Air pollution is fourth major cause of death worldwide.Recent evidence suggests that particulate matter(PM)may affect kidneys,and the effect may be size and composition dependent.In this study,PM_(0.1),PM_(2.5),and PM...Air pollution is fourth major cause of death worldwide.Recent evidence suggests that particulate matter(PM)may affect kidneys,and the effect may be size and composition dependent.In this study,PM_(0.1),PM_(2.5),and PM_(10)were collected from ambient air and given to BALB/c male mice at 0.25 mg/m^(3) concentration in whole-body inhalation chamber for 28days(6 h/day,5 days/week)to assess their effect on kidney.Physico-chemical characterization of PM particles by SEM,ICP-MS and HPLC showed their various shapes along with the presence of metals and poly aromatic hydrocarbons(PAHs).Following PM exposure,increased serum creatinine levels were observed in animals along with dilated tubules,protein cast deposition,necrosis,immune infiltration,collagen deposition,and shrunken glomeruli in kidney.Immunofluorescence staining showed higher expressions of kidney injury molecule1(KIM-1),cystatin C,β2 microglobulin(β2M),and alpha smooth muscle actin(α-SMA)and fibronectin,suggesting renal injury and fibrosis.PM exposure also increased malondialdehyde(MDA)content and decreased superoxide dismutase 2(SOD2)activity,which in turn leads to induction of inflammation.Mechanistically,PM exposure further inhibited the nuclear factor erythroid 2-related factor 2(Nrf2)signalling and induced kelch-like ECH-associated protein 1(Keap1)and nuclear factor kappa-light-chain-enhancer of activated B(NF-κB).Interestingly,the effect of PM_(2.5)was more severe than PM_(0.1)and PM_(10),leading to higher levels of proinflammatory NF-κB and greater Nrf2 inhibition.Overall,our findings suggested that inhalation exposure to size-segregated PM can cause kidney damage and fibrosis,and PM_(2.5)showed higher toxicity than PM_(0.1)and PM_(10).展开更多
Metabolic dysfunction-associated steatotic liver disease(MASLD),formerly referred to as non-alcoholic fatty liver disease,is a major cause of end-stage liver disease worldwide.Numerous studies have demonstrated that t...Metabolic dysfunction-associated steatotic liver disease(MASLD),formerly referred to as non-alcoholic fatty liver disease,is a major cause of end-stage liver disease worldwide.Numerous studies have demonstrated that the liver is predominantly influenced by environmental and lifestyle risk factors that lead to obesity and diabetes,excessive alcohol consumption,and exposure to environmental pollutants.Microplastics(MPs)are a significant global concern,having been detected in human blood,lungs,kidneys,and liver,and may have deleterious effects on these tissues.Although the effects of MP exposure on the liver have only been partially elucidated,further research is necessary to integrate the direct and extrahepatic effects of MPs on the pathogenesis of MASLD.This review offers a comprehensive analysis of the impact of MPs on hepatic metabolism,including their effects on mitochondrial homeostasis and the endocrine system,with potential implications for the progression of MASLD.展开更多
Metabolic dysfunction-associated steatohepatitis(MASH)and alcoholic steatohepatitis(ASH)are severe forms of chronic liver disease,characterized by inflammation,oxidative stress,lipid dysregulation,and fibrosis.Epigene...Metabolic dysfunction-associated steatohepatitis(MASH)and alcoholic steatohepatitis(ASH)are severe forms of chronic liver disease,characterized by inflammation,oxidative stress,lipid dysregulation,and fibrosis.Epigenetic changes,including acetylation,methylation,phosphorylation,ubiquitination,sumoylation,and lactylation of histones,dynamically regulate gene expression by altering the chromatin structure.Emerging evidence highlights histone modifications as chief contributors to the pathogenesis of chronic liver diseases.Lactylation which is a novel post-translational modification(PTM)of histone,has been observed as a crucial contributor to liver physiology as well as pathobiology.This modification,characterized by the addition of lactate to lysine residues on histones,influences gene expression and cellular metabolism in the liver.Intriguingly,elevated lactate levels in the liver,resulting from either chronic alcohol consumption or a highfat/fructose-rich diet,may promote histone lactylation,particularly at histone 3 at lysine 18(H3K18),which facilitates the transcription of pro-inflammatory and fibrogenic genes.This process not only intensifies hepatic inflammation and fibrosis but also disrupts normal metabolic pathways,resulting in further liver damage.This review aims to elucidate the role of histone lactylation in MASH.Although a direct demonstration of histone lactylation in ASH has not yet been reported,the altered lactate metabolism in ASH suggests that histone lactylation may significantly contribute to its pathogenesis.Finally,we explore novel strategies targeting histone lactylation to mitigate liver injury and improve disease management in MASH and ASH.展开更多
基金supported by the institutional fund MLP004 and Science and Engineering Research Board(SERB)(No.CRG/2021/002625)financial assistance from DBT-JRF,Department of Biotechnology,Gov of India,New Delhi India(DBT/2018/1111)。
文摘Air pollution is fourth major cause of death worldwide.Recent evidence suggests that particulate matter(PM)may affect kidneys,and the effect may be size and composition dependent.In this study,PM_(0.1),PM_(2.5),and PM_(10)were collected from ambient air and given to BALB/c male mice at 0.25 mg/m^(3) concentration in whole-body inhalation chamber for 28days(6 h/day,5 days/week)to assess their effect on kidney.Physico-chemical characterization of PM particles by SEM,ICP-MS and HPLC showed their various shapes along with the presence of metals and poly aromatic hydrocarbons(PAHs).Following PM exposure,increased serum creatinine levels were observed in animals along with dilated tubules,protein cast deposition,necrosis,immune infiltration,collagen deposition,and shrunken glomeruli in kidney.Immunofluorescence staining showed higher expressions of kidney injury molecule1(KIM-1),cystatin C,β2 microglobulin(β2M),and alpha smooth muscle actin(α-SMA)and fibronectin,suggesting renal injury and fibrosis.PM exposure also increased malondialdehyde(MDA)content and decreased superoxide dismutase 2(SOD2)activity,which in turn leads to induction of inflammation.Mechanistically,PM exposure further inhibited the nuclear factor erythroid 2-related factor 2(Nrf2)signalling and induced kelch-like ECH-associated protein 1(Keap1)and nuclear factor kappa-light-chain-enhancer of activated B(NF-κB).Interestingly,the effect of PM_(2.5)was more severe than PM_(0.1)and PM_(10),leading to higher levels of proinflammatory NF-κB and greater Nrf2 inhibition.Overall,our findings suggested that inhalation exposure to size-segregated PM can cause kidney damage and fibrosis,and PM_(2.5)showed higher toxicity than PM_(0.1)and PM_(10).
基金Supported by the Science and Engineering Research Board,No.CRG/2022/002149Indian Council of Medical Research,No.ICMR/02/833/IGP-2024.
文摘Metabolic dysfunction-associated steatotic liver disease(MASLD),formerly referred to as non-alcoholic fatty liver disease,is a major cause of end-stage liver disease worldwide.Numerous studies have demonstrated that the liver is predominantly influenced by environmental and lifestyle risk factors that lead to obesity and diabetes,excessive alcohol consumption,and exposure to environmental pollutants.Microplastics(MPs)are a significant global concern,having been detected in human blood,lungs,kidneys,and liver,and may have deleterious effects on these tissues.Although the effects of MP exposure on the liver have only been partially elucidated,further research is necessary to integrate the direct and extrahepatic effects of MPs on the pathogenesis of MASLD.This review offers a comprehensive analysis of the impact of MPs on hepatic metabolism,including their effects on mitochondrial homeostasis and the endocrine system,with potential implications for the progression of MASLD.
基金Supported by the Science and Engineering Research Board,No.CRG/2022/002149the Indian Council of Medical Research,No.ICMR/02/833/IGP-2024 and No.R.12016/12/2023-HR.
文摘Metabolic dysfunction-associated steatohepatitis(MASH)and alcoholic steatohepatitis(ASH)are severe forms of chronic liver disease,characterized by inflammation,oxidative stress,lipid dysregulation,and fibrosis.Epigenetic changes,including acetylation,methylation,phosphorylation,ubiquitination,sumoylation,and lactylation of histones,dynamically regulate gene expression by altering the chromatin structure.Emerging evidence highlights histone modifications as chief contributors to the pathogenesis of chronic liver diseases.Lactylation which is a novel post-translational modification(PTM)of histone,has been observed as a crucial contributor to liver physiology as well as pathobiology.This modification,characterized by the addition of lactate to lysine residues on histones,influences gene expression and cellular metabolism in the liver.Intriguingly,elevated lactate levels in the liver,resulting from either chronic alcohol consumption or a highfat/fructose-rich diet,may promote histone lactylation,particularly at histone 3 at lysine 18(H3K18),which facilitates the transcription of pro-inflammatory and fibrogenic genes.This process not only intensifies hepatic inflammation and fibrosis but also disrupts normal metabolic pathways,resulting in further liver damage.This review aims to elucidate the role of histone lactylation in MASH.Although a direct demonstration of histone lactylation in ASH has not yet been reported,the altered lactate metabolism in ASH suggests that histone lactylation may significantly contribute to its pathogenesis.Finally,we explore novel strategies targeting histone lactylation to mitigate liver injury and improve disease management in MASH and ASH.
