epidermal growth factor receptor (EGFR pharmDx / EGFR pharmDx Kit)

Niemann-Pick type C1 protein regulates epidermal growth factor receptor stability in hepatic cells and facilitates the early steps of Hepatitis B virus infection.

Stefan-Buzatoiu Stefania Ariadna SA, Alexandru Flintoaca Petruta-Ramona PR, Dobrica Mihaela-Olivia MO, Petrescu Stefana-Maria SM et al.

Chronic Hepatitis B virus (HBV) infection affects more than 250 million individuals worldwide, causing up to 1 million deaths yearly. Despite the significant disease burden, no curative therapy against HBV is currently available. Accumulating evidence indicate a strong and complex relationship between HBV and the host-cell lipid metabolism. HBV hijacks host lipoprotein transport pathways to gain access to hepatocytes and uses cellular cholesterol and sphingolipids for morphogenesis, while viral replication induces diverse and profound alterations of the hepatic lipid metabolism driving disease progression and tumorigenesis. As a key regulator of the cellular cholesterol homeostasis, the Niemann-Pick C1 (NPC1) protein has increasingly been associated with a wide range of pathologies, including viral infections. In this study, we investigated HBV entry, replication, viral particle envelopment and secretion in cells depleted of NPC1 expression or treated with various FDA-approved NPC1 inhibitors. Our work revealed that both genetic depletion and pharmacological inhibition of NPC1 impaired the early steps of HBV infection while significantly reducing the level and intracellular distribution of the HBV co-receptor, the Epidermal Growth Factor Receptor (EGFR). Mechanistically, NPC1 inhibition promoted EGFR depletion from the plasma membrane by enhancing the endocytic trafficking and degradation of the receptor within the endosomal-lysosomal compartment of hepatic cells. Considering the crucial roles of EGFR in tumorigenesis across multiple cancer types, our study promotes the newly identified NPC1-EGFR regulatory axis as a promising dual target for the development of antiviral and anticancer therapies.

Computational blueprint and stereochemical validation of a small peptide derived from Lacticaseibacillus casei VITCM05 targeting estrogen receptor alpha and human epidermal growth factor receptor 2.

Shree Kumari G R GR, Vaithilingam Mohanasrinivasan M

Breast cancer remains one of the leading causes of cancer-related mortality among women worldwide, necessitating the development of safer and more targeted therapeutic strategies. This study computationally extends our previous experimental investigation of a peptide derived from Lacticaseibacillus casei by evaluating its interactions with two clinically relevant breast cancer targets, estrogen receptor alpha (ERα; PDB ID: 3ERT) and human epidermal growth factor receptor 2 (HER2; PDB ID: 1N8Z). The peptide structure was predicted using PEP-FOLD and its stereochemical quality was assessed using a Ramachandran plot. Molecular docking was performed against ERα and HER2, followed by molecular dynamics simulations to evaluate structural stability. Binding free energy, binding affinity, dissociation constant, principal component analysis (PCA), free energy landscape (FEL), molecular mechanics (MM)/Poisson-Boltzmann surface area (PBSA) calculations, and in silico ADMET and toxicity predictions were performed to comprehensively characterise peptide-protein interactions. The predicted peptide model exhibited 84.8% of residues located in the most favoured regions, while 15.2% were located in additionally allowed regions of the Ramachandran plot, indicating satisfactory stereochemical quality. Molecular docking demonstrated favourable interactions with both ERα and HER2, with HER2 showing a marginally more favourable docking score. Molecular dynamics simulations indicated stable peptide-protein complexes throughout the simulation period, as supported by root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (Rg), solvent-accessible surface area (SASA), and hydrogen-bond analyses. MM/PBSA calculations predicted stronger binding for the HER2 (1N8Z) complex (ΔG = -28.83 kJ/mol) than for the ERα (3ERT) complex (ΔG = -11.65 kJ/mol), highlighting the complementary nature of docking and dynamic free-energy estimation, which produced different receptor rankings. PCA and FEL analyses further demonstrated stable conformational sampling for both complexes. ADMET predictions suggested favourable peptide-like physicochemical properties while identifying pharmacokinetic and toxicity parameters that require further experimental validation. This computational study suggests that the L. casei-derived peptide exhibits favourable predicted interactions with ERα and HER2 and forms structurally stable peptide-protein complexes under simulated physiological conditions. These findings provide a computational framework for prioritising this probiotic-derived peptide for subsequent experimental validation and further investigation as a potential peptide-based therapeutic candidate for breast cancer.

WITHDRAWAL-Administrative Duplicate Publication: Corrigendum to: Suppression of Cardiac Autophagy by Hyperinsulinemia in Insulin Receptor-Deficient Hearts Is Mediated by Insulin-Like Growth Factor Receptor Signaling.

Diagnostic and prognostic value of fibroblast growth factor 23 in acute kidney injury: systematic review and meta-analysis.

Pei Xiaohang X, Gao Hang H, Zhang Lina L

Background: Acute kidney injury (AKI) is associated with high mortality and adverse outcomes. Fibroblast growth factor 23 (FGF23) has emerged as a potential biomarker for AKI; however, its diagnostic and prognostic utility remains inconsistent.Methods: We conducted a systematic review and meta-analysis of studies evaluating circulating intact FGF23 (iFGF23) or C-terminal FGF23 (cFGF23) (PROSPERO: CRD42022302659). PubMed, EMBASE, CNKI, and Wanfang databases were searched through June 9, 2026. QUADAS-2 was used for quality assessment. A random-effects bivariate model pooled sensitivity, specificity, positive/negative likelihood ratio (PLR/NLR), diagnostic odds ratio (DOR), and area under the summary receiver operating characteristic curve (SROC AUC).Results: Twenty-three studies were included: 17 diagnostic, 6 prognostic (one addressing both). For AKI diagnosis, the pooled sensitivity was 0.79 (95% CI 0.73-0.86), specificity 0.82 (95% CI 0.75-0.89), PLR 4.40 (95% CI 2.59-6.21), NLR 0.25 (95% CI 0.16-0.34), DOR 17.49 (95% CI 8.67-35.16), and SROC AUC 0.87 (95% CI 0.81-0.92). Substantial heterogeneity was observed (I2 = 67%), with iFGF23 demonstrating higher accuracy than cFGF23 (AUC 0.91 vs 0.81). For AKI mortality, pooled sensitivity was 0.77 (95% CI 0.69-0.84), specificity 0.76 (95% CI 0.70-0.82), DOR 10.89 (95% CI 6.86-17.30), and SROC AUC 0.77 (95% CI 0.70-0.83). Significant heterogeneity was noted (I2 = 86.2% for sensitivity, 80.4% for specificity). No significant publication bias was detected.Conclusions: Circulating FGF23 exhibits moderate-to-high diagnostic and moderate prognostic performance in AKI, though interpretation is limited by substantial heterogeneity. It may serve as a complementary biomarker for risk stratification, pending further validation with standardized protocols.