The development of rodent models that accurately reflect the pathogenesis of alcoholic liver disease(ALD)in humans is crucial for evaluating the nutritional intervention of food bioactive ingredients in ALD.Although v...The development of rodent models that accurately reflect the pathogenesis of alcoholic liver disease(ALD)in humans is crucial for evaluating the nutritional intervention of food bioactive ingredients in ALD.Although various models have been employed to establish ALD models over the past few decades,most successful cases are associated with high mortality rates,operational difficulties,and incompatibility formation mechanism compared to human ALD.However,the ALD models established by oral administration that simulate human drinking behavior often fail to induce significant liver damage.Therefore,it is imperative to explore simple and effective modes of oral administration for establishing ALD models consistent with the pathophysiological process of human ALD.Herein,we summarized the pathogenesis of ALD and discussed several issues related to construct ALD models with rodents(mainly mice and rats)by oral administration,including animal selection,animal feeding,alcohol intervention,and evaluation criteria.The purpose of this review is to provide a standardized and efficient formula for ALD modeling,so as to facilitate efficacy evaluation and mechanism analysis of food bioactive ingredients in ALD.展开更多
Medication-related osteonecrosis of the jaw(MRONJ)is primarily associated with administering antiresorptive or antiangiogenic drugs.Despite significant research on MRONJ,its pathogenesis and effective treatments are s...Medication-related osteonecrosis of the jaw(MRONJ)is primarily associated with administering antiresorptive or antiangiogenic drugs.Despite significant research on MRONJ,its pathogenesis and effective treatments are still not fully understood.Animal models can be used to simulate the pathophysiological features of MRONJ,serving as standardized in vivo experimental platforms to explore the pathogenesis and therapies of MRONJ.Rodent models exhibit excellent effectiveness and high reproducibility in mimicking human MRONJ,but classical methods cannot achieve a complete replica of the pathogenesis of MRONJ.Modified rodent models have been reported with improvements for better mimicking of MRONJ onset in clinic.This review summarizes representative classical and modified rodent models of MRONJ created through various combinations of systemic drug induction and local stimulation and discusses their effectiveness and efficiency.Currently,there is a lack of a unified assessment system for MRONJ models,which hinders a standard definition of MRONJ-like lesions in rodents.Therefore,this review comprehensively summarizes assessment systems based on published peer-review articles,including new approaches in gross observation,histological assessments,radiographic assessments,and serological assessments.This review can serve as a reference for model establishment and evaluation in future preclinical studies on MRONJ.展开更多
A penetrating traumatic brain injury（pTBI）occurs when an object impacts the head with sufficient energy to penetrate skin,cranial bone and meninges to inflict injury directly to the brain parenchyma.This type of inj...A penetrating traumatic brain injury（pTBI）occurs when an object impacts the head with sufficient energy to penetrate skin,cranial bone and meninges to inflict injury directly to the brain parenchyma.This type of injury is particularly common in areas plagued by armed conflicts or gun-related violence.展开更多
Non-alcoholic fatty liver disease(NAFLD)prevalence has increased drastically in recent decades,affecting up to 25%of the world’s population.NAFLD is a spectrum of different diseases that starts with asymptomatic stea...Non-alcoholic fatty liver disease(NAFLD)prevalence has increased drastically in recent decades,affecting up to 25%of the world’s population.NAFLD is a spectrum of different diseases that starts with asymptomatic steatosis and continues with development of an inflammatory response called steatohepatitis,which can progress to fibrosis.Several molecular and metabolic changes are required for the hepatocyte to finally vary its function;hence a“multiple hit”hypothesis seems a more accurate proposal.Previous studies and current knowledge suggest that in most cases,NAFLD initiates and progresses through most of nine hallmarks of the disease,although the triggers and mechanisms for these can vary widely.The use of animal models remains crucial for understanding the disease and for developing tools based on biological knowledge.Among certain requirements to be met,a good model must imitate certain aspects of the human NAFLD disorder,be reliable and reproducible,have low mortality,and be compatible with a simple and feasible method.Metabolism studies in these models provides a direct reflection of the workings of the cell and may be a useful approach to better understand the initiation and progression of the disease.Metabolomics seems a valid tool for studying metabolic pathways and crosstalk between organs affected in animal models of NAFLD and for the discovery and validation of relevant biomarkers with biological understanding.In this review,we provide a brief introduction to NAFLD hallmarks,the five groups of animal models available for studying NAFLD and the potential role of metabolomics in the study of experimental NAFLD.展开更多
The weakened protective efficacy of COVID-19 vaccines and antibodies caused by SARS-CoV-2 variants presents a global health emergency,which underscores the urgent need for universal therapeutic antibody intervention f...The weakened protective efficacy of COVID-19 vaccines and antibodies caused by SARS-CoV-2 variants presents a global health emergency,which underscores the urgent need for universal therapeutic antibody intervention for clinical patients.Here,we screened three alpacas-derived nanobodies(Nbs)with neutralizing activity from twenty RBD-specific Nbs.The three Nbs were fused with the Fc domain of human IgG,namely aVHH-11-Fc,aVHH-13-Fc and aVHH-14-Fc,which could specifically bind RBD protein and competitively inhibit the binding of ACE2 receptor to RBD.They effectively neutralized SARS-CoV-2 pseudoviruses D614G,Alpha,Beta,Gamma,Delta,and Omicron sub-lineages BA.1,BA.2,BA.4,and BA.5 and authentic SARS-CoV-2 prototype,Delta,and Omicron BA.1,BA.2 strains.In mice-adapted COVID-19 severe model,intranasal administration of aVHH-11-Fc,aVHH-13-Fc and aVHH-14-Fc effectively protected mice from lethal challenges and reduced viral loads in both the upper and lower respiratory tracts.In the COVID-19 mild model,aVHH-13-Fc,which represents the optimal neutralizing activity among the above three Nbs,effectively protected hamsters from the challenge of SARS-CoV-2 prototype,Delta,Omicron BA.1 and BA.2 by significantly reducing viral replication and pathological alterations in the lungs.In structural modeling of aVHH-13 and RBD,aVHH-13 binds to the receptor-binding motif region of RBD and interacts with some highly conserved epitopes.Taken together,our study illustrated that alpaca-derived Nbs offered a therapeutic countermeasure against SARS-CoV-2,including those Delta and Omicron variants which have evolved into global pandemic strains.展开更多
Treating ischemic stroke(IS)presents significant challenges;however,recent advancements suggest that glial cell-derived extracellular vesicles(GD-EVs)may offer a promising therapeutic strategy.This systematic review a...Treating ischemic stroke(IS)presents significant challenges;however,recent advancements suggest that glial cell-derived extracellular vesicles(GD-EVs)may offer a promising therapeutic strategy.This systematic review and meta-analysis evaluated the potential benefits of GD-EVs in IS by synthesizing data from preclinical studies.The review protocol was pre-registered with PROSPERO(CRD42024541149).Comprehensive literature searches were conducted across multiple databases,including PubMed,EMBASE,Web of Science,Cochrane Library,China National Knowledge Infrastructure,VIP Database for Chinese Technical Periodicals,Wanfang Database,and SinoMed,until April 10,2024,to identify relevant studies.Preclinical studies investigating the utilization of GD-EVs in animal models of IS were included.Study quality was assessed using the risk of bias tool from the Systematic Review Center for Laboratory Animal Experimentation.From an initial pool of 3028 studies,11 studies met the inclusion criteria.The analysis demonstrated that GD-EVs significantly improved neurological function,as evidenced by a reduction in the modified neurological severity score(standardized mean difference[SMD]:−1.69,95%confidence interval[CI]:−2.15 to−1.22,p<0.00001,and I2=0%).GD-EVs also significantly reduced infarct volume in rodent models(SMD:−4.78,95%CI:−6.91 to−2.66,p<0.0001,Tau2=0.99,and I2=42%)and decreased brain water content and the release of pro-inflammatory factors post-stroke.The methodological rigor of the included studies indicated sufficiently high overall quality.These findings suggest that GD-EVs hold significant promise as a novel therapeutic approach for IS and warrant further preclinical investigations before translation into clinical trials.展开更多
The uterus is an indispensable organ for the development of a new life in eutherian mammals.The female mammalian reproductive capacity diminishes with age.In this respect,the senescence of uterine endometrium is convi...The uterus is an indispensable organ for the development of a new life in eutherian mammals.The female mammalian reproductive capacity diminishes with age.In this respect,the senescence of uterine endometrium is convinced to contribute to this failure.This review focuses on the physiological function of the uterus and the related influence of aging mainly in rodent models.A better understanding of the underlying mechanisms governing the process of uterine aging is hoped to generate new strategies to prolong the reproductive lifespan in humans.展开更多
Spinal cord injuries （SCI） in rodents have been created by laceration, contusion, compression, or intramedullary injection of toxic agents. The choice of an appropriate SCI model should be made for each study based ...Spinal cord injuries （SCI） in rodents have been created by laceration, contusion, compression, or intramedullary injection of toxic agents. The choice of an appropriate SCI model should be made for each study based on the experimental design, with care taken to avoid unintended complications such as hemorrhage. Technical comments will be made in this communication describing the 1） importance of vertebral stabi- lization, 2） injury preparation, and 3） landmarks to improve the preci- sion and reproducibility of the SCI.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
An infection by Zika virus(ZIKV), a mosquito-borne flavivirus, broke out in South American regions in 2015, and recently showed a tendency of spreading to North America and even worldwide. ZIKV was first detected in 1...An infection by Zika virus(ZIKV), a mosquito-borne flavivirus, broke out in South American regions in 2015, and recently showed a tendency of spreading to North America and even worldwide. ZIKV was first detected in 1947 and only 14 human infection cases were reported until 2007. This virus was previously observed to cause only mild flu-like symptoms.However, recent ZIKV infections might be responsible for the increasing cases of neurological disorders such as GuillainBarre′ syndrome and congenital defects, including newborn microcephaly. Therefore, researchers have established several animal models to study ZIKV transmission and pathogenesis, and test therapeutic candidates. This review mainly summarizes the reported animal models of ZIKV infection, including mice and non-human primates.展开更多
The health benefits of physical exercise are well established and have been observed in both human studies and rodent models[1],improving overall health and stress resilience.However,the underlying molecular mechanism...The health benefits of physical exercise are well established and have been observed in both human studies and rodent models[1],improving overall health and stress resilience.However,the underlying molecular mechanisms have not been comprehensively investigated.Previous studies have focused extensively on its neuromodulatory effects and have also identified multiple exercise-associated molecular substrates and blood-borne metabolites,including neurotrophic factors,monoamine neurotransmitters,neuroinflammatory cytokines,kynurenine,N-lactoylphenylalanine,and the ketone bodyβ-hydroxybutyrate[2].Notably,lactate,a common energy source derived from cellular glycolysis in response to intensive exercise,has recently been reported to exert antidepressant activity[3].However,a detailed mechanistic explanation is lacking.展开更多
Background:Although widely used in periodontal research,rodents are naturally resistant to periodontitis.Conventional models,such as ligature-induced periodontitis,often fail to sustain defects due to spontaneous tiss...Background:Although widely used in periodontal research,rodents are naturally resistant to periodontitis.Conventional models,such as ligature-induced periodontitis,often fail to sustain defects due to spontaneous tissue regeneration after ligature removal.To address this,we refined a rat ligature-induced model of experimental periodontitis to better mimic the chronic,progressive nature of human periodontitis.Methods:As a first step,following a split-mouth design,we compared the effectiveness of 3/0 silk thread and 0.008-inch orthodontic wire as ligature materials.Ligatures were applied around the left mandibular first molar for 6,10,and 14 days.Periodontal pocket irrigation was performed every second day using a suspension of P.gingivalis,P.intermedia,and S.gordonii.As a second step,we evaluated whether silk-ligature alone,without human periopathogens,would be sufficient to induce a stable and progressive periodontal lesion.For that purpose,a silk ligature was removed on day 14,and the bone defect dynamics were monitored at 14-,21-,and 28-days post-removal using micro-CT.Results:Both wire and silk ligatures,in combination with bacterial irrigation,effectively induced rapid interproximal alveolar bone loss.However,silk ligature only,without periodontopathogen colonization,resulted in significantly lower bone loss(1.076±0.22 mm vs.2.012±0.374 mm;p=0.003)and the induced alveolar bone defects gradually resolved again over time.Conclusions:The proposed rat model of periodontitis is well characterized and replicates human disease by sustaining colonization with viable periopathogens,leading to progressive disease with alveolar bone loss.The suggested model is straightforward,easy to establish and can be used reliably in preclinical studies.展开更多
Functional magnetic resonance imaging(fMRI) is em-ployed in many behavior analysis studies, with blood oxygen level dependent-(BOLD-) contrast imaging being the main method used to generate images. The use of BOLD-con...Functional magnetic resonance imaging(fMRI) is em-ployed in many behavior analysis studies, with blood oxygen level dependent-(BOLD-) contrast imaging being the main method used to generate images. The use of BOLD-contrast imaging in f MRI has been refined over the years, for example, the inclusion of a spin echo pulse and increased magnetic strength were shown to produce better recorded images. Taking careful precautions to control variables during measurement, comparisons between different specimen groups can be illustrated by f MRI imaging using both quantitative and qualitative methods. Differences have been observed in comparisons of active and resting, developing and aging, and defective and damaged brains in various studies. However, cognitive studies using f MRI still face a number of challenges in interpretation that can only be overcome by imaging large numbers of samples. Furthermore, f MRI studies of brain cancer, lesions and other brain pathologies of both humans and animals are still to be explored.展开更多
Schwann cells,the myelinating glia of the peripheral nervous system,wrap axons multiple times to build their myelin sheath.Myelin is of paramount importance for axonal integrity and fast axon potential propagation.How...Schwann cells,the myelinating glia of the peripheral nervous system,wrap axons multiple times to build their myelin sheath.Myelin is of paramount importance for axonal integrity and fast axon potential propagation.However,myelin is lacking or dysfunctional in several neuropathies including demyelinating and dysmyelinating Charcot-M arie-To oth disease.Charcot-Marie-To oth disease represents the most prevalent inherited neuropathy in humans and is classified either as axonal,demyelinating or dysmyelinating,or as intermediate.The demyelinating or dysmyelinating forms of Charcot-Marie-Tooth disease constitute the majority of the disease cases and are most frequently due to mutations in the three following myelin genes:peripheral myelin protein 22,myelin protein ze ro and gap junction beta 1(coding for Connexin 32) causing Charcot-M arie-Tooth disease type 1A,Charcot-Marie-Tooth disease type 1B,and X-linked Charcot-M arie-Tooth disease type 1,respectively.The resulting perturbation of myelin structure and function leads to axonal demyelination or dysmyelination and causes severe disabilities in affected patients.No treatment to cure or slow down the disease progression is currently available on the market,howeve r,scientific discoveries led to a better understanding of the pathomechanisms of the disease and to potential treatment strategies.In this review,we describe the features and molecular mechanisms of the three main demyelinating or dysmyelinating forms of Charcot-Marie-Tooth disease,the rodent models used in research,and the emerging therapeutic approaches to cure or counteract the progression of the disease.展开更多
Traumatic brain injury has a complex pathophysiology that produces both rapid and delayed brain damage. Rapid damage initiates immediately after injury. Treatment of traumatic brain injury is typically delayed many ho...Traumatic brain injury has a complex pathophysiology that produces both rapid and delayed brain damage. Rapid damage initiates immediately after injury. Treatment of traumatic brain injury is typically delayed many hours, thus only delayed damage can be targeted with drugs. Delayed traumatic brain injury includes neuroinflammation, oxidative damage, apoptosis, and glutamate toxicity. Both the speed and complexity of traumatic brain injury pathophysiology present large obstacles to drug development. Repurposing of Food and Drug Administration-approved drugs may be a highly efficient approach to get therapeutics to the clinic. This review examines the preclinical outcomes of minocycline and N-acetylcysteine as individual drugs and compares them to the minocycline plus N-acetylcysteine combination. Both minocycline and N-acetylcysteine are Food and Drug Administration-approved drugs with pleiotropic therapeutic effects. As individual drugs, minocycline and N-acetylcysteine are well tolerated, with known pharmacokinetics, and enter the brain through an intact blood-brain barrier. At concentrations greater than needed for antimicrobial action, minocycline is a potent anti-inflammatory minocycline, also acts as an antioxidant and inhibits multiple enzymes that promote brain injury including metalloproteases, caspases, and polyADP-ribose-polymerase-1. N-acetylcysteine alone is also an antioxidant. It increases brain glutathione, prevents lipid oxidation, and protects mitochondria. N-acetylcysteine also acts as an anti-inflammatory as well as increases extracellular glutamate by activating the X;cystine-glutamate antitransporter. These multiple actions of minocycline and N-acetylcysteine have made them attractive candidates to treat traumatic brain injury. When first dosed within the one hour after injury, either minocycline or N-acetylcysteine improves a diverse set of therapeutic outcome measures in multiple traumatic brain injury animal models. A small number of clinical trials for traumatic brain injury have established the safety of minocycline or N-acetylcysteine and suggested that either drug has some efficacy. Preclinical studies have shown that minocycline plus N-acetylcysteine have positive synergy resulting in therapeutic effects and a more prolonged therapeutic time window not seen with the individual drugs. This review compares the actions of minocycline and N-acetylcysteine, individually and in combination. Evidence supports that the combination has greater utility to treat traumatic brain injury than the individual drugs.展开更多
This is a very attractive article. It combines fascinating new methodology with a most interesting dataset, and a highly motivating presentation. However, despite the many
The authors are to be congratulated for an innovative paper in terms of both modelling methodology and subject matter significance. The analysis of short time series is known to be
Although multi-view monitoring techniques have been widely applied in skinned model reconstruction and movement analysis,traditional systems using high-performance Personal Computers(PCs),or industrial cameras are oft...Although multi-view monitoring techniques have been widely applied in skinned model reconstruction and movement analysis,traditional systems using high-performance Personal Computers(PCs),or industrial cameras are often prohibitive due to high costs and limited scalability.Here,we introduce an affordable,scalable multi-view image acquisition system for skinned model reconstruction in animal studies,utilizing consumer Android devices and a wireless network for synchronized monitoring named Rodent Arena Multi-View Monitor(RAMM).It uses smartphones as camera nodes with local data storage,enabling cost-effective scalability.Its custom synchronization solution and portability make it ideal for research and education in rodent behavior analysis,offering a practical alternative for institutions with limited budgets.Furthermore,the portability and flexibility of this system make it an ideal tool for rodent skinned model research based on multi-view image acquisition.To evaluate the performance,we perform an oscilloscope analysis to ensure effectiveness of synchronization.A 45-camera node setup is built to highlight RAMM’s cost efficiency and ease in constructing large-scale systems.Additionally,the data quality is validated using the Instant Neural Graphics Primitives(Instant-NGP)method.Remarkable results were achieved with a 30.49 dB PSNR by utilizing only 25 images with intrinsic and extrinsic parameters,fulfilling the requirements for well-synchronized data used in 3D representation algorithms.展开更多
Numerous seemingly promising cerebroprotectants previously validated in rodents almost all have failed in stroke clinical trials.The failure of clinical translation strikes an essential need to employ more ideal anima...Numerous seemingly promising cerebroprotectants previously validated in rodents almost all have failed in stroke clinical trials.The failure of clinical translation strikes an essential need to employ more ideal animal models in stroke research.Compared with the most commonly used rodent models of stroke,non-human primates(NHPs)are far more comparable to humans regarding brain anatomy,functionality and pathological features.The aim of this perspective was to summarise the advantages of NHPs stroke models over rodents,discuss the current limitations of NHPs models,and cast an outlook on the future development of NHPs in stroke preclinical research.展开更多
A remarkable study by Guo et al.,published in Cell,suggests a compelling new direction for improving pain management:biased allosteric modulation of the neurotensin receptor 1(NTSR1),using the drug-like molecule SBI-8...A remarkable study by Guo et al.,published in Cell,suggests a compelling new direction for improving pain management:biased allosteric modulation of the neurotensin receptor 1(NTSR1),using the drug-like molecule SBI-810,promotesβ-arrestin2(βarr2)recruitment while avoiding canonical G protein signaling–thereby providing robust analgesia across a plethora of rodent models of both acute and chronic pain without impairing motor function,cognition,or causing opioid-like dependency.1,2 SBI-810 is introduced as a highly promising molecule underscoring the therapeutic potential of biased and allosteric G protein-coupled receptor(GPCR)ligands to address an urgent unmet medical need.展开更多
基金supported by the National Natural Science Foundation of China(32430083).
文摘The development of rodent models that accurately reflect the pathogenesis of alcoholic liver disease(ALD)in humans is crucial for evaluating the nutritional intervention of food bioactive ingredients in ALD.Although various models have been employed to establish ALD models over the past few decades,most successful cases are associated with high mortality rates,operational difficulties,and incompatibility formation mechanism compared to human ALD.However,the ALD models established by oral administration that simulate human drinking behavior often fail to induce significant liver damage.Therefore,it is imperative to explore simple and effective modes of oral administration for establishing ALD models consistent with the pathophysiological process of human ALD.Herein,we summarized the pathogenesis of ALD and discussed several issues related to construct ALD models with rodents(mainly mice and rats)by oral administration,including animal selection,animal feeding,alcohol intervention,and evaluation criteria.The purpose of this review is to provide a standardized and efficient formula for ALD modeling,so as to facilitate efficacy evaluation and mechanism analysis of food bioactive ingredients in ALD.
基金supported by the National Natural Science Foundation of China(No.81921002,No.81900970)Young Physician Innovation Team Project(No.QC202003)from Ninth People’s Hospital,Shanghai Jiao Tong University School of MedicineShanghai Sailing Program(19YF1426000)jointly。
文摘Medication-related osteonecrosis of the jaw(MRONJ)is primarily associated with administering antiresorptive or antiangiogenic drugs.Despite significant research on MRONJ,its pathogenesis and effective treatments are still not fully understood.Animal models can be used to simulate the pathophysiological features of MRONJ,serving as standardized in vivo experimental platforms to explore the pathogenesis and therapies of MRONJ.Rodent models exhibit excellent effectiveness and high reproducibility in mimicking human MRONJ,but classical methods cannot achieve a complete replica of the pathogenesis of MRONJ.Modified rodent models have been reported with improvements for better mimicking of MRONJ onset in clinic.This review summarizes representative classical and modified rodent models of MRONJ created through various combinations of systemic drug induction and local stimulation and discusses their effectiveness and efficiency.Currently,there is a lack of a unified assessment system for MRONJ models,which hinders a standard definition of MRONJ-like lesions in rodents.Therefore,this review comprehensively summarizes assessment systems based on published peer-review articles,including new approaches in gross observation,histological assessments,radiographic assessments,and serological assessments.This review can serve as a reference for model establishment and evaluation in future preclinical studies on MRONJ.
文摘A penetrating traumatic brain injury（pTBI）occurs when an object impacts the head with sufficient energy to penetrate skin,cranial bone and meninges to inflict injury directly to the brain parenchyma.This type of injury is particularly common in areas plagued by armed conflicts or gun-related violence.
文摘Non-alcoholic fatty liver disease(NAFLD)prevalence has increased drastically in recent decades,affecting up to 25%of the world’s population.NAFLD is a spectrum of different diseases that starts with asymptomatic steatosis and continues with development of an inflammatory response called steatohepatitis,which can progress to fibrosis.Several molecular and metabolic changes are required for the hepatocyte to finally vary its function;hence a“multiple hit”hypothesis seems a more accurate proposal.Previous studies and current knowledge suggest that in most cases,NAFLD initiates and progresses through most of nine hallmarks of the disease,although the triggers and mechanisms for these can vary widely.The use of animal models remains crucial for understanding the disease and for developing tools based on biological knowledge.Among certain requirements to be met,a good model must imitate certain aspects of the human NAFLD disorder,be reliable and reproducible,have low mortality,and be compatible with a simple and feasible method.Metabolism studies in these models provides a direct reflection of the workings of the cell and may be a useful approach to better understand the initiation and progression of the disease.Metabolomics seems a valid tool for studying metabolic pathways and crosstalk between organs affected in animal models of NAFLD and for the discovery and validation of relevant biomarkers with biological understanding.In this review,we provide a brief introduction to NAFLD hallmarks,the five groups of animal models available for studying NAFLD and the potential role of metabolomics in the study of experimental NAFLD.
基金This work was supported by Jilin Province Youth Talent Support Project(grant number QT202115).
文摘The weakened protective efficacy of COVID-19 vaccines and antibodies caused by SARS-CoV-2 variants presents a global health emergency,which underscores the urgent need for universal therapeutic antibody intervention for clinical patients.Here,we screened three alpacas-derived nanobodies(Nbs)with neutralizing activity from twenty RBD-specific Nbs.The three Nbs were fused with the Fc domain of human IgG,namely aVHH-11-Fc,aVHH-13-Fc and aVHH-14-Fc,which could specifically bind RBD protein and competitively inhibit the binding of ACE2 receptor to RBD.They effectively neutralized SARS-CoV-2 pseudoviruses D614G,Alpha,Beta,Gamma,Delta,and Omicron sub-lineages BA.1,BA.2,BA.4,and BA.5 and authentic SARS-CoV-2 prototype,Delta,and Omicron BA.1,BA.2 strains.In mice-adapted COVID-19 severe model,intranasal administration of aVHH-11-Fc,aVHH-13-Fc and aVHH-14-Fc effectively protected mice from lethal challenges and reduced viral loads in both the upper and lower respiratory tracts.In the COVID-19 mild model,aVHH-13-Fc,which represents the optimal neutralizing activity among the above three Nbs,effectively protected hamsters from the challenge of SARS-CoV-2 prototype,Delta,Omicron BA.1 and BA.2 by significantly reducing viral replication and pathological alterations in the lungs.In structural modeling of aVHH-13 and RBD,aVHH-13 binds to the receptor-binding motif region of RBD and interacts with some highly conserved epitopes.Taken together,our study illustrated that alpaca-derived Nbs offered a therapeutic countermeasure against SARS-CoV-2,including those Delta and Omicron variants which have evolved into global pandemic strains.
基金supported by National Natural Science Foundation of China(No.82274457 and No.82104822)Young Elite Scientists Sponsorship Program by CACM(No.CACM-(2022-QNRC2-B06))+1 种基金Funding for Clinical Research at High-Level Traditional Chinese Medicine Hospitals in China Central(DZMG-QNGG0005)the Fundamental Research Funds for the Central Universities(2025-BUCMXJKY045).
文摘Treating ischemic stroke(IS)presents significant challenges;however,recent advancements suggest that glial cell-derived extracellular vesicles(GD-EVs)may offer a promising therapeutic strategy.This systematic review and meta-analysis evaluated the potential benefits of GD-EVs in IS by synthesizing data from preclinical studies.The review protocol was pre-registered with PROSPERO(CRD42024541149).Comprehensive literature searches were conducted across multiple databases,including PubMed,EMBASE,Web of Science,Cochrane Library,China National Knowledge Infrastructure,VIP Database for Chinese Technical Periodicals,Wanfang Database,and SinoMed,until April 10,2024,to identify relevant studies.Preclinical studies investigating the utilization of GD-EVs in animal models of IS were included.Study quality was assessed using the risk of bias tool from the Systematic Review Center for Laboratory Animal Experimentation.From an initial pool of 3028 studies,11 studies met the inclusion criteria.The analysis demonstrated that GD-EVs significantly improved neurological function,as evidenced by a reduction in the modified neurological severity score(standardized mean difference[SMD]:−1.69,95%confidence interval[CI]:−2.15 to−1.22,p<0.00001,and I2=0%).GD-EVs also significantly reduced infarct volume in rodent models(SMD:−4.78,95%CI:−6.91 to−2.66,p<0.0001,Tau2=0.99,and I2=42%)and decreased brain water content and the release of pro-inflammatory factors post-stroke.The methodological rigor of the included studies indicated sufficiently high overall quality.These findings suggest that GD-EVs hold significant promise as a novel therapeutic approach for IS and warrant further preclinical investigations before translation into clinical trials.
基金supported by the National Basic Research Program of China (Grant Nos. 2011CB944401 and 2010CB945002)the National Natural Science Foundation of China(Grant Nos. 30825015 and 81130009)
文摘The uterus is an indispensable organ for the development of a new life in eutherian mammals.The female mammalian reproductive capacity diminishes with age.In this respect,the senescence of uterine endometrium is convinced to contribute to this failure.This review focuses on the physiological function of the uterus and the related influence of aging mainly in rodent models.A better understanding of the underlying mechanisms governing the process of uterine aging is hoped to generate new strategies to prolong the reproductive lifespan in humans.
文摘Spinal cord injuries （SCI） in rodents have been created by laceration, contusion, compression, or intramedullary injection of toxic agents. The choice of an appropriate SCI model should be made for each study based on the experimental design, with care taken to avoid unintended complications such as hemorrhage. Technical comments will be made in this communication describing the 1） importance of vertebral stabi- lization, 2） injury preparation, and 3） landmarks to improve the preci- sion and reproducibility of the SCI.
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supported by the National Natural Science Foundation of China (31770176)the Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher learningthe Shanghai Rising-Star Program (17QA1403200) for QL
文摘An infection by Zika virus(ZIKV), a mosquito-borne flavivirus, broke out in South American regions in 2015, and recently showed a tendency of spreading to North America and even worldwide. ZIKV was first detected in 1947 and only 14 human infection cases were reported until 2007. This virus was previously observed to cause only mild flu-like symptoms.However, recent ZIKV infections might be responsible for the increasing cases of neurological disorders such as GuillainBarre′ syndrome and congenital defects, including newborn microcephaly. Therefore, researchers have established several animal models to study ZIKV transmission and pathogenesis, and test therapeutic candidates. This review mainly summarizes the reported animal models of ZIKV infection, including mice and non-human primates.
基金supported by grants from the National Natural Science Foundation of China(32271062 and 82305117)Science and Technology Program of Guangzhou,China(2023A04J0458)+1 种基金Guangdong Provincial Key Laboratory of Chinese Medicine for Prevention and Treatment of Refractory Chronic Diseases(2023KT15524)the China Postdoctoral Science Foundation(2024M751343).
文摘The health benefits of physical exercise are well established and have been observed in both human studies and rodent models[1],improving overall health and stress resilience.However,the underlying molecular mechanisms have not been comprehensively investigated.Previous studies have focused extensively on its neuromodulatory effects and have also identified multiple exercise-associated molecular substrates and blood-borne metabolites,including neurotrophic factors,monoamine neurotransmitters,neuroinflammatory cytokines,kynurenine,N-lactoylphenylalanine,and the ketone bodyβ-hydroxybutyrate[2].Notably,lactate,a common energy source derived from cellular glycolysis in response to intensive exercise,has recently been reported to exert antidepressant activity[3].However,a detailed mechanistic explanation is lacking.
基金supported by funding from the School of Dentistry,The University of Sydney.
文摘Background:Although widely used in periodontal research,rodents are naturally resistant to periodontitis.Conventional models,such as ligature-induced periodontitis,often fail to sustain defects due to spontaneous tissue regeneration after ligature removal.To address this,we refined a rat ligature-induced model of experimental periodontitis to better mimic the chronic,progressive nature of human periodontitis.Methods:As a first step,following a split-mouth design,we compared the effectiveness of 3/0 silk thread and 0.008-inch orthodontic wire as ligature materials.Ligatures were applied around the left mandibular first molar for 6,10,and 14 days.Periodontal pocket irrigation was performed every second day using a suspension of P.gingivalis,P.intermedia,and S.gordonii.As a second step,we evaluated whether silk-ligature alone,without human periopathogens,would be sufficient to induce a stable and progressive periodontal lesion.For that purpose,a silk ligature was removed on day 14,and the bone defect dynamics were monitored at 14-,21-,and 28-days post-removal using micro-CT.Results:Both wire and silk ligatures,in combination with bacterial irrigation,effectively induced rapid interproximal alveolar bone loss.However,silk ligature only,without periodontopathogen colonization,resulted in significantly lower bone loss(1.076±0.22 mm vs.2.012±0.374 mm;p=0.003)and the induced alveolar bone defects gradually resolved again over time.Conclusions:The proposed rat model of periodontitis is well characterized and replicates human disease by sustaining colonization with viable periopathogens,leading to progressive disease with alveolar bone loss.The suggested model is straightforward,easy to establish and can be used reliably in preclinical studies.
文摘Functional magnetic resonance imaging(fMRI) is em-ployed in many behavior analysis studies, with blood oxygen level dependent-(BOLD-) contrast imaging being the main method used to generate images. The use of BOLD-contrast imaging in f MRI has been refined over the years, for example, the inclusion of a spin echo pulse and increased magnetic strength were shown to produce better recorded images. Taking careful precautions to control variables during measurement, comparisons between different specimen groups can be illustrated by f MRI imaging using both quantitative and qualitative methods. Differences have been observed in comparisons of active and resting, developing and aging, and defective and damaged brains in various studies. However, cognitive studies using f MRI still face a number of challenges in interpretation that can only be overcome by imaging large numbers of samples. Furthermore, f MRI studies of brain cancer, lesions and other brain pathologies of both humans and animals are still to be explored.
基金supported by the Deutsche Forschungsgemeinshaft (to CJ)。
文摘Schwann cells,the myelinating glia of the peripheral nervous system,wrap axons multiple times to build their myelin sheath.Myelin is of paramount importance for axonal integrity and fast axon potential propagation.However,myelin is lacking or dysfunctional in several neuropathies including demyelinating and dysmyelinating Charcot-M arie-To oth disease.Charcot-Marie-To oth disease represents the most prevalent inherited neuropathy in humans and is classified either as axonal,demyelinating or dysmyelinating,or as intermediate.The demyelinating or dysmyelinating forms of Charcot-Marie-Tooth disease constitute the majority of the disease cases and are most frequently due to mutations in the three following myelin genes:peripheral myelin protein 22,myelin protein ze ro and gap junction beta 1(coding for Connexin 32) causing Charcot-M arie-Tooth disease type 1A,Charcot-Marie-Tooth disease type 1B,and X-linked Charcot-M arie-Tooth disease type 1,respectively.The resulting perturbation of myelin structure and function leads to axonal demyelination or dysmyelination and causes severe disabilities in affected patients.No treatment to cure or slow down the disease progression is currently available on the market,howeve r,scientific discoveries led to a better understanding of the pathomechanisms of the disease and to potential treatment strategies.In this review,we describe the features and molecular mechanisms of the three main demyelinating or dysmyelinating forms of Charcot-Marie-Tooth disease,the rodent models used in research,and the emerging therapeutic approaches to cure or counteract the progression of the disease.
基金funded by an award “Minocycline plus N-acetylcysteine improves brain structure and function after experimental brain injury with clinically useful time window”(NS108190) to PJB
文摘Traumatic brain injury has a complex pathophysiology that produces both rapid and delayed brain damage. Rapid damage initiates immediately after injury. Treatment of traumatic brain injury is typically delayed many hours, thus only delayed damage can be targeted with drugs. Delayed traumatic brain injury includes neuroinflammation, oxidative damage, apoptosis, and glutamate toxicity. Both the speed and complexity of traumatic brain injury pathophysiology present large obstacles to drug development. Repurposing of Food and Drug Administration-approved drugs may be a highly efficient approach to get therapeutics to the clinic. This review examines the preclinical outcomes of minocycline and N-acetylcysteine as individual drugs and compares them to the minocycline plus N-acetylcysteine combination. Both minocycline and N-acetylcysteine are Food and Drug Administration-approved drugs with pleiotropic therapeutic effects. As individual drugs, minocycline and N-acetylcysteine are well tolerated, with known pharmacokinetics, and enter the brain through an intact blood-brain barrier. At concentrations greater than needed for antimicrobial action, minocycline is a potent anti-inflammatory minocycline, also acts as an antioxidant and inhibits multiple enzymes that promote brain injury including metalloproteases, caspases, and polyADP-ribose-polymerase-1. N-acetylcysteine alone is also an antioxidant. It increases brain glutathione, prevents lipid oxidation, and protects mitochondria. N-acetylcysteine also acts as an anti-inflammatory as well as increases extracellular glutamate by activating the X;cystine-glutamate antitransporter. These multiple actions of minocycline and N-acetylcysteine have made them attractive candidates to treat traumatic brain injury. When first dosed within the one hour after injury, either minocycline or N-acetylcysteine improves a diverse set of therapeutic outcome measures in multiple traumatic brain injury animal models. A small number of clinical trials for traumatic brain injury have established the safety of minocycline or N-acetylcysteine and suggested that either drug has some efficacy. Preclinical studies have shown that minocycline plus N-acetylcysteine have positive synergy resulting in therapeutic effects and a more prolonged therapeutic time window not seen with the individual drugs. This review compares the actions of minocycline and N-acetylcysteine, individually and in combination. Evidence supports that the combination has greater utility to treat traumatic brain injury than the individual drugs.
文摘This is a very attractive article. It combines fascinating new methodology with a most interesting dataset, and a highly motivating presentation. However, despite the many
文摘The authors are to be congratulated for an innovative paper in terms of both modelling methodology and subject matter significance. The analysis of short time series is known to be
文摘Although multi-view monitoring techniques have been widely applied in skinned model reconstruction and movement analysis,traditional systems using high-performance Personal Computers(PCs),or industrial cameras are often prohibitive due to high costs and limited scalability.Here,we introduce an affordable,scalable multi-view image acquisition system for skinned model reconstruction in animal studies,utilizing consumer Android devices and a wireless network for synchronized monitoring named Rodent Arena Multi-View Monitor(RAMM).It uses smartphones as camera nodes with local data storage,enabling cost-effective scalability.Its custom synchronization solution and portability make it ideal for research and education in rodent behavior analysis,offering a practical alternative for institutions with limited budgets.Furthermore,the portability and flexibility of this system make it an ideal tool for rodent skinned model research based on multi-view image acquisition.To evaluate the performance,we perform an oscilloscope analysis to ensure effectiveness of synchronization.A 45-camera node setup is built to highlight RAMM’s cost efficiency and ease in constructing large-scale systems.Additionally,the data quality is validated using the Instant Neural Graphics Primitives(Instant-NGP)method.Remarkable results were achieved with a 30.49 dB PSNR by utilizing only 25 images with intrinsic and extrinsic parameters,fulfilling the requirements for well-synchronized data used in 3D representation algorithms.
基金supported by the Natural Science Foundation of China(Key Program:82130035,General Program:81771137,81971103 and 82371308,Youth Program:82201436)the Basic and Applied Basic Research Foundation Natural Science Foundation of Guangdong Province(2021A1515012216)+5 种基金the Medical Scientific Research Foundation of Guangdong Province(A2022093)Sun Yat-sen University Clinical Research 5010 Program(2018001)Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases(2020B1212060017)Guangdong Provincial Clinical Research Center for Neurological Diseases(2020B1111170002)Guangdong Province International Cooperation Base for Early Intervention and Functional Rehabilitation of Neurological Diseases(2020A0505020004)Guangdong Provincial Engineering Center for Major Neurological Disease Treatment,Guangdong Provincial Translational Medicine Innovation Platform for Diagnosis and Treatment of Major Neurological Disease and Guangzhou Clinical Research and Translational Center for Major Neurological Diseases.
文摘Numerous seemingly promising cerebroprotectants previously validated in rodents almost all have failed in stroke clinical trials.The failure of clinical translation strikes an essential need to employ more ideal animal models in stroke research.Compared with the most commonly used rodent models of stroke,non-human primates(NHPs)are far more comparable to humans regarding brain anatomy,functionality and pathological features.The aim of this perspective was to summarise the advantages of NHPs stroke models over rodents,discuss the current limitations of NHPs models,and cast an outlook on the future development of NHPs in stroke preclinical research.
基金funding by the Deutsche Forschungsgemeinschaft(DFG,German Research Foundation)under DFG DE 1546/12-1(M.D.),559839626(M.D.),and 538291523(S.A.M.S.)funding from Ghent University BOF program grant number BOF23/PDO/073funding enabled and organized by Projekt DEAL.
文摘A remarkable study by Guo et al.,published in Cell,suggests a compelling new direction for improving pain management:biased allosteric modulation of the neurotensin receptor 1(NTSR1),using the drug-like molecule SBI-810,promotesβ-arrestin2(βarr2)recruitment while avoiding canonical G protein signaling–thereby providing robust analgesia across a plethora of rodent models of both acute and chronic pain without impairing motor function,cognition,or causing opioid-like dependency.1,2 SBI-810 is introduced as a highly promising molecule underscoring the therapeutic potential of biased and allosteric G protein-coupled receptor(GPCR)ligands to address an urgent unmet medical need.
