Coated-PMMA microspheres consisting of poly （methyl methacrylate）（PMMA） core and barium titanate （BaTiO3） shell were synthesized by the modified sol-gel processing and then adopted as an electrorheological （ER...Coated-PMMA microspheres consisting of poly （methyl methacrylate）（PMMA） core and barium titanate （BaTiO3） shell were synthesized by the modified sol-gel processing and then adopted as an electrorheological （ER） materials. The structure and morphology of coated powders were chyfecterized by SEM and FT-IR; the shear stress of the suspensions of coated-PMMA particles and pure PMMA particles in silicone oil with a 20 vol% were investigated. The results show that the BaTiO3 coated PMMA microspheres based suspension in silicone oil exhibited typical ER behavior and stronger ER effects.展开更多
Potassium channels regulate diverse biological processes,ranging from cell proliferation to immune responses.However,the functions of potassium homeostasis and its regulatory mechanisms in adult stem cells and tumors ...Potassium channels regulate diverse biological processes,ranging from cell proliferation to immune responses.However,the functions of potassium homeostasis and its regulatory mechanisms in adult stem cells and tumors remain poorly characterized.Here,we identify Sandman(Sand),a two-pore-domain potassium channel in Drosophila melanogaster,as an essential regulator for the proliferation of intestinal stem cells and malignant tumors,while dispensable for the normal development processes.Mechanistically,loss of sand elevates intracellular K+concentration,leading to growth inhibition.This phenotype is rescued by pharmacological reduction of intracellular K+levels using the K+ionophore.Conversely,overexpression of sand triggers stem cell death in most regions of the midgut,inhibits tumor growth,and induces a Notch loss-of-function phenotype in the posterior midgut.These effects are mediated predominantly via the induction of endoplasmic reticulum(ER)stress,as demonstrated by the complete rescue of phenotypes through the co-expression of Ire1 or Xbp1s.Additionally,human homologues of Sand demonstrated similar ER stress-inducing capabilities,suggesting an evolutionarily conserved relationship between this channel and ER stress.Together,our findings identify Sand as a shared regulatory node that governs Drosophila adult stem cell dynamics and tumorigenesis through bioelectric homeostasis,and reveal a link between the two-pore potassium channel and ER stress signaling.展开更多
Since the first electron micrograph of“lace-like structures”over 75 years ago,the endoplasmic reticulum(ER)is now viewed as a highly dynamic,constantly remodeling,continuous network of tubules and cisternae that pla...Since the first electron micrograph of“lace-like structures”over 75 years ago,the endoplasmic reticulum(ER)is now viewed as a highly dynamic,constantly remodeling,continuous network of tubules and cisternae that plays an important role in a broad range of cellular activities from calcium regulation to protein synthesis and trafficking.In neurons,the ER extends from the soma through the axon to presynaptic terminals,and throughout the dendritic arbor into as many as half of all postsynaptic dendritic spines at any given time(Falahati et al.,2022).展开更多
Objective:To assess the antitumor activity of the novel chitinase produced by fermented,isolated Trichoderma viride in a hepatocellular carcinoma(HCC)male rat model.Methods:Diethyl-nitrosamine induction combined with ...Objective:To assess the antitumor activity of the novel chitinase produced by fermented,isolated Trichoderma viride in a hepatocellular carcinoma(HCC)male rat model.Methods:Diethyl-nitrosamine induction combined with ionizing radiation exposure was used to establish the HCC rat model.All rats were divided into 4 groups:the control group,the chitinase group,the HCC group,and the HCC+chitinase group.The antiproliferative effect of chitinase was evaluated in human HCC cells.The effect of chitinase in vivo on oxidative stress,endoplasmic reticulum stress chaperones,autophagy markers,PI3K/AKT/mTOR,AMPK pathway expression,and apoptotic indicators was determined and confirmed by histological examination.Results:Chitinase significantly inhibited the viabilities of HepG2 cells.Moreover,in the Wistar male rat model of HCC,chitinase decreased ATP levels,modulated endoplasmic reticulum stress,mediated autophagy factors,and promoted apoptosis.Conclusions:Chitinase might play a role in the apoptosis as well as autophagy pathways and may act as a potential tumor suppressor.展开更多
Objective:To investigate the efficacy and underlying mechanisms of standardized Salvia miltiorrhiza extract(SMEX)in alleviating menopausal symptoms using MCF-7 cells and an ovary-intact menopause mouse model resulting...Objective:To investigate the efficacy and underlying mechanisms of standardized Salvia miltiorrhiza extract(SMEX)in alleviating menopausal symptoms using MCF-7 cells and an ovary-intact menopause mouse model resulting from hypothalamic-pituitary-ovarian axis aging.Methods:Estrogen receptor(ER)-related molecular responses were first assessed in MCF-7 cells treated with SMEX.In vivo efficacy was then evaluated in 52-week-old female mice orally administered SMEX(50 or 100 mg/kg/day)or 17β-estradiol(E2)for 12 weeks.ER expression and downstream AKT/ERK signaling pathways in uterine tissues were determined.In addition,histological analysis of reproductive organs,assessment of serum lipid and hormone levels,neurotransmitter measurements,and behavioral tests were performed.Results:SMEX upregulated ERαand ERβexpression and suppressed pS2 mRNA in MCF-7 cells,indicating selective ER modulation.In SMEX-treated mice,uterine ER expression and activation of the AKT and ERK pathways were significantly increased,leading to partial restoration of epithelial thickness and stratification in the oviduct and vagina.SMEX also significantly reduced serum low-density lipoprotein cholesterol levels and reversed menopausal alterations in the follicle-stimulating hormone/luteinizing hormone ratio.Additionally,it elevated serotonin and norepinephrine levels in the pituitary,thereby alleviating depression-like behavior.Conclusions:SMEX modulates ER signaling and improves neurohormonal balance,effectively alleviating menopausal symptoms in both in vitro and in vivo models.This highlights its potential as a safe,natural alternative to hormone replacement therapy and as a promising functional ingredient in therapeutic natural products.展开更多
Previous studies have shown that endoplasmic reticulum stress induces neuronal apoptosis,necrosis,and pro-inflammatory microenvironment after spinal cord injury.The JNK pathway is activated by endoplasmic reticulum st...Previous studies have shown that endoplasmic reticulum stress induces neuronal apoptosis,necrosis,and pro-inflammatory microenvironment after spinal cord injury.The JNK pathway is activated by endoplasmic reticulum stress and reactive oxygen species.Our previous research demonstrated that cerebral dopamine neurotrophic factor has anti-inflammatory effects and promotes the repair of the damaged spinal cord after injury.However,the molecular mechanism remains unclear.In this study,we found that cerebral dopamine neurotrophic factor binds JNK1 and regulates JNK1/2-c-Jun-p53 signaling in lipopolysaccharide-induced microglia.Cerebral dopamine neurotrophic factor also alleviated neuroinflammation by reducing the secretion of pro-inflammatory cytokines.Overexpression of cerebral dopamine neurotrophic factor in a mouse model of spinal cord injury promoted nerve regeneration and motor function recovery.These findings indicate the possibility for cerebral dopamine neurotrophic factor treating spinal cord injury by targeting the JNK1/2-c-Jun-p53 pathway.展开更多
基金Funded by the National Natural Science Foundation of China (Nos. 10418014 and 10474074).
文摘Coated-PMMA microspheres consisting of poly （methyl methacrylate）（PMMA） core and barium titanate （BaTiO3） shell were synthesized by the modified sol-gel processing and then adopted as an electrorheological （ER） materials. The structure and morphology of coated powders were chyfecterized by SEM and FT-IR; the shear stress of the suspensions of coated-PMMA particles and pure PMMA particles in silicone oil with a 20 vol% were investigated. The results show that the BaTiO3 coated PMMA microspheres based suspension in silicone oil exhibited typical ER behavior and stronger ER effects.
基金supported by the National Natural Science Foundation of China to L.H.(32470754 and 32070750)to X.M.(32170824 and 32322027)HRHl program of Westlake Laboratory of Life Sciences and Biomedicine to X.M.(1011103360222B1).
文摘Potassium channels regulate diverse biological processes,ranging from cell proliferation to immune responses.However,the functions of potassium homeostasis and its regulatory mechanisms in adult stem cells and tumors remain poorly characterized.Here,we identify Sandman(Sand),a two-pore-domain potassium channel in Drosophila melanogaster,as an essential regulator for the proliferation of intestinal stem cells and malignant tumors,while dispensable for the normal development processes.Mechanistically,loss of sand elevates intracellular K+concentration,leading to growth inhibition.This phenotype is rescued by pharmacological reduction of intracellular K+levels using the K+ionophore.Conversely,overexpression of sand triggers stem cell death in most regions of the midgut,inhibits tumor growth,and induces a Notch loss-of-function phenotype in the posterior midgut.These effects are mediated predominantly via the induction of endoplasmic reticulum(ER)stress,as demonstrated by the complete rescue of phenotypes through the co-expression of Ire1 or Xbp1s.Additionally,human homologues of Sand demonstrated similar ER stress-inducing capabilities,suggesting an evolutionarily conserved relationship between this channel and ER stress.Together,our findings identify Sand as a shared regulatory node that governs Drosophila adult stem cell dynamics and tumorigenesis through bioelectric homeostasis,and reveal a link between the two-pore potassium channel and ER stress signaling.
基金supported by AHA Career Development Award 938683 (to PJD)NIH grant R01MH123700 (to MLD)
文摘Since the first electron micrograph of“lace-like structures”over 75 years ago,the endoplasmic reticulum(ER)is now viewed as a highly dynamic,constantly remodeling,continuous network of tubules and cisternae that plays an important role in a broad range of cellular activities from calcium regulation to protein synthesis and trafficking.In neurons,the ER extends from the soma through the axon to presynaptic terminals,and throughout the dendritic arbor into as many as half of all postsynaptic dendritic spines at any given time(Falahati et al.,2022).
文摘Objective:To assess the antitumor activity of the novel chitinase produced by fermented,isolated Trichoderma viride in a hepatocellular carcinoma(HCC)male rat model.Methods:Diethyl-nitrosamine induction combined with ionizing radiation exposure was used to establish the HCC rat model.All rats were divided into 4 groups:the control group,the chitinase group,the HCC group,and the HCC+chitinase group.The antiproliferative effect of chitinase was evaluated in human HCC cells.The effect of chitinase in vivo on oxidative stress,endoplasmic reticulum stress chaperones,autophagy markers,PI3K/AKT/mTOR,AMPK pathway expression,and apoptotic indicators was determined and confirmed by histological examination.Results:Chitinase significantly inhibited the viabilities of HepG2 cells.Moreover,in the Wistar male rat model of HCC,chitinase decreased ATP levels,modulated endoplasmic reticulum stress,mediated autophagy factors,and promoted apoptosis.Conclusions:Chitinase might play a role in the apoptosis as well as autophagy pathways and may act as a potential tumor suppressor.
基金funded by UNDBIO Co.,Ltd.No specific grant number was assigned.
文摘Objective:To investigate the efficacy and underlying mechanisms of standardized Salvia miltiorrhiza extract(SMEX)in alleviating menopausal symptoms using MCF-7 cells and an ovary-intact menopause mouse model resulting from hypothalamic-pituitary-ovarian axis aging.Methods:Estrogen receptor(ER)-related molecular responses were first assessed in MCF-7 cells treated with SMEX.In vivo efficacy was then evaluated in 52-week-old female mice orally administered SMEX(50 or 100 mg/kg/day)or 17β-estradiol(E2)for 12 weeks.ER expression and downstream AKT/ERK signaling pathways in uterine tissues were determined.In addition,histological analysis of reproductive organs,assessment of serum lipid and hormone levels,neurotransmitter measurements,and behavioral tests were performed.Results:SMEX upregulated ERαand ERβexpression and suppressed pS2 mRNA in MCF-7 cells,indicating selective ER modulation.In SMEX-treated mice,uterine ER expression and activation of the AKT and ERK pathways were significantly increased,leading to partial restoration of epithelial thickness and stratification in the oviduct and vagina.SMEX also significantly reduced serum low-density lipoprotein cholesterol levels and reversed menopausal alterations in the follicle-stimulating hormone/luteinizing hormone ratio.Additionally,it elevated serotonin and norepinephrine levels in the pituitary,thereby alleviating depression-like behavior.Conclusions:SMEX modulates ER signaling and improves neurohormonal balance,effectively alleviating menopausal symptoms in both in vitro and in vivo models.This highlights its potential as a safe,natural alternative to hormone replacement therapy and as a promising functional ingredient in therapeutic natural products.
基金National Natural Science Foundation of China,No.81601067(to HZ)Shandong Natural Science Foundation of Shandong Province,Nos.ZR2021MH134(to HZ)and ZR2020MH080(to PD).
文摘Previous studies have shown that endoplasmic reticulum stress induces neuronal apoptosis,necrosis,and pro-inflammatory microenvironment after spinal cord injury.The JNK pathway is activated by endoplasmic reticulum stress and reactive oxygen species.Our previous research demonstrated that cerebral dopamine neurotrophic factor has anti-inflammatory effects and promotes the repair of the damaged spinal cord after injury.However,the molecular mechanism remains unclear.In this study,we found that cerebral dopamine neurotrophic factor binds JNK1 and regulates JNK1/2-c-Jun-p53 signaling in lipopolysaccharide-induced microglia.Cerebral dopamine neurotrophic factor also alleviated neuroinflammation by reducing the secretion of pro-inflammatory cytokines.Overexpression of cerebral dopamine neurotrophic factor in a mouse model of spinal cord injury promoted nerve regeneration and motor function recovery.These findings indicate the possibility for cerebral dopamine neurotrophic factor treating spinal cord injury by targeting the JNK1/2-c-Jun-p53 pathway.
