Search Results (1,331)

Background: The golden apple snail (Pomacea canaliculata), an invasive species originating from South America, has inflicted considerable agricultural and ecological harm in non-native habitats. While the molluscicide niclosamide is currently effective against P. canaliculata, its prolonged use raises environmental concerns and the risk of resistance development. Results: BAM 15 possesses strong molluscicidal activity against P. canaliculata, with 72 h LC₅₀ values of 0.4564 mg/L for adults (shell height: 20–25 mm), 0.3352 mg/L for subadults (10–15 mm), and 0.1142 mg/L for juveniles (2–3 mm). Metabolomic and proteomic profiling revealed that the altered metabolites and proteins both converged on energy metabolism and oxidative stress. Experimental validation revealed that BAM15 collapsed the mitochondrial membrane potential, drove MDA and H₂O₂ upward while depleting NADPH, boosted CAT, SOD and GPX activities, yet suppressed GR, and ultimately inflicted overt damage in the head-foot tissue of P. canaliculata. Conclusions: Our findings reveal that BAM 15 operates via a three-stage mechanism: (1) it disrupts membrane potential (ΔΨm) and impairs ATP production, severely disturbing energy metabolism; (2) energy deficits stimulate excessive electron transport chain activity, generating reactive oxygen species (ROS) and initiating oxidative stress; (3) persistent metabolic imbalance and oxidative damage culminate in extensive tissue injury. These results identify BAM 15 as a promising candidate for molluscicide development. Full article

Background/Objectives: Malaria remains a major global health burden, increasingly complicated by resistance to artemisinin-based therapies. Because artemisinin activation depends on heme and porphyrin chemistry, we sought to exploit host red blood cell (RBC) heme metabolism as a therapeutic vulnerability. This study aims to develop and evaluate a host-directed “bait-and-kill” strategy that selectively sensitizes malaria-infected RBCs to artemisinin. Methods: We integrated quantitative proteomics, erythropoiesis transcriptomic analyses, flow cytometry, and in vitro malaria culture assays to characterize heme metabolism in mature RBCs and Plasmodium falciparum-infected RBCs (iRBCs). The heme precursor 5-aminolevulinic acid (ALA) was used to induce porphyrin accumulation, and dihydroartemisinin (DHA) was applied as the killing agent. Drug synergy, porphyrin accumulation, reactive oxygen species (ROS) induction, and parasite survival were assessed, including ring-stage survival assays using artemisinin-resistant clinical isolates. Results: Mature RBCs retain a truncated heme biosynthesis pathway capable of accumulating porphyrin intermediates, while uninfected RBCs are impermeable to ALA. In contrast, iRBCs exhibit increased membrane permeability, allowing selective ALA uptake and porphyrin accumulation. ALA alone did not induce cytotoxicity or ROS, whereas DHA induced ROS and parasite killing. The ALA + DHA combination resulted in synergistic parasite elimination, including complete clearance of artemisinin-resistant P. falciparum isolates from the Greater Mekong Subregion, with no recrudescence observed over three weeks of culture. Evidence supports a predominant role for host-derived heme metabolites in mediating this synergy. Conclusions: The bait-and-kill strategy selectively exploits host RBC heme metabolism to restore and enhance artemisinin efficacy while sparing uninfected cells. Using clinically safe compounds, this host-directed approach provides a promising, resistance-bypassing framework for malaria treatment and combination drug development. Full article

Edible flowers have garnered increasing attention due to their high content of bioactive compounds, making them promising candidates for biomedical and functional food applications. This work evaluated the metabolomic data of fresh Rosa x hybrida petals, revealing seven types of metabolites, including amino acids, organic acids, vitamins, sugars, phenolic acids, and flavonoids. Notably, quercetin, kaempferol and their derivatives were the main flavonoids determined. Furthermore, in vitro studies were conducted to evaluate the potential antiproliferative effects against triple-negative breast cancer (TNBC). Thus, the methanolic extract derived from Rosa x hybrida petals demonstrated significant antitumoral activity against both sensitive and resistant TNBC cells, as evidenced by reduced MTT metabolization, colony formation, and wound healing activity. Furthermore, the cell death mechanism associated with the petal extract was studied. The antiproliferative activity was mediated by reactive oxygen species generation, triggering cell death mechanisms such as apoptosis and autophagy. In conclusion, these results propose Rosa x hybrida could be a new tool for nutraceuticals and functional food production. Full article

Postoperative delirium (POD) is a neurocognitive complication that commonly occurs after cardiac surgery. Despite the association of POD with increased morbidity and mortality, reliable perioperative biomarkers for predicting POD remain scarce. This retrospective observational study investigated whether temporal changes in perioperative redox balance are associated with POD development. Fifty adult patients who underwent elective cardiac surgery at Osaka University Hospital were included. Serum levels of derivatives of reactive oxygen metabolites (d-ROMs) and biological antioxidant potential (BAP) were measured preoperatively, immediately after intensive care unit admission, and on postoperative days 1–4. POD was assessed twice daily using the Intensive Care Delirium Screening Checklist (ICDSC), with an ICDSC score of ≥3 indicating delirium. POD occurred in 18 (36%) out of 50 patients. Compared with non-POD patients, those with POD exhibited higher preoperative d-ROMs levels, a lower BAP/d-ROMs ratio, a transient postoperative increase in BAP, and a relatively higher BAP/d-ROMs ratio during the early postoperative period. Preoperative d-ROMs levels showed a positive correlation with the maximum ICDSC score. In conclusion, perioperative redox dynamics are associated with POD risk and severity. Redox-related markers, particularly d-ROMs, may have potential as biomarkers for identifying patients at higher risk of POD after cardiac surgery, and their clinical utility warrants further prospective validation. Full article

The diterpene sessein, isolated from Salvia sessei, is a metabolite of interest due to its conjugated p-quinone system, δ-lactone ring, and phenolic hydroxyl in C-12. These functionalities make it an ideal starting point for reactivity studies and semi-synthetic derivatization. In this work, we report the obtainment of two derivatives by selective esterification of phenolic hydroxyl in C-12, through acetylation and benzoylation reactions under mild conditions and with high yields. The structures were characterized by UPLC-MS, FTIR, and NMR spectroscopy ¹H, ¹³C, and 2D, which allowed to precisely confirm the modifications made in the derivatives. These results confirm that hydroxyl in C-12 constitutes a privileged site of reactivity within the royleanone family, consolidating sessein as a versatile nucleus for the generation of derivatives. Finally, the preliminary evaluation of the antimicrobial activity showed that sessein shows a broad spectrum of action against Gram-positive, Gram-negative, and Candida albicans strains. The acetylated derivative showed an increase in activity against gram-negative bacteria, while the benzoyl derivative had a loss of effect at the concentrations evaluated. These findings demonstrate that structural modifications influence the properties of the derivatives with respect to the compound sessein. Full article

Nanoplastics are persistent environmental pollutants with potential risks to human health. Due to their small size, nanoplastics are internalized by macrophages, potentially altering their function. In this study we found that, in macrophages, 50 nm polystyrene nanoplastics were predominantly present in endosomes, lysosomes, and in the endoplasmic reticulum. Internalization of polystyrene nanoplastics increased the bactericidal activity of macrophages, which was inhibited by the NADPH oxidase inhibitor diphenyleneiodonium. Consistently, measurements of cellular and mitochondrial reactive oxygen species by flow cytometry revealed that polystyrene nanoplastics induced reactive oxygen species production in macrophages. In contrast, internalization of polystyrene nanoplastics reduced the levels of nitric oxide released by macrophages in response to E. coli. Internalization of polystyrene nanoplastics followed by the addition of E. coli induced high expression levels of the aconitate decarboxylase 1 gene. In the absence of this gene, killing of E. coli by macrophages exposed to polystyrene nanoplastics was significantly attenuated with respect to control macrophages, indicating a role for the mitochondrial metabolite itaconate in the increased bactericidal activity of macrophages exposed to polystyrene nanoplastics. Collectively, our results indicate that exposure of macrophages to polystyrene nanoplastics increases their bactericidal activity through the production of reactive oxygen species and of itaconate. Full article

Currently, the differences in the responses of the organic acid metabolism in rapeseed (Brassica napus L.) roots to saline and alkaline stresses are still unknown. To clarify the differences, different saline (100 (LS) and 200 (HS) mmol/L NaCl) and alkaline (20 (LA) and 40 (HA) mmol/L Na₂CO₃) treatments were applied to rapeseed. Then, targeted metabolomics was used to quantitatively analyze the changes in organic acid metabolism in the root system. The results showed that compared with the control group without stress (CK), 21, 18, 27, and 20 differentially accumulated organic acid metabolites were detected in the rapeseed roots under LS, HS, LA, and HA, respectively. In addition, 26, 6, 34, and 14 differentially accumulated organic acids were detected in the rapeseed root exudates under LS, HS, LA, and HA, respectively. Based on the activities of key enzymes related to the tricarboxylic acid cycle (TCA), antioxidant enzyme activities, organic acid metabolism, and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis in rapeseed roots, rapeseed mainly resisted saline and alkaline stresses by increasing organic acid synthesis and scavenging reactive oxygen species. Specifically, rapeseed resisted saline stress mainly by increasing the secretion of TCA cycle-related organic acids such as succinic acid, L-malic acid, fumaric acid, and cis-aconitic acid. In addition to secreting organic acids, rapeseed also resisted alkaline stress by increasing the secretion of phenolic acids such as 4-hydroxybenzoic acid, ferulic acid, and 4-coumaric acid. Notably, the number of secreted organic acid types and the increase in organic acid content under alkaline stress were higher than those under saline stress. The results of this study provide an important basis for the breeding of saline and alkaline stress-tolerant rapeseed varieties. Full article

Background: Obesity is characterized by chronic low-grade inflammation and metabolic disturbances, including an altered tryptophan (Trp) catabolism through the kynurenine pathway (KP). Since the KP is closely linked to immune activity, energy metabolism, and hepatic function, modulating its flux through lifestyle interventions has gained interest as a potential therapeutic strategy. Objective: This exploratory study aimed to investigate the impact of a structured 12-week weight loss program (WLP) on serum KP metabolites in a sample of Mexican women with obesity. Methods: This study involved a pre–post-intervention design conducted in twenty-four women with clinically diagnosed obesity from the Mexican Navy who underwent a structured 12-week weight loss program combining a hypocaloric diet with moderate-intensity aerobic exercise; no control group was included. Anthropometric parameters, serum biochemistry, and circulating levels of Trp, kynurenine (KYN), kynurenic acid (KYNA), and 3-hydroxykynurenine (3-HK) were assessed before and after intervention. Psychological assessments of anxiety and depression were also conducted in a subset of participants. Results: The WLP significantly reduced body weight, BMI, fat mass, fasting insulin, and C-reactive protein levels. Serum concentrations of Trp, KYN, and KYNA decreased, while 3-HK showed a non-significant upward trend. Enzymatic indexes revealed a significant increase in the 3-HK/KYN ratio and a decrease in the KYNA/3-HK ratio, suggesting a shift toward kynurenine monooxygenase (KMO) branch. Notably, higher KYNA-related ratios were inversely associated with depressive symptoms. Conclusions: These findings position the KP as a responsive metabolic interface potentially linking improvements in body composition, liver function, and psychological status during structured weight loss efforts. Full article

Autoimmune flares are often accompanied by abrupt surges of circulating plasmablasts—short-lived, high-output antibody-secreting cells generated through extrafollicular B-cell activation in response to microbial cues. Three categories of microbial input appear to repeatedly trigger these “plasmablast storms”: latent herpesvirus reactivations (Epstein–Barr virus, cytomegalovirus, human herpesvirus-6, varicella–zoster virus), acute respiratory or gastrointestinal infections including SARS-CoV-2, and chronic oral or gut dysbiosis. Although biologically distinct, these stimuli converge on innate sensing pathways driven by pathogen-associated molecular patterns such as unmethylated CpG DNA, single-stranded RNA, lipopolysaccharide, and bacterial lipoglycans. Through Toll-like receptors and type I interferon signalling, microbial signatures accelerate class switching, amplify inflammatory cytokine milieus, and lower B-cell activation thresholds, enabling rapid plasmablast mobilisation. Dysbiosis further maintains B cells in a hyper-responsive state by disrupting mucosal homeostasis and altering microbial metabolite profiles, thereby reducing the stimulus required to trigger plasmablast bursts. Once generated, these waves of oligoclonal plasmablasts home to inflamed tissues, where chemokine and adhesion landscapes shape their retention during flares. Emerging evidence suggests that such episodic plasmablast expansions promote autoantibody diversification, somatic hypermutation, and epitope spreading, progressively eroding tolerance. This review synthesizes these insights into a unified model in which infections and dysbiosis promote microbe-licensed plasmablast storms that influence the tempo and severity of autoimmune disease. Full article

Antimicrobial resistance (AMR) is one of the major health threats of the 21st century and demands innovative sources of bioactive compounds. In 2019, infections caused by resistant bacteria directly accounted for 1.27 million deaths and contributed to an additional 4.95 million associated deaths, underscoring the urgency of exploring new strategies. Among emerging alternatives, specialized plant metabolites stand out, as their biosynthesis is enhanced under biotic or abiotic stress. These stimuli increase reactive oxygen species (ROS), activate cascades regulated by mitogen-activated protein kinases (MAPKs), and trigger defense-related hormonal pathways involving salicylic acid (SA), jasmonic acid (JA), ethylene (ET), and abscisic acid (ABA), which in turn regulate transcription factors and biosynthetic modules, promoting the accumulation of compounds with antimicrobial activity. In this review, we synthesize recent literature (2020–2025) with emphasis on studies that report quantitative activity metrics. We integrate evidence linking stress physiology and metabolite production, summarize mechanisms of action, and propose a conceptual multi-omics pipeline, synthesized from current best practices, that combines RNA sequencing and LC/GC-MS-based metabolomics with bioinformatic tools to prioritize candidates with antimicrobial potential. We discuss elicitation strategies and green extraction, highlight bryophytes (e.g., Pseudocrossidium replicatum) as a differentiated chemical source, and explore citrus Huanglongbing (HLB) as a translational case study. We conclude that integrating stress physiology, multi-omics, and functional validation can accelerate the transition of stress-induced metabolites toward more sustainable and scalable medical and agricultural applications. Full article

Herpes simplex viruses (HSV-1 and HSV-2) are highly prevalent human pathogens that establish lifelong latency in sensory neurons, posing a persistent challenge to global public health. Their clinical manifestations range from mild, self-limiting orolabial lesions to severe, life-threatening conditions such as disseminated neonatal infections, focal encephalitis, and herpetic stromal keratitis, which can lead to irreversible corneal blindness. Beyond direct pathology, HSV-mediated genital ulcerative disease (GUD) significantly enhances mucosal susceptibility to HIV-1 and other sexually transmitted infections, amplifying co-infection risk and disease burden. Despite decades of clinical reliance on nucleoside analogues such as acyclovir, the therapeutic landscape has stagnated with rising antiviral resistance, toxicity associated with prolonged use, and the complete inability of current drugs to eliminate latency or prevent reactivation continue to undermine effective disease control. These persistent gaps underscore an urgent need for next-generation antivirals that operate through fundamentally new mechanisms. Marine ecosystems, the planet’s most chemically diverse environments, are providing an expanding repertoire of antiviral compounds with significant therapeutic promise. Recent discoveries reveal that marine-derived polysaccharides, sulfated glycans, peptides, alkaloids, and microbial metabolites exhibit remarkably potent and multi-targeted anti-HSV activities, disrupting viral attachment, fusion, replication, and egress, while also reshaping host antiviral immunity. Together, these agents showcase mechanisms and scaffolds entirely distinct from existing therapeutics. This review integrates emerging evidence on structural diversity, mechanistic breadth, and translational promise of marine natural products with anti-HSV activity. Collectively, these advances position marine-derived compounds as powerful, untapped scaffolds capable of reshaping the future of HSV therapeutics. Full article

Mushrooms like Inonotus obliquus and Ganoderma lucidum show significant pharmacological promise. This review analyzes fungi as sources of natural inhibitors against Advanced Glycation End-products (AGEs)—key drivers of diabetes and neurodegeneration. We highlight that extracts from Lignosus rhinocerus and Auricularia auricula exhibit antiglycation potency (IC₅₀ as low as 0.001 mg/mL) superior to aminoguanidine. Inhibitory effects are attributed to bioactive fractions including FYGL proteoglycans, uronic acid-rich polysaccharides, and fungal-specific metabolites like ergothioneine. These compounds act through multi-target mechanisms across the glycation cascade: competitive inhibition of Schiff base formation, trapping reactive dicarbonyls (e.g., methylglyoxal), transition metal chelation, and direct scavenging of reactive oxygen species (ROS). Furthermore, the review addresses the transition from in vitro potency to in vivo efficacy (RAGE pathway modulation), stability during food processing (UV-B irradiation), and critical safety issues regarding heavy metal bioaccumulation. Mushroom-derived inhibitors represent a sustainable therapeutic alternative to synthetic agents, offering broader protection against glycative stress. This synthesis provides a foundation for developing standardized mushroom-based nutraceuticals for managing AGE-related chronic disorders. Full article

Periodontitis is a chronic non-communicable inflammatory disease in which oxidative stress plays an important role in tissue destruction and alveolar bone loss. Excessive production of reactive oxygen species disrupts redox homeostasis, activates inflammatory signaling pathways, and promotes regulated cell death processes such as pyroptosis and ferroptosis. The Nrf2/Keap1 pathway is a key regulator of antioxidant defense and cellular adaptation to redox imbalance. Impaired Nrf2 signaling has been associated with enhanced oxidative injury, NF-κB and NLRP3 inflammasome activation, osteoclast-driven bone resorption, and reduced regenerative capacity in periodontal tissues. Experimental studies suggest that Nrf2 activation can restore the redox balance and attenuate inflammation and bone destructive responses in a periodontal model. Moreover, therapeutic approaches involving phytochemicals, microbial-derived metabolites, and redox-responsive biomaterials have been reported to influence Nrf2-related signaling in experimental settings. However, the majority of the available evidence is derived from in vitro or animal studies, and the relevance of these findings to clinical periodontitis remains to be established. This review summarizes the current advances linking oxidative stress, redox signaling, cell death pathways, and bone remodeling with Nrf2 dysfunction in periodontitis and outlines the key mechanistic insights while highlighting the existing knowledge gaps. Full article

Background/Objectives: Diabetes mellitus is a serious global disease characterized by chronic hyperglycemia, resulting from defects in insulin secretion, insulin action, or both. It represents a major health concern affecting millions of people worldwide. This condition can lead to severe complications significantly affecting patients’ quality of life. Due to the limitations and side effects of current therapies, the search for safer and more effective antidiabetic agents, particularly from natural sources, has gained considerable attention. This study investigates the antidiabetic potential of seaweed-derived compounds through structure-based virtual screening targeting α-glucosidase. Methods: A library of compounds derived from the Seaweed Metabolite Database was subjected to a hierarchical molecular docking protocol against α-glucosidase. Extra Precision (XP) docking was employed to identify the top-ranked ligands based on their binding affinities. Drug-likeness was assessed according to Lipinski’s Rule of Five, followed by pharmacokinetic and toxicity predictions to evaluate ADMET properties. Density Functional Theory (DFT) calculations were performed to analyze the electronic properties and chemical reactivity of the selected compounds. Furthermore, molecular dynamics simulations were carried out to examine the stability and dynamic behavior of the ligand–enzyme complexes. Results: Following XP docking and ADMET prediction, four promising compounds were selected: Colensolide A, Rhodomelol, Callophycin A, and 7-(2,3-dibromo-4,5-dihydroxybenzyl)-3,7-dihydro-1H-purine-2,6-dione. Molecular dynamics simulations further confirmed the structural stability and strong binding interactions of these compounds within the α-glucosidase active site. Conclusions: This investigation demonstrated the important role of seaweed-derived compounds in inhibiting α-glucosidase activity. Further experimental validation is warranted to confirm their biological activity and therapeutic potential. Full article

Rheumatoid arthritis (RA) is frequently accompanied by depression, a comorbidity arising from the interplay of chronic systemic inflammation, neuroimmune activation, oxidative stress, and dysregulation of the gut–brain axis. Increasing evidence suggests that nanomedicine offers unique opportunities for the integrated management of RA-associated depression by enabling precise modulation of both peripheral inflammation and central nervous system (CNS) pathology. This review outlines the biological mechanisms linking RA and depression—including cytokine cascades, mitochondrial dysfunction, reactive oxygen species (ROS) accumulation, and microbial metabolite imbalance—and highlights recent progress in nanocarrier platforms capable of dual-site intervention. Liposomes, polymeric nanoparticles (NPs), exosomes, inorganic nanozymes, and emerging carbon-based nanomaterials have demonstrated the ability to target inflamed synovium, reprogram macrophage phenotypes, traverse the blood–brain barrier (BBB), suppress microglial overactivation, enhance neuroplasticity, and restore gut microbial homeostasis. Furthermore, stimulus-responsive nanoplatforms activated by ROS, pH, enzymes, or hypoxia provide spatiotemporally controlled drug release, thereby improving therapeutic precision. Finally, we discuss integrative designs such as dual-targeting nanomedicines, co-delivery systems, and microbiota-modulating nano-interventions, which offer promising strategies for the comprehensive treatment of RA-associated depression. This review aims to provide mechanistic insights and design principles to guide the development of next-generation nanomedicine for coordinated systemic-central modulation in RA comorbidity. Full article