The activation of Ca2+ entry through store-operated channels by agonists that deplete Ca2+ from the endoplasmic reticulum (ER) is a ubiquitous signaling mechanism, the molecular basis of which has remained elusive for...The activation of Ca2+ entry through store-operated channels by agonists that deplete Ca2+ from the endoplasmic reticulum (ER) is a ubiquitous signaling mechanism, the molecular basis of which has remained elusive for the past two decades. Store-operated Ca2+-release-activated Ca2+ (CRAC) channels constitute the sole pathway for Ca2+ entry following antigen-receptor engagement. In a set of breakthrough studies over the past two years, stromal interaction molecule 1 (STIM1, the ER Ca2+ sensor) and Orai1 (a pore-forming subunit of the CRAC channel) have been identified. Here we review these recent studies and the insights they provide into the mechanism of store-operated Ca2+ channels (SOCCs).展开更多
The stromal interaction molecule(STIM)-calcium release-activated calcium channel protein(ORAI) and inositol1,4,5-trisphosphate receptors(IP_3Rs) play pivotal roles in the modulation of Ca^(2+)-regulated pathways from ...The stromal interaction molecule(STIM)-calcium release-activated calcium channel protein(ORAI) and inositol1,4,5-trisphosphate receptors(IP_3Rs) play pivotal roles in the modulation of Ca^(2+)-regulated pathways from gene transcription to cell apoptosis by driving calcium-dependent signaling processes.Increasing evidence has implicated the dysregulation of STIM-ORAI and IP_3Rs in tumorigenesis and tumor progression.By controlling the activities,structure,and/or expression levels of these Ca^(2+)-transporting proteins,malignant cancer cells can hijack them to drive essential biological functions for tumor development.However,the molecular mechanisms underlying the participation of STIM-ORAI and IP_3Rs in the biological behavior of cancer remain elusive.In this review,we summarize recent advances regarding STIM-ORAI and IP_3Rs and discuss how they promote cell proliferation,apoptosis evasion,and cell migration through temporal and spatial rearrangements in certain types of malignant cells.An understanding of the essential roles of STIM-ORAI and IP_3Rs may provide new pharmacologic targets that achieve a better therapeutic effect by inhibiting their actions in key intracellular signaling pathways.展开更多
<strong>Background:</strong> Anxiety disorders are the most common mental disorders, typically treated with psychotherapy and medication. These treatments are not suitable for, acceptable to, or effective ...<strong>Background:</strong> Anxiety disorders are the most common mental disorders, typically treated with psychotherapy and medication. These treatments are not suitable for, acceptable to, or effective for everyone. Alpha-Stim AID is a Cranial Electrotherapy Stimulation (CES) treatment with evidence of effectiveness in treating anxiety disorders. <strong>Objective:</strong> The aim of this paper is to present outcomes on anxiety, depression, and quality of life of Alpha-Stim use in primary care patients in the United Kingdom’s (UK) National Health Service (NHS) who reported symptoms of anxiety. <strong>Methods: </strong>Open label patient cohort design. Self-report measures: PHQ-9 (depression), GAD-7 (anxiety) and EQ-5D-5L (health related quality of life). Twenty-three patients with symptoms of anxiety completed a six-week course of Alpha-Stim intervention. <strong>Results:</strong> Reliable improvement and remission rates respectively were 60.9% and 17.4% for the GAD-7;42.9% and 22.7% for the PHQ-9. Significant improvement and medium/large effect sizes (n2 = 0.59 and 0.56 respectively). EQ-5D-5L results showed significant improvements in quality of life. Perceived quality of life doubled with an improvement of 0.36 on the health index score, this intervention adds 3.64 Quality Adjusted Life Years (QALYs). <strong>Limitations:</strong> The study was not an RCT, there was no control group. <strong>Conclusions:</strong> Alpha-Stim AID CES can be delivered through a UK primary care practice, and can have a significant impact on symptoms of anxiety and depression, and improve quality of life in primary care patients with anxiety symptoms. Further feasibility studies in primary care and sufficiently powered RCT are required.展开更多
文摘The activation of Ca2+ entry through store-operated channels by agonists that deplete Ca2+ from the endoplasmic reticulum (ER) is a ubiquitous signaling mechanism, the molecular basis of which has remained elusive for the past two decades. Store-operated Ca2+-release-activated Ca2+ (CRAC) channels constitute the sole pathway for Ca2+ entry following antigen-receptor engagement. In a set of breakthrough studies over the past two years, stromal interaction molecule 1 (STIM1, the ER Ca2+ sensor) and Orai1 (a pore-forming subunit of the CRAC channel) have been identified. Here we review these recent studies and the insights they provide into the mechanism of store-operated Ca2+ channels (SOCCs).
文摘The stromal interaction molecule(STIM)-calcium release-activated calcium channel protein(ORAI) and inositol1,4,5-trisphosphate receptors(IP_3Rs) play pivotal roles in the modulation of Ca^(2+)-regulated pathways from gene transcription to cell apoptosis by driving calcium-dependent signaling processes.Increasing evidence has implicated the dysregulation of STIM-ORAI and IP_3Rs in tumorigenesis and tumor progression.By controlling the activities,structure,and/or expression levels of these Ca^(2+)-transporting proteins,malignant cancer cells can hijack them to drive essential biological functions for tumor development.However,the molecular mechanisms underlying the participation of STIM-ORAI and IP_3Rs in the biological behavior of cancer remain elusive.In this review,we summarize recent advances regarding STIM-ORAI and IP_3Rs and discuss how they promote cell proliferation,apoptosis evasion,and cell migration through temporal and spatial rearrangements in certain types of malignant cells.An understanding of the essential roles of STIM-ORAI and IP_3Rs may provide new pharmacologic targets that achieve a better therapeutic effect by inhibiting their actions in key intracellular signaling pathways.
文摘<strong>Background:</strong> Anxiety disorders are the most common mental disorders, typically treated with psychotherapy and medication. These treatments are not suitable for, acceptable to, or effective for everyone. Alpha-Stim AID is a Cranial Electrotherapy Stimulation (CES) treatment with evidence of effectiveness in treating anxiety disorders. <strong>Objective:</strong> The aim of this paper is to present outcomes on anxiety, depression, and quality of life of Alpha-Stim use in primary care patients in the United Kingdom’s (UK) National Health Service (NHS) who reported symptoms of anxiety. <strong>Methods: </strong>Open label patient cohort design. Self-report measures: PHQ-9 (depression), GAD-7 (anxiety) and EQ-5D-5L (health related quality of life). Twenty-three patients with symptoms of anxiety completed a six-week course of Alpha-Stim intervention. <strong>Results:</strong> Reliable improvement and remission rates respectively were 60.9% and 17.4% for the GAD-7;42.9% and 22.7% for the PHQ-9. Significant improvement and medium/large effect sizes (n2 = 0.59 and 0.56 respectively). EQ-5D-5L results showed significant improvements in quality of life. Perceived quality of life doubled with an improvement of 0.36 on the health index score, this intervention adds 3.64 Quality Adjusted Life Years (QALYs). <strong>Limitations:</strong> The study was not an RCT, there was no control group. <strong>Conclusions:</strong> Alpha-Stim AID CES can be delivered through a UK primary care practice, and can have a significant impact on symptoms of anxiety and depression, and improve quality of life in primary care patients with anxiety symptoms. Further feasibility studies in primary care and sufficiently powered RCT are required.
