Dysregulation of G9a,a histone-lysine N-methyltransferase,has been observed in Alzheimer’s disease and has been correlated with increased levels of chronic inflammation and oxidative stress.Likewise,microRNAs are inv...Dysregulation of G9a,a histone-lysine N-methyltransferase,has been observed in Alzheimer’s disease and has been correlated with increased levels of chronic inflammation and oxidative stress.Likewise,microRNAs are involved in many biological processes and diseases playing a key role in pathogenesis,especially in multifactorial diseases such as Alzheimer’s disease.Therefore,our aim has been to provide partial insights into the interconnection between G9a,microRNAs,oxidative stress,and neuroinflammation.To better understand the biology of G9a,we compared the global microRNA expression between senescence-accelerated mouse-prone 8(SAMP8)control mice and SAMP8 treated with G9a inhibitor UNC0642.We found a downregulation of miR-128 after a G9a inhibition treatment,which interestingly binds to the 3′untranslated region(3′-UTR)of peroxisome-proliferator activator receptor γ(PPARG)mRNA.Accordingly,Pparg gene expression levels were higher in the SAMP8 group treated with G9a inhibitor than in the SAMP8 control group.We also observed modulation of oxidative stress responses might be mainly driven Pparg after G9a inhibitor.To confirm these antioxidant effects,we treated primary neuron cell cultures with hydrogen peroxide as an oxidative insult.In this setting,treatment with G9a inhibitor increases both cell survival and antioxidant enzymes.Moreover,up-regulation of PPARγby G9a inhibitor could also increase the expression of genes involved in DNA damage responses and apoptosis.In addition,we also described that the PPARγ/AMPK axis partially explains the regulation of autophagy markers expression.Finally,PPARγ/GADD45αpotentially contributes to enhancing synaptic plasticity and neurogenesis after G9a inhibition.Altogether,we propose that pharmacological inhibition of G9a leads to a neuroprotective effect that could be due,at least in part,by the modulation of PPARγ-dependent pathways by miR-128.展开更多
Objective:To evaluate the effect of chaetocin on pyroptosis of gastric cancer cells and its underlying mechanisms.Methods:The proliferation of gastric cancer cells was detected by trypan blue staining.Flow cytometry a...Objective:To evaluate the effect of chaetocin on pyroptosis of gastric cancer cells and its underlying mechanisms.Methods:The proliferation of gastric cancer cells was detected by trypan blue staining.Flow cytometry and Hoechst/propidium iodide double staining were used to detect apoptosis and pyroptosis.Cellular ultrastructure was observed by transmission electron microscopy.The levels of p-mixed lineage kinase domain-like(MLKL),gasdermin-D(GSDMD),gasdermin E(GSDME),N-GSDMD,and N-GSDME proteins were detected by Western blotting.In addition,lactate dehydrogenase(LDH)release assay was used to verify pyroptosis induced by chaetocin,and caspase 3 inhibition test and siRNA interference test were conducted to investigate pyroptosis mechanisms.Results:Chaetocin at concentrations of 200 nmol/L to 600 nmol/L inhibited the proliferation of AGS,HGC27,MKN28,and SGC7901gastric cancer cells in a dose-dependent and time-dependent manner by inducing apoptosis and pyroptosis.Significant ultrastructure changes,such as chromatin condensation,vacuolization,disrupted mitochondrial cristae,and increased nuclear occupancy,were observed after treatment with chaetocin in SGC7901 cells.Chaetocin at a concentration of 400 nmol/L significantly increased the number of pyroptotic cells,LDH release,and the ratio of N-GSDME/GSDME(P<0.01),which were reversed by Z-DEVD-FMK.In addition,chaetocin did not affect the expression of GSDMD.G9a silencing abolished the effect of chaetocin on the expression levels of GSDME and N-GSDME and LDH release(P>0.05).Conclusions:In addition to inducing apoptosis,chaetocin inhibits gastric cancer cells by inducing pyroptosis via the caspase 3/GSDME pathway.G9a was the target of chaetocin to induce pyroptosis of gastric cancer cells.展开更多
Two Rotavirus G9P[8] strains (LL52696 and LL52727) were recognized during a sentinel-based survey in Lulong, China. Phylogenetic analysis of the VP7 gene showed that both strains isolated constituted a divergent genet...Two Rotavirus G9P[8] strains (LL52696 and LL52727) were recognized during a sentinel-based survey in Lulong, China. Phylogenetic analysis of the VP7 gene showed that both strains isolated constituted a divergent genetic cluster distinct from the other G9 strains isolated in China. Analysis of VP4, VP6, and NSP4 genes revealed that these strains were closely related to Lulong strains. We hold that two strains were reassortant between G9 and Lulong predominant strains.展开更多
基金supported by the Ministerio de Economía,Industria y Competitividad(Agencia Estatal de Investigación,AEI,to CGF and MP)Fondo Europeo de Desarrollo Regional(MINECO-FEDER)(PID2022-139016OA-I00,PDC2022-133441-I00,to CGF and MP),Generalitat de Catalunya(2021 SGR 00357+3 种基金to CGF and MP)co-financed by Secretaria d’Universitats i Recerca del Departament d’Empresai Coneixement de la Generalitat de Catalunya 2021(Llavor 00086,to CGF)the recipient of an Alzheimer’s Association Research Fellowship(AARF-21-848511)the Agència de Gestiód’Ajuts Universitaris i de Recerca(AGAUR)for her FI-SDUR fellowship(2021FISDU 00182).
文摘Dysregulation of G9a,a histone-lysine N-methyltransferase,has been observed in Alzheimer’s disease and has been correlated with increased levels of chronic inflammation and oxidative stress.Likewise,microRNAs are involved in many biological processes and diseases playing a key role in pathogenesis,especially in multifactorial diseases such as Alzheimer’s disease.Therefore,our aim has been to provide partial insights into the interconnection between G9a,microRNAs,oxidative stress,and neuroinflammation.To better understand the biology of G9a,we compared the global microRNA expression between senescence-accelerated mouse-prone 8(SAMP8)control mice and SAMP8 treated with G9a inhibitor UNC0642.We found a downregulation of miR-128 after a G9a inhibition treatment,which interestingly binds to the 3′untranslated region(3′-UTR)of peroxisome-proliferator activator receptor γ(PPARG)mRNA.Accordingly,Pparg gene expression levels were higher in the SAMP8 group treated with G9a inhibitor than in the SAMP8 control group.We also observed modulation of oxidative stress responses might be mainly driven Pparg after G9a inhibitor.To confirm these antioxidant effects,we treated primary neuron cell cultures with hydrogen peroxide as an oxidative insult.In this setting,treatment with G9a inhibitor increases both cell survival and antioxidant enzymes.Moreover,up-regulation of PPARγby G9a inhibitor could also increase the expression of genes involved in DNA damage responses and apoptosis.In addition,we also described that the PPARγ/AMPK axis partially explains the regulation of autophagy markers expression.Finally,PPARγ/GADD45αpotentially contributes to enhancing synaptic plasticity and neurogenesis after G9a inhibition.Altogether,we propose that pharmacological inhibition of G9a leads to a neuroprotective effect that could be due,at least in part,by the modulation of PPARγ-dependent pathways by miR-128.
基金supported by Natural Science Foundation of Hainan Province,China(No.820MS048)。
文摘Objective:To evaluate the effect of chaetocin on pyroptosis of gastric cancer cells and its underlying mechanisms.Methods:The proliferation of gastric cancer cells was detected by trypan blue staining.Flow cytometry and Hoechst/propidium iodide double staining were used to detect apoptosis and pyroptosis.Cellular ultrastructure was observed by transmission electron microscopy.The levels of p-mixed lineage kinase domain-like(MLKL),gasdermin-D(GSDMD),gasdermin E(GSDME),N-GSDMD,and N-GSDME proteins were detected by Western blotting.In addition,lactate dehydrogenase(LDH)release assay was used to verify pyroptosis induced by chaetocin,and caspase 3 inhibition test and siRNA interference test were conducted to investigate pyroptosis mechanisms.Results:Chaetocin at concentrations of 200 nmol/L to 600 nmol/L inhibited the proliferation of AGS,HGC27,MKN28,and SGC7901gastric cancer cells in a dose-dependent and time-dependent manner by inducing apoptosis and pyroptosis.Significant ultrastructure changes,such as chromatin condensation,vacuolization,disrupted mitochondrial cristae,and increased nuclear occupancy,were observed after treatment with chaetocin in SGC7901 cells.Chaetocin at a concentration of 400 nmol/L significantly increased the number of pyroptotic cells,LDH release,and the ratio of N-GSDME/GSDME(P<0.01),which were reversed by Z-DEVD-FMK.In addition,chaetocin did not affect the expression of GSDMD.G9a silencing abolished the effect of chaetocin on the expression levels of GSDME and N-GSDME and LDH release(P>0.05).Conclusions:In addition to inducing apoptosis,chaetocin inhibits gastric cancer cells by inducing pyroptosis via the caspase 3/GSDME pathway.G9a was the target of chaetocin to induce pyroptosis of gastric cancer cells.
文摘Two Rotavirus G9P[8] strains (LL52696 and LL52727) were recognized during a sentinel-based survey in Lulong, China. Phylogenetic analysis of the VP7 gene showed that both strains isolated constituted a divergent genetic cluster distinct from the other G9 strains isolated in China. Analysis of VP4, VP6, and NSP4 genes revealed that these strains were closely related to Lulong strains. We hold that two strains were reassortant between G9 and Lulong predominant strains.
