Microtubule-severing enzymes(MTSEs)play important roles in mitosis and meiosis of the primitive organisms.However,their roles in mammalian female meiosis,which accounts for over 80%of gamete-originated human reproduct...Microtubule-severing enzymes(MTSEs)play important roles in mitosis and meiosis of the primitive organisms.However,their roles in mammalian female meiosis,which accounts for over 80%of gamete-originated human reproductive diseases,remain unexplored.In the current study,we reported that katanin-like 2(KL2)was the only MTSE concentrating at chromosomes.Furthermore,the knockdown of KL2 significantly reduced the chromosome-based increase in the microtubule(MT)polymer,increased aberrant kinetochore-MT(K-MT)attachment,delayed meiosis,and severely affected normal fertility.We demonstrated that the inhibition of aurora B,a key kinase for correcting aberrant K-MT attachment,significantly eliminated KL2 expression from chromosomes.Additionally,KL2 interacted with phosphorylated eukaryotic elongation factor-2 kinase,and they competed for chromosome binding.Phosphorylated KL2 was also localized at spindle poles,with its phosphorylation regulated by extracellular signal-regulated kinase 1/2.In summary,the current study reveals a novel function of MTSEs in mammalian female meiosis and demonstrates that multiple kinases coordinate to regulate the levels of KL2 at chromosomes.展开更多
Breast cancer metastasis is responsible for most breast cancer-related deaths and is influenced by many factors within the tumor ecosystem,including tumor cells and microenvironment.Breast cancer stem cells(BCSCs)cons...Breast cancer metastasis is responsible for most breast cancer-related deaths and is influenced by many factors within the tumor ecosystem,including tumor cells and microenvironment.Breast cancer stem cells(BCSCs)constitute a small population of cancer cells with unique characteristics,including their capacity for self-renewal and differentiation.Studies have shown that BCSCs not only drive tumorigenesis but also play a crucial role in promoting metastasis in breast cancer.The tumor microenvironment(TME),composed of stromal cells,immune cells,blood vessel cells,fibroblasts,and microbes in proximity to cancer cells,is increasingly recognized for its crosstalk with BCSCs and role in BCSC survival,growth,and dissemination,thereby influencing metastatic ability.Hence,a thorough understanding of BCSCs and the TME is critical for unraveling the mechanisms underlying breast cancer metastasis.In this review,we summarize current knowledge on the roles of BCSCs and the TME in breast cancer metastasis,as well as the underlying regulatory mechanisms.Furthermore,we provide an overview of relevant mouse models used to study breast cancer metastasis,as well as treatment strategies and clinical trials addressing BCSC-TME interactions during metastasis.Overall,this study provides valuable insights for the development of effective therapeutic strategies to reduce breast cancer metastasis.展开更多
Cutaneous exposure to food allergens through a disrupted skin barrier is recognized as an important cause of food allergy,and the cutaneous sensitized mouse model has been established to investigate relevant allergic ...Cutaneous exposure to food allergens through a disrupted skin barrier is recognized as an important cause of food allergy,and the cutaneous sensitized mouse model has been established to investigate relevant allergic disorders.However,the role of different genetic backgrounds of mice on immune responses to food allergens upon epicutaneous sensitization is largely unknown.In this study,two strains of mice,i.e.,the BALB/c and C57BL/6 mice,were epicutaneously sensitized with ovalbumin on atopic dermatitis(AD)-like skin lesions,followed by intragastric challenge to induce IgE-mediated food allergy.Allergic outcomes were measured as clinical signs,specific antibodies and cytokines,and immune cell subpopulations,as well as changes in intestinal barrier function and gut microbiota.Results showed that both strains of mice exhibited typical food-allergic symptoms with a Th2-skewed response.The C57BL/6 mice,rather than the BALB/c mice,were fitter for establishing an epicutaneously sensitized model of food allergy since a stronger Th2-biased response and severer disruptions in the intestinal barrier and gut homeostasis were observed.This study provides knowledge for selecting an appropriate mouse model to study food-allergic responses associated with AD-like skin lesions and highlights the role of genetic variations in the immune mechanism underlying pathogenesis of food allergy.展开更多
[Objectives]To explore a new method for induction of allergic rhinitis in mice,and compare and evaluate it with common modeling methods.[Methods]36 mice were randomly divided into the control group,blank group and exp...[Objectives]To explore a new method for induction of allergic rhinitis in mice,and compare and evaluate it with common modeling methods.[Methods]36 mice were randomly divided into the control group,blank group and experimental group,and there were 12 mice in each group.The mice in the control group were conventionally induced.That is,the mice were first injected intraperitoneally with the mixture composed of OVA 50μg,[Al(OH)3]5 mg and 1ml of normal saline once every other day,and then since the 15 th d,20μL of 5%OVA solution was dropped into each nasal cavity once a day,which lasted for 7 d.The blank group was treated with the same amount of normal saline according to the control group,and received intraperitoneal injection and bilateral nasal drip respectively.In the experimental group,mice were first given intraperitoneal injection of the mixture composed of ovalbumin(OVA)75μg,aluminum hydroxide gel[Al(OH)3]8 mg and normal saline 1.5 mL for basic sensitization.On the 26 th d,20μL of 3%OVA solution was dropped into each nasal cavity once a day,which lasted for 10 d.The number of sneezes,the number of nose scratching,the amount of nasal discharge,and the activity of mice in each group were observed,and the behavior of allergic reaction was scored.Meanwhile,the number of eosinophils in the nasal discharge of mice and the IgE content in serum were measured.[Results]The score of nasal stimulation symptoms,the number of eosinophils and serum IgE level of mice in the control group and the experimental group were higher than those in the blank group(P<0.05),and there was no statistical significance between the two groups in the three indicators(P>0.05).[Conclusions]The modeling method was more suitable for the development of allergic rhinitis patients condition,and reduced the probability of death of mice due to modeling,and simplified the experimental operation.展开更多
BACKGROUND ATP sensitive K+(K_(ATP))channels are ubiquitously distributed in various of cells and tissues,including the liver.They play a role in the pathogenesis of myocardial and liver ischemia.AIM To evaluate the r...BACKGROUND ATP sensitive K+(K_(ATP))channels are ubiquitously distributed in various of cells and tissues,including the liver.They play a role in the pathogenesis of myocardial and liver ischemia.AIM To evaluate the radiation-induced changes in the expression of K_(ATP)channel subunits in the mouse liver to understand the potential role of K_(ATP)channels in radiation injury.METHODS Adult C57BL/6 mice were randomly exposed toγ-rays at 0 Gy(control,n=2),0.2 Gy(n=6),1 Gy(n=6),or 5 Gy(n=6).The livers were removed 3 and 24 h after radiation exposure.Hematoxylin and eosin staining was used for morphological observation;immunohistochemical staining was applied to determine the expression of K_(ATP)channel subunits in the liver tissue.RESULTS Compared with the control group,the livers exposed to 0.2 Gyγ-ray showed an initial increase in the expression of Kir6.1 at 3 h,followed by recovery at 24 h after exposure.Exposure to a high dose of 5.0 Gy resulted in decreased expression of Kir6.1 and increased expression of SUR2B at 24 h.However,the expression of Kir6.2,SUR1,or SUR2A had no remarkable changes at 3 and 24 h after exposure to any of these doses.CONCLUSION The expression levels of Kir6.1 and SUR2B in mouse liver changed differently in response to different radiation doses,suggesting a potential role for them in radiation-induced liver injury.展开更多
[Objectives]To explore the effects of Polygona fallax Hemsl water extract on gastrointestinal motility in normal mice and gastric motility disorder model mice and approximate mechanism.[Methods]Using normal mice and m...[Objectives]To explore the effects of Polygona fallax Hemsl water extract on gastrointestinal motility in normal mice and gastric motility disorder model mice and approximate mechanism.[Methods]Using normal mice and mice with gastric motility disorders(modeled with atropine),the effects of different mass concentration groups of P.fallax Hemsl water extract(0.125,0.250,0.500 g/mL)and domperidone groups on gastric residual rate,small intestine propulsion rate,serum motilin(MLT),vasoactive intestinal peptide(VIP),and tissue morphology were studied.[Results]There was a highly significant difference(P<0.01)in the small intestine propulsion rate of liquid in normal mice among the different concentration groups of P.fallax Hemsl water extract compared to the blank group.The small intestine propulsion rate and gastric residue rate of semi-solid paste were statistically significant compared to the blank group(P<0.05).Among them,there was a highly significant difference between the high concentration group(67.75%±7.65%,46.5%±10.62%)and the medium concentration group(60.90%±5.87%,59.27%±7.82%)(P<0.01).There was statistical significance in normal mouse serum MLT content in the high concentration group(P<0.05).There was no effect on serum VIP levels in normal mice;no effect on the morphology of stomach and intestinal tissues of normal mice.The small intestine propulsion rate and gastric residue rate of liquid and semi-solid paste in mice with gastric motility disorders were statistically significant compared to the atropine group,with extremely significant differences(P<0.01).[Conclusions]P.fallax Hemsl water extract has a promoting effect on gastrointestinal motility.One of the specific mechanisms by which P.fallax Hemsl promotes gastrointestinal motility in normal mice may be related to the content of MLT in mouse serum.The mechanism of action in atropine induced gastric paresis mice may be related to the reactivation of M receptors,and the action mechanism of P.fallax Hemsl does not change the original histological basis.It can be inferred that P.fallax Hemsl water extract has a synergistic effect on promoting gastrointestinal motility through other mechanisms,but it is not fully understood and further in-depth research is needed.展开更多
β-Nerve growth factor (β NGF) mRNA levels in hippocampa from C57BL/6J mice of different ages were compared by semi-quantitative RT-PCR method, taking β-actin gene as an internal control. The levels of 6-and 12-mon...β-Nerve growth factor (β NGF) mRNA levels in hippocampa from C57BL/6J mice of different ages were compared by semi-quantitative RT-PCR method, taking β-actin gene as an internal control. The levels of 6-and 12-month-old C57 mice were much lower compared with that of the l-month-old mouse. However, there was no significant difference between these two groups. This result suggests that gene transcription level of hippocampus β NGF in a C57, mouse descends evidently as it grows up. Base T at Site 294 of β NGF cDNA was substituted by C in the C57, mouse, as revealed by DNA sequencing for the first time. Nevertheless, this polymorphism of nucleotide did not make any difference in amino acid composition.展开更多
Epilepsy is a common and serious neurological disease that causes recurrent seizures. The brain damage caused by seizures can lead to depression, anxiety, cognitive impairment, or disability. In almost all cases chron...Epilepsy is a common and serious neurological disease that causes recurrent seizures. The brain damage caused by seizures can lead to depression, anxiety, cognitive impairment, or disability. In almost all cases chronic seizures are difficult to cure. MicroRNAs are widely expressed in the central nervous system and play important roles in the pathogenesis of several neurological disorders, including epilepsy. A variety of animals(mostly mice and rats) have been used to induce experimental epilepsy using different protocols and miRNA profiling performed. Most of the recent studies reviewed had performed miRNA profiling in hippocampal tissues and a large number of microRNAs were dysregulated when compared to controls. Most notably, miR-132-3p,-146a-5p,-10a-5p,-21a-3p,-27a-3p,-142a-5p,-212-3p,-431-5p, and-155 were upregulated in both the mouse and rat studies. Overexpression of miR-137 and miR-219 decreased seizure severity in a mouse epileptic model, and suppression of miR-451,-10a-5p,-21a-5p,-27a-5p,-142a-5p,-431-5p,-155, and-134 had a positive influence on seizure behavior. In the rat studies, overexpression of miR-139-5p decreased neuronal damage in drug-resistant rats and inhibition of miR-129-2-3p,-27a-3p,-155,-134,-181a, and-146a had a positive effect on seizure behavior and/or reduced the loss of neuronal cells. Further studies are warranted using adult female and immature male and female animals. It would also be helpful to test the ability of specific agomirs and antagomirs to control seizure activity in a subhuman primate model of epilepsy such as adult marmosets injected intraperitoneally with pilocarpine or cynomolgus monkeys given intrahippocampal injections of kainic acid.展开更多
Severe acute respiratory syndrome coronavirus 2(SARSCo V-2)infection can result in more severe syndromes and poorer outcomes in patients with diabetes and obesity.However,the precise mechanisms responsible for the com...Severe acute respiratory syndrome coronavirus 2(SARSCo V-2)infection can result in more severe syndromes and poorer outcomes in patients with diabetes and obesity.However,the precise mechanisms responsible for the combined impact of coronavirus disease 2019(COVID-19)and diabetes have not yet been elucidated,and effective treatment options for SARS-Co V-2-infected diabetic patients remain limited.To investigate the disease pathogenesis,K18-h ACE2 transgenic(h ACE2^(Tg))mice with a leptin receptor deficiency(h ACE2-Lepr^(-/-))and high-fat diet(h ACE2-HFD)background were generated.The two mouse models were intranasally infected with a 5×10^(5) median tissue culture infectious dose(TCID_(50))of SARSCo V-2,with serum and lung tissue samples collected at 3days post-infection.The h ACE2-Lepr^(-/-)mice were then administered a combination of low-molecular-weight heparin(LMWH)(1 mg/kg or 5 mg/kg)and insulin via subcutaneous injection prior to intranasal infection with1×10^(4) TCID_(50)of SARS-Co V-2.Daily drug administration continued until the euthanasia of the mice.Analyses of viral RNA loads,histopathological changes in lung tissue,and inflammation factors were conducted.Results demonstrated similar SARS-Co V-2 susceptibility in h ACE2^(Tg)mice under both lean(chow diet)and obese(HFD)conditions.However,compared to the h ACE2-Lepr^(+/+)mice,h ACE2-Lepr^(-/-)mice exhibited more severe lung injury,enhanced expression of inflammatory cytokines and hypoxia-inducible factor-1α(HIF-1α),and increased apoptosis.Moreover,combined LMWH and insulin treatment effectively reduced disease progression and severity,attenuated lung pathological changes,and mitigated inflammatory responses.In conclusion,preexisting diabetes can lead to more severe lung damage upon SARS-Co V-2 infection,and LMWH may be a valuable therapeutic approach for managing COVID-19patients with diabetes.展开更多
Anti β NGF antiserum was prepared by immunizing rabbits with purified mouse β NGF. It presented immunopositivity to β NGF on Western blot, resulting in a single band approximately at the molecular weight of 14 kD...Anti β NGF antiserum was prepared by immunizing rabbits with purified mouse β NGF. It presented immunopositivity to β NGF on Western blot, resulting in a single band approximately at the molecular weight of 14 kDa. The antiserum was further purified into anti β NGF IgG by affinity chromatography. Chicken embryonic dorsal root ganglia (DRG) were cultured to test the biological activities of β NGF and its antibody.展开更多
Reproduction is subtlety regulated by the hypothalamic-pituitary-gonad(HPG)axis in vertebrates.Pituitary gland is the center of the HPG axis,while pituitary gonadotropins follicle stimulating hormone(FSH)and luteinizi...Reproduction is subtlety regulated by the hypothalamic-pituitary-gonad(HPG)axis in vertebrates.Pituitary gland is the center of the HPG axis,while pituitary gonadotropins follicle stimulating hormone(FSH)and luteinizing hormone(LH)were identified the key elements of the HPG axis in teleost and mammal.Morphology,cell lines,and gonadotropins cell localization of female turbot and mouse pituitary were determined at mature stage to illustrate the anatomical difference and cell characteristics in this study.Results show that turbot pituitary is chicken heart-shaped,dorsoventral,located on the ventral surface of the diencephalon.The mouse pituitary is oval,located in the pituitary fossa of the sella turcica at the skull base.Two well-distinguished areas adenohypophysis(AH)and neurohypophysis(NH)in pituitary were identified in turbot and mouse.Turbot AH comprised the rostral pars distalis(RPD),proximal pars distalis(PPD),and pars intermedia(PI).NH was not pronounced and with finger-like protrusions into PPD.However,mouse AH only comprised the pars distalis(PD)and PI.NH distribution was semicircular.Three main types of cells(acidophilic,basophilic,and chromophobic cells)were distributed in the mouse PD region,whereas appeared in the turbot PPD,RPD,and PI.Moreover,the percentage of mouse chromophobic and basophilic cells was higher and lower than that of turbot,respectively.The diameter of the aforementioned three cells in the mouse was significantly higher than turbot.fshβ-and lhβ-immunoreactive signals were identified in turbot-distinct pituitary cells that primarily occupied the peripheral and central regions of AH.However,mouse fsh-and lh-immunoreactive cells were expressed in the same cells and present in the PD.These results demonstrate the significantly difference of pituitary morphology,cell lines and gonadotropins(fshβand lhβ)location in female turbot and mouse.These differences help for fully understand the evolution and endocrinological functions of pituitary.展开更多
Biomedical data classification has become a hot research topic in recent years,thanks to the latest technological advancements made in healthcare.Biome-dical data is usually examined by physicians for decision making ...Biomedical data classification has become a hot research topic in recent years,thanks to the latest technological advancements made in healthcare.Biome-dical data is usually examined by physicians for decision making process in patient treatment.Since manual diagnosis is a tedious and time consuming task,numerous automated models,using Artificial Intelligence(AI)techniques,have been presented so far.With this motivation,the current research work presents a novel Biomedical Data Classification using Cat and Mouse Based Optimizer with AI(BDC-CMBOAI)technique.The aim of the proposed BDC-CMBOAI technique is to determine the occurrence of diseases using biomedical data.Besides,the proposed BDC-CMBOAI technique involves the design of Cat and Mouse Optimizer-based Feature Selection(CMBO-FS)technique to derive a useful subset of features.In addition,Ridge Regression(RR)model is also utilized as a classifier to identify the existence of disease.The novelty of the current work is its designing of CMBO-FS model for data classification.Moreover,CMBO-FS technique is used to get rid of unwanted features and boosts the classification accuracy.The results of the experimental analysis accomplished by BDC-CMBOAI technique on benchmark medical dataset established the supremacy of the proposed technique under different evaluation measures.展开更多
Mitochondrial dysfunction is proposed to be substantially associated with ageing and ageing-related diseases like Alzheimer's disease(AD). However, it is unclear whether different mouse models with mitochondrialre...Mitochondrial dysfunction is proposed to be substantially associated with ageing and ageing-related diseases like Alzheimer's disease(AD). However, it is unclear whether different mouse models with mitochondrialrelated diseases have similar changes in mitochondrial morphology of the same tissues. Moreover, whether similarities in mitochondrial morphology can be a suitable marker for screening and/or discovering mitochondrial-protective substances remains unknown. Mitochondria morphology in different tissues of a novel mitochondrial outer membrane protein Slc25a46 knockout mouse and a traditional APP_(SWE)/PS1ΔE9 transgenic mouse were examined using transmission electron microscope(TEM). Both young Slc25a46 knockout mice and aged APP_(SWE)/PS1ΔE9 mice models showed similar mitochondrial damage in cerebellum tissues. The results indicated that different mitochondrial-related diseases shared similar alteration and defects in mitochondrial morphology. Furthermore, Lycium ruthenicum Murr. extract, a bioactive food substance with cognition-improving property, could effectively improve muscle strength and increase body weight in the Slc25a46 knockout mice. These findings suggest that mitochondrial morphology defects in mice models, particularly in the mitochondrial compartment, represent a unified and effective marker for screening and validating natural product-derived functional substances with mitochondrial protective properties. It also holds potential application in mitochondrial-impaired senile neurodegenerative diseases, especially in AD.展开更多
BACKGROUND The low survival rate of mesenchymal stem cells(MSCs)caused by anoikis,a form of apoptosis,limits the therapeutic efficacy of MSCs.As a proapoptotic molecule,mammalian Ste20-like kinase 1(Mst1)can increase ...BACKGROUND The low survival rate of mesenchymal stem cells(MSCs)caused by anoikis,a form of apoptosis,limits the therapeutic efficacy of MSCs.As a proapoptotic molecule,mammalian Ste20-like kinase 1(Mst1)can increase the production of reactive oxygen species(ROS),thereby promoting anoikis.Recently,we found that Mst1 inhibition could protect mouse bone marrow MSCs(mBMSCs)from H 2 O 2-induced cell apoptosis by inducing autophagy and reducing ROS production.However,the influence of Mst1 inhibition on anoikis in mBMSCs remains unclear.AIM To investigate the mechanisms by which Mst1 inhibition acts on anoikis in isolated mBMSCs.METHODS Poly-2-hydroxyethyl methacrylate-induced anoikis was used following the silencing of Mst1 expression by short hairpin RNA(shRNA)adenovirus transfection.Integrin(ITGs)were tested by flow cytometry.Autophagy and ITGα5β1 were inhibited using 3-methyladenine and small interfering RNA,respe-ctively.The alterations in anoikis were measured by Terminal-deoxynucleoitidyl Transferase Mediated Nick End Labeling and anoikis assays.The levels of the anoikis-related proteins ITGα5,ITGβ1,and phospho-focal adhesion kinase and the activation of caspase 3 and the autophagy-related proteins microtubules associated protein 1 light chain 3 II/I,Beclin1 and p62 were detected by Western blotting.RESULTS In isolated mBMSCs,Mst1 expression was upregulated,and Mst1 inhibition significantly reduced cell apoptosis,induced autophagy and decreased ROS levels.Mechanistically,we found that Mst1 inhibition could upregulate ITGα5 and ITGβ1 expression but not ITGα4,ITGαv,or ITGβ3 expression.Moreover,autophagy induced by upregulated ITGα5β1 expression following Mst1 inhibition played an essential role in the protective efficacy of Mst1 inhibition in averting anoikis.CONCLUSION Mst1 inhibition ameliorated autophagy formation,increased ITGα5β1 expression,and decreased the excessive production of ROS,thereby reducing cell apoptosis in isolated mBMSCs.Based on these results,Mst1 inhibition may provide a promising strategy to overcome anoikis of implanted MSCs.展开更多
β-Nerve growth factor (β NGF) mRNA levels in hippocampa from C57BL/6J mice of different ages were compared by semi-quantitative RT-PCR method, taking β-actin gene as an internal control. The levels of 6-and 12-mon...β-Nerve growth factor (β NGF) mRNA levels in hippocampa from C57BL/6J mice of different ages were compared by semi-quantitative RT-PCR method, taking β-actin gene as an internal control. The levels of 6-and 12-month-old C57 mice were much lower compared with that of the l-month-old mouse. However, there was no significant difference between these two groups. This result suggests that gene transcription level of hippocampus β NGF in a C57, mouse descends evidently as it grows up. Base T at Site 294 of β NGF cDNA was substituted by C in the C57, mouse, as revealed by DNA sequencing for the first time. Nevertheless, this polymorphism of nucleotide did not make any difference in amino acid composition.展开更多
基金supported by the Youth Program of National Natural Science Foundation of China(Grant No.82001539 to Leilei Gao)the Zhejiang Province Health Innovation Talent Project(Grant No.2021RC001 to Zhen Jin)+1 种基金the General Program of the National Natural Science Foundation of China(Grant No.31671561 to Dong Zhang)the Regional Program of National Natural Science Foundation of China(Grant No.82260126 to Xiaocong Liu).
文摘Microtubule-severing enzymes(MTSEs)play important roles in mitosis and meiosis of the primitive organisms.However,their roles in mammalian female meiosis,which accounts for over 80%of gamete-originated human reproductive diseases,remain unexplored.In the current study,we reported that katanin-like 2(KL2)was the only MTSE concentrating at chromosomes.Furthermore,the knockdown of KL2 significantly reduced the chromosome-based increase in the microtubule(MT)polymer,increased aberrant kinetochore-MT(K-MT)attachment,delayed meiosis,and severely affected normal fertility.We demonstrated that the inhibition of aurora B,a key kinase for correcting aberrant K-MT attachment,significantly eliminated KL2 expression from chromosomes.Additionally,KL2 interacted with phosphorylated eukaryotic elongation factor-2 kinase,and they competed for chromosome binding.Phosphorylated KL2 was also localized at spindle poles,with its phosphorylation regulated by extracellular signal-regulated kinase 1/2.In summary,the current study reveals a novel function of MTSEs in mammalian female meiosis and demonstrates that multiple kinases coordinate to regulate the levels of KL2 at chromosomes.
基金supported by the National Key Research and Development Program of China(2023YFC2506400,2020YFA0112300)National Natural Science Foundation of China(82230103,81930075,82073267,82203399,82372689)+1 种基金Program for Outstanding Leading Talents in ShanghaiInnovative Research Team of High-level Local University in Shanghai。
文摘Breast cancer metastasis is responsible for most breast cancer-related deaths and is influenced by many factors within the tumor ecosystem,including tumor cells and microenvironment.Breast cancer stem cells(BCSCs)constitute a small population of cancer cells with unique characteristics,including their capacity for self-renewal and differentiation.Studies have shown that BCSCs not only drive tumorigenesis but also play a crucial role in promoting metastasis in breast cancer.The tumor microenvironment(TME),composed of stromal cells,immune cells,blood vessel cells,fibroblasts,and microbes in proximity to cancer cells,is increasingly recognized for its crosstalk with BCSCs and role in BCSC survival,growth,and dissemination,thereby influencing metastatic ability.Hence,a thorough understanding of BCSCs and the TME is critical for unraveling the mechanisms underlying breast cancer metastasis.In this review,we summarize current knowledge on the roles of BCSCs and the TME in breast cancer metastasis,as well as the underlying regulatory mechanisms.Furthermore,we provide an overview of relevant mouse models used to study breast cancer metastasis,as well as treatment strategies and clinical trials addressing BCSC-TME interactions during metastasis.Overall,this study provides valuable insights for the development of effective therapeutic strategies to reduce breast cancer metastasis.
基金the financial support received from the Natural Science Foundation of China(32202202 and 31871735)the Zhejiang Provincial Natural Science Foundation of China(LGN22C200027)the Open Fund of the Key Laboratory of Biosafety Detection for Zhejiang Market Regulation(2022BS004)。
文摘Cutaneous exposure to food allergens through a disrupted skin barrier is recognized as an important cause of food allergy,and the cutaneous sensitized mouse model has been established to investigate relevant allergic disorders.However,the role of different genetic backgrounds of mice on immune responses to food allergens upon epicutaneous sensitization is largely unknown.In this study,two strains of mice,i.e.,the BALB/c and C57BL/6 mice,were epicutaneously sensitized with ovalbumin on atopic dermatitis(AD)-like skin lesions,followed by intragastric challenge to induce IgE-mediated food allergy.Allergic outcomes were measured as clinical signs,specific antibodies and cytokines,and immune cell subpopulations,as well as changes in intestinal barrier function and gut microbiota.Results showed that both strains of mice exhibited typical food-allergic symptoms with a Th2-skewed response.The C57BL/6 mice,rather than the BALB/c mice,were fitter for establishing an epicutaneously sensitized model of food allergy since a stronger Th2-biased response and severer disruptions in the intestinal barrier and gut homeostasis were observed.This study provides knowledge for selecting an appropriate mouse model to study food-allergic responses associated with AD-like skin lesions and highlights the role of genetic variations in the immune mechanism underlying pathogenesis of food allergy.
基金the National Innovation and Entrepreneurship Project for University Students(202110599012).
文摘[Objectives]To explore a new method for induction of allergic rhinitis in mice,and compare and evaluate it with common modeling methods.[Methods]36 mice were randomly divided into the control group,blank group and experimental group,and there were 12 mice in each group.The mice in the control group were conventionally induced.That is,the mice were first injected intraperitoneally with the mixture composed of OVA 50μg,[Al(OH)3]5 mg and 1ml of normal saline once every other day,and then since the 15 th d,20μL of 5%OVA solution was dropped into each nasal cavity once a day,which lasted for 7 d.The blank group was treated with the same amount of normal saline according to the control group,and received intraperitoneal injection and bilateral nasal drip respectively.In the experimental group,mice were first given intraperitoneal injection of the mixture composed of ovalbumin(OVA)75μg,aluminum hydroxide gel[Al(OH)3]8 mg and normal saline 1.5 mL for basic sensitization.On the 26 th d,20μL of 3%OVA solution was dropped into each nasal cavity once a day,which lasted for 10 d.The number of sneezes,the number of nose scratching,the amount of nasal discharge,and the activity of mice in each group were observed,and the behavior of allergic reaction was scored.Meanwhile,the number of eosinophils in the nasal discharge of mice and the IgE content in serum were measured.[Results]The score of nasal stimulation symptoms,the number of eosinophils and serum IgE level of mice in the control group and the experimental group were higher than those in the blank group(P<0.05),and there was no statistical significance between the two groups in the three indicators(P>0.05).[Conclusions]The modeling method was more suitable for the development of allergic rhinitis patients condition,and reduced the probability of death of mice due to modeling,and simplified the experimental operation.
基金Supported by the Program of the Network-type Joint Usage/Research Center for Radiation Disaster Medical Science of Hiroshima University,Nagasaki University.
文摘BACKGROUND ATP sensitive K+(K_(ATP))channels are ubiquitously distributed in various of cells and tissues,including the liver.They play a role in the pathogenesis of myocardial and liver ischemia.AIM To evaluate the radiation-induced changes in the expression of K_(ATP)channel subunits in the mouse liver to understand the potential role of K_(ATP)channels in radiation injury.METHODS Adult C57BL/6 mice were randomly exposed toγ-rays at 0 Gy(control,n=2),0.2 Gy(n=6),1 Gy(n=6),or 5 Gy(n=6).The livers were removed 3 and 24 h after radiation exposure.Hematoxylin and eosin staining was used for morphological observation;immunohistochemical staining was applied to determine the expression of K_(ATP)channel subunits in the liver tissue.RESULTS Compared with the control group,the livers exposed to 0.2 Gyγ-ray showed an initial increase in the expression of Kir6.1 at 3 h,followed by recovery at 24 h after exposure.Exposure to a high dose of 5.0 Gy resulted in decreased expression of Kir6.1 and increased expression of SUR2B at 24 h.However,the expression of Kir6.2,SUR1,or SUR2A had no remarkable changes at 3 and 24 h after exposure to any of these doses.CONCLUSION The expression levels of Kir6.1 and SUR2B in mouse liver changed differently in response to different radiation doses,suggesting a potential role for them in radiation-induced liver injury.
基金2022 National College Student Innovation and Entrepreneurship Training Program(202210599004).
文摘[Objectives]To explore the effects of Polygona fallax Hemsl water extract on gastrointestinal motility in normal mice and gastric motility disorder model mice and approximate mechanism.[Methods]Using normal mice and mice with gastric motility disorders(modeled with atropine),the effects of different mass concentration groups of P.fallax Hemsl water extract(0.125,0.250,0.500 g/mL)and domperidone groups on gastric residual rate,small intestine propulsion rate,serum motilin(MLT),vasoactive intestinal peptide(VIP),and tissue morphology were studied.[Results]There was a highly significant difference(P<0.01)in the small intestine propulsion rate of liquid in normal mice among the different concentration groups of P.fallax Hemsl water extract compared to the blank group.The small intestine propulsion rate and gastric residue rate of semi-solid paste were statistically significant compared to the blank group(P<0.05).Among them,there was a highly significant difference between the high concentration group(67.75%±7.65%,46.5%±10.62%)and the medium concentration group(60.90%±5.87%,59.27%±7.82%)(P<0.01).There was statistical significance in normal mouse serum MLT content in the high concentration group(P<0.05).There was no effect on serum VIP levels in normal mice;no effect on the morphology of stomach and intestinal tissues of normal mice.The small intestine propulsion rate and gastric residue rate of liquid and semi-solid paste in mice with gastric motility disorders were statistically significant compared to the atropine group,with extremely significant differences(P<0.01).[Conclusions]P.fallax Hemsl water extract has a promoting effect on gastrointestinal motility.One of the specific mechanisms by which P.fallax Hemsl promotes gastrointestinal motility in normal mice may be related to the content of MLT in mouse serum.The mechanism of action in atropine induced gastric paresis mice may be related to the reactivation of M receptors,and the action mechanism of P.fallax Hemsl does not change the original histological basis.It can be inferred that P.fallax Hemsl water extract has a synergistic effect on promoting gastrointestinal motility through other mechanisms,but it is not fully understood and further in-depth research is needed.
文摘β-Nerve growth factor (β NGF) mRNA levels in hippocampa from C57BL/6J mice of different ages were compared by semi-quantitative RT-PCR method, taking β-actin gene as an internal control. The levels of 6-and 12-month-old C57 mice were much lower compared with that of the l-month-old mouse. However, there was no significant difference between these two groups. This result suggests that gene transcription level of hippocampus β NGF in a C57, mouse descends evidently as it grows up. Base T at Site 294 of β NGF cDNA was substituted by C in the C57, mouse, as revealed by DNA sequencing for the first time. Nevertheless, this polymorphism of nucleotide did not make any difference in amino acid composition.
文摘Epilepsy is a common and serious neurological disease that causes recurrent seizures. The brain damage caused by seizures can lead to depression, anxiety, cognitive impairment, or disability. In almost all cases chronic seizures are difficult to cure. MicroRNAs are widely expressed in the central nervous system and play important roles in the pathogenesis of several neurological disorders, including epilepsy. A variety of animals(mostly mice and rats) have been used to induce experimental epilepsy using different protocols and miRNA profiling performed. Most of the recent studies reviewed had performed miRNA profiling in hippocampal tissues and a large number of microRNAs were dysregulated when compared to controls. Most notably, miR-132-3p,-146a-5p,-10a-5p,-21a-3p,-27a-3p,-142a-5p,-212-3p,-431-5p, and-155 were upregulated in both the mouse and rat studies. Overexpression of miR-137 and miR-219 decreased seizure severity in a mouse epileptic model, and suppression of miR-451,-10a-5p,-21a-5p,-27a-5p,-142a-5p,-431-5p,-155, and-134 had a positive influence on seizure behavior. In the rat studies, overexpression of miR-139-5p decreased neuronal damage in drug-resistant rats and inhibition of miR-129-2-3p,-27a-3p,-155,-134,-181a, and-146a had a positive effect on seizure behavior and/or reduced the loss of neuronal cells. Further studies are warranted using adult female and immature male and female animals. It would also be helpful to test the ability of specific agomirs and antagomirs to control seizure activity in a subhuman primate model of epilepsy such as adult marmosets injected intraperitoneally with pilocarpine or cynomolgus monkeys given intrahippocampal injections of kainic acid.
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences (CAS) (XDB29010102)National Natural Science Foundation of China (NSFC) (91957124,82161148010,32041010)+4 种基金Self-supporting Program of Guangzhou Laboratory (SRPG22-001)National Science and Technology Infrastructure of China (National Pathogen Resource Center-NPRC-32)Management Strategy of the Tertiary Prevention and Treatment of Diabetes Based on DIP system (supported by China Health Promotion Foundation)supported by the Youth Innovation Promotion Association of CAS (Y2021034)Innovation Team and Talents Cultivation Program of the National Administration of Traditional Chinese Medicine (ZYYCXTD-D-202208)。
文摘Severe acute respiratory syndrome coronavirus 2(SARSCo V-2)infection can result in more severe syndromes and poorer outcomes in patients with diabetes and obesity.However,the precise mechanisms responsible for the combined impact of coronavirus disease 2019(COVID-19)and diabetes have not yet been elucidated,and effective treatment options for SARS-Co V-2-infected diabetic patients remain limited.To investigate the disease pathogenesis,K18-h ACE2 transgenic(h ACE2^(Tg))mice with a leptin receptor deficiency(h ACE2-Lepr^(-/-))and high-fat diet(h ACE2-HFD)background were generated.The two mouse models were intranasally infected with a 5×10^(5) median tissue culture infectious dose(TCID_(50))of SARSCo V-2,with serum and lung tissue samples collected at 3days post-infection.The h ACE2-Lepr^(-/-)mice were then administered a combination of low-molecular-weight heparin(LMWH)(1 mg/kg or 5 mg/kg)and insulin via subcutaneous injection prior to intranasal infection with1×10^(4) TCID_(50)of SARS-Co V-2.Daily drug administration continued until the euthanasia of the mice.Analyses of viral RNA loads,histopathological changes in lung tissue,and inflammation factors were conducted.Results demonstrated similar SARS-Co V-2 susceptibility in h ACE2^(Tg)mice under both lean(chow diet)and obese(HFD)conditions.However,compared to the h ACE2-Lepr^(+/+)mice,h ACE2-Lepr^(-/-)mice exhibited more severe lung injury,enhanced expression of inflammatory cytokines and hypoxia-inducible factor-1α(HIF-1α),and increased apoptosis.Moreover,combined LMWH and insulin treatment effectively reduced disease progression and severity,attenuated lung pathological changes,and mitigated inflammatory responses.In conclusion,preexisting diabetes can lead to more severe lung damage upon SARS-Co V-2 infection,and LMWH may be a valuable therapeutic approach for managing COVID-19patients with diabetes.
文摘Anti β NGF antiserum was prepared by immunizing rabbits with purified mouse β NGF. It presented immunopositivity to β NGF on Western blot, resulting in a single band approximately at the molecular weight of 14 kDa. The antiserum was further purified into anti β NGF IgG by affinity chromatography. Chicken embryonic dorsal root ganglia (DRG) were cultured to test the biological activities of β NGF and its antibody.
基金Supported by the National Natural Science Foundation of China(No.31972811)the Special Fund for Basic Scientific Research of Central Public Research Institutes(No.2020T51)。
文摘Reproduction is subtlety regulated by the hypothalamic-pituitary-gonad(HPG)axis in vertebrates.Pituitary gland is the center of the HPG axis,while pituitary gonadotropins follicle stimulating hormone(FSH)and luteinizing hormone(LH)were identified the key elements of the HPG axis in teleost and mammal.Morphology,cell lines,and gonadotropins cell localization of female turbot and mouse pituitary were determined at mature stage to illustrate the anatomical difference and cell characteristics in this study.Results show that turbot pituitary is chicken heart-shaped,dorsoventral,located on the ventral surface of the diencephalon.The mouse pituitary is oval,located in the pituitary fossa of the sella turcica at the skull base.Two well-distinguished areas adenohypophysis(AH)and neurohypophysis(NH)in pituitary were identified in turbot and mouse.Turbot AH comprised the rostral pars distalis(RPD),proximal pars distalis(PPD),and pars intermedia(PI).NH was not pronounced and with finger-like protrusions into PPD.However,mouse AH only comprised the pars distalis(PD)and PI.NH distribution was semicircular.Three main types of cells(acidophilic,basophilic,and chromophobic cells)were distributed in the mouse PD region,whereas appeared in the turbot PPD,RPD,and PI.Moreover,the percentage of mouse chromophobic and basophilic cells was higher and lower than that of turbot,respectively.The diameter of the aforementioned three cells in the mouse was significantly higher than turbot.fshβ-and lhβ-immunoreactive signals were identified in turbot-distinct pituitary cells that primarily occupied the peripheral and central regions of AH.However,mouse fsh-and lh-immunoreactive cells were expressed in the same cells and present in the PD.These results demonstrate the significantly difference of pituitary morphology,cell lines and gonadotropins(fshβand lhβ)location in female turbot and mouse.These differences help for fully understand the evolution and endocrinological functions of pituitary.
基金Princess Nourah bint Abdulrahman University Researchers Supporting Project number(PNURSP2022R203)Princess Nourah bint Abdulrahman University,Riyadh,Saudi ArabiaThe authors would like to thank the Deanship of Scientific Research at Umm Al-Qura University for supporting this work by Grant Code:22UQU4340237DSR03.
文摘Biomedical data classification has become a hot research topic in recent years,thanks to the latest technological advancements made in healthcare.Biome-dical data is usually examined by physicians for decision making process in patient treatment.Since manual diagnosis is a tedious and time consuming task,numerous automated models,using Artificial Intelligence(AI)techniques,have been presented so far.With this motivation,the current research work presents a novel Biomedical Data Classification using Cat and Mouse Based Optimizer with AI(BDC-CMBOAI)technique.The aim of the proposed BDC-CMBOAI technique is to determine the occurrence of diseases using biomedical data.Besides,the proposed BDC-CMBOAI technique involves the design of Cat and Mouse Optimizer-based Feature Selection(CMBO-FS)technique to derive a useful subset of features.In addition,Ridge Regression(RR)model is also utilized as a classifier to identify the existence of disease.The novelty of the current work is its designing of CMBO-FS model for data classification.Moreover,CMBO-FS technique is used to get rid of unwanted features and boosts the classification accuracy.The results of the experimental analysis accomplished by BDC-CMBOAI technique on benchmark medical dataset established the supremacy of the proposed technique under different evaluation measures.
基金supported by National Key R&D Program of China (2018YFD0901101)the Natural Science Foundation of Guangdong Province Research (2019A1515012230)+1 种基金Development Program in Key Areas of Guangdong Province (2019B020210002)the Fundamental Research Funds for the Central Universities (2019KZ01)。
文摘Mitochondrial dysfunction is proposed to be substantially associated with ageing and ageing-related diseases like Alzheimer's disease(AD). However, it is unclear whether different mouse models with mitochondrialrelated diseases have similar changes in mitochondrial morphology of the same tissues. Moreover, whether similarities in mitochondrial morphology can be a suitable marker for screening and/or discovering mitochondrial-protective substances remains unknown. Mitochondria morphology in different tissues of a novel mitochondrial outer membrane protein Slc25a46 knockout mouse and a traditional APP_(SWE)/PS1ΔE9 transgenic mouse were examined using transmission electron microscope(TEM). Both young Slc25a46 knockout mice and aged APP_(SWE)/PS1ΔE9 mice models showed similar mitochondrial damage in cerebellum tissues. The results indicated that different mitochondrial-related diseases shared similar alteration and defects in mitochondrial morphology. Furthermore, Lycium ruthenicum Murr. extract, a bioactive food substance with cognition-improving property, could effectively improve muscle strength and increase body weight in the Slc25a46 knockout mice. These findings suggest that mitochondrial morphology defects in mice models, particularly in the mitochondrial compartment, represent a unified and effective marker for screening and validating natural product-derived functional substances with mitochondrial protective properties. It also holds potential application in mitochondrial-impaired senile neurodegenerative diseases, especially in AD.
基金Supported by Natural Science Foundation of Shandong Province,China,No.ZR2020MH014,No.ZR2021QH179 and No.ZR2021MH182.
文摘BACKGROUND The low survival rate of mesenchymal stem cells(MSCs)caused by anoikis,a form of apoptosis,limits the therapeutic efficacy of MSCs.As a proapoptotic molecule,mammalian Ste20-like kinase 1(Mst1)can increase the production of reactive oxygen species(ROS),thereby promoting anoikis.Recently,we found that Mst1 inhibition could protect mouse bone marrow MSCs(mBMSCs)from H 2 O 2-induced cell apoptosis by inducing autophagy and reducing ROS production.However,the influence of Mst1 inhibition on anoikis in mBMSCs remains unclear.AIM To investigate the mechanisms by which Mst1 inhibition acts on anoikis in isolated mBMSCs.METHODS Poly-2-hydroxyethyl methacrylate-induced anoikis was used following the silencing of Mst1 expression by short hairpin RNA(shRNA)adenovirus transfection.Integrin(ITGs)were tested by flow cytometry.Autophagy and ITGα5β1 were inhibited using 3-methyladenine and small interfering RNA,respe-ctively.The alterations in anoikis were measured by Terminal-deoxynucleoitidyl Transferase Mediated Nick End Labeling and anoikis assays.The levels of the anoikis-related proteins ITGα5,ITGβ1,and phospho-focal adhesion kinase and the activation of caspase 3 and the autophagy-related proteins microtubules associated protein 1 light chain 3 II/I,Beclin1 and p62 were detected by Western blotting.RESULTS In isolated mBMSCs,Mst1 expression was upregulated,and Mst1 inhibition significantly reduced cell apoptosis,induced autophagy and decreased ROS levels.Mechanistically,we found that Mst1 inhibition could upregulate ITGα5 and ITGβ1 expression but not ITGα4,ITGαv,or ITGβ3 expression.Moreover,autophagy induced by upregulated ITGα5β1 expression following Mst1 inhibition played an essential role in the protective efficacy of Mst1 inhibition in averting anoikis.CONCLUSION Mst1 inhibition ameliorated autophagy formation,increased ITGα5β1 expression,and decreased the excessive production of ROS,thereby reducing cell apoptosis in isolated mBMSCs.Based on these results,Mst1 inhibition may provide a promising strategy to overcome anoikis of implanted MSCs.
文摘β-Nerve growth factor (β NGF) mRNA levels in hippocampa from C57BL/6J mice of different ages were compared by semi-quantitative RT-PCR method, taking β-actin gene as an internal control. The levels of 6-and 12-month-old C57 mice were much lower compared with that of the l-month-old mouse. However, there was no significant difference between these two groups. This result suggests that gene transcription level of hippocampus β NGF in a C57, mouse descends evidently as it grows up. Base T at Site 294 of β NGF cDNA was substituted by C in the C57, mouse, as revealed by DNA sequencing for the first time. Nevertheless, this polymorphism of nucleotide did not make any difference in amino acid composition.
