Nanoplastics-induced developmental and reproductive toxicity,neurotoxicity and immunotoxicity are a focus of widespread attention.However,the effects of nanoplastics(NPs)on glycolipid metabolism and the precise underl...Nanoplastics-induced developmental and reproductive toxicity,neurotoxicity and immunotoxicity are a focus of widespread attention.However,the effects of nanoplastics(NPs)on glycolipid metabolism and the precise underlying mechanisms are unclear at present.Here,we showed that oral administration of polystyrene nanoparticles(PS-NPs)disrupts glycolipid metabolism,with reactive oxygen species(ROS)identified as a potential key signaling molecule.After PS-NPs treatment,excessive production of ROS induced the infammatory response and activated the antioxidant pathway through nuclear factor-erythroid factor 2-related factor 2.The activation of nuclear factor-κB(NFκB)signaling pathway induced the phosphorylation of the mitogen-activated protein kinases(MAPK)signaling pathway,which induced the activation of extracellular regulated kinases(ERK)and p38.Constitutive activation of the MAPK signaling proteins induced high continued phosphorylation of insulin receptor substrate-1,in turn,leading to decreased protein kinase B(Akt)activity,which weakened the sensitivity of liver cells to insulin signals and induced insulin resistance.In parallel,phosphorylation of Akt led to loss of control of Fo XO1,a key gene of gluconeogenesis,activating transcription of glucose-6-phosphatase(G6PC)and phosphoenolpyruvate carboxykinase(PEPCK)in a manner dependent on PGC1α.Moreover,the activated ERK promoted lipid accumulation through ERK-PPARγcascades.Therefore,sterol regulatory element-binding protein-1 and levels of its downstream lipogenic enzymes,ACC-1,were up-regulated.Upon treatment with the antioxidant resveratrol,PS-NPs-induced glucose and lipid metabolic disorders were improved by inhibiting ROS-induced activation of NFκB and MAPK signaling pathway in mice.Based on above,PS-NPs exposure disrupts glycolipid metabolism in mice,with ROS identified as a potential key signaling molecule.展开更多
As an ultrasmall derivative of black phosphorus(BP)sheets,BP quantum dots(BP-QDs)have been effectively used in many fields.Currently,information on the cardiotoxicity induced by BP-QDs remains limited.We aimed to eval...As an ultrasmall derivative of black phosphorus(BP)sheets,BP quantum dots(BP-QDs)have been effectively used in many fields.Currently,information on the cardiotoxicity induced by BP-QDs remains limited.We aimed to evaluate BP-QD-induced cardiac toxicity in mice.Histopathological examination of heart tissue sections was performed.Transcriptome sequencing,real-time quantitative PCR(RT–qPCR),western blotting,and enzyme-linked immunosorbent assay(ELISA)assays were used to detect the m RNA and/or protein expression of proinfammatory cytokines,nuclear factor kappa B(NF-κB),phosphatidylinositol3 kinase-protein kinase B(PI3K-AKT),peroxisome proliferator-activated receptor gamma(PPARγ),and glucose/lipid metabolism pathway-related genes.We found that heart weight and heart/body weight index(HBI)were significantly reduced in mice after intragastric administration of 0.1 or 1 mg/kg BP-QDs for 28 days.In addition,obvious infammatory cell infiltration and increased cardiomyocyte diameter were observed in the BP-QD-treated groups.Altered expression of proinfammatory cytokines and genes related to the NF-κB signaling pathway further confirmed that BP-QD exposure induced infammatory responses.In addition,BP-QD treatment also affected the PI3K-AKT,PPARγ,thermogenesis,oxidative phosphorylation,and cardiac muscle contraction signaling pathways.The expression of genes related to glucose/lipid metabolism signaling pathways was dramatically affected by BP-QD exposure,and the effect was primarily mediated by the PPAR signaling pathway.Our study provides new insights into the toxicity of BP-QDs to human health.展开更多
Guo-Qiang XuFor a long time, it was believed that apoptosis and necrosis were the main pathways for cell death, but a growing body of research has shown that there are other pathways. Among these, necroptosis, a regul...Guo-Qiang XuFor a long time, it was believed that apoptosis and necrosis were the main pathways for cell death, but a growing body of research has shown that there are other pathways. Among these, necroptosis, a regulatory caspase-independent, programmed cell death pathway, is supposed to be of importance in the pathogenesis of many diseases. The mechanism of regulating, in-ducing and blocking necroptosis is a complex process that involves expression and regulation of a series of molecules including receptor interacting protein kinase 1 （RIPK1）, RIPK3, and mixed lineage kinase like protein. By blocking or downregulating expression of key molecules in the necroptotic pathway, intestinal inflammation can be affected to some extent. In this paper, we introduce the concept of necroptosis, its main pathway, and its impact on the pathogenesis ofinfammatory bowel disease （IBD） and other intestinal diseases, to explore new drug targets for intestinal diseases, including IBD.展开更多
The incidence rate of anxiety and depression is significantly higher in patients with inflammatory bowel diseases(IBD)than in the general population.The mechanisms underlying dextran sulfate sodium(DSS)-induced depres...The incidence rate of anxiety and depression is significantly higher in patients with inflammatory bowel diseases(IBD)than in the general population.The mechanisms underlying dextran sulfate sodium(DSS)-induced depressive-like behaviors are still unclear.We clarified that IBD mice induced by repeated administration of DSS presented depressive-like behaviors.The paraventricular thalamic nucleus(PVT)was regarded as the activated brain region by the number of c-fos-labeled neurons.RNA-sequencing analysis showed that lipocalin 2(Lcn2)was upregulated in the PVT of mice with DSS-induced depressive behaviors.Upregulating Lcn2 from neuronal activity induced dendritic spine loss and the secreted protein induced chemokine expression and subsequently contributed to microglial activation leading to blood-brain barrier permeability.Moreover,Lcn2 silencing in the PVT alleviated the DSS-induced depressive-like behaviors.The present study demonstrated that elevated Lcn2 in the PVT is a critical factor for DSS-induced depressive behaviors.展开更多
A 19-year-old female was diagnosed with ulcerative colitis when she presented with persistent melena, and has been treated with 5-aminosalicylic acid for 4 years, with additional azathioprine for 2 years at our hospit...A 19-year-old female was diagnosed with ulcerative colitis when she presented with persistent melena, and has been treated with 5-aminosalicylic acid for 4 years, with additional azathioprine for 2 years at our hospital. The patient experienced high-grade fevers, chills, and cough fve d prior to presenting to the outpatient unit. At frst, the patient was suspected to have developed neutropenic fever; however, she was diagnosed with Epstein-Barr virus-associated hemophagocytic syndr-ome （EB-VAHS） upon fulfilling the diagnostic criteria after bone marrow aspiration. When patients withinflammatory bowel disease treated with immunomo-dulators, such as thiopurine preparations, develop fever, EB-VAHS should be considered in the differential diagnosis.展开更多
Inflammatory bowel diseases(IBDs)are complex chronic disorders of the gastrointestinal tract with the following two subtypes:Crohn's disease and ulcerative colitis.Disease presentation and progression within and a...Inflammatory bowel diseases(IBDs)are complex chronic disorders of the gastrointestinal tract with the following two subtypes:Crohn's disease and ulcerative colitis.Disease presentation and progression within and across IBDs,especially Crohn's disease,are highly heterogeneous in the location,severity of inflammation,intestinal stenosis and obstruction,and extraintestinal manifestations.Clinical classifications fail to accurately predict the disease course and response to therapies.To date,most IBD genetic associations are derived from individuals of European ancestries,leading to a limitation of the discovery and application of IBD genetics in the rest of the world populations.In this mini-review,we summarize the latest progress of genome-wide association studies of IBD across global ancestries especially the Chinese population,the similarities and differences in genetic architecture between European and East Asian ancestries,as well as,the clinical significances relevant to IBD genetic study.展开更多
基金supported by the State Key Laboratory of Urban Water Resource and Environment (Harbin Institute of Technology) (No.2022TS28)the Natural Science Foundation of Heilongjiang Province (No.LH2021B012)the Fundamental Research Funds for the Central Universities (No.HIT.NSRIF202209)。
文摘Nanoplastics-induced developmental and reproductive toxicity,neurotoxicity and immunotoxicity are a focus of widespread attention.However,the effects of nanoplastics(NPs)on glycolipid metabolism and the precise underlying mechanisms are unclear at present.Here,we showed that oral administration of polystyrene nanoparticles(PS-NPs)disrupts glycolipid metabolism,with reactive oxygen species(ROS)identified as a potential key signaling molecule.After PS-NPs treatment,excessive production of ROS induced the infammatory response and activated the antioxidant pathway through nuclear factor-erythroid factor 2-related factor 2.The activation of nuclear factor-κB(NFκB)signaling pathway induced the phosphorylation of the mitogen-activated protein kinases(MAPK)signaling pathway,which induced the activation of extracellular regulated kinases(ERK)and p38.Constitutive activation of the MAPK signaling proteins induced high continued phosphorylation of insulin receptor substrate-1,in turn,leading to decreased protein kinase B(Akt)activity,which weakened the sensitivity of liver cells to insulin signals and induced insulin resistance.In parallel,phosphorylation of Akt led to loss of control of Fo XO1,a key gene of gluconeogenesis,activating transcription of glucose-6-phosphatase(G6PC)and phosphoenolpyruvate carboxykinase(PEPCK)in a manner dependent on PGC1α.Moreover,the activated ERK promoted lipid accumulation through ERK-PPARγcascades.Therefore,sterol regulatory element-binding protein-1 and levels of its downstream lipogenic enzymes,ACC-1,were up-regulated.Upon treatment with the antioxidant resveratrol,PS-NPs-induced glucose and lipid metabolic disorders were improved by inhibiting ROS-induced activation of NFκB and MAPK signaling pathway in mice.Based on above,PS-NPs exposure disrupts glycolipid metabolism in mice,with ROS identified as a potential key signaling molecule.
基金supported by the National Natural Science Foundation of China (Nos.32071301 and 31971234)。
文摘As an ultrasmall derivative of black phosphorus(BP)sheets,BP quantum dots(BP-QDs)have been effectively used in many fields.Currently,information on the cardiotoxicity induced by BP-QDs remains limited.We aimed to evaluate BP-QD-induced cardiac toxicity in mice.Histopathological examination of heart tissue sections was performed.Transcriptome sequencing,real-time quantitative PCR(RT–qPCR),western blotting,and enzyme-linked immunosorbent assay(ELISA)assays were used to detect the m RNA and/or protein expression of proinfammatory cytokines,nuclear factor kappa B(NF-κB),phosphatidylinositol3 kinase-protein kinase B(PI3K-AKT),peroxisome proliferator-activated receptor gamma(PPARγ),and glucose/lipid metabolism pathway-related genes.We found that heart weight and heart/body weight index(HBI)were significantly reduced in mice after intragastric administration of 0.1 or 1 mg/kg BP-QDs for 28 days.In addition,obvious infammatory cell infiltration and increased cardiomyocyte diameter were observed in the BP-QD-treated groups.Altered expression of proinfammatory cytokines and genes related to the NF-κB signaling pathway further confirmed that BP-QD exposure induced infammatory responses.In addition,BP-QD treatment also affected the PI3K-AKT,PPARγ,thermogenesis,oxidative phosphorylation,and cardiac muscle contraction signaling pathways.The expression of genes related to glucose/lipid metabolism signaling pathways was dramatically affected by BP-QD exposure,and the effect was primarily mediated by the PPAR signaling pathway.Our study provides new insights into the toxicity of BP-QDs to human health.
基金Supported by Medical Science Research Foundation of Health Bureau of Zhejiang Province,No.WKJ-ZJ-1516
文摘Guo-Qiang XuFor a long time, it was believed that apoptosis and necrosis were the main pathways for cell death, but a growing body of research has shown that there are other pathways. Among these, necroptosis, a regulatory caspase-independent, programmed cell death pathway, is supposed to be of importance in the pathogenesis of many diseases. The mechanism of regulating, in-ducing and blocking necroptosis is a complex process that involves expression and regulation of a series of molecules including receptor interacting protein kinase 1 （RIPK1）, RIPK3, and mixed lineage kinase like protein. By blocking or downregulating expression of key molecules in the necroptotic pathway, intestinal inflammation can be affected to some extent. In this paper, we introduce the concept of necroptosis, its main pathway, and its impact on the pathogenesis ofinfammatory bowel disease （IBD） and other intestinal diseases, to explore new drug targets for intestinal diseases, including IBD.
基金supported by the National Natural Science Foundation of China(82001424,82171176)the Key Program of the Natural Science Foundation of Zhejiang,China(LZ19H090003).
文摘The incidence rate of anxiety and depression is significantly higher in patients with inflammatory bowel diseases(IBD)than in the general population.The mechanisms underlying dextran sulfate sodium(DSS)-induced depressive-like behaviors are still unclear.We clarified that IBD mice induced by repeated administration of DSS presented depressive-like behaviors.The paraventricular thalamic nucleus(PVT)was regarded as the activated brain region by the number of c-fos-labeled neurons.RNA-sequencing analysis showed that lipocalin 2(Lcn2)was upregulated in the PVT of mice with DSS-induced depressive behaviors.Upregulating Lcn2 from neuronal activity induced dendritic spine loss and the secreted protein induced chemokine expression and subsequently contributed to microglial activation leading to blood-brain barrier permeability.Moreover,Lcn2 silencing in the PVT alleviated the DSS-induced depressive-like behaviors.The present study demonstrated that elevated Lcn2 in the PVT is a critical factor for DSS-induced depressive behaviors.
文摘A 19-year-old female was diagnosed with ulcerative colitis when she presented with persistent melena, and has been treated with 5-aminosalicylic acid for 4 years, with additional azathioprine for 2 years at our hospital. The patient experienced high-grade fevers, chills, and cough fve d prior to presenting to the outpatient unit. At frst, the patient was suspected to have developed neutropenic fever; however, she was diagnosed with Epstein-Barr virus-associated hemophagocytic syndr-ome （EB-VAHS） upon fulfilling the diagnostic criteria after bone marrow aspiration. When patients withinflammatory bowel disease treated with immunomo-dulators, such as thiopurine preparations, develop fever, EB-VAHS should be considered in the differential diagnosis.
基金supported by the Shanghai Hospital Development Center Foundation(Grant No.SHDC12022118)the National Natural Science Foundation of China(Grant No.91942312).
文摘Inflammatory bowel diseases(IBDs)are complex chronic disorders of the gastrointestinal tract with the following two subtypes:Crohn's disease and ulcerative colitis.Disease presentation and progression within and across IBDs,especially Crohn's disease,are highly heterogeneous in the location,severity of inflammation,intestinal stenosis and obstruction,and extraintestinal manifestations.Clinical classifications fail to accurately predict the disease course and response to therapies.To date,most IBD genetic associations are derived from individuals of European ancestries,leading to a limitation of the discovery and application of IBD genetics in the rest of the world populations.In this mini-review,we summarize the latest progress of genome-wide association studies of IBD across global ancestries especially the Chinese population,the similarities and differences in genetic architecture between European and East Asian ancestries,as well as,the clinical significances relevant to IBD genetic study.
