Last update 01 Nov 2024

Cytokine receptors x RANK

Last update 01 Nov 2024

Basic Info

Related Targets

Cytokine receptorsRANK

Drugs associated with Cytokine receptors x RANK

AFX-200 series (Aphoenix)

Target

Cytokine receptors x RANK

Mechanism

Cytokine receptors antagonists [+1]

Active Org.-

Originator Org.

Aphoenix, Inc.

Active Indication-

Inactive Indication

Osteoporosis

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with Cytokine receptors x RANK

100 Translational Medicine associated with Cytokine receptors x RANK

0 Patents (Medical) associated with Cytokine receptors x RANK

206

Literatures (Medical) associated with Cytokine receptors x RANK

01 Dec 2024·International Immunopharmacology

RANKL/RANK contributes to the pathological process of type 2 diabetes mellitus through TRAF3 activation of NIK

Article

Author: Jin, Ting ; Hu, Yanfen ; Tian, Ningyan ; Yu, Junxia

Diabetic osteoporosis is a complication of diabetes mellitus (DM). Denosumab (DMB) is an effective anti-osteoporotic drug functions by inhibiting NF-κB ligand receptor-activating factor (RANKL). Previous study found that osteoprotegerin (OPG) regulated βcell homeostasis through the RNAK/RANKL pathway. The present study aimed to investigate the effect of RANKL/RANK on the pathological process of DM and the underlying mechanism. We used D-glucose-induced RINm5F cells to construct in vitro type 2 diabetes models (T2DM). A high-fat diet combined with intraperitoneal injection of streptozotocin (STZ) was used to establish a T2DM model in SD rats. The apoptosis of β-cells was determined by TdT-mediated dUTP nick-end labeling (TUNEL) analysis. qRT-PCR and western blotting assays were used to explore the mRNA and protein expression of the TRAF3 (Tumor necrosis factor receptor-associated factor)/NIK (NF-κB-inducible kinase) pathway. Furthermore, insulin expression was detected by ELISA and immunohistochemistry assay. The islet morphology was analyzed by H&E. In vivo experiments demonstrated that sRANKL-IN-3 down-regulated insulin secretion levels by significantly ameliorating pancreatic tissue damage and mitigating apoptosis of high glucose induced β-cells. Subsequently, sRANKL-IN-3, acting as an inhibitor of RANKL, mitigated functional decline in β-cells induced by high glucose, mainly manifested by the low expression of PDX-1 (pancreatic duodenal homeobox 1), BETA2 (beta-2 adrenoceptors), INS-1 (insulin 1), and INS-2 (insulin 2). Mechanistic studies revealed that deletion of TRAF3 combined with sRANKL-IN-3 administration reduced the activity of NIK, NF-κB2, and RelB in RINm5F cells. In addition, our study demonstrated that inhibition of either RANKL or TRAF3 had a protective effect on high glucose induced apoptosis. Moreover, the combined action of sRANKL-IN-3 and shTRAF3 had a more pronounced inhibitory effect on high glucose-induced apoptosis. In summary, RANKL/RANK deficiency may attenuate apoptosis of β-cells, a phenomenon associated with the TRAF3/NIK pathway. Therefore, RANKL/RANK could be regarded as a potential therapeutic strategy for DM.

25 Sep 2024·Korean Journal of Orthodontics

Genetic polymorphisms in external apical root resorption and orthodontic tooth movements: A systematic review

Article

Author: Maia, Bernardo Emerenciano Barros ; Miranda, Diogo de Azevedo ; Lima, Izabella Lucas de Abreu ; Corrêa, Joice Dias ; Manzi, Flávio Ricardo ; Pinto, Yasmin Dias de Almeida ; Andrade, Ana Luiza Cabral de Ávila

ObjectiveExternal apical root resorption (EARR) is characterized by permanent loss of dental structure at the root apex. This study aimed to systematically review gene polymorphisms associated with EARR in orthodontic patients.MethodsElectronic database searches were performed across several databases.ResultsThis systematic review included 21 studies. Outcome measures were based on tooth dimensions observed on radiographs obtained before and after treatment. Polymorphisms in the following genes were genotyped using polymerase chain reaction-restriction fragment length polymorphism analysis: purinergic-receptor-P2X, ligand-gated ion channel 7 (P2RX7), caspase-1/interleukin-converting enzyme (CASP1/ICE), caspase-5 (CASP5), IL-1beta (IL1B), IL-1alpha (IL1A), interleukin-1 receptor antagonist gene (IL1RN), tissue non-specific alkaline phosphatase (TNSALP), tumor necrosis factor-alpha (TNFα), tumor necrosis factor receptor superfamily gene member 11a (TNFRSF11A), secreted phosphoprotein 1 (SPP1), tumor necrosis factor receptor superfamily gene member 11b (TNFRSF11B), interleukin 17A (IL17), interleukin 6 (IL6), receptor activator of nuclear factor-kappa B (RANK), osteoprotegerin (OPG), stromal antigen 2 (STAG2), vitamin D receptor (VDR), cytochrome P450 family 24 subfamily A member 1 (CYP24A1), cytochrome P450 family 27 subfamily B (CYP27B1), group-specific component (GC), and interleukin-1 receptor-associated kinases 1 (IRAK1).ConclusionsAlmost all studies suggested that IL1 gene is associated with EARR. Additionally, P2RX7 may be an important factor contributing to the etiopathogenesis of EARR. TNFRSF11A, SPP1, IL1RN, IL6, TNFRSF11B, STAG2, VDR, IRAK1, IL-17, CASP1/ICE and CASP5 have been identified in isolated studies. Further observational studies are needed to better explain the association between these genes and EARR.

01 Sep 2024·American Journal of Human Biology

Targeted proteomics involved in cardiovascular health and heart rate variability in children with overweight/obesity

Article

Author: Radom‐Aizik, Shlomit ; Plaza‐Florido, Abel ; Ortega, Francisco B. ; Alcantara, Juan M. A. ; Olvera‐Rojas, Marcos

AbstractBackgroundChildren with overweight/obesity often exhibit alterations in their plasma protein profiles and reduced heart rate variability (HRV). Plasma proteomics is at the forefront of identifying biomarkers for various clinical conditions. We aimed to examine the association between plasma‐targeted proteomics involved in cardiovascular health and resting vagal‐related HRV parameters in children with overweight/obesity.MethodsForty‐four children with overweight/obesity (10.2 ± 1.1 years old; 52% boys) participated in the study. Olink's technology was used to quantify 92 proteins involved in cardiovascular health. HRV was measured using a heart rate monitor (Polar RS800CX). Four resting vagal‐related HRV parameters were derived in time‐ and frequency‐domain.ResultsEight proteins (KIM1, IgG Fc receptor II‐b, IDUA, BOC, IL1RL2, TNFRSF11A, VSIG2, and TF) were associated with at least one out of the four vagal‐related HRV parameters (β values ranging from −0.188 to 0.288; all p < .05), while KIM1, IDUA, and BOC associated with ≥ three vagal‐related HRV parameters. Multiple hypothesis testing corrections did not reach statistical significance (false discovery rate [FDR >0.05]).ConclusionPlasma‐targeted proteomics suggested novel biomarkers for resting vagal‐related HRV parameters in children with overweight/obesity. Future studies using larger cohorts and longitudinal designs should confirm our findings and their potential clinical implications.

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