Pathological dry skin is a disturbing and intractable healthcare burden,characterized by epithelial hyperplasia and severe itch.Atopic dermatitis(AD)and psoriasis models with complications of dry skin have been studie...Pathological dry skin is a disturbing and intractable healthcare burden,characterized by epithelial hyperplasia and severe itch.Atopic dermatitis(AD)and psoriasis models with complications of dry skin have been studied using single-cell RNA sequencing(scRNA-seq).However,scRNA-seq analysis of the dry skin mouse model(acetone/ether/water(AEW)-treated model)is still lacking.Here,we used scRNA-seq and in situ hybridization to identify a novel proliferative basal cell(PBC)state that exclusively expresses transcription factor CUT-like homeobox 1(Cux1).Further in vitro study demonstrated that Cux1 is vital for keratinocyte proliferation by regulating a series of cyclin-dependent kinases(CDKs)and cyclins.Clinically,Cux1+PBCs were increased in patients with psoriasis,suggesting that Cux1+PBCs play an important part in epidermal hyperplasia.This study presents a systematic knowledge of the transcriptomic changes in a chronic dry skin mouse model,as well as a potential therapeutic target against dry skin-related dermatoses.展开更多
Hepatic ischemia–reperfusion(IR)injury is a serious clinical problem that complicates liver resection and transplantation.Despite recent advances in understanding of the pathophysiology of hepatic IR injury,effective...Hepatic ischemia–reperfusion(IR)injury is a serious clinical problem that complicates liver resection and transplantation.Despite recent advances in understanding of the pathophysiology of hepatic IR injury,effective interventions and therapeutics are still lacking.Here,we examined the role of transient receptor potential melastatin 2(TRPM2),a Ca^(2+)-permeable,non-selective cation channel,in mediating hepatic IR injury.Our data showed that TRPM2 deficiency attenuated IR-induced liver dysfunction,inflammation,and cell death in mice.Moreover,RNA sequencing analysis indicated that TRPM2-induced IR injury occurs via ferroptosis-related pathways.Consistently,as a ferroptosis inducer,(1S,3R)-RSL3 treatment induced mitochondrial dysfunction in hepatocytes and a TRPM2 inhibitor suppressed this.Interestingly,TRPM2-mediated calcium influx caused mitochondrial calcium accumulation via the mitochondrial Ca^(2+)-selective uniporter and increased the expression level of arachidonate 12-lipoxygenase(ALOX12),which results in mitochondrial lipid peroxidation during hepatic IR injury.Furthermore,hepatic IR injury-induced ferroptosis was obviously relieved by a TRPM2 inhibitor or calcium depletion,both in vitro and in vivo.Collectively,these findings demonstrate a crucial role for TRPM2-mediated ferroptosis in hepatic IR injury via increased Ca^(2+)-induced ALOX12 expression,indicating that pharmacological inhibition of TRPM2 may provide an effective therapeutic strategy for hepatic IR injury-related diseases,such as during liver resection and transplantation.展开更多
The prevalence of domestic and industrial electrical appliances has raised concerns about the health risk of extremely low-frequency magnetic fields(ELF-MFs). At present, the effects of ELF-MFs on the central nervous ...The prevalence of domestic and industrial electrical appliances has raised concerns about the health risk of extremely low-frequency magnetic fields(ELF-MFs). At present, the effects of ELF-MFs on the central nervous system are still highly controversial, and few studies have investigated its effects on cultured neurons. Here, we evaluated the biological effects of different patterns of ELF-MF exposure on primary cultured hippocampal neurons in terms of viability, apoptosis, genomic instability,and oxidative stress. The results showed that repeated exposure to 50-Hz 2-mT ELF-MF for 8 h per day after different times in culture decreased the viability and increased the production of intracellular reactive oxidative species in hippocampal neurons. The mechanism was potentially related to the up-regulation of Nox2 expression.Moreover, none of the repeated exposure patterns had significant effects on DNA damage, apoptosis, or autophagy, which suggested that ELF-MF exposure has no severe biological consequences in cultured hippocampal neurons.展开更多
基金supported by Technological Innovation 2030-Major Projects of Brain Science and Brain-like Research(Grant No.:2022zD0206200)the Natural Science Foundation of China(Grant Nos.:31872796,82030108 to W.Yang,32071102 to P.Yu)+3 种基金the National Major Special Project on New Drug Innovation of China(Grant No.:2018ZX09711001-004-005)the key research and development program of Ningxia Hui Autonomous Region(Grant No.:2019BFH02003)Fundamental Research Funds for the Central Universities of China(Grant No.:2016QNA7002 to P.Yu)Zhejiang Provincial Natural Science Foundation(Grant No.:LR16H090001 to W.Yang).
文摘Pathological dry skin is a disturbing and intractable healthcare burden,characterized by epithelial hyperplasia and severe itch.Atopic dermatitis(AD)and psoriasis models with complications of dry skin have been studied using single-cell RNA sequencing(scRNA-seq).However,scRNA-seq analysis of the dry skin mouse model(acetone/ether/water(AEW)-treated model)is still lacking.Here,we used scRNA-seq and in situ hybridization to identify a novel proliferative basal cell(PBC)state that exclusively expresses transcription factor CUT-like homeobox 1(Cux1).Further in vitro study demonstrated that Cux1 is vital for keratinocyte proliferation by regulating a series of cyclin-dependent kinases(CDKs)and cyclins.Clinically,Cux1+PBCs were increased in patients with psoriasis,suggesting that Cux1+PBCs play an important part in epidermal hyperplasia.This study presents a systematic knowledge of the transcriptomic changes in a chronic dry skin mouse model,as well as a potential therapeutic target against dry skin-related dermatoses.
基金the National Key Research and Development Project[2017YFC0110802]the Zhejiang Province Key Research and Development Project[2020C01059,2020]+4 种基金the Natural Science Foundation of China[82030108,31872796,81874059,32071102,and 82102105]the Natural Science Foundation of Zhejiang Province[LQ22H160017]the Zhejiang Engineering Research Center of Cognitive Healthcare[2017E10011]the National Key Scientific Instrument and Equipment Development Project[81827804]the China Postdoctoral Science Foundation[2021M702825].
文摘Hepatic ischemia–reperfusion(IR)injury is a serious clinical problem that complicates liver resection and transplantation.Despite recent advances in understanding of the pathophysiology of hepatic IR injury,effective interventions and therapeutics are still lacking.Here,we examined the role of transient receptor potential melastatin 2(TRPM2),a Ca^(2+)-permeable,non-selective cation channel,in mediating hepatic IR injury.Our data showed that TRPM2 deficiency attenuated IR-induced liver dysfunction,inflammation,and cell death in mice.Moreover,RNA sequencing analysis indicated that TRPM2-induced IR injury occurs via ferroptosis-related pathways.Consistently,as a ferroptosis inducer,(1S,3R)-RSL3 treatment induced mitochondrial dysfunction in hepatocytes and a TRPM2 inhibitor suppressed this.Interestingly,TRPM2-mediated calcium influx caused mitochondrial calcium accumulation via the mitochondrial Ca^(2+)-selective uniporter and increased the expression level of arachidonate 12-lipoxygenase(ALOX12),which results in mitochondrial lipid peroxidation during hepatic IR injury.Furthermore,hepatic IR injury-induced ferroptosis was obviously relieved by a TRPM2 inhibitor or calcium depletion,both in vitro and in vivo.Collectively,these findings demonstrate a crucial role for TRPM2-mediated ferroptosis in hepatic IR injury via increased Ca^(2+)-induced ALOX12 expression,indicating that pharmacological inhibition of TRPM2 may provide an effective therapeutic strategy for hepatic IR injury-related diseases,such as during liver resection and transplantation.
基金supported by the National Natural Science Foundation(31170799 and 30872082)the National Basic Research Development Program(973 Program)of China(2011CB503702)
文摘The prevalence of domestic and industrial electrical appliances has raised concerns about the health risk of extremely low-frequency magnetic fields(ELF-MFs). At present, the effects of ELF-MFs on the central nervous system are still highly controversial, and few studies have investigated its effects on cultured neurons. Here, we evaluated the biological effects of different patterns of ELF-MF exposure on primary cultured hippocampal neurons in terms of viability, apoptosis, genomic instability,and oxidative stress. The results showed that repeated exposure to 50-Hz 2-mT ELF-MF for 8 h per day after different times in culture decreased the viability and increased the production of intracellular reactive oxidative species in hippocampal neurons. The mechanism was potentially related to the up-regulation of Nox2 expression.Moreover, none of the repeated exposure patterns had significant effects on DNA damage, apoptosis, or autophagy, which suggested that ELF-MF exposure has no severe biological consequences in cultured hippocampal neurons.
