Concern about the biological hazards involved in microbiological research, especially research involving laboratory animals, has increased in recent years. Working in an animal biosafety level 2 facility （ABSL-2）, c...Concern about the biological hazards involved in microbiological research, especially research involving laboratory animals, has increased in recent years. Working in an animal biosafety level 2 facility （ABSL-2）, commonly used for research on infectious diseases, poses various biological hazards. Here, the regulations and standards related to laboratory biosafety in China are introduced, the potential biological hazards present in ABSL-2 facilities are analyzed, and a series of strategies to control the hazards are presented.展开更多
Laboratory animals and animal experiments are foundations and important support conditions for life sciences, especially for medical research. The animal experiments have drawn extensive attention from the society bec...Laboratory animals and animal experiments are foundations and important support conditions for life sciences, especially for medical research. The animal experiments have drawn extensive attention from the society because of the ethical issue. This paper takes Wenzhou Medical University as an example to give a brief introduction to the ethical review about laboratory animals in the university so as to further draw attention and concerns from the public about the ethical issue of laboratory animals. We successively introduce its scientific projects, nurturing environment and ethical review of laboratory animals.展开更多
The supply and demand of laboratory animals for teaching in colleges and universities has its own internal characteristics.To grasp the supply and demand characteristics of laboratory animals for teaching is of vital ...The supply and demand of laboratory animals for teaching in colleges and universities has its own internal characteristics.To grasp the supply and demand characteristics of laboratory animals for teaching is of vital importance to the planning,supply and use of teaching animals,the realization of teaching objectives and the completion of teaching tasks.Based on the supply of teaching experimental animals and the work of animal experimental teaching in our university in recent years,this paper expounds the inherent characteristics and practice of supply and demand of teaching experimental animals.展开更多
The rodent running-wheel recording apparatus is a reliable approach for studying cir-cadian rhythm.This study demonstrated how to construct a simple and intelligent running-wheel recording system.The running wheel was...The rodent running-wheel recording apparatus is a reliable approach for studying cir-cadian rhythm.This study demonstrated how to construct a simple and intelligent running-wheel recording system.The running wheel was attached to the cage's base,whereas the Hall sensor was attached to the cage's cover.Then,the RJ25 adaptor relayed the running signal to the main control board.Finally,the main control board was connected to the USB port of the computer with the USB connection.Data were collected using the online-accessible,self-created software Magturning.Through Magturning,generated data were saved and exported in real time.Afterward,the device was validated by collecting data on the locomotor activities of mice under dif-ferent light conditions.In conclusion,this new device can record circadian activity of rodents.Our device is appropriate for interdisciplinary investigations related to biological clock research.展开更多
Timothy (Phleum pretense L.) pastures of 3 Total mixed ration (TMR) centers in Hokkaido were selected, the first cutting grasses were continuously collected from the same pastures on different harvest days over 4 year...Timothy (Phleum pretense L.) pastures of 3 Total mixed ration (TMR) centers in Hokkaido were selected, the first cutting grasses were continuously collected from the same pastures on different harvest days over 4 years (2011-2014), and changes in the water soluble carbohydrates (WSC) content were analyzed to investigate the relationship with weather conditions. The harvest days in the 4-year period were June 17-22, June 24-26, June 27-30, and July 2-5, and grasses on these dates were designated as the harvest date groups. The weather data during the cutting period in each year were utilized. The WSC content tended to change yearly and it was significantly lower in the 4 groups (67.3 - 82.1 g/kg DM) in 2011 than in the groups (101.5 - 130.3 g/kg DM) in 2013 excluding the June 24-26 group (P < 0.05, P < 0.01). The WSC content tended to increase as the harvest date progressed in 2011-2013 and it significantly increased even though the harvest date was delayed only in 2013 (P < 0.01). It was suggested that differences in the WSC content among the years were related to the weather condition and dry matter yield of the grass.展开更多
Copper,one of the most prolific transition metals in the body,is required for normal brain physiological activity and allows various functions to work normally through its range of concentrations.Copper homeostasis is...Copper,one of the most prolific transition metals in the body,is required for normal brain physiological activity and allows various functions to work normally through its range of concentrations.Copper homeostasis is meticulously maintained through a complex network of copper-dependent proteins,including copper transporters(CTR1 and CTR2),the two copper ion transporters the Cu-transporting ATPase 1(ATP7A)and Cu-transporting beta(ATP7B),and the three copper chaperones ATOX1,CCS,and COX17.Disruptions in copper homeostasis can lead to either the deficiency or accumulation of copper in brain tissue.Emerging evidence suggests that abnormal copper metabolism or copper binding to various proteins,including ceruloplasmin and metallothionein,is involved in the pathogenesis of neurodegenerative disorders.However,the exact mechanisms underlying these processes are not known.Copper is a potent oxidant that increases reactive oxygen species production and promotes oxidative stress.Elevated reactive oxygen species levels may further compromise mitochondrial integrity and cause mitochondrial dysfunction.Reactive oxygen species serve as key signaling molecules in copper-induced neuroinflammation,with elevated levels activating several critical inflammatory pathways.Additionally,copper can bind aberrantly to several neuronal proteins,including alphasynuclein,tau,superoxide dismutase 1,and huntingtin,thereby inducing neurotoxicity and ultimately cell death.This study focuses on the latest literature evaluating the role of copper in neurodegenerative diseases,with a particular focus on copper-containing metalloenzymes and copper-binding proteins in the regulation of copper homeostasis and their involvement in neurodegenerative disease pathogenesis.By synthesizing the current findings on the functions of copper in oxidative stress,neuroinflammation,mitochondrial dysfunction,and protein misfolding,we aim to elucidate the mechanisms by which copper contributes to a wide range of hereditary and neuronal disorders,such as Wilson's disease,Menkes'disease,Alzheimer's disease,Parkinson's disease,amyotrophic lateral sclerosis,Huntington's disease,and multiple sclerosis.Potential clinically significant therapeutic targets,including superoxide dismutase 1,D-penicillamine,and 5,7-dichloro-2-[(dimethylamino)methyl]-8-hydroxyquinoline,along with their associated therapeutic agents,are further discussed.Ultimately,we collate evidence that copper homeostasis may function in the underlying etiology of several neurodegenerative diseases and offer novel insights into the potential prevention and treatment of these diseases based on copper homeostasis.展开更多
Alzheimer'sdisease(AD)isaprogressive neurodegenerative disorder characterized by cognitive impairment and distinct neuropathological features,including amyloid-βplaques,neurofibrillary tangles,and reactive astrog...Alzheimer'sdisease(AD)isaprogressive neurodegenerative disorder characterized by cognitive impairment and distinct neuropathological features,including amyloid-βplaques,neurofibrillary tangles,and reactive astrogliosis.Developing effective diagnostic,preventative,and therapeutic strategies for AD necessitates the establishment of animal models that accurately recapitulate the pathophysiological processes of the disease.Existing transgenic mouse models have significantly contributed to understanding AD pathology but often fail to replicate the complexity of human AD.Additionally,these models are limited in their ability to elucidate the interplay among amyloid-βplaques,neurofibrillary tangles,and reactive astrogliosis due to the absence of spatially and temporally specific genetic manipulation.In this study,we introduce a novel AD mouse model(APP/PS1-TauP301L-Adeno mice)designed to rapidly induce pathological symptoms and enhance understanding of AD mechanisms.Neurofibrillary tangles and severe reactive astrogliosis were induced by injecting AAVDJ-EF1a-hTauP301L-EGFP and Adeno-GFAP-GFP viruses into the hippocampi of 5-month-old APP/PS1 mice.Three months post-injection,these mice exhibited pronounced astrogliosis,substantial amyloid-βplaque accumulation,extensiveneurofibrillarytangles,accelerated neuronal loss,elevated astrocytic GABA levels,and significant spatial memory deficits.Notably,these pathological features were less severe in AAVTauP301L-expressing APP/PS1 mice without augmented reactive astrogliosis.These findings indicate an exacerbating role of severe reactive astrogliosis in amyloid-βplaque and neurofibrillary tangle-associated pathology.The APP/PS1-TauP301L-Adeno mouse model provides a valuable tool for advancing therapeutic research aimed at mitigating the progression of AD.展开更多
Tongue squamous cell carcinoma(TSCC)is a prevalent malignancy that afflicts the head and neck area and presents a high incidence of metastasis and invasion.Accurate diagnosis and effective treatment are essential for ...Tongue squamous cell carcinoma(TSCC)is a prevalent malignancy that afflicts the head and neck area and presents a high incidence of metastasis and invasion.Accurate diagnosis and effective treatment are essential for enhancing the quality of life and the survival rates of TSCC patients.The current treatment modalities for TSCC frequently suffer from a lack of specificity and efficacy.Nanoparticles with diagnostic and photothermal therapeutic properties may offer a new approach for the targeted therapy of TSCC.However,inadequate accumulation of photosensitizers at the tumor site diminishes the efficacy of photothermal therapy(PTT).This study modified gold nanodots(AuNDs)with the TSCC-targeting peptide HN-1 to improve the selectivity and therapeutic effects of PTT.The Au-HN-1 nanosystem effectively targeted the TSCC cells and was rapidly delivered to the tumor tissues compared to the AuN Ds.The enhanced accumulation of photosensitizing agents at tumor sites achieved significant PTT effects in a mouse model of TSCC.Moreover,owing to its stable long-term fluorescence and high X-ray attenuation coefficient,the Au-HN-1 nanosystem can be used for fluorescence and computed tomography imaging of TSCC,rendering it useful for early tumor detection and accurate delineation of surgical margins.In conclusion,Au-HN-1 represents a promising nanomedicine for imaging-based diagnosis and targeted PTT of TSCC.展开更多
Previous studies have shown that the compound(E)-2-(3,4-dihydroxystyryl)-3-hydroxy-4H-pyran-4-one(D30),a pyromeconic acid derivative,possesses antioxidant and anti-inflammatory properties,inhibits amyloid-β aggregati...Previous studies have shown that the compound(E)-2-(3,4-dihydroxystyryl)-3-hydroxy-4H-pyran-4-one(D30),a pyromeconic acid derivative,possesses antioxidant and anti-inflammatory properties,inhibits amyloid-β aggregation,and alleviates scopolamine-induced cognitive impairment,similar to the phase Ⅲ clinical drug resveratrol.In this study,we established a mouse model of Alzheimer's disease via intracerebroventricular injection of fibrillar amyloid-β to investigate the effect of D30 on fibrillar amyloid-β-induced neuropathology.Our results showed that D30 alleviated fibrillar amyloid-β-induced cognitive impairment,promoted fibrillar amyloid-β clearance from the hippocampus and cortex,suppressed oxidative stress,and inhibited activation of microglia and astrocytes.D30 also reversed the fibrillar amyloid-β-induced loss of dendritic spines and synaptic protein expression.Notably,we demonstrated that exogenous fibrillar amyloid-βintroduced by intracerebroventricular injection greatly increased galectin-3 expression levels in the brain,and this increase was blocked by D30.Considering the role of D30 in clearing amyloid-β,inhibiting neuroinflammation,protecting synapses,and improving cognition,this study highlights the potential of galectin-3 as a promising treatment target for patients with Alzheimer's disease.展开更多
Creutzfeldt-Jakob disease(CJD)is a rare neurodegenerative disorder characterized by abnormalities in the prion protein(PrP),the most common form of human prion disease.Although Genome-Wide Association Studies(GWAS)hav...Creutzfeldt-Jakob disease(CJD)is a rare neurodegenerative disorder characterized by abnormalities in the prion protein(PrP),the most common form of human prion disease.Although Genome-Wide Association Studies(GWAS)have identified numerous risk genes for CJD,the mechanisms underlying these risk loci remain poorly understood.This study aims to elucidate novel genetically prioritized candidate proteins associated with CJD in the human brain through an integrative analytical pipeline.Utilizing datasets from Protein Quantitative Trait Loci(pQTL)(NpQTL1=152,NpQTL2=376),expression QTL(eQTL)(N=452),and the CJD GWAS(NCJD=4110,NControls=13569),we implemented a systematic analytical pipeline.This pipeline included Proteome-Wide Association Study(PWAS),Mendelian randomization(MR),Bayesian colocalization,and Transcriptome-Wide Association Study(TWAS)to identify novel genetically prioritized candidate proteins implicated in CJD pathogenesis within the brain.Through PWAS,we identified that the altered abundance of six brain proteins was significantly associated with CJD.Two genes,STX6 and PDIA4,were established as lead causal genes for CJD,supported by robust evidence(False Discovery Rate<0.05 in MR analysis;PP4/(PP3+PP4)≥0.75 in Bayesian colocalization).Specifically,elevated levels of STX6 and PDIA4 were associated with an increased risk of CJD.Additionally,TWAS demonstrated that STX6 and PDIA4 were associated with CJD at the transcriptional level.展开更多
Mechanical stress modulates bone formation and organization of the extracellular matrix(ECM),the interaction of which affects heterotopic ossification(HO).However,the mechanically sensitive cell populations in HO and ...Mechanical stress modulates bone formation and organization of the extracellular matrix(ECM),the interaction of which affects heterotopic ossification(HO).However,the mechanically sensitive cell populations in HO and the underlying mechanism remain elusive.Here,we show that the mechanical protein Polysyctin-1(PC1,Pkd1)regulates CTSK lineage tendon-derived mesenchymal stem cell(TDMSC)fate and ECM organization,thus affecting HO progression.First,we revealed that CTSK lineage TDMSCs are the major source of osteoblasts and fibroblasts in HO and are responsive to mechanical cues via single-cell RNA sequencing analysis and experiments with a lineage tracing mouse model.Moreover,we showed that PC1 mediates the mechanosignal transduction of CTSK lineage TDMSCs to regulate osteogenic and fibrogenic differentiation and alters the ECM architecture by facilitating TAZ nuclear translocation.Conditional gene depletion of Pkd1 or Taz in CTSK lineage cells and pharmaceutical intervention in the PC1-TAZ axis disrupt osteogenesis,fibrogenesis and ECM organization,and consequently attenuate HO progression.These findings suggest that mechanically sensitive CTSK-lineage TDMSCs contribute to heterotopic ossification through PC1-TAZ signaling axis mediated cell fate determination and ECM organization.展开更多
Rheumatoid arthritis(RA)is an autoimmune disease characterized by inflammation and abnormal osteoclast activation,leading to bone destruction.We previously demonstrated that the large extracellular loop(LEL)of Tm4sf19...Rheumatoid arthritis(RA)is an autoimmune disease characterized by inflammation and abnormal osteoclast activation,leading to bone destruction.We previously demonstrated that the large extracellular loop(LEL)of Tm4sf19 is important for its function in osteoclast differentiation,and LEL-Fc,a competitive inhibitor of Tm4sf19,effectively suppresses osteoclast multinucleation and prevent bone loss associated with osteoporosis.This study aimed to investigate the role of Tm4sf19 in RA,an inflammatory and abnormal osteoclast disease,using a mouse model of collagen-induced arthritis(CIA).Tm4sf19 expression was observed in macrophages and osteoclasts within the inflamed synovium,and Tm4sf19 expression was increased together with inflammatory genes in the joint bones of CIA-induced mice compared with the sham control group.Inhibition of Tm4sf19 by LEL-Fc demonstrated both preventive and therapeutic effects in a CIA mouse model,reducing the CIA score,swelling,inflammation,cartilage damage,and bone damage.Knockout of Tm4sf19 gene or inhibition of Tm4sf19 activity by LEL-Fc suppressed LPS/IFN-γ-induced TLR4-mediated inflammatory signaling in macrophages.LEL-Fc disrupted not only the interaction between Tm4sf19 and TLR4/MD2,but also the interaction between TLR4 and MD2.μCT analysis showed that LEL-Fc treatment significantly reduced joint bone destruction and bone loss caused by hyperactivated osteoclasts in CIA mice.Taken together,these findings suggest that LELFc may be a potential treatment for RA and RA-induced osteoporosis by simultaneously targeting joint inflammation and bone destruction caused by abnormal osteoclast activation.展开更多
A decomposable and sono-enzyme co-triggered nanoparticle(p TCP-CR NP)with“AND gate”logic was synthesized,combining a meso–carboxyl-porphyrin-based sonosensitizer(5,10,15,20-tetrakis(carboxyl)porphyrin,TCP)and a thi...A decomposable and sono-enzyme co-triggered nanoparticle(p TCP-CR NP)with“AND gate”logic was synthesized,combining a meso–carboxyl-porphyrin-based sonosensitizer(5,10,15,20-tetrakis(carboxyl)porphyrin,TCP)and a thiophenyl-croconium(2,5-bis[(2-(2-(2-hydroxyethoxy)ethoxy)ethyl-4-carboxylate-piperidylamino)thiophenyl]-croconium,CR)via ester groups.TCP releases carbon monoxide(CO)under ultrasound(US)irradiation,offering both sonodynamic and gas therapy.CR decomposes into stronger reactive oxygen species(ROS)compared to oxygen-based radicals.The F?rster resonance energy transfer(FRET)effect between TCP and CR inhibits ROS and CO generation until triggered by tumor cell overexpressed carboxylesterase(CEs).p TCP-CR NPs“AND gate”logic ensures activation only in the presence of both CEs and US,targeting tumor cells while safety in normal tissues.The ROS and CO generation abilities,as well as the releasing of SO_(4)^(·-)have been systemically examined.p TCP-CR can be thoroughly decomposed into low-toxic molecules post the treatment,showing the safety with negligible phototoxic reactions.In vivo anti-cancer therapy has been evaluated using mice bearing hepatocellular carcinoma.展开更多
OBJECTIVE:To explore the mechanism of action of Tiaogeng decoction(调更汤,TG)in alleviating oxidative stress damage in the hippocampus of a mouse model of cognitive impairment.METHODS:Amyloid precursor protein/preseni...OBJECTIVE:To explore the mechanism of action of Tiaogeng decoction(调更汤,TG)in alleviating oxidative stress damage in the hippocampus of a mouse model of cognitive impairment.METHODS:Amyloid precursor protein/presenilin-1(APP/PS1)transgenic female mice were randomly divided into model,estradiol valerate,low-,medium-,and high-dose TG groups,female C57 mice were used as the control group(n=12/group).After 12 weeks of treatment,the behavior of mice was tested with the Morris water maze,and brain tissue samples were collected,and changes in hippocampal neurons were observed using electron microscopy.The deposition of beta-amyloid protein(Aβ)amyloid plaques in the hippocampus was determined by light microscopy.Aβ1-42 protein levels were detected through immunofluorescence.Oxidative stress indicators in the hippocampus were detected by enzyme linked immunosorbent assay.The expressions of nuclear factor-erythroid 2-related factor 2(Nrf2),c-Jun N-terminal kinase(JNK),phospho-JNK(p-JNK),B-cell lymphoma-2(Bcl-2),caspase-9,and cleaved caspase-9 were detected by Western blot.Hippocampal cell apoptosis was detected using the terminal deoxynucleotidyl transferase-mediated nick end Labeling.RESULTS:TG improved the cognitive function of APP/PS1 mice,as judged by improvements in several indices from the Morris water maze test.TG increased Nrf2,superoxide dismutase,and heme oxygenase-1 protein expression and reduced malondialdelyde and reactive oxygen species expression.TG also inhibited the expression of JNK proteins,upregulated the expression of Bcl-2,and downregulated the expression of caspase-9,reducing cell apoptosis.TG decreased the percentage of the hippocampal cornu ammonis 1 area positive for Aβ1-42,reducing mitochondrial damage caused by oxidative stress and Aβprotein deposition.CONCLUSIONS:TG may improve memory ability while reducing oxidative stress and apoptosis.It also reduces Aβprotein deposition in the hippocampus,protecting the central nervous system and improving memory function.TG may reduce the risk of AD.展开更多
Background:Makorin ring finger protein 3 gene(MKRN3)gene mutation is the most common genetic cause of central precocious puberty(CPP)in children.Due to the lack of ideal MKRN3-modified animal model(MKRN3-modified mice...Background:Makorin ring finger protein 3 gene(MKRN3)gene mutation is the most common genetic cause of central precocious puberty(CPP)in children.Due to the lack of ideal MKRN3-modified animal model(MKRN3-modified mice enter puberty only 4–5 days earlier than normal mice),the related research is limited.Methods:Therefore,the MKRN3-modified rabbit was developed using CRISPR(clus-tered regularly interspaced short palindromic repeats)gene editing technology.The genotype identification and phenotype evaluation of MKRN3-modified rabbits were carried out.Results:The first estrus of MKRN3-modified female rabbits was observed~27 days earlier than that of wild-type female rabbits,with a typical CPP phenotype.This study found increased gonadotropin releasing hormone(GnRH)and decreased gonadotropin inhibiting hormone(GnIH)in the hypothalamus of the CPP rabbit model with MKRN3 gene mutation.Although this study failed to fully clarify the pathogenesis of CPP caused by MKRN3 mutation,it found some differentially expressed genes and potential pathways through transcriptome sequencing.Conclusions:This study established a novel CPP model:paternal MKRN3 gene-modified rabbit.It is hoped that the establishment of this model will help researchers better understand,treat,and prevent CPP in the future.展开更多
Experimental mice play a critical role in biomedical research.The phenotype and application of different substrains vary due to genetic differentiation and variation.To ensure validity and reliability of results,it is...Experimental mice play a critical role in biomedical research.The phenotype and application of different substrains vary due to genetic differentiation and variation.To ensure validity and reliability of results,it is imperative to adhere to standardized experiments and controls.This paper objectively reviews the origin,differentiation,and phenotypic and genetic differences between the C57BL/6 and BALB/c mouse substrains.Furthermore,an optimal selection strategy is proposed based on the genetic quality control technology to facilitate the precise application of these two mouse substrains.展开更多
Dysfunction of drug transporters significantly affects therapeutic outcomes and drug efficacy in patients with liver injury.Clinical and experimental evidence demonstrates that liver injury involves complex inter-orga...Dysfunction of drug transporters significantly affects therapeutic outcomes and drug efficacy in patients with liver injury.Clinical and experimental evidence demonstrates that liver injury involves complex inter-organ interactions among the brain,eye,liver,intestine,and kidney.Recent advances in basic and clinical research have illuminated the physiologic and molecular mechanisms underlying transporter alterations in liver injury,particularly those associated with bilirubin,reactive oxygen species,ammonia,bile acid,and inflammatory factors.Notably,the influence of these transporter modifications on drug pharmacokinetics in liver injury patients remains inadequately understood.Additional research is necessary to fully comprehend these effects and their therapeutic implications.The documented alterations of transporters in distant organs across various liver diseases indicate that dosage modifications may be required when administering transporter-substrate drugs,including both traditional Chinese and Western medicines,to patients with liver dysfunction.This strategy helps maintain drug concentrations within therapeutic ranges while reducing adverse reactions.Furthermore,when utilizing transporter inducers or inhibitors clinically,consideration of their long-term effects on transporters and subsequent therapeutic impact is essential.Careful attention must be paid to avoid compromising the elimination of toxic metabolites and proteins when inhibiting these transporters.Similarly,prudent use of inducers or inducertype therapeutic drugs is necessary to prevent enhanced drug resistance.This review examines recent clinical and experimental findings regarding the inter-organ interaction of drug transporters in liver injury conditions and their clinical relevance.展开更多
Chinese hamster with Chinese characteristics is used in experiments,and it is of great value in the field of medical biology research.However,at present,there is no high-efficiency method for evaluating the genetic qu...Chinese hamster with Chinese characteristics is used in experiments,and it is of great value in the field of medical biology research.However,at present,there is no high-efficiency method for evaluating the genetic quality of Chinese hamsters.Here,we developed a novel Chinese hamster genetic quality detection system using single-nucleotide polymorphism(SNP)markers.To find SNP loci,we conducted whole genome sequencing on 24 Chinese hamsters.Then,we employed an SNP locus screening criterion that we set up previously and initially screened 214 SNP loci with wide genome distribution and high polymorphism level.Subsequently,we developed the SNP detection system using a multitarget region capture technique based on second-generation sequencing,and a 55 SNP panel for genetic evaluation of Chinese hamster populations was developed.PopGen.32.analysis results showed that the average effective allele number,Shannon index,observed heterozygosity,expected heterozygosity,average heterozygosity,polymorphism information,and other genetic parameters of Chinese hamster population A were higher than those in population B.Using scientific screening and optimization,we successfully developed a novel Chinese hamster SNP genetic detection system that can efficiently and accurately analyze the genetic quality of the Chinese hamster population.展开更多
Glioma is a severe malignant brain tumor marked by an exceedingly dire prognosis and elevated incidence of recurrence.The resilience of such tumors to chemotherapeutic agents,coupled with the formidable obstacle the b...Glioma is a severe malignant brain tumor marked by an exceedingly dire prognosis and elevated incidence of recurrence.The resilience of such tumors to chemotherapeutic agents,coupled with the formidable obstacle the blood-brain barrier(BBB)presents to most pharmacological interventions are major challenges in anti-glioma therapy.In an endeavor to surmount these impediments,we have synergized pH-sensitive nanoparticles carrying doxorubicin and apatinib to amplify the anti-neoplastic efficacy with cyclic arginine-glycine-aspartate acid(cRGD)modification.In this study,we found that the combination of doxorubicin(DOX)and apatinib(AP)showed a significant synergistic effect,achieved through cytotoxicity and induction of apoptosis,which might be due to the increased intracellular uptake of DOX following AP treatment.Besides,polycaprolactone-polyethylene glycol-cRGD(PCL-PEG-cRGD)drug carrier could cross the BBB by its targeting ability,and then deliver the drug to the glioma site via pH-responsive release,increasing the concentration of the drugs in the tumor.Meanwhile,DOX/AP-loaded PCL-PEGcRGD nanoparticles effectively inhibited cell proliferation,enhanced glioma cell apoptosis,and retarded tumor growth in vivo.These results collectively identified DOX/AP-loaded PCL-PEG-cRGD nanoparticles as a promising therapeutic candidate for the treatment of glioma.展开更多
Avian metapneumovirus(aMPV),a paramyxovirus,causes acute respiratory diseases in turkeys and swollen head syndrome in chickens.This study established a reverse genetics system for aMPV subtype B LN16-A strain based on...Avian metapneumovirus(aMPV),a paramyxovirus,causes acute respiratory diseases in turkeys and swollen head syndrome in chickens.This study established a reverse genetics system for aMPV subtype B LN16-A strain based on T7 RNA polymerase.Full-length cDNA of the LN16-A strain was constructed by assembling 5 cDNA fragments between the T7 promoter and hepatitis delta virus ribozyme.Transfection of this plasmid,along with the supporting plasmids encoding the N,P,M2-1,and L proteins of LN16-A into BSR-T7/5 cells,resulted in the recovery of aMPV subtype B.To identify an effective insertion site,the enhanced green fluorescent protein(EGFP)gene was inserted into different sites of the LN16-A genome to generate recombinant LN16-As.The results showed that the expression levels of EGFP at the site between the G and L genes of LN16-A were significantly higher than those at the other two sites(between the leader and N genes or replacing the SH gene).To verify the availability of the site between G and L for foreign gene expression,the VP2 gene of very virulent infectious bursal disease virus(vvIBDV)was inserted into this site,and recombinant LN16-A(rLN16A-vvVP2)was successfully rescued.Single immunization of specificpathogen-free chickens with rLN16A-vvVP2 induced high levels of neutralizing antibodies and provided 100%protection against the virulent aMPV subtype B and vvIBDV.Establishing a reverse genetics system here provides an important foundation for understanding aMPV pathogenesis and developing novel vector vaccines.展开更多
基金supported by the National Science and Technology Major Projects of Infectious Disease(2012ZX10004-404)
文摘Concern about the biological hazards involved in microbiological research, especially research involving laboratory animals, has increased in recent years. Working in an animal biosafety level 2 facility （ABSL-2）, commonly used for research on infectious diseases, poses various biological hazards. Here, the regulations and standards related to laboratory biosafety in China are introduced, the potential biological hazards present in ABSL-2 facilities are analyzed, and a series of strategies to control the hazards are presented.
基金supported by fund of science and technology project of Wenzhou(Y20140601)
文摘Laboratory animals and animal experiments are foundations and important support conditions for life sciences, especially for medical research. The animal experiments have drawn extensive attention from the society because of the ethical issue. This paper takes Wenzhou Medical University as an example to give a brief introduction to the ethical review about laboratory animals in the university so as to further draw attention and concerns from the public about the ethical issue of laboratory animals. We successively introduce its scientific projects, nurturing environment and ethical review of laboratory animals.
文摘The supply and demand of laboratory animals for teaching in colleges and universities has its own internal characteristics.To grasp the supply and demand characteristics of laboratory animals for teaching is of vital importance to the planning,supply and use of teaching animals,the realization of teaching objectives and the completion of teaching tasks.Based on the supply of teaching experimental animals and the work of animal experimental teaching in our university in recent years,this paper expounds the inherent characteristics and practice of supply and demand of teaching experimental animals.
基金Startup Fund for scientific research,Fujian Medical University,Grant/Award Number:2020QH1039Joint Funds for the Innovation of Science and Technology,Fujian Province,Grant/Award Number:2020Y9114 and 2020Y9119。
文摘The rodent running-wheel recording apparatus is a reliable approach for studying cir-cadian rhythm.This study demonstrated how to construct a simple and intelligent running-wheel recording system.The running wheel was attached to the cage's base,whereas the Hall sensor was attached to the cage's cover.Then,the RJ25 adaptor relayed the running signal to the main control board.Finally,the main control board was connected to the USB port of the computer with the USB connection.Data were collected using the online-accessible,self-created software Magturning.Through Magturning,generated data were saved and exported in real time.Afterward,the device was validated by collecting data on the locomotor activities of mice under dif-ferent light conditions.In conclusion,this new device can record circadian activity of rodents.Our device is appropriate for interdisciplinary investigations related to biological clock research.
文摘Timothy (Phleum pretense L.) pastures of 3 Total mixed ration (TMR) centers in Hokkaido were selected, the first cutting grasses were continuously collected from the same pastures on different harvest days over 4 years (2011-2014), and changes in the water soluble carbohydrates (WSC) content were analyzed to investigate the relationship with weather conditions. The harvest days in the 4-year period were June 17-22, June 24-26, June 27-30, and July 2-5, and grasses on these dates were designated as the harvest date groups. The weather data during the cutting period in each year were utilized. The WSC content tended to change yearly and it was significantly lower in the 4 groups (67.3 - 82.1 g/kg DM) in 2011 than in the groups (101.5 - 130.3 g/kg DM) in 2013 excluding the June 24-26 group (P < 0.05, P < 0.01). The WSC content tended to increase as the harvest date progressed in 2011-2013 and it significantly increased even though the harvest date was delayed only in 2013 (P < 0.01). It was suggested that differences in the WSC content among the years were related to the weather condition and dry matter yield of the grass.
基金supported by the Notional Natural Science Foundation of Chino,No.82160690Colloborotive Innovation Center of Chinese Ministry of Education,No.2020-39Science and Technology Foundation of Guizhou Province,No.ZK[2021]-014(all to FZ)。
文摘Copper,one of the most prolific transition metals in the body,is required for normal brain physiological activity and allows various functions to work normally through its range of concentrations.Copper homeostasis is meticulously maintained through a complex network of copper-dependent proteins,including copper transporters(CTR1 and CTR2),the two copper ion transporters the Cu-transporting ATPase 1(ATP7A)and Cu-transporting beta(ATP7B),and the three copper chaperones ATOX1,CCS,and COX17.Disruptions in copper homeostasis can lead to either the deficiency or accumulation of copper in brain tissue.Emerging evidence suggests that abnormal copper metabolism or copper binding to various proteins,including ceruloplasmin and metallothionein,is involved in the pathogenesis of neurodegenerative disorders.However,the exact mechanisms underlying these processes are not known.Copper is a potent oxidant that increases reactive oxygen species production and promotes oxidative stress.Elevated reactive oxygen species levels may further compromise mitochondrial integrity and cause mitochondrial dysfunction.Reactive oxygen species serve as key signaling molecules in copper-induced neuroinflammation,with elevated levels activating several critical inflammatory pathways.Additionally,copper can bind aberrantly to several neuronal proteins,including alphasynuclein,tau,superoxide dismutase 1,and huntingtin,thereby inducing neurotoxicity and ultimately cell death.This study focuses on the latest literature evaluating the role of copper in neurodegenerative diseases,with a particular focus on copper-containing metalloenzymes and copper-binding proteins in the regulation of copper homeostasis and their involvement in neurodegenerative disease pathogenesis.By synthesizing the current findings on the functions of copper in oxidative stress,neuroinflammation,mitochondrial dysfunction,and protein misfolding,we aim to elucidate the mechanisms by which copper contributes to a wide range of hereditary and neuronal disorders,such as Wilson's disease,Menkes'disease,Alzheimer's disease,Parkinson's disease,amyotrophic lateral sclerosis,Huntington's disease,and multiple sclerosis.Potential clinically significant therapeutic targets,including superoxide dismutase 1,D-penicillamine,and 5,7-dichloro-2-[(dimethylamino)methyl]-8-hydroxyquinoline,along with their associated therapeutic agents,are further discussed.Ultimately,we collate evidence that copper homeostasis may function in the underlying etiology of several neurodegenerative diseases and offer novel insights into the potential prevention and treatment of these diseases based on copper homeostasis.
基金supported by the National Research Foundation of Korea (NRF)funded by the Ministry of Science,ICT&Future Planning (2022R1A2C2006229,2022R1A6A3A01086868)Korea Dementia Research Project through the Korea Dementia Research Center (KDRC)funded by the Ministry of Health&Welfare and Ministry of Science and ICT,Republic of Korea (RS-2024-00345328)KIST Institutional Grant (2E32851)。
文摘Alzheimer'sdisease(AD)isaprogressive neurodegenerative disorder characterized by cognitive impairment and distinct neuropathological features,including amyloid-βplaques,neurofibrillary tangles,and reactive astrogliosis.Developing effective diagnostic,preventative,and therapeutic strategies for AD necessitates the establishment of animal models that accurately recapitulate the pathophysiological processes of the disease.Existing transgenic mouse models have significantly contributed to understanding AD pathology but often fail to replicate the complexity of human AD.Additionally,these models are limited in their ability to elucidate the interplay among amyloid-βplaques,neurofibrillary tangles,and reactive astrogliosis due to the absence of spatially and temporally specific genetic manipulation.In this study,we introduce a novel AD mouse model(APP/PS1-TauP301L-Adeno mice)designed to rapidly induce pathological symptoms and enhance understanding of AD mechanisms.Neurofibrillary tangles and severe reactive astrogliosis were induced by injecting AAVDJ-EF1a-hTauP301L-EGFP and Adeno-GFAP-GFP viruses into the hippocampi of 5-month-old APP/PS1 mice.Three months post-injection,these mice exhibited pronounced astrogliosis,substantial amyloid-βplaque accumulation,extensiveneurofibrillarytangles,accelerated neuronal loss,elevated astrocytic GABA levels,and significant spatial memory deficits.Notably,these pathological features were less severe in AAVTauP301L-expressing APP/PS1 mice without augmented reactive astrogliosis.These findings indicate an exacerbating role of severe reactive astrogliosis in amyloid-βplaque and neurofibrillary tangle-associated pathology.The APP/PS1-TauP301L-Adeno mouse model provides a valuable tool for advancing therapeutic research aimed at mitigating the progression of AD.
基金supported by the Science and Technology Projects of Jilin Provincial Department of Science and Technology(Grant/Award Numbers:20240305037YY)National Key Research and Development Program of China(2021YFC2400603)+1 种基金the Joint Funds of the National Natural Science Foundation of China(Grant No.U23A20269)the Jilin University young teachers and students cross-disciplinary training project(Grant No.2023-JCXK-08,2024-JCXK-07)。
文摘Tongue squamous cell carcinoma(TSCC)is a prevalent malignancy that afflicts the head and neck area and presents a high incidence of metastasis and invasion.Accurate diagnosis and effective treatment are essential for enhancing the quality of life and the survival rates of TSCC patients.The current treatment modalities for TSCC frequently suffer from a lack of specificity and efficacy.Nanoparticles with diagnostic and photothermal therapeutic properties may offer a new approach for the targeted therapy of TSCC.However,inadequate accumulation of photosensitizers at the tumor site diminishes the efficacy of photothermal therapy(PTT).This study modified gold nanodots(AuNDs)with the TSCC-targeting peptide HN-1 to improve the selectivity and therapeutic effects of PTT.The Au-HN-1 nanosystem effectively targeted the TSCC cells and was rapidly delivered to the tumor tissues compared to the AuN Ds.The enhanced accumulation of photosensitizing agents at tumor sites achieved significant PTT effects in a mouse model of TSCC.Moreover,owing to its stable long-term fluorescence and high X-ray attenuation coefficient,the Au-HN-1 nanosystem can be used for fluorescence and computed tomography imaging of TSCC,rendering it useful for early tumor detection and accurate delineation of surgical margins.In conclusion,Au-HN-1 represents a promising nanomedicine for imaging-based diagnosis and targeted PTT of TSCC.
基金supported by the Research Foundation for Talented Scholars of Fujian Medical University,No.XRCZX2018014(to DZ)Startup Fund for Scientific Research,Fujian Medical University,No.2019QH1017(to CW)the Natural Science Foundation of Fujian Province,China,Nos.2021J01693(to DZ),2021J02032(to ZCY)。
文摘Previous studies have shown that the compound(E)-2-(3,4-dihydroxystyryl)-3-hydroxy-4H-pyran-4-one(D30),a pyromeconic acid derivative,possesses antioxidant and anti-inflammatory properties,inhibits amyloid-β aggregation,and alleviates scopolamine-induced cognitive impairment,similar to the phase Ⅲ clinical drug resveratrol.In this study,we established a mouse model of Alzheimer's disease via intracerebroventricular injection of fibrillar amyloid-β to investigate the effect of D30 on fibrillar amyloid-β-induced neuropathology.Our results showed that D30 alleviated fibrillar amyloid-β-induced cognitive impairment,promoted fibrillar amyloid-β clearance from the hippocampus and cortex,suppressed oxidative stress,and inhibited activation of microglia and astrocytes.D30 also reversed the fibrillar amyloid-β-induced loss of dendritic spines and synaptic protein expression.Notably,we demonstrated that exogenous fibrillar amyloid-βintroduced by intracerebroventricular injection greatly increased galectin-3 expression levels in the brain,and this increase was blocked by D30.Considering the role of D30 in clearing amyloid-β,inhibiting neuroinflammation,protecting synapses,and improving cognition,this study highlights the potential of galectin-3 as a promising treatment target for patients with Alzheimer's disease.
文摘Creutzfeldt-Jakob disease(CJD)is a rare neurodegenerative disorder characterized by abnormalities in the prion protein(PrP),the most common form of human prion disease.Although Genome-Wide Association Studies(GWAS)have identified numerous risk genes for CJD,the mechanisms underlying these risk loci remain poorly understood.This study aims to elucidate novel genetically prioritized candidate proteins associated with CJD in the human brain through an integrative analytical pipeline.Utilizing datasets from Protein Quantitative Trait Loci(pQTL)(NpQTL1=152,NpQTL2=376),expression QTL(eQTL)(N=452),and the CJD GWAS(NCJD=4110,NControls=13569),we implemented a systematic analytical pipeline.This pipeline included Proteome-Wide Association Study(PWAS),Mendelian randomization(MR),Bayesian colocalization,and Transcriptome-Wide Association Study(TWAS)to identify novel genetically prioritized candidate proteins implicated in CJD pathogenesis within the brain.Through PWAS,we identified that the altered abundance of six brain proteins was significantly associated with CJD.Two genes,STX6 and PDIA4,were established as lead causal genes for CJD,supported by robust evidence(False Discovery Rate<0.05 in MR analysis;PP4/(PP3+PP4)≥0.75 in Bayesian colocalization).Specifically,elevated levels of STX6 and PDIA4 were associated with an increased risk of CJD.Additionally,TWAS demonstrated that STX6 and PDIA4 were associated with CJD at the transcriptional level.
基金National Natural Science Foundation of China(Grant Nos.82261160397,82272560)Central South University Research Programme of Advanced Interdisciplinary Studies(2023QYJC011)+4 种基金National Natural Science Foundation of China(Grant Nos.82472521,81922017)Hunan Provincial Science and Technology Department(2023JJ30896)Key Research and Development Program of Hunan Province(2022SK2023)Science and Technology Innovation Program of Hunan Province(2023RC1027)Major Basic Research Projects in Hunan Province(No.2024JC0004)。
文摘Mechanical stress modulates bone formation and organization of the extracellular matrix(ECM),the interaction of which affects heterotopic ossification(HO).However,the mechanically sensitive cell populations in HO and the underlying mechanism remain elusive.Here,we show that the mechanical protein Polysyctin-1(PC1,Pkd1)regulates CTSK lineage tendon-derived mesenchymal stem cell(TDMSC)fate and ECM organization,thus affecting HO progression.First,we revealed that CTSK lineage TDMSCs are the major source of osteoblasts and fibroblasts in HO and are responsive to mechanical cues via single-cell RNA sequencing analysis and experiments with a lineage tracing mouse model.Moreover,we showed that PC1 mediates the mechanosignal transduction of CTSK lineage TDMSCs to regulate osteogenic and fibrogenic differentiation and alters the ECM architecture by facilitating TAZ nuclear translocation.Conditional gene depletion of Pkd1 or Taz in CTSK lineage cells and pharmaceutical intervention in the PC1-TAZ axis disrupt osteogenesis,fibrogenesis and ECM organization,and consequently attenuate HO progression.These findings suggest that mechanically sensitive CTSK-lineage TDMSCs contribute to heterotopic ossification through PC1-TAZ signaling axis mediated cell fate determination and ECM organization.
基金supported by GILO Foundation.This research is in part supported by Korea Drug Development Fund funded by Ministry of Science and ICT,Ministry of Trade,Industry,and Energy,and Ministry of Health and Welfare(RS-2023-00282595,Republic of Korea).
文摘Rheumatoid arthritis(RA)is an autoimmune disease characterized by inflammation and abnormal osteoclast activation,leading to bone destruction.We previously demonstrated that the large extracellular loop(LEL)of Tm4sf19 is important for its function in osteoclast differentiation,and LEL-Fc,a competitive inhibitor of Tm4sf19,effectively suppresses osteoclast multinucleation and prevent bone loss associated with osteoporosis.This study aimed to investigate the role of Tm4sf19 in RA,an inflammatory and abnormal osteoclast disease,using a mouse model of collagen-induced arthritis(CIA).Tm4sf19 expression was observed in macrophages and osteoclasts within the inflamed synovium,and Tm4sf19 expression was increased together with inflammatory genes in the joint bones of CIA-induced mice compared with the sham control group.Inhibition of Tm4sf19 by LEL-Fc demonstrated both preventive and therapeutic effects in a CIA mouse model,reducing the CIA score,swelling,inflammation,cartilage damage,and bone damage.Knockout of Tm4sf19 gene or inhibition of Tm4sf19 activity by LEL-Fc suppressed LPS/IFN-γ-induced TLR4-mediated inflammatory signaling in macrophages.LEL-Fc disrupted not only the interaction between Tm4sf19 and TLR4/MD2,but also the interaction between TLR4 and MD2.μCT analysis showed that LEL-Fc treatment significantly reduced joint bone destruction and bone loss caused by hyperactivated osteoclasts in CIA mice.Taken together,these findings suggest that LELFc may be a potential treatment for RA and RA-induced osteoporosis by simultaneously targeting joint inflammation and bone destruction caused by abnormal osteoclast activation.
基金supported by grants from the National Natural Science Foundation of China(No.22375027)the Natural Science Foundation of Jiangsu Province(Nos.BK20221265,BK20211100)+1 种基金the Fundamental Research Funds for the Central Universities(No.DUT23YG133)the Research Funds from Liaoning Cancer Hospital(No.2024ZLKF-35)。
文摘A decomposable and sono-enzyme co-triggered nanoparticle(p TCP-CR NP)with“AND gate”logic was synthesized,combining a meso–carboxyl-porphyrin-based sonosensitizer(5,10,15,20-tetrakis(carboxyl)porphyrin,TCP)and a thiophenyl-croconium(2,5-bis[(2-(2-(2-hydroxyethoxy)ethoxy)ethyl-4-carboxylate-piperidylamino)thiophenyl]-croconium,CR)via ester groups.TCP releases carbon monoxide(CO)under ultrasound(US)irradiation,offering both sonodynamic and gas therapy.CR decomposes into stronger reactive oxygen species(ROS)compared to oxygen-based radicals.The F?rster resonance energy transfer(FRET)effect between TCP and CR inhibits ROS and CO generation until triggered by tumor cell overexpressed carboxylesterase(CEs).p TCP-CR NPs“AND gate”logic ensures activation only in the presence of both CEs and US,targeting tumor cells while safety in normal tissues.The ROS and CO generation abilities,as well as the releasing of SO_(4)^(·-)have been systemically examined.p TCP-CR can be thoroughly decomposed into low-toxic molecules post the treatment,showing the safety with negligible phototoxic reactions.In vivo anti-cancer therapy has been evaluated using mice bearing hepatocellular carcinoma.
基金Supported by Natural Science Foundation-funded Project:Mechanism of Tiaogeng Decoction improving Cognitive Function via Regulating Nuclear Factor-erythroid 2-related Factor 2/c-Jun N-terminal kinase/Aβ Oxidative Stress Network in Hippocampus Neurons (No. 81874482)
文摘OBJECTIVE:To explore the mechanism of action of Tiaogeng decoction(调更汤,TG)in alleviating oxidative stress damage in the hippocampus of a mouse model of cognitive impairment.METHODS:Amyloid precursor protein/presenilin-1(APP/PS1)transgenic female mice were randomly divided into model,estradiol valerate,low-,medium-,and high-dose TG groups,female C57 mice were used as the control group(n=12/group).After 12 weeks of treatment,the behavior of mice was tested with the Morris water maze,and brain tissue samples were collected,and changes in hippocampal neurons were observed using electron microscopy.The deposition of beta-amyloid protein(Aβ)amyloid plaques in the hippocampus was determined by light microscopy.Aβ1-42 protein levels were detected through immunofluorescence.Oxidative stress indicators in the hippocampus were detected by enzyme linked immunosorbent assay.The expressions of nuclear factor-erythroid 2-related factor 2(Nrf2),c-Jun N-terminal kinase(JNK),phospho-JNK(p-JNK),B-cell lymphoma-2(Bcl-2),caspase-9,and cleaved caspase-9 were detected by Western blot.Hippocampal cell apoptosis was detected using the terminal deoxynucleotidyl transferase-mediated nick end Labeling.RESULTS:TG improved the cognitive function of APP/PS1 mice,as judged by improvements in several indices from the Morris water maze test.TG increased Nrf2,superoxide dismutase,and heme oxygenase-1 protein expression and reduced malondialdelyde and reactive oxygen species expression.TG also inhibited the expression of JNK proteins,upregulated the expression of Bcl-2,and downregulated the expression of caspase-9,reducing cell apoptosis.TG decreased the percentage of the hippocampal cornu ammonis 1 area positive for Aβ1-42,reducing mitochondrial damage caused by oxidative stress and Aβprotein deposition.CONCLUSIONS:TG may improve memory ability while reducing oxidative stress and apoptosis.It also reduces Aβprotein deposition in the hippocampus,protecting the central nervous system and improving memory function.TG may reduce the risk of AD.
基金National Natural Science Foundation of China,Grant/Award Number:82101937Guangdong Medical Science and Technology Research Fund Project,China,Grant/Award Number:B2024069Guangzhou Science and Technology Plan Project,China,Grant/Award Number:2024A04J4923 and SL2023A04J02229。
文摘Background:Makorin ring finger protein 3 gene(MKRN3)gene mutation is the most common genetic cause of central precocious puberty(CPP)in children.Due to the lack of ideal MKRN3-modified animal model(MKRN3-modified mice enter puberty only 4–5 days earlier than normal mice),the related research is limited.Methods:Therefore,the MKRN3-modified rabbit was developed using CRISPR(clus-tered regularly interspaced short palindromic repeats)gene editing technology.The genotype identification and phenotype evaluation of MKRN3-modified rabbits were carried out.Results:The first estrus of MKRN3-modified female rabbits was observed~27 days earlier than that of wild-type female rabbits,with a typical CPP phenotype.This study found increased gonadotropin releasing hormone(GnRH)and decreased gonadotropin inhibiting hormone(GnIH)in the hypothalamus of the CPP rabbit model with MKRN3 gene mutation.Although this study failed to fully clarify the pathogenesis of CPP caused by MKRN3 mutation,it found some differentially expressed genes and potential pathways through transcriptome sequencing.Conclusions:This study established a novel CPP model:paternal MKRN3 gene-modified rabbit.It is hoped that the establishment of this model will help researchers better understand,treat,and prevent CPP in the future.
基金National Key R&D Program of China,Grant/Award Number:2021YFF0703200Key Technology Fund of the National Institutes for Food and Drug Control,Grant/Award Number:GJJS-2022-1-5。
文摘Experimental mice play a critical role in biomedical research.The phenotype and application of different substrains vary due to genetic differentiation and variation.To ensure validity and reliability of results,it is imperative to adhere to standardized experiments and controls.This paper objectively reviews the origin,differentiation,and phenotypic and genetic differences between the C57BL/6 and BALB/c mouse substrains.Furthermore,an optimal selection strategy is proposed based on the genetic quality control technology to facilitate the precise application of these two mouse substrains.
基金the National Natural Science Foundation of China(No.82173884).
文摘Dysfunction of drug transporters significantly affects therapeutic outcomes and drug efficacy in patients with liver injury.Clinical and experimental evidence demonstrates that liver injury involves complex inter-organ interactions among the brain,eye,liver,intestine,and kidney.Recent advances in basic and clinical research have illuminated the physiologic and molecular mechanisms underlying transporter alterations in liver injury,particularly those associated with bilirubin,reactive oxygen species,ammonia,bile acid,and inflammatory factors.Notably,the influence of these transporter modifications on drug pharmacokinetics in liver injury patients remains inadequately understood.Additional research is necessary to fully comprehend these effects and their therapeutic implications.The documented alterations of transporters in distant organs across various liver diseases indicate that dosage modifications may be required when administering transporter-substrate drugs,including both traditional Chinese and Western medicines,to patients with liver dysfunction.This strategy helps maintain drug concentrations within therapeutic ranges while reducing adverse reactions.Furthermore,when utilizing transporter inducers or inhibitors clinically,consideration of their long-term effects on transporters and subsequent therapeutic impact is essential.Careful attention must be paid to avoid compromising the elimination of toxic metabolites and proteins when inhibiting these transporters.Similarly,prudent use of inducers or inducertype therapeutic drugs is necessary to prevent enhanced drug resistance.This review examines recent clinical and experimental findings regarding the inter-organ interaction of drug transporters in liver injury conditions and their clinical relevance.
基金National Key Research and Development Program for Young scientists,Grant/Award Number:2021YFF0703200National Natural Foundation Joint Fund for Regional Innovation and Development,Grant/Award Number:U21A20194+1 种基金National Natural Science Foundation of China,Grant/Award Number:32170540National Key Research and Development Program,Grant/Award Number:2022YFF0711005。
文摘Chinese hamster with Chinese characteristics is used in experiments,and it is of great value in the field of medical biology research.However,at present,there is no high-efficiency method for evaluating the genetic quality of Chinese hamsters.Here,we developed a novel Chinese hamster genetic quality detection system using single-nucleotide polymorphism(SNP)markers.To find SNP loci,we conducted whole genome sequencing on 24 Chinese hamsters.Then,we employed an SNP locus screening criterion that we set up previously and initially screened 214 SNP loci with wide genome distribution and high polymorphism level.Subsequently,we developed the SNP detection system using a multitarget region capture technique based on second-generation sequencing,and a 55 SNP panel for genetic evaluation of Chinese hamster populations was developed.PopGen.32.analysis results showed that the average effective allele number,Shannon index,observed heterozygosity,expected heterozygosity,average heterozygosity,polymorphism information,and other genetic parameters of Chinese hamster population A were higher than those in population B.Using scientific screening and optimization,we successfully developed a novel Chinese hamster SNP genetic detection system that can efficiently and accurately analyze the genetic quality of the Chinese hamster population.
基金supported by Sichuan Science and Technology Program,China(No.2023YFS0273)the 1·3·5 Project for Disciplines of Excellence,West China Hospital,Sichuan University,China(No.ZYJC21022).
文摘Glioma is a severe malignant brain tumor marked by an exceedingly dire prognosis and elevated incidence of recurrence.The resilience of such tumors to chemotherapeutic agents,coupled with the formidable obstacle the blood-brain barrier(BBB)presents to most pharmacological interventions are major challenges in anti-glioma therapy.In an endeavor to surmount these impediments,we have synergized pH-sensitive nanoparticles carrying doxorubicin and apatinib to amplify the anti-neoplastic efficacy with cyclic arginine-glycine-aspartate acid(cRGD)modification.In this study,we found that the combination of doxorubicin(DOX)and apatinib(AP)showed a significant synergistic effect,achieved through cytotoxicity and induction of apoptosis,which might be due to the increased intracellular uptake of DOX following AP treatment.Besides,polycaprolactone-polyethylene glycol-cRGD(PCL-PEG-cRGD)drug carrier could cross the BBB by its targeting ability,and then deliver the drug to the glioma site via pH-responsive release,increasing the concentration of the drugs in the tumor.Meanwhile,DOX/AP-loaded PCL-PEGcRGD nanoparticles effectively inhibited cell proliferation,enhanced glioma cell apoptosis,and retarded tumor growth in vivo.These results collectively identified DOX/AP-loaded PCL-PEG-cRGD nanoparticles as a promising therapeutic candidate for the treatment of glioma.
基金supported by the grants from the National Key Research and Development Program of China(2022YFD1800604)the China Agriculture Research System(CARS-41)the Heilongjiang Touyan Innovation Team Program,China。
文摘Avian metapneumovirus(aMPV),a paramyxovirus,causes acute respiratory diseases in turkeys and swollen head syndrome in chickens.This study established a reverse genetics system for aMPV subtype B LN16-A strain based on T7 RNA polymerase.Full-length cDNA of the LN16-A strain was constructed by assembling 5 cDNA fragments between the T7 promoter and hepatitis delta virus ribozyme.Transfection of this plasmid,along with the supporting plasmids encoding the N,P,M2-1,and L proteins of LN16-A into BSR-T7/5 cells,resulted in the recovery of aMPV subtype B.To identify an effective insertion site,the enhanced green fluorescent protein(EGFP)gene was inserted into different sites of the LN16-A genome to generate recombinant LN16-As.The results showed that the expression levels of EGFP at the site between the G and L genes of LN16-A were significantly higher than those at the other two sites(between the leader and N genes or replacing the SH gene).To verify the availability of the site between G and L for foreign gene expression,the VP2 gene of very virulent infectious bursal disease virus(vvIBDV)was inserted into this site,and recombinant LN16-A(rLN16A-vvVP2)was successfully rescued.Single immunization of specificpathogen-free chickens with rLN16A-vvVP2 induced high levels of neutralizing antibodies and provided 100%protection against the virulent aMPV subtype B and vvIBDV.Establishing a reverse genetics system here provides an important foundation for understanding aMPV pathogenesis and developing novel vector vaccines.
