Search Results (19,965)

Background/Objectives: Phillygenin (PHI), a natural lignan derived from Forsythia suspensa, has garnered attention for its potential to alleviate chronic diseases, including chronic colitis, pulmonary fibrosis, and diabetes. Chronic kidney disease (CKD) poses a global health challenge, characterized by high morbidity and mortality rates and associated with a spectrum of secondary complications. In this study, we aim to investigate the therapeutic effectiveness of PHI on CKD and also identify molecular signals by using a unilateral ureteral obstruction (UUO) mouse model and in vitro experiments. Methods: C57BL/6 mice were administered PHI at 50 mg/kg/day to assess its therapeutic effectiveness. In vitro, lipopolysaccharide (LPS) and adenosine triphosphate (ATP) were used to induce pyroptosis, also known as pyroptosis, in renal proximal tubular cells (NRK52E). Results: After PHI treatment for 14 consecutive days, the collagen deposition and extracellular matrix (ECM) accumulation, the expression of oxidative stress response proteins (catalase, superoxide dismutase 2, NADPH oxidase 4, and thioredoxin reductase 1), pro-inflammatory markers (TNF-α and Cyclooxygenase-2(COX-2), and infiltration of neutrophils and macrophages were significantly ameliorated in the UUO mice. Interestingly, the pyroptosis-related proteins (NLRP3/Caspase-1/GSDMD/IL-1β) and cell apoptotic death were also conspicuously relieved after treatment with PHI. Furthermore, PHI administration significantly attenuated the ATP/LPS-induced NF-κB/NLRP3/Caspase-1/GSDMD pyroptosis signal pathway in NRK52E cells. Conclusions: These results demonstrate, for the first time, that PHI treatment ameliorates inflammation and the related pyroptosis via inhibitory regulation of the NF-κB/NLRP3/Caspase-1/GSDMD axis, leading to attenuated renal fibrosis and progressive CKD in UUO mice and in vitro. Our findings suggest that PHI could be a nutraceutical candidate for attenuating CKD progression. Full article

Nowadays, it is central to generate innovations that convert agricultural by-products and food waste into valuable animal products while promoting the long-term resilience and sustainability of vulnerable animal production systems. Nutraceuticals (i.e., ‘nutrition + pharmaceutical’) are derived from foods that offer health benefits. In animal production, nutraceutical supplementation with Withania somnifera and Lepidium meyenii has shown positive effects on the endocrine, cardiopulmonary, and central nervous systems. We aimed to evaluate the possible impact of nutraceutical supplementation on rams fed a diet based on surplus feed from a highly industrialized Holstein cow production system, on corporal (live weight [LW], kg; body condition score [BCS], units), metabolic (blood glucose [GLU], mg dL⁻¹; serum protein [PRO], g 100 mL⁻¹), and sexual–testicular variables [sexual odor (ODOR, units); scrotal circumference (SC, cm); testicular volumes (TVOL, cm³); and estimated daily sperm production (EDSP, millions)]. Black Belly rams (n = 12; LW = 70.36 ± 1.2 kg; BCS = 2.96 ± 0.03 units; age = 3.8 ± 0.2 years; 25° N) were divided into 3 experimental groups: (1) WITH, supplemented with Withania somnifera (400 mg kg⁻¹ LW d⁻¹); (2) LEPI, supplemented with Lepidium meyenii (400 mg kg⁻¹ LW d⁻¹); and (3) CONT, not supplemented. The variables LW, BCS, GLU, PRO, and SC, as well as some components of TVOL, did not differ (p > 0.05) among the main effects of treatment or time; only ODOR, right transverse testicular diameter, and total testicular volume differed among treatments, generally favoring the WITH group. Furthermore, the TRT × T interaction demonstrated superior performance (p < 0.05) in the WITH group, with the largest values for LW, GLU, PRO, ODOR, SC, width of the right testicle, volume of the right testicle, total testicular volume, and EDSP. From a productive–reproductive perspective, the Robin Hood Effect—through the use of rejected dairy cattle rations as the base diet for rams—and supplemented with nutraceuticals (WITH and LEPI), emerges as a viable alternative to improve not only the productive–reproductive performance of Black Belly rams, but also other productive and socioeconomic outcomes; the latter contributing to the strengthening of producer and family well-being. Full article

Cannabis is the most widely consumed illicit substance worldwide, and the rise of synthetic and semi-synthetic cannabinoids poses growing public health concerns due to their high potency and unpredictable effects. This study presents a new analytical methodology for the simultaneous determination of natural and semi-synthetic cannabinoids (cannabidiol (CDB), Δ⁸-tetrahydrocannabinol (∆⁸-THC), Δ⁹-tetrahydrocannabinol (∆⁹-THC), and hexahydrocannabinol (HHC)) in saliva using gas chromatography coupled with mass spectrometry (GC-MS) in combination with bar adsorptive microextraction (BAμE) as a green sample preparation. The optimized method showed satisfactory recoveries (57.3–80.6%), low detection and quantification limits (1.25 and 4.13 ng/mL, respectively), excellent linearity (r² ≥ 0.9963), and robust precision and accuracy. Application to authentic saliva samples demonstrated cannabinoid levels consistent with literature values. Overall, the proposed methodology offers a cost-effective, miniaturized, and environmentally sustainable platform for routine oral fluid cannabinoid analysis, highlighting its potential for forensic, clinical, and toxicological applications. Full article

This study aimed to investigate the impact of dietary L-citrulline supplementation on the health of mares during late gestation. Thirty-two healthy mares in late pregnancy were randomly assigned to four groups: a control group (CON, 0 g/d) and three treatment groups receiving 15, 30, and 45 g/d/head of L-citrulline, respectively. The trial spanned 72 days, including a 12-day adaptation phase and a 60-day formal feeding period. A fixed daily feeding amount of 11.2 kg/head was provided, ensuring complete consumption and consistent dry matter intake across all groups. Results demonstrated that supplementation with 30 g/d/head of L-citrulline significantly improved the apparent digestibility of crude protein and nitrogen metabolism rate (p < 0.05), while notably increasing plasma superoxide dismutase (SOD) activity (p < 0.01) and reducing plasma malondialdehyde (MDA) concentration by 10.53% (p < 0.01). Furthermore, mares receiving 30 g/d of L-citrulline showed a 14.81% increase in plasma estradiol (E2) concentration (p < 0.01). Urinary concentrations of E2, estrone sulfate (ESS), and 17α-dihydroequilin sulfate (17α-DHEQS) were also significantly elevated (p < 0.05). This supplementation also enhanced plasma amino acid levels related to the urea cycle and improved the diversity of fecal microbiota, increasing the abundance of beneficial bacteria. A multi-indicator scoring system identified 30 g/d as the optimal supplemental dose of L-citrulline. These findings suggest that 30 g/d of L-citrulline may act as a nutritional regulator, offering valuable insights for enhancing the physiological and metabolic health of mares during late gestation. Full article

Background/Objectives: Multidrug-resistant (MDR) Escherichia coli resistant to third-generation cephalosporins are a growing One Health concern, but data on extraintestinal pathogenic E. coli (ExPEC) from wildlife in North Africa remain scarce. We aimed to characterize ESBL/AmpC-producing ExPEC from captive wild mammals in Tunisia and to situate these isolates in a global genomic context. Methods: In 2018, 30 fecal samples from 14 captive wild mammals in a private farm were screened on cefotaxime agar. Four cefotaxime-resistant E. coli isolates were recovered from a llama, lion, hyena, and tiger. Antimicrobial susceptibility testing and Illumina whole-genome sequencing were combined with in silico typing, resistome and virulome profiling, plasmid and mobile element analysis, human pathogenicity prediction and core-genome MLST-based minimum-spanning trees. Results: All isolates were MDR but remained susceptible to carbapenems, colistin and tigecycline. Two ST162/B1 isolates from the llama and tiger carried bla_CMY-2, whereas two ST69/D isolates from the lion and hyena harbored bla_CTX-M-15 and qnrS1. Genomes encoded 61–68 antimicrobial resistance genes and 114–131 virulence-associated genes, together with IncF-, IncI1- and IncY-type plasmids and IS26-rich insertion sequence profiles. Mating-out assays yielded cefotaxime-resistant transconjugants, supporting plasmid transferability of bla_CMY-2 or bla_CTX-M-15. PathogenFinder predicted a ≥0.93 probability of human pathogenicity for all isolates. cgMLST-based trees showed that Tunisian ST69 and ST162 clustered within internationally disseminated lineages containing human, animal and food isolates, rather than forming wildlife-restricted branches. Conclusions: Captive wild mammals in Tunisia can harbor high-risk ExPEC lineages combining ESBL/AmpC production, multidrug resistance and extensive virulence and mobility gene repertoires. These findings highlight captive wildlife as potential reservoirs and sentinels of clinically relevant E. coli and underscore the need for integrated WGS-based One Health surveillance at the human–animal–environment interface in North Africa. Full article

Neurodegenerative diseases, characterized by progressive neuronal loss and functional decline, impose a substantial global health burden. Autophagy, the principal intracellular degradative pathway for clearing misfolded proteins and damaged organelles, is vital for neuronal homeostasis, whereas maladaptive neuroinflammation is increasingly being recognized as a central driver of disease progression. A growing body of evidence indicates a bidirectional, tightly coupled relationship between autophagy and neuroinflammation: impaired autophagic flux promotes accumulation of damage-associated molecules that activate innate immune responses, while sustained inflammatory signaling further disrupts autophagy, together forming a self-reinforcing cycle that accelerates neurodegeneration. This interplay is regulated by diverse genetic, molecular, cellular, and environmental factors and manifests in cell-type-specific ways across microglia, astrocytes. Therapeutic strategies emerging from these insights include modulation of autophagic pathways (e.g., mTOR, AMPK, TFEB), targeted inhibition of inflammasome and pro-inflammatory mediators (notably NLRP3-related signaling), and delivery platforms for small molecules or nucleic acids, with increasing interest in multi-target and stage-specific interventions. This review integrates mechanistic evidence and translational advances, highlights gaps in cell-type and stage-specific understanding, and outlines priorities for developing safe, effective therapies that target the autophagy–neuroinflammation axis in neurodegenerative disorders. Full article

Circulating tumor DNA (ctDNA) has many potential applications in the management of cancer, including detection, monitoring, and treatment response assessment. This study evaluates pre-treatment ctDNA detection in a single-institution pan-cancer cohort using a highly sensitive tumor-informed ctDNA assay. Participant samples were collected at the University Health Network across six study cohorts. A total of 273 patients with stage II-IV cancers spanning 16 tumor types were analyzed using a personalized tumor-informed assay (RaDaR^®). Harmonized methods were employed to mitigate the impact of variables known to influence ctDNA detection and its quantification. Pre-treatment ctDNA was detected in 83% of participants (226/273) across all stages and cancer types. Detection rates varied by clinical characteristics, including cancer type and stage; ctDNA was detected in 100% of stage IV metastatic recurrent high-grade serous ovarian cancer (HGSOC) patients (n = 8/8) and 54% of stage IV melanoma patients (n = 6/11). The median estimated variant allele fraction (eVAF) across all patients with a positive ctDNA result was 0.25% (range: 0.000029–37.7%), varied by tumor type and increased with cancer stage. A total of 11% of positive samples (24/226) had an eVAF of <0.01%. This pan-cancer ctDNA analysis using a highly sensitive assay reveals high detection rates overall, including ~10% at low levels (<0.01% eVAF), offering a reference for future clinical ctDNA applications and furthering our understanding of factors influencing ctDNA measurements. Full article

Background/Objectives: Anthocyanins are dietary pigments associated with reduced risk of chronic diseases, yet their low systemic bioavailability challenges the traditional direct antioxidant hypothesis. This review aims to reconceptualize anthocyanin bioactivity by proposing the gut microbiome as a key mediator that biotransforms these compounds into bioactive metabolites responsible for systemic health effects. Methods: This review synthesizes evidence on the microbial metabolism of anthocyanins and includes a structured appraisal of the literature using an evidence evaluation framework analogous to GRADE, focusing on their transit to the colon, enzymatic biotransformation by gut microbiota, and resulting production of phenolic metabolites such as protocatechuic acid (PCA). It also examines the role of specific bacterial taxa (e.g., Bifidobacterium and Lactobacillus) in enhancing bioavailability and explores the downstream cellular pathways modulated by these metabolites. Results: Gut microbiota convert anthocyanins into smaller phenolic metabolites such as PCA, syringic acid, gallic acid, and other respective metabolites, which achieve plasma concentrations up to 100-fold higher than parent compounds and can cross the blood–brain barrier. These metabolites exert systemic effects by modulating key signaling pathways (NF-κB and Nrf2) and restoring redox homeostasis. Additionally, beneficial gut bacteria enhance anthocyanin bioavailability and support the production of short-chain fatty acids (SCFAs). Conclusions: Systemic health benefits of anthocyanins are largely mediated by gut microbiota through the generation of bioactive metabolites. This microbiota-driven process redefines the mechanistic understanding of anthocyanin action and highlights the microbiome as a critical determinant of their efficacy in preventing cardiometabolic and neurodegenerative diseases. Full article

Cardiometabolic diseases, encompassing obesity, insulin resistance, type 2 diabetes (T2D), metabolic dysfunction-associated steatotic liver disease (MASLD), hypertension, and atherosclerotic cardiovascular disease (ASCVD), represent a vast continuum driven by multi-organ network dysregulation. Clinical risk assessment remains dominated by late-stage measures (e.g., fasting glucose, HbA1c, standard lipids). While these assessments predominate the literature and clinical trial endpoints, each incompletely capture early mechanistic risk, inter-individual heterogeneity, and differential response to interventions. Multiomics (genomics, epigenomics, transcriptomics, proteomics, metabolomics, lipidomics, microbiomics, and extracellular vesicle/exosome cargo profiling) expands the biomarker landscape but introduces translational barriers: high dimensionality, cohort heterogeneity, limited causal inference, and insufficient validation pipelines. AI-driven systems biology platforms can support cardiometabolic biomarker discovery and therapeutic translation by enabling systems-level biological inference across heterogeneous datasets, prioritizing mechanism and traceability over purely correlation-based models. GATC Health’s Operon™ platform is described as a proprietary, AI-driven internal scientific computing platform designed to support therapeutic discovery and development decision-making across the pharmaceutical lifecycle, including evaluation of drug efficacy, safety, off-target effects, pharmacokinetics (PK), pharmacodynamics (PD), and overall development risk. Operon evolved from earlier generations of GATC Health’s internal multiomic modeling systems (formerly referred to as the Multiomics Advanced Technology, MAT) and incorporates expanded data types, orchestration layers, validation workflows, and productization frameworks. Operon is operated by GATC scientists and generates structured, productized outputs (e.g., formal assessments, analyses, and decision frameworks) that are reviewed by experts. Operon methodologies have undergone internal validation and independent academic evaluation under blinded conditions, with reported classification performance (true positive rate 86% and true negative rate 91%) in controlled evaluation settings; these performance metrics should not be interpreted as guarantees of clinical success. This review provides a T2D-centered cardiometabolic biomarker landscape with cardiovascular extension and outlines how Operon-enabled multiomic integration and scenario-based simulation can support early screening, endotype stratification, mechanistic interpretation, and precision intervention design, including AI-guided polypharmacology strategies. Full article

Background: Cost-utility analysis (CUA) is frequently used by reimbursement agencies and national advisory bodies to make informed decisions on whether or not to reimburse surgical interventions. Health state preferences (utilities) are a key component in valuing health outcomes in that they are used in calculating quality-adjusted life-years (QALY). Unfortunately, disease-specific HRQoL measures commonly lack the preference weights necessary to produce health-state utility values for use in CUA. A solution to this problem is to map a disease-specific quality-of-life measure to a generic preference-based measure. The aim of this study was to develop health-state utility values for cerebral palsy (CP) patients with scoliosis by mapping disease-specific quality-of-life scores (CPCHILD outcome questionnaire) to the Health Utility Index Mark 3 (HUI3) questionnaire. Methods: A prospective, multicentre CP scoliosis database was analysed identifying consecutive CP patients with ≥2 years follow-up who completed both the CPCHILD and HUI3 at enrolment, at 1-, and at 2 years follow-up. Ordinary least squared regression models were constructed to estimate HUI3 utility values from CPCHILD scores and clinical variables. The model was developed using enrolment data, while 1- and 2-years follow-up data were used for confirmatory analysis of the goodness of fit of the model (i.e., paired t test between observed and calculated HUI utility values). Results: A total of 232 patients were included, 91.9% were GMFCS IV and V, 87.9% underwent surgery during the study period, and the average magnitude of scoliosis deformity at enrolment was 81.93° ± 25.13°. A log-linear regression model was developed, including three predicting variables: CPCHILD total score (β = 0.016, p = 0.0001), communication (β = −0.436, p = 0.0001), and feeding ability (β = −0.289, p = 0.0001). The R² of the model was 0.578, and F 49.73 (p = 0.0001). The mean difference of means between observed HUI3 values and calculated HUI3 values at 1- and 2 years was −0.020 (p = 0.129) and 0.017 points (p = 0.187), respectively. Conclusions: Although the use of a preference-based HRQoL measure is the ideal method to generate health-state utility values, we demonstrate that HUI3 scores can be accurately predicted using the CPCHILD questionnaire. This mapping algorithm will be useful in estimating health-state utilities in clinical trials, and hence CUA, of CP patients undergoing scoliosis surgery to help better inform patients, care-givers, health-care providers, and decision makers of the economic burden of surgery in this patient population. Full article

As a probiotic lactic acid bacterium, E. faecalis regulates intestinal flora, strengthens the intestinal barrier, and enhances immunity in the host. However, as a new strain isolated from healthy feline gut, E. faecalis HHP003 has an unclear effect on feline intestinal health. Twenty cats with mild diarrhea were randomly assigned to two groups: one group received the standard diet (MD), while the other group received supplemental E. faecalis HHP003 (EF). Meanwhile, 10 healthy cats were enrolled as a healthy control group (CON). After 42 days of intervention, the EF group exhibited significantly reduced serum inflammatory markers (TNF-α and IL-1β), as well as decreased levels of calprotectin and lipopolysaccharide, compared with the MD group (p < 0.05). The intestinal microbial diversity was altered in the EF group, with increased Chao and Shannon indices (p < 0.05). Specifically, the relative abundances of Bacillota, Bacteroidota, and Ruminococcaceae were significantly higher in the EF group than those in the MD group (p < 0.05). Metabolomic analysis identified 697 differential metabolites and nine KEGG metabolic pathways (p < 0.05) between the EF and MD groups. Furthermore, the study identified significant associations between the gut microbiota and selected serum metabolites. In summary, E. faecalis HHP003 supplementation was associated with reduced serum inflammatory responses, improved intestinal inflammation and barrier markers, and altered gut microbiota and serum metabolite levels in cats with mild diarrhea. Full article

Wireless sensor networks (WSNs) have increasing demand on lightweight, efficient, and secure encryption techniques for devices with limited resources, since traditional algorithms require high computation which make them impractical. This preliminary study presents an encryption algorithm based on chaos designed for transmitting short data, using the Lorenz system and Euler’s method for computation. It is combined with a synchronization model based on data array. It inserts iteration parameters within the ciphertext to ensure consistent key reproduction while decrypting. Within the broader context of e-health data streams, encryption efficiency is critical: continuous ECG signals generate large volumes of data that challenge real-time secure transmission, whereas individual blood pressure readings are far smaller and lightweight. While this work delimits its scope to short, low-power transmissions, simulations and hardware implementation on an nRF chip using the Enhanced ShockBurst (ESB) protocol demonstrated efficiency, with the lowest encryption speed of 0.154 ms for a 1-byte payload. Security analysis using the NIST Statistical Test Suite confirmed high statistical randomness of the generated keystream, and theoretical key-space analysis supports robustness. By focusing on short-stream encryption in preliminary form, the scheme contributes toward inclusive secure communication technologies for resource-constrained IoT healthcare systems and diverse user populations. Full article

Stress has been prevalent and has become an epidemic health burden, loaded with chronic disorders. The stress response is an adaptive mechanism that prepares an individual to respond to threats or other stressors in a fight-or-flight situation. The stress response involves the induction of neurological and hormonal networks and is usually resolved when stress subsides; however, persistent stress leads to permanent and detrimental impacts on health. With the rise of advanced single-cell analysis technologies, a wave of basic and translational research aimed at elucidating stress has shed light on the underlying mechanisms. Among 80 studies in this review, stressors are classified into acute/chronic physical, physiological, and psychological groups, whereas some studies have more than one stress source. Single-cell RNA-seq was the dominant technology utilized in these studies. This advanced technique systematically reveals cellular heterogeneity in gene expression patterns and the differential transcriptomic landscape of stress response in a wide array of tissues and organ systems, e.g., the nervous system, the endocrine system, the immune system, and others. Bioinformatics identified a single-cell atlas of stress-specific cell subtypes, cell-to-cell interactions, and enriched pathways, showing promise for stress syndrome biomarkers, attenuation, and targeted therapy. The limits of these stress studies were mainly focused on transcriptomics, so future studies using multi-omics approaches across multiple organ systems will yield insights into stress disorders and novel therapeutic strategies. Full article

Background/Objectives: Antimicrobial resistance (AMR) is a global threat to human, animal, and environmental health. Among bacteria, E. coli is frequently used as a key indicator of AMR. Despite their genetic proximity to humans, studies on AMR in Non-Human Primates (NHPs) remain limited, particularly in semi-anthropized environments. This study aims to characterize the antibiotic resistance profiles and phylo-groups of E. coli isolated from NHPs and humans at a primatology center. Methods: A total of 143 stool samples were collected, including 125 from NHPs and 18 from humans. Isolates were cultured on Eosin Methylene Blue agar and then identified by MALDI-TOF mass spectrometry. Antibiotic susceptibility was assessed using the Kirby–Bauer disk diffusion method, with 30 antibiotics following CASFM-EUCAST recommendations. E. coli phylo-groups were characterized by quadruplex PCR according to the Clermont method, targeting the genes. Results: A total of 122 E. coli isolates (85.31%) were recovered, with comparable prevalence observed across NHPs and human staff. More than half of the isolates (55.74%) were resistant to at least one antibiotic tested, and 12.3% were classified as multi-drug resistant (MDR). Resistance rates of isolates in Mandrillus sphinx, Pan troglodytes, and humans were 50.6%, 57.7%, and 80.0%, respectively, with no significant statistical difference (p = 0.11). A single Extended-Spectrum Beta-Lactamase (ESBL) producing isolate was identified in the mandrill. Phylo-group analysis revealed the dominance of group A (50%), followed by groups B1, D, and C. Conclusions: Resistance profiles and phylo-group distribution among NHPs could suggest bacterial exchange and potential for cross-transmission of AMR within the shared environment. Full article

The biliary tract, long considered a sterile environment, is now recognized to harbor a resident microbiota with important implications for health and disease. This review aims to summarize current knowledge on the composition and function of the biliary microbiota in physiological conditions, and its alterations in pathological states such as infection and lithiasis, with a particular focus on antimicrobial resistance. In healthy individuals, the biliary microbiota appears to be shaped by bile acids and gut–bile axis interactions, playing a role in local immune modulation. In disease, microbial dysbiosis contributes to conditions such as acute cholecystitis, cholangitis, and gallstone formation, with distinct microbial signatures linked to specific stone types. Common biliary pathogens, including E. coli, Enterococcus spp., Pseudomonas spp., and K. pneumoniae, often exhibit concerning resistance patterns, impacting therapeutic strategies. Emerging evidence highlights the interplay between intestinal and biliary microbiota, suggesting potential diagnostic and prognostic applications. Understanding these dynamics opens new avenues for microbiota-informed antibiotic stewardship, targeted microbiota modulation, and precision medicine approaches. Further research, particularly culture-independent and longitudinal studies, is crucial to fully elucidate the clinical significance of the biliary microbiota and to integrate microbiota profiling into patient management strategies. Full article