Search Results (796)

Cardiomyopathies affect over 3 million individuals globally, with conventional treatments exhibiting up to 60% resistance and 25% 30-day readmission rates. This review synthesizes the current evidence on the role of neuro-immune interactions in the pathogenesis of cardiomyopathy and evaluates emerging therapies targeting this axis. We systematically examined clinical trials and mechanistic and multi-omics data across cardiomyopathy phenotypes, focusing on autonomic-immune dysregulation. Sympathetic overactivation, present in approximately 85% of patients, correlates with elevated pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) and contributes significantly to therapeutic non-response. Concurrent parasympathetic withdrawal impairs cholinergic anti-inflammatory pathways, as reflected by reduced heart rate variability and baroreflex sensitivity. At the molecular level, shared mechanisms include inflammasome activation, neuroimmune synaptic signaling, and neurogenic inflammation. Emerging therapies targeting this axis are promising. Vagus nerve stimulation, as demonstrated in the INOVATE-HF trial, improves functional outcomes, whereas IL-1β antagonists reduce cardiovascular events by 15–20% in the context of inflammatory diseases. Bioelectronic interventions, such as transcutaneous vagal nerve stimulation and baroreflex activation therapy, offer noninvasive dual-modulatory strategies that address both neural and immune pathways, positioning the neuroimmune axis as a central driver of cardiomyopathy, regardless of etiology. The integration of genetic and metabolomic profiling may enable precision therapies targeting neuroimmune circuits, thereby overcoming the limitations of hemodynamic-focused care. This mechanistic framework shifts the therapeutic paradigm from symptomatic relief to targeted modulation of pathogenic pathways, with implications for millions of patients with cardiomyopathy and broader inflammatory cardiovascular disorders. Full article

Breast cancer is a heterogeneous disease and a leading cause of cancer-related deaths worldwide, underscoring the urgent need for effective biomarkers to guide diagnosis, prognosis, and therapeutic decisions. Bioinformatics methodologies, including genomics, transcriptomics, proteomics, and metabolomics data analysis, are essential for deciphering the complex molecular landscape of breast cancer. Bioinformatics tools facilitate the identification of differentially expressed genes, non-coding RNAs, and proteins, unraveling crucial pathways involved in tumor initiation, progression, and metastasis. By constructing and analyzing protein–protein interaction networks and signaling pathways, bioinformatics approaches can identify potential diagnostic, prognostic, and predictive biomarkers. Herein, we explore the role of bioinformatics in breast cancer research and its potential application in identifying novel therapeutic targets and predicting drug response, ultimately enabling the development of tailored treatment strategies. We also address the challenges and future directions in utilizing bioinformatics for biomarker discovery and validation, emphasizing the need for robust statistical methods, standardized data analysis pipelines, and collaborative efforts to translate bioinformatics insights into improved clinical outcomes for breast cancer patients. Full article

Endometrial carcinoma (EC) is the most common malignancy of the female reproductive tract, with increasing incidence driven by aging populations and obesity. While molecular classification has improved diagnostic precision, the identification of clinically relevant metabolic biomarkers remains incomplete, and targeted therapies are not yet standardized. In this study, we investigated metabolic alterations in four EC cell lines (AN3-CA, EFE-184, HEC-1B and MFE-296) compared to non-malignant controls under normoxic and stress conditions (hypoxia and lactic acidosis) to identify metabolomic differences with potential clinical relevance. Untargeted gas chromatography–mass spectrometry (GC/MS) and targeted liquid chromatography–mass spectrometry (LC/MS) profiling revealed two distinct metabolic subtypes of EC. Cells of metabolic subtype 1 (AN3-CA and EFE-184) exhibited high biosynthetic and energy demands, enhanced cholesterol and hexosyl-ceramides synthesis and increased RNA stability, consistent with classical cancer-associated metabolic reprogramming. Cells of metabolic subtype 2 (HEC-1B and MFE-296) displayed a phospholipid-dominant metabolic profile and greater hypoxia tolerance, suggesting enhanced tumor aggressiveness and metastatic potential. Key metabolic findings were validated via real-time quantitative PCR. This study identifies and characterizes distinct metabolic subtypes of EC within the investigated cancer cell lines, thereby contributing to a better understanding of tumor heterogeneity. The results provide a basis for potential diagnostic differentiation based on specific metabolic profiles and may support the identification of novel therapeutic targets. Further validation in three-dimensional culture models and ultimately patient-derived samples is required to assess clinical relevance and integration with current molecular classifications. Full article

Fresh mulberry juice (MJ) faces industrial challenges due to its short shelf life and inconsistent flavor. This study innovatively addressed these limitations by applying L. plantarum (LP) and L. fermentum (LF) fermentation to MJ, combining non-targeted metabolomics and GC-IMS to systematically elucidate metabolic remodeling and flavor enhancement. Fermentation (36 h) achieved LAB counts > 7 log CFU/mL, significantly reducing soluble solids and pH from 15.00 to 13.90, 14.01 °Brix and 3.74 to 3.21, 3.13, respectively. In contrast, the bioactive compounds as detected by the increase in flavonoids and phenolics from 254.85 mg/100 g to 289.36, 291.39 mg/100 g and 286.21 mg/100 g to 294.55, 302.2033 mg/100 g, respectively. Anthocyanin content as high as 165.88 and 156.69 mg/L. Metabolomics identified enriched amino acid pathways, and GC-IMS revealed unique flavor profiles. The study fills a research gap by demonstrating LAB fermentation’s dual role in extending MJ’s shelf life and improving its functional nutritional quality, offering a novel strategy for functional food development. Full article

To improve the deep processing and utilization of wild blueberries, this study presents a green and highly efficient method for extracting flavonoids from blueberries. The approach combines natural deep eutectic solvents (NADESs) with ultrasound-assisted extraction. Among the 22 tested NADES, Betaine/urea (BU), was the most effective solvent for extracting flavonoids from blueberries. The extraction parameters of ultrasound-assisted betaine/urea (UABU) were optimized using a response surface methodology (RSM). This optimization procedure yielded the optimized conditions outlined below: a molar ratio of urea to betaine of 3.3:1, a water content of 60% (m/v), an ultrasonic power of 330 W, a solid-to-liquid ratio of 1:30, an extraction temperature of 50 °C, and an ultrasonic extraction duration of 30 min. Under these conditions, the total flavonoid content (TFC) extracted using UABU reached 6.06 ± 0.024 mg_RE/g_DW, a 1.44-fold increase compared to ultrasound-assisted 70% (v/v) ethanol (UAE). Liquid Chromatography–Tandem Mass Spectrometry (LC-MS/MS) nontargeted metabolomics analysis revealed that the flavonoids extracted by UABU had highly relative content (RC) of Oenin, 3′-methoxy-4′,5,7-trihydroxyflavonol, Isorhamnetin-3-O-glucoside and Isoquercitrin. Significant disparities exist regarding the types and RC of flavonoids obtained via UAE. Results from in vitro antioxidant assays demonstrated that UABU has superior antioxidant activity relative to UAE. This study demonstrated the feasibility of using NADESs, specifically BU, as an efficient and eco-friendly extraction medium for flavonoids from wild blueberries. The yield of flavonoids was increased by this method, and bioactive compounds were also protected—findings that underscore the potential of green solvents for application in the food industry. Full article

Ficus lindsayana is recognized for its medicinal properties, with previous studies highlighting the antioxidant and anti-inflammatory effects of its latex (FLtA) and root (FRE) extracts. Harvesting these plant parts, however, raises ecological concerns. This study evaluates the phytochemical profiles, safety, and biological activities of F. lindsayana leaf (FL) extracts as more sustainable alternatives. Leaves were extracted using hot water (FLA) and 80% ethanol (FLE), yielding 32.9% and 11.4%, respectively. Metabolomic and targeted HPLC-MS/MS analyses revealed distinct phytochemical compositions. FLE was enriched in flavonoid aglycones and lipophilic compounds, while FLA contained higher levels of polar phenolics. FLA showed greater total phenolic and flavonoid contents and stronger antioxidant activity, with an SC₅₀ of 159 μg/mL for the DPPH assay. In contrast, FLE demonstrated more pronounced anti-inflammatory activity. In LPS-stimulated RAW 264.7 macrophages, FLE significantly reduced nitric oxide production and iNOS expression at both the protein and mRNA levels. FLE also reduced IL-6 secretion in a dose-dependent manner without affecting TNF-α, suggesting selective cytokine modulation. Both extracts exhibited low cytotoxicity (IC₂₀ > 800 µg/mL in most cell types), non-hemolytic properties, and no mutagenic activity in the Drosophila wing spot assay. Compared to root and latex extracts, FLE ranked second in anti-inflammatory potency (FRE > FLE > FLA = FLtA). FLE, therefore represents a promising candidate, combining potent bioactivity with environmental responsibility and supporting the further development of F. lindsayana leaf-derived products for use in functional foods or botanical therapeutics. Full article

The genus Camellia offers valuable resources for tea production, oil extraction, and ornamental purposes, and its applications are expanding beyond traditional regions due to increasing human demands and advancements in research. To explore new therapeutic resources and identify key active metabolites, we conducted a non-targeted metabolomics analysis on three camellias. We also utilized network pharmacology to identify the potential targets of key metabolites involved in anti-inflammatory, antioxidant, antibacterial, and antiviral effects. A total of 385 significantly different metabolites were identified, with organic acids and derivatives, lipids and lipid-like molecules, and phenylpropanoids and polyketides being the top three metabolite classes. Of the 71 different phenylpropanoids and polyketides identified, 54 were common across all three cultivars, while 17 were unique. Network pharmacology further identified 78 potential molecular targets associated with the four therapeutic activities under study. Seven flavonoid glycosides, two flavans, two biflavonoids/polyflavonoids, and one flavone were highlighted as key active metabolites. Notably, Camellia japonica ‘Kōshi’ emerged as a promising material for future applications. The key active ingredients may contribute to the development of novel approaches for cosmetic, food, and medicinal applications, as well as germplasm innovation for new functional camellias. Full article

The absorption, transport, and distribution of antibiotics in animals are influenced by the composition and function of the intestinal microbial community. However, most existing studies have focused on intensive farming systems involving the artificial addition of antibiotics. For free-range local chicken breeds in mountainous areas without antibiotic additives, systematic research on the presence of antibiotic residues in their muscle tissues and their association with the gut microbiota is lacking. Therefore, in this study, mountainous free-range Lueyang black-bone chickens were selected as the research subjects, employing non-targeted metabolomics and microbiomics to analyze the distribution of antibiotics in intestinal tissues (duodenum and caecum) and muscle tissues (breast and leg muscles), and their correlations with the intestinal microbiota. Metabolomics detected 47 antibiotics in intestinal tissues and 22 in muscle tissues, with 9 common to both tissues, including clinically and veterinary relevant antibiotics such as oxacillin, kanamycin, and tobramycin. Microbiomics analysis indicated significant differences in microbial communities between the duodenum and caecum at the genus level. LEfSe analysis identified seven characteristic genera in the duodenum (e.g., Bacteroides, Alistipes) and five in the caecum (e.g., Lactobacillus, Ureaplasma). Pearson correlation analysis further revealed that these shared antibiotics were significantly associated with the differential genera in the intestine. For instance, oxacillin exhibited a positive correlation with both Bacteroides and Alistipes. Kanamycin was positively correlated with Alistipes, whereas tobramycin showed a negative correlation with Bacteroides. These results indicate that antibiotic residues were present in both intestinal and muscle tissues of Lueyang black-bone chickens raised under free-range mountainous conditions. The nine antibiotics common to both tissues are likely absorbed in the intestines and transported to muscles via the bloodstream. It is hypothesized that the gut microbiota may play a potential regulatory role in this process, providing a theoretical basis for understanding microecological mechanisms under environmental antibiotic exposure. Full article

As a major source of high-quality protein in China, duck meat such as the renowned Beijing Duck plays a critical role in the poultry industry. Sansui duck, a prized native breed, is valued for its tender meat and rich flavor, yet molecular mechanisms underlying its meat quality remain poorly studied. This study employed metabolomics and proteomics techniques to conduct a comprehensive comparative analysis of the breast and thigh muscles from 90-day-old (90X, 90T) and 468-day-old (468X, 468T) Sansui ducks. The meat quality traits indicated that the shear force and redness (a*) were significantly higher in the 468T and 468X groups compared to the 90X and 90T groups (p < 0.05). Similarly, the shear force values of the 90T and 468T groups were significantly higher than those of the 90X and 468X groups (p < 0.05). Quantitative proteomics analysis revealed differentially expressed proteins (DEPs) significantly enriched in oxidative phosphorylation and ribosomal biogenesis pathways. Non-targeted metabolomics identified differentially expressed metabolites (DEMs) concentrated in amino acid and lipid metabolism pathways. Correlation analysis indicated that in the comparison between 90X and 468X, 18 DEPs and 10 DEMs were closely associated with fleshiness, whereas in the comparison between 468X and 468T, 23 DEPs and 19 DEMs were closely associated with fleshiness. Integrating proteomics and metabolomics data analysis, proteins such as A0A8B9TTI1, R0JRM6, and A0A8B9SQI5, along with metabolites including L-lysine, L-pyrrolidone, and γ-aminobutyric acid from lysine degradation, butanoate metabolism, and 2-oxocarboxylic acid metabolism pathways, can be proposed as key factors influencing meat quality through pathways including lysine degradation, butanoate metabolism, and 2-oxocarboxylic acid metabolism in older ducks. In contrast, the protein R0JXJ3 and metabolites choline and L-glutamine may determine meat quality differences between anatomical sites through the ABC transporter pathway. These findings provide molecular insights and potential biomarkers for genetic breeding and meat quality improvement in Sansui ducks. Full article

In recent years, as two globally recognized green grain storage technologies, CO₂-modified atmosphere (CO₂) storage and temperature-controlled (TC) storage have gained prominence. However, research on their integrated application remains limited. This study monitored quality dynamics and microbial activity in rice stored for 360 days under CO₂ + TC versus conventional storage (control), with analyses conducted at stratified sampling points (upper, middle, and lower layers). Compared to conventional storage, CO₂ + TC preserved rice color more effectively, while retarding the increase in fatty acid value and the decline in brown rice yield, head rice yield, and germination percentage. Furthermore, CO₂ + TC storage effectively suppresses the proliferation of Fusarium and Aspergillus, thereby retarding aflatoxin B1 (AFB1) accumulation by inhibiting fungal metabolic activity. Non-targeted metabolomics analysis further verified that CO₂ + TC storage enhanced rice antioxidant capacity and disease resistance by modulating amino acid, carbohydrate, and linolipid metabolic pathways. This technology effectively maintained nutrient retention (e.g., amino acids and proteins) and delayed quality deterioration in stored rice. These findings elucidated the underlying mechanism of CO₂ + TC on rice quality, offering a novel perspective for grain storage technology. Full article

Objectives: This study systematically compared the differences in egg quality between the BIAN chicken, an indigenous breed of Shanxi Province, and the Hy-Line Brown, a commercial breed, through the integration of non-targeted metabolomics and volatile flavoromics methods. Methods: A total of 675 metabolites and 84 volatile flavor compounds were identified in eggs from 300-day-old laying hens using LC-MS and GC × GC-TOF MS techniques. Results: BIAN chicken eggs exhibited notable advantages in flavor quality. The relative odor activity value (ROAV) of 1-octen-3-ol, a key flavor component, was 27.01 in BIAN compared with 13.46 in Hy-Line Brown, contributing to the characteristic mushroom aroma of BIAN eggs. Furthermore, the levels of heptaldehyde, 2-pentylfuran, and styrene in BIAN chicken eggs were significantly elevated, contributing to its characteristic flavor profile. Metabolomic analysis identified 40 breed-specific metabolites in BIAN chicken, with 21 up-regulated and 19 down-regulated. These metabolites were primarily involved in biological processes such as α-linolenic acid metabolism, cholesterol metabolism, and unsaturated fatty acid biosynthesis, highlighting the distinctive lipid metabolism regulation in BIAN chicken. Sensory evaluation based on relative odor activity values (ROAV) demonstrated that BIAN chicken eggs exhibited enhanced sweet, fruity, herbal, and citrus aromas, which correlated with the enriched lipid metabolism pathways. Conclusions: This study elucidates the molecular basis of distinctive egg quality characteristics in local chicken breeds, offering a scientific rationale for the conservation and utilization of indigenous breeds and the documentation of their unique metabolic and sensory properties. Furthermore, it furnishes a theoretical framework for understanding breed-specific flavor development and provides baseline data for future genetic selection and nutritional intervention strategies. Full article

Background: This study aimed to analyze metabolic changes in blood samples from patients with confirmed COVID-19 to explore the correlation between metabolomics and cytokines in survivors and non-survivors of SARS-CoV-2 infection. Understanding the complex biochemical and immunometabolic mechanisms underlying SARS-CoV-2 infection is essential for elucidating the pathophysiology and virulence of COVID-19. Methods: This study included 40 hospitalized COVID-19 patients and 40 healthy controls. Serum metabolic profiles were analyzed using ultra-high-pressure liquid chromatography-mass spectrometry (UHPLC-MS), and cytokine levels were measured using ELISA. Results: Our study defined three clear metabolic phenotypes among survivors and non-survivors of COVID-19 compared with healthy controls, which might be related to mortality, severity, and disease burden. A strong relationship was observed between certain inflammatory markers, including IL-1β, IL-2, IFN-β, IFN-γ, IL-17, and GM-CSF, as well as several metabolites, particularly in COVID-19 non-survivors, such as LysoPCs, 3-hydroxykynurenine, and serotonin. Different metabolite-cytokine correlation patterns were observed according to patient outcomes, indicating unique correlations between metabolic and immune responses in survivors and non-survivors. Metabolic phenotypes were associated with clinical outcomes, comorbidities, and sex-related differences. Kynurenine and related metabolites of tryptophan metabolism were closely correlated with COVID-19 severity, age, and mortality. Compared with survivors and healthy controls, non-survivors displayed higher IL-6, together with distinct metabolic changes. These included increased kynurenine through the IDO1 pathway, elevated glucose and lactate reflecting hyperglycolysis and energy stress, and higher xanthosine from purine turnover. Stronger cytokine–metabolite correlations in this group point to tightly linked immunometabolic activation. Conclusions: Metabolomic profiling revealed distinct metabolic phenotypes that could be associated with the severity and inflammation levels of COVID-19. Correlation analysis between metabolites and cytokines demonstrated strong intercorrelations between specific metabolites and cytokines, indicating a strong interrelationship between inflammatory markers and metabolic alterations. Specific metabolic pathways associated with cytokines and their clinical relevance may serve as potential therapeutic targets. Full article

Imperial chrysanthemum teas ‘Wuyuan Huangju’ (WYHJ) and ‘Jinsi Huangju’ (JSHJ), dried from the flowers of Chrysanthemum morifolium cv. Huangju, are traditional and popular herbal teas in China. However, their metabolite profiles and bioactivities remain unclear. In this study, we aimed to comprehensively elucidate the non-volatile and volatile metabolites of these two imperial chrysanthemum teas and assess their antioxidant activities and inhibitory effects on hyperglycemia and inflammation enzymes. Thus, we employed a widely targeted metabolomics approach based on UPLC-ESI-MS/MS and GC-MS/MS to characterize metabolite profiles of the two teas. In total, 1971 non-volatile and 1039 volatile metabolites were explored, and among these, 744 differential non-volatiles (classified into 11 categories) and 517 differential volatiles (classified into 12 categories) were identified. Further, 474 differential non-volatiles were upregulated in WYHJ, particularly flavonoids, terpenoids, and phenolic acids. In contrast, JSHJ exhibited a greater number of upregulated differential volatiles compared to WYHJ, contributing primarily to its sweet, fruity, and floral aroma. The results of scavenging activities towards DPPH·, ABTS·⁺, OH·⁻, and reducing power demonstrated that both imperial chrysanthemum teas, especially WYHJ, displayed high antioxidant capacity. We also noted that WYHJ exhibited stronger α-amylase, α-glucosidase, xanthine oxidase, and lipoxygenase inhibitory effects owing to its high active substance content. Therefore, this study provides insights into the metabolites of Chinese traditional medicinal herbal teas and highlights strategies for the comprehensive development and utilization of these traditional plant resources. Full article

Background: Accumulating evidence underscores the potential role of the gut microbiome in the pathogenesis of Alzheimer’s disease, but much remains to be clarified. This review examines current evidence linking gut microbiome dysbiosis to Alzheimer’s disease, focusing on microbial metabolomes and their mechanistic role, as well as on the potential of therapeutic approaches targeting the gut microbiome. Methods: A narrative, non-systematic examination of the literature was conducted to provide a comprehensive overview of the subject under examination. Database searches were performed in PubMed, Scopus, and Web of Science between June and July 2025. Results: Alzheimer’s disease is linked to reduced gut microbial diversity and altered bacterial taxa. Gut microbiome shifts correlate with inflammation and may drive Alzheimer’s disease progression via the microbiota–gut–brain axis. Microbial amyloids and bacterial products can cross both the intestinal and blood–brain barrier, triggering neuroinflammation and promoting amyloid and tau pathologies. Short-chain fatty acids produced by the gut microbiome regulate neuroinflammation, lipid metabolism, and gene expression, impacting Alzheimer’s disease pathology. Therapeutics targeting the gut microbiome, including probiotics, prebiotics, and fecal microbiota transplantation, show promise in modulating neuroinflammation, reducing amyloid and tau pathology, and improving cognitive function in Alzheimer’s disease. Conclusions: The gut microbiome significantly influences Alzheimer’s disease pathogenesis, and its modulation offers potential to slow progression. However, further research is required to validate effective clinical interventions. Full article

Bacterial disease infections pose a major challenge to the healthy growth of crucian carp. Hawthorn polysaccharide (HP) is a natural active ingredient in hawthorn and has a wide range of pharmacological effects. However, the mechanism of HP against Aeromonas hydrophila infection in crucian carp cultures is unknown. In this study, it was found that 0.4% HP could significantly reduce the mortality of crucian carp, significantly increase the activities of T-AOC, SOD, CAT, and GSH-PX of crucian carp infected with A. hydrophila (p < 0.05), decrease the activity of MDA, and decrease the expression levels of TGF-β, TNF-α, IFN-γ, and IL-8 genes. Increased IL-10 gene expression levels (p < 0.05) significantly improved the disease resistance of crucian carp. HP could relieve intestinal inflammation caused by A. hydrophila infection, restoring intestinal structural integrity. At the same time, HP increased the diversity and improved the structure of intestinal microbiota. At the phylum level, the abundance of Proteobacteria and Firmicutes increased, while that of Bacteroidota and Fusobacteriota decreased. At the genus level, the abundance of Aeromonas increased, while the abundance of Cetobacterium decreased. Non-targeted metabolomics analysis of crucian carp LC-MS revealed 147 different metabolites, 62 of which were up-regulated and 85 of which were down-regulated, and Linoleic acid metabolism and Glycerophospholipids were one of the most important metabolic pathways. In conclusion, the supplementation of HP in feed can promote the healthy breeding of crucian carp, and the effect of resisting A. hydrophila is better. Full article