,and modified groups(n=10 each).The treatments for the modified groups were as follows:SD rats received ovalbumin/aluminum hydroxide suspension+acid perfusion±tail clamping(40 minutes/day for 7 days),while Wistar rats received fructose water+tail clamping.Esophageal pathology,visceral sensitivity,and behavior were assessed.Serum CRH,calcitonin gene-related peptide(CGRP),5-hydroxytryptamine(5-HT),and mast cell tryptase(MCT)and central amygdala(CeA)CRH mRNA were measured via ELISA and qRT-PCR.RESULTS Tail clamping induced anxiety,worsening visceral hypersensitivity(lower abdominal withdrawal reflex thresholds,P<0.05)and esophageal injury(dilated intercellular spaces and mitochondrial edema).Both models showed raised serum CRH,CGRP,5-HT,and MCT(P<0.01)and CeA CRH mRNA expression(P<0.01).Behavioral tests confirmed anxiety-like phenotypes.NERD-anxiety rats showed clinical-like symptom severity without erosion.CONCLUSION Tail clamping induces anxiety in NERD models,worsening visceral hypersensitivity via CRH neuroimmune dysregulation,offering a translational model and highlighting CRH as a treatment target.
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Supported by Lanzhou City Science and Technology Development Guiding Plan Project,No.2023-ZD-170Lanzhou Science and Technology Plan Project,No.2023-2-11High-Level Talent Training Project At the 940th Hospital of the Joint Logistics Force,No.2024-G3-5.
文摘BACKGROUND Tuberculosis is among the most devastating infectious diseases worldwide.Spinal tuberculosis is not easy to detect at an early stage,which without effective treatment often leads to spinal deformity and spinal cord damage which in turn cause complications such as paraplegia and quadriplegia.In this study,we established a model using three concentrations of bacteria and carried out a comprehensive evaluation of the model by imaging,general observations,and histopathological and bacteriological studies.AIM To establish a rabbit model of spinal tuberculosis and examine the effect on the model’s efficacy using different concentrations of Mycobacterium tuberculosis(M.tuberculosis)inoculum.METHODS New Zealand rabbits were randomly divided into experimental,control and blank groups.The experimental and control animals were sensitized with complete Freund′s adjuvant,a hole was drilled beneath the upper endplate of the L6 vertebral body and filled with gelfoam sponge.The experimental group was divided into three subgroups(experimental 1,experimental 2,experimental 3)and infused with M.tuberculosis suspension at various concentrations.The control group was inoculated with saline and the blank group received no treatment.The 12-week post-operative survival rates were 100%,80%and 30%in the experimental groups inoculated with concentrations of 106,107 and 108 CFU/mL bacteria,respectively.RESULTS The survival rate of the control and blank groups was 100%.Vertebral body destruction at 8 weeks in the three experimental groups as determined by X-ray analysis was 33.3%,62.5%and 66.7%,and by computed tomography(CT)and 3-dimensional CT 44.4%,75%and 100%,respectively.At 12 weeks,the figures were 44.4%,75%and 100%by X-ray analysis and 44.4%,100%and 100%by CT and 3-dimensional CT,respectively.All surviving rabbits of the experimental groups had vertebral destruction.The positive bacterial culture rates were 22.2%,75%and 66.7%,respectively,in the experimental groups.After being sensitized with complete Freund's adjuvant,large differences were observed in the extent of spinal tuberculosis after inoculation of the rabbits with different concentrations of H37RV standard M.tuberculosis.CONCLUSION The experimental 1 had a low success rate at establishing an infection.The experimental 3 resulted in high mortality and complication rates.The experimental 2 was optimum for establishing a spinal tuberculosis model based on the high level of symptoms observed and the low rabbit mortality.
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Despite the well-established functions of neurotransmitters and their receptors in depression studies,the aetiology of depression remains unknown.Further research into the field of animal studies is required in order to facilitate a more comprehensive understanding of the underlying mechanisms that contribute to the development of depression.While the potential of animal behaviour to elucidate the molecular underpinnings of depression remains to be elucidated,the establishment of animal models can facilitate the identification of analogous pathogenic pathways through the application of rigorous methodologies.Animal models that are suitable for simulating the illness state of human depression can be utilised to investigate the pathophysiology of depression and the development of novel antidepressant medications.Currently,there is an absence of an optimal animal model that can fully replicate the pathogenic pathways of human depression,which limits future research in this field.It is evident that stress constitutes the primary catalyst for the onset of depressive states,a phenomenon that has been observed in both human and animal subjects.From this standpoint,animal models of stress-induced depression should be better equipped to simulate the onset process of human depression.This study offers a comprehensive summary and analysis of the most frequently employed rodent models of depression,with a view to providing a more diverse range of models and resources for animal studies in the field of depression research.
基金German Heart Foundation/German Foundation of Heart Research。
文摘Background:Aortic atherosclerosis increases the risk of embolic events under extracorporeal circulation(ECC).To evaluate the hemodynamic impact of ECC on atheromatous plaques,an atherosclerosis animal model,which is also eligible for ECC,is required.Methods:Twenty-nine New Zealand White rabbits received a pro-atherosclerotic diet(group diet,n=10),a pro-atherosclerotic diet and additional intraaortic balloon insufflation injury(group BI,n=9),or served as controls(n=10).After 3 or 6 months,aortic explants were analyzed by(immuno-)histology and RT-PCR.Results:Blood serum analyses revealed increased cholesterol-levels in groups diet and BI compared to controls(3 months:p=0.03 each,6 months:p<0.0001 each).Aortic inflammatory infiltration was significantly enhanced in groups diet(CD3 at 3 months:p<0.0001,6 months:p=0.02;CD68 at 3 months:p=0.01)and BI(CD3 at 3 months:p<0.0001,6 months:p=0.03;CD68 at 3 months:p=0.04,6 months:p=0.02).Increased intima hyperplasia occurred in both groups(p<0.0001 each).Macroscopic analyses after 3 and 6 months showed ubiquitous lumen-narrowing aortic plaques.Calcification of the intima and media was increased in groups diet(intima:p<0.0001 at 3 and 6 months;media at 3 months:p<0.0001,6 months:p=0.01)and BI(intima:p<0.0001 at 3 and 6 months;media at 3 months:p<0.0001,6 months:p=0.02).Extensive lipid accumulation was found in the intima in both treatment groups(p<0.0001 each).Conclusions:A rabbit model with high aortic calcific plaque burden—diet-induced with no implicit need of an additional intimal injury by an intraaortic balloon insufflation due to comparable outcome—exhibiting multiple pathophysiological aspects of human atherosclerosis has been designed and thoroughly characterized.It is suitable for use in future studies on the interaction between atherosclerotic plaques and the arterial blood flow under ECC.
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.
文摘Robust preclinical models of transgender male(TGM) gender-affirming hormone therapy(GAHT) can inform clinicians of the isolated effects of GAHT;however existing models vary significantly in approach. We aimed to assess existing methodology and how it influences circulating sex-hormone levels in rodent models of TGM GAHT to provide recommendations of best practise. Pub Med, Embase, and Scopus databases were systematically searched for studies that investigated GAHT in rodent models and were published from inception to the 1st of August 2024. Study characteristics and methodology were extracted and compared. Post-intervention circulating sex hormone concentrations were the primary outcome used to determine whether successful gender affirming hormone therapy had been achieved. Sixteen experimental rodent studies were included. Studies were performed on mice( n = 11) and rats( n = 5). Subcutaneous(SC) pellets and SC silastic implants were featured in some studies but weekly SC injections of testosterone enanthate was the preferred method. Sesame oil was the preferred solvent for injected testosterone formulations. Weekly doses of ~ 450 μg(mice) and ~ 420–900 μg(rats) consistently induced the testosterone levels of the male counterpart. Similarly, 10 mg of unesterified testosterone in a SC silastic implant in mice or 10 mg/100 g in rats were also successful methods. Most studies administered hormones for 6–8 weeks before performing post-treatment assessments. This review demonstrates that methods largely varied across studies and successfully identifies the effective methodological approaches that improve the reproducibility and accuracy of preclinical models. Representing an integral step forward to bridging gaps in preclinical transgender healthcare 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.
基金This study was supported by Development Project of Key Laboratory of Big Data Analysis and Knowledge Service of Science and Technology Innovation Platform of Yangzhou-Yangzhou University Cooperation,Grant/Award Number:YBK202204Jiangsu Province 333 High-level Talent.Training Project,Grant/Award Number:BRA2020176。
文摘Backgroud:Thoracic Trauma and Limb Fractures Are the Two most Common Injuries in Multiple Trauma.However,there Is Still a Lack of Mouse Models of Trauma Combining Tibial Shaft Fracture(TSF)and Thoracic Trauma.In this Study,we Attempted to Develop a Novel Mouse Model of TSF Combined with Blunt Chest Trauma(BCT).Methods:A total of 84 C57BL/6J male mice were used as the multiple trauma model.BCT was induced by hitting the chests of mice with heavy objects,and TSF was in-duced by hitting the tibia of mice with heavy objects after intramedullary fixation.Serum specimens of mice were received by cardiac puncture at defined time points of 0,6,12,24,48,and 72 h.Results:Body weight and body temperature tended to decrease within 24 h after mul-tiple trauma.Hemoglobin analyses revealed a decrease during the first 24 h after mul-tiple trauma.Some animals died by cardiac puncture immediately after chest trauma.These animals exhibited the most severe pulmonary contusion and hemorrhage.The level of lung damage varied in diverse mice but was apparent in all animals.Classic he-matoxylin and eosin(H&E)-stained paraffin pulmonary sections of mice with multiple trauma displayed hemorrhage and an immunoinflammatory reaction.Bronchoalveolar lavage fluid(BALF)and serum samples of mice with multiple trauma showed an upreg-ulation of interleukin-1β(IL-1β),IL-6,and tumor necrosis factor-1α(TNF-1α)compared with the control group.Microimaging confirmed the presence of a tibia fracture and pulmonary contusion.Conclusions:The novel mouse multiple trauma model established in this study is a common trauma model that shows similar pathological mechanisms and imaging characteristics in patients with multiple injuries.This study is useful for determining whether blockade or intervention of the cytokine response is beneficial for the treat-ment of patients with multiple trauma.Further research is needed in the future.
基金Natural Science Foundation of Guangdong Province,Grant/Award Number:2023A1515110032 and 2022A1515220152Guangzhou Key Research and Development Program Foundation,Grant/Award Number:202206010199National Natural Science Foundation of China,Grant/Award Number:82100407,82272602 and 82370242。
文摘Background:The mechanisms underlying cardiac remodeling in aortic valvular(AoV)disease remain poorly understood,partially due to the insufficiency of appropriate preclinical animal models.Here,we present a novel murine model of aortic regurgitation(AR)generated by transapical wire destruction of the AoV.Methods:Directed by echocardiography,apical puncture of the left ventricle(LV)was performed in adult male C57BL/6 mice,and a metal guidewire was used to induce AoV destruction.Echocardiography,invasive LV hemodynamic and histological examination were conducted to assess the degree of AR,LV function and remodeling.Results:AR mice exhibited rapid aortic regurgitation velocity(424±15.22 mm/s)immediately following successful surgery.Four weeks post-surgery,echocardiography revealed a 54.6%increase in LV diastolic diameter and a 55.1%decrease in LV ejection fraction in AR mice compared to sham mice.Pressure-volume catheterization indicated that AR mice had significantly larger LV end-diastolic volumes(66.2±1.5μL vs.41.8±3.4μL),reduced LV contractility(lower dP/dt max and Ees),and diminished LV compliance(smaller dP/dt min and longer Tau)compared to sham mice.Histological examination demonstrated that AR mice had significantly larger cardiomyocyte area and more myocardial fibrosis in LV tissue,as well as a 107%and a 122%increase of heart weight/tibial length and lung weight/tibial length,respectively,relative to sham mice.Conclusions:The trans-apex wire-induced destruction of the AoV establishes a novel and efficient murine model to develop AR,characterized by significant eccentric LV hypertrophy,heart failure,and pulmonary congestion.
基金Natural Science Foundation of Hubei Province,Grant/Award Number:2024AFB877the Chongqing Medical Scientific Research Project(Joint Project of Chongqing Health Commission and Science&Technology Bureau),Grant/Award Number:2023GGXM003+3 种基金Chongqing Municipal Health Commission,Grant/Award Number:YXGD202451Organization Department of Chongqing Municipal Party Committee,Grant/Award Number:cstc2024ycjh-bgzxm0103National Natural Science Foundation of China,Grant/Award Number:82371361Jingmen Science and Technology Bureau,Grant/Award Number:2024ZDYF012。
文摘Background:Hemorrhagic expansion into the fourth ventricle is an independent risk factor for poor outcomes in intraventricular hemorrhage(IVH)patients.However,to date,available animal models of IVH are limited to models of supratentorial ventricular hemorrhage,and there are no specific models of fourth ventricle hemorrhage.This limitation hinders comprehensive basic research and the understanding of the pathophysiological changes that occur following fourth ventricle hemorrhage.Therefore,the development of an animal model of fourth ventricle hemorrhage is highly important.Methods:In this study,a novel rat model of fourth ventricle hemorrhage was established via autologous blood injection through the foramen of Magendie.Anesthetized rats were positioned in a stereotaxic apparatus with their heads tilted downward at an angle of approximately 20°relative to the vertical axis.A needle was inserted through the foramen,and autologous blood obtained from the rat's heart was injected into the fourth ventricle via a microinfusion pump.Systematic evaluations of the model were conducted using small-animal magnetic resonance imaging,histopathological analysis,and neurological function assessment.Results:The rats developed stable and reproducible fourth ventricle hematomas and ventricular dilation.They also exhibited acute-phase hydrocephalus and pathological features of perilesional brain tissue injury,with observed neurological deficits comparable to patients with fourth ventricle hemorrhage.Conclusion:This model successfully recapitulates the clinicopathological and pathophysiological characteristics of patients with fourth ventricle hemorrhage and can be utilized for further investigation into the pathophysiological mechanisms underlying posthemorrhagic hydrocephalus and perilesional brainstem tissue injury.
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 Beijing Natural Science Foundation(Grant No.Z210014)National Natural Science Foundation of China(Grant No.32070543)+1 种基金National Key Research and Development Project of China(Grant No.2022YFC2303404)CAMS Innovation Fund for Medical Sciences(CIFMS)(Grant No.2022-12M-CoV19-002)
文摘Background:SARS-CoV-2,first identified in late 2019,has given rise to numerous variants of concern(VOCs),posing a significant threat to human health.The emer-gence of Omicron BA.1.1 towards the end of 2021 led to a pandemic in early 2022.At present,the lethal mouse model for the study of SARS-CoV-2 needs supplementation,and the alterations in neutrophils and monocytes caused by different strains remain to be elucidated.Methods:Human ACE2 transgenic mice were inoculated with the SARS-CoV-2 proto-type and Omicron BA.1,respectively.The pathogenicity of the two strains was evalu-ated by observing clinical symptoms,viral load and pathology.Complete blood count,immunohistochemistry and flow cytometry were performed to detect the alterations of neutrophils and monocytes caused by the two strains.Results:Our findings revealed that Omicron BA.1 exhibited significantly lower vir-ulence compared to the SARS-CoV-2 prototype in the mouse model.Additionally,we observed a significant increase in the proportion of neutrophils late in infection with the SARS-CoV-2 prototype and Omicron BA.1.We found that the proportion of monocytes increased at first and then decreased.The trends in the changes in the proportions of neutrophils and monocytes induced by the two strains were similar.Conclusion:Our study provides valuable insights into the utility of mouse models for simulating the severe disease of SARS-CoV-2 prototype infection and the milder manifestation associated with Omicron BA.1.SARS-CoV-2 prototype and Omicron BA.1 resulted in similar trends in the changes in neutrophils and monocytes.
文摘Psychoneuroimmunology is a scientific discipline exploring the interconnectedness of the nervous system,emotion state,and immune system.The current review examines the distinct mechanisms through which the mind and body interact when subjected to stress.Manifestations of psychoneuroimmunological stress encompass symptoms such as depression,aggression,fear,and social withdrawal,which can exert a profound impact on physiological well-being.Some observations suggest that humans and nonhuman animals exhibit similar stress-related symptoms,aiding in the identification of pharmacological pathways and potential clinical implications of therapeutic interventions.Animal stress models are predicated on varying approaches aimed at eliciting a motivational state to navigate and confront aversive circumstances.The current review describes the diverse stress induction models that have been investigated internationally,incorporating an ethological perspective that involves evaluating innate and unpunished behaviors through methodologies like the elevated plus maze,elevated zero maze,light-dark box,and open field test.Additionally,conditioned operant conflict tests,such as the Vogel conflict test,fall under the purview of learning and punishment models.This category encompasses classic conditioning models like fear conditioning,psychosocial models such as social defeat,and physical and chronic unpredictable stress paradigms.In this review,we critically evaluate existing cognitive and behavioral frameworks underpinning the development and perpetuation of stress-related disorders,while also elucidating the impact of immune system responses on the mental and physical health of animals.The primary objective of this review is to elucidate the array of animal models employed in previous research and the testing protocols used to assess animal performance in stress induction scenarios,with the ultimate aim of reducing mortality rates among research animals.
基金Supported by the Ministry of Health of the Czech Republic,Grant/Award Number:NU22-05-00475 and NV19-05-00214。
文摘Background:In view of the ever-increasing representation of Staphylococcus spp.strains resistant to various antibiotics,the development of in vivo models for evaluation of novel antimicrobials is of utmost importance.Methods:In this article,we describe the development of a fully immunocompetent porcine model of extensive skin and soft tissue damage suitable for testing topical anti-microbial agents that matches the real clinical situation.The model was developed in three consecutive stages with protocols for each stage amended based on the results of the previous one.Results:In the final model,10 excisions of the skin and underlying soft tissue were created in each pig under general anesthesia,with additional incisions to the fascia performed at the base of the defects and immediately inoculated with Staphylococcus aureus suspension.One pig was not inoculated and used as the negative control.Subsequently,the bandages were changed on Days 4,8,11,and 15.At these time points,a filter paper imprint technique(FPIT)was made from each wound for semi-quantitative microbiological evaluation.Tissue samples from the base of the wound together with the adjacent intact tissue of three randomly selected defects of each pig were taken for microbiological,histopathological,and molecular-biological examination.The infection with the inoculated S.aureus strains was sufficient during the whole experiment as confirmed by both FPIT and from tissue samples.The dynamics of the inflammatory markers and clinical signs of infection are also described.Conclusions:A successfully developed porcine model is suitable for in vivo testing of novel short-acting topical antimicrobial agents.
