Objective:To screen plant extract fractions and elucidate the components present in Caesalpinia crista(C.crista)leaves for cholinergic and anti-amyloidogenic activities for the treatment of Alzheimer's diseases.Me...Objective:To screen plant extract fractions and elucidate the components present in Caesalpinia crista(C.crista)leaves for cholinergic and anti-amyloidogenic activities for the treatment of Alzheimer's diseases.Methods:This work has been carried out to study the action of C.crista extracts from nonpolar to polar solvents toward inhibition of oxidative stress,cholinergic and amyloidosis.The antioxidant activity was studied using DPPH total antioxidant assay;cholinergic assay by Ellman's method and anti-amyloidogenic assay by thioflavin-T fluorescence and transmission electron microscopy.Results:The quantification of polyphenols was carried out following C.crista methanolic extract(CCMeOH)HPLC fingerprinting,along with LC-MS and elucidated by MS LAMPS database.GC-MS of CCMeOH was screened for potential moieties.In vitro experimental results showed that the CCMe OH was potential extract that exhibited active inhibition of antioxidant property,cholinergic enzymes acetylcholinesterase and butyrylcholinesterase.For anti-amyloidogenic evaluations,among all the extracts,the CCMe OH was found to have the potential toward inhibiting the oligomers,fibrillation of Aβ42 with good defibrillation of amyloid cascading properties.Conclusions:These results are also supported by the presence of polyphenols as the active ingredients.Multi-potent target drug therapy is a promising option in treating the Alzheimer's diseases.Methanolic extract of C.crista shows potential activity against cholinergic enzymes,Aβ42 aggregation with antioxidant activity.展开更多
Acanthosis nigricans is characterized by papillomatous brownish lesions mainly in the intertriginous areas. We used dermoscopy to examine such lesions in a family with acanthosis nigricans. The dermoscopic images show...Acanthosis nigricans is characterized by papillomatous brownish lesions mainly in the intertriginous areas. We used dermoscopy to examine such lesions in a family with acanthosis nigricans. The dermoscopic images showed an aberrant skin structure of linear crista cutis and sulcus cutis, and hyperpigmented dots in crista cutis. The hyperpigmented dots, which could not be seen with the naked eyes, may contribute to the color of the pigmented skin. Dermoscopy can be useful for evaluating disorders involving the structure of area cutanea and a change in skin color.展开更多
Microglia are the first immune cells that are activated in the brain following ischemic stroke.Mitochondrial dysfunction exacerbates microglia-mediated neuroinflammation post-stroke.Caspase activation and recruitment ...Microglia are the first immune cells that are activated in the brain following ischemic stroke.Mitochondrial dysfunction exacerbates microglia-mediated neuroinflammation post-stroke.Caspase activation and recruitment domain 19(CARD19)is involved in innate immune response and inflammatory response,which are also important functions of microglia.However,the role of CARD19 in microglial biology and ischemic stroke remains unknown.Here,we observed that CARD19 expression was significantly elevated in microglia in the penumbra after ischemic stroke via analyzing the spatial transcriptomic sequencing data of ischemic brain tissue,as well as in an in vitro model of microglial activation.Remarkably,conditional knockdown of Card19 in microglia promoted post-stroke neuroinflammation and worsened neurological outcomes in a mouse model of ischemic stroke.Mechanistically,we found that CARD19 localized to mitochondria and promoted the assembly of mitochondrial intermembrane bridge components,while CARD19 deficiency in microglia caused ultrastructural and functional damage to the mitochondrial cristae,leading to an exaggerated pro-inflammatory response.Thus,our findings suggest that preserving mitochondrial cristae,by targeting CARD19 could be a novel therapeutic strategy for ameliorating neuroinflammation post-stroke and decreasing the volume of the ischemic penumbra.展开更多
Ischemic/hypoxic injury significantly damages vascular function,detrimentally impacting patient outcomes.Changes in mitochondrial structure and function are closely associated with ischemia/hypoxia-induced vascular dy...Ischemic/hypoxic injury significantly damages vascular function,detrimentally impacting patient outcomes.Changes in mitochondrial structure and function are closely associated with ischemia/hypoxia-induced vascular dysfunction.The mechanism of this process remains elusive.Using rat models of ischemia and hypoxic vascular smooth muscle cells(VSMCs),we combined transmission electron microscopy,super-resolution microscopy,and metabolic analysis to analyze the structure and function change of mitochondrial cristae.Multi-omics approaches revealed arginase 1(Arg1)upregulation in ischemic VSMCs,confirmed by in vivo and in vitro knockout models showing Arg1's protective effects on mitochondrial cristae,mitochondrial and vascular function,and limited the release of mtDNA.Mechanistically,Arg1 interacting with Mic1o led to mitochondrial cristae remodeling,together with hypoxia-induced VDAC1 lactylation resulting in the opening of MPTP and release of mtDNA of VSMCs.The released mtDNA led to PANoptosis of VSMCs via activation of the cGAS-STING pathway.ChIP-qPCR results demonstrated that lactatemediated Arg1 up-regulation was due to H3K18la upregulation.VSMCs targeted nano-material PLGA-PEl-siRNA@PM-a-SMA(NPsiArg1)significantly improved vascular dysfunction.This study uncovers a new mechanism of vascular dysfunction following ischemic/hypoxic injury:a damaging positive feedback loop mediated by lactate-regulated Arg1 expression between the nucleus and mitochondria,leading to mitochondria cristae disorder and mtDNA release,culminating in VSMCs PANoptosis.Targeting VSMCs Arg1 inhibition offers a potential therapeutic strategy to alleviate ischemia/hypoxia-induced vascular impairments.展开更多
A 62-year-old woman with frequent occurrence of symptomatic atrial tachycardia with a foci located at the root of the upper crista terminalis was found to have right diaphragm paresis after receiving a total of 8 radi...A 62-year-old woman with frequent occurrence of symptomatic atrial tachycardia with a foci located at the root of the upper crista terminalis was found to have right diaphragm paresis after receiving a total of 8 radiofrequency energy deliveries （40-60 W, 50-60℃） and a total duration of 540 seconds of ablation therapy （7Fr 8 mm deflectable ablation catheter）. The right diaphragm paresis remained resolved up to 14 months after the procedure as confirmed by repeated chest X-rays.展开更多
Objective:To investigate the hepatoprotective activity of ethanolic extract of leaves of Caesalpenia crista(C.crista)against paracetamol induced hepatotoxicity in rats.Methods:Paracetamol(2 g/kg body weight)was used t...Objective:To investigate the hepatoprotective activity of ethanolic extract of leaves of Caesalpenia crista(C.crista)against paracetamol induced hepatotoxicity in rats.Methods:Paracetamol(2 g/kg body weight)was used to induce hepatotoxicity in albino rats.Ethanolic extract of leaves of C.crista was administered at the dose levels of 200 and 400 mg/kg body weight orally for 7 d.Silymarin(100 mg/kg)was used as standard drug.The hepatoprotective effect of ethanolic extract was evaluated by assessment of biochemical parameters such as serum glutamic oxaloacetic transaminase,serum glutamic pyruvic transaminase,serum alkaline phosphatase,bilirubin(total and direct),and triglycerides content.Histopathological study of rat liver was also done.Results:Administration of ethanolic extract at doses 200 mg/kg and 400 mg/kg body weight exhibited significant reduction in elevated level of serum marker enzymes,bilirubin(total and direct)and triglycerides when compared to positive control group.Conclusions:It is concluded that the ethanolic extract of C.crista leaves seems to justify the promising hepatoprotective effect on paracetamol induced liver damage in rats.展开更多
基金Jain University,Bangalore for the financial support
文摘Objective:To screen plant extract fractions and elucidate the components present in Caesalpinia crista(C.crista)leaves for cholinergic and anti-amyloidogenic activities for the treatment of Alzheimer's diseases.Methods:This work has been carried out to study the action of C.crista extracts from nonpolar to polar solvents toward inhibition of oxidative stress,cholinergic and amyloidosis.The antioxidant activity was studied using DPPH total antioxidant assay;cholinergic assay by Ellman's method and anti-amyloidogenic assay by thioflavin-T fluorescence and transmission electron microscopy.Results:The quantification of polyphenols was carried out following C.crista methanolic extract(CCMeOH)HPLC fingerprinting,along with LC-MS and elucidated by MS LAMPS database.GC-MS of CCMeOH was screened for potential moieties.In vitro experimental results showed that the CCMe OH was potential extract that exhibited active inhibition of antioxidant property,cholinergic enzymes acetylcholinesterase and butyrylcholinesterase.For anti-amyloidogenic evaluations,among all the extracts,the CCMe OH was found to have the potential toward inhibiting the oligomers,fibrillation of Aβ42 with good defibrillation of amyloid cascading properties.Conclusions:These results are also supported by the presence of polyphenols as the active ingredients.Multi-potent target drug therapy is a promising option in treating the Alzheimer's diseases.Methanolic extract of C.crista shows potential activity against cholinergic enzymes,Aβ42 aggregation with antioxidant activity.
文摘Acanthosis nigricans is characterized by papillomatous brownish lesions mainly in the intertriginous areas. We used dermoscopy to examine such lesions in a family with acanthosis nigricans. The dermoscopic images showed an aberrant skin structure of linear crista cutis and sulcus cutis, and hyperpigmented dots in crista cutis. The hyperpigmented dots, which could not be seen with the naked eyes, may contribute to the color of the pigmented skin. Dermoscopy can be useful for evaluating disorders involving the structure of area cutanea and a change in skin color.
基金National Natural Science Foundation of China,Nos.81920108017(to YX),82401546(to HL)Jiangsu Province Key Medical Discipline,No.ZDXK202216(to YX)the Key Research and Development Program of Jiangsu Province of China,No.BE2020620(to YX).
文摘Microglia are the first immune cells that are activated in the brain following ischemic stroke.Mitochondrial dysfunction exacerbates microglia-mediated neuroinflammation post-stroke.Caspase activation and recruitment domain 19(CARD19)is involved in innate immune response and inflammatory response,which are also important functions of microglia.However,the role of CARD19 in microglial biology and ischemic stroke remains unknown.Here,we observed that CARD19 expression was significantly elevated in microglia in the penumbra after ischemic stroke via analyzing the spatial transcriptomic sequencing data of ischemic brain tissue,as well as in an in vitro model of microglial activation.Remarkably,conditional knockdown of Card19 in microglia promoted post-stroke neuroinflammation and worsened neurological outcomes in a mouse model of ischemic stroke.Mechanistically,we found that CARD19 localized to mitochondria and promoted the assembly of mitochondrial intermembrane bridge components,while CARD19 deficiency in microglia caused ultrastructural and functional damage to the mitochondrial cristae,leading to an exaggerated pro-inflammatory response.Thus,our findings suggest that preserving mitochondrial cristae,by targeting CARD19 could be a novel therapeutic strategy for ameliorating neuroinflammation post-stroke and decreasing the volume of the ischemic penumbra.
基金supported by the National Natural Science Foundation of China(Nos.82300561,82270523,and 82305006)the Natural Science Foundation of Chongqing(No.CSTB2023NSCQ-MSX0713)+5 种基金the Chongqing Medical Young Talents Program(No.YXQN202452 and No.YXQN202415)the High-Level Military Technological Innovation Talent Program,the Chongqing Talent Program:Innovative Leading Talents(No.CSTC2024YCJH-BGZXM0011)the Sprint Program of Joint Medical Research of Chongqing Science and Chongqing Health Commission(No.2025CCXM-001)the Youth Program of Joint Medical Research of Chongqing Science and Chongqing Health Commission(No.2025QNXM038)the Special Funding for Postdoctoral Research Projects in Chongqing,the Science Foundation of State Key Laboratory of Trauma and Chemical Poisoning(No.2024K003)the Chongqing Natural Science Foundation Innovation and Development Joint Fund(Chongqing Education Commission)(No.CSTB2024NSCQLZX0079).
文摘Ischemic/hypoxic injury significantly damages vascular function,detrimentally impacting patient outcomes.Changes in mitochondrial structure and function are closely associated with ischemia/hypoxia-induced vascular dysfunction.The mechanism of this process remains elusive.Using rat models of ischemia and hypoxic vascular smooth muscle cells(VSMCs),we combined transmission electron microscopy,super-resolution microscopy,and metabolic analysis to analyze the structure and function change of mitochondrial cristae.Multi-omics approaches revealed arginase 1(Arg1)upregulation in ischemic VSMCs,confirmed by in vivo and in vitro knockout models showing Arg1's protective effects on mitochondrial cristae,mitochondrial and vascular function,and limited the release of mtDNA.Mechanistically,Arg1 interacting with Mic1o led to mitochondrial cristae remodeling,together with hypoxia-induced VDAC1 lactylation resulting in the opening of MPTP and release of mtDNA of VSMCs.The released mtDNA led to PANoptosis of VSMCs via activation of the cGAS-STING pathway.ChIP-qPCR results demonstrated that lactatemediated Arg1 up-regulation was due to H3K18la upregulation.VSMCs targeted nano-material PLGA-PEl-siRNA@PM-a-SMA(NPsiArg1)significantly improved vascular dysfunction.This study uncovers a new mechanism of vascular dysfunction following ischemic/hypoxic injury:a damaging positive feedback loop mediated by lactate-regulated Arg1 expression between the nucleus and mitochondria,leading to mitochondria cristae disorder and mtDNA release,culminating in VSMCs PANoptosis.Targeting VSMCs Arg1 inhibition offers a potential therapeutic strategy to alleviate ischemia/hypoxia-induced vascular impairments.
文摘A 62-year-old woman with frequent occurrence of symptomatic atrial tachycardia with a foci located at the root of the upper crista terminalis was found to have right diaphragm paresis after receiving a total of 8 radiofrequency energy deliveries （40-60 W, 50-60℃） and a total duration of 540 seconds of ablation therapy （7Fr 8 mm deflectable ablation catheter）. The right diaphragm paresis remained resolved up to 14 months after the procedure as confirmed by repeated chest X-rays.
基金Supported by Teerthanker Mahaveer University,Delhi Road,Bagarpur,Moradabad,Uttar Pradesh,India(Grant No.TMU/TMCOP/2013-14/RES.GRANT-05/PGN).
文摘Objective:To investigate the hepatoprotective activity of ethanolic extract of leaves of Caesalpenia crista(C.crista)against paracetamol induced hepatotoxicity in rats.Methods:Paracetamol(2 g/kg body weight)was used to induce hepatotoxicity in albino rats.Ethanolic extract of leaves of C.crista was administered at the dose levels of 200 and 400 mg/kg body weight orally for 7 d.Silymarin(100 mg/kg)was used as standard drug.The hepatoprotective effect of ethanolic extract was evaluated by assessment of biochemical parameters such as serum glutamic oxaloacetic transaminase,serum glutamic pyruvic transaminase,serum alkaline phosphatase,bilirubin(total and direct),and triglycerides content.Histopathological study of rat liver was also done.Results:Administration of ethanolic extract at doses 200 mg/kg and 400 mg/kg body weight exhibited significant reduction in elevated level of serum marker enzymes,bilirubin(total and direct)and triglycerides when compared to positive control group.Conclusions:It is concluded that the ethanolic extract of C.crista leaves seems to justify the promising hepatoprotective effect on paracetamol induced liver damage in rats.
