Oxidative processes influence several aspects of biology, from the subtle balance of redox signaling to the destructive cascade of oxidative damage associated with chronic disease and aging [...].
Oxidative processes influence several aspects of biology, from the subtle balance of redox signaling to the destructive cascade of oxidative damage associated with chronic disease and aging [...].
Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality. It usually arises in cirrhotic liver, where chronic inflammation and fibrosis create a tumor-permissive microenvironment. Dysregulation of microRNAs (miRNAs), particularly upregulation of the oncomiR miR-221 and loss of the tumor suppressor miR-199a-3p represent key drivers of liver carcinogenesis. The TG221 transgenic mouse, designed to overexpress miR-221 in hepatocytes, provides a relevant in vivo platform for mechanistic studies and for testing preventive and therapeutic approaches. The TG221 model recapitulates miR-221-driven tumorigenesis, including suppression of p27, p57 and Bmf. It is characterized by steatohepatitic injury and accelerated tumor formation after genotoxic challenge. In the cirrhotic CCl4-induced background, TG221 mice develop fibrosis and cirrhosis followed by dysplastic and malignant lesions, mirroring the natural history of human HCC. Metformin administered during early fibrosis prevented macroscopic tumor formation and suppressed PI3K/AKT/mTOR signaling. Anti-miR-221 and miR-199a-3p mimics reduced tumor burden, restored tumor-suppressive pathways and improved liver integrity, thus indicating feasible chemopreventive strategies. From a therapeutic point of view, miR-199a-3p replacement synergized with palbociclib and overcame sorafenib resistance. A miR-199a-3p-responsive oncolytic adenovirus achieved tumor-selective replication with minimal toxicity. This review highlights the importance of the TG221 transgenic mouse as a powerful model for studying miRNA-driven hepatocarcinogenesis and enables preclinical evaluation of RNA-based chemopreventive and therapeutic approaches. Metformin, miRNA inhibition, miRNA replacement and miRNA-guided viral therapies emerge as promising approaches for advancing precision prevention and treatment strategies in HCC.
By analyzing Food and Drug Administration (FDA) enforcement reports from 2004 to 2025, we can determine the incidence of microbial contamination in non-sterile and sterile drugs in the United States of America and, at the same time, compare the trends and patterns over a period of 21 years to determine the distribution and frequency of microbial contaminants. The most common microorganisms detected from 2019 to 2025 were the mold Aspergillus penicilloides, with 17 citations for sterile products, followed by 16 citations for non-sterile products of Burkholderia cepacia complex (BCC) bacteria. Analysis from the last 21 years revealed the dominant microbial contaminants belong to the BCC, reaching a maximum level between 2012 and 2019. Some of the previous microbial contaminants, such as Salmonella and Clostridium, decline in the 2019-2025 period, with no notifications issued. S. aureus and Pseudomonas contamination persisted through the years but at very low levels. Gram-negative bacteria contaminated non-sterile drugs more frequently than Gram-positive. A worrisome trend continued with unacceptable levels of enforcement reports not providing any information on the identity of the microbial contaminant. New species of Bacillus and Acetobacter nitrogenifigens were responsible for a significant increase in non-sterile drug recalls. The main driver for sterile product recalls over a 21-year period is the lack of assurance of sterility (LAS) where major failures in process design, control, and operational execution were not conducive to the control of microbial proliferation and destruction. Enforcement data analysis identified the problematic trends and patterns regarding microbial contamination of drugs, providing important information to optimize process control and provide a framework for optimizing risk mitigation. Although the 21-year landscape demonstrated that some microbial contaminants have been successfully mitigated, others remain resilient. The emergence of new contaminants highlights the evolving nature of microbial risk. The consistent problem with LAS is not only a major regulatory violation but also a potential catalyst for the next major healthcare-associated outbreak.
Iron-containing alcohol dehydrogenases (Fe-ADHs) from hyperthermophiles represent a distinct class of oxidoreductases characterized by exceptional thermostability, catalytic versatility, and unique metal-dependent properties. Despite considerable sequence diversity, Fe-ADHs share conserved motifs and a two-domain architecture essential for iron coordination and NAD(P)H cofactor binding. Physiologically, these enzymes are predicted to function primarily in aldehyde detoxification and redox homeostasis, with some also participating in fermentative alcohol production. Their remarkable stability and catalytic efficiency highlight their potential as robust biocatalysts for high-temperature industrial bioprocesses. This review presents a comprehensive comparative analysis of the biophysical, biochemical, and kinetic properties of Fe-ADHs, focusing on their thermostability, metal ion specificity, and catalytic mechanisms, as well as highlighting their potential for industrial biocatalytic applications.
The tumor immune microenvironment (TIME) is closely involved in tumor initiation, malignant progression, immune escape, and response to immunotherapy. With the continued development of high-throughput sequencing technologies, transcriptomic approaches have become essential for examining the cellular and molecular features of the TIME. Bulk RNA sequencing offers tissue-level gene expression profiles and allows the estimation of immune cell composition through computational deconvolution. Single-cell RNA sequencing provides finer resolution, revealing cellular heterogeneity, lineage relationships, and functional states. Spatial transcriptomics (ST) retains the native anatomical context, making it possible to localize gene expression patterns and cell-cell interactions within intact tissues. These approaches, when considered together, have shifted TIME research from averaged measurements toward a more detailed and mechanistic understanding. This review summarizes the principles, applications and limitations of bulk, single-cell and spatial transcriptomic methods, highlighting emerging strategies for integrative analysis. Such multi-scale frameworks are increasingly important for studying immune dynamics and may contribute to the development of more precise biotechnological and immunotherapeutic strategies.
Medicinal honeys from Oceania have gained considerable attention due to their peculiar bioactive constituents and potential health applications. Apart from small molecules such as methylglyoxal and hydrogen peroxide, these honeys are rich in phenolic compounds, volatile terpenes, and other bioactive molecules, which collectively contribute to their antioxidant, antimicrobial, anti-inflammatory, and wound-healing properties. Recent studies have highlighted the distinctive composition of Oceania honeys such as Manuka (Leptospermum scoparium), Jarrah (Eucalyptus marginata), and Agastache (Agastache rugosa) from New Zealand and Australia, demonstrating variability in bioactivity depending on floral source, geographical origin, and processing methods. This review synthesizes the current knowledge on the chemical profiles of these honeys with a particular focus on bioactive compounds and distinctive markers, and evaluates their therapeutic potential. Emphasis is placed on the mechanisms underlying their bioactivities, as well as emerging clinical and preclinical evidence supporting their medicinal use. By consolidating recent findings, this work provides an updated perspective on the functional properties of Oceania honeys, underscoring their relevance as natural products with significant health-promoting potential.
Bacillus-derived lipopeptides are known to possess diverse biological activities, including antimicrobial and anticancer properties, though the mechanisms of such effects at the molecular level remain incompletely understood. We investigated whether non-ribosomal peptide metabolites from Bacillus can directly interact with transmembrane receptors implicated in oxidative stress regulation and cancer progression (NOX4, EGFR, PDGFR, and OCTN2) using molecular docking and 200 ns molecular dynamics simulations of 11 lipopeptide metabolites. Molecular docking revealed several strong ligand-protein interactions, with plipastatin and fengycin emerging as lead compounds demonstrating the highest binding affinities to multiple receptors. For NOX4, iturin D showed the strongest docking score of -7.85 kcal/mol. Fengycin demonstrated a high docking score of -7.38 kcal/mol for PDGFR and -8.1 kcal/mol for EGFR. Plipastatin showed the strongest docking scores of -11.12 kcal/mol for EGFR and -8.7 kcal/mol for OCTN2. Molecular dynamics simulations confirmed complex stability for these lead compounds, with protein RMSD remaining stable at ~1.5 Å and ligand RMSD between 1.9 and 6 Å over 200 ns. Our findings suggest that plipastatin and fengycin may act as modulators of key receptors involved in oxidative stress and cancer-related signaling. However, those in silico predictions require experimental validation. This work provides the first computational evidence of potential lipopeptide-receptor interactions and establishes a foundation for future experimental investigation of probiotic-derived therapeutics.
Torularhodin is the monocyclic C40 carotenoid with the β-ring and a terminal carboxyl group at the acyclic part, with long conjugated double bonds, only synthesized in fungi called red (oleaginous) yeasts, e.g., the genera Rhodotorula and Sporobolomyces. This unique red pigment with strong antioxidant properties is promising for use in food additives, nutritional supplements, and cosmetics. We aimed to produce torularhodin in Escherichia coli through the identification of the biosynthesis genes needed for its heterologous production, while no genes oxidizing torulene to torularhodin had been reported. The Rhodotorula toruloides crtI (CAR1) and crtYB (CAR2) genes, which were chemically synthesized, proved to lead to the complete conversion of phytoene into torulene when they were introduced into an E. coli cell that carried the Pantoea ananatis crtE and Haematococcus pluvialis IDI genes. We found that the Planococcus maritimus genes coding for C30 carotenoid terminal oxidase (crtP/crtNb/cruO) and aldehyde dehydrogenase (aldH/crtNc), through their introduction into the E. coli transformant synthesizing torulene, mediated the efficient oxidations of torulene to torularhodin, and resulted in the production of torularhodin as the dominant carotenoid. This is the first report of torularhodin production in a heterologous host. We also identified the aldH/crtNc gene in R. toruloides.
Reusable enzyme carriers are valuable for proteomic workflows, yet many supports are expensive or lack robustness. This study describes the covalent immobilization of recombinant trypsin on micrometer-sized corundum particles and assesses their performance in protein digestion and antibody analysis. The corundum surface was cleaned with potassium hydroxide, silanized with 3-aminopropyltriethoxysilane and activated with glutaraldehyde. Recombinant trypsin was then attached, and the resulting imines were reduced with sodium cyanoborohydride. Aromatic amino acid analysis (AAAA) estimated an enzyme loading of approximately 1 µg/mg. Non-specific adsorption of human plasma proteins was suppressed by blocking residual aldehydes with a Tris-glycine-lysine buffer. Compared with free trypsin, immobilization shifted the temperature optimum from 50 to 60 °C and greatly improved stability in 1 M guanidinium hydrochloride. Activity remained above 80% across several reuse cycles, and storage at 4 °C preserved functionality for weeks. When applied to digesting the NISTmAb, immobilized trypsin provided peptide yields and sequence coverage comparable to soluble enzyme and outperformed it at elevated temperatures. MALDI-TOF MS analysis of Herceptin digests yielded fingerprint spectra that correctly identified the antibody and achieved >60% sequence coverage. The combination of low cost, robustness and analytical performance makes corundum-immobilized trypsin an attractive option for research and routine proteomic workflows.
The transition toward a circular bioeconomy requires efficient conversion of biogenic wastes and biomass into renewable fuels. This study explores the gasification potential of wastewater sludge (WWS) and food waste (FW), representing high moisture-content biowastes, compared with softwood (SW), a lignocellulosic biomass reference. An Aspen Plus equilibrium model incorporating the drying stage was developed to evaluate the performance of air and steam gasification. The effects of temperature (400-1200 °C), equivalence ratio (ER = 0.1-1), and steam-to-biomass ratio (S/B = 0.1-1) on gas composition and energy efficiency (EE) were examined. Increasing temperature enhanced H2 and CO generation but reduced CH4, resulting in a maximum EE at intermediate temperatures, after which it declined due to the lower heating value of the gases. Although EE followed the order SW > FW > WWS, both biowastes maintained robust efficiencies (60-80%) despite high drying energy requirements. Steam gasification increased H2 content up to 53% (WWS), 54% (FW), and 51% (SW) near S/B = 0.5-0.6, while air gasification achieved 23-27% H2 and 70-80% EE at ER ≈ 0.1-0.2. The results confirm that wet bio-wastes such as WWS and FW can achieve performance comparable to lignocellulosic biomass, highlighting their suitability as sustainable feedstocks for waste-to-syngas conversion and supporting bioenergy integration into waste management systems.
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