Ask about this productRelated genes to: CHK2 antibody
- Gene:
- CHEK2 NIH gene
- Name:
- checkpoint kinase 2
- Previous symbol:
- RAD53
- Synonyms:
- CDS1, CHK2, HuCds1, PP1425, bA444G7
- Chromosome:
- 22q12.1
- Locus Type:
- gene with protein product
- Date approved:
- 2001-09-19
- Date modifiied:
- 2019-04-23
Related products to: CHK2 antibody
Related articles to: CHK2 antibody
- Diabetic nephropathy (DN) is a severe microvascular complication of diabetes with limited therapeutic options. Berberine exhibits renoprotective potential, yet its precise molecular targets and mechanisms of action in DN remain unclear. Berberine targets were retrieved from TCMSP, SEA, and SwissTargetPrediction databases. Bulk transcriptomic microarray datasets (GSE96804, GSE30122) and single-cell RNA sequencing (scRNA-seq) dataset (GSE131882) were obtained from the Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) and weighted gene co-expression network analysis (WGCNA) were applied to GSE96804, followed by single-cell analysis and high-dimensional WGCNA (hdWGCNA) on podocytes. Key targets were refined via protein-protein interaction (PPI) network topology, random forest, and SHAP analysis. Molecular docking, 100 ns molecular dynamics (MD) simulations, and MM/PBSA calculations were performed to elucidate binding mechanisms. In vitro validation used human podocytes exposed to high glucose (30 mM, 48 h) ± berberine, with knockdown and overexpression plasmids transfected for rescue experiments. Single-cell analysis identified a total of 11 renal cell types; in DN, the number of podocytes was significantly reduced, and their intercellular communication was the most intense. CHEK2 and HPGD were identified as key targets-CHEK2 expression is upregulated in DN, whilst HPGD expression is downregulated-and both targets demonstrated robust diagnostic performance using nomogram, receiver operating characteristic curves, and decision curve analysis. Molecular docking revealed high binding affinities (CHEK2: -8.8 kcal/mol; HPGD: -9.9 kcal/mol), supported by stable molecular dynamics trajectories and favourable MM/PBSA binding free energies. In vitro, berberine normalised CHEK2 and HPGD expression, improved cell viability, reduced apoptosis, and restored structural markers of podocytes (Nephrin, Podocin, WT1), inhibited fibrotic proteins (Collagen I, fibronectin, α-SMA), and alleviated oxidative stress (decreased ROS, decreased MDA, increased SOD, increased GSH-Px). Importantly, rescue experiments demonstrated that the renoprotective effects of berberine were functionally dependent on CHEK2 and HPGD modulation in this in vitro model: CHEK2 gene silencing or HPGD overexpression further enhanced berberine's protective effects, whereas CHEK2 overexpression or HPGD gene silencing abolished this protection and restored the cellular phenotype to that observed under hyperglycaemic conditions. This comprehensive multi-omics study, incorporating rescue experiments, identified CHEK2 and HPGD as functionally important candidate mediators of berberine's renoprotective effects in DN, providing preliminary mechanistic insights to inform precision diagnosis and targeted therapeutic strategies. - Source: PubMed
Publication date: 2026/10/01
Pu YouminChang HuanChen WeiZhang HuhaiChen WenjieZhao HongwenSun Daodong - DNA methylation profiling of CNS tumors led to the identification of HPAP (high-grade glioma with pleomorphic and pseudopapillary features), a recently proposed entity with variable morphology, recurrent MAP-kinase pathway activating events, and longer survival compared to glioblastoma. We aimed to independently validate and further characterize this entity. We retrieved a multicentric cohort of gliomas compatible with HPAP and performed t-SNE dimensionality reduction on their DNA methylation profile. Clinical, radiological, histological, and molecular data were reviewed. Twenty tumors clustering with previously reported HPAP cases were identified. Median age at diagnosis was 37 years. Radiologically, the tumors appeared as expansive lesions with heterogeneous enhancement and frequent cysts. Histologically, they were well-circumscribed, with papillary and pleomorphic features variably present. Marked histological signs of aggressivity were present in seven. Immunostainings showed expression of GFAP, OLIG2, and CD34. All cases were IDH1/2 wildtype and pMGMT unmethylated. Recurrently mutated genes included TP53, ATRX, RB1, and BRAF. Five patients had germline pathogenic variants in genes associated with hereditary tumor predisposition syndromes (MLH1, BRCA2, CHEK2, NF2, RB1). All patients underwent surgical resection, but subsequent management was heterogeneous. Ten-year estimated survival was 85%. CDKN2A homozygous deletion seemed to identify more aggressive tumors. In conclusion, our data suggest the existence of a novel entity of circumscribed gliomas with long-term survival despite possible high-grade histological presentation, for which we propose the nomenclature "Gliomas with pleomorphic and pseudopapillary features" with a spectrum encompassing provisory grade 2 and 3. A proper identification could guide treatment choices. - Source: PubMed
Publication date: 2026/09/29
Picca AlbertoBarresi ValeriaTrinquet AudeBertero LucaNichelli LuciaChotard GuillaumeBernier MichèleGareau ThomasKacimi Salah Eddine OussamaBhalshankar JayduttFilser MathildeMasliah-Planchon JulienIollo MartaMalaize HenriMathon BertrandBauchet LucKhouri KifahBarka BesmaMadry HélèneRossi SabrinaMiele EvelinaRicciardi Giuseppe KennethCarpentier CatherineCoin IrinaSanson MarcTouat MehdiDehais CarolinePellerino AlessiaRudà RobertaCassoni PaolaRigau ValérieUro-Coste EmmanuelleMokhtari KarimaIdbaih AhmedBenusiglio Patrick RBielle Franck - Compare the clinical and imaging features of prostate cancer (PCa) patients harboring a germline pathogenic variant (PV) to sporadic controls. - Source: PubMed
Publication date: 2026/09/28
Cochran Rory LParameswaran MadhangiNakrour NabihGhosh SoumyadeepElshikh AbdelrahmanRawal MirajPohl MaximillianAleenajitpong NuttaphonCatalano Onofrio AMojtahed AmirkasraMcCormick Shelley RRodgers-Fouche Linda HHarisinghani Mukesh GSalari Keyan - Integrated tumour and germline testing is recommended for all patients with metastatic prostate cancer (mPCa), yet real-world implementation varies widely. Use of tumour analysis to stratify patients for germline testing (tumour-first workflow (TFW)) has emerged as an efficient triage strategy, but its performance relative to family history (FH)-based referral remains insufficiently characterised. - Source: PubMed
Publication date: 2026/09/19
Kloots Iris S HKets C MarleenSchuurs-Hoeijmakers JannekeKroeze Leonie IPillay Stephanievan Oort Inge MBloemendal Haiko JGerritsen Winald RLigtenberg Marjolijn J LMehra Niven - Hereditary factors account for a significant lifetime risk of breast cancer. Approximately 20% is attributable to pathogenic variants in the highly penetrant BRCA1/2 of the homologous recombination repair (HRR) pathway. Other HRR pathway genes (ATM, CHEK2, BARD1, TP53) are also linked to breast cancer susceptibility; however, the contribution of these genes remains underexplored in Pakistani populations. - Source: PubMed
Publication date: 2026/09/22
Saleem HumairaNasir MahrukhKhan SamraIrfan MuhammadShakeel MuhammadSaleem LubnaShafiq-Ur-Rehman Khan Ishtiaq Ahmad