While RNA-sequencing (RNA-seq) is cost-effective and widely available, obtaining comprehensive DNA methylation profiles remains resource-intensive. To bridge this gap, we developed a deep variational autoencoder (VAE) framework for predicting DNA methylation patterns directly from RNA-seq data in renal clear cell carcinoma. Using The Cancer Genome Atlas–Kidney Renal Clear Cell Carcinoma dataset-sourced from cBioPortal and selected for its clinical relevance in renal clear cell carcinoma and high-quality paired omics data-we implemented a rigorous pre-processing pipeline including quality control, missing data imputation, and RNA feature selection based on variance and predictive power. A patient-wise 80/20 train–test split was employed to prevent data leakage. A deep VAE (NetVAE) with residual encoder blocks was trained to learn a compressed latent representation of the methylome and reconstruct genome-wide beta values directly from RNA-seq input. On the independent test set ( n = 55 patients), the NetVAE achieved R² = 0.627, mean absolute error = 0.135, and Pearson correlation coefficient r = 0.792 ( p < 0.001). Spearman correlation was 0.641 ( p < 0.001). Scatter and density plots confirmed strong predictive power across the full range of beta values. This framework offers a practical, cost-effective method for inferring methylation landscapes from RNA-seq data, with significant potential for biomarker discovery and retrospective epigenetic studies in renal clear cell carcinoma, where direct methylation profiling is unavailable.

With the rollout of multiple COVID-19 vaccines, adjunctive treatments for COVID-19 have received less attention. Breakthrough infections post-vaccination (including boosters) underscore the need to continue evaluating repurposed drugs and nutraceuticals as candidate adjunctive treatments. Early clinical studies of antihistamines hypothesized that targeting mast cells (and/or histamine receptors) might benefit COVID-19 patients. In cultured human coronary artery endothelial cells, histamine potentiated spike-mediated angiotensin-converting enzyme 2 internalization; this effect can be blocked by the antihistamine famotidine. This literature review focuses on clinical studies of antihistamines, mast cell stabilizers, and leukotriene receptor antagonists for COVID-19 patients. Several antihistamines and mast cell-targeting agents, including fluvoxamine, cyproheptadine, hydroxyzine, and antihistamines used alone or with azithromycin (dexchlorpheniramine, cetirizine, loratadine, and ebastine), as well as azelastine, famotidine (standard or high-dose), high-dose famotidine with celecoxib, and the flavonoid mast cell stabilizer quercetin, have been reported to be associated with clinical benefits in COVID-19 patients. Multiple studies have reported mixed results for aspirin, montelukast, and normal-dose famotidine; patients taking aspirin often have associated COVID-19 risk factors. In the context of current standard-of-care treatments, clinical studies evaluating candidate adjunctive treatments should carefully consider and avoid known drug–drug interactions, such as those involving celecoxib and dexamethasone. Further clinical studies of the identified treatments targeting mast cells and/or histamine receptors in COVID-19 patients associated with clinical benefits are therefore strongly recommended.

Heparin, a sulfated glycosaminoglycan composed of glucosamine and hexuronic acids in alternating sequence, binds a myriad of proteins collectively termed the “heparinome,” mainly through electrostatic interactions. Heparin prevents blood coagulation and is clinically applied to prevent thrombosis. The more sparsely sulfated polysaccharide heparan sulfate binds heparinome proteins more selectively, thereby regulating development, homeostasis, and disease. Biosynthesis of heparan sulfate yields products of variable, but controlled average composition. Dysregulation of heparinome interactions occurs in diseases, including cancer, inflammatory conditions, and amyloid diseases. Established structure–function relations provide a basis for drug development. The discovery of a specific pentasaccharide sequence in heparin, containing a rare glucosamine 3-O-sulfate group essential for anticoagulant activity, facilitated the development of various low-molecular-weight heparins with favorable pharmacokinetic properties. The 3-O-sulfate group has since been implicated in diverse aspects of heparan sulfate function. Heparin derivatives lacking anticoagulant activity can be administered at higher doses. Non-anticoagulant effects of heparin are increasingly exploited in the clinic, for instance, to curb the “cytokine storm” in severely ill COVID-19 patients. Other applications, such as in cancer and inflammatory conditions, are suggested by various incidental beneficial effects observed during heparin treatment for thromboembolic disease. Such effects are likely due to displacement of regulatory proteins from heparan sulfate proteoglycans at epithelial surfaces, or alternatively to inhibition of heparanase, a heparan sulfate-degrading enzyme. Exploitation in such cases would involve identification of key protein mediators followed by generation of minimally sulfated oligosaccharide drug candidates (or mimetics) with selective binding properties.

Currently, the detection of lung cancer depends on chest X-ray, low-dose computed tomography (CT) scans, and tissue biopsy. However, harmful radiation from X-rays and CT scans may increase cancer risk. In contrast, biopsy of the lungs is highly laborious and painful. These diagnostic limitations contribute to delayed diagnosis, and treatment is therefore less effective at advanced stages. DNA methylation is a mechanism in which DNA methyltransferases add a methyl group to the cytosine–phosphate–guanine islands of a gene, which can either enhance or suppress its expression. Previous research has shown that promoter methylation of proto-oncogenes and tumor suppressor genes begins at the early stages of tumorigenesis and can be detected in cell-free DNA derived from blood plasma. With this primary objective, we highlight DNA hypomethylation in proto-oncogenes and hypermethylation in tumor suppressor genes in lung cancer patients, which may serve as therapeutic targets for the development of treatments that may increase the survival rate of lung cancer patients.

Mineral trioxide aggregate (MTA)-based dental materials are widely used in endodontic therapy due to their favorable sealing ability, biocompatibility, and bioactivity; however, ongoing research seeks to enhance their functional performance and biological responses by incorporating advanced biomimetic and nanostructured fillers. This study reports the development and comprehensive characterization of a novel MTA-type dental material based on a nanostructured calcium phosphate biomimetic filler. The base MTA was obtained from synthesized dental cement and commercial bismuth oxide, which served as the radiopacifier. To obtain the biomimetic obturating composition (BOC), base MTA was mixed with biomimetic filler consisting of nanostructured calcium-deficient, silicon- and fluorine-substituted hydroxyapatite synthesized using the authors’ methodology. Structural-morphological and physicochemical characteristics of all components were investigated using X-ray diffraction, Fourier-transform infrared spectroscopy, and scanning and transmission electron microscopy. In accordance with International Organization for Standardization (ISO) 6876:1986 requirements, key functional properties of BOC samples, such as flowability (20–23 mm), working time (630–660 s), setting time (420–680 s), radiopacity (>3 mmAl), and solubility (1.6–2.1%) were studied. In vitro bioactivity of BOC samples was evaluated through calcium ion release in simulated body fluid (SBF) and acetate buffer, as well as apatite-forming ability in SBF. It was found that incorporating the nanostructured biomimetic filler significantly enhanced calcium ion release and promoted the formation of a surface apatite layer, the thickness of which increased with filler content. The results demonstrate that the proposed BOC exhibits improved bioactivity while maintaining acceptable physicochemical and functional characteristics, indicating its potential for dental application.

The increasing prevalence of methicillin-resistant Staphylococcus aureus (MRSA) highlights the need for alternative therapeutic strategies. Natural product-derived resistance-modifying compounds are gaining attention as antibiotic adjuvants to restore drug activity. Epicatechin gallate (EPCG) has antibacterial and anti-virulence properties. This study investigates the antibacterial activity of EPCG and its potential to enhance the efficacy of selected antibiotics against S. aureus and MRSA. Standard broth microdilution assays were used to determine the minimum inhibitory concentration (MIC) of EPCG against S. aureus and MRSA. Synergistic interactions with selected antibiotics were evaluated using checkerboard and isobologram assays. Furthermore, cytotoxicity was evaluated using Artemia franciscana nauplii (brine shrimp) lethality and human dermal fibroblast (HDF) assays. The impact of EPCG, cefotaxime, and their combinations on cells and biofilms was visualised through confocal and cryo-electron microscopy. EPCG demonstrated strong antibacterial activity (MIC = 208 µg/mL against S. aureus and 188 µg/mL against MRSA). Isobologram assays also revealed strong synergy for the EPCG–cefotaxime combination (∑ fractional inhibitory concentration = 0.15 for MRSA; 0.25 for S. aureus). EPCG exhibited moderate toxicity toward HDF cells (LC₅₀ = 100 µg/mL), whereas the optimised cefotaxime: EPCG (90:10 [v/v]) combination was non-toxic across all assays. Additionally, confocal microscopy revealed reduced bacterial aggregation and diminished biofilm-associated fluorescence following EPCG treatment. Cryo-electron microscopy revealed pronounced ultrastructural disruptions in MRSA cells treated with the combination. In conclusion, EPCG enhances the antibacterial activity of antibiotics such as cefotaxime against S. aureus and MRSA. Its synergistic action, lower cytotoxicity at optimal ratios, and confirmed damage to bacterial cells highlight EPCG’s potential as a natural antibiotic adjuvant.