ADRBK1 Pre-design Chimera RNAi
- Known as:
- ADRBK1 Pre-design Chimera RNAi
- Catalog number:
- H00000156-R04
- Product Quantity:
- 10 nmol
- Category:
- -
- Supplier:
- Abno
- Gene target:
- ADRBK1 Pre-design Chimera RNAi
Related genes to: ADRBK1 Pre-design Chimera RNAi
- Gene:
- GRK2 NIH gene
- Name:
- G protein-coupled receptor kinase 2
- Previous symbol:
- ADRBK1
- Synonyms:
- BARK1
- Chromosome:
- 11q13.2
- Locus Type:
- gene with protein product
- Date approved:
- 1992-03-25
- Date modifiied:
- 2016-10-05
Related products to: ADRBK1 Pre-design Chimera RNAi
Related articles to: ADRBK1 Pre-design Chimera RNAi
- Neuropathic pain (NP) is a debilitating chronic condition driven by maladaptive neuroimmune interactions in the spinal cord, with microglia playing a central pathological role. Electroacupuncture (EA) has shown analgesic effects in clinical and preclinical studies, but the microglia-centered mechanisms underlying these effects remain incompletely integrated. This review aims to provide a comprehensive mechanistic synthesis of how EA modulates microglia-associated neuroinflammatory pathways in neuropathic pain. This systematic search-narrative review used systematic search and screening procedures to identify English-language animal studies published between 2015 and 2025 in PubMed, CINAHL, Web of Science, and Cochrane Library. Twenty-six animal studies investigating EA effects on microglia-associated signaling pathways in neuropathic pain models met the inclusion criteria. Because of substantial heterogeneity in neuropathic pain models, EA parameters, molecular endpoints, and behavioral outcomes, findings were synthesized narratively, and no meta-analysis was performed. The reviewed evidence revealed four convergent mechanistic categories through which EA modulates microglial activity: (1) attenuation of purinergic microglial activation via downregulation of IRF8, P2X4R, P2X7R; (2) suppression of innate immune sensing and inflammasome pathways, including TLR4/MyD88/NF-κB and NLRP3 signaling; (3) inhibition of downstream inflammatory amplification through p38 MAPK, PI3K/AKT, and COX-2 pathways; and (4) promotion of pro-resolution mechanisms involving IL-10/β-endorphin, PD-L1, GRK2/TREM2/DAP12, α7nAChR, GLP-1R, and GABAergic signaling. The available preclinical evidence suggests that EA modulates multiple microglia-associated pathways, attenuating inflammatory signaling while enhancing selected pro-resolution mechanisms. These findings provide a mechanistic framework for understanding EA-induced analgesia in neuropathic pain and highlight microglial signaling networks as important targets for future experimental and translational investigation. - Source: PubMed
Publication date: 2026/08/27
Teoh Boon KhaiNguyen Trang Thi HoaiPeddanna KothaQuach Tran Van BaoLin Jaung-GengChen Yi-Hung - GRK2 is a key regulator of GPCR desensitization through its kinase and RGS homology (RH) domains. Because increased GRK2 activity contribute to cardiovascular diseases, including heart failure, cardiac hypertrophy and hypertension, GRK2 has emerged as an attractive therapeutic target. Most GRK2 inhibitors target its kinase activity, whereas the RH domain has remained largely unexplored. In the present study, we developed novel inhibitors directed against the RH domain of GRK2, characterized them in vitro, and evaluated their effects in cardiovascular physiology of spontaneously hypertensive rats. - Source: PubMed
Publication date: 2026/09/20
Echeverría Emiliana BMartínez Valeria RAcebedo Sofía LMonczor FedericoMatiller ValentinaVelez-Rueda Jorge ORipoll SoniaPortiansky EnriqueDavio CarlosShayo CarinaAiello Ernesto ARamírez Javier ADe Giusti Verónica CFernández Natalia C - To explore the role and mechanism of G-protein coupled receptor kinase 2 (GRK2)-mediated phosphorylation of adiponectin receptor 1 (AdipoR1) in diabetic cardiomyopathy (DCM), and to verify the therapeutic effect of site-directed mutagenesis targeting serine at position 205 (Ser205) of AdipoR1. Twenty 4-week-old C57BL/6J mice were randomly assigned to the normal control (NC) group and the DCM model group using a random-number table, with 10 mice per group. The DCM model was established in the DCM group by high-fat diet (HFD) feeding combined with intraperitoneal injection of streptozotocin (STZ). After 21-week intervention, 6 mice from each group were selected using a random-number table for measurements of serum biochemical parameters, adiponectin (APN) levels and cardiac diastolic function. Following euthanasia, myocardial tissues were harvested for Masson's trichrome staining to evaluate the degree of myocardial fibrosis. Co-immunoprecipitation and Western blot (WB) assays were performed to determine GRK2 expression, phosphorylated serine (p-Ser) levels, and the binding capacity between AdipoR1 and adaptor protein, phosphotyrosine-binding domain and leucine zipper motif 1 (APPL1). The remaining 4 mice per group were used for isolation of primary adult cardiomyocytes, which were treated with exogenous APN or phosphate-buffered saline (PBS). Phosphorylation status of the downstream adenosine monophosphate-activated protein kinase (AMPK)/protein kinase B (Akt) signaling pathway was subsequently detected. Twenty-eight 3-day-old AdipoR1-knockout neonatal mice were included in further experiments. Four of these AdipoR1-knockout neonatal mice were randomly selected by a random-number table to isolate primary cardiomyocytes. Plasmid co-transfection was conducted to assess AdipoR1-APPL1 interaction and downstream AMPK/Akt phosphorylation upon GRK2 overexpression. Four experimental subgroups were set: Adenovirus-empty(Ad-empty)+3×Flag-AdipoR1, Ad-empty+3×Flag-AdipoR1, adenovirus-mediated GRK2(Ad-GRK2)+3×Flag-AdipoR1, and Ad-GRK2+3×Flag-AdipoR1. This experiment aimed to identify whether Ser205 phosphorylation serves as the key molecular event whereby GRK2 blocks APN signaling. From the remaining 24 AdipoR1-knockout neonatal mice, 12 were randomly allocated into two groups (6 mice per group) using a random-number table. On postnatal day 3, mice received an injection of either adeno-associated virus serotype 9 (AAV9)-AdipoR1 or AAV9-AdipoR1. Ten weeks later, primary adult cardiomyocytes were isolated and divided into 4 subgroups: AAV9-AdipoR1+Ad-empty, AAV9-AdipoR1+Ad-GRK2, AAV9-AdipoR1+Ad-empty, and AAV9-AdipoR1+Ad-GRK2. GRK2 was overexpressed in vitro, and immunofluorescence co-localization was applied to quantify the co-localization of AdipoR1 and APPL1. The leftover 12 AdipoR1-knockout neonatal mice were randomized into two groups (6 mice per group) with a random-number table, and injected with the aforementioned viruses on postnatal day 3. Four weeks after virus injection, DCM was induced by HFD plus STZ administration, yielding two in-vivo groups: AAV9-AdipoR1+DCM (wild-type group) and AAV9-AdipoR1+DCM (point-mutation group). APN was continuously delivered via osmotic minipumps. Eight weeks after APN intervention, cardiac function and myocardial fibrosis were evaluated. In C57BL/6J mice, the DCM group exhibited significantly higher levels of blood glucose, triglycerides, low-density lipoprotein-cholesteral and adiponectin (APN) compared with the NC group (all <0.001). Statistically significant differences were observed between the two groups in the E/A ratio, radial strain rate, reverse radial strain rate (rRSR), longitudinal strain rate (LSR), and reverse longitudinal strain rate (rLSR) (all <0.05). The fraction of myocardial fibrotic area was larger in the DCM group than in the NC group (9.20±1.66 vs 1.24±0.51, <0.001). Myocardial protein levels of GRK2 (4.81±0.46 vs 1.03±0.09, <0.001) and p-Ser (1.75±0.21 vs 0.98±0.05, <0.001) were elevated in the DCM group relative to the NC group. The binding ratio of APPL1 to AdipoR1 in myocardial tissue was decreased in the DCM group versus the NC group (0.398±0.085 vs 0.978±0.088, <0.001). APN-stimulated AMPK/Akt phosphorylation was blunted in primary adult cardiomyocytes isolated from DCM-model C57BL/6J mice. In-vitro experiments using AdipoR1-knockout neonatal mouse cardiomyocytes demonstrated that following AdipoR1 Ser205 site mutation, the ratios of p-AMPK/AMPK (4.025±0.767 vs 1.003±0.087, <0.001) and p-Akt/Akt (4.125±0.544 vs 0.990±0.034, <0.001) were markedly increased in the 3×Flag-AdipoR1+APN group compared with the 3×Flag-AdipoR1+PBS group. In primary adult cardiomyocytes derived from AdipoR1-knockout mice, the AAV9-AdipoR1+Ad-GRK2 group restored the AdipoR1-APPL1 interaction in the presence of GRK2 when compared with the AAV9-AdipoR1+Ad-GRK2 group (=0.014). In the in-vivo DCM model established in AdipoR1-knockout mice, the AAV9-AdipoR1+DCM group displayed higher E/A ratio, rRSR, LSR and rLSR values, together with a lower myocardial fibrotic area fraction (all <0.05), relative to the AAV9-AdipoR1+DCM group. GRK2-mediated phosphorylation of AdipoR1 at serine 205 triggers APN-AdipoR1 metabolic dysfunction, which represents a critical contributor to aggravated cardiac dysfunction in DCM. This mechanism is associated with the decoupling of AdipoR1 from APPL1. Targeted inhibition of AdipoR1 phosphorylation via site-directed mutagenesis restores APN-AdipoR1 signaling and ameliorates cardiac dysfunction in DCM. - Source: PubMed
Yang Z JHu S CZhu DZhang Z YKang Y FTian Y MZhang LYe QFang L M - L. leaf extracts are regulated expectorants for productive cough, yet their evidence is dispersed across pharmaceutical quality, nonclinical pharmacology, disposition, toxicology, clinical pharmacology, efficacy, safety, and regulatory assessment. This review integrates those domains in a single study-level account and explicitly distinguishes isolated constituents, incompletely specified extracts, defined monograph preparations, proprietary extracts, and combination products. Hederacoside C is the pharmacopoeial marker, while α-hederin is the constituent most extensively examined in β2-adrenergic receptor models. Cell studies documented reduced agonist-induced receptor internalisation, greater ligand binding and cAMP responsiveness, and altered GRK2/β-arrestin signalling. Isolated tissue and animal studies reported antispasmodic, anti-inflammatory, antitussive, and tracheobronchial secretory effects. Rat studies showed low, matrix-dependent oral exposure to hederacoside C and α-hederin. Small exploratory human studies detected no or only trace α-hederin and did not permit conventional pharmacokinetic analysis. Clinical evidence includes placebo-controlled adult trials, active comparator studies, paediatric investigations, postmarketing cohorts, systematic reviews, and pharmacovigilance reports. Controlled adult trials of EA 575 reported greater short-term improvement in cough or Bronchitis Severity Score than placebo; paediatric efficacy evidence is dominated by observational studies and small airway function trials. Short-term tolerability was generally favourable, with gastrointestinal and hypersensitivity reactions as the principal recognised adverse effects. The European Union monograph recognises specified extracts for productive cough, contraindicates use below two years, and does not recommend use during pregnancy or lactation. The distinctive contribution of this review is the complete quality-to-clinic evidence map, including dose, model, endpoint, study design, extract identity, and unresolved evidence domain for each major dataset. - Source: PubMed
Publication date: 2026/08/27
Pawłowska Agata Maria - - Source: PubMed
Publication date: 2026/09/14
Nabil MahmoudAbdel-Ghany RashaAbo-Dya Nader EBarakat WaleedElbatreek Mahmoud H