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
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
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
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
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: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
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
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
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
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
The potential of a plant sterol food supplement(PS-FS)in addressing intestinal inflammation in vivo and in vitro was evaluated.As in vivo model,C57BL/6J mice were exposed to1.5%dextran sulfate sodium in three 5-day pe...The potential of a plant sterol food supplement(PS-FS)in addressing intestinal inflammation in vivo and in vitro was evaluated.As in vivo model,C57BL/6J mice were exposed to1.5%dextran sulfate sodium in three 5-day periods,with 10-day rest intervals in between,daily reciving PS-FS(35 mg PS/kg body weight).The in vitro approach involved a bi-cameral system with 8-day-differentiated Caco-2(apical)and RAW264.7 cells(basolateral).The bioaccessible fraction of PS-FS,obtained after INFOGEST 2.0 simulated gastrointestinal digestion,was added to the apical part(90 min),followed by stimulation with lipopolysaccharide(1μg/mL,24 h).PS-FS alleviated rectal bleeding and rebalanced pro-(tumor necrosis factorα,interleukin(IL)-6,and IL-8)and anti-inflammatory cytokines(IL-10).Additionally,PS-FS ameliorated histopathological damage and enhancing occludin expression.A reduction in oxidative stress was evidenced by decreased myeloperoxidase activity and reactive oxygen species production.The anti-inflammatory mechanism included suppressing cyclooxygenase 2 expression,reducing prostaglandin E_(2) production,and inhibiting the phosphorylation and nuclear translocation of the nuclear factor kB p65 subunit.This study reveals the potential of PS-FS as a therapeutic intervention for colitis.The alignment between in vivo and in vitro outcomes substantiates the appropriateness of the co-culture model to evaluate the anti-inflammatory activity of foods.展开更多
Background:Baitouweng decoction is a classic prescription for treating chronic dysentery and mainly used to treat heat-toxic dysentery and is widely used in damp-heat ulcerative colitis(UC)in China.Methods:Meta-analys...Background:Baitouweng decoction is a classic prescription for treating chronic dysentery and mainly used to treat heat-toxic dysentery and is widely used in damp-heat ulcerative colitis(UC)in China.Methods:Meta-analysis and network pharmacology were used to examine the pharmacological properties of Baitouweng decoction in the treatment of UC.Additionally,the potential mechanisms of action were investigated.In the meta-analysis,studies were searched from databases up to March 2024.Data from the included studies were extracted.The results were quantified by calculating the standardized mean difference(SMD).Additionally,95%confidence intervals(CI)were used to assess the precision of the estimates.Results:It was found that 201 components of Baitouweng decoction,including Pulsatillae Radix(Baitouweng),Coptidis Rhizoma(Huanglian),Phellodendri Chinensis Cortex(Huangbo),Fraxini Cortex(Qinpi),and 106 intersecting targets of UC,were obtained from INPUT.PPI and enrichment analyses showed Baitouweng decoction might regulate inflammatory response to improve UC injury.Seventeen included studies were published between 2004 and 2024.The meta-analysis results suggested that Baitouweng decoction may help increase body weight,decrease DAI and CMDI,reduce colon length shortening associated with UC,lower the spleen index,and alleviate tissue damage in colitis.In addition,Baitouweng decoction could inhibit inflammatory response and repair intestinal barrier in UC model.The protective mechanism of Baitouweng decoction was consistent with the predicted targets of network pharmacology,which suggested the results were accurate.Conclusion:Baitouweng decoction could improve UC injury by regulating the inflammatory response,cell apoptosis,and body metabolism through the integration of network pharmacology and meta-analysis.Its protective mechanisms are related to anti-inflammation,regulation of intestinal flora,brain-gut peptides,and protection of the intestinal mucosal barrier,along with modulation of body metabolism,including SCFA,bile acids,and tryptophan metabolism.展开更多
The autoimmune response directed against pancreatic β cells is the most essential pathogenic process in type 1 diabetes(T1D)in humans.Spontaneous animal models of T1D greatly contribute to our understanding of the di...The autoimmune response directed against pancreatic β cells is the most essential pathogenic process in type 1 diabetes(T1D)in humans.Spontaneous animal models of T1D greatly contribute to our understanding of the disease pathogenesis and therapeutic options.Amongst many disease models,a significant proportion of T1D research is performed on multiple low dose streptozotocin induced diabetes in experimental animals,in parallel.Here,we discuss advantages of this model for contemporary T1D research.Additionally,challenges and perspectives for further improvement of the model are presented.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
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: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
Backgroud:Intervertebral disc degeneration(IDD)is one of the common degenerative diseases.Due to ethical constraints,it is difficult to obtain sufficient research on humans,so the use of an animal model of IDD is very...Backgroud:Intervertebral disc degeneration(IDD)is one of the common degenerative diseases.Due to ethical constraints,it is difficult to obtain sufficient research on humans,so the use of an animal model of IDD is very important to clarify the pathogenesis and treatment mechanism of the disease.Methods:In this study,thirty 2-month-old mice were selected for operation to establish a coccygeal IDD model.The distal tail portion of the tail(beyond the 17th coccygeal vertebra)and a small piece of skin above the 8th coccygeal vertebra were excised,and the two incisions were brought together after flexion,and secured with sutures.The heights and signal intensities of the intervertebral discs(IVDs)were assessed using microcomputed tomography(μCT)and magnetic resonance imaging(MRI)at 0,6,12 weeks postoperatively.The overall tissue morphology,cell distribution and density,and extracellular matrix of the IVDs were also assessed using Hematoxylin and Eosin(HE),Safranin O-Fast Green and immunohistochemical staining.Results:All mice in the experimental group survived after the operation,and there were no complications such as wound infection,tail necrosis and suture shedding.The experimental results demonstrated that the suturing method can successfully initiate IDD.Different severity levels of IDD can be induced by controlling the bending angle of the IVDs within the tail loop;however,for consistency,histologic and imaging results should be obtained at the same bending angle and looping period.Conclusions:This IDD model is an effective method for studying the etiology and treatment of degenerative IVD disease.展开更多
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.
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 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.
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the Generalitat Valenciana,Spain(protocol code 2022/VSC/PEA/0256,date November 10,2022).
文摘The potential of a plant sterol food supplement(PS-FS)in addressing intestinal inflammation in vivo and in vitro was evaluated.As in vivo model,C57BL/6J mice were exposed to1.5%dextran sulfate sodium in three 5-day periods,with 10-day rest intervals in between,daily reciving PS-FS(35 mg PS/kg body weight).The in vitro approach involved a bi-cameral system with 8-day-differentiated Caco-2(apical)and RAW264.7 cells(basolateral).The bioaccessible fraction of PS-FS,obtained after INFOGEST 2.0 simulated gastrointestinal digestion,was added to the apical part(90 min),followed by stimulation with lipopolysaccharide(1μg/mL,24 h).PS-FS alleviated rectal bleeding and rebalanced pro-(tumor necrosis factorα,interleukin(IL)-6,and IL-8)and anti-inflammatory cytokines(IL-10).Additionally,PS-FS ameliorated histopathological damage and enhancing occludin expression.A reduction in oxidative stress was evidenced by decreased myeloperoxidase activity and reactive oxygen species production.The anti-inflammatory mechanism included suppressing cyclooxygenase 2 expression,reducing prostaglandin E_(2) production,and inhibiting the phosphorylation and nuclear translocation of the nuclear factor kB p65 subunit.This study reveals the potential of PS-FS as a therapeutic intervention for colitis.The alignment between in vivo and in vitro outcomes substantiates the appropriateness of the co-culture model to evaluate the anti-inflammatory activity of foods.
基金supported by the National Natural Science Foundation of China(No.82405237,82373835,82173781)Guangdong Basic and Applied Basic Research Foundation(No.2023A1515110768,2019A1515010806)+3 种基金Foshan Science and Technology Bureau’s self funded project(No.2320001007283)Key Field Projects(Intelligent Manufacturing)of General Universities in Guangdong Province(No.2020ZDZX2057)the Scientific Research Projects(Characteristic Innovation)of General Universities in Guangdong Province(No.2019KTSCX195)Guangdong Provincial Medical Research Foundation(No.A2022061).
文摘Background:Baitouweng decoction is a classic prescription for treating chronic dysentery and mainly used to treat heat-toxic dysentery and is widely used in damp-heat ulcerative colitis(UC)in China.Methods:Meta-analysis and network pharmacology were used to examine the pharmacological properties of Baitouweng decoction in the treatment of UC.Additionally,the potential mechanisms of action were investigated.In the meta-analysis,studies were searched from databases up to March 2024.Data from the included studies were extracted.The results were quantified by calculating the standardized mean difference(SMD).Additionally,95%confidence intervals(CI)were used to assess the precision of the estimates.Results:It was found that 201 components of Baitouweng decoction,including Pulsatillae Radix(Baitouweng),Coptidis Rhizoma(Huanglian),Phellodendri Chinensis Cortex(Huangbo),Fraxini Cortex(Qinpi),and 106 intersecting targets of UC,were obtained from INPUT.PPI and enrichment analyses showed Baitouweng decoction might regulate inflammatory response to improve UC injury.Seventeen included studies were published between 2004 and 2024.The meta-analysis results suggested that Baitouweng decoction may help increase body weight,decrease DAI and CMDI,reduce colon length shortening associated with UC,lower the spleen index,and alleviate tissue damage in colitis.In addition,Baitouweng decoction could inhibit inflammatory response and repair intestinal barrier in UC model.The protective mechanism of Baitouweng decoction was consistent with the predicted targets of network pharmacology,which suggested the results were accurate.Conclusion:Baitouweng decoction could improve UC injury by regulating the inflammatory response,cell apoptosis,and body metabolism through the integration of network pharmacology and meta-analysis.Its protective mechanisms are related to anti-inflammation,regulation of intestinal flora,brain-gut peptides,and protection of the intestinal mucosal barrier,along with modulation of body metabolism,including SCFA,bile acids,and tryptophan metabolism.
基金Ministry of Science,Technological Development,and Innovation,Republic of Serbia,Grant/Award Number:451-03-66/2024-03/200007。
文摘The autoimmune response directed against pancreatic β cells is the most essential pathogenic process in type 1 diabetes(T1D)in humans.Spontaneous animal models of T1D greatly contribute to our understanding of the disease pathogenesis and therapeutic options.Amongst many disease models,a significant proportion of T1D research is performed on multiple low dose streptozotocin induced diabetes in experimental animals,in parallel.Here,we discuss advantages of this model for contemporary T1D research.Additionally,challenges and perspectives for further improvement of the model are presented.
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.
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.
基金the Youth Foundation of The 909th Hospital of Xiamen University,Grant/Award Number:22QN001Natural Science Foundation of Fujian Province,China,Grant/Award Number:2019J01144,2022J011482,2023J011839 and 2023J011844+2 种基金National Natural Science Foundation of China,Grant/Award Number:81600696 and 82172477the Fujian Medical University Union Hospital Talent Research Launch Project,Grant/Award Number:2024XH001Natural Science Foundation of Zhangzhou,China,Grant/Award Number:ZZ2024J59。
文摘Backgroud:Intervertebral disc degeneration(IDD)is one of the common degenerative diseases.Due to ethical constraints,it is difficult to obtain sufficient research on humans,so the use of an animal model of IDD is very important to clarify the pathogenesis and treatment mechanism of the disease.Methods:In this study,thirty 2-month-old mice were selected for operation to establish a coccygeal IDD model.The distal tail portion of the tail(beyond the 17th coccygeal vertebra)and a small piece of skin above the 8th coccygeal vertebra were excised,and the two incisions were brought together after flexion,and secured with sutures.The heights and signal intensities of the intervertebral discs(IVDs)were assessed using microcomputed tomography(μCT)and magnetic resonance imaging(MRI)at 0,6,12 weeks postoperatively.The overall tissue morphology,cell distribution and density,and extracellular matrix of the IVDs were also assessed using Hematoxylin and Eosin(HE),Safranin O-Fast Green and immunohistochemical staining.Results:All mice in the experimental group survived after the operation,and there were no complications such as wound infection,tail necrosis and suture shedding.The experimental results demonstrated that the suturing method can successfully initiate IDD.Different severity levels of IDD can be induced by controlling the bending angle of the IVDs within the tail loop;however,for consistency,histologic and imaging results should be obtained at the same bending angle and looping period.Conclusions:This IDD model is an effective method for studying the etiology and treatment of degenerative IVD disease.
