(Dap22)-ShK, Selective blocker of Kv1.3
- Known as:
- (Dap22)-ShK, Selective blocker Kv1.3
- Catalog number:
- 13SHD001-50010
- Product Quantity:
- 5 x 10 ug
- Category:
- -
- Supplier:
- Smartox
- Gene target:
- (Dap22)-ShK Selective blocker Kv1.3
Related products to: (Dap22)-ShK, Selective blocker of Kv1.3
Related articles to: (Dap22)-ShK, Selective blocker of Kv1.3
- Sepsis is a systemic inflammatory response syndrome caused by an infection featuring high morbidity and mortality due to complex mechanisms underlying immune dysfunction. In this study, based on the sepsis transcriptome profiles from the GEO datasets (GSE65682, GSE28750, GSE95233, and GSE167363), we used the machine learning method and other computational algorithms, such as differential gene expression analysis, weighted gene coexpression network analyses (WGCNA), and the building of PPI networks to identify four hub genes (DDX24, GZMM, KCNA3, and NCL). The quantitative reverse transcription PCR performed preliminary validation that all four hub genes were significantly downregulated in patients with sepsis. DDX24 had the highest diagnostic performance (AUC > 0.8) for discriminating patients from normal subjects. GZMM was found to be significantly related to the prognoses of patients as well as APACHE II scores, and the downregulated expression pattern might represent T cell and NK cell exhaustion. Analysis based on single-cell RNA sequencing showed that DDX24 and GZMM were mainly expressed in T cells and NK cells, and the expression trends strongly correlate with patient survival. Functional enrichment analysis suggested that the hub genes likely participate in regulation of immune responses, especially those pertaining to T cells. Drug prediction found 25 candidate drugs that will serve as new therapeutic targets for precision medicine to treat sepsis. Overall, the multifaceted study shed light on key roles played by these hub genes (especially DDX24 and GZMM) in the development of sepsis and will be useful references in diagnosing patients and estimating prognosis. - Source: PubMed
Publication date: 2026/04/03
Zhang YiTang LiangWu JuanYang LinLiu WenLiang YiHan JianfangHe ShuangYang Yulian - The voltage-gated potassium channel K1.3 (KCNA3) is a critical ion channel regulating membrane potential in immune cells, facilitating sustained calcium influx and activating downstream signaling events. Besides its canonical role as an ion channel, K1.3 has been postulated to exert additional functions in immune biology. In this review, we summarize how recruitment of K1.3 into cholesterol-rich lipid raft microdomains positions K1.3 as a scaffold (demonstrated directly in T cells and microglia) for kinases, adaptor proteins, and transcriptional regulators, integrating ion flux with receptor signaling pathways that control adhesion, migration, and damage-associated molecular pattern release in immune cells. We further discuss how these observations may explain recent findings in K1.3 function in neutrophil biology and how its inhibition may offer a refined strategy to selectively modulate immune responses in sterile inflammation and beyond. This highlights the need for neutrophil-specific K1.3 interactomics and spatiotemporal raft/adhesion nanodomain mapping. - Source: PubMed
Publication date: 2026/03/03
Ku JohnAnders Hans-JoachimSperandio MarkusImmler Roland - De novo KCNA3 variants cause a Developmental and Epileptic Encephalopathy (DEE). We describe a 14-year-old boy presenting with DEE and carrying a heterozygous de novo KCNA3 (NM_002232.4) variant (c.1433T>A, p.Val478Glu) and an inherited KCNQ3 (NM_004519.3) variant (c.1720C>T, p.Pro574Ser). Human dermal fibroblasts (HDFs) were isolated from the patient and an age-matched control. KCNA3 and KCNQ3 transcript levels were quantified by qRT-PCR, showing in patient-HDFs a reduction of 77% and 40%, respectively (p < 0.0001; p = 0.0002). Western blot confirmed decreased KCNA3 and KCNQ3 protein levels by 50% and 35%, respectively (p < 0.05). The contributing role of both variants supports the rationale for a channel-targeted treatment strategy. - Source: PubMed
Publication date: 2026/01/30
Marchionni EnricaColona Vito LuigiAgolini EmanueleMurdocca MichelaRusso MoniaStellato MariaLatini ValeriaCampione ElenaNardone Anna MariaSpitalieri PaolaMazzone LuigiNovelli AntonioSangiuolo FedericaNovelli Giuseppe - Potassium (K) channels are essential transmembrane proteins that regulate ion flow, playing a critical role in regulating action potentials and neuronal transmission. Although K channel openers (agonists, K Ag) are widely used in treating neurological and psychiatric disorders, their precise mechanisms of action remain unclear. Our study explored how K channel openers might influence the expression of voltage-gated K channels (Kv) in rat brain. : Briefly, eight rats per group received intraperitoneal injections of diazoxide (Dia), chlorzoxazone (Chl), or flupirtine (Flu). Two hours post-injection, the prefrontal cortex (PFC), nucleus accumbens (NAc), dorsal striatum (dSTR), dorsal hippocampus (dHIP), and ventral hippocampus (vHIP) were collected for mRNA expression analysis of various Kv. : Dia administration altered expression of in the NAc, dSTR, and vHIP, and in the PFC, dSTR, and dHIP. The mRNA levels of and changed in the NAc, dHIP, and vHIP, while expression increased in the PFC, dHIP, and vHIP of rats treated with Chl. Injection of Flu resulted in altered expression for in the NAc, dSTR, and dHIP; in the PFC, NAc, dHIP, and vHIP; in the dSTR, dHIP, and vHIP; and and in the PFC, dHIP, and vHIP. We also found dose-dependent changes. : To our knowledge, this is the first study to identify the effects of potassium channel openers on gene expression within the mesocorticolimbic and nigrostriatal dopaminergic systems. These findings reveal a novel molecular mechanism underlying the action of these drugs in the brain. Importantly, our results have broader implications for translational neuroscience, particularly in the context of repurposing FDA-approved drugs, such as diazoxide and chlorzoxazone, for the treatment of neurological disorders. - Source: PubMed
Publication date: 2025/09/26
McCoy Michael TLadenheim BruceCadet Jean LudDaiwile Atul P - Studying DNA methylation (DNAm) can provide insights into gene-regulatory mechanisms underlying attention-deficit/hyperactivity disorder (ADHD). While most DNAm studies were performed in bulk tissue, this study used statistical deconvolution to identify cell type-specific DNAm profiles, from five major blood cell types, associated with childhood ADHD symptoms. We performed meta-analyses of methylome-wide association studies (MWAS) for ADHD symptoms (age=4-16 years) in peripheral blood collected during childhood and in cord blood. The investigated cohorts included seven array-based methylation datasets assaying up to 450 K CpGs from the Pregnancy And Childhood Epigenetics Consortium (N=2 934 peripheral blood; N=2 546 cord blood) and a sequencing-based methylation dataset assaying nearly all 28 million CpGs in blood from the Great Smoky Mountain Study (GSMS; N=583). The meta-analyses resulted in methylome-wide significant (FDR<0.05) ADHD associations in CD8T cells (RPL31P11 and KCNJ5) for peripheral blood, and, in cord blood, in monocytes (PDE6B), CD8T cells (KCNA3 and HAND2), and NK cells (KIFC1). Notably, several significant sites detected in peripheral blood (RPL31P11 and KCNJ5) were also detected in cord blood. Furthermore, extended MWAS of all sites available for GSMS detected 69 and 17 additional CpGs in monocytes and granulocytes, respectively. In this first cell type-specific MWAS for ADHD, we identified DNAm associations for ADHD symptoms; some associations were seen in both peripheral blood and cord blood, suggesting potential susceptibility markers for increased ADHD risk. These findings show that cell type-specific analyses and sequencing-based approaches can increase insights into the epigenetic patterns associated with ADHD symptoms in childhood. - Source: PubMed
Publication date: 2025/10/26
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