A large amount of evidence has supported a clinical link between diabetes and inflammatory diseases,e.g.,cancer,dementia,and hypertension.In addition,it is also suggested that dysregulations related to Ca^(2+)signalin...A large amount of evidence has supported a clinical link between diabetes and inflammatory diseases,e.g.,cancer,dementia,and hypertension.In addition,it is also suggested that dysregulations related to Ca^(2+)signaling could link these diseases,in addition to 3'-5'-cyclic adenosine monophosphate(cAMP)signaling pathways.Thus,revealing this interplay between diabetes and inflammatory diseases may provide novel insights into the pathogenesis of these diseases.Publications involving signaling pathways related to Ca^(2+)and cAMP,inflammation,diabetes,dementia,cancer,and hypertension(alone or combined)were collected by searching PubMed and EMBASE.Both signaling pathways,Ca^(2+)and cAMP signaling,control the release of neurotransmitters and hormones,in addition to neurodegeneration,and tumor growth.Furthermore,there is a clear relationship between Ca^(2+)signaling,e.g.,increased Ca^(2+)signals,and inflammatory responses.cAMP also regulates pro-and anti-inflammatory responses.Due to the experience of our group in this field,this article discusses the role of Ca^(2+)and cAMP signaling in the correlation between diabetes and inflammatory diseases,including its pharmacological implications.As a novelty,this article also includes:(1)A timeline of the major events in Ca^(2+)/cAMP signaling;and(2)As coronavirus disease 2019(COVID-19)is an emerging and rapidly evolving situation,this article also discusses recent reports on the role of Ca^(2+)channel blockers for preventing Ca^(2+)signaling disruption due to COVID-19,including the correlation between COVID-19 and diabetes.展开更多
Objective To evaluate the chemical composition and effects of Artemisia vulgaris(AV)hydroalcoholic extract(HEAV)on breast cancer cells(MCF-7 and SKBR-3),chronic myeloid leukemia(K562)and NIH/3T3 fibroblasts.Methods Ph...Objective To evaluate the chemical composition and effects of Artemisia vulgaris(AV)hydroalcoholic extract(HEAV)on breast cancer cells(MCF-7 and SKBR-3),chronic myeloid leukemia(K562)and NIH/3T3 fibroblasts.Methods Phytochemical analysis of HEAV was done by high-performance liquid chromatography-mass(HPLC)spectrometry.Viability and cell death studies were performed using trypan blue and Annexin/FITC-7AAD,respectively.Ferrostatin-1(Fer-1)and necrostatin-1(Nec-1)were used to assess the mode of HEAV-induced cell death and acetoxymethylester(BAPTA-AM)was used to verify the involvement of cytosolic calcium in this event.Cytosolic calcium measurements were made using Fura-2-AM.Results HEAV decreased the viability of MCF-7,SKBR-3 and K562 cells(P<0.05).The viability of HEAV-treated K562 cells was reduced compared to HEAV-exposed fibroblasts(P<0.05).Treatment of K562 cells with HEAV induced cell death primarily by late apoptosis and necrosis in assays using annexin V-FITC/7-AAD(P<0.05).The use of Nec-1 and Fer-1 increased the viability of K562 cells treated with HEAV relative to cells exposed to HEAV alone(P<0.01).HEAV-induced Ca^(2+)release mainly from lysosomes in K562 cells(P<0.01).Furthermore,BAPTA-AM,an intracellular Ca^(2+)chelator,decreased the number of non-viable cells treated with HEAV(P<0.05).Conclusions HEAV is cytotoxic and activates several modalities of cell death,which are partially dependent on lysosomal release of Ca^(2+).These effects may be related to artemisinin and caffeoylquinic acids,the main compounds identified in HEAV.展开更多
Temporal lobe epilepsy is a multifactorial neurological dysfunction syndrome that is refractory,resistant to antiepileptic drugs,and has a high recurrence rate.The pathogenesis of temporal lobe epilepsy is complex and...Temporal lobe epilepsy is a multifactorial neurological dysfunction syndrome that is refractory,resistant to antiepileptic drugs,and has a high recurrence rate.The pathogenesis of temporal lobe epilepsy is complex and is not fully understood.Intracellular calcium dynamics have been implicated in temporal lobe epilepsy.However,the effect of fluctuating calcium activity in CA1 pyramidal neurons on temporal lobe epilepsy is unknown,and no longitudinal studies have investigated calcium activity in pyramidal neurons in the hippocampal CA1 and primary motor cortex M1 of freely moving mice.In this study,we used a multichannel fiber photometry system to continuously record calcium signals in CA1 and M1 during the temporal lobe epilepsy process.We found that calcium signals varied according to the grade of temporal lobe epilepsy episodes.In particular,cortical spreading depression,which has recently been frequently used to represent the continuously and substantially increased calcium signals,was found to correspond to complex and severe behavioral characteristics of temporal lobe epilepsy ranging from gradeⅡto gradeⅤ.However,vigorous calcium oscillations and highly synchronized calcium signals in CA1 and M1 were strongly related to convulsive motor seizures.Chemogenetic inhibition of pyramidal neurons in CA1 significantly attenuated the amplitudes of the calcium signals corresponding to gradeⅠepisodes.In addition,the latency of cortical spreading depression was prolonged,and the above-mentioned abnormal calcium signals in CA1 and M1 were also significantly reduced.Intriguingly,it was possible to rescue the altered intracellular calcium dynamics.Via simultaneous analysis of calcium signals and epileptic behaviors,we found that the progression of temporal lobe epilepsy was alleviated when specific calcium signals were reduced,and that the end-point behaviors of temporal lobe epilepsy were improved.Our results indicate that the calcium dynamic between CA1 and M1 may reflect specific epileptic behaviors corresponding to different grades.Furthermore,the selective regulation of abnormal calcium signals in CA1 pyramidal neurons appears to effectively alleviate temporal lobe epilepsy,thereby providing a potential molecular mechanism for a new temporal lobe epilepsy diagnosis and treatment strategy.展开更多
Background:This study will be aimed at investigating the effects of Polygonatum sibiricum polysaccharide(PSP)in a rat model of type 2 diabetes mellitus(T2DM).Methods:Thirty Sprague–Dawley male rats were evenly distri...Background:This study will be aimed at investigating the effects of Polygonatum sibiricum polysaccharide(PSP)in a rat model of type 2 diabetes mellitus(T2DM).Methods:Thirty Sprague–Dawley male rats were evenly distributed into three groups:normal,T2DM,and PSP groups,by applying a random sample table method.The typical cluster was served balanced food every day,whereas the others were supplied with a high-fat diet and streptozotocin injections to make T2DM rat models.The changes in humor organic chemistry indicators and liver histopathology were determined following the model institution for every cluster.After PSP intervention,western blotting was applied to research the expression levels of crucial transcription factors concerned within the nuclear factor erythroid 2-related factor 2(Nrf2)signal pathway,as well as Nrf2,glutamate-cysteine ligase chemical process fractional monetary unit,NQO1 and HO-1 within the liver tissues of the rat models,and to seem into the therapeutic edges of PSP and the way it happens in T2DM rats.Results:PSP intervention considerably reduced the concentration levels of aldohexose,lipids,liver-operated indicators,and alternative organic chemistry indicators within the humor of T2DM rat models and improved the histopathological changes within the liver.In addition,the activity of SOD and GSH-Px were increased,and the levels of MDA were decreased in the liver tissues of T2DM rat models following PSP intervention.Western blotting revealed that the expression levels of the Nrf2,HO-1,glutamate-cysteine ligase chemical,and NQO1 proteins were increased in rat liver tissues following PSP intervention.Conclusion:PSP has therapeutic effects in T2DM rat models,and its mechanism of motion might also be related to regulating the Nrf2 signaling pathway in liver tissues and alleviating oxidative stress.展开更多
文摘A large amount of evidence has supported a clinical link between diabetes and inflammatory diseases,e.g.,cancer,dementia,and hypertension.In addition,it is also suggested that dysregulations related to Ca^(2+)signaling could link these diseases,in addition to 3'-5'-cyclic adenosine monophosphate(cAMP)signaling pathways.Thus,revealing this interplay between diabetes and inflammatory diseases may provide novel insights into the pathogenesis of these diseases.Publications involving signaling pathways related to Ca^(2+)and cAMP,inflammation,diabetes,dementia,cancer,and hypertension(alone or combined)were collected by searching PubMed and EMBASE.Both signaling pathways,Ca^(2+)and cAMP signaling,control the release of neurotransmitters and hormones,in addition to neurodegeneration,and tumor growth.Furthermore,there is a clear relationship between Ca^(2+)signaling,e.g.,increased Ca^(2+)signals,and inflammatory responses.cAMP also regulates pro-and anti-inflammatory responses.Due to the experience of our group in this field,this article discusses the role of Ca^(2+)and cAMP signaling in the correlation between diabetes and inflammatory diseases,including its pharmacological implications.As a novelty,this article also includes:(1)A timeline of the major events in Ca^(2+)/cAMP signaling;and(2)As coronavirus disease 2019(COVID-19)is an emerging and rapidly evolving situation,this article also discusses recent reports on the role of Ca^(2+)channel blockers for preventing Ca^(2+)signaling disruption due to COVID-19,including the correlation between COVID-19 and diabetes.
基金Supported by the São Paulo Research Foundation[FAPESP,No.2020/14406(CB)]Brazilian National Council for Scientific and Technological Development(CNPq,No.PQ-302148/2019-1)Coordination of Superior Level Staff Improvement(CAPES)。
文摘Objective To evaluate the chemical composition and effects of Artemisia vulgaris(AV)hydroalcoholic extract(HEAV)on breast cancer cells(MCF-7 and SKBR-3),chronic myeloid leukemia(K562)and NIH/3T3 fibroblasts.Methods Phytochemical analysis of HEAV was done by high-performance liquid chromatography-mass(HPLC)spectrometry.Viability and cell death studies were performed using trypan blue and Annexin/FITC-7AAD,respectively.Ferrostatin-1(Fer-1)and necrostatin-1(Nec-1)were used to assess the mode of HEAV-induced cell death and acetoxymethylester(BAPTA-AM)was used to verify the involvement of cytosolic calcium in this event.Cytosolic calcium measurements were made using Fura-2-AM.Results HEAV decreased the viability of MCF-7,SKBR-3 and K562 cells(P<0.05).The viability of HEAV-treated K562 cells was reduced compared to HEAV-exposed fibroblasts(P<0.05).Treatment of K562 cells with HEAV induced cell death primarily by late apoptosis and necrosis in assays using annexin V-FITC/7-AAD(P<0.05).The use of Nec-1 and Fer-1 increased the viability of K562 cells treated with HEAV relative to cells exposed to HEAV alone(P<0.01).HEAV-induced Ca^(2+)release mainly from lysosomes in K562 cells(P<0.01).Furthermore,BAPTA-AM,an intracellular Ca^(2+)chelator,decreased the number of non-viable cells treated with HEAV(P<0.05).Conclusions HEAV is cytotoxic and activates several modalities of cell death,which are partially dependent on lysosomal release of Ca^(2+).These effects may be related to artemisinin and caffeoylquinic acids,the main compounds identified in HEAV.
基金supported by the National Natural Science Foundation of China,Nos.62027812(to HS),81771470(to HS),and 82101608(to YL)Tianjin Postgraduate Research and Innovation Project,No.2020YJSS122(to XD)。
文摘Temporal lobe epilepsy is a multifactorial neurological dysfunction syndrome that is refractory,resistant to antiepileptic drugs,and has a high recurrence rate.The pathogenesis of temporal lobe epilepsy is complex and is not fully understood.Intracellular calcium dynamics have been implicated in temporal lobe epilepsy.However,the effect of fluctuating calcium activity in CA1 pyramidal neurons on temporal lobe epilepsy is unknown,and no longitudinal studies have investigated calcium activity in pyramidal neurons in the hippocampal CA1 and primary motor cortex M1 of freely moving mice.In this study,we used a multichannel fiber photometry system to continuously record calcium signals in CA1 and M1 during the temporal lobe epilepsy process.We found that calcium signals varied according to the grade of temporal lobe epilepsy episodes.In particular,cortical spreading depression,which has recently been frequently used to represent the continuously and substantially increased calcium signals,was found to correspond to complex and severe behavioral characteristics of temporal lobe epilepsy ranging from gradeⅡto gradeⅤ.However,vigorous calcium oscillations and highly synchronized calcium signals in CA1 and M1 were strongly related to convulsive motor seizures.Chemogenetic inhibition of pyramidal neurons in CA1 significantly attenuated the amplitudes of the calcium signals corresponding to gradeⅠepisodes.In addition,the latency of cortical spreading depression was prolonged,and the above-mentioned abnormal calcium signals in CA1 and M1 were also significantly reduced.Intriguingly,it was possible to rescue the altered intracellular calcium dynamics.Via simultaneous analysis of calcium signals and epileptic behaviors,we found that the progression of temporal lobe epilepsy was alleviated when specific calcium signals were reduced,and that the end-point behaviors of temporal lobe epilepsy were improved.Our results indicate that the calcium dynamic between CA1 and M1 may reflect specific epileptic behaviors corresponding to different grades.Furthermore,the selective regulation of abnormal calcium signals in CA1 pyramidal neurons appears to effectively alleviate temporal lobe epilepsy,thereby providing a potential molecular mechanism for a new temporal lobe epilepsy diagnosis and treatment strategy.
基金Su Xiuhai National Traditional Chinese Medicine Expert Heritage Workplace,project number:National Traditional Chinese Medicine project[2022]75.
文摘Background:This study will be aimed at investigating the effects of Polygonatum sibiricum polysaccharide(PSP)in a rat model of type 2 diabetes mellitus(T2DM).Methods:Thirty Sprague–Dawley male rats were evenly distributed into three groups:normal,T2DM,and PSP groups,by applying a random sample table method.The typical cluster was served balanced food every day,whereas the others were supplied with a high-fat diet and streptozotocin injections to make T2DM rat models.The changes in humor organic chemistry indicators and liver histopathology were determined following the model institution for every cluster.After PSP intervention,western blotting was applied to research the expression levels of crucial transcription factors concerned within the nuclear factor erythroid 2-related factor 2(Nrf2)signal pathway,as well as Nrf2,glutamate-cysteine ligase chemical process fractional monetary unit,NQO1 and HO-1 within the liver tissues of the rat models,and to seem into the therapeutic edges of PSP and the way it happens in T2DM rats.Results:PSP intervention considerably reduced the concentration levels of aldohexose,lipids,liver-operated indicators,and alternative organic chemistry indicators within the humor of T2DM rat models and improved the histopathological changes within the liver.In addition,the activity of SOD and GSH-Px were increased,and the levels of MDA were decreased in the liver tissues of T2DM rat models following PSP intervention.Western blotting revealed that the expression levels of the Nrf2,HO-1,glutamate-cysteine ligase chemical,and NQO1 proteins were increased in rat liver tissues following PSP intervention.Conclusion:PSP has therapeutic effects in T2DM rat models,and its mechanism of motion might also be related to regulating the Nrf2 signaling pathway in liver tissues and alleviating oxidative stress.
