Effects of mesenchymal stem cell on dopaminergic neurons,motor and memory functions in animal models of Parkinson's disease:a systematic review and meta-analysis

Parkinson’s disease is chara cterized by the loss of dopaminergic neurons in the substantia nigra pars com pacta,and although restoring striatal dopamine levels may improve symptoms,no treatment can cure or reve rse the disease itself.Stem cell therapy has a regenerative effect and is being actively studied as a candidate for the treatment of Parkinson’s disease.Mesenchymal stem cells are considered a promising option due to fewer ethical concerns,a lower risk of immune rejection,and a lower risk of teratogenicity.We performed a meta-analysis to evaluate the therapeutic effects of mesenchymal stem cells and their derivatives on motor function,memory,and preservation of dopamine rgic neurons in a Parkinson’s disease animal model.We searched bibliographic databases(PubMed/MEDLINE,Embase,CENTRAL,Scopus,and Web of Science)to identify articles and included only pee r-reviewed in vivo interve ntional animal studies published in any language through J une 28,2023.The study utilized the random-effect model to estimate the 95%confidence intervals(CI)of the standard mean differences(SMD)between the treatment and control groups.We use the systematic review center for laboratory animal expe rimentation’s risk of bias tool and the collaborative approach to meta-analysis and review of animal studies checklist for study quality assessment.A total of 33studies with data from 840 Parkinson’s disease model animals were included in the meta-analysis.Treatment with mesenchymal stem cells significantly improved motor function as assessed by the amphetamine-induced rotational test.Among the stem cell types,the bone marrow MSCs with neurotrophic factor group showed la rgest effect size(SMD[95%CI]=-6.21[-9.50 to-2.93],P=0.0001,I^(2)=0.0%).The stem cell treatment group had significantly more tyrosine hydroxylase positive dopamine rgic neurons in the striatum([95%CI]=1.04[0.59 to 1.49],P=0.0001,I^(2)=65.1%)and substantia nigra(SMD[95%CI]=1.38[0.89 to 1.87],P=0.0001,I^(2)=75.3%),indicating a protective effect on dopaminergic neurons.Subgroup analysis of the amphetamine-induced rotation test showed a significant reduction only in the intracranial-striatum route(SMD[95%CI]=-2.59[-3.25 to-1.94],P=0.0001,I^(2)=74.4%).The memory test showed significant improvement only in the intravenous route(SMD[95%CI]=4.80[1.84 to 7.76],P=0.027,I^(2)=79.6%).Mesenchymal stem cells have been shown to positively impact motor function and memory function and protect dopaminergic neurons in preclinical models of Parkinson’s disease.Further research is required to determine the optimal stem cell types,modifications,transplanted cell numbe rs,and delivery methods for these protocols.

Manure substitution improves maize yield by promoting soil fertility and mediating the microbial community in lime concretion black soil

Synthetic nitrogen(N)fertilizer has made a great contribution to the improvement of soil fertility and productivity,but excessive application of synthetic N fertilizer may cause agroecosystem risks,such as soil acidification,groundwater contamination and biodiversity reduction.Meanwhile,organic substitution has received increasing attention for its ecologically and environmentally friendly and productivity benefits.However,the linkages between manure substitution,crop yield and the underlying microbial mechanisms remain uncertain.To bridge this gap,a three-year field experiment was conducted with five fertilization regimes:i)Control,non-fertilization;CF,conventional synthetic fertilizer application;CF_(1/2)M_(1/2),1/2 N input via synthetic fertilizer and 1/2 N input via manure;CF_(1/4)M_(3/4),1/4 N input synthetic fertilizer and 3/4 N input via manure;M,manure application.All fertilization treatments were designed to have equal N input.Our results showed that all manure substituted treatments achieved high soil fertility indexes(SFI)and productivities by increasing the soil organic carbon(SOC),total N(TN)and available phosphorus(AP)concentrations,and by altering the bacterial community diversity and composition compared with CF.SOC,AP,and the soil C:N ratio were mainly responsible for microbial community variations.The co-occurrence network revealed that SOC and AP had strong positive associations with Rhodospirillales and Burkholderiales,while TN and C:N ratio had positive and negative associations with Micromonosporaceae,respectively.These specific taxa are implicated in soil macroelement turnover.Random Forest analysis predicted that both biotic(bacterial composition and Micromonosporaceae)and abiotic(AP,SOC,SFI,and TN)factors had significant effects on crop yield.The present work strengthens our understanding of the effects of manure substitution on crop yield and provides theoretical support for optimizing fertilization strategies.

Immunobiology of COVID-19: Mechanistic and therapeutic insights from animal models

The distribution of the immune system throughout the body complicates in vitro assessments of coronavirus disease 2019(COVID-19)immunobiology,often resulting in a lack of reproducibility when extrapolated to the whole organism.Consequently,developing animal models is imperative for a comprehensive understanding of the pathology and immunology of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.This review summarizes current progress related to COVID-19 animal models,including non-human primates(NHPs),mice,and hamsters,with a focus on their roles in exploring the mechanisms of immunopathology,immune protection,and long-term effects of SARS-CoV-2 infection,as well as their application in immunoprevention and immunotherapy of SARS-CoV-2 infection.Differences among these animal models and their specific applications are also highlighted,as no single model can fully encapsulate all aspects of COVID-19.To effectively address the challenges posed by COVID-19,it is essential to select appropriate animal models that can accurately replicate both fatal and non-fatal infections with varying courses and severities.Optimizing animal model libraries and associated research tools is key to resolving the global COVID-19 pandemic,serving as a robust resource for future emerging infectious diseases.

Genetically modified pigs:Emerging animal models for hereditary hearing loss

Hereditary hearing loss(HHL),a genetic disorder that impairs auditory function,significantly affects quality of life and incurs substantial economic losses for society.To investigate the underlying causes of HHL and evaluate therapeutic outcomes,appropriate animal models are necessary.Pigs have been extensively used as valuable large animal models in biomedical research.In this review,we highlight the advantages of pig models in terms of ear anatomy,inner ear morphology,and electrophysiological characteristics,as well as recent advancements in the development of distinct genetically modified porcine models of hearing loss.Additionally,we discuss the prospects,challenges,and recommendations regarding the use pig models in HHL research.Overall,this review provides insights and perspectives for future studies on HHL using porcine models.

Large animal models for Huntington's disease research

Huntington'sdisease(HD)isahereditary neurodegenerative disorder for which there is currently no effectivetreatmentavailable.Consequently,the development of appropriate disease models is critical to thoroughly investigate disease progression.The genetic basis of HD involves the abnormal expansion of CAG repeats in the huntingtin(HTT)gene,leading to the expansion of a polyglutamine repeat in the HTT protein.Mutant HTT carrying the expanded polyglutamine repeat undergoes misfolding and forms aggregates in the brain,which precipitate selective neuronal loss in specific brain regions.Animal models play an important role in elucidating the pathogenesis of neurodegenerative disorders such as HD and in identifying potential therapeutic targets.Due to the marked species differences between rodents and larger animals,substantial efforts have been directed toward establishing large animal models for HD research.These models are pivotal for advancing the discovery of novel therapeutic targets,enhancing effective drug delivery methods,and improving treatment outcomes.We have explored the advantages of utilizing large animal models,particularly pigs,in previous reviews.Since then,however,significant progress has been made in developing more sophisticated animal models that faithfully replicate the typical pathology of HD.In the current review,we provide a comprehensive overview of large animal models of HD,incorporating recent findings regarding the establishment of HD knock-in(KI)pigs and their genetic therapy.We also explore the utilization of large animal models in HD research,with a focus on sheep,non-human primates(NHPs),and pigs.Our objective is to provide valuable insights into the application of these large animal models for the investigation and treatment of neurodegenerative disorders.

Knee osteoarthritis:A review of animal models and intervention of traditional Chinese medicine

Background:Knee osteoarthritis(KOA)characterized by degeneration of knee cartilage and subsequent bone hyperplasia is a prevalent joint condition primarily affecting aging adults.The pathophysiology of KOA remains poorly understood,as it involves complex mechanisms that result in the same outcome.Consequently,researchers are interested in studying KOA and require appropriate animal models for basic research.Chinese herbal compounds,which consist of multiple herbs with diverse pharmacological properties,possess characteristics such as multicomponent,multipathway,and multitarget effects.The potential benefits in the treatment of KOA continue to attract attention.Purpose:This study aims to provide a comprehensive overview of the advantages,limitations,and specific considerations in selecting different species and methods for KOA animal models.This will help researchers make informed decisions when choosing an animal model.Methods:Online academic databases(e.g.,PubMed,Google Scholar,Web of Science,and CNKI)were searched using the search terms“knee osteoarthritis,”“animal models,”“traditional Chinese medicine,”and their combinations,primarily including KOA studies published from 2010 to 2023.Results:Based on literature retrieval,this review provides a comprehensive overview of the methods of establishing KOA animal models;introduces the current status of advantages and disadvantages of various animal models,including mice,rats,rabbits,dogs,and sheep/goats;and presents the current status of methods used to establish KOA animal models.Conclusion:This study provides a review of the animal models used in recent KOA research,discusses the common modeling methods,and emphasizes the role of traditional Chinese medicine compounds in the treatment of KOA.

Genome-edited rabbits:Unleashing the potential of a promising experimental animal model across diverse diseases

Animal models are extensively used in all aspects of biomedical research,with substantial contributions to our understanding of diseases,the development of pharmaceuticals,and the exploration of gene functions.The field of genome modification in rabbits has progressed slowly.However,recent advancements,particularly in CRISPR/Cas9-related technologies,have catalyzed the successful development of various genome-edited rabbit models to mimic diverse diseases,including cardiovascular disorders,immunodeficiencies,agingrelated ailments,neurological diseases,and ophthalmic pathologies.These models hold great promise in advancing biomedical research due to their closer physiological and biochemical resemblance to humans compared to mice.This review aims to summarize the novel gene-editing approaches currently available for rabbits and present the applications and prospects of such models in biomedicine,underscoring their impact and future potential in translational medicine.

Neurophysiological, histological, and behavioral characterization of animal models of distraction spinal cord injury: a systematic review

Distraction spinal cord injury is caused by some degree of distraction or longitudinal tension on the spinal cord and commonly occurs in patients who undergo corrective operation for severe spinal deformity.With the increased degree and duration of distraction,spinal cord injuries become more serious in terms of their neurophysiology,histology,and behavior.Very few studies have been published on the specific characteristics of distraction spinal cord injury.In this study,we systematically review 22 related studies involving animal models of distraction spinal cord injury,focusing particularly on the neurophysiological,histological,and behavioral characteristics of this disease.In addition,we summarize the mechanisms underlying primary and secondary injuries caused by distraction spinal cord injury and clarify the effects of different degrees and durations of distraction on the primary injuries associated with spinal cord injury.We provide new concepts for the establishment of a model of distraction spinal cord injury and related basic research,and provide reference guidelines for the clinical diagnosis and treatment of this disease.

Finding biomarkers of experience in animals

At a time when there is a growing public interest in animal welfare,it is critical to have objective means to assess the way that an animal experiences a situation.Objectivity is critical to ensure appropriate animal welfare outcomes.Existing behavioural,physiological,and neurobiological indicators that are used to assess animal welfare can verify the absence of extremely negative outcomes.But welfare is more than an absence of negative outcomes and an appropriate indicator should reflect the full spectrum of experience of an animal,from negative to positive.In this review,we draw from the knowledge of human biomedical science to propose a list of candidate biological markers(biomarkers)that should reflect the experiential state of non-human animals.The proposed biomarkers can be classified on their main function as endocrine,oxidative stress,non-coding molecular,and thermobiological markers.We also discuss practical challenges that must be addressed before any of these biomarkers can become useful to assess the experience of an animal in real-life.

Call for Papers from Food Science of Animal Products

Food Science of Animal Products(ISSN:2958-4124,e-ISSN:2958-3780)is a peer-reviewed,open access international journal that publishes the latest research findings in the field of animal-origin foods,involving food materials such as meat,aquatic products,milk,eggs,animal offals and edible insects.

Call for Papers from Food Science of Animal Products

Food Science of Animal Products(ISSN:2958-4124,e-ISSN:2958-3780)is a peer-reviewed,open access international journal that publishes the latest research findings in the field of animal-origin foods,involving food materials such as meat,aquatic products,milk,eggs,animal offals and edible insects.The research scope includes the quality and processing characteristics of food raw materials.

Call for Papers from Food Science of Animal Products

Food Science of Animal Products (ISSN:2958-4124,e-ISSN:2958-3780)is a peer-reviewed,open access international journal that publishes the latest research findings in the field of animal-origin foods,involving food materials such as meat,aquatic products,milk,eggs,animal offals and edible insects.

Animal Model of Aortic Valve Calcification: Their Methodology Helps Us Understand Aortic Valve Calcification

Aortic valve calcification disease (CAVD) is the most prevalent degenerative valve disease in humans, leading to significant morbidity and mortality. Despite its common occurrence, our understanding of the underlying mechanisms remains incomplete, and available treatment options are limited and risky. A more comprehensive understanding of the biology of CAVD is essential to identify new therapeutic strategies. Animal models have played a crucial role in advancing our knowledge of CAVD and exploring potential treatments. However, these models have inherent limitations as they cannot fully replicate the complex physiological mechanisms of human CAVD. In this review, we examine various CAVD models ranging from pigs to mice, highlighting the unique characteristics of each model to enhance our understanding of CAVD. While these models offer valuable insights, they also have limitations and shortcomings. We propose that the guide wire model shows promise for future CAVD research, and streamlining the methodology could enhance our understanding and expand the research scope in this field.

Biodiversity metrics on ecological networks: Demonstrated with animal gastrointestinal microbiomes

Biodiversity has become a terminology familiar to virtually every citizen in modern societies.It is said that ecology studies the economy of nature,and economy studies the ecology of humans;then measuring biodiversity should be similar with measuring national wealth.Indeed,there have been many parallels between ecology and economics,actually beyond analogies.For example,arguably the second most widely used biodiversity metric,Simpson(1949)’s diversity index,is a function of familiar Gini-index in economics.One of the biggest challenges has been the high“diversity”of diversity indexes due to their excessive“speciation”-there are so many indexes,similar to each country’s sovereign currency-leaving confused diversity practitioners in dilemma.In 1973,Hill introduced the concept of“numbers equivalent”,which is based on Renyi entropy and originated in economics,but possibly due to his abstruse interpretation of the concept,his message was not widely received by ecologists until nearly four decades later.What Hill suggested was similar to link the US dollar to gold at the rate of$35 per ounce under the Bretton Woods system.The Hill numbers now are considered most appropriate biodiversity metrics system,unifying Shannon,Simpson and other diversity indexes.Here,we approach to another paradigmatic shift-measuring biodiversity on ecological networks-demonstrated with animal gastrointestinal microbiomes representing four major invertebrate classes and all six vertebrate classes.The network diversity can reveal the diversity of species interactions,which is a necessary step for understanding the spatial and temporal structures and dynamics of biodiversity across environmental gradients.

Animal models of tendon calcification:Past,present,and future

Tendon calcification is a common clinical condition that frequently occurs as a complication after tendon injury and surgery,or as an expression of fibrodysplasia ossificans progressiva.This condition can be referred to by various names in clinical practice and literature,including tendon ossification,tendon mineralization,heterotopic ossification,and calcific tendonitis.The exact pathogenesis of tendon calcification remains uncertain,but current mainstream research suggests that calcification is mostly cell mediated.To further elucidate the pathogenesis of tendon calcification and to better simulate the overall process,selecting appropriate experimental animal models is important.Numerous animal models have been utilized in various clinical studies,each with its own set of advantages and limitations.In this review,we have discussed the advancements made in research on animal models of tendon calcification,with a focus on the selection of experimental animals,the sites of injury in these models,and the methods employed for modeling.

Staphylococcus aureus and biofilms:transmission, threats, and promising strategies in animal husbandry

Staphylococcus aureus(S. aureus) is a common pathogenic bacterium in animal husbandry that can cause diseases such as mastitis, skin infections, arthritis, and other ailments. The formation of biofilms threatens and exacerbates S. aureus infection by allowing the bacteria to adhere to pathological areas and livestock product surfaces, thus triggering animal health crises and safety issues with livestock products. To solve this problem, in this review, we provide a brief overview of the harm caused by S. aureus and its biofilms on livestock and animal byproducts(meat and dairy products). We also describe the ways in which S. aureus spreads in animals and the threats it poses to the livestock industry. The processes and molecular mechanisms involved in biofilm formation are then explained. Finally, we discuss strategies for the removal and eradication of S. aureus and biofilms in animal husbandry, including the use of antimicrobial peptides, plant extracts, nanoparticles, phages, and antibodies. These strategies to reduce the spread of S. aureus in animal husbandry help maintain livestock health and improve productivity to ensure the ecologically sustainable development of animal husbandry and the safety of livestock products.

Production traits and fertility of reciprocal hybrids between Argopecten irradians irradians and A.i.concentricus

The two bay scallop subspecies,Argopecten irradians irradians(NN)and A.i.concentricus(SS),are fast growing and major cultured bivalves in China.However,their relatively small sizes and decreasing production traits caused by long-term inbreeding have been major concerns to the industry in the last two decades.Hybridization between the two bay scallop subspecies may provide a new approach to breed a new variety with superior production traits for the industry.For this end,in this study,we hybridized the two bay scallop subspecies in order to obtain a new strain that incorporates the genes of both subspecies.No significant difference was found in fertilization rate,hatching rate and metamorphosis rate between the purebred and crossbred cohorts(NN♀×SS♂,denoted as NS;SS♀×NN♂,denoted as SN).Both mating strategy(intra-vs.inter-population crosses)and egg origin had significant effects on growth and survival at the larval stage.Heterosis was observed in the crossbred and was more pronounced in older stages.Genetic diversity of the reciprocal hybrids,especially that of SN,was increased compared with the purebred cohorts.Almost all hybrids were completely fertile and able to reproduce by selffertilization or by backcrossing with either parent.Apparently,male sterile individuals whose gonads were fully occupied by the ovary part at mature stage were found in the hybrids for the first time.The hybrids,especially SN,may provide precious germplasm resources for the production of ternary hybrids with the Peruvian scallop,A.purpuratus.

Animal models of eosinophilic esophagitis,review and perspectives

Eosinophilic oesophagitis(EoE)is an allergen/immune-mediated chronic esophageal disease characterized by esophageal mucosal eosinophilic infiltration and esophageal dysfunction.Although the disease was originally attributed to a delayed allergic reaction to allergens and a Th2-type immune response,the exact pathogenesis is complex,and the efficacy of existing treatments is unsatisfactory.Therefore,the study of the pathophysiological process of EOE has received increasing attention.Animal models have been used extensively to study the molecular mechanism of EOE pathogenesis and also provide a preclinical platform for human clinical intervention studies of novel therapeutic agents.To maximize the use of existing animal models of EOE,it is important to understand the advantages or limitations of each modeling approach.This paper systematically describes the selection of experimental animals,types of allergens,and methods of sensitization and excitation during the preparation of animal models of EoE.It also discusses the utility and shortcomings of each model with the aim of providing the latest perspectives on EoE models and leading to better choices of animal models.

Sperm function, mitochondrial activity and in vivo fertility are associated to their mitochondrial DNA content in pigs

Background Despite their low abundance in sperm, mitochondria have diverse functions in this cell type, includ-ing energy production, signalling and calcium regulation. In humans, sperm mitochondrial DNA content(mtDNAc) has been reported to be negatively linked to sperm function and fertility. Yet, the association between mtDNAc and sperm function in livestock remains unexplored. For this reason, this study aimed to shed some light on the link between mtDNAc and sperm function and fertilising potential in pigs. A qPCR method for mtDNAc quantification was optimised for pig sperm, and the association of this parameter with sperm motility, kinematics, mitochondrial activity, and fertility was subsequently interrogated.Results First, the q PCR method was found to be sensitive and efficient for mtDNAc quantification in pig sperm. By using this technique, mtDNAc was observed to be associated to sperm motility, mitochondrial activity and in vivo, but not in vitro, fertility outcomes. Specifically, sperm with low mtDNAc were seen to exhibit greater motility but decreased mitochondrial activity and intracellular reactive oxygen species. Interestingly, samples with lower mtD-NAc showed higher conception and farrowing rates, but similar in vitro fertilisation rates and embryo development, when compared to those with greater mtDNAc.Conclusions These findings enrich our comprehension of the association of mtDNAc with sperm biology, and lay the foundation for future research into employing this parameter as a molecular predictor for sperm function and fer-tility in livestock.

Animal models of hepatitis E infection: Advances and challenges

Hepatitis E virus(HEV)is one of the leading causes of acute viral hepatitis worldwide.Although most of HEV infections are asymptomatic,some patients will develop the symptoms,especially pregnant women,the elderly,and patients with preexisting liver diseases,who often experience anorexia,nausea,vom-iting,malaise,abdominal pain,and jaundice.HEV infection may become chronic in immunosuppressed individuals.In addition,HEV infection can also cause several extrahepatic manifestations.HEV exists in a wide range of hosts in nature and can be transmitted across species.Hence,animals susceptible to HEV can be used as models.The establishment of animal models is of great significance for studying HEV transmission,clinical symptoms,extrahepatic manifestations,and therapeutic strategies,which will help us understand the pathogenesis,prevention,and treatment of hepatitis E.This review summarized the animal models of HEV,including pigs,monkeys,rabbits,mice,rats,and other animals.For each animal species,we provided a concise summary of the HEV genotypes that they can be infected with,the cross-species transmission pathways,as well as their role in studying extrahepatic manifestations,prevention,and treatment of HEV infection.The advantages and disadvantages of these animal models were also emphasized.This review offers new perspectives to enhance the current understanding of the research landscape surrounding HEV animal models.