Search Results (2,722)

Brown adipose tissue (BAT) and beige adipocytes play a crucial role in adaptive thermogenesis, primarily via uncoupling protein 1 (UCP1)-driven heat production. Once considered physiologically irrelevant in adults, BAT is now recognized as an active tissue that contributes to energy expenditure and metabolic homeostasis and represents a potential therapeutic target for obesity and metabolic disorders. This review provides an integrated overview of the molecular regulation of thermogenic adipocytes, emphasizing both canonical UCP1-dependent as well as non-canonical UCP1-independent mechanisms of heat generation. Key transcriptional and epigenetic regulators are discussed in the context of mitochondrial biogenesis, substrate utilization, and thermogenic gene programs. Major upstream signaling routes are further summarized, encompassing classical β-adrenergic pathways, as well as alternative regulatory nodes including AMP-activated protein kinase (AMPK) and mechanistic target of rapamycin (mTOR) together with diverse nutrient- and hormone-responsive cues that converge to activate brown and beige adipocytes. Finally, the cross-talk among neuronal, endocrine, immune, and gut microbiota-derived signals is highlighted as a key determinant of thermogenic adipocyte function. Together, these multilayered regulatory inputs provide a comprehensive framework for understanding how thermogenic adipose tissue integrates environmental, metabolic, and microbial cues to regulate systemic energy balance—knowledge that is essential for developing targeted therapies to combat obesity and metabolic diseases. Full article

Berberine (BBR), a protoberberine alkaloid with a long history of medicinal use, has consistently demonstrated benefits in glucose–lipid metabolism and inflammatory balance across both preclinical and human studies. These diverse effects are not mediated by a single molecular target but by BBR’s capacity to restore network coordination among metabolic, immune, and microbial systems. At the core of this regulation is an AMP-activated Protein Kinase (AMPK)-centered mechanistic hub, integrating signals from insulin and nutrient sensing, Sirtuin 1/3 (SIRT1/3)-mediated mitochondrial adaptation, and inflammatory pathways such as nuclear Factor Kappa-light-chain-enhancer of Activated B cells (NF-κB) and NOD-, LRR- and Pyrin Domain-containing Protein 3 (NLRP3). This hub is dynamically regulated by system-level inputs from the gut, mitochondria, and epigenome, which in turn strengthen intestinal barrier function, reshape microbial and bile-acid metabolites, improve redox balance, and potentially reverse the epigenetic imprint of metabolic stress. These interactions propagate through multi-organ axes, linking the gut, liver, adipose, and vascular systems, thus aligning local metabolic adjustments with systemic homeostasis. Within this framework, BBR functions as a negentropic modulator, reducing metabolic entropy by fostering a coordinated balance among these interconnected systems, thereby restoring physiological order. Combination strategies, such as pairing BBR with metformin, Sodium-Glucose Cotransporter 2 (SGLT2) inhibitors, and agents targeting the microbiome or inflammation, have shown enhanced efficacy and substantial translational potential. Berberine ursodeoxycholate (HTD1801), an ionic-salt derivative of BBR currently in Phase III trials and directly compared with dapagliflozin, exemplifies the therapeutic promise of such approaches. Within the hub–axis paradigm, BBR emerges as a systems-level modulator that recouples energy, immune, and microbial circuits to drive multi-organ remodeling. Full article

Platycladus orientalis exhibits significant potential as an antioxidant, anti-inflammatory, and hair growth-promoting ingredient, while the low bioavailability of raw Platycladus orientalis leaves extracts limits their further application. In this study, yeast fermentation was employed to prepare Platycladus orientalis Leaves Yeast Fermented Solution (PYFS). Its performance on human dermal papilla cells (HDPCs) was systematically investigated. The optimal fermentation strain was screened using the methyl thiazolyl tetrazolium (MTT) assay, and Saccharomycopsis fibuligera RTNY119002 (SF) was identified as the most suitable strain for fermentation. The effects of PYFS on the cell cycle distribution, growth factors, inflammatory factors of HDPCs, as well as its hair growth-promoting mechanism, were investigated. Experiments revealed that after fermentation, the proportion of cells in the G0/G1 phase decreased by 11.09%, while the proportion of cells in the S phase increased by 35.44%. Additionally, the level of the growth factor VEGF increased by 42.34%, while the level of the inflammatory factor TGF-β1 decreased by 23.81%. Moreover, the fermentation process correlates with altered mRNA expression of Wnt/β-catenin pathway-related genes by upregulating the mRNA expression levels of β-catenin, DVL1, and LEF1, and downregulating the mRNA expression level of DKK-1. Finally, non-targeted metabolomics technology was used to analyze the metabolite changes after fermentation. The most significant differential metabolites mainly include flavonoids, amino acids and their derivatives, and organic acids and their derivatives. This study utilized microbial fermentation technology to prepare the yeast fermentation solution, selected the optimal fermentation strain, and demonstrated that its fermentation product significantly promotes HDPC metabolic activity, supports hair follicle health by regulating the balance of growth factors, alters expression patterns of Wnt/β-catenin pathway-related genes, and substantially alters the metabolite composition of Platycladus orientalis leaves extract through fermentation. Full article

Background/Objectives: Hepatocellular carcinoma (HCC) is one of the most common causes of cancer and cancer-related death worldwide. Beyond the well-known factors influencing the risk of HCC, experimental data from animal models and observational human studies support a significant role of the gut microbiota (GM) in HCC initiation and progression. Dysbiosis and increased intestinal permeability synergistically disrupt the ‘gut–liver axis,’ exposing the liver to bacterial metabolites and microbial-associated molecular patterns, thereby contributing to hepatocarcinogenesis. While these findings have expanded our understanding of HCC pathogenesis, a critical translational gap persists as most data derive from preclinical settings, with limited validation in large-scale clinical studies. Methods: This narrative review aimed to contextualise the current evidence on the GM-HCC axis and its clinical translatability. A literature search was conducted in PubMed/MEDLINE, Scopus, and Web of Science up to July 2025 using Medical Subject Headings and related keywords, including HCC, GM, dysbiosis, intestinal permeability, gut–liver axis, microbial metabolites, inflammation/immune modulation, and microbiota-targeted interventions (probiotics, antibiotics, and faecal microbiota transplantation). Reference lists of relevant articles were also screened to identify additional studies. Results: Preclinical models consistently indicate that dysbiosis and impaired gut barrier function can promote hepatic inflammation, immune dysregulation, and pro-tumorigenic signalling through microbe-derived products and metabolite perturbations, supporting a contributory role of the GM in hepatocarcinogenesis. In humans, HCC and advanced chronic liver disease are associated with altered microbial composition and function, increased markers of intestinal permeability, and changes in bile acid and other metabolite profiles; however, reported signatures are heterogeneous across cohorts and analytical platforms. Conclusions: The GM is a biologically plausible and experimentally supported contributor to HCC initiation and progression, with potential for biomarker development and therapeutic targeting. However, clinical translation is limited by predominantly preclinical/associative evidence, interindividual variability, and non-standardised microbiome methods. Large longitudinal studies and adequately powered randomised trials are needed to establish causality, validate biomarkers, and determine whether GM modulation improves HCC prevention, detection, stratification, or outcomes. Full article

Immunodeficiency presents a significant clinical challenge in contexts such as tumour radiotherapy, chemotherapy, and organ transplantation. Current therapeutic interventions are constrained by single-target approaches and substantial adverse effects. As natural bioactive compounds, the immunomodulatory activities of Lactobacillus exopolysaccharides (EPS) are intimately linked to their monosaccharide composition. Mannose and fucose, two rare functional monosaccharides, fulfil critical roles in physiological processes including immune recognition and inflammatory regulation. However, the functional optimisation of EPS through mannose and fucose enrichment remains incompletely characterised. This study established a cyclophosphamide (CTX)-induced immunodeficient mouse model to investigate the immunomodulatory effects of mannose-enriched and fucose-enriched EPS derived from Lactobacillus helveticus. Intervention efficacy was evaluated through a comprehensive assessment of immune organ indices, cytokine profiles, histopathological alterations, and gut microbiota composition. Both mannose-enriched and fucose-enriched EPS significantly elevated splenic indices and ameliorated white pulp atrophy. Furthermore, these EPS variants restored cytokine homeostasis in serum and small intestinal tissues, attenuated hepatic steatosis, and restructured the gut microbiota by enhancing microbial diversity, increasing Firmicutes abundance, and elevating the relative proportions of Bacteroides, Faecalibacterium, and Bifidobacterium. Collectively, mannose-enriched and fucose-enriched EPS from Lactobacillus helveticus alleviated CTX-induced immunodeficiency through multiple mechanisms, including restoration of immune organ integrity, modulation of cytokine networks, and re-establishment of gut microbiota homeostasis. This study provides a theoretical foundation for developing immunomodulatory functional foods and offers novel insights into the microbiota-immunity axis in immune regulation. Full article

Heat stress during summer significantly impairs seminal quality in swine production. As a key genetic resource for enhancing indigenous Chinese fatty pig breeds, Ningxiang boars require effective nutritional strategies to maintain reproductive performance under thermal challenge. This study aimed to investigate the effects of a combined antioxidant dietary supplement on seminal quality, antioxidant status, and gut microbiota in heat-stressed Ningxiang boars. Ten Ningxiang boars were randomly assigned to two groups (n = 5 per group). The control group received a basal diet, while the experimental group was fed the same basal diet supplemented with 400 mg/kg vitamin E, 5 g/kg yeast-derived zinc, 250 mg/kg yeast-derived selenium, and 800 mg/kg N-carbamylglutamate (NCG). Results demonstrated that sperm and seminal plasma superoxide dismutase (SOD) activity was significantly elevated in the supplemented group compared to the control (p < 0.05), whereas malondialdehyde (MDA) levels and total antioxidant capacity (T-AOC) did not differ significantly (p > 0.05). 16S rRNA gene sequencing revealed that dietary supplementation combined antioxidant markedly altered gut microbiota composition: the abundance of short-chain fatty acid-producing bacteria, particularly members of the Muribaculaceae family, increased significantly (p < 0.05), while opportunistic pathogens within the Acholeplasmataceae family were reduced (p < 0.05). These findings suggest that dietary supplementation with this antioxidant combination improves seminal quality in Ningxiang boars, potentially by enhancing endogenous antioxidant defenses and modulating gut microbial balance. Full article

Considering the challenges associated with implementing emerging technologies and bacterial-derived antimicrobial metabolites at an industrial scale in the meat industry, this comprehensive review investigates the interactions between lactic acid bacteria-producing antimicrobial metabolites and emerging food preservation technologies applied to meat systems. By integrating evidence from microbiology, food engineering, and molecular physiology, the review characterizes how metabolites-derived compounds exert inhibitory activity through pH modulation, membrane permeabilization, disruption of proton motive force, and interference with cell wall biosynthesis. These biochemical actions are evaluated in parallel with the mechanistic effects of high-pressure processing, pulsed electric fields, cold plasma, irradiation, pulsed light, ultrasound, ohmic heating and nanotechnology. Across the literature, consistent patterns of synergy emerge: many emerging technologies induce structural and metabolic vulnerabilities in microbial cells, thereby amplifying the efficacy of antimicrobial metabolites while enabling reductions in process intensity. The review consolidates these findings to elucidate multi-hurdle strategies capable of improving microbial safety, extending shelf life, and preserving the physicochemical integrity of meat products. Remaining challenges include optimizing combinational parameters, ensuring metabolite stability within complex matrices, and aligning integrated preservation strategies with regulatory and industrial constraints. Full article

Coffea, a plant species of significant agricultural value used in coffee production, is a key commodity that supports the livelihoods of millions of people worldwide. However, coffee cultivation faces substantial threats from various pathogens, including Pseudomonas coronafaciens pv. garcae (Pcg), the causative agent of bacterial blight. This pathogen compromises coffee plant health, leading to reduced yields and plant death and impacting farmers and large-scale producers. Understanding the mechanisms underlying resistance to Pcg in the leaves of the resistant IAC 2211-6 Coffea arabica accession is crucial for developing effective control strategies. This study aimed to identify candidate biomarkers of resistance by comparing the leaf metabolome of (i) the resistant IAC 2211-6 and the susceptible IAC 125 RN Coffea arabica accessions and (ii) Pcg-infected and uninfected leaves. Untargeted metabolomics revealed distinct metabolic profiles between accessions. Flavonoids were more abundant in susceptible leaves. In contrast, resistant leaves showed increased levels of pipecolic acid ethyl ester, a structural derivative of a key systemic acquired resistance signal, and spiropreussione B, a compound associated with fungal endophytes. These findings highlight candidates potentially linked to resistance and suggest that systemic signaling and beneficial microbial interactions may contribute to resilience. Full article

Microbial polysaccharides are promising components for wound-care products. This study reports the development of wound-healing antimicrobial hydrogels, based on pullulan from Aureobasidium pullulans, combined with mesenchymal cell-derived conditioned medium. Structural characterization of pullulan was confirmed by FTIR and NMR. Twenty-three formulations containing pullulan, chitosan, gelatin, citric acid, and antimicrobial agents were prepared. Physicochemical screening identified optimal hydrogels: No. 22 (1.2% pullulan, 1.2% chitosan, 0.2% citric acid, 2.4% gelatin, 0.1% conditioned medium, 0.4% glutaraldehyde) and No. 23 (2.4% pullulan, no chitosan, the remaining components identical to those in No. 22). Both exhibited pH values of 5.34 and 5.49, moisture content of 92%, swelling capacities of 175% and 213%, and dynamic viscosity between 58–120 mPa·s. Cytotoxicity testing with human mesenchymal stem cells showed no significant toxicity, with both hydrogels supporting cell adhesion and proliferation. Antimicrobial assays demonstrated inhibitory activity against Staphylococcus aureus and Escherichia coli for both formulations; only hydrogel No. 23 inhibited Pseudomonas aeruginosa. In vitro scratch assays revealed that hydrogel No. 23 significantly promoted fibroblast migration, achieving 30.25% scratch closure after 24 h. The developed formulations combine favorable physicochemical properties with antimicrobial efficacy and regenerative potential, supporting further evaluation as advanced wound-healing and anti-burn dressings. Full article

Background: Gut barrier dysfunction and altered gut microbial metabolism are emerging signatures of chronic gut disorders. Considering growing interest in combining structurally and mechanistically distinct bioactives, we investigated the individual and combined effects of serum-derived bovine immunoglobulin (SBI) and N-acetylglucosamine (NAG) on the gut microbiome and barrier integrity. Methods: The validated ex vivo SIFR^® (Systemic Intestinal Fermentation Research) technology, using microbiota from healthy adults (n = 6), was combined with a co-culture of epithelial/immune (Caco-2/THP-1) cells. Results: While SBI and NAG already significantly improved gut barrier integrity (TEER, transepithelial electrical resistance, +21% and +29%, respectively), the strongest effect was observed for SBI_NAG (+36%). This potent combined effect related to the observation that SBI and NAG each induced distinct, complementary shifts in microbial composition and metabolite output. SBI most selectively increased propionate (~Bacteroidota families) and health-associated indole derivatives (e.g., indole-3-propionic acid), while NAG most specifically boosted acetate and butyrate (~Bifidobacteriaceae, Ruminococcaceae, and Lachnospiraceae). The combination of SBI_NAG displayed effects of the individual ingredients, thus, for instance, enhancing all three short-chain fatty acids (SCFA) and elevating microbial diversity (CMS, community modulation score). Conclusions: Overall, SBI and NAG exert complementary, metabolically balanced effects on the gut microbiota, supporting combined use, particularly in individuals with gut barrier impairment or dysbiosis linked to lifestyle or early-stage gastrointestinal disorders. Full article

Microorganisms have emerged as prolific and versatile producers of steroidal natural products, displaying a remarkable capacity for structural diversification that extends far beyond classical sterol frameworks. This review critically examines steroidal metabolites isolated from microbial sources, with a particular emphasis on marine-derived and endophytic fungi belonging to the genera Aspergillus and Penicillium, alongside selected bacterial and lesser-studied fungal taxa. Comparative analysis reveals that these organisms repeatedly generate distinctive steroid scaffolds, including highly oxygenated ergostanes, secosteroids, rearranged polycyclic systems, and hybrid architectures arising from oxidative cleavage, cyclization, and Diels–Alder-type transformations. While many reported compounds exhibit cytotoxic, anti-inflammatory, antimicrobial, or enzyme-inhibitory activities, the biological relevance of these metabolites varies considerably, highlighting the need to distinguish broadly recurring bioactivities from isolated or strain-specific observations. By integrating structural classification with biosynthetic considerations and bioactivity trends, this review identifies key steroidal frameworks that recur across taxa and appear particularly promising for further pharmacological investigation. In addition, current gaps in mechanistic understanding and compound prioritization are discussed. Finally, emerging strategies such as genome mining, biosynthetic gene cluster analysis, co-culture approaches, and synthetic biology are highlighted as powerful tools to unlock the largely untapped potential of microbial genomes for the discovery of novel steroidal scaffolds. Together, this synthesis underscores the importance of microorganisms as a dynamic and expandable source of structurally unique and biologically relevant steroids, and provides a framework to guide future discovery-driven and mechanism-oriented research in the field. Full article

Microbial lipid production from renewable carbon sources, particularly lignocellulosic hydrolysates, is a promising alternative to plant-derived oils and fats for food applications, as it can minimize the land use by utilizing agricultural wastes and byproducts from food production. In this context, a standard approach to prevent oxygen limitation at reduced air gassing rates during long-term aerobic microbial processes is to operate bioreactors at increased pressure for elevating the gas solubility in the fermentation broth. This study investigates the effect of absolute pressures of up to 2.5 bar on the conversion of the carbon sources (glucose, xylose, and acetate), growth, and lipid biosynthesis by Cutaneotrichosporon oleaginosus converting a synthetic nutrient-rich lignocellulosic hydrolysate at low air gassing rates of 0.1 vessel volume per minute (vvm). Increasing pressure delayed xylose uptake, reduced acetic acid consumption, and reduced biomass formation. Lipid accumulation decreased with increasing pressure, except for fermentations at 1.5 bar, which achieved a maximum lipid content of 83.6% (±1.6, w/w) (weight per weight in %). At an absolute pressure of 1.5 bar, a lipid yield from glucose, xylose, and acetic acid of 38% (w/w) was reached after 6 days of fermentation. The pressure sensitivity of C. oleaginosus may pose challenges on an industrial scale due to the dynamic changes in pressure when the yeast cells pass through the bioreactor. Increasing liquid heights in full-scale bioreactors will result in increased hydrostatic pressures at the bottom, substantially reducing lipid yields, e.g., to only 23% (w/w) at 2.0–2.5 bar, as shown in this study. However, further scale-up studies with dynamic pressure regimes (1–2.5 bar) may help to evaluate scale-up feasibility. Full article

Marine invertebrates are a prime source of biologically active peptides due to their role in humoral immunity. These peptides typically exhibit broad-spectrum functions, including antibacterial, antifungal, anticancer, and immunomodulatory activities. In this report, we describe the identification and biological characterization of five novel bioactive peptides from the marine mollusk Pisania pusio. An extract of P. pusio was analyzed using nanoLC-ESI-MS-MS, and five peptides (PP1–5) were selected via bioinformatic screening as potential antimicrobial and anticancer peptides and subsequently validated experimentally. Among these, PP1, PP2, and PP4 were identified as cryptides derived from the proteolytic cleavage of actin, while PP3 and PP5 are novel peptides with no known protein precursors. All peptides exhibited moderate activity against Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, and Klebsiella pneumoniae with minimum inhibitory concentrations (MICs) predominantly at 100 µM. In contrast, only PP1 and PP5 were active against cancer cells, with PP1 being the most effective against A375 melanoma cells (IC₅₀ = 17.08 µM). This experimental validation confirmed the utility of the integrated in silico/peptidomic pipeline for lead identification. None of these peptides showed significant hemolytic activity or toxicity on fetal lung fibroblasts over 800 μM, demonstrating promising in vitro selectivity. These results highlight the multifunctional nature of P. pusio-derived peptides and their potential as lead compounds for further optimization and development into therapeutic agents against microbial infections and cancer, subject to more comprehensive safety evaluations in relevant models Full article

In precision agriculture, the delineation of Management Zones (MZs) is essential for optimizing input use efficiency and site-specific nutrient management. MZs are established based on spatial variability derived from remote sensing data—such as Normalized Difference Vegetation Index (NDVI) from satellite or UAV-based imagery—and yield maps collected during harvest. However, the microbial community composition of the soil is often overlooked in MZ delineation. To address this gap, we investigated the soil bacterial community structure across different MZs in an arable field. The zones were delineated using NDVI data, soil profiles were described, and bulk soil samples were collected. Soil physicochemical parameters were analyzed in parallel with 16S rRNA gene amplicon sequencing to characterize bacterial community composition and diversity. The results demonstrated that soil texture and soil organic matter content were the primary drivers influencing bacterial community structure across the field. Moreover, patterns in microbial composition aligned closely with MZ delineations, indicating that microbial profiles could aid in better understanding and supporting the nutrient management practices. Our findings suggest that soil microbiological data can enhance the stability and biological relevance of MZ definitions, thereby improving resource allocation, soil health management, and overall sustainability in precision farming systems. Full article

Gut microbial community assembly involves a critical bioenergetic trade-off, yet the gut microbes with roles in influencing intestinal metabolic homeostasis remain poorly understood in pelagic ecosystems. A central unresolved question is whether microbiome structure is primarily governed by stochastic geographic drift or by deterministic metabolic filters imposed by diet. Here, we test the metabolic release hypothesis, which posits that access to high-quality prey physiologically “releases” the host from obligate dependence on diverse fermentative symbionts. By integrating δ15N analysis with 16S rRNA metabarcoding in the anchoveta from the South Pacific waters (Engraulis ringens), we reveal a profound, diet-induced restructuring of the gut ecosystem. We demonstrate that trophic ascent triggers a deterministic collapse in microbial alpha diversity (rs = −0.683), driven by the near-complete competitive exclusion of fermentative bacteria (rs = −0.874) and the resulting dominance of a specialized proteolytic core. Mechanistically, the bioavailability of zooplankton-derived protein favors efficient endogenous hydrolysis over costly microbial fermentation, rendering functional redundancy obsolete. Crucially, we find that while metabolic function converges, taxonomic identity remains geographically structured (r = 0.532), suggesting that local environments supply the specific taxa to fulfill universal metabolic roles. These findings establish a link between δ15N as a nutritional physiology proxy of anchoveta and its gut for microbial functional state, bridging the gap between nutritional physiology and ecosystem modeling to better inform the management of global forage fish stocks. Full article