Search Results (1,721)

Women of reproductive age, especially those with polycystic ovarian syndrome (PCOS), often use glucagon-like peptide-1 receptor agonists (GLP-1RAs) to improve their metabolic functions. A growing body of evidence suggests that GLP-1R signaling may directly affect ovarian physiology, influencing granulosa cell proliferation, survival pathways, and steroidogenic production, in addition to its systemic metabolic effects. Nonetheless, there is a limited comprehension of the molecular mechanisms that regulate these activities and their correlation with menstrual function, reproductive potential, and assisted reproduction. This comprehensive review focuses on ovarian biology, granulosa cell signaling networks, steroidogenesis, and translational fertility outcomes, integrating clinical, in vivo, and in vitro information to elucidate the effects of GLP-1 receptor agonists on reproductive health. We conducted a thorough search of PubMed, Scopus, and Web of Science for randomized trials, prospective studies, animal models, and cellular experiments evaluating the effects of GLP-1RA on reproductive or ovarian outcomes, in accordance with PRISMA criteria. The retrieved data included metabolic changes, androgen levels, monthly regularity, ovarian structure, granulosa cell growth and death, FOXO1 signaling, FSH-cAMP-BMP pathway activity, and fertility or IVF results. Clinical trials shown that GLP-1 receptor agonists improve menstrual regularity, decrease body weight and central adiposity, increase sex hormone-binding globulin levels, and lower free testosterone in overweight and obese women with PCOS. Liraglutide, when combined with metformin, significantly improved IVF pregnancy rates, whereas exenatide increased natural conception rates. Mechanistic studies demonstrate that GLP-1R activation affects FOXO1 phosphorylation, hence promoting granulosa cell proliferation and anti-apoptotic processes. Incretin signaling altered steroidogenesis by reducing the levels of StAR, P450scc, and 3β-HSD, so inhibiting FSH-induced progesterone synthesis, while simultaneously enhancing BMP-Smad signaling. Animal studies demonstrated both beneficial (enhanced follicular growth, anti-apoptotic effects) and detrimental results (oxidative stress, granulosa cell death, uterine inflammation), indicating a context- and dose-dependent response. GLP-1 receptor agonists influence female reproductive biology by altering overall physiological processes and specifically impacting the ovaries via FOXO1 regulation, steroidogenic enzyme expression, and BMP-mediated FSH signaling. Preliminary clinical data indicate improved reproductive function in PCOS, as seen by increased pregnancy rates in both natural and IVF cycles; nevertheless, animal studies reveal a potential risk of ovarian and endometrial damage. These results highlight the need for controlled human research to clarify reproductive safety, molecular pathways, and optimum therapy timing, particularly in non-PCOS patients and IVF settings. 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

Background and Objectives: This study was designed to evaluate the potential cardioprotective effect of Exenatide against doxorubicin (DOX)-induced myocardial injury in rats by assessing scintigraphic alterations together with oxidative stress and inflammation. Materials and Methods: This study included 28 adult male Wistar albino rats that were randomized to 4 groups (n = 7): control, Exenatide alone, DOX (receiving DOX (18 mg/kg, i.p) on days 5–7; Exenatide + DOX (treated with Exenatide together with the DOX). On day 8, ECG, 99mTc-PYP scintigraphy, and biochemical parameters were evaluated. Results: DOX caused ECG abnormalities—bradycardia, significant QT prolongation, and elevated ST-segment amplitude—along with increased myocardial PYP uptake. Exenatide + DOX group significantly improved ECG changes. Biochemically, DOX markedly increased cardiac injury biomarkers (cTnT, CK, CK-MB), hepatic and renal injury markers (ALT, AST, LDH, BUN, creatinine), SIRT-1 level, inflammatory marker (NF-κB, TNF-α, IL-6, NO) and oxidative stress indicators (MDA, TOS), while decreasing antioxidant defenses (GSH, TAS, Nrf2). Exenatide co-treatment significantly attenuated all DOX-induced changes. Conclusions: Exenatide markedly attenuates DOX-induced cardiotoxicity by improving electrical conduction, reducing myocardial radiotracer uptake, and restoring oxidative–inflammatory balance through partial recovery of the SIRT-1/Nrf2/NF-κB pathway. Full article

Objective: Advanced glycation end-products (AGEs) contribute to oxidative stress and inflammation, leading to various disorders, including skin inflammation. Here, we investigated the anti-inflammatory effects of Aloe vera flower (AVF) extract and its active constituents, vitexin (V) and isovitexin (IV), in a glyoxal-derived AGE (GO-AGE)-induced skin inflammaging model. Methods: We evaluated the effects of AVF, V, and IV in epidermal keratinocytes (HaCaT cells) using enzyme-linked immunosorbent assay, Western blotting, quantitative real-time polymerase chain reaction, and in silico molecular docking. Results: Treatment of HaCaT cells with AVF, V, or IV significantly suppressed the secretion and expression of interleukins (IL-6 and IL-8) at both the mRNA and protein level, and reduced the expression of key inflammatory proteins, including kappa-light-chain-enhancer of activated B cells (NF-κB) and cyclooxygenase-2 (COX-2), and phosphorylation of mitogen-activated protein kinase (MAPK) pathway proteins. Notably, the inhibitory effects of V and IV on COX-2 expression were more comparable to or exceeded those of the positive control (Epigallocatechin gallate), even at a lower concentration. Conversely, the expression of sirtuin 1 (SIRT1) was upregulated by AVF, V, and IV, with IV showing 1.5-fold upregulation. Molecular docking analyses supported these findings, with IV displaying a particularly high binding affinity for COX-2 (−11.0 kcal/mol). Conclusions: These findings highlight the potential of AVF, V, and IV as novel therapeutic agents for managing skin inflammaging by modulating inflammatory pathways. Full article

Background: Irisin, an exercise-induced myokine, has emerged as a potent neuroprotective factor, though a systematic synthesis of its role across neurological disorders is lacking. This review systematically evaluates clinical and preclinical evidence on irisin’s association with neurological diseases and its underlying mechanisms. Methods: Following PRISMA 2020 guidelines, a systematic search of PubMed/MEDLINE, Scopus, Web of Science, Embase, and Cochrane Library was conducted. The review protocol was prospectively registered in PROSPERO. Twenty-one studies were included, comprising predominantly preclinical evidence (n = 14), alongside clinical observational studies (n = 6), and a single randomized controlled trial (RCT) investigating irisin in cerebrovascular diseases, Parkinson’s disease (PD), Alzheimer’s disease (AD), and other neurological conditions. Eligible studies were original English-language research on irisin or FNDC5 and their neuroprotective effects, excluding reviews and studies without direct neuronal outcomes. Risk of bias was independently assessed using SYRCLE, the Newcastle–Ottawa Scale, and RoB 2, where disagreements between reviewers were resolved through discussion and consensus. Results were synthesized narratively, integrating mechanistic, pre-clinical, and clinical evidence to highlight consistent neuroprotective patterns of irisin across disease categories. Results: Clinical studies consistently demonstrated that reduced circulating irisin levels predict poorer outcomes. Lower serum irisin was associated with worse functional recovery and post-stroke depression after ischemic stroke, while decreased plasma irisin in PD correlated with greater motor severity, higher α-synuclein, and reduced dopamine uptake. In AD, cerebrospinal fluid irisin levels were significantly correlated with global cognitive efficiency and specific domain performance, and correlation analyses within studies suggested a closer association with amyloid-β pathology than with markers of general neurodegeneration. However, diagnostic accuracy metrics (e.g., AUC, sensitivity, specificity) for irisin as a standalone biomarker are not yet established. Preclinical findings revealed that irisin exerts neuroprotection through multiple mechanisms: modulating microglial polarization from pro-inflammatory M1 to anti-inflammatory M2 phenotype, suppressing NLRP3 inflammasome activation, enhancing autophagy, activating integrin αVβ5/AMPK/SIRT1 signaling, improving mitochondrial function, and reducing neuronal apoptosis. Irisin administration improved outcomes across models of stroke, PD, AD, postoperative cognitive dysfunction, and epilepsy. Conclusions: Irisin represents a critical mediator linking exercise to brain health, with consistent neuroprotective effects across diverse neurological conditions. Its dual ability to combat neuroinflammation and directly protect neurons, demonstrated in preclinical models, positions it as a promising therapeutic candidate for future investigation. Future research must prioritize the resolution of fundamental methodological challenges in irisin measurement, alongside investigating pharmacokinetics and sex-specific effects, to advance irisin toward rigorous clinical evaluation. Full article

Fibroblasts play a fundamental role in maintaining tissue architecture, regulating repair processes, and adapting to metabolic and inflammatory stress. Increasing evidence indicates that endogenous bioelectrical states contribute to gene expression regulation and cellular homeostasis. In this study, we investigated the effects of Radio Electric Asymmetric Conveyer (REAC) Metabolic Optimization–Inside Blue Zone (MO-IBZ) treatment on key regulators of stress response and metabolic control in human foreskin fibroblasts (HFF-1). Cells were exposed to nine standardized REAC MO-IBZ sessions, and changes in gene and protein expression were evaluated. Quantitative RT-PCR revealed a significant downregulation of SIRT1 and an upregulation of PPAR-γ expression in treated cells compared with untreated controls. These findings indicate molecular changes involving stress-responsive and metabolic regulatory pathways; however, they should be interpreted primarily as transcriptional signatures, as no direct functional stress-response or metabolic assays were performed. Immunofluorescence analysis showed visually increased expression of mTOR, IGF-1 receptor, and cytochrome c in REAC-treated fibroblasts, supporting a qualitative indication of activation of pathways associated with anabolic signaling, mitochondrial function, and metabolic efficiency. Taken together, these findings indicate that REAC MO-IBZ induces a coordinated molecular profile compatible with changes in cellular metabolic regulatory capacity. Within the framework of current bioelectrical literature, these changes may plausibly reflect broader regulatory adaptations; however, the present work does not provide direct measurements of bioelectrical parameters, functional metabolic activity, or epigenetic regulation, and therefore such interpretations remain speculative. These results provide descriptive mechanistic evidence supporting further investigation of REAC-based bioelectrical modulation as a potential strategy to influence cellular pathways involved in metabolic balance and tissue repair, encouraging future studies incorporating direct bioelectrical, epigenetic, and functional analyses. Full article

Metabolic reprogramming allows cancer cells to proliferate rapidly, survive nutrient limitation, and resist stress, making tumor metabolism an important therapeutic target. However, pharmacological inhibition of metabolic enzymes often causes systemic toxicity and compensatory pathway activation. To overcome these limitations, recent studies have highlighted an alternative host-centered strategy based on increasing systemic energy expenditure. Recent studies highlight an alternative strategy in which the host increases energy expenditure through uncoupling protein 1 (UCP1) dependent thermogenesis, thereby lowering systemic glucose, fatty acid, and nucleotide availability for tumors. Engineered beige adipocytes overexpressing UCP1, PR domain-containing protein 16 (PRDM16), or peroxisome proliferator–activated receptor gamma coactivator 1 alpha (PPARGC1A/PGC1A) suppress tumor growth through nutrient competition, suggesting that activating endogenous UCP1 may provide a non-genetic and physiologically aligned anticancer approach. Building on this concept, natural products such as polyphenols, terpenoids, alkaloids, and carotenoids have emerged as promising UCP1 activators that stimulate beige and brown adipocyte thermogenesis through pathways involving AMP-activated protein kinase (AMPK), sirtuin 1 (SIRT1), PGC1A, PRDM16, and mitochondrial biogenesis. In parallel, computational studies further indicate that several plant-derived compounds bind directly to the central cavity of UCP1 with high affinity, offering structural support for their thermogenic action. Importantly, many of these compounds also inhibit cancer cell intrinsic metabolism by reducing glycolysis, oxidative phosphorylation, lipid synthesis, and amino acid dependent anaplerosis. This review integrates UCP1 biology, natural product mediated thermogenesis, molecular docking evidence, and tumor metabolic suppression, proposing a unified framework in which natural compounds impose coordinated metabolic pressure on cancer through both adipocyte-driven nutrient competition and direct inhibition of tumor metabolism. Full article

Activation of microglia and resulting neuroinflammation are central processes that significantly contribute to neurodegenerative disease progression. Treatments capable of attenuating neuroinflammation are therefore an urgent medical need. Vitis vinifera L., cultivated since ancient times for its fruits, is known for its antioxidant and anti-inflammatory activities. However, polyphenols, the main bioactive molecules in V. vinifera extracts, exhibit considerable variability due to numerous hard-to-control factors, which complicates the production of standardized extracts with consistent biological activity. To address this issue, plant cell culture biotechnology was used to produce a highly standardized V. vinifera phytocomplex (VP), and its anti-neuroinflammatory profile was investigated in LPS-stimulated microglial cells, an in vitro model of neuroinflammation. VP reduced the LPS-induced pro-inflammatory phenotype, improved cell viability and cell number, attenuated NF-κB activation and ERK1/2 phosphorylation, and increased SIRT1 levels. To overcome VP’s poor water solubility, water-soluble cellulose nanocrystal (CNC)-based formulations were developed and tested. VP-CNC formulations markedly reduced the BV2 pro-inflammatory phenotype and increased cell viability under both basal and LPS-stimulated conditions. The nanoformulations also decreased pERK1/2 levels and increased SIRT1 expression, exhibiting biological activities comparable to VP alone. V. vinifera phytocomplex derived from plant cell cultures represents an innovative and standardized product with promising anti-neuroinflammatory properties. Full article

Atherosclerosis seriously endangers human health. Quercetin has drawn attention for its potential anti-atherosclerotic pharmacological effects. This study aimed to comprehensively assess quercetin’s effect and potential mechanism in treating atherosclerosis through a systematic review and meta-analysis. Preclinical studies published before 20 January 2025 were searched for in databases including PubMed, Embase, Web of Science, CNKI, Wanfang, and VIP. The CAMARADES list was used to assess the quality of the included studies. Stata 12 was applied for overall effect, sensitivity, subgroup, and publication bias analyses. Time–dose interval analyses were conducted to explore how quercetin dose and dosing cycle affect intervention effects. Finally, trial sequential analyses were performed using TSA 0.9 software. A total of 22 studies involving 421 animals were included, with a mean methodological quality score of 7.73/10. Meta-analysis showed that relative to the control group, quercetin reduced aortic plaque area, adjusted lipids (lowered TC, TG, and LDL-C and raised HDL-C), downregulated adhesion factors (e.g., VCAM-1) and pro-inflammatory factors (e.g., IL-1β and IL-6), upregulated anti-inflammatory factor IL-10 and antioxidant enzymes (SOD, CAT) while decreasing MDA content, and regulated atherosclerosis-related targets (e.g., LXRα, SIRT1, and mTOR). Subgroup analyses found model establishment time and quercetin administration time affected aortic lesion areas, TC, and TG. Time–dose analysis indicated quercetin had better ameliorative effects on atherosclerosis at 25–100 mg/kg with an 8–10-week intervention. Quercetin significantly improves atherosclerosis and inhibits its occurrence and progression through multiple pathways, such as regulating lipid metabolism, anti-inflammatory effects, and counteracting oxidative stress. Based on current evidence, quercetin is a potential therapeutic agent for treating atherosclerosis. Full article

Background: Sepsis-induced myocardial dysfunction (SIMD) is a life-threatening complication with limited therapeutic options. Jaceosidin (JAC), a natural flavonoid from Folium Artemisiae Argyi, shows potential in cardiovascular diseases, but its role and mechanism in SIMD remain unclear. This study aims to investigate the protective effects of JAC against SIMD and explore the underlying molecular mechanisms. Methods: In vitro, AC16 human cardiomyocytes were stimulated with TNF-α and treated with JAC. Cell viability and apoptosis were assessed using CCK−8 and flow cytometry, respectively. Transcriptomic and metabolomic analyses were performed to identify altered pathways. Molecular docking evaluated JAC’s interaction with SIRT2. The SIRT2 inhibitor AGK2 was used to validate its role. Chromatin immunoprecipitation quantitative PCR (ChIP-qPCR) determined H3K18la enrichment on target gene promoters. In vivo, a murine SIMD model was established via LPS injection, and cardiac function was evaluated by echocardiography. Serum markers (cTnT, CK−MB) and myocardial lactylation levels were measured. Results: JAC significantly attenuated TNF-α−induced injury in AC16 cells by enhancing viability and reducing apoptosis. Multi-omics analyses revealed JAC suppressed glycolysis and lactate production. JAC specifically inhibited histone H3K18 lactylation (H3K18la), and molecular docking indicated strong binding affinity with SIRT2. AGK2 treatment reversed JAC-mediated suppression of H3K18la. ChIP-qPCR confirmed H3K18la directly regulates IL-6, BAX, and BCL-2 expression. In vivo, JAC improved cardiac function (LVEF, LVFS, LVDd, LVDs), reduced serum cTnT and CK−MB levels, and decreased myocardial H3K18la in LPS−treated mice. Conclusions: JAC alleviates SIMD by activating SIRT2, which inhibits H3K18la, thereby modulating inflammatory and apoptotic pathways. This study identifies JAC as a novel metabolic-epigenetic therapeutic agent for SIMD. Full article

This study identified genomic regions associated with carcass traits and primal cut yields in Hanwoo cattle using weighted single-step genome-wide association study (WssGWAS). A total of 50,227 carcass records and genomic data from 23,573 animals with 45,057 single-nucleotide polymorphisms were analyzed. Heritability estimates were 0.24 for carcass weight, 0.22 for eye muscle area, 0.31 for backfat thickness, and 0.36 for marbling score, while those for primal cut yields ranged from 0.02 to 0.26. For carcass traits, candidate genes were identified for carcass weight (XKR4 2.35%, COBL 1.26%), eye muscle area (LCORL 1.56%, TGFBR2 1.49%), backfat thickness (ATG7 1.27%, MYPN 1.33%), and marbling score (TWIST2 1.16%, BMP4 1.14%). For primal cut yields, the chromosome 6 region containing WDR1 was commonly identified across six traits and the chromosome 4 region containing CACNA2D1 across five traits; the chromosome 28 region containing SIRT1 explained the highest genetic variance (6.46%) for striploin. These pleiotropic regions are potential targets for genomic selection to improve production efficiency and carcass value in Hanwoo. Full article

The microglia, first identified by Pío del Río-Hortega, are resident macrophages in the CNS that aid in immune monitoring, synaptic remodeling, and tissue repair. Microglial biology’s dual functions in maintaining homeostasis and contributing to neurodegeneration are examined in this review, with a focus on neurodegenerative disease treatment targets. Methods: We reviewed microglial research using single-cell transcriptomics, molecular genetics, and neuroimmunology to analyze heterogeneity and activation states beyond the M1/M2 paradigm. Results: Microglia maintains homeostasis through phagocytosis, trophic factor production, and synaptic pruning. They acquire activated morphologies in pathological conditions, releasing proinflammatory cytokines and reactive oxygen species via NF-κB, MAPK, and NLRP3 signaling. Single-cell investigations show TREM2 and APOE-expressing disease-associated microglia (DAM) in neurodegenerative lesions. Microglial senescence, mitochondrial failure, and chronic inflammation result from Nrf2/Keap1 redox pathway malfunction in ageing. Microglial interactions with astrocytes via IL-1α, TNF-α, and C1q result in neurotoxic or neuroprotective A2 astrocytes, demonstrating linked glial responses. Microglial inflammatory or reparative responses are influenced by epigenetic and metabolic reprogramming, such as regulation of PGC-1α, SIRT1, and glycolytic flux. Microglia are essential to neuroprotection and neurodegeneration. TREM2 agonists, NLRP3 inhibitors, and epigenetic modulators can treat chronic neuroinflammation and restore CNS homeostasis in neurodegenerative illnesses by targeting microglial signaling pathways. Full article

Growing evidence has revealed that gut dysbiosis is associated with the development of anxio-depressive disorders through mechanisms that involve neuroimmune signaling, neurotransmitter changes, and neuroplasticity in the brain. This study investigated the effects of gingerol-enriched ginger (GEG) on specifically anxiety-related neuroinflammation-, neuroimmunity-, neuroplasticity-, neurotransmission-, and neurotoxicity-associated genes in different brain regions, as well as on alterations linked to colonic microflora-driven dysbiosis, in the spinal nerve ligation (SNL) rat model of neuropathic pain (NP). Twenty-seven male rats were assigned to 3 groups: sham, SNL, and SNL-treated with GEG at 200 mg/kg body weight (SNL+200GEG) via oral gavage for 5 weeks. Anxiety-like behavior was assessed on the elevated plus maze (EPM). mRNA expression was assessed by qRT-PCR using respective primers. Correlation between behavioral parameters and colonic microbiome composition was analyzed using the Spearman rank correlation. The SNL+200GEG group demonstrated decreased anxiety-like behavior in the SNL model. Compared to the SNL group, the SNL+200GEG group had increased mRNA expression of NRF2 (amygdala: left), LXRα (amygdala: both sides), and CX3CR1 (amygdala: both sides, hippocampus: right). GEG modulated neuroplasticity as shown by increased gene expression of PGK1 (amygdala: right, hippocampus: both sides), MEK1 (frontal cortex: both sides), LDHA (frontal cortex: both sides), GPM6A (frontal cortex: both sides, amygdala: right, hippocampus: right, and hypothalamus), and GLUT1 (amygdala: right) as well by decreased gene expression of HIF1α (in all brain regions except for the hypothalamus). GEG modulated neurotransmission via clearance of excessive glutamate release as suggested by increased gene expression of SLC1A3 (frontal cortex: both sides, hippocampus: right) and via augmenting mGluR5 signaling as shown by increased gene expression of GRM5 (hippocampus: both sides, hypothalamus) as well as downregulation of KMO, HAAO, GRIN2B, and GRIN2C influencing downstream serotonergic neurotransmission and NMDA receptor-mediated glutamatergic pathways in different brain regions. GEG further alleviated neurotoxicity through downregulated gene expression of SIRT1, KMO, IDO1, and HAAO in different brain regions. Moreover, the increased relative abundance of Bilophila spp., accompanied by decreased time spent in the EPM open arms, suggests that increased Bilophila abundance increases anxiety-like behavior. GEG supplementation mitigated anxiety-like behavior in male rats with NP, at least in part, by reducing SNL-induced inflammatory sequelae-related mRNA gene expression in different brain regions. In addition, there is a positive correlation between the abundance of Bilophila wadsworthia and the degree of anxiety-like behavior. Full article

Ceramides are central to stratum corneum barrier organization and hydration. Beyond topical replenishment, ceramide-stimulating strategies increasingly aim to enhance endogenous ceramide biosynthesis, processing, and homeostatic remodeling in coordination with keratinocyte differentiation. In this review, we summarize the three major metabolic routes that shape epidermal ceramide output—de novo synthesis, salvage, and sphingomyelin hydrolysis—and organize representative bioactive ingredients by their primary molecular targets rather than by origin. Specifically, we map ingredients to tractable regulatory nodes, including transcriptional “liposensors” (PPAR/LXR), the induction of biosynthetic/elongation and processing enzymes (e.g., SPT, CerS3, ELOVL4), the provision of structural substrates and precursors (e.g., linoleate-rich lipids and glycosylceramides), salvage-pathway sphingoid bases that can reshape ceramide subclass output, and metabolic sensing/stress-response pathways centered on AMPK–mTOR–SIRT1/autophagy. Across these mechanisms, agents spanning botanical and fermented extracts, vitamins, sphingoid intermediates, lipid precursors, and pathway modulators (including autophagy-focused probes) have been reported to increase ceramide abundance and, in some contexts, favor barrier-relevant ultra-long-chain species and ω-O-acylceramides that support lamellar organization and the corneocyte lipid envelope. Translational and clinical studies in dry, sensitive, and aged skin generally associate such interventions with improved barrier function and reduced dryness. Aligning ingredient selection with defined biosynthetic and processing checkpoints—and verifying outcomes with lipidomics alongside clinical endpoints—may accelerate the development of evidence-based, ceramide-stimulating cosmetics. Full article

The objective of this study was to investigate the effects of replacing fishmeal with H. illucens larval meal on the colonic immune homeostasis in weaned piglets in enterotoxigenic Escherichia coli (ETEC)-challenged pig housing. Seventy-two weaned piglets, aged 28 days, were randomly divided into three groups for dietary treatment: the basal diet (negative control, NC), the positive control diet (PC) supplemented with 1445 mg zinc/kg zinc oxide in the basal diet, and the H. illucens larval meal complete replacement of fishmeal in the basal diet (HILM), for 28 days in ETEC-challenged pig housing. The results showed that the relative transcript abundances of ZO-1, pBD2, PR39, and PG1–5 were increased (p < 0.05) in pigs fed the HILM diet compared with those fed the NC diet. In addition, the HILM diet reduced (p < 0.05) the serum contents of IL-8 and increased (p < 0.05) the serum contents of IL-10 and IgG compared with the NC diet. In terms of the molecular mechanisms by which immune homeostasis is improved, the p-NF-κB/ NF-κB ratio and TLR2 protein expression in the colon were decreased (p < 0.05) in pigs fed the HILM diet compared with those fed the NC diet. Compared with the NC diet, the HILM diet reduced (p < 0.05) the protein expression of HDAC3 and HDAC7 in the colon of pigs. The SIRT1, acH3K9, and pH3S10 protein expressions in the colon were the greatest (p < 0.05) in pigs fed the HILM diet compared with the NC diet. HILM diets improved the colonic immune homeostasis in weaned piglets by enhancing the antimicrobial peptide expression, thereby mitigating ETEC challenges in pig housing. Mechanistically, HILM diets promote antimicrobial peptide expression through increased histone acetylation (acH3K9 and pH3S10). Full article