Search Results (162)

Osteoarthritis (OA) remains a major contributor to pain and disability; however, the current management is largely reactive, focusing on symptoms rather than preventing irreversible cartilage loss. This review first examines the mechanistic foundations for pharmacological chondroprotection—illustrating how conventional agents, such as glucosamine sulfate and chondroitin sulfate, can potentially restore extracellular matrix (ECM) components, may attenuate catabolic enzyme activity, and might enhance joint lubrication—and explores the delivery challenges posed by avascular cartilage and synovial diffusion barriers. Subsequently, a practical “What–How–When” framework is introduced to guide community pharmacists in risk screening, DMOAD selection, chronotherapeutic dosing, safety monitoring, and lifestyle integration, as exemplified by the CHONDROMOVING infographic brochure designed for diverse health literacy levels. Building on these strategies, the P4–4P Chondroprotection Framework is proposed, integrating predictive risk profiling (physicians), preventive pharmacokinetic and chronotherapy optimization (pharmacists), personalized biomechanical interventions (physiotherapists), and participatory self-management (patients) into a unified, feedback-driven OA care model. To translate this framework into routine practice, I recommend the development of DMOAD-specific clinical guidelines, incorporation of chondroprotective chronotherapy and interprofessional collaboration into health-professional curricula, and establishment of multidisciplinary OA management pathways—supported by appropriate reimbursement structures, to support preventive, team-based management, and prioritization of large-scale randomized trials and real-world evidence studies to validate the long-term structural, functional, and quality of life benefits of synchronized DMOAD and exercise-timed interventions. This comprehensive, precision-driven paradigm aims to shift OA care from reactive palliation to true disease modification, preserving cartilage integrity and improving the quality of life for millions worldwide. Full article

Agriculture and its related industries produce annually a vast amount of byproducts and waste which comprise a large proportion of global waste. Only a small percentage is managed with environmentally acceptable procedures, while a large proportion is either incinerated or discarded into nearby open fields, causing serious environmental burdens. Since these byproducts exhibit a rich nutritional and phytochemical content, they may be considered as raw materials for various industrial applications, initiating the need for the development of sustainable and eco-friendly methods for their valorization. Among the various methods considered, Solid-State Fermentation (SSF) constitutes an intriguing eco-friendly bioprocess, being suitable for water-insoluble mixtures and providing products with improved stability and depleted catabolic suppression. Thus, there are several literature studies highlighting the aspects and efficacy of SSF for improving the nutritional and phytochemical contents of diverse agro-industrial waste. The review herein aspires to summarize these literature results with a special focus on the enhancement of their antioxidant potency. For this purpose, specific keywords were used for searching multiple scientific databases with an emphasis on the most recent studies and higher impact journals. The presented data establish the usefulness and efficacy of the SSF bioprocess to obtain fermentation products with enhanced antioxidant profiles. Full article

The hydroxycarboxylic acid receptor (HCAR) family belongs to G-protein-coupled receptors (GPCRs) implicated in a diverse array of physiological and pathological mechanisms. Kynurenic acid, a metabolite of the tryptophan catabolic pathway, has been proposed as a putative ligand of HCAR3. This receptor, among other HCARs, has garnered particular attention due to its exclusive expression in humans and closely related primates, and its emerging role in immunometabolic regulation. This review focuses on the potential role of HCAR3 in cancer initiation, progression, and metastasis. Moreover, it presents a comprehensive analysis of the potential functional and molecular interactions between kynurenic acid and HCAR3 in the context of cancer pathophysiology, which may have significant implications for tumor immunomodulation and the development of new therapeutic strategies. Full article

Polyamine oxidase (PAO) is an important enzyme that functions in the catabolism of polyamines. While plant PAOs have been studied in several species, there is a lack of research on this gene family in soybean (Glycine max L.), one of the major food crops worldwide. Here, a genome-wide analysis identified 16 GmPAOs from the soybean genome, which were unevenly distributed in nine soybean chromosomes and were then phylogenetically classified into three groups. Collinearity analysis identified 17 duplicated gene pairs from the GmPAO family, and their Ka/Ks values were all less than one, indicating that the GmPAO family has undergone purifying selection during evolution. Analyses of the conserved motif and gene structure revealed the sequence differences among the GmPAOs of the three groups, suggestive of their functional differentiation. Additionally, the prediction of the secondary and tertiary structure of the GmPAOs provided a further basis for revealing their biological functions. A number of cis-acting elements relevant to development, phytohormone, and stress response were discovered in the promoter regions of the GmPAOs, which might be responsible for their functional diversities. Expression pattern analysis indicated that more than half of the GmPAOs showed preference in flower, two showed specificity in stem and shoot apical meristem, whereas four were barely expressed in all samples. Expression profiling of the GmPAOs also revealed that they were involved in the response to abiotic stresses, including cold, drought, and especially submergence stress. All these results lay an important foundation for further characterizing the functional roles of GmPAOs in soybean development and response to abiotic stresses. Full article

Antibiotic pressure exerts profound effects on bacterial physiology, not limited to classical genetic resistance mechanisms. Increasing evidence highlights the ability of pathogens to undergo metabolic rewiring—an adaptive, reversible reorganization of core metabolic pathways that promotes survival under antimicrobial stress. This review provides a comprehensive analysis of antibiotic-induced metabolic adaptations, encompassing glycolysis, the tricarboxylic acid cycle, fermentation, redox balance, amino acid catabolism, and membrane biosynthesis. We critically examine how diverse antibiotic classes—including β-lactams, aminoglycosides, quinolones, glycopeptides, polymyxins, and antimetabolites—interact with bacterial metabolism to induce tolerance and persistence, often preceding stable resistance mutations. In parallel, we explore the ecological and host-derived signals—such as immunometabolites and quorum sensing—that modulate these metabolic responses. Therapeutically, targeting metabolic pathways offers promising strategies to potentiate antibiotic efficacy, including enzyme inhibition, metabolic adjuvants, and precision-guided therapy based on pathogen metabolic profiling. By framing metabolic plasticity as a dynamic and evolutionarily relevant phenomenon, this review proposes a unifying model linking transient tolerance to stable resistance. Integrating metabolic rewiring into antimicrobial research, clinical diagnostics, and therapeutic design represents a necessary paradigm shift in combating bacterial persistence and resistance. Full article

This review first provides an overview of the functional diversity of Orthoptera-associated microbiota and the services they provide to their hosts. However, data are widely scattered across the different families studied, making it difficult to establish whether a core microbiota is present. The abundance of some genera (Pantoea, Enterococcus, Enterobacter, Acinetobacter) is associated with the degradation of cellulose compounds, although their clear contribution remains to be determined. In addition, P. agglomerans may play a role in the production of aggregation pheromones in the desert locust. In terms of gut compartmentalisation, the diversity of the bacterial community in the foregut appears to be highly variable between individuals and species, whereas it is more uniform in other parts of the gut. Metabolic pathways of the gut microbiota revealed differences in amino acid metabolism between the midgut and hindgut. Bacteria in the midgut are associated with amino acid synthesis and anaerobic metabolism, whereas pathways in the hindgut may be involved in amino acid catabolism and ace-tyl-CoA-mediated processes. Further research is needed to better understand these different components of the bacterial community in digestive processes, and to identify bacterial species of particular interest in explaining species’ lifestyles or for bioconversion. Full article

Treelines are advancing upward on mountain slopes due to climate warming and reduced grazing intensity. However, the effects of initial vegetation changes on soil C, N, and P retention, microbial biomass, and catabolic diversity in the subalpine meadows during the early stages of treeline shifts remain poorly understood. This research aimed to better understand the direction and drivers of microbial processes related to C, N, and P cycles in the soil of subalpine natural and grazed meadows, with treatments involving meadow grasses alone (GR, control) and as a mixture with forest litter, specifically birch leaves (BLs), in a one-year microcosm experiment. The addition of BLs with GR resulted in a 12–67% decrease in the retention of C, N, and P in soil microbial biomass, but an 8–9% increase in catabolic diversity compared to the control. The most pronounced effect was observed in the N content of the soil microbial biomass (MBN) for both land uses. The increased proportion of recalcitrant plant residue fractions (acid-insoluble and non-polar extractables) contributed to the decrease in soil MBN content. This shift also reduced the microbial metabolic response to carbohydrates in total substrate-induced respiration, leading to a more balanced and catabolically diverse microbial community. These results improve our understanding of the early response of C, N, and P cycling in mountain soils to treeline shifts mediated by climate warming. Full article

Background: Critical illness induces profound metabolic alterations, characterized by a hypermetabolic state, insulin resistance, protein catabolism, and gut barrier dysfunction, which contribute to increased morbidity and mortality. Emerging evidence highlights the role of the gut microbiome and its metabolites in modulating systemic inflammation and immune responses during critical illness. This narrative review explores the metabolic evolution of critically ill patients, the impact of gut dysbiosis on disease progression, and the potential role of nutrition in modulating metabolism and improving patient outcomes. Methods: A comprehensive literature search was conducted across PubMed and Google Scholar for articles published up to February 2025. Search terms included “critical illness”, “metabolism”, “gut microbiota”, “nutrition”, and related keywords. Articles published in English addressing metabolic alterations, microbiome changes, and nutritional strategies in critically ill patients were included. After screening for eligibility, relevant articles were synthesized to outline current knowledge and identify gaps. Results: Metabolic changes in critical illness progress through distinct phases, from catabolism-driven hypermetabolism to gradual recovery. Gut dysbiosis, characterized by a loss of microbial diversity and increased gut permeability, contributes to systemic inflammation and organ dysfunction. Nutritional strategies, including enteral nutrition, probiotics, prebiotics, and metabolomics-driven interventions, may help restore microbial balance, preserve gut barrier integrity, and modulate immune and metabolic responses. Future nutrition therapy should focus on metabolic modulation rather than solely addressing nutrient deficits. Conclusions: Advances in gut microbiome research and metabolomics offer new avenues for personalized nutrition strategies tailored to the metabolic demands of critically ill patients. Integrating these approaches may improve clinical and functional recovery while mitigating the long-term consequences of critical illness. Full article

β-Hydroxy-β-methylbutyrate (HMB), a metabolite of the essential amino acid leucine, is acknowledged for its powerful role in facilitating muscle protein synthesis, reducing muscle catabolism, and promoting fat-free mass accumulation. With well-documented anticatabolic, anabolic, and lipolytic effects, HMB has been extensively studied in clinical settings and has exhibited potential in mitigating muscle loss induced by aging, cancer cachexia, and sarcopenia. Moreover, HMB finds applications in specialized medical nutrition, sports nutrition, and animal husbandry, with recent research illustrating its benefits in enhancing animal growth and immunity. This review highlights the current understanding of HMB’s physiological mechanisms, its diverse applications, and recent advancements in detection methods such as High-Performance Liquid Chromatography (HPLC), Gas Chromatography (GC), and Liquid Chromatography–Mass Spectrometry (LC–MS). Additionally, it discusses the future prospects of HMB bio-manufacturing. The establishment of standardized guidelines for its safe use and testing is crucial for its broader adoption in the food industry. Future research should focus on further elucidating HMB’s muscle growth mechanisms and broadening its applications across the food, health, and agricultural sectors. In sum, future studies should prioritize mechanistic exploration, safety and synergy, along with standardization to fully harness HMB’s potential. Full article

The endocannabinoid system (ECS) plays a crucial role in maintaining homeostasis by regulating immune response, energy metabolism, cognitive functions, and neuronal activity. It consists of endocannabinoids (eCBs), cannabinoid receptors (CBRs), and enzymes involved in eCB biosynthesis and degradation. Increasing evidence highlights the involvement of the ECS under several pathological conditions, making it a promising therapeutic target. Recent research efforts have focused on modulating endogenous eCB levels, particularly through the inhibition of fatty acid amide hydrolase (FAAH), the main catabolic enzyme of the major eCB anandamide. Natural substances, including plant extracts and purified compounds, can inhibit FAAH and represent a promising area of pharmacological research. Natural FAAH inhibitors are particularly attractive due to their potentially lower toxicity compared to synthetic compounds, making them safer candidates for therapeutic applications. Phytocannabinoids, flavonoids, and flavolignans have been shown to efficiently inhibit FAAH. The structural diversity and bioactivity of these natural substances provide a valuable alternative to synthetic inhibitors, and may open new avenues for developing innovative pharmacological tools. Full article

This review summarizes recent findings on the diverse roles of bacterial sialidases in microbial biology. Bacterial sialidases, also known as neuraminidases, are exog α-lycosidases that cleave terminal sialic acid residues from a number of complex compounds designated as sialoglycoconjugates (glycoproteins, glycolipids and oligosaccharides). Metabolically, they are involved in sialic acid catabolism, providing energy, carbon and nitrogen sources. Catabolic degradation of sialic acids is a physiological feature that can be considered an important virulence factor in pathogenic microorganisms. Sialidases play a pivotal role in host–pathogen interactions and promotion of bacterial colonization. The activity of these enzymes enables bacterial adhesion, biofilm formation, tissue invasion, and also provides immune evasion by exposing cryptic receptors and modifying immune components. Many different perspectives are being developed for the potential application of sialidases. In the field of medicine, they are being explored as appropriate targets for antimicrobials, vaccines, diagnostic preparations and in tumor immunotherapy. In the field of enzymatic synthesis, they are used for the regioselective production of oligosaccharide analogs, enzymatic separation of isoenzymes and as a tool for structural analysis of sialylated glycans, among other applications. Full article

Branched-chain amino acid aminotransferases (BCATs), existing as the two isoforms BCAT1 and BCAT2, are responsible for the catabolism of branched-chain amino acids (BCAAs) and are highly upregulated and implicated in a diverse range of cancers. BCAT1 inhibitors represent a potential class of therapeutic agents for cancers; however, none have yet progressed to clinical development. Our earlier research identified WQQ-345 as a novel BCAT1 inhibitor featuring a unique bridged bicyclic skeleton and demonstrating both in vitro and in vivo antitumor activity against tyrosine kinase inhibitor (TKI)-resistant lung cancer with high BCAT1 expression. In the present study, we proceeded to modify the structure of WQQ-345 by two-round structure–activity relationship (SAR) exploration, leading to the discovery of a bicyclo[3.2.1]octene-bearing GABA derivative 7. Compound 7 exhibited a 6-fold enhancement in BCAT1 enzymatic inhibitory activity compared to the parent compound WQQ-345 and could effectively suppress the growth of 67R cells that highly expressed BCAT1 and was resistant to third-generation TKIs. GABA derivatives are an important chemical class of BCAT1 inhibitors, and therefore, the findings in the present study represent great progress both in the discovery of potent BCAT1 inhibitors with new chemical structures and in the treatment of cancer resistance. Full article

Carnitine O-acetyltransferase (CRAT) is a key mitochondrial enzyme involved in maintaining metabolic homeostasis by mediating the reversible transfer of acetyl groups between acetyl-CoA and carnitine. This enzymatic activity ensures the optimal functioning of mitochondrial carbon flux by preventing acetyl-CoA accumulation, buffering metabolic flexibility, and regulating the balance between fatty acid and glucose oxidation. CRAT’s interplay with the mitochondrial carnitine shuttle, involving carnitine palmitoyltransferases (CPT1 and CPT2) and the carnitine carrier (SLC25A20), underscores its critical role in energy metabolism. Emerging evidence highlights the structural and functional diversity of CRAT and structurally related acetyltransferases across cellular compartments, illustrating their coordinated role in lipid metabolism, amino acid catabolism, and mitochondrial bioenergetics. Moreover, the structural insights into CRAT have paved the way for understanding its regulation and identifying potential modulators with therapeutic applications for diseases such as diabetes, mitochondrial disorders, and cancer. This review examines CRAT’s structural and functional aspects, its relationships with carnitine shuttle members and other carnitine acyltransferases, and its broader role in metabolic health and disease. The potential for targeting CRAT and its associated pathways offers promising avenues for therapeutic interventions aimed at restoring metabolic equilibrium and addressing metabolic dysfunction in disease states. Full article

Target of rapamycin complex 1 (TORC1) is a key regulator of metabolism in eukaryotes across multiple pathways. Although TORC1 has been extensively studied in vertebrates and some invertebrates, research on this complex in scallops is limited. In this study, we identified the genes encoding TORC1 complex subunits in the scallop Argopecten irradians irradians through genome-wide in silico scanning. Five genes, including TOR, RAPTOR, LST8, DEPTOR, and PRAS40, that encode the subunits of TORC1 complex were identified in the bay scallop. We then conducted structural characterization and phylogenetic analysis of the A. i. irradians TORC1 (AiTORC1) subunits to determine their structural features and evolutionary relationships. Next, we analyzed the spatiotemporal expressions of AiTORC1-coding genes during various embryo/larvae developmental stages and across different tissues in healthy adult scallops. The results revealed stage- and tissue-specific expression patterns, suggesting diverse roles in development and growth. Furthermore, the regulation of AiTORC1-coding genes was examined in temperature-sensitive tissues (the mantle, gill, hemocyte, and heart) of bay scallops exposed to high-temperature (32 °C) stress over different durations (0 h, 6 h, 12 h, 24 h, 3 d, 6 d, and 10 d). The expression of AiTORC1-coding genes was predominantly suppressed in the hemocyte but was generally activated in the mantle, gill, and heart, indicating a tissue-specific response to heat stress. Finally, functional validation was performed using the TOR inhibitor rapamycin to suppress AiTORC1, leading to an enhanced catabolism, a decreased antioxidant capacity, and a significant reduction in thermotolerance in bay scallops. Collectively, this study elucidates the presence, structural features, evolutional relationships, expression profiles, and roles in antioxidant capacity and metabolism regulation of AiTORC1 in the bay scallop, providing a preliminary understanding of its versatile functions in response to high-temperature challenges in marine mollusks. Full article

The glyoxalase pathway, consisting of glyoxalase I (GLYI) and glyoxalase II (GLYII), is an enzymatic system that converts cytotoxic methylglyoxal to non-toxic S-D-lactoylglutathione. Although the GLY gene family has been analyzed in Arabidopsis, rice, grape, cabbage, and soybean, cucumber studies are lacking. Here, we analyzed the cucumber GLY gene family, identifying 13 CsGLYI and 2 CsGLYII genes. Furthermore, we investigated the physicochemical properties, phylogenetic relationships, chromosomal localization and colinearity, gene structure, conserved motifs, cis-regulatory elements, and protein–protein interaction networks of the CsGLY family. They were primarily localized in the cytoplasm, chloroplasts, and mitochondria, with a minor presence in the nucleus. The classification of CsGLYI and CsGLYII genes into five classes closely resembled the homologous genes in Arabidopsis and soybean. Additionally, hormone-responsive elements dominated the promoter region of GLY genes, alongside light- and stress-responsive elements. The predicted interaction proteins of CsGLYIs and CsGLYIIs exerted a significant role in cellular respiration, amino acid synthesis, and metabolism, as well as methylglyoxal catabolism. In addition, the expression profiles of GLY genes were distinct in different tissues of cucumber as well as under diverse abiotic stresses. This study is conducive to the further exploration of the functional diversity among glyoxalase genes and the mechanisms of stress responses in cucumber. Full article