The increasing incidence and mortality associated with advanced stages of melanoma are cause for concern. Few treatment options are available for advanced melanoma and the 5-year survival rate is less than 15%. Target...The increasing incidence and mortality associated with advanced stages of melanoma are cause for concern. Few treatment options are available for advanced melanoma and the 5-year survival rate is less than 15%. Targeted therapies may revolutionize melanoma treatment by providing less toxic and more effective strategies. However, maximizing effectiveness requires further understanding of the molecular alterations that drive tumor formation, progression, and maintenance, as well as elucidating the mechanisms of resistance. Several different genetic alterations identified in human melanoma have been recapitulated in mice. This review outlines recent progress made in the development of mouse models of melanoma and summarizes what these findings reveal about the human disease. We begin with a discussion of traditional models and conclude with the recently developed RCAS/TVA somatic cell gene delivery mouse model of melanoma.展开更多
The incidence of benign airway stenosis(BAS)is on the rise,and current treatment options are associated with a significant risk of restenosis.Therefore,there is an urgent need to explore new and effective prevention a...The incidence of benign airway stenosis(BAS)is on the rise,and current treatment options are associated with a significant risk of restenosis.Therefore,there is an urgent need to explore new and effective prevention and treatment methods.Animal models serve as essential tools for investigating disease mechanisms and assessing novel therapeutic strategies,and the scientific rigor of their construction and validation significantly impacts the reliability of research findings.This paper systematically reviews the research progress and evaluation systems of BAS animal models over the past decade,aiming to provide a robust foundation for the optimized construction of BAS models,intervention studies,and clinical translation.This effort is intended to facilitate the innovation and advancement in BAS prevention and treatment strategies.展开更多
Neurodegenerative diseases are increasing in prevalence due largely to aging populations worldwide and improved medical care for the elderly.Currently approved drugs can reduce some of the symptoms of neurodegenerativ...Neurodegenerative diseases are increasing in prevalence due largely to aging populations worldwide and improved medical care for the elderly.Currently approved drugs can reduce some of the symptoms of neurodegenerative diseases but cannot cure them.Inflammation is involved in the development and progression of neurodegenerative diseases,and oxidative stress is implicated in neurodegeneration associated with cognitive decline and age-related cognitive impairment.Polyphenols such as curcumin,quercetin,and resveratrol possess potent anti-inflammatory and antioxidant properties.Nanoformulations of curcumin and quercetin can optimize their pharmacological effects in the treatment of neurodegenerative diseases.Nanocarriers play a crucial role in delivering drugs across the blood-brain barrier,thereby lowering the risk of peripheral side effects.Various nanoforms have been developed to induce bioavailability and solubility of curcumin and quercetin,including nanoparticles and nanoemulsions.The studies reviewed included 17 using curcumin nanoformulations and seven with quercetin nanoformulations and were tested in widely used animal models of Alzheimer’s disease,Parkinson’s disease,Huntington’s disease,and multiple sclerosis.Many of the curcumin and quercetin nanoformulations brought about improvements in learning and memory in behavioral tests of Alzheimer’s disease models and were effective in reducing oxidative stress in the brain.Both nanocurcumin and nanoquercetin decreased the levels of inflammatory markers in the brain.Nanocurcumin formulations improved motor behavior,gait,and memory in Parkinson’s disease models and increased dopaminergic neurons in the striatum and substantia nigra.Furthermore,nanocurcumin improved locomotor activity,memory,and learning,and the number of dendrites of medium spiny neurons in Huntington’s disease models.Nanocurcumin formulations decreased oxidative stress and inflammation in a model of demyelination.Several important limitations were identified in the studies reviewed and these need to be considered in future studies.Also,clinical trials could be performed using the currently available nanoforms of curcumin and quercetin.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
This study summarizes the theoretical basis,modeling strategies,pathological mechanisms,and therapeutic advances related to high-altitude qi-deficiency and blood-stasis pattern.Traditional concepts such as“qi drives ...This study summarizes the theoretical basis,modeling strategies,pathological mechanisms,and therapeutic advances related to high-altitude qi-deficiency and blood-stasis pattern.Traditional concepts such as“qi drives blood”and“deficiency leads to stasis”closely align with modern evidence demonstrating that hypoxia disrupts energy metabolism,impairs microcirculation,and amplifies inflammation and oxidative stress.Current animal models commonly use hypobaric hypoxia combined with fatigue loading,dietary restriction,ice-water stimulation,or adrenaline injection to mimic the combined effects of qi deficiency,blood stasis,and hypoxic injury.These composite approaches reproduce systemic abnormalities,including reduced arterial oxygen partial pressure,increased blood viscosity,impaired cardiac and pulmonary function,microcirculatory obstruction,and mitochondrial dysfunction.Enhanced inflammatory signaling,oxidative stress,and disturbances in metabolic and epigenetic networks further characterize the pattern.The findings indicate that its pathogenesis arises from multi-system,multi-target interactions rather than a single pathway.Representative herbal formulas,such as Buyang Huanwu decoction,Xuefu Zhuyu decoction,and prescriptions rich in Astragalus membranaceus(Fisch.)Bunge(A.membranaceus,Huang qi)or Salvia miltiorrhiza Bunge(S.miltiorrhiza,Dan Shen)have demonstrated the ability to improve energy metabolism,attenuate endothelial injury,enhance microcirculation,and suppress inflammation through network-level regulation.Future research should focus on standardizing exposure parameters,developing quantitative syndrome evaluation systems,and integrating multi-omics,systems biology and artificial intelligence to improve model reproducibility and mechanistic precision.These efforts may help establish objective criteria for high-altitude qi-deficiency and blood-stasis pattern and support the development of targeted therapeutic strategies.展开更多
Pathological scarring,manifested in the form of hypertrophic scars(HTS)and keloid scars(KS),represents a major clinical challenge due to its aesthetic and functional implications for patients.Understanding the molecul...Pathological scarring,manifested in the form of hypertrophic scars(HTS)and keloid scars(KS),represents a major clinical challenge due to its aesthetic and functional implications for patients.Understanding the molecular mechanisms involved in these types of scars and developing effective treatments requires the use of controlled ex-perimental models,especially animals,to overcome the limitations of clinical studies.The aim of this sistematic review is to critically analyze the animal models used in the last five years(2020-2025)for the study of pathological scars,highlighting their advantages,limitations and applicability in the development of new therapeutic strat-egies.Murine,rabbit and porcine models,as well as alternative models,offer varied perspectives on the formation and treatment of HTS and KS,with an emphasis on histological and molecular correlations with human pathology.By synthesizing recent data,the paper highlights the essential role of preclinical research in optimizing an-tifibrotic treatments and in advancing the translation of data into the clinical sphere.Overall,animal models remain essential for bridging mechanistic insights with clinical translation,supporting the development of more effective and personalized anti-scar therapies.展开更多
Lung cancer has one of the highest rates of incidence and mortality worldwide,mak-ing research on its mechanisms and treatments crucial.Animal models are essential in lung cancer research as they accurately replicate ...Lung cancer has one of the highest rates of incidence and mortality worldwide,mak-ing research on its mechanisms and treatments crucial.Animal models are essential in lung cancer research as they accurately replicate the biological characteristics and treatment outcomes seen in human diseases.Currently,various lung cancer models have been established,including chemical induction models,orthotopic transplan-tation models,ectopic transplantation models,metastasis models,and gene editing mouse models.Additionally,lung cancer grafts can be categorized into two types:tissue-based and cell-based grafts.This paper summarizes the phenotypes,advan-tages,and disadvantages of various induction methods based on their modeling tech-niques.The goal is to enhance the simulation of clinical lung cancer characteristics and to establish a solid foundation for future clinical research.展开更多
Epithelial ovarian cancer(EOC) is the leading cause of gynecological cancer-related mortality in the developed world. EOC is a heterogeneous disease represented by several histological and molecular subtypes. Therefor...Epithelial ovarian cancer(EOC) is the leading cause of gynecological cancer-related mortality in the developed world. EOC is a heterogeneous disease represented by several histological and molecular subtypes. Therefore, exploration of relevant preclinical animal models that consider the heterogenic nature of EOC is of great importance for the development of novel therapeutic strategies that can be translated clinically to combat this devastating disease. In this review, we discuss recent progress in the development of preclinical mouse models for EOC study as well as their advantages and limitations.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
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
Tauopathies represent a class of neurodegenerative diseases(NDs),including Alzheimer’s disease(AD),progressive supranuclear palsy(PSP),Pick’s disease(PiD),and corticobasal degeneration(CBD),defined by intracellular ...Tauopathies represent a class of neurodegenerative diseases(NDs),including Alzheimer’s disease(AD),progressive supranuclear palsy(PSP),Pick’s disease(PiD),and corticobasal degeneration(CBD),defined by intracellular accumulation of misfolded and hyperphosphorylated tau protein.The pathogenic cascade involves hyperphosphorylation,conformational changes,and aggregation into neurofibrillary tangles(NFTs),which are spatially and functionally linked to neuronal dysfunction,synaptic loss,and progressive cognitive and motor decline.To elucidate tau-mediated mechanisms,diverse transgenic rodent models expressing wild-type or mutant forms of human TAU have been generated.Although these models have advanced understanding of tau aggregation and propagation,tau-targeting therapies have failed to produce clinical benefits,raising concerns about the precise mechanism underlying tauopathies and the fidelity of animal models in evaluating therapeutic targets.This review systematically examines the neuropathological and behavioral phenotypes across established rodent and non-human primate(NHP)tauopathy models,highlighting mechanistic insights into tau-driven pathology.The advantages,limitations,and translational barriers of each model are critically evaluated to inform the development of more predictive preclinical platforms for therapeutic discovery.展开更多
Photodynamic therapy(PDT)is an emerging minimally invasive therapeutic modality that relies on the activation of a photosensitizing agent by light of a specific wavelength in the presence of molecular oxygen,leading t...Photodynamic therapy(PDT)is an emerging minimally invasive therapeutic modality that relies on the activation of a photosensitizing agent by light of a specific wavelength in the presence of molecular oxygen,leading to the generation of reactive oxygen species(ROS).This mechanism facilitates selective cytotoxic effects within pathological tissues and has demonstrated therapeutic potential across diverse disease contexts.However,the broader clinical applications remain limited by photosensitizer selectivity,shallow light penetration,and the risk of off-target cytotoxicity.Recent advancements in PDT have focused on the development of next-generation photosensitizers,the integration of nanotechnology for enhanced delivery and targeting,and the strategic combination of PDT with complementary therapeutic approaches.Experimental animal models play a crucial role in validating the efficacy and safety of PDT,optimizing its therapeutic parameters,and determining its mechanisms of action.This review provides a comprehensive overview of PDT applications in various disease models,including oncological,infectious,and nonconventional indications.Special emphasis is placed on the importance of large animal models in PDT research,such as rabbits,pigs,dogs,and non-human primates,which provide experimental platforms that more closely resemble human physiological and pathological states.The use of these models for understanding the mechanisms of PDT,optimizing therapeutic regimens,and evaluating clinical outcomes is also discussed.This review aims to inform future directions in PDT research and emphasizes the importance of selecting appropriate preclinical animal models to facilitate successful clinical translation.展开更多
Background:Colocasia esculenta(L.)Schott,known as the taro vegetable,possesses various beneficial effects and is traditionally used in folk medicine.This study explores the ameliorative antioxidant and hepatoprotectiv...Background:Colocasia esculenta(L.)Schott,known as the taro vegetable,possesses various beneficial effects and is traditionally used in folk medicine.This study explores the ameliorative antioxidant and hepatoprotective effect of a methanolic extract of the C.esculenta flower(ME-CEF)against oxidative damage and hepatotoxicity in mice.Methods:The antioxidant efficacy of ME-CEF was assessed using 2,2′-azino-bis-(3-ethylbenzothiazoline-6-sulfonic)(ABTS)and 2,2-diphenyl-1-picrylhydrazyl(DPPH)scavenging assay.The hepatoprotective effect was investigated by an assessment of liver injury indicators(amino transferase[ALT],aspartate amino transferase[AST],alkaline phosphatase[ALP],bilirubin,creatinine)and normalizing lipid profiles(cho-lesterol[CHO],triglyceride[TG],high-density lipoprotein[HDL],and low-density li-poprotein[LDL])along with histopathological study and antioxidant enzymes(CAT).A phytochemical analysis,both qualitative and quantitative,was conducted,including gas chromatography-tandem mass spectrometry(GC-MS/MS)analysis and an in silico molecular docking study.Results:The Result Showed that ME-CEF Possesses Moderate ABTS and DPPH Scavenging Activity with IC_(50) Values of 117.18 and 160.41μg/mL.As Illustrated by Reducing Liver Enzymes(ALT,AST,ALP,Bilirubin,Creatinine)and Lipid Profile(CHO,TG,LDL)and Raising HDL Levels(p<0.01),ME-CEF Dose Dependently Mitigated CCl_(4)-Induced Acute Liver Injury.Furthermore,ME-CEF Blocked Hepatic Oxidative Stress by Boosting Antioxidant Enzymes(CAT)and Preventing Liver Tissue Damage and Apoptosis.In Silico Investigations Also Showed a Promising Binding Affinity with Tumor Necrosis Factor α(TNF-α),Interleukin 6(IL-6),PRAP-1,and Xanthin Oxidoreductase,which Displayed Antioxidant and Hepatoprotective Candidacy while Notable Safety and Efficacy Profile Was Also Documented through ADME/T Studies.Histopathological Analysis Showed Reduced Hepatocellular Necrosis and Vascular Congestion in Silymarin and Extract Groups.Conclusion:Based on these results,our findings strongly recommend the medicinal use of the plant,highlighting its antioxidant and hepatoprotective potentials.展开更多
Cisplatin chemotherapy has been used as the main treatment for different types of cancer.However,cisplatin chemotherapy-induced peripheral neuropathic pain(CIPNP)seriously affects the treatment process and quality of ...Cisplatin chemotherapy has been used as the main treatment for different types of cancer.However,cisplatin chemotherapy-induced peripheral neuropathic pain(CIPNP)seriously affects the treatment process and quality of life of patients.In addition,it impacts the underlying mechanism and prevention and treatment strategies,indicating that drug selection and efficacy evaluation need to be further investigated.Furthermore,an animal model that is more consistent with the pathological mechanism needs to be developed.In this study,we describe and discuss the methods of developing and detecting CIPNP models in rats and mice induced by cisplatin chemotherapy.The aim was to improve the modeling rate and develop animal models that are more consistent with the developmental pattern of the disease.In addition,the study provides ideal reference animal models for clinical research and drug discovery and development.展开更多
Multimorbidity—the co-occurrence of more than two chronic conditions in the same individual—is associated with premature death,diminished function,reduced quality of life,and increased societal burden.This complex s...Multimorbidity—the co-occurrence of more than two chronic conditions in the same individual—is associated with premature death,diminished function,reduced quality of life,and increased societal burden.This complex state involves dynamic interactions across multiple conditions,organ systems,and physiological pathways;yet research progress remains constrained by inadequate animal models that recapitulate human complexity.This review summarizes the predominant patterns of multimorbidity and evaluates current animal models spanning invertebrates,rodents,and large mammals.While no single model fully captures the multifaceted nature of human multimorbidity,we propose several strategic directions to address existing limitations:implementing a cross-species validation framework(from simple organisms to rodents to large mammals),standardizing protocols integrating multimodal risk factors,developing advanced non-animal models,and enhancing ethical oversight.Advancing multimorbidity models is crucial for decoding disease interactions and accelerating translation of research findings into improved patients outcomes.展开更多
Post-stroke depression(PSD) is a common psychiatric complication affecting nearly one-third of stroke survivors, leading to increased disability, mortality, and cognitive decline. Traditional Chinese Medicine(TCM) has...Post-stroke depression(PSD) is a common psychiatric complication affecting nearly one-third of stroke survivors, leading to increased disability, mortality, and cognitive decline. Traditional Chinese Medicine(TCM) has proven effective in treating PSD through syndrome differentiation, yet existing animal models primarily reflect Western medical concepts and fail to incorporate the TCM principle of “同病异治”( treating the same disease with different methods). This paper provides a review of the current methods for constructing animal models of post-stroke depression(PSD) from the perspective of Traditional Chinese Medicine(TCM) syndrome differentiation and proposes multi-dimensional assessment indicators. By integrating TCM theories with modern biomedical techniques, this study offers a comprehensive framework for deepening the understanding of the pathogenesis and therapeutic evaluation of PSD. This approach not only contributes to advancing PSD research but also paves the way for innovative treatment strategies that combine traditional and modern medicine.展开更多
BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)is a prevalent chronic liver disorder driven by obesity and metabolic dysfunction.MASLD progresses to metabolic dysfunction-associated steatohe...BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)is a prevalent chronic liver disorder driven by obesity and metabolic dysfunction.MASLD progresses to metabolic dysfunction-associated steatohepatitis,which is characterized by inflammation,hepatocyte injury,and fibrosis,increasing the risk of cirrhosis and liver failure.Recent studies suggest that neutrophil extracellular traps(NETs)and extracellular DNA(ecDNA)contribute to liver inflammation and fibrogenesis.However,their role in MASLD pathogenesis remains incompletely understood.AIM To investigate the dynamics of circulating NETs and ecDNA as potential biomarkers of liver injury in MASLD.METHODS Using three complementary mouse models,thioacetamide(TAA)-induced fibrosis,choline-deficient L-amino acid-defined(CDAA)diet-induced metabolic dysfunction-associated steatohepatitis,and cafeteria(CAF)diet-induced MASLD,we assessed the association between NET-related markers and liver damage.Blood samples were collected biweekly to analyze ecDNA and NET markers,including myeloperoxidase(MPO)and MPO-DNA complexes,using ELISA and real-time PCR.Liver histopathology was assessed for inflammation,fibrosis,and neutrophil infiltration.RESULTS The TAA and CDAA models exhibited significant liver injury,characterized by increased plasma alanine aminotransferase and aspartate aminotransferase levels,hepatocellular damage,and fibrosis.Elevated circulating NET markers(MPO and ecDNA)were observed in these models,with a strong correlation between NET formation and liver pathology.The CAF diet model induced steatosis but failed to elicit significant liver fibrosis or an increase in NET markers,suggesting that NETosis is associated with more severe liver damage.Notably,ecDNA and MPO levels correlated with neutrophil infiltration and fibrosis scores,indicating their potential as biomarkers of MASLD progression.CONCLUSION NETosis and ecDNA levels reflect liver injury severity in MASLD.NET markers and liver fibrosis were strongly associated in TAA and CDAA models,whereas CAF model showed minimal NET involvement.展开更多
Osteoclasts are essential for maintaining healthy bone.Pathological elevation of os-teoclastogenesis or osteoclast activity can cause osteoporosis and increase the risk of bone fracture.However,a few options are avail...Osteoclasts are essential for maintaining healthy bone.Pathological elevation of os-teoclastogenesis or osteoclast activity can cause osteoporosis and increase the risk of bone fracture.However,a few options are available for directly measuring osteoclast activity in vivo to test interventions that may affect osteoclasts.Here,we describe an in vivo method to measure osteoclast-mediated bone loss targeted at normal mouse calvaria.The method employs a novel procedure for measuring osteoclast resorption pits using micro-computed tomography.The potential utility of this mouse calvaria model to assess therapies targeting osteoclasts was validated using zoledronic acid,which is a nitrogen-containing bisphosphonate drug used to treat osteoporosis.展开更多
Realistic models for cancer research representing disease progression that commensurately respond to therapeutics consistent with clinical observation are the holy grail for pre-clinical research and screening.Althoug...Realistic models for cancer research representing disease progression that commensurately respond to therapeutics consistent with clinical observation are the holy grail for pre-clinical research and screening.Although such an ideal is elusive,well-characterized in vivo models facilitate our understanding of disease,progression,and therapeutic opportunities.Here,we characterize a commonly used syngeneic BALB/c mouse model of triple negative breast cancer(4T1)after establishing tumors in their flanks.Tumors developed at the subcutaneous injection site for all experimental mice and their volumes were monitored.We quantified a rare subset of breast cancer stemlike cells(CSCs),classified as CD44^(+)/CD24^(−)phenotypes in in vitro and ex vivo cell populations.Chromosome numbers in ex vivo metaphase cells were greater than cells cultured in vitro(89.4±3.4,range of 70-132 and 82.6±1.1,range of 70-128;respectively).Further,we observed different types of chromosome aberrations,including gap,deletion,exchange,interstitial deletion,terminal deletion,ring,dicentric,and Robertsonian translocations.For both sources of cells,the number of aberrations was dominated by deletions,terminal deletions,and Robertsonian translocations.Ex vivo cells exhibited greater prevalence of deletions and terminal deletions,whereas in vitro cells displayed more ring aberrations and Robertsonian translocations.In conclusion,we successfully characterized cancer cells from a syngeneic mouse model of breast cancer in terms of rare CSC proportion and a variety of chromosomal aberrations,which is useful for understanding tumor traits associated with cancer development and therapeutic action.The data act as a valuable resource for other studies using the 4T1 BALB/c model.展开更多
Background:In recent decades,the global incidence of dengue fever has been stead-ily increasing,with continuous geographical expansion.Researchers have successfully modeled most clinical symptoms of human dengue fever...Background:In recent decades,the global incidence of dengue fever has been stead-ily increasing,with continuous geographical expansion.Researchers have successfully modeled most clinical symptoms of human dengue fever using interferon type I(IFN-I)or combined IFN-I/II receptor knockout mice infected with dengue virus(DENV).However,this model requires further optimization to better support related studies.Methods:This study aimed to establish a stable dengue infection model by evaluating the effects of different genetic backgrounds and injection routes on DENV infection in interferon receptor knockout mice.We first infected various strains of interferon receptor-deficient mice with DENV and compared their susceptibility based on clini-cal symptoms,viremia levels,organ indices,histopathological findings,and vascular leakage markers.Subsequently,we selected the most susceptible strain to further investigate the impact of different injection methods on infection outcomes.Results:We found that BALB/c background mice with type 1 interferon recep-tor knockout(IFNAR)had the most obvious symptoms.Subsequently,we selected IFNAR−/−BALB/c mice to further explore the effects of different injection methods on dengue virus infection.The results showed that the intraperitoneal injection group had the most severe clinical symptoms,the longest duration of viremia,and the most obvious degree of organ damage.Conclusion:Through systematic screening and optimization,we established a robust animal model of dengue virus infection via intraperitoneal injection in IFNAR−/−BALB/c mice.This model offers a valuable tool for future dengue research.展开更多
文摘The increasing incidence and mortality associated with advanced stages of melanoma are cause for concern. Few treatment options are available for advanced melanoma and the 5-year survival rate is less than 15%. Targeted therapies may revolutionize melanoma treatment by providing less toxic and more effective strategies. However, maximizing effectiveness requires further understanding of the molecular alterations that drive tumor formation, progression, and maintenance, as well as elucidating the mechanisms of resistance. Several different genetic alterations identified in human melanoma have been recapitulated in mice. This review outlines recent progress made in the development of mouse models of melanoma and summarizes what these findings reveal about the human disease. We begin with a discussion of traditional models and conclude with the recently developed RCAS/TVA somatic cell gene delivery mouse model of melanoma.
基金National Natural Science Foundation of China,Grant/Award Number:82000102 and 82270112。
文摘The incidence of benign airway stenosis(BAS)is on the rise,and current treatment options are associated with a significant risk of restenosis.Therefore,there is an urgent need to explore new and effective prevention and treatment methods.Animal models serve as essential tools for investigating disease mechanisms and assessing novel therapeutic strategies,and the scientific rigor of their construction and validation significantly impacts the reliability of research findings.This paper systematically reviews the research progress and evaluation systems of BAS animal models over the past decade,aiming to provide a robust foundation for the optimized construction of BAS models,intervention studies,and clinical translation.This effort is intended to facilitate the innovation and advancement in BAS prevention and treatment strategies.
文摘Neurodegenerative diseases are increasing in prevalence due largely to aging populations worldwide and improved medical care for the elderly.Currently approved drugs can reduce some of the symptoms of neurodegenerative diseases but cannot cure them.Inflammation is involved in the development and progression of neurodegenerative diseases,and oxidative stress is implicated in neurodegeneration associated with cognitive decline and age-related cognitive impairment.Polyphenols such as curcumin,quercetin,and resveratrol possess potent anti-inflammatory and antioxidant properties.Nanoformulations of curcumin and quercetin can optimize their pharmacological effects in the treatment of neurodegenerative diseases.Nanocarriers play a crucial role in delivering drugs across the blood-brain barrier,thereby lowering the risk of peripheral side effects.Various nanoforms have been developed to induce bioavailability and solubility of curcumin and quercetin,including nanoparticles and nanoemulsions.The studies reviewed included 17 using curcumin nanoformulations and seven with quercetin nanoformulations and were tested in widely used animal models of Alzheimer’s disease,Parkinson’s disease,Huntington’s disease,and multiple sclerosis.Many of the curcumin and quercetin nanoformulations brought about improvements in learning and memory in behavioral tests of Alzheimer’s disease models and were effective in reducing oxidative stress in the brain.Both nanocurcumin and nanoquercetin decreased the levels of inflammatory markers in the brain.Nanocurcumin formulations improved motor behavior,gait,and memory in Parkinson’s disease models and increased dopaminergic neurons in the striatum and substantia nigra.Furthermore,nanocurcumin improved locomotor activity,memory,and learning,and the number of dendrites of medium spiny neurons in Huntington’s disease models.Nanocurcumin formulations decreased oxidative stress and inflammation in a model of demyelination.Several important limitations were identified in the studies reviewed and these need to be considered in future studies.Also,clinical trials could be performed using the currently available nanoforms of curcumin and quercetin.
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 Research and Development Program,China(2022YFC3502103,2022YFC3502102)the National Natural Science Foundation of China,China(82204751).
文摘This study summarizes the theoretical basis,modeling strategies,pathological mechanisms,and therapeutic advances related to high-altitude qi-deficiency and blood-stasis pattern.Traditional concepts such as“qi drives blood”and“deficiency leads to stasis”closely align with modern evidence demonstrating that hypoxia disrupts energy metabolism,impairs microcirculation,and amplifies inflammation and oxidative stress.Current animal models commonly use hypobaric hypoxia combined with fatigue loading,dietary restriction,ice-water stimulation,or adrenaline injection to mimic the combined effects of qi deficiency,blood stasis,and hypoxic injury.These composite approaches reproduce systemic abnormalities,including reduced arterial oxygen partial pressure,increased blood viscosity,impaired cardiac and pulmonary function,microcirculatory obstruction,and mitochondrial dysfunction.Enhanced inflammatory signaling,oxidative stress,and disturbances in metabolic and epigenetic networks further characterize the pattern.The findings indicate that its pathogenesis arises from multi-system,multi-target interactions rather than a single pathway.Representative herbal formulas,such as Buyang Huanwu decoction,Xuefu Zhuyu decoction,and prescriptions rich in Astragalus membranaceus(Fisch.)Bunge(A.membranaceus,Huang qi)or Salvia miltiorrhiza Bunge(S.miltiorrhiza,Dan Shen)have demonstrated the ability to improve energy metabolism,attenuate endothelial injury,enhance microcirculation,and suppress inflammation through network-level regulation.Future research should focus on standardizing exposure parameters,developing quantitative syndrome evaluation systems,and integrating multi-omics,systems biology and artificial intelligence to improve model reproducibility and mechanistic precision.These efforts may help establish objective criteria for high-altitude qi-deficiency and blood-stasis pattern and support the development of targeted therapeutic strategies.
基金Ministry of Research,Innovation and Digitization,CCCDI-UEFISCDI,Grant/Award Number:PN-IV-P7-7.1-PED-2024-1578,within PNCDI Ⅳ.
文摘Pathological scarring,manifested in the form of hypertrophic scars(HTS)and keloid scars(KS),represents a major clinical challenge due to its aesthetic and functional implications for patients.Understanding the molecular mechanisms involved in these types of scars and developing effective treatments requires the use of controlled ex-perimental models,especially animals,to overcome the limitations of clinical studies.The aim of this sistematic review is to critically analyze the animal models used in the last five years(2020-2025)for the study of pathological scars,highlighting their advantages,limitations and applicability in the development of new therapeutic strat-egies.Murine,rabbit and porcine models,as well as alternative models,offer varied perspectives on the formation and treatment of HTS and KS,with an emphasis on histological and molecular correlations with human pathology.By synthesizing recent data,the paper highlights the essential role of preclinical research in optimizing an-tifibrotic treatments and in advancing the translation of data into the clinical sphere.Overall,animal models remain essential for bridging mechanistic insights with clinical translation,supporting the development of more effective and personalized anti-scar therapies.
基金Sichuan Provincial Administration of Traditional Chinese Medicine,Grant/Award Number:2023MS564National Natural Science Foundation of China,Grant/Award Number:82474436。
文摘Lung cancer has one of the highest rates of incidence and mortality worldwide,mak-ing research on its mechanisms and treatments crucial.Animal models are essential in lung cancer research as they accurately replicate the biological characteristics and treatment outcomes seen in human diseases.Currently,various lung cancer models have been established,including chemical induction models,orthotopic transplan-tation models,ectopic transplantation models,metastasis models,and gene editing mouse models.Additionally,lung cancer grafts can be categorized into two types:tissue-based and cell-based grafts.This paper summarizes the phenotypes,advan-tages,and disadvantages of various induction methods based on their modeling tech-niques.The goal is to enhance the simulation of clinical lung cancer characteristics and to establish a solid foundation for future clinical research.
基金supported by the US National Institutes of Health (R01CA160331, R01CA163377, R01CA202919,R01CA239128, P01AG031862, P50CA228991 to R.G.Z. and K99CA241395 to S.K.)US Department of Defense (OC180109 and OC190181 to R.G.Z.)+2 种基金The Honorable Tina Brozman Foundation for Ovarian Cancer Research (to R.G.Z.)Ovarian Cancer Research Alliance Collaborative Research Development Grant (to R.G.Z.)Core facilities support was provided by a Cancer Centre Support Grant(CA010815) to the Wistar Institute。
文摘Epithelial ovarian cancer(EOC) is the leading cause of gynecological cancer-related mortality in the developed world. EOC is a heterogeneous disease represented by several histological and molecular subtypes. Therefore, exploration of relevant preclinical animal models that consider the heterogenic nature of EOC is of great importance for the development of novel therapeutic strategies that can be translated clinically to combat this devastating disease. In this review, we discuss recent progress in the development of preclinical mouse models for EOC study as well as their advantages and limitations.
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National Natural Science Foundation of China,Grant/Award Number:82222041 and 82241068CAMS Innovation Fund for Medical Sciences,Grant/Award Number:2021-I2M-1-037 and 2023-I2M-2-001+1 种基金National Key Research and Development Project of China,Grant/Award Number:2023YFC2309000Beijing Natural Science Foundation,Grant/Award Number:Z220018。
文摘Human herpesvirus,a specific group within the herpesvirus family,is responsible for a variety of human diseases.These viruses can infect humans and other vertebrates,primarily targeting the skin,mucous membranes,and neural tissues,thereby signifi-cantly impacting the health of both humans and animals.Animal models are crucial for studying virus pathogenesis,vaccine development,and drug testing.Despite several vaccine candidates being in preclinical and clinical stages,no vaccines are current available to prevent lifelong infections caused by these human herpesviruses,except for varicella-zoster virus(VZV)vaccine.However,the strict host tropism of herpes-viruses and other limitations mean that no single animal model can fully replicate all key features of human herpesvirus-associated diseases.This makes it challeng-ing to evaluate vaccines and antivirals against human herpesvirus comprehensively.Herein,we summarize the current animal models used to study the human herpesvi-ruses includingα-herpesviruses(herpes simplex virus type 1(HSV-1),HSV-2,VZV),β-herpesviruses(human cytomegalovirus(HCMV),γ-herpesviruses(Epstein-Barr virus(EBV))and Kaposi's sarcoma herpesvirus(KSHV)).By providing concise information and detailed analysis of the potential,limitations and applications of various models,such as non-human primates,mice,rabbits,guinea pigs,and tree shrews,this sum-mary aims to help researchers efficiently select the most appropriate animal model,offering practical guidance for studying human herpesvirus.
基金supported by the National Key Research and Development Program of China(2021YFF0702201,2021YFF0702204)Natural Science Foundation of Guangdong Province(2022A1515012651)。
文摘Tauopathies represent a class of neurodegenerative diseases(NDs),including Alzheimer’s disease(AD),progressive supranuclear palsy(PSP),Pick’s disease(PiD),and corticobasal degeneration(CBD),defined by intracellular accumulation of misfolded and hyperphosphorylated tau protein.The pathogenic cascade involves hyperphosphorylation,conformational changes,and aggregation into neurofibrillary tangles(NFTs),which are spatially and functionally linked to neuronal dysfunction,synaptic loss,and progressive cognitive and motor decline.To elucidate tau-mediated mechanisms,diverse transgenic rodent models expressing wild-type or mutant forms of human TAU have been generated.Although these models have advanced understanding of tau aggregation and propagation,tau-targeting therapies have failed to produce clinical benefits,raising concerns about the precise mechanism underlying tauopathies and the fidelity of animal models in evaluating therapeutic targets.This review systematically examines the neuropathological and behavioral phenotypes across established rodent and non-human primate(NHP)tauopathy models,highlighting mechanistic insights into tau-driven pathology.The advantages,limitations,and translational barriers of each model are critically evaluated to inform the development of more predictive preclinical platforms for therapeutic discovery.
基金supported by the China Postdoctoral Science Foundation(2024M751098,2024M761134)Jilin Province Development and Reform Commission Program(ZKJCFGW2023015)+1 种基金Wenzhou Science&Technology Bureau Basic Public Welfare Research Program(Y20240006)Jilin University Young Teachers and Students Cross-disciplinary Training Project(2023-JCXK-08)。
文摘Photodynamic therapy(PDT)is an emerging minimally invasive therapeutic modality that relies on the activation of a photosensitizing agent by light of a specific wavelength in the presence of molecular oxygen,leading to the generation of reactive oxygen species(ROS).This mechanism facilitates selective cytotoxic effects within pathological tissues and has demonstrated therapeutic potential across diverse disease contexts.However,the broader clinical applications remain limited by photosensitizer selectivity,shallow light penetration,and the risk of off-target cytotoxicity.Recent advancements in PDT have focused on the development of next-generation photosensitizers,the integration of nanotechnology for enhanced delivery and targeting,and the strategic combination of PDT with complementary therapeutic approaches.Experimental animal models play a crucial role in validating the efficacy and safety of PDT,optimizing its therapeutic parameters,and determining its mechanisms of action.This review provides a comprehensive overview of PDT applications in various disease models,including oncological,infectious,and nonconventional indications.Special emphasis is placed on the importance of large animal models in PDT research,such as rabbits,pigs,dogs,and non-human primates,which provide experimental platforms that more closely resemble human physiological and pathological states.The use of these models for understanding the mechanisms of PDT,optimizing therapeutic regimens,and evaluating clinical outcomes is also discussed.This review aims to inform future directions in PDT research and emphasizes the importance of selecting appropriate preclinical animal models to facilitate successful clinical translation.
基金partially funded by the Bangladesh Council of Scientific and Industrial Research (BCSIR) as an R&D project work of the 2022–2023 fiscal year,reference no.:39.02.0000.011.14.157.2022/172 (Date:10.11.2022).
文摘Background:Colocasia esculenta(L.)Schott,known as the taro vegetable,possesses various beneficial effects and is traditionally used in folk medicine.This study explores the ameliorative antioxidant and hepatoprotective effect of a methanolic extract of the C.esculenta flower(ME-CEF)against oxidative damage and hepatotoxicity in mice.Methods:The antioxidant efficacy of ME-CEF was assessed using 2,2′-azino-bis-(3-ethylbenzothiazoline-6-sulfonic)(ABTS)and 2,2-diphenyl-1-picrylhydrazyl(DPPH)scavenging assay.The hepatoprotective effect was investigated by an assessment of liver injury indicators(amino transferase[ALT],aspartate amino transferase[AST],alkaline phosphatase[ALP],bilirubin,creatinine)and normalizing lipid profiles(cho-lesterol[CHO],triglyceride[TG],high-density lipoprotein[HDL],and low-density li-poprotein[LDL])along with histopathological study and antioxidant enzymes(CAT).A phytochemical analysis,both qualitative and quantitative,was conducted,including gas chromatography-tandem mass spectrometry(GC-MS/MS)analysis and an in silico molecular docking study.Results:The Result Showed that ME-CEF Possesses Moderate ABTS and DPPH Scavenging Activity with IC_(50) Values of 117.18 and 160.41μg/mL.As Illustrated by Reducing Liver Enzymes(ALT,AST,ALP,Bilirubin,Creatinine)and Lipid Profile(CHO,TG,LDL)and Raising HDL Levels(p<0.01),ME-CEF Dose Dependently Mitigated CCl_(4)-Induced Acute Liver Injury.Furthermore,ME-CEF Blocked Hepatic Oxidative Stress by Boosting Antioxidant Enzymes(CAT)and Preventing Liver Tissue Damage and Apoptosis.In Silico Investigations Also Showed a Promising Binding Affinity with Tumor Necrosis Factor α(TNF-α),Interleukin 6(IL-6),PRAP-1,and Xanthin Oxidoreductase,which Displayed Antioxidant and Hepatoprotective Candidacy while Notable Safety and Efficacy Profile Was Also Documented through ADME/T Studies.Histopathological Analysis Showed Reduced Hepatocellular Necrosis and Vascular Congestion in Silymarin and Extract Groups.Conclusion:Based on these results,our findings strongly recommend the medicinal use of the plant,highlighting its antioxidant and hepatoprotective potentials.
基金Liaoning Provincial Key Research and Development Program,Grant/Award Number:2024JH2/102500062China Health Promotion Foundation Spark Program,Grant/Award Number:XH-D001National Natural Science Foundation of China,Grant/Award Number:82104838。
文摘Cisplatin chemotherapy has been used as the main treatment for different types of cancer.However,cisplatin chemotherapy-induced peripheral neuropathic pain(CIPNP)seriously affects the treatment process and quality of life of patients.In addition,it impacts the underlying mechanism and prevention and treatment strategies,indicating that drug selection and efficacy evaluation need to be further investigated.Furthermore,an animal model that is more consistent with the pathological mechanism needs to be developed.In this study,we describe and discuss the methods of developing and detecting CIPNP models in rats and mice induced by cisplatin chemotherapy.The aim was to improve the modeling rate and develop animal models that are more consistent with the developmental pattern of the disease.In addition,the study provides ideal reference animal models for clinical research and drug discovery and development.
基金supported by the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2023-I2M-2-001)the State Key Laboratory Special Fund(2060204)+1 种基金the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(2023-PT180-01)the Young Elite Scientists Sponsorship Program of China Association for Science and Technology(grant 2020QNRC001).
文摘Multimorbidity—the co-occurrence of more than two chronic conditions in the same individual—is associated with premature death,diminished function,reduced quality of life,and increased societal burden.This complex state involves dynamic interactions across multiple conditions,organ systems,and physiological pathways;yet research progress remains constrained by inadequate animal models that recapitulate human complexity.This review summarizes the predominant patterns of multimorbidity and evaluates current animal models spanning invertebrates,rodents,and large mammals.While no single model fully captures the multifaceted nature of human multimorbidity,we propose several strategic directions to address existing limitations:implementing a cross-species validation framework(from simple organisms to rodents to large mammals),standardizing protocols integrating multimodal risk factors,developing advanced non-animal models,and enhancing ethical oversight.Advancing multimorbidity models is crucial for decoding disease interactions and accelerating translation of research findings into improved patients outcomes.
基金Jilin Provincial Department of Education,Grant/Award Number:JJKH20230958KJJilin Scientific and Technological Development Program,Grant/Award Number:YDZJ202401092ZYTS。
文摘Post-stroke depression(PSD) is a common psychiatric complication affecting nearly one-third of stroke survivors, leading to increased disability, mortality, and cognitive decline. Traditional Chinese Medicine(TCM) has proven effective in treating PSD through syndrome differentiation, yet existing animal models primarily reflect Western medical concepts and fail to incorporate the TCM principle of “同病异治”( treating the same disease with different methods). This paper provides a review of the current methods for constructing animal models of post-stroke depression(PSD) from the perspective of Traditional Chinese Medicine(TCM) syndrome differentiation and proposes multi-dimensional assessment indicators. By integrating TCM theories with modern biomedical techniques, this study offers a comprehensive framework for deepening the understanding of the pathogenesis and therapeutic evaluation of PSD. This approach not only contributes to advancing PSD research but also paves the way for innovative treatment strategies that combine traditional and modern medicine.
基金Supported by Slovak Research and Development Agency,No.APVV-21-0370Ministry of Education,Science,Research and Sport of the Slovak Republic,No.VEGA 1/0706/25 and No.VEGA 1/0341/23.
文摘BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)is a prevalent chronic liver disorder driven by obesity and metabolic dysfunction.MASLD progresses to metabolic dysfunction-associated steatohepatitis,which is characterized by inflammation,hepatocyte injury,and fibrosis,increasing the risk of cirrhosis and liver failure.Recent studies suggest that neutrophil extracellular traps(NETs)and extracellular DNA(ecDNA)contribute to liver inflammation and fibrogenesis.However,their role in MASLD pathogenesis remains incompletely understood.AIM To investigate the dynamics of circulating NETs and ecDNA as potential biomarkers of liver injury in MASLD.METHODS Using three complementary mouse models,thioacetamide(TAA)-induced fibrosis,choline-deficient L-amino acid-defined(CDAA)diet-induced metabolic dysfunction-associated steatohepatitis,and cafeteria(CAF)diet-induced MASLD,we assessed the association between NET-related markers and liver damage.Blood samples were collected biweekly to analyze ecDNA and NET markers,including myeloperoxidase(MPO)and MPO-DNA complexes,using ELISA and real-time PCR.Liver histopathology was assessed for inflammation,fibrosis,and neutrophil infiltration.RESULTS The TAA and CDAA models exhibited significant liver injury,characterized by increased plasma alanine aminotransferase and aspartate aminotransferase levels,hepatocellular damage,and fibrosis.Elevated circulating NET markers(MPO and ecDNA)were observed in these models,with a strong correlation between NET formation and liver pathology.The CAF diet model induced steatosis but failed to elicit significant liver fibrosis or an increase in NET markers,suggesting that NETosis is associated with more severe liver damage.Notably,ecDNA and MPO levels correlated with neutrophil infiltration and fibrosis scores,indicating their potential as biomarkers of MASLD progression.CONCLUSION NETosis and ecDNA levels reflect liver injury severity in MASLD.NET markers and liver fibrosis were strongly associated in TAA and CDAA models,whereas CAF model showed minimal NET involvement.
基金National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health,Grant/Award Number:R01AR069044Rutgers-New Jersey Medical School Department of Orthopaedics。
文摘Osteoclasts are essential for maintaining healthy bone.Pathological elevation of os-teoclastogenesis or osteoclast activity can cause osteoporosis and increase the risk of bone fracture.However,a few options are available for directly measuring osteoclast activity in vivo to test interventions that may affect osteoclasts.Here,we describe an in vivo method to measure osteoclast-mediated bone loss targeted at normal mouse calvaria.The method employs a novel procedure for measuring osteoclast resorption pits using micro-computed tomography.The potential utility of this mouse calvaria model to assess therapies targeting osteoclasts was validated using zoledronic acid,which is a nitrogen-containing bisphosphonate drug used to treat osteoporosis.
基金National Research,Development and Innovation Fund of the Ministry of Culture and Innovation under the National Laboratories Program(National Tumor Biology Laboratory,Grant/Award Number:2022-2.1.1-NL-2022-00010)Senior Research Fellowship from National Health and Medical Research Council of Australia,Grant/Award Number:1156693+1 种基金Hungarian Thematic Excellence Program,Grant/Award Number:TKP2021-EGA-44Tour de Cure,Pioneering Grant,Grant/Award Number:RSP-253-18/19。
文摘Realistic models for cancer research representing disease progression that commensurately respond to therapeutics consistent with clinical observation are the holy grail for pre-clinical research and screening.Although such an ideal is elusive,well-characterized in vivo models facilitate our understanding of disease,progression,and therapeutic opportunities.Here,we characterize a commonly used syngeneic BALB/c mouse model of triple negative breast cancer(4T1)after establishing tumors in their flanks.Tumors developed at the subcutaneous injection site for all experimental mice and their volumes were monitored.We quantified a rare subset of breast cancer stemlike cells(CSCs),classified as CD44^(+)/CD24^(−)phenotypes in in vitro and ex vivo cell populations.Chromosome numbers in ex vivo metaphase cells were greater than cells cultured in vitro(89.4±3.4,range of 70-132 and 82.6±1.1,range of 70-128;respectively).Further,we observed different types of chromosome aberrations,including gap,deletion,exchange,interstitial deletion,terminal deletion,ring,dicentric,and Robertsonian translocations.For both sources of cells,the number of aberrations was dominated by deletions,terminal deletions,and Robertsonian translocations.Ex vivo cells exhibited greater prevalence of deletions and terminal deletions,whereas in vitro cells displayed more ring aberrations and Robertsonian translocations.In conclusion,we successfully characterized cancer cells from a syngeneic mouse model of breast cancer in terms of rare CSC proportion and a variety of chromosomal aberrations,which is useful for understanding tumor traits associated with cancer development and therapeutic action.The data act as a valuable resource for other studies using the 4T1 BALB/c model.
基金Guangdong Province Medical Research Fund Project,Grant/Award Number:B2024112The Scientific Research Special Project of the Joint Construction Project of High-level Hospitals between Guangzhou University of Chinese Medicine and the Scientific Research Fund Project,Grant/Award Number:GZYZS2024G09+2 种基金Special Project of the Research Platform of Guangdong Provincial Department of Traditional Chinese Medicine,Grant/Award Number:20254040the Project of the Incubation Program for the Science and Technology Development of Chinese Medicine Guangdong Laboratory/Hengqin Laboratory,Grant/Award Number:HQL2024PZ043Guangdong Province Natural Science Foundation-Guangzhou-South China Joint Youth Fund Project,Grant/Award Number:2023A1515110849。
文摘Background:In recent decades,the global incidence of dengue fever has been stead-ily increasing,with continuous geographical expansion.Researchers have successfully modeled most clinical symptoms of human dengue fever using interferon type I(IFN-I)or combined IFN-I/II receptor knockout mice infected with dengue virus(DENV).However,this model requires further optimization to better support related studies.Methods:This study aimed to establish a stable dengue infection model by evaluating the effects of different genetic backgrounds and injection routes on DENV infection in interferon receptor knockout mice.We first infected various strains of interferon receptor-deficient mice with DENV and compared their susceptibility based on clini-cal symptoms,viremia levels,organ indices,histopathological findings,and vascular leakage markers.Subsequently,we selected the most susceptible strain to further investigate the impact of different injection methods on infection outcomes.Results:We found that BALB/c background mice with type 1 interferon recep-tor knockout(IFNAR)had the most obvious symptoms.Subsequently,we selected IFNAR−/−BALB/c mice to further explore the effects of different injection methods on dengue virus infection.The results showed that the intraperitoneal injection group had the most severe clinical symptoms,the longest duration of viremia,and the most obvious degree of organ damage.Conclusion:Through systematic screening and optimization,we established a robust animal model of dengue virus infection via intraperitoneal injection in IFNAR−/−BALB/c mice.This model offers a valuable tool for future dengue research.
