Objective To investigate whether there are sex differences in inflammatory bowel disease(IBD)among the offspring of mice with IBD.Methods BALB/c female mice were randomly divided into Na?ve and DSS groups.The mice in the Na?ve group drank autoclaved water freely,and the DSS group freely drank 2％dextran sodium sulfate(DSS)for 7 days before it was replaced with autoclaved water for 10 days.A total of 3～4 cycles were applied,and the IBD female mice were paired with healthy male mice in cages.When the pups were 8 weeks old,they were divided into the Con group and IBD group.The Con group drank autoclaved water freely for 7 days,and the IBD group drank 3％DSS for 7 days.During the modeling period,disease activity index was scored by monitoring body weight,fecal consistency,and the presence of blood in stool every day.Pathological sections were taken to observe changes in goblet cells and the mucus layer of colon tissues.The concentrations of interleukin(IL)-6,IL-1β,IL-33,and IL-10 in the colon were detected by enzyme-linked immunosorbent assay.Real-time quantitative PCR was used to determine the mRNA expression levels of tight-junction proteins and MUC-2 in the colon.Results Compared with female IBD mice,male IBD mice had higher DAI scores,significantly shorter colons,larger amounts of inflammatory infiltrate,more crypt abnormalities,and a higher absence of goblet cells in the colon;their relative mRNA expression of occludin mRNA was significantly reduced,levels of IL-6 and IL-33 were significantly increased,and level of IL-10 was significantly decreased.Conclusions The symptoms of colitis in the offspring of IBD mice were more severe in male than in female mice,a result that was mainly attributed to the more severely impaired intestinal epithelial barrier function in males.

Objective In this study,we aimed to use network pharmacology techniques to predict the key targets of a prescription of Ziziphi spinosae semen formula(ZSSF)compound for depression,and to verify its mechanism of action using a zebrafish model of rifampicin-induced depression.Methods The drug targets of ZSSF were retrieved from the TCMSP database,and the target names were corrected using the UniProt database.Depression-related targets were identified using the GeneCards,OMIM,and NCBI databases.Protein-protein interaction information for the shared targets was predicted using the STRING database.The collected data were then analyzed using the Metascape database to determine GO and KEGG pathway enrichment,and the result were visualized using microbiotics.Behavioral experiments and reverse-transcription quantitative PCR experiments were conducted to verify the therapeutic effects of ZSSF on a zebrafish depression model induced by risperdal.Results 188 targets were screened to find the interactions between depression and ZSSF.The protein-protein interaction result showed that ZSSF primarily targeted TNF-α,IL-2,IL-6,IL-1β,and IL-10 to produce its antidepressant effect.KEGG pathway enrichment analysis revealed that ZSSF exerted its effects on depression through various signaling pathways,including the TNF,PI3K-Akt,and cGMP-PKG signaling pathways.The result of the animal experiments showed that the treatment groups given high,medium,and low doses of ZSSF exhibited significant improvements in movement distance under acoustic and light stimulation compared with the model group(P＜0.05).The speed of movement of the treatment groups was also significantly faster(P＜0.01).Additionally,the mRNA expression levels of TNF-α,IL-2,IL-6,IL-1β,and IL-10 were up-regulated in the brain tissues of zebrafish in the high-,medium-,and low-dosage groups of ZSSF compared those in the model group(P＜0.001).Conclusions ZSSF exerts its antidepressant effect through multiple components and targets,and its antidepressant effects may be associated with its inhibition of inflammatory factors.

Objective To investigate the effects of alcoholic extract of Hemerocallis citrina Baroni on the depressive-like behaviors in zebrafish larvae(Danio rerio)induced by reserpine.Methods Zebrafish larvae were divided into various groups:control(Con)group,reserpine group,fluoxetine group,H.citrina alcohol extract(HCE)low dose group(1.5 mg/L),HCE medium dose group(3 mg/L),and HCE high dose group(4.5 mg/L).Depressive-like behaviors were analyzed using sound and light stimulation.Real-time PCR was used to investigate the effects of HCE on depression related astrocyte markers(GFAP,C3,C4B,EMP-1,S100α-10)and the neurotrophic factor BDNF and its receptor genes(P75,TrkB).Results In comparison to the control group,the model group demonstrated significantly shorter movement distance and reduced movement time under sound and light stimulation(P＜0.05,P＜0.001,P＜0.0001).Following the administration of HCE,zebrafish larvae exhibited significantly heightened sensitivity to light and sound stimulation compared to the model group(P＜0.05,P＜0.0001).Astrocyte marker genes were up-regulated in the model group zebrafish brains compared to the control group(P＜0.0001).However,when the model group was administered HCE,the expression of astrocyte markers was significantly down-regulated compared to the model group(P＜0.0001).Neurotrophic factor and its receptor genes(BDNF,P75,TrkB)were down-regulated in zebrafish brains in the model group compared to those in the control group(P＜0.0001).However,in the group administered HCE,the expression of BDNF,P75,and TrkB was significantly up-regulated compared to that in the model group(P＜0.01,P＜0.0001).These findings suggest that HCE suppressed the inflammatory responses caused by astrocyte activation and promoted the production of neurotrophic factors and their receptor genes,thereby exerting an ameliorative effect on depression.Conclusions Alcoholic extracts of H.citrina can ameliorate the depression-like behavioral changes induced by reserpine in zebrafish larvae.They reduce the expression of astrocyte markers in the zebrafish brain and promote the production of neurotrophic factors and their receptor genes,playing an antidepressant role.

Objective To examine the hypoglycemic effect of Chinese yam polysaccharide on the 3T3-L1 insulin resistance cell model.Methods IR-3T3-L1 adipocytes were randomly divided into control group(Con),model group(DEX),metformin group(Met,positive drug group)and CYPS group(0.05,0.15,0.45 mg/mL).After the creation of the IR-3T3-L1 cell model by dexamethasone(DEX)(1 μmol/L)stimulation,Chinese yam polysaccharide treatment was applied.Glucose intake and the levels of TC,TG,LDL-C,HDL-C,GSH-Px,MDA,HK,and PK were then measured.AMPK-PI3K/Akt signaling pathway-associated gene expression was identified using qRT-PCR.Results The glucose consumption of IR-3T3-L1 cells was considerably decreased after 48 hours of treatment with 1 μmol/L DEX compared to that of the Con group(P＜0.01),and the reduction persisted for 60 hours.0.05,0.15,0.45 mg/mL CYPS treatment significantly increased glucose consumption(P＜0.01),HK,PK,GSH-Px enzyme activities(P＜0.01),HDL-C content(P＜0.01),and decreased MDA enzyme activity(P＜0.01),T-CHO,TG,LDL-C content(P＜0.01)in IR-3T3-L1 cells.01).Additionally,CYPS administration dramatically decreased PI3K,Akt,GLUT-4,AMPK,IRS-2,PPARa,and adiponectin mRNA expression levels(P＜0.05)and reduced IRS-1,GSK-3β,ACC,and FAS mRNA expression levels(P＜0.01).Conclusions In IR-3T3-L1 cells,CYPS can reduce oxidative stress,control lipid metabolism disorders,and enhance DEX-induced glucose intake.AMPK-PI3K/Akt signaling pathway-associated genes may be connected to the process.

Objective To construct a prognostic risk model for exploring the prognostic value of copper metabolism related genes(CMRGs)in lung adenocarcinoma(LUAD),thereby providing a reference for personalized treatment of LUAD patients.Methods The RNA-seq data of LUAD tissues and adjacent or normal lung tissues were downloaded from the Cancer Genome Atlas(TCGA)database and Genotype-tissue Expression(GTEx)database.The risk scoring model was established using univariate Cox regression analysis,Lasso analysis and multivariate Cox regression analysis,and the receiver operating characteristic(ROC)curves and nomogram were used to evaluate the model performance.The LUAD data in the Gene Expression Omnibus(GEO),the Tumor Immune Single-cell Hub(TISCH)single-cell sequencing analysis,and the Human Protein Atlas(HPA)immunohistochemistry analysis were used for external validation.Additionally,the immune microenvironment and drug sensitivity of high-and low-risk groups were analyzed.Results A risk model consisting of 6 genes was constructed.The overall survival rate of low-risk group was higher than that of high-risk group(P<0.001).ROC analysis showed that the area under curve of the risk model in training set reached 0.729,0.749 and 0.707 at 1-,3-and 5-year,respectively,and the C index of C-index curve was 0.721(95%CI:0.678-0.764).The immune microenvironment differed significantly between high-and low-risk groups(P<0.001),and the drug sensitivity analysis in high-and low-risk groups revealed that there was statistically significant for gemcitabine,gefitinib,crizotinib and savolitinib(P<0.001).Conclusion The risk model constructed with 6 CMRGs enable the prediction of the prognosis of LUAD patients.The immune microenvironment differs in high-and low-risk group,and high-risk patients are more sensitive to drugs such as gemcitabine,gefitinib,crizotinib and savolitinib,which provide a reference for the personalized treatment of LUAD patients.

Diabetes has long been considered a risk factor in implant therapy and impaired wound healing in soft and hard oral tissues. Magnesium has been proved to promote bone healing under normal conditions. Here, we elucidate the mechanism by which Mg²⁺ promotes angiogenesis and osseointegration in diabetic status. We generated a diabetic mice model and demonstrated the alveolar bone healing was compromised, with significantly decreased angiogenesis. We then developed Mg-coating implants with hydrothermal synthesis. These implants successfully improved the vascularization and osseointegration in diabetic status. Mechanically, Mg²⁺ promoted the degradation of Kelch-like ECH-associated protein 1 (Keap1) and the nucleation of nuclear factor erythroid 2-related factor 2 (Nrf2) by up-regulating the expression of sestrin 2 (SESN2) in endothelial cells, thus reducing the elevated levels of oxidative stress in mitochondria and relieving endothelial cell dysfunction under hyperglycemia. Altogether, our data suggested that Mg²⁺ promoted angiogenesis and osseointegration in diabetic mice by regulating endothelial mitochondrial metabolism.
Mice ; Animals ; Kelch-Like ECH-Associated Protein 1/metabolism* ; Magnesium/metabolism* ; Osseointegration ; Diabetes Mellitus, Experimental/metabolism* ; Endothelial Cells/metabolism* ; NF-E2-Related Factor 2/metabolism*

Diabetes has long been considered a risk factor in implant therapy and impaired wound healing in soft and hard oral tissues.Magnesium has been proved to promote bone healing under normal conditions.Here,we elucidate the mechanism by which Mg2+ promotes angiogenesis and osseointegration in diabetic status.We generated a diabetic mice model and demonstrated the alveolar bone healing was compromised,with significantly decreased angiogenesis.We then developed Mg-coating implants with hydrothermal synthesis.These implants successfully improved the vascularization and osseointegration in diabetic status.Mechanically,Mg2+ promoted the degradation of Kelch-like ECH-associated protein 1(Keap1)and the nucleation of nuclear factor erythroid 2-related factor 2(Nrf2)by up-regulating the expression of sestrin 2(SESN2)in endothelial cells,thus reducing the elevated levels of oxidative stress in mitochondria and relieving endothelial cell dysfunction under hyperglycemia.Altogether,our data suggested that Mg2+ promoted angiogenesis and osseointegration in diabetic mice by regulating endothelial mitochondrial metabolism.

Diabetes has long been considered a risk factor in implant therapy and impaired wound healing in soft and hard oral tissues.Magnesium has been proved to promote bone healing under normal conditions.Here,we elucidate the mechanism by which Mg2+ promotes angiogenesis and osseointegration in diabetic status.We generated a diabetic mice model and demonstrated the alveolar bone healing was compromised,with significantly decreased angiogenesis.We then developed Mg-coating implants with hydrothermal synthesis.These implants successfully improved the vascularization and osseointegration in diabetic status.Mechanically,Mg2+ promoted the degradation of Kelch-like ECH-associated protein 1(Keap1)and the nucleation of nuclear factor erythroid 2-related factor 2(Nrf2)by up-regulating the expression of sestrin 2(SESN2)in endothelial cells,thus reducing the elevated levels of oxidative stress in mitochondria and relieving endothelial cell dysfunction under hyperglycemia.Altogether,our data suggested that Mg2+ promoted angiogenesis and osseointegration in diabetic mice by regulating endothelial mitochondrial metabolism.

Diabetes has long been considered a risk factor in implant therapy and impaired wound healing in soft and hard oral tissues.Magnesium has been proved to promote bone healing under normal conditions.Here,we elucidate the mechanism by which Mg2+ promotes angiogenesis and osseointegration in diabetic status.We generated a diabetic mice model and demonstrated the alveolar bone healing was compromised,with significantly decreased angiogenesis.We then developed Mg-coating implants with hydrothermal synthesis.These implants successfully improved the vascularization and osseointegration in diabetic status.Mechanically,Mg2+ promoted the degradation of Kelch-like ECH-associated protein 1(Keap1)and the nucleation of nuclear factor erythroid 2-related factor 2(Nrf2)by up-regulating the expression of sestrin 2(SESN2)in endothelial cells,thus reducing the elevated levels of oxidative stress in mitochondria and relieving endothelial cell dysfunction under hyperglycemia.Altogether,our data suggested that Mg2+ promoted angiogenesis and osseointegration in diabetic mice by regulating endothelial mitochondrial metabolism.

Diabetes has long been considered a risk factor in implant therapy and impaired wound healing in soft and hard oral tissues.Magnesium has been proved to promote bone healing under normal conditions.Here,we elucidate the mechanism by which Mg2+ promotes angiogenesis and osseointegration in diabetic status.We generated a diabetic mice model and demonstrated the alveolar bone healing was compromised,with significantly decreased angiogenesis.We then developed Mg-coating implants with hydrothermal synthesis.These implants successfully improved the vascularization and osseointegration in diabetic status.Mechanically,Mg2+ promoted the degradation of Kelch-like ECH-associated protein 1(Keap1)and the nucleation of nuclear factor erythroid 2-related factor 2(Nrf2)by up-regulating the expression of sestrin 2(SESN2)in endothelial cells,thus reducing the elevated levels of oxidative stress in mitochondria and relieving endothelial cell dysfunction under hyperglycemia.Altogether,our data suggested that Mg2+ promoted angiogenesis and osseointegration in diabetic mice by regulating endothelial mitochondrial metabolism.