Search Results (53,724)

The relationship between epilepsy, obesity, and metabolic syndrome (MetS) has emerged as a rapidly evolving area of neurobiology inquiry. Emerging evidence suggests that epilepsy extends beyond neuronal hyperexcitability, reframing it as a systemic condition characterized by significant metabolic dysregulation. Converging supports a bidirectional relationship while seizures, antiseizure medications (ASM), and neuroinflammation induce exacerbate potentiate epileptogenesis through shared molecular pathways. At the cellular level, chronic epileptic activity induces oxidative stress, mitochondrial dysfunction, and the activation of microglia and astrocytes. This, in turn, leads to the release of pro-inflammatory cytokines including TNF-α, IL-1β, and IL-6. These mediators traverse the blood-brain barrier (BBB), subsequently modifying insulin signaling, and disrupting glucose homeostasis, which collectively fosters a pro-inflammatory and insulin-resistant environment. Furthermore, antiseizure medications such as valproate can exacerbate these effects by directly impairing insulin receptor signaling and altering adipokine production, ultimately contributing to weight gain and systemic metabolic dysregulation. Obesity and MetS induce neuroinflammatory and excitotoxic states that promote seizure onset via leptin resistance, reduced adiponectin levels, and compromised AMP-activated protein kinase (AMPK) signaling. Emerging evidence emphasizes the gut-brain axis as a crucial regulator in this reciprocal interaction. Dysbiosis, altered microbial metabolites (e.g., short-chain fatty acids), and heightened intestinal permeability facilitate systemic inflammation and BBB disruption, enhancing neuronal excitability. Insulin resistance in the brain disrupts synaptic transmission, impairs mitochondrial biogenesis, and compromises redox equilibrium, perpetuating a pathological cycle linking metabolic stress to epileptic activity. This review synthesizes the cellular, molecular, and systemic pathways connecting epilepsy, obesity, and MetS, and proposes that epilepsy be reconceptualized as a neuro-metabolic disorder. Insights into these convergent pathways provide a rationale for novel therapeutic strategies that simultaneously target seizure control and metabolic regulation, encompassing microbiota modulation, antioxidant therapy, and insulin-sensitizing interventions with the overarching aim of restoring neuro-metabolic homeostasis. Full article

Antibiotic therapy represents one of the strongest ecological perturbations of the human gut microbiota, inducing rapid and often prolonged alterations in community structure, metabolic activity, and functional resilience. While the use of probiotics to mitigate antibiotic-associated dysbiosis is widely adopted in clinical practice, probiotic selection is still largely empirical and insufficiently grounded in biological compatibility with specific antibiotic pressures. In this conceptual review, antibiotics are reframed not merely as antimicrobial agents, but as ecological forces that shape microbial survival, quiescence, and recolonization dynamics. We propose a biologically informed framework that distinguishes genetic antibiotic resistance from functional or ecological insensitivity, highlighting how microbial traits, such as the absence or inaccessibility of the antibiotic target, metabolic state, sporulation, and cellular architecture, influence the persistence of probiotics during antibiotic exposure. By integrating the mechanisms of action of antibiotics with key physiological and structural features of probiotic microorganisms, we develop a conceptual framework aimed at rationalizing the compatibility of probiotics and antibiotics. This framework does not imply clinical efficacy but provides an interpretative tool to guide hypothesis generation, experimental validation, and the design of future targeted probiotic strategies. A more ecologically grounded approach to probiotic selection may ultimately improve microbiota support during antibiotic therapy and advance personalized microbiome modulation. Full article

Cancer is an alarming health concern and economic burden in both developed and developing countries. Recently, there has been a growing demand for new alternative medications with more effectiveness and fewer harmful effects. During the past decades, a set of chemotherapeutic agents has been developed to fight against a large spectrum of cancer types. Unfortunately, their use is associated with a high level of toxicity; they are expensive, also, and their deployment is restricted by the emergence of cellular resistance. Plant-based components are garnering attention due to their low toxicity, selectivity, efficiency, and ease of accessibility. Alkaloids are one of these targeted compounds. Indeed, they are a highly diverse group with basic heterocyclic nitrogen-containing alkaloids that exhibit potent anticancer effects against a large panel of solid and liquid tumors, such as lung, breast, leukemia, liver, and colon cancer. The main molecular mechanisms involved in alkaloids’ anticancer effect are the induction of apoptosis via the extrinsic and intrinsic pathways, DNA damage, and the inhibition of cell cycle progression. Amazingly, these auspicious compounds exhibited strenuous inhibitory effects against a whole range of key enzymes involved in cancer progression and metastasis, such as Cytochrome P450 (CYP450), Cyclooxygenase-2 (Cox-2), Lysine-Specific Demethylase 1 (LSD1), Poly [ADP-ribose] polymerase (PARP), and topoisomerase, mainly through two action modes, namely irreversible and reversible inhibition. Furthermore, several conventional extraction methods have been developed to extract bioactive compounds from natural matrices, such as Soxhlet and hot water extraction. However, these techniques have many drawbacks, as they require a large amount of organic solvents, which not only affect human health but also generate severe environmental issues. To overcome these limitations, multiple eco-extraction techniques have emerged as potential alternatives to traditional extraction methods such as ultrasonic extraction, microwave-assisted extraction, and supercritical fluid extraction. In fact, they are considered eco-friendly and efficient technologies with less time and solvent consumption. Overall, this review aims to provide an updated overview of the most prominent anticancer alkaloids that have not been well reviewed already, as well as the main green extraction techniques relevant to the extraction of antineoplastic alkaloids. Full article

Growth, reproduction, and survival are fundamental biological priorities that animals balance by evaluating dietary cues. Cholesterol occupies a unique position among nutrients, serving both as a structural component of cellular membranes and as a precursor for steroid hormones, yet its regulation differs fundamentally across taxa. In mammals, cholesterol availability is buffered by endogenous synthesis and post-ingestive metabolic control. In contrast, insects have evolutionarily lost sterol biosynthesis and are therefore sterol auxotrophs that rely entirely on dietary sources. Here, we synthesize current understanding of cholesterol biology in Drosophila melanogaster, with a focus on sterol auxotrophy, life-stage–specific allocation, and endocrine and lifespan outcomes in a comparative framework. We highlight cholesterol not only as a metabolic substrate but also as a sensory-encoded nutrient that shapes feeding behavior. We further examine how lipophorin (Lpp)-mediated transport, Niemann–Pick type C proteins, ATP-binding cassette transporters, and the nuclear receptor DHR96 coordinate systemic sterol distribution and endocrine output in the absence of endogenous synthesis. By integrating these mechanisms across development, we illustrate how cholesterol availability governs larval growth, ecdysteroid production, adult reproduction, neural function, and lifespan through coupled endocrine and nutrient-signaling networks. This review positions cholesterol as a multifunctional signal linking sensory perception, metabolic regulation, and life-history strategy in sterol-auxotrophic insects, offering a framework for understanding how evolutionary loss of biosynthetic capacity reshapes nutrient sensing and homeostatic control. Full article

Radish (Raphanus sativus L.) is an important vegetable resource in the food industry, generating substantial amounts of by-products during cultivation and distribution. Despite their richness in functional components, these by-products are largely underutilized. Accordingly, there is increasing interest in their valorization as functional food ingredients. This study evaluated the functional potential of radish by-products removed prior to distribution by applying cellulase pretreatment and Lactiplantibacillus plantarum fermentation individually or in combination. Radish samples were separated into leaf blade, stem, and taproot tissues and processed as untreated control, enzyme-treated, fermented, and enzyme-treated and fermented (EF) groups. The EF treatment significantly increased reducing sugar content, total polyphenols, and total flavonoids across all tissues, with the most pronounced enhancement observed in leaf by-products. In antioxidant assays, EF samples showed decreased IC₅₀ values in DPPH and ABTS radical scavenging assays and increased FRAP values, indicating superior antioxidant capacity. In lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages, EF-treated leaf extracts effectively suppressed nitric oxide and intracellular ROS production without cytotoxicity and exhibited the highest GSH/GSSG ratio, suggesting improved cellular redox balance. In contrast, interleukin-6 (IL-6) secretion varied depending on tissue type and processing condition, indicating that antioxidant enhancement does not necessarily correspond to uniform cytokine regulation. Collectively, these findings demonstrate that enzymatic pretreatment combined with lactic acid fermentation serves as an effective strategy to enhance the antioxidant and cell-protective properties of radish by-products, supporting their potential use as value-added functional food ingredients. Full article

Vesicular stomatitis virus (VSV), a member of the Vesiculovirus genus within the Rhabdoviridae family, is a widespread pathogen affecting all hoofed livestock species, leading to reduced animal growth and productivity. To date, no effective therapeutic treatment for VSV infection has been developed. Natural medicinal compounds with immunomodulatory properties represent a promising supportive strategy for infection control. Ginsenoside Rh1, a primary bioactive component of ginseng plants, has been reported to possess broad pharmacological and immunoregulatory activities. Nevertheless, its potential antiviral effects against VSV remain unexplored. In this study, we demonstrate that Ginsenoside Rh1 exhibits considerable antiviral activity against VSV in cellular models. Mechanistically, its antiviral effect is primarily mediated through the inhibition of VSV-induced autophagy, thereby enhancing interferon-mediated antiviral responses. Collectively, our findings identify Ginsenoside Rh1 as a novel antiviral agent active against VSV and potentially related vesiculoviruses, clarify its mechanism of action, and highlight an autophagy-dependent immunomodulatory approach that could be critical for confronting existing and emerging RNA viral infections. Full article

Sonchus oleraceus L., a member of the Asteraceae family native to Eurasia, is a herbaceous plant whose young stems and leaves are consumed globally as a medicinal and edible wild vegetable; it is rich in flavonoids and exhibits various pharmacological activities, including anti-inflammatory and anti-tumor effects. This study optimized the extraction process of flavonoids from Xinjiang S. oleraceus using response surface methodology and evaluated the anti-inflammatory activity of luteoloside in vitro. Based on single-factor experiments and Box–Behnken design, the effects of ethanol concentration, extraction time, solid-to-liquid ratio, and extraction temperature on flavonoid yield were investigated. The optimal extraction conditions were determined as ethanol concentration 62%, extraction time 30 min, solid-to-liquid ratio 1:91 g/mL, and extraction temperature 64 °C, with a flavonoid yield of 21.64 mg/g. After purification via polyamide column chromatography, the luteoloside content was determined by HPLC to be 44.06 μg/g. Cytotoxicity assays revealed that a luteoloside concentration of 100 μmol/L reduced the viability of Oryctolagus cuniculus colon epithelial cells to approximately 80%. ELISA results demonstrated that luteoloside significantly inhibited the release of pro-inflammatory factors, including TNF-α, while promoting the expression of the anti-inflammatory factor IL-10. These findings indicate that luteoloside effectively alleviates LPS-induced cellular inflammation. Full article

When using traditional approaches, such as pharmacokinetics and pharmacodynamics, the entire cellular or molecular response to drugs in the body cannot be fully ascertained or established. The oral medication process involves pharmacokinetics, followed by oral microbiomics and then gut microbiomics and pharmacodynamics. Recently, there has been increasing interest in the role of genetics (pharmacogenetics and pharmacogenomics) in both humans and microbiomes, as well as omics alterations (e.g., epigenetic, transcriptomic, proteomic, and metabolomic alterations as a consequence of drug exposure), which can help to ascertain the cellular responses to medications. Both the efficacy and toxicity of a drug are influenced by these factors. To assess these at an individual level, an integrative Personalized Medicine Model may be needed to help with medication management. Two example application cases for SSRIs and statins demonstrate the clinical usefulness of such a model, which can guide clinicians during drug selection and dosing to reduce reliance on trial-and-error, thus potentially improving patient outcomes and safety. Integrating this framework into practical clinical workflows requires the capture, analysis, and translation of multi-omics data in order to realize decision support protocols and actionable drug recommendations. This review also discusses IT requirements and different stakeholder roles. Although the proposed model can guide the treatment of diseases at the individual patient level, further research is still needed before it can be implemented as part of drug development research, clinical care, and healthcare delivery systems. Full article

The cultivation of asparagus (Asparagus officinalis L.) is plagued by two serious issues: “asparagus decline” and “asparagus replant problem”. The average lifespan of an asparagus plant is 15 to 20 years. However, its productivity decreases after a few years (asparagus decline). Even when these asparagus plants are replaced with new ones, the new plants remain unproductive (asparagus replant problem). The main causes of these problems are a Fusarium infection and asparagus autotoxicity. Several reviews have been conducted on Fusarium. Despite the accumulation of evidence on asparagus autotoxicity in the literature over the past four decades, no review has focused specifically on asparagus autotoxicity. It has been reported that asparagus growth is inhibited by asparagus root residues, leachates, root exudates, and rhizosphere soils. Several phenylpropanoids, including trans-cinnamic acid, p-coumaric acid, caffeic acid, and ferulic acid, have been identified as asparagus autotoxic substances in these root residues, root exudates, rhizosphere soils, growth media, and/or plant tissues. Tryptophan, 3,4-methylenedioxycinnamic acid, and iso-agatharesinol were also identified as asparagus autotoxic substances. These substances may cause autotoxicity by disrupting phytohormone levels, cellular metabolism, impairing membrane function, and by inducing oxidative stress. Although cinnamic, p-coumaric, caffeic, and ferulic acids have been reported to act as antibiotics, these compounds have also been shown to weaken the defense mechanisms of asparagus against pathogen infection, and enhance the Fusarium pathogenicity. The presence of these autotoxic substances, coupled with a Fusarium infection, may create a vicious cycle that worsens “asparagus decline” and “asparagus replant problem”. This is the first review to focus on the asparagus autotoxicity. Full article

Africa reported lower COVID-19-related morbidity and mortality compared to other continents, despite widespread SARS-CoV-2 transmission and limited vaccine access. Proposed immunological explanations include potential pre-existing immunity such as cross-reactive humoral or cellular responses from earlier coronavirus exposures. However, functional immune responses to SARS-CoV-2 in African populations remain poorly characterized. To address this gap, we assessed post-pandemic neutralizing antibody responses against the SARS-CoV-2 D614G variant. We analyzed plasma samples from 989 participants in a cross-sectional survey in Ghana’s Eastern and Greater Accra regions. A live virus neutralization assay using Vero E6 TMPRSS2 cells was employed to quantify SARS-CoV-2 D614G-specific neutralizing antibodies. Responses were assessed across collected demographic data. Urban participants exhibited higher median neutralizing antibody titers than rural counterparts, in both vaccinated and unvaccinated groups (p < 0.0001). Among unvaccinated individuals, median neutralizing antibody titers were comparable across age groups in urban settings. Vaccinated individuals showed elevated median titers across all age groups, with urban residents demonstrating stronger responses. Significant sex-based differences in neutralizing titres were also identified. Our findings reveal marked disparities in functional antibody responses between urban and rural populations, likely shaped by differences in SARS-CoV-2 exposure and vaccination. Continued surveillance and immunological profiling remain key for informing vaccine strategies and future pandemic preparedness. Full article

In patients, extraintestinal manifestations of inflammatory bowel disease (IBD) are attenuated ventricular contractile function and arrhythmia. To determine the mechanism of IBD-induced changes in ventricular function, we used a mouse model of dextran sodium sulfate (3.5% weight/volume; 7 days)-induced colitis. Changes in cardiac function were quantified in isolated ventricular myocytes (VM) by cell shortening, imaging of [Ca²⁺]_i, reactive oxygen species (ROS), and t-tubular density. During colitis, VMs exhibited attenuated cell-shortening and altered Ca²⁺-handling properties. A prolonged Ca²⁺ transient (CaT) rise time correlated with an increased coefficient of variation in the subcellular Ca²⁺ release and an attenuated t-tubular density. T-tubular loss was accompanied by increased ROS production, calpain-2 (CAPN2) expression, junctophilin-2 (JPH-2) cleavage, and autophagy. Inhibition of Angiotensin-converting enzyme during colitis (Perindopril: 3 mg/kg/day) prevented the increase in CAPN2, ROS production, autophagy, and t-tubular remodeling. It failed, however, to restore full length JPH-2. We conclude that, during IBD, the angiotensin II (AngII)-induced loss of t-tubular integrity and altered cellular Ca²⁺ handling can be prevented by suppression of the AngII-dependent increase in CAPN2 and autophagy and thus suppression of AngII signaling might benefit IBD patients with cardiac manifestations of the disease. Full article

Background: Rapidly progressive glomerulonephritis (RPGN) is a severe nephrological emergency, frequently secondary to anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. In older adults, the coexistence of comorbidities and monoclonal gammopathy of undetermined significance (MGUS) makes it difficult to distinguish between ANCA vasculitis and monoclonal gammopathy of renal significance (MGRS), which differ in prognosis and treatment. The coexistence of PR3-ANCA-associated vasculitis and MGUS is uncommon and sparsely documented. Case Presentation: A 72-year-old woman with hypertension and type 2 diabetes presented with acute deterioration and rapidly progressive renal failure, requiring hemodialysis. She had subnephrotic proteinuria, hematuria, and an active urinary sediment. The autoimmune workup showed ANCA negativity using immunofluorescence, but PR3-ANCA positivity using ELISA. Hematologic characterization documented an IgG kappa monoclonal spike; no bone lesions, amyloidosis, or criteria for multiple myeloma were found; and the patient was classified as MGUS. Renal biopsy revealed necrotizing extracapillary pauci-immune glomerulonephritis with cellular and fibrocellular crescents and no monoclonal deposits, consistent with PR3-ANCA vasculitis. Induction therapy with methylprednisolone pulses and oral prednisone was initiated; cyclophosphamide was not administered because of catheter-associated Staphylococcus aureus bacteremia and upper gastrointestinal bleeding complicated by disseminated intravascular coagulation. The patient died on day 25 due to infectious and hemorrhagic complications. Conclusions: This case provides additional documentation of an uncommon overlap between PR3-ANCA-associated vasculitis and MGUS in a Latin American patient and highlights the role of renal biopsy in distinguishing MGRS from pauci-immune vasculitis in the presence of paraproteinemia. It also underscores the need to tailor immunosuppression in frail older adults, balancing disease control against the risk of severe infection. Full article

The progressive decline in functional β-cell mass in Type 2 Diabetes (T2D) is increasingly recognized not as a simple apoptotic loss, but as a complex erosion of cellular identity termed “dedifferentiation.” Central to this phenotypic shift is the metabolo-epigenetic axis, where mitochondria act as the primary sensing hub, transducing nutrient flux into biochemical signals that govern the chromatin landscape. This review synthesizes current evidence on how mitochondrial metabolites—including Acetyl-CoA, α-ketoglutarate, and NAD+—serve as obligatory co-factors for the epigenetic machinery. We explore how chronic metabolic stress triggers a “Systemic epigenetic destabilization,” leading to the loss of lineage-specific markers and the formation of persistent “metabolic scars.” Furthermore, we discuss the clinical implications of these changes, specifically regarding the phenomenon of metabolic memory and the molecular limits of β-cell reversibility. By integrating foundational transcriptional studies with emerging epigenomic data, we propose that targeting the mitochondrial–epigenetic axis offers a strategic window for re-differentiating failing β-cells and restoring glycemic homeostasis. Full article

Magnetic Resonance Imaging (MRI) plays a pivotal role in evaluating treatment response following radiation-based therapies for hepatocellular carcinoma (HCC). As radiation modalities such as stereotactic body radiotherapy (SBRT) and transarterial radioembolization (TARE) gain prominence, understanding the underlying mechanisms of radiation-induced cellular senescence is essential for accurate interpretation of imaging. The physiological changes of radiation treatment manifest as altered diffusion characteristics and delayed regression of enhancement and tumor volumes on MRI, challenging conventional response criteria. Herein, functional and temporal imaging biomarkers are necessary. However, current imaging strategies lack standardization and robust validation, underscoring the need for prospective studies to correlate MRI findings with treatment outcomes. This review synthesizes emerging evidence on MRI-based evaluation of radiation-treated HCC, explores the physiological rationale linking senescence to imaging phenotypes, and advocates for optimized imaging protocols and criteria to enhance post-treatment surveillance and therapeutic decision-making. Full article

The rapid expansion of cardiac imaging has substantially increased patient and occupational exposure to low-dose ionizing radiation. Evidence suggests that cumulative exposures below 100 mSv may contribute to long-term risks of cancer and non-cancer diseases, including cardiovascular disease. However, establishing causality at these dose levels is challenging, as epidemiological studies are limited by heterogeneous endpoints, uncertainties in dose reconstruction, and incomplete control of confounding factors. Molecular biomarkers offer a promising strategy to bridge the gap between radiation exposure and clinically manifest disease, enabling more precise individualized risk assessment and targeted preventive strategies. This review summarizes current evidence on genetic and epigenetic biomarkers for evaluating the biological effects of radiation in cardiac imaging and interventional cardiology and examines their potential role in risk stratification and occupational surveillance. Genetic markers—including γ-H2AX foci, micronucleus assays, and telomere length alterations—alongside epigenetic modifications such as DNA methylation changes and microRNA expression profiles provide sensitive indicators of radiation-induced cellular damage. Integrating biomarker profiling with individualized dosimetry and longitudinal follow-up may improve risk prediction, enhance occupational protection, and support safer, more sustainable imaging practices in contemporary cardiovascular care. Full article