Search Results (301)

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease (NAFLD), is a prevalent, multisystem disease affecting approximately 30% of adults worldwide. Obesity, along with dyslipidemia, type 2 diabetes mellitus, and hypertension, are closely intertwined with MASLD. In people with obesity, MASLD prevalence is estimated to be about 75%. Despite various approaches to MASLD treatment, dietary changes remain the most accessible and safe interventions in MASLD, especially in obese and overweight patients. Whey proteins are rich in bioactive compounds, essential amino acids with antioxidant properties, offering potential benefits for MASLD prevention and management. This state-of-the-art review summarizes whey protein impacts on a spectrum of MASLD-related manifestations, such as obesity, impaired glucose and lipid metabolism, hypertension, liver injury, oxidative stress, and inflammation. The results obtained in clinical environments, with a focus on meta-analysis, propose whey protein supplementation as a promising strategy aimed at managing multifaced MASLD disorders. Well-designed cohort studies are needed for validation of the efficacy and long-term safety of whey proteins in MASLD patients. Full article

Fungal infections pose a significant yet under-recognised global health burden, affecting over one billion individuals annually and contributing to approximately 2.5 million direct deaths. The World Health Organisation (WHO) has recently reemphasised this issue through the publication of its Fungal Priority Pathogens List (FPPL) and its 2025 report evaluating current antifungal diagnostics and therapeutics. Among the most prevalent fungal pathogens is Trichophyton rubrum, an anthropophilic dermatophyte responsible for up to 70% of superficial fungal infections, including onychomycosis. The emergence of antifungal resistance further complicates management, necessitating the development of novel, effective, and sustainable treatment alternatives. Natural compounds are increasingly being explored for their antifungal potential due to their broad-spectrum activity and lower toxicity. Coconut oil has gained particular attention for its therapeutic properties attributed to medium-chain fatty acids (MCFAs), especially lauric acid. The aim of this study was to understand how innate and modified coconut oils can alter the rheological properties of Pluronic hydrogels while retaining antifungal activity for downstream application in treating fungal infections. Results identified hydrophobic interactions by FTIR and DSC between the hydrocarbon chains of the coconut triglycerides and the hydrophobic core of the Pluronic micelles, leading to gel stabilisation as identified by rheological analysis. Full article

Anaerobic digestion (AD) has long been valued for producing a biogas–digestate pair, yet its profitability is tightening. Next-generation AD biorefineries now position syngas both as a supplementary feedstock and as a springboard to capture high-value intermediates, hydrogen (H₂) and volatile fatty acids (VFA). This review dissects how complex natural consortia “decide” between hydrogenogenesis and acetogenesis when CO, H₂, and CO₂ co-exist in the feedstocks, bridging molecular mechanisms with process-scale levers. The map of the bioenergetic contest between the biological water–gas shift reaction and Wood–Ljungdahl pathways is discussed, revealing how electron flow, thermodynamic thresholds, and enzyme inhibition dictate microbial “decision”. Kinetic evidence from pure and mixed cultures is integrated with practical operating factors (gas composition and pressure, pH–temperature spectrum, culture media composition, hydraulic retention time, and cell density), which can bias consortia toward the desired product. Full article

The global antimicrobial resistance crisis demands innovative strategies to combat bacterial infections, including those caused by drug-sensitive pathogens that evade treatment through biofilm formation or metabolic adaptations. Here, we demonstrate that Squama Manitis extract (SME)—a traditional Chinese medicine component—exhibits broad-spectrum bactericidal activity against clinically significant pathogens, including both Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) species (MIC = 31.25 mg/mL), achieving significant reduction in bacterial viability within 24 h. Through integrated multi-omics analysis combining scanning electron microscopy and RNA sequencing, we reveal SME’s unprecedented tripartite mechanism of action: (1) direct membrane disruption causing cell envelope collapse, (2) metabolic paralysis through coordinated suppression of TCA cycle and fatty acid degradation pathways, and (3) inhibition of DNA repair systems (SOS response and recombination downregulation). Despite its potent activity, SME shows low cytotoxicity toward mammalian cells (>90% viability) and can penetrate Gram-negative outer membranes. These features highlight SME’s potential to address drug-resistant infections through synthetic lethality across stress response, energy metabolism, and DNA integrity pathways. While advocating for synthetic alternatives to endangered animal products, this study establishes SME as a polypharmacological template for resistance-resilient antimicrobial design, demonstrating how traditional knowledge and modern systems biology can converge to guide sustainable anti-infective development. Full article

In recent decades, there has been a marked surge in the development of marine-by-product-derived ingredients for cosmetic applications, driven by the increasing demand for natural, sustainable, and high-performance formulations. Marine animal by-products, particularly those from fish, crustaceans, and mollusks, represent an abundant yet underutilized source of bioactive compounds with notable potential in cosmeceutical innovation. Generated as waste from the fishery and seafood-processing industries, these materials are rich in valuable bioactives, such as chitosan, collagen, peptides, amino acids, fatty acids, polar lipids, lipid-soluble vitamins, carotenoids, pigments, phenolics, and mineral-based substrates like hydroxyapatite. Marine by-product bioactives can be isolated via several extraction methods, and most importantly, green ones. These compounds exhibit a broad spectrum of skin-health-promoting effects, including antioxidant, anti-aging, anti-inflammatory, antitumor, anti-wrinkle, anti-hyperpigmentation, and wound-healing properties. Moreover, applications extend beyond skincare to include hair, nail, and oral care. The present review provides a comprehensive analysis of bioactives obtained from marine mollusks, crustaceans, and fish by-products, emphasizing modern extraction technologies with a focus on green and sustainable approaches. It further explores their mechanisms of action and documented efficacy in cosmetic formulations. Finally, the review outlines current limitations and offers future perspectives for the industrial valorization of marine by-products in functional and environmentally-conscious cosmetic development. Full article

Propionate is a short-chain fatty acid (SCFA) produced by gut microbiota through the fermentation of dietary fibers. Among the SCFAs, butyrate stands out and has been extensively studied for its beneficial effects; however, propionate has received less attention despite its relevant roles in immune modulation, metabolism, and mucosal homeostasis. This narrative review focuses on propionate’s effects on metabolism, inflammation, microbiota, and gastrointestinal diseases. Propionate acts as a signalling molecule through FFAR2/FFAR3 receptors and modulates immunity, energy metabolism, and gut–brain communication. It has beneficial effects in metabolic disorders, inflammatory bowel disease (IBD), and alcohol-related liver disease (ALD). However, excessive accumulation is linked to neurotoxicity, autism spectrum disorder (ASD), and mitochondrial dysfunction. Its effects are dose-dependent and tissue-specific, with both protective and harmful potentials depending on the context. Propionate use requires a personalized approach, considering the pathological context, host microbiota composition, and appropriate dosage to avoid adverse effects. Full article

There is a present need to develop alternative biotherapeutic drugs to mitigate the exacerbated inflammatory immune responses characteristic of sepsis. The potent endotoxin lipopolysaccharide (LPS), a major component of Gram-negative bacterial outer membrane, activates the immune system via Toll-like receptor 4 (TLR4), triggering macrophages and a persistent cascade of inflammatory mediators. Our previous studies have demonstrated that Fh15, a recombinant member of the Fasciola hepatica fatty acid binding protein family, can significantly increase the survival rate by suppressing many inflammatory mediators induced by LPS in a septic shock mouse model. Although Fh15 has been proposed as a TLR4 antagonist, the specific mechanisms underlying its immunomodulatory effect remained unclear. In the present study, we employed a quantitative proteomics approach using tandem mass tag (TMT) followed by LC-MS/MS analysis to identify and quantify differentially expressed proteins that participate in signaling pathways downstream TLR4 of macrophages, which can be dysregulated by Fh15. Data are available via ProteomeXchange with identifier PXD065520. Based on significant fold change (FC) cut-off of 1.5 and p-value ≤ 0.05 criteria, we focused our attention to 114 proteins that were upregulated by LPS and downregulated by Fh15. From these proteins, TNFα, IL-1α, Lck, NOS2, SOD2 and CD36 were selected for validation by Western blot on murine bone marrow-derived macrophages due to their relevant roles in the NF-κB, iNOS, oxidative stress, and phagosome signaling pathways, which are closely associated with sepsis pathogenesis. These results suggest that Fh15 exerts a broad spectrum of action by simultaneously targeting multiple downstream pathways activated by TLR4, thereby modulating various aspects of the inflammatory responses during sepsis. Full article

Transmembrane protein 43 (TMEM43 or LUMA) encodes a highly conserved protein found in the nuclear and endoplasmic reticulum membranes of many cell types and the intercalated discs and adherens junctions of cardiac myocytes. TMEM43 is involved in facilitating intra/extracellular signal transduction to the nucleus via the linker of the nucleoskeleton and cytoskeleton complex. Genetic mutations may result in reduced TMEM43 expression and altered TMEM43 protein cellular localization, resulting in impaired cell polarization, intracellular force transmission, and cell–cell connections. The p.S358L mutation causes arrhythmogenic right ventricular cardiomyopathy type-5 and is associated with increased absorption of lipids, fatty acids, and cholesterol in the mouse small intestine, which may promote fibro-fatty replacement of cardiac myocytes. Mutations (p.E85K and p.I91V) have been identified in patients with Emery–Dreifuss Muscular Dystrophy-related myopathies. Other mutations also lead to auditory neuropathy spectrum disorder-associated hearing loss and have a negative association with cancer progression and tumor cell survival. This review explores the pathogenesis of TMEM43 mutation-associated diseases in humans, highlighting animal and in vitro studies that describe the molecular details of disease processes and clinical, histologic, and molecular manifestations. Additionally, we discuss TMEM43 expression-related conditions and how each disease may progress to severe and life-threatening states. Full article

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by restricted social communication and repetitive behaviors. Prenatal stress is critical in neurodevelopment and increases risk for ASD, particularly in those with greater genetic susceptibility to stress. Docosahexaenoic acid (DHA) is one of the most abundant ω-3 fatty acids in the membrane phospholipids of the mammalian brain, and dietary DHA plays an important role in brain development and maintenance of brain structure. In this study, we investigated whether peri-natal supplementation of DHA can alleviate autistic-like behaviors in a genetic risk/stress mouse model and how it alters lipid peroxidation activity and GABAergic system gene expression in the forebrain. Pregnant heterozygous serotonin transporter knockout (SERT-KO) and wild-type (WT) dams were placed in either non-stressed control conditions or chronic variable stress (CVS) conditions and fed either a control diet or a DHA-rich (1% by weight) diet. Offspring of each group were assessed for anxiety and autism-associated behavior at post-natal day 60 using an open field test, elevated plus maze test, repetitive behavior, and the 3-chamber social approach test. A liquid chromatography-mass spectrometry (LC-MS)-based method was used to follow changes in levels of lipid peroxidation products in the cerebral cortex. Male offspring of prenatally stressed SERT-het KO dams exhibited decreased social preference behaviors and increased repetitive grooming behaviors compared to WT control offspring. Moreover, DHA supplementation in male SERT-het mice decreased frequency of grooming behaviors albeit showing no associated effects on social behaviors. Regardless of stress conditions, supplementation of DHA to the WT mice did not result in alterations in grooming nor social interaction in the offspring. Furthermore, no apparent changes were observed in the lipid peroxidation products comparing the stressed and non-stressed brains. Gad2 was downregulated in the cortex of female offspring of prenatally stressed SERT-KO dams, and this change appeared to be rescued by DHA supplementation in offspring. Gad2 was upregulated in the striatum of male offspring of prenatally stressed SERT-KO dams, but DHA did not significantly alter the expression compared to the control diet condition. Full article

Nuclear Magnetic Resonance (NMR) and Magnetic Resonance Imaging (MRI) are powerful techniques that have been employed to analyze foodstuffs comprehensively. These techniques offer in-depth information about the chemical composition, structure, and spatial distribution of components in a variety of food products. Quantitative NMR is widely applied for precise quantification of metabolites, authentication of food products, and monitoring of food quality. Low-field ¹H-NMR relaxometry is an important technique for investigating the most abundant components of intact foodstuffs based on relaxation times and amplitude of the NMR signals. In particular, information on water compartments, diffusion, and movement can be obtained by detecting proton signals because of H₂O in foodstuffs. Saffron adulterations with calendula, safflower, turmeric, sandalwood, and tartrazine have been analyzed using benchtop NMR, an alternative to the high-field NMR approach. The fraudulent addition of Robusta to Arabica coffee was investigated by ¹H-NMR Spectroscopy and the marker of Robusta coffee can be detected in the ¹H-NMR spectrum. MRI images can be a reliable tool for appreciating morphological differences in vegetables and fruits. In kiwifruit, the effects of water loss and the states of water were investigated using MRI. It provides informative images regarding the spin density distribution of water molecules and the relationship between water and cellular tissues. ¹H-NMR spectra of aqueous extract of kiwifruits affected by elephantiasis show a higher number of small oligosaccharides than healthy fruits do. One of the frauds that has been detected in the olive oil sector reflects the addition of hazelnut oils to olive oils. However, using the NMR methodology, it is possible to distinguish the two types of oils, since, in hazelnut oils, linolenic fatty chains and squalene are absent, which is also indicated by the ¹H-NMR spectrum. NMR has been applied to detect milk adulterations, such as bovine milk being spiked with known levels of whey, urea, synthetic urine, and synthetic milk. In particular, T2 relaxation time has been found to be significantly affected by adulteration as it increases with adulterant percentage. The ¹H spectrum of honey samples from two botanical species shows the presence of signals due to the specific markers of two botanical species. NMR generates large datasets due to the complexity of food matrices and, to deal with this, chemometrics (multivariate analysis) can be applied to monitor the changes in the constituents of foodstuffs, assess the self-life, and determine the effects of storage conditions. Multivariate analysis could help in managing and interpreting complex NMR data by reducing dimensionality and identifying patterns. NMR spectroscopy followed by multivariate analysis can be channelized for evaluating the nutritional profile of food products by quantifying vitamins, sugars, fatty acids, amino acids, and other nutrients. In this review, we summarize the importance of NMR spectroscopy in chemical profiling and quality assessment of food products employing magnetic resonance technologies and multivariate statistical analysis. Full article

Autism spectrum disorder (ASD) is a neurodevelopmental condition frequently associated with gastrointestinal symptoms, gut dysbiosis, and metabolic dysfunctions such as insulin resistance (IR). Recent evidence suggests that the gut microbiota may influence both metabolic and neurological processes through the gut–brain–metabolic axis. This review explores the molecular mechanisms linking dysbiosis, IR, and ASD, focusing on pathways such as TLR/NF-κB activation, PI3K/Akt/mTOR disruption, and the action of microbial metabolites, like short-chain fatty acids (SCFAs), lipopolysaccharide (LPS), and γ-aminobutyric acid (GABA). We discuss how dysbiosis may contribute to increased intestinal permeability, systemic inflammation, and neuroimmune activation, ultimately affecting brain development and behavior. Common microbial alterations in ASD and IR—including increased Clostridium, Desulfovibrio, and Alistipes, and reduced Bifidobacterium and butyrate-producing genera—suggest a shared pathophysiology. We also highlight potential therapeutic strategies, such as microbiota modulation, insulin-like growth factor 1 (IGF-1) treatment, and dietary interventions. Understanding these interconnected mechanisms may support the development of microbiota-targeted approaches for individuals with ASD metabolic comorbidities. Full article

Mitochondrial dysfunction is a key driver of neurological disorders due to the brain’s high energy demands and reliance on mitochondrial homeostasis. Despite advances in genetic characterization, the heterogeneity of mitochondrial diseases complicates diagnosis and treatment. Mitochondrial dysfunction spans a broad clinical spectrum, from early-onset encephalopathies to adult neurodegeneration, with phenotypic and genetic variability necessitating integrated models of mitochondrial neuropathology. Mutations in nuclear or mitochondrial DNA disrupt energy production, induce oxidative stress, impair mitophagy and biogenesis, and lead to neuronal degeneration and apoptosis. This narrative review provides a structured synthesis of current knowledge by classifying mitochondrial-related neurological disorders according to disrupted biochemical pathways, in order to clarify links between genetic mutations, metabolic impairments, and clinical phenotypes. More specifically, a pathway-oriented framework was adopted that organizes disorders based on the primary mitochondrial processes affected: oxidative phosphorylation (OXPHOS), pyruvate metabolism, fatty acid β-oxidation, amino acid metabolism, phospholipid remodeling, multi-system interactions, and neurodegeneration with brain iron accumulation. Genetic, clinical and molecular data were analyzed to elucidate shared and distinct pathophysiological features. A comprehensive table synthesizes genetic causes, inheritance patterns, and neurological manifestations across disorders. This approach offers a conceptual framework that connects molecular findings to clinical practice, supporting more precise diagnostic strategies and the development of targeted therapies. Advances in whole-exome sequencing, pharmacogenomic profiling, mitochondrial gene editing, metabolic reprogramming, and replacement therapy—promise individualized therapeutic approaches, although hurdles including heteroplasmy, tissue specificity, and delivery challenges must be overcome. Ongoing molecular research is essential for translating these advances into improved patient care and quality of life. Full article

This study investigated the treatment of unsterilized, undiluted, and unfiltered liquid digestate in a large-scale photobioreactor over a period of 33 weeks using a consortium of microalgae and bacteria. The generated biomass was analyzed for a wide spectrum of value-added compounds. The impact of organic loading rates (OLR) on the microbial culture was determined, and the influence of the biomass storage method on its qualitative composition was also analyzed. The experiment showed optimal growth of microalgae at OLR = 0.1 gCOD/L/day (where COD is Chemical Oxygen Demand), while a higher OLR value led to culture destabilization. Microglena sp., an algae not commonly applied for digestate treatment, showed low tolerance to changes in process conditions (OLR increase) but high readaptation potential when the OLR was lowered to its initial value. Significant changes in the microbial community were observed during the treatment. In Phases 1 and 2, Desmodesmus subspicatus and Actinomycetota phylum dominated in the community, while in Phase 3, Microglena sp. and Firmicutes were the most abundant. Total nitrogen, orthophosphates, and soluble COD were reduced by 89–99%. The biomass storage method had a notable impact on the content of lipids, fatty acids, and pigments. The protein amount was 32.75–33.59% of total solids (TS), while total lipid content was 15.76–19.00% TS, with stearic and palmitic acid being dominant. The effect of the storage regime on the potential biomass valorization was also discussed. Full article

Background/Objectives: Autism Spectrum Disorder (ASD) etiology is complex, involving genetics and environmental factors, and associated with impaired energy metabolism. Mitochondrial fatty acid oxidation (mFAO) is instrumental to energy production through the oxidation of acylcarnitines (ACs). We performed a comprehensive investigation of blood AC profiles in a pediatric ASD cohort, aiming to define ASD subgroups based on AC profiles and link these profiles to key clinical features and comorbidities using a phenotype-first approach. Methods: Blood levels of 31 ACs (μmol/L) collected from 102 ASD patients and 117 healthy controls (HCs) were evaluated via tandem mass spectrometry. The percentile distribution of blood AC levels in HC samples was computed to define the normal reference range (RR) and identify values corresponding to the 10th and 90th percentiles. Cognitive levels, emotional–behavioral disturbances and the severity of ASD symptoms (Autism Diagnostic Observation Schedule-Calibrated Severity Score ADOS-CSS) were assessed. Clinical correlates of ASD groups based on AC profiles were evaluated. Results: Three ASD subgroups were identified based on the percentile distribution of AC levels: group A (ACs < 10th percentile), group B (ACs 10th–90th percentile) and group C (ACs > 90th percentile) (abnormal AC number ≥ 3). Out of the thirty-one analyzed ACs in DBSs, fifteen (48.4%) were significantly different when comparing ASD group A to ASD group C. There was a significant difference in the severity of autism symptoms (ADOS CSS) related to the repetitive and restricted behaviors domain (CSS RRB) among the different groups (χ²(2) = 6.26; p = 0.044). The post hoc Dunn’s test with Bonferroni correction showed that ADOS-CSS RRB was significantly higher in ASD group A compared to ASD group B (p = 0.013). AC C14 was more frequently decreased (<10th pc) in patients with more severe symptoms (p = 0.006); C10:1 tended to be more frequently increased (>90th pc) in patients with lower clinical severity (p = 0.052). Conclusions: This study highlights differences across blood AC levels in children with ASD and conveys novel information on clinical severity in ASD patients with abnormal blood AC profiles. Thus, examining metabolic profiles may provide helpful insights to understand the variability of ASD symptoms. Full article

Fetal alcohol spectrum disorder (FASD) is a significant public health issue that affects children. It results from ethanol exposure during pregnancy, leading to considerable physical, neurodevelopmental, behavioral, and cognitive deficits. The exact mechanism is not well understood. Recently, considerable attention has been focused on the influence of gut microbiome on brain development through the gut–brain axis. Changes in the gut microbiome resulting from ethanol exposure may contribute to the pathology of FASD, potentially involving neuroinflammation. This literature review summarizes the existing research and primary animal studies on the impact of early ethanol exposure on the gut microbiome, neuroinflammation, brain development, and behavioral consequences. The evidence suggests that early ethanol exposure alters the gut microbiome, which may induce neuroinflammation, brain damage, and cognitive impairment. However, a clear causal relationship among these factors remains to be fully elucidated. Full article