Ovarian cancer is often diagnosed at an advanced stage because its early symptoms are nonspecific, and the prognosis remains poor due to frequent recurrence and the development of drug resistance even after standard treatment. This review includes 19 in vitro studies and seeks to mechanistically summarize how reactive oxygen species (ROS) reinforce the tumorigenic program from the early stages of ovarian carcinogenesis to tumor progression, metastasis, and treatment resistance. Collectively, the selected studies suggest that exposure to environmental toxicants can increase ROS levels in ovarian epithelial cells, accompanied by inflammatory responses and elevated DNA damage markers, thereby creating a carcinogenesis-priming environment. During the progression stage, hypoxia, hormones, growth factors, and lipid signaling repeatedly activate survival and growth pathways, such as those involving HIF-1α/VEGF, JAK/STAT3, and AKT/mTOR, through ROS-mediated mechanisms to promote tumor cell proliferation, anti-apoptotic activity, and angiogenesis. In addition, ROS are associated with alterations in epithelial-to-mesenchymal transition-related markers, remodeling of the extracellular matrix, and regulation of matrix metalloproteinases, which enhance the metastatic and invasive potential of tumor cells. In the therapeutic context, ROS have been suggested to contribute to platinum-based chemotherapy resistance through mechanisms including changes in mitochondrial dynamics, activation of the DNA damage response, and reprogramming of ROS-dependent phosphorylation networks. Understanding the diverse molecular mechanisms and clinical manifestations associated with ROS expression in high-grade serous ovarian cancer (HGSOC) will contribute to a more precise understanding of its pathophysiology. Furthermore, studies on redox-targeted therapeutic strategies, particularly the application of mitochondria-targeted antioxidants, may provide valuable translational insights for the treatment of ovarian cancer and other ROS-related diseases.

In ovarian cancer, reactive oxygen species (ROS) are both toxic byproducts and mediators of signaling and stress adaptation, such that the same "ROS change" can suppress or promote tumors in vivo. Here, we integratively summarize how ROS modulation reshapes tumor growth, metastasis, and treatment response in ovarian cancer, based on 22 original in vivo-containing studies that were selected from a five-database search of papers published from January 1990 to December 2025. On the antitumor axis, ROS amplification in xenograft models is accompanied by reduced tumor burden and increased markers of cell death, and can operate through diverse death programs beyond apoptosis, including pyroptosis and ferroptosis. ROS-based anticancer effects may vary depending on whether cytoprotective autophagy is co-induced. For example, in models treated with daphnetin, ROS-dependent cell death occurs together with induction of cytoprotective autophagy and the anticancer effect is strengthened when an autophagy inhibitor is added. In a therapeutic context, autophagy may thus function as an adaptive response in tumor cells to partially buffer ROS-induced stress. Conversely, on the pro-tumor axis, ROS can serve as an upstream signal driving inflammatory and metastatic processes. In a peritoneal metastasis model, GPX1 inhibition-induced ROS elevation was linked to increased metastatic burden. In the context of drug resistance, platinum resistance is proposed to be an adaptive state shaped not by the absolute level of ROS alone, but by integrated ROS-sensing and buffering circuits, the DNA damage response (DDR), and NF-κB networks. In vivo, AMPK-ROS axis activation through ACLY inhibition or resetting of drug responsiveness can be connected to tumor suppression and increased sensitivity. Furthermore, ROS modulation is not limited to tumor cell-intrinsic targets: it can also be linked to therapeutic response reprogramming at the tumor microenvironment (TME) level, such as via regulation of acidity/ROS conditions and coupling to macrophage polarization in immunocompetent syngeneic models. Taken together, these lines of in vivo evidence indicate that, in ovarian cancer, ROS should not be interpreted in a binary "increase/decrease" manner, but rather in terms of redox-buffering capacity, the engaged signaling axes (cell death, DDR, metastasis/inflammation), and interactions with TME factors.

Hypercholesterolemia is a major risk factor for cardiovascular disease, necessitating the development of effective and safe lipid-lowering interventions. This study evaluated the antihypercholesterolemic effects of KGC11o, a red ginseng oil obtained via supercritical fluid extraction, using both HepG2 cells and a high-fat/high-cholesterol diet-induced hypercholesterolemic rat model. KGC11o treatment significantly improved serum and hepatic lipid profiles, reduced markers of liver injury, and enhanced fecal cholesterol excretion. At the molecular level, KGC11o modulated the expression of key genes involved in cholesterol biosynthesis (3-hydroxy-3-methylglutaryl-CoA reductase), esterification (acyl-CoA:cholesterol acyltransferase), transport (CETP, LPL), and catabolism (LCAT, cholesterol 7α-hydroxylase). Collectively, these findings suggest that KGC11o may serve as a safe, food-derived functional ingredient with potential benefits for the management of hypercholesterolemia and related metabolic disorders. Further studies are warranted to elucidate its molecular mechanisms and to confirm its clinical efficacy.

Chronic rhinosinusitis (CRS) is an inflammatory disease of the sinonasal mucosa whose pathogenesis is characterized by complex interactions of immunological and environmental factors. The maintenance of normal sinonasal function requires a balance of sinus ostial patency, mucociliary clearance, and mucus secretion, and disruption of this balance can lead to CRS. Although many studies have examined the pathophysiology of CRS, the role of reactive oxygen species (ROS) remains incompletely understood. In this review, we analyzed 22 studies of CRS that examined the effects of ROS on epithelial barrier function, local immune responses, and tissue remodeling. The results from in vitro studies, animal models, and human tissue analyses suggest that ROS are not merely by-products of inflammation, but appear to function as key mediators in the pathophysiology of CRS, particularly in the formation and persistence of the CRS phenotype with nasal polyps (CRSwNP). In particular, CRSwNP is characterized by increased activity of enzymes in the dual oxidase (DUOX) and NADPH oxidase (NOX) families, mitochondrial dysfunction, and decreased activity of superoxide dismutase (SOD) and peroxiredoxin 2 (PRDX2). At the molecular level, these alterations increase the generation of ROS and impair antioxidant defense. At the cellular level, these alterations disrupt the epithelial barrier, activate inflammasomes, increase pyroptosis, and induce the formation of neutrophilic and eosinophilic extracellular traps. These changes culminate in the epithelial–mesenchymal transition (EMT), with the formation of nasal polyps and tissue remodeling. Increased oxidative stress can also occur in CRS without nasal polyps (CRSsNP), but this phenotype appears to have relatively preserved antioxidant defense systems, which may partly explain the more limited structural remodeling. External stimuli, such as fungal proteases, bacterial toxins, and certain antibiotics, can also increase the production of ROS and may contribute to disease chronicity. Taken together, the level and pathophysiological roles of ROS differ in the two primary phenotypes of CRS. Further mechanistic studies are needed to clarify the specific alterations of redox pathways in these two phenotypes and to develop novel therapeutic strategies that target ROS.

Non-alcoholic fatty liver disease (NAFLD) involves lipid accumulation in liver without consumption of alcohol and affects many people worldwide. NAFLD is associated with metabolic syndrome disease such as obesity, insulin resistance, hyperlipidemia, and diabetes. However, there are no pharmacologic therapies for NAFLD. Recently, there are increasing reports that several natural plants can inhibit lipid accumulation in hepatocytes. Bay laurel (Laurus nobilis L.) leaves have been used in traditional medicine for rheumatism, stomach ache, emetic, skin rashes, and earaches. Our objective was to investigate the effect of bay laurel leaves water extract (BLW) on free fatty acid (FFA) treated hepatocyte and high fructose, high fat (HFHF) diet in a mouse model of NAFLD. In vitro, lipid accumulation increased only in the FFA treated group, while BLW reduced lipid accumulation to a level comparable to that only in the FFA treated group. Cellular antioxidants were increased in the BLW compared to the only FFA-treated group, but cellular MDA levels were decreased in the BLW compared to the only FFA treated group. Cellular lipid accumulation, inflammation, and apoptosis were reduced in the BLW compared to the only FFA treated group. In vivo, serum ALT, AST, and GGT levels in the BLW supplementation group were significantly decreased compared with the HFHF group. Hepatic TC, TG, and MDA levels were significantly decreased in the HFHF+100 and HFHF+200 groups compared to the HFHF group. The hepatic antioxidant activities in the BLW supplementation groups were significantly increased compared to the HFHF group. The expression of proteins related to hepatic inflammation and apoptosis was reduced in the BLW supplementation groups compared to the HFHF group. These results suggest that BLW could be potentially useful in the treatment of NAFLD due to its inhibitory effects on hepatic lipogenesis, hepatic inflammation, and hepatic apoptosis.

Reactive oxygen species (ROS) play dual roles in the pathophysiology of endometrial cancer (EC). Oxidative stress induced by ROS can promote the survival and proliferation of cancer cells, whereas excessive accumulation of ROS can lead to various forms of programmed cell death—including ferroptosis and apoptosis—making ROS potential therapeutic targets in cancer treatment. EC is the most common gynecologic malignancy in developed countries, and its global incidence and mortality rates have been steadily increasing. Although significant research has been conducted on the etiology and treatment of EC, progress remains limited. Thus, further exploration of the role of ROS in the pathogenesis of EC is warranted. In this study, we conducted a literature review using databases including the Cochrane Library, EMBASE, Google Scholar, PubMed, and SCOPUS with the search terms “endometrial cancer” and “nitric oxide.” Of the 142 identified articles, 18 were selected for detailed review. The analysis revealed that ROS contributes to EC progression through mechanisms such as DNA damage and genomic instability, interactions with estrogen and progesterone signaling, and immune dysregulation. Potential therapeutic agents targeting ROS identified in the literature include hinokitiol, α-terthienylmethanol, ellipticine, fructose-1,6-bisphosphate, oleanolic acid 3-acetate, CaBP-28 k, simvastatin, and amentoflavone. These findings suggest that oxidative stress plays a critical role in the progression of EC. A deeper understanding of ROS regulatory mechanisms may open new avenues for the development of targeted therapies for EC.

Lactic acid bacteria (LAB) exhibit antimicrobial and health-benefitting properties, offering a promising nontoxic alternative to antibiotics for preserving food and combating pathogenic infections. However, strain-dependent antimicrobial efficacy, reduced effectiveness against multidrug-resistant pathogens, and difficulties in largescale production without bacterial contamination hinder broader LAB applications. Research has increasingly focused on leveraging endolysins-enzymes produced by engineered LAB cultures-to inhibit pathogen growth. However, challenges such as limited bactericidal activity, susceptibility to protease degradation, and high purification and quality control costs persist. These issues can be mitigated by utilizing engineered LAB-derived extracellular vesicles (LEVs) that display pathogen-specific endolysins on their surface and enable targeted pathogen recognition and elimination. To date, no LEV surface-displaying proteins (SDPs) have been characterized. Herein, we identified a Lacticaseibacillus paracasei-derived LEV SDP (LP-SDP3) and characterized it through proteomic analysis, heterologous expression of candidate SDPs, biochemical assays, and SpyCatcher-SpyTag bioconjugation reactions. We also identified homologs of LP-SDP3 in Escherichia coli and other LAB strains, confirming its functionality in E. coli and Lactococcus lactis. LEVs derived from L. paracasei (LPEVs) displaying the endolysin PlyF307SQ-8C selectively targeted and eliminated Staphylococcus aureus. Compared with purified PlyF307SQ-8C, these LPEVs exhibited a comparable biocompatibility and resistance development potential while featuring a higher production efficiency and resistance to temperature and pH variations. This study represents the first identification of a universal EV SDP for E. coli and LAB strains, highlighting its potential as a platform for developing endolysin-EV-based antibacterial agents and bypassing the need for labor-intensive and costly endolysin production processes.

EstroG-100®, a functional ingredient blend that has been used for menopausal health in women. However, detailed studies on its effects and their underlying mechanisms have been lacking. Herein, we evaluated the antifatigue effects of EstroG-100 using C2C12 cells exposed to oxidative stress and mice subjected to a forced swimming test. EstroG-100 significantly increased the viability and adenosine triphosphate (ATP) content of C2C12 cells under oxidative stress, while notably inhibiting the generation of reactive oxygen species. EstroG-100 tended to prolong the forced swimming time in mice. It also significantly inhibited the serum lactate dehydrogenase activity, increased intramuscular glycogen content, and upregulated the expression of peroxisme proliferator-activated receptor (PPAR)-δ and uncoupling protein (UCP)3 genes involved in β-oxidation of fatty acids. Furthermore, EstroG-100 significantly increased the activities of antioxidant enzymes, including catalase, superoxide dismutase, glutathione S-transferase, and glutathione levels, and decreased the malondialdehyde levels in the liver. These results indicate that EstroG-100 may contribute to recovery from physical fatigue by enhancing the antioxidant activity to alleviate oxidative stress and improving muscle function via modulation of glycogen and fatty acid metabolism.

Benign prostatic hyperplasia (BPH) is a noncancerous urinary disorder that is common in older adult men; however, its underlying mechanisms remain unclear. Fenugreek has some biological effects, including hyperglycemia regulation, immune response modulation, and anti-cancer properties; In this study, we investigated the ameliorative effects of fenugreek seed extract (Forceterone® [FCT]) in a testosterone propionate (TP)-induced BPH animal model and its mechanisms in BPH-1 human prostate epithelial cells. Sprague Dawley (SD) rats were injected subcutaneously with TP (3 mg/kg) for 8 weeks to induce BPH while FCT was administered orally at 25, 50, and 100 mg/kg. In addition, BPH-1 cells were used to evaluate the inhibitory effects on cell proliferation and examine inflammatory cytokine expression. Treating rats with FCT decreased prostate weight, dihydrotestosterone (DHT) level, and proliferating cell nuclear antigen (PCNA) expression in the prostate. Furthermore, it decreased androgen receptor (AR), 5α-reductase 2, B-cell lymphoma 2 (Bcl-2), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and NF-κB expression in vitro and in vivo and increased Bcl-2-associated X protein (Bax) expression. FCT also inhibited cell proliferation dose dependently in BPH-1 cells. These findings showed the potential use of FCT as an alternative treatment for BPH.

This review explores the dual role of reactive oxygen species (ROS) and free radicals in the pathogenesis of endometriosis, aiming to deepen our understanding of these processes through a systematic literature review. To assess the induction and involvement of ROS in endometriosis, we conducted a comprehensive literature review using Cochrane Libraries, EMBASE, Google Scholar, PubMed, and SCOPUS databases. Of 30 qualifying papers ultimately reviewed, 28 reported a significant contribution of ROS to the pathogenesis of endometriosis, while two found no association. The presence of ROS in endometriosis is associated with infertility, irregular menstrual cycles, painful menstruation, and chronic pelvic discomfort. Among individual ROS types studied, hydrogen peroxide was most frequently investigated, followed by lipid peroxides and superoxide radicals. Notable polymorphisms associated with ROS in endometriosis include those for AT-rich interactive domain 1A (ARID1A) and quinone oxidoreductase 1 (NQO1) isoforms. Key enzymes for ROS scavenging and detoxification include superoxide dismutase, glutathione, and glutathione peroxidase. Effective inhibitors of ROS related to endometriosis are vitamins C and E, astaxanthin, fatty acid-binding protein 4, cerium oxide nanoparticles (nanoceria), osteopontin, sphingosine 1-phosphate, N-acetyl-L-cysteine, catalase, and a high-antioxidant diet. Elevated levels of ROS and free radicals are involved in the pathogenesis of endometriosis, suggesting that targeting these molecules could offer potential therapeutic strategies.

Background : Osteoarthritis (OA), the most prevalent form of arthritis, is a degenerative joint disease marked by the progressive deterioration of articular cartilage, leading to clinical manifestations such as joint pain. Objective : This study investigated the effects of Curcuma longa L. extract (CL) containing curcumin, demethoxycurcumin, and bisdemethoxycurcumin on monosodium iodoacetate (MIA)-induced OA rats. Design : Sprague-Dawley rats with MIA-induced OA received CL supplementation at doses of 5, 25, and 40 mg/kg body weight. Results : CL extract administration suppressed mineralisation parameters and morphological modifications and decreased arachidonate 5-lipoxygenase and leukotriene B4 levels in articular cartilage. Additionally, it decreased serum prostaglandin E2, NO, and glycosaminoglycan levels as well as the protein expression of phosphorylated inhibitor kappa B-alpha, phosphorylated p65, cyclooxygenase-2, and inducible nitric oxide synthase in the cartilage of MIA-injected rats. Furthermore, it also reduced matrix metalloproteinases and elevated SMAD family member 3 phosphorylation, tissue inhibitor of metalloproteinases, aggrecan, collagen type I, and collagen type II levels in the articular cartilage of MIA-induced OA rats. Conclusions : This study's findings suggest that CL supplementation helps prevent OA development and is an effective therapy for OA.

Acorus gramineus has a number of beneficial effects, including protective effects against age-related disorders. In this study, the effects of A. gramineus on testosterone production and andropause symptoms were evaluated. We first treated TM3 mouse Leydig cells, responsible for testosterone production, with A. gramineus aqueous extract at different concentrations. In TM3 cells, the testosterone concentration increased in a concentration-dependent manner compared with those in the control. In addition, at 400 mu g/mL extract, the mRNA expression level of the steroidogenic enzyme CYP11A1 was increased. Subsequently, 23-week-old Sprague-Dawley (SD) rats exhibiting an age-related reduction in serum testosterone (approximately 80% lower than that in 7-week-old SD rats) were administered A. gramineus aqueous extract for 8 weeks. Serum total testosterone and free testosterone levels were higher and serum estradiol, prostate-specific antigen levels, and total cholesterol levels were lower in the AG50 group (A. gramineus aqueous extract 50 mg/kg of body weight/day) than in the OLD (control group). The AG50 group also showed significant elevations in sperm count, grip strength, and mRNA expression of StAR, CYP11A1, 17 beta-HSD, and CYP17A1 compared with those in the OLD group. In conclusion, A. gramineus aqueous extract facilitated steroidogenesis in Leydig cells, elevated testosterone levels, lowered serum estradiol and total cholesterol levels, and increased muscle strength and sperm count, thus alleviating the symptoms of andropause. These findings suggest that A. gramineus aqueous extract is a potentially effective therapeutic agent against various symptoms associated with andropause.

Synucleins, including α-synuclein (α-syn), β-syn, and γ-syn, have been implicated in various synucleinopathies, notably Parkinson’s disease (PD), which has generated increased interest in understanding their roles. Although α-syn and β-syn have contrasting neuropathological consequences, the precise role of γ-syn remains unclear. This study validated non-motor symptoms, specifically anxiety-like behavior, along with the degradation of dopaminergic (DAergic) neurons in the nigrostriatal system and DAergic neurites in the prefrontal cortex and hippocampus of rats infused with striatal 6-hydroxydopamine (6-OHDA). Our study further investigated the alterations in γ-syn expression levels in the prefrontal cortices and hippocampi of these 6-OHDA–treated rats, aiming to establish foundational insights into the neuropathophysiology of DA depletion, a central feature of PD. Our findings revealed a significant increase in the expression of γ-syn mRNA and protein in these brain regions, in contrast to unaltered α- and β-syn expression levels. This suggests a distinct role of γ-syn within the neurobiological milieu under conditions of DA deficiency. Overall, our data shed light on the neurobiological changes observed in the hemiparkinsonian rat model induced with 6-OHDA, underscoring the potential significance of γ-syn in PD pathology.