King Faisal Specialist Hospital & Research Centre

Acute interstitial nephritis (AIN) is a recognized cause of acute kidney injury (AKI), most commonly associated with medications. Increasing evidence also implicates exposure to environmental chemicals, including hair‑straightening products marketed as "formaldehyde‑free," which may still contain or release nephrotoxic compounds. Reports have linked these products to oxalate nephropathy that may occur concurrently with interstitial nephritis, underscoring the need for awareness of their renal risks. We describe a 26-year-old healthy woman who presented with nausea, vomiting, and bilateral flank pain three days after undergoing a professional hair-straightening treatment. Laboratory investigations revealed Stage 3 AKI with serum creatinine level 372 µmol/L, while serologic and infectious workup was unremarkable. Urinalysis showed leukocyturia, hematuria, and proteinuria. Kidney ultrasound was normal. Shortly after product application, the patient had experienced scalp pruritus and erythema. Kidney biopsy demonstrated mild mixed interstitial infiltrates with eosinophils, tubulitis, and rare intratubular oxalate crystals, consistent with acute hypersensitivity interstitial nephritis. Treatment with intravenous methylprednisolone followed by oral prednisolone resulted in clinical improvement and normalization of renal function within one month. Product review identified glycolic acid, a compound metabolized to oxalate, as a potential etiological factor. This case illustrates severe AKI due to AIN with oxalate deposition following exposure to a hair-straightening product marketed as FA-free. Clinicians should maintain high suspicion for cosmetic exposures in patients with unexplained AKI. Awareness of these potential nephrotoxic effects is essential to support early recognition, appropriate management, and preventive public health measures.

Background: Gene expression and cellular identity are regulated by epigenetics that occurs through chromatin modifications, RNA changes, chromatin accessibility, and three-dimensional genome organization. Although DNA methylation has been the focus of most epigenetics studies in the past, other non-methyl epigenetic processes, including histone post-translational modifications (PTMs), epitranscriptomic marks, and chromatin remodeling, are dynamic, reversible, and context-dependent, and thus are difficult to accurately interrogate using endpoint sequencing-based assays, especially in heterogeneous tissues, developing systems, and therapeutic response environments. Scope and Approach: The present review discusses epigenetic modifications other than DNA methylation regarding sensor-based technologies that can measure live, dynamic, and spatially resolved measurements. Epigenetic sensors include any genetically encoded sensors (GECs) based on resonance energy transfer, CRISPR/dCas-derived sensors, or aptamer-based sensors, and hybrid biochemical/imaging sensors that can be used in live or semi-live settings. It lays emphasis on the technologies, which have been developed recently, that allow real-time kinetic measurements, working in three-dimensional and organoid models, and being applied to disease-relevant perturbations. On these platforms, performance properties such as specificity, sensitivity, spatial and temporal resolution, ability to perform dynamic versus locus-specific interrogation, and perturbed endogenous chromatin states are compared. Key Conclusions and Outlook: Together, these sensing strategies are complementary to the traditional methods of measuring epigenomics in that they show epigenetic dynamics unobservable with static measurements. We list the important technical issues, including specificity, quantitation, multiplexing, and chromatin perturbation, and report the barriers and solutions in development and design. Lastly, we provide a conceptual map of how live epigenetic sensing and multi-omics and translational models can be integrated, and how the two methodologies can be used to develop functional epigenetics and guide disease modeling and drug development.

BackgroundBiosimilars are increasingly used in rheumatology practice; however, knowledge gaps and regulatory uncertainties may affect their acceptance. This study assessed the knowledge, perceptions, and clinical practices related to biosimilars among rheumatologists in the Arab League of Associations for Rheumatology (ArLAR) countries.MethodsA web-based survey of 19 questions, adapted from a European Society for Medical Oncology (ESMO) tool, was distributed among ArLAR-affiliated rheumatologists between July 2024 and January 2025. The questionnaire assessed knowledge, attitudes, clinical use, and educational preferences. A French version was developed and validated by the study steering committee. Responses were analyzed using descriptive statistics.ResultsA total of 105 rheumatologists from various Arab countries participated in the survey. The mean age of participants was 43.6 ± 11.7 years, and 61.9% were females. Most participants were adult rheumatologists (94.3%), primarily from Iraq (37.1%), Morocco (19%), and Algeria (16.2%). While 85.7% reported using biosimilars in practice, only 50.5% correctly identified the formal definition. Comfort with EMA/FDA-approved biosimilars was high (mean score 4.22/5), while concerns remained about switching in stable patients and among multiple biosimilars. The majority (80%) expressed interest in additional biosimilar education, particularly on regulatory approval, extrapolation, and safety.ConclusionArLAR rheumatologists show high uptake of biosimilars but moderate understanding of key regulatory and clinical concepts. Regionally adapted educational programs are needed to support evidence-based biosimilar use and improve confidence in clinical decision-making.

Programmed Death-Ligand 1 (PD-L1) promotes tumor progression through several mechanisms, including its intrinsic effect on breast cancer cell proliferation via the S-Phase Kinase-Associated Protein 2 (SKP2)-p21Cip1/p27Kip1 (SKP2-p21/p27) axis. However, the specific regulatory signaling through which PD-L1 influences the SKP2-p21/p27 axis to drive cell proliferation remains unclear. To investigate how PD-L1 mediates SKP2-dependent proliferation, proteomic analyses, gene-expression manipulation via knockdown or overexpression, Western blotting, quantitative immunofluorescence, colony-forming assays, real-time cell analysis, and Xenograft-derived cells were used. Proteomic data analysis identified several PD-L1 downstream targets as potential candidate regulators of the SKP2-p21/p27 axis and activators of the PI3K/AKT pathway. Candidate screening by gene knockdown, followed by analyses of SKP2, p21, and p27 protein expression, revealed Livin and Galectin-1 as upstream regulators of the SKP2-p21/p27 axis. Moreover, Western blotting and quantitative immunofluorescence in three breast cancer cell lines confirmed that PD-L1 is an upstream regulator of Livin, Galectin-1, and SKP2 protein expression. Mechanistically, Livin and Galectin-1 enhanced AKT phosphorylation (Ser473) to sustain PI3K/AKT pathway activation in a positive feedback loop to upregulate SKP2 expression. Functional assays, including colony-forming assays and real-time cell analyzer, demonstrated that Livin and Galectin-1 are critical for PD-L1-mediated, SKP2-dependent proliferation. These findings were corroborated in vivo using xenograft-derived cells. Overall, these findings delineate a tumor-intrinsic signaling axis in which PD-L1 upregulates Livin and Galectin-1 to sustain PI3K/AKT activity and drive SKP2-dependent cell proliferation. Targeting Livin and/or Galectin-1 may provide a rational strategy to disrupt PD-L1-associated proliferative signaling and improve combinatorial therapeutic approaches in breast cancer.

[This corrects the article DOI: 10.3389/fmed.2026.1763735.].

Breast cancer is the most prevalent and leading cause of cancer-related mortality among women worldwide. The triple-negative subtype, the most aggressive form of the disease, is associated with the poorest prognosis. In order to improve the treatment of these patients, we have synthesized a phyto-chemo drug conjugate composed of cisplatin and eugenol, two molecules with synergistic anti-cancer effects. Eugenoplatin was synthesized and characterized by HPLC, LC/MS, and 1H-NMR, while its physicochemical properties were predicted by in silico analysis using the Biovia Discovery Studio. The cytotoxic effects of eugenoplatin were first tested in vitro using the WST1 and the flow cytometry techniques. Cell proliferation, migration, and invasion abilities were assessed using the xCELLigence Real-Time Cell Analysis. The changes in gene expression were determined by proteomics analysis (LC/MS), immunoblotting, immunofluorescence, and quantitative RT-PCR. The effect of the drug on breast cancer stem cells was determined by the tumorsphere formation assay, and cell sorting was utilized to isolate a specific breast cancer sub-population of cells. Furthermore, orthotopic tumor xenografts were used to test the potential therapeutic value of eugenoplatin in vivo. The novel DNA-damaging molecule (eugenoplatin) has shown higher cytotoxicity through induction of apoptosis, and strong inhibition of cell growth via cell cycle delay at G2/M phase in different cell lines. In addition, eugenoplatin targeted cancer stem cells through inhibition of the β-catenin signaling pathway. These effects were confirmed in humanized orthotopic tumor xenografts, wherein the eugenoplatin-dependent tumor growth inhibition was more than 10-fold stronger than the cisplatin repressive effect, with a potent inhibitory effect on cancer stem cell biomarkers. This was associated with the suppression of various cancer-related signaling pathways, including STAT3/NF-κB, AKT/mTOR, and ERK. Furthermore, eugenoplatin down-regulated the pro-angiogenic factors VEGF-A, IL-6, and IL-8, and repressed angiogenesis both in vitro and in tumor xenografts. In silico analysis has suggested good permeability, good absorption, and higher bioavailability for eugenoplatin, which is also unlikely to be mutagenic, carcinogenic, or hepatotoxic. These results indicate that eugenoplatin, a novel DNA-damaging agent that can also target cancer stem cells, could be of great therapeutic value for TNBC patients.

PALB2 plays a crucial role in DNA repair by interacting with BRCA1 and BRCA2. To clarify the clinicopathological impact of somatic PALB2 variants, we analyzed tumor DNA extracted from formalin-fixed, paraffin-embedded (FFPE) breast cancer specimens from 81 patients. Targeted next-generation sequencing identified 1 514 variants, including 84 pathogenic or likely pathogenic variants and 9 genes with high mutation frequency; 2 deleterious somatic PALB2 variants were detected in 33% of samples. To explore transcriptional effects, we analyzed publicly available METABRIC mRNA expression data and found that elevated PALB2 mRNA levels were significantly associated with ER-/PR- tumors and poorer survival outcomes. High PALB2 expression remained an independent predictor of shorter overall survival and relapse-free survival. These findings highlight the clinical importance of somatic PALB2 mutations and the prognostic value of PALB2 expression in breast cancer.