Search Results (2,865)

This study evaluated olive leaf extract (OLE) as a multifunctional dermocosmetic candidate for sebum-related and inflammatory responses relevant to oily and acne-prone skin using an axis-aligned in vitro panel: (i) sebocyte lipogenesis, (ii) inflammatory mediator production in keratinocytes, and (iii) fibroblast-mediated collagen gel contraction. In addition, supportive mechanistic evidence for the sebum-related effects of OLE was obtained by examining signaling proteins associated with sebocyte lipogenesis, including PPAR-γ and SREBP-1. As a result, OLE significantly inhibited linoleic acid-induced lipid accumulation in SEB-1 sebocytes without cytotoxicity. In HaCaT keratinocytes, OLE significantly reduced the production of pro-inflammatory cytokines, including IL-8, TNF-α, and PGE₂, induced by Cutibacterium acnes or UVB. In dermal fibroblast-containing collagen gels, OLE enhanced fibroblast-mediated gel contraction. Additionally, analysis of the main mechanisms of lipid inhibition using SEB-1 sebocytes revealed that OLE exerts a dual regulatory role in lipid synthesis and inflammation by downregulating AKT and ERK phosphorylation and inhibiting PPAR-γ and SREBP-1 expression. Furthermore, among the tested extracts, the 70% ethanol extract (OLE70) exhibited the strongest antioxidant activity, the greatest gel contraction response, and the highest content of oleuropein, a major bioactive phenolic compound derived from olive. Like OLE, oleuropein also showed sebum-regulatory activity by reducing lipid accumulation in SEB-1 sebocytes, an inhibitory effect on IL-8 expression in HaCaT keratinocytes, and an inhibitory effect on the expression of PPAR-γ and SREBP-1, which are involved in sebum secretion. Taken together, these findings suggest that OLE and its major phenolic constituent, oleuropein, may modulate sebum-related, inflammatory, oxidative, and dermal remodeling-associated responses in skin cell models. These results should be interpreted as exploratory and provide a basis for further mechanistic and translational investigation. Full article

Peptide therapeutics have emerged as a versatile class of biomolecules bridging the gap between small-molecule drugs and large biologics. Advantages of such molecules include high target specificity, potent bioactivity and reduced off-target toxicity. Despite these, broader clinical translation remains constrained by inherent limitations like poor metabolic stability, rapid renal clearance, limited membrane permeability and scalable synthesis. This review aims to systematically integrate advances in peptide science across natural discovery, synthetic methodologies, structural engineering, and translational delivery systems, while identifying critical research gaps hindering clinical adoption. We highlight diverse natural sources of bioactive peptides, including plant- (lunasin), animal- (Val-Pro-Pro (VPP) and Ile-Pro-Pro (IPP)), microbial- (nisin and cyclosporine), marine- (dolastatins) and venom-derived (chlorotoxin and ω-conotoxin MVIIA (ziconotide)) agents. Advances in solid-phase peptide synthesis (SPPS), green chemistry, and catalytic strategies are discussed alongside emerging in silico approaches, including artificial intelligence-driven sequence design and molecular modeling. Structural modifications such as cyclization, hydrocarbon stapling, PEGylation, and lipidation are critically evaluated for their role in enhancing pharmacokinetic and pharmacodynamic properties. Furthermore, nanoformulation strategies, including self-assembling peptides and cell-penetrating systems, are examined for their potential to overcome biological barriers. Importantly, this review identifies key unresolved challenges, including the lack of predictive models for peptide delivery systems, safety concerns associated with long-term modifications, and limited in vivo validation of naturally derived peptides. Addressing these gaps through integrated computational and experimental approaches will be essential for advancing next-generation peptide therapeutics. Collectively, this work provides a comprehensive framework for the rational design and translation of peptide-based precision medicines. Full article

In this paper, we review the literature regarding metformin’s action on blood lipid concentrations in metformin-treated diabetic patients. Published data indicate that metformin reduces serum total cholesterol (T-C), LDL-cholesterol (LDL-C) and triacylglycerol (TAG) concentrations and raises serum HDL-cholesterol (HDL-C) concentrations in diabetic patients. The beneficial effect of metformin on serum lipid profiles in diabetic patients can result from (a) its action on AMP-activated protein kinase, which inhibits lipogenesis and cholesterol synthesis and stimulates fatty acid oxidation; (b) decreased plasma TAG concentrations, via promoting VLDL-TAG clearance by brown adipose tissue; (c) the inhibition of nuclear factor erythroid 2-related factor 2 (Nrf2) gene expression, affecting lipid profile in diabetic patients; (d) the inhibition of the expression of genes encoding proprotein convertase subtilisin/kexin 9 (PCSK9) and lipogenic enzymes; (e) the downregulation of carbohydrate-response element-binding protein (ChREBP), which affects liver TAG and cholesterol synthesis from acetate formed by gut microbiota; (f) the inhibition of angiopoietin-like 3 protein (ANGPTL3) gene expression, and consequent effects on plasma TAG concentrations; (g) the activation of AMPK, which inhibits LXRα activity; and (h) reverse cholesterol transport. In conclusion, one can assume that beyond its primary antihyperglycemic effect, metformin exerts pleiotropic effects that modulate lipid metabolism and blood lipid profile in T2D patients. These beneficial effects of metformin on blood lipid profile may play a role in the reduction in cardiovascular risk in diabetic patients. Full article

Background/Objectives: Sebocytes, the primary cell type in sebaceous glands (SGs), produce a lipid mixture called sebum that is released onto the skin surface and is required for skin homeostasis. The lipid receptor Peroxisome Proliferator-Activated Receptor gamma (PPARγ) regulates sebocyte proliferation and lipid synthesis and is involved in acne development. As inhibition of PPARγ has been shown to reduce insulin-induced lipogenesis and Akt/mTOR signalling in SZ95 sebocytes, we here investigated the effects of PPARγ deletion on lipid homeostasis and autophagic stress responses and how the secretomes affect dermal fibroblasts. Methods: SZ95 sebocytes wildtype (WT) and PPARγ knockout (KO) were shifted to low serum and EGF-deficient conditions permissive for autophagy. Untargeted and targeted HPLC-MS/MS analyses were used to analyze native and oxidized lipids, respectively. Protein levels of LC3I/II and p62 were assessed using immunoblots and immunofluorescence microscopy to investigate the autophagic flux. Dermal fibroblasts were exposed to conditioned media. Results: In low serum culture media, KO SZ95 sebocytes displayed significantly altered levels of 23 lipid classes. We observed a significant increase in ether-linked fatty acids as components of complex lipids and detected elevated levels of phospholipid hydroperoxides and aldehydolipids in the KO sebocytes. KO SZ95 sebocytes failed to show the typical responses to lipoxidative stress, such as elevated p62 crosslinking or inclusion body formation, and had reduced LC3II/I ratios as compared to WT cells. PPARγ KO conditioned media promoted a trend towards an inflammatory fibroblast phenotype. Conclusions: These findings suggest that PPARγ in sebocytes may alter the lipidome, elevate redox stress, and affect the autophagic machinery, which could cause accumulation of oxidized lipids and other potentially harmful compounds in sebocytes. Full article

The liver circadian clock coordinates hepatic lipid metabolism, bile acid synthesis, and glucose homeostasis through interlocking transcription–translation feedback loops. Disruption of this temporal organization is increasingly recognized as a shared pathological feature across the chronic liver disease spectrum. Transcriptomic profiling alone cannot capture the full scope of circadian dysregulation. Approximately half of rhythmically abundant hepatic proteins lack correspondingly rhythmic mRNAs. Roughly 25% of hepatic phosphosites oscillate with a 24-h period. Integrating transcriptomics, proteomics, post-translational modification profiling, metabolomics, and emerging single-cell and spatial approaches is therefore necessary for an accurate account of how circadian programs are remodeled in disease. This narrative review delineates the multi-omics landscape of circadian clock dysregulation across six chronic liver disease categories. These encompass metabolic dysfunction-associated fatty liver disease (MAFLD), alcoholic liver disease (ALD), viral hepatitis, hepatocellular carcinoma (HCC), liver fibrosis, and cholestatic disease. Four molecular features recur across these contexts. BMAL1 functional downregulation, REV-ERBα oscillatory output attenuation, NAD⁺ oscillatory amplitude reduction, and gut–liver axis circadian desynchronization together constitute an inferential framework for hepatic circadian failure. These features represent recurring disease-associated motifs rather than an established pan-disease mechanism. The upstream mechanisms and evidence depth differ substantially by disease category. Oncogenic kinase-driven CLOCK post-translational modifications in HCC, phosphoproteomic remodeling in MAFLD, and epigenomic clock disruption persisting after HCV clearance represent findings that transcriptomics alone would not resolve. The near-complete absence of temporally resolved human tissue data remains the principal barrier to translational progress. This evidence gap limits the clinical actionability of current mechanistic findings across all disease categories. Circadian phase inference algorithms and prospective temporally designed cohort studies offer a methodologically grounded path toward clinically actionable circadian hepatology. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) has replaced older exclusion-based terminology as the preferred term for steatotic liver disease associated with cardiometabolic risk factors. MASLD is now among the most common causes of chronic liver disease and may progress from simple steatosis to metabolic dysfunction-associated steatohepatitis (MASH), fibrosis, cirrhosis, and hepatocellular carcinoma. This updated rigorous narrative review synthesizes current evidence on MASLD diagnosis and management, with emphasis on the gut–liver axis and the therapeutic potential of combining probiotics with metformin. A structured narrative search was conducted in PubMed, PMC, ScienceDirect, Taylor & Francis, Cochrane Library, and Google Scholar using the keywords “MASLD”, “MAFLD”, “NAFLD”, “MASH”, “probiotics”, “synbiotics”, “metformin”, and “gut-liver axis”. The review was designed as a narrative synthesis rather than a systematic review. Current guidance supports stepwise risk stratification using serum fibrosis scores followed by elastography or advanced imaging when indicated. Ultrasonography remains accessible but has limited sensitivity for mild steatosis, is operator-dependent, and is not sufficient for comprehensive assessment of fibrosis or disease activity. Metformin is appropriate for type 2 diabetes mellitus and improves insulin resistance, but current guidelines do not recommend it as a targeted treatment for MASH because histological benefit has not been consistently demonstrated. Probiotics and synbiotics may improve aminotransferases, inflammatory markers, lipid parameters, intestinal barrier function, and gut dysbiosis; however, findings vary by strain, formulation, dose, treatment duration, population, and endpoint. The combination of probiotics and metformin is mechanistically plausible because it targets both metabolic dysfunction and intestinal dysbiosis, but human evidence remains limited. Larger, strain-specific, adequately powered trials using standardized MASLD criteria and clinically meaningful endpoints are required before routine clinical recommendations. Full article

Females with iron overload suffer from follicular dysplasia, and effective therapeutic strategies for preserving fertility remain lacking. As a natural aliphatic polyamine, spermidine exerts antioxidant activity and plays an anti-ferroptosis role in the pathogenesis of various diseases. However, the role and underlying mechanism of spermidine in iron overload-induced ovarian ferroptosis remain largely elusive. This study aimed to investigate the therapeutic potential of spermidine against iron overload-induced ferroptosis in ovarian granulosa cells and elucidate its molecular mechanism. As a result, iron overload models were established in female mice (in vivo, ferrous sulfate) and porcine ovarian granulosa cells (in vitro, ferric ammonium citrate), with spermidine administered at 3 mM (in vivo) or 150 μM (in vitro). Ferritin heavy chain (FHC) and solute carrier family 7 member 11 (SLC7A11) silencing were performed via siRNA transfection, and relevant controls were set. In vivo studies showed that spermidine elevated serum estradiol and progesterone levels, enhanced ovarian catalase (CAT) and superoxide dismutase (SOD) activities, improved granulosa cell mitochondrial morphology, and increased estrous cycle regularity from 35.6% (high-iron group) to 63.1%. In vitro, spermidine improved ferric ammonium citrate (FAC)-impaired cell viability; attenuated reactive oxygen species (ROS) accumulation; upregulated FHC, Nrf2/p-Nrf2/GPX4, SLC7A11 and anti-müllerian hormone (AMH) expression; and inhibited excessive autophagy (decreased LC3BII/I ratio). Mechanistically, spermidine activated AKT-mediated autophagy, modulated iron homeostasis and glutathione (GSH) synthesis via FHC, alleviated ferroptosis-related Nrf2/p-Nrf2/HO-1 pathway overactivation, reduced lipid peroxidation and DNA damage, and restored mitochondrial function. SLC7A11 silencing disrupted glutathione metabolism, induced mitochondrial ROS accumulation, and inhibited autophagy. Proteomic analysis identified microsomal glutathione S-transferase 3 (MGST3) as a potential key downstream target of spermidine in suppressing SLC7A11-mediated ferroptosis. This study reveals a novel therapeutic strategy wherein spermidine protects against ovarian ferroptosis and preserves ovarian function by regulating iron homeostasis through the FHC/SLC7A11 axis. Full article

The discovery of melatonin as a multifunctional free radical scavenger and its possible synthesis in the mitochondrial matrix of peripheral eukaryotic somatic cells highlights a critical new perspective on the importance of this indole. Experimental evidence supporting these findings is substantial, but there are still lingering questions whether melatonin is a direct radical scavenger in vivo and whether it is synthesized in the mitochondrial matrix. We systematically analyze the innovative experimental approaches that support melatonin’s radical scavenging actions and assess the compelling data supporting its production in mitochondria. Melatonin concentrations are reportedly higher in this organelle than in other cellular compartments. Proteins for the enzymes required to convert serotonin to melatonin are present in the mitochondrial matrix and purified mitochondria synthesize melatonin. In the mitochondrial matrix, melatonin is likely located within the “damage radius” of highly reactive oxygen species. We also summarize novel actions of melatonin associated with its regulation of membrane fluidity, determine the molecular composition of membrane lipid rafts, and modulate liquid–liquid phase separation and biomolecular condensates intracellularly. If the findings discussed herein continue to be validated, melatonin would be in an optimal position to function as an antioxidant and may be a key driver in the context of preserving mitochondrial redox homeostasis and disease mitigation. Full article

Laser therapy is commonly associated with transient skin reactions such as erythema and edema, creating a need for effective post-procedural skincare strategies. In this study, we developed and characterized a novel bio-mask that integrates a hydrogel matrix with a lipid nanodispersion system designed to simultaneously deliver hydrophilic and hydrophobic active compounds. The key innovation of this formulation lies in the combination of a highly hydrophilic hydrogel structure with lipid nanoparticles embedded within a polymeric network, enabling enhanced bioavailability of active ingredients. Preliminary observations from instrumental measurements in a small group of healthy volunteers suggest that a single 60 min application resulted in notable improvements in skin hydration and elasticity, along with a reduction in transepidermal water loss (TEWL), erythema, and skin sensitivity. Furthermore, both the complete formulation and its individual components exhibited inhibitory activity against collagen and elastin glycation, while promoting type I procollagen synthesis. Importantly, this study provides new evidence for the synergistic interaction between hydrogel matrices and lipid nanodispersion systems in modulating skin barrier function and biochemical aging markers. The formulation, composed entirely of ingredients of natural origin, proved to be an effective carrier for active compounds and showed measurable benefits for skin hydration and barrier-related parameters. Full article

Neural tube defects (NTD) are congenital malformations that lead to structural abnormalities of the brain or spine. Mouse embryos deficient in Scavenger Receptor Class B Type 1 (SR-B1 KO), the main receptor for high-density lipoproteins, exhibit a high incidence of anterior NTD, which is associated with vitamin E deficiency and elevated levels of reactive oxygen species (ROS). Maternal supplementation with vitamin E, a micronutrient with antioxidant properties, completely prevents the occurrence of NTD and normalizes ROS levels in SR-B1 KO embryos, suggesting a contribution of oxidative stress to NTD in this model. In this work, we showed that SR-B1 KO embryos at gestational day E9.5 display higher levels of lipoperoxidative damage markers. Analysis of data obtained through shotgun lipidomics evidenced a selective and coordinated reorganization of fatty acid distribution, characterized by altered polyunsaturated and monounsaturated composition, together with reduced phosphatidylcholine and increased lysophosphatidylcholine levels, and diversion of fatty acids into triacylglyceride storage. Transcriptomic analysis revealed a coordinated upregulation of genes involved in phospholipid synthesis and remodeling, consistent with the altered lipid homeostasis observed in SR-B1 KO embryos. Together, these results provide novel information showing a potential link between oxidative stress and disruptions in mammalian embryonic lipid metabolism, highlighting phospholipid remodeling as a potential determinant of susceptibility to NTD. Full article

Previous studies have demonstrated that phloretic acid (PA), a phenolic compound, exerts beneficial effects on inflammation, oxidative stress, and aging. However, its effects on obesity and associated metabolic abnormalities, including dyslipidemia and metabolic dysfunction-associated steatotic liver disease (MASLD), remain unclear. To evaluate the effects of PA on these obesity-related metabolic alterations and explore the underlying mechanisms, male C57BL/6J mice were divided into three groups and fed for 10 weeks with a low-fat diet (10 kcal% fat), a high-fat diet (HFD, 60 kcal% fat), or an HFD containing 0.02% (w/w) PA. PA-supplemented mice showed no significant weight loss and fat loss. However, PA supplementation significantly reduced circulating levels of free fatty acid, triglyceride, and non-high-density lipoprotein cholesterol (HDL-C) while increasing HDL-C levels in HFD-fed mice. It also reduced hepatic lipid deposition and alleviated hepatocellular injury. These effects were accompanied by the coordinated modulation of hepatic lipid metabolism, including reduced lipogenesis and cholesterol esterification, enhanced fatty acid oxidation, and increased bile acid synthesis and excretion. Furthermore, PA attenuated hepatic oxidative stress and suppressed systemic and hepatic inflammation. These observations suggest that PA may counteract HFD-induced MASLD by modulating hepatic lipid metabolism, and that its anti-inflammatory and antioxidant effects may also contribute to these metabolic improvements. Full article

Soybean (Glycine max) is a vital food and oil crop in China, yet its yield and quality are severely threatened by piercing–sucking damage caused by Riptortus pedestris (Hemiptera: Alydidae) to soybean pods. Under global climate warming and expanded soybean cultivation, temperature has become a key environmental factor driving the spread of and aggravated damage caused by R. pedestris. We investigated the effects of temperature (32, 36, 40, 42, and 44 °C) and exposure duration (1–4 h) on the energy substances and antioxidant enzyme activities in adult R. pedestris. These two factors also had significant effects on the pest’s energy substances and antioxidant defense. Under short-term high-temperature stress, the water loss rate and fat, total sugar, and glycogen contents increased significantly, while protein content showed a fluctuating upward trend, with distinct sexual differences in these responses; the water loss and energy substance levels within the lethal high-temperature range, around 44 °C, were generally higher than those in the sublethal range (36–42 °C). R. pedestris showed physiological changes consistent with enhanced heat tolerance and adaptability, including water balance regulation, carbohydrate and lipid accumulation, and modulation of protein synthesis and degradation. In the sublethal high-temperature range, antioxidant enzyme activity patterns were altered, and SOD activity was increased; meanwhile, the MDA content also rose, and POD and CAT activities decreased. In the lethal high-temperature range, the overall antioxidant enzyme activities were lower than in the suitable temperature range, with the POD activities and MDA content still rising. These results suggest that the dynamic adjustment of antioxidant enzyme activities may contribute to alleviating oxidative damage and rapid adaptation to temperature-induced oxidative stress in R. pedestris. These findings indicate that R. pedestris possesses physiological plasticity to cope with sublethal heat stress through metabolic reallocation and antioxidant defense activation, but extreme temperatures cause severe physiological disruption. This study provides insights into the thermal biology and heat resistance mechanisms of this pest under climate warming scenarios. Full article

This study presents the first tissue-resolved targeted metabolomic analysis of artificially cultivated Termitomyces upsilocystidiatus fruiting bodies using LC-MS/MS. We identified pronounced metabolic divergence between the pileus and stipe. The pileus was enriched in a nitrogen-recycling and antioxidant module, exemplified by L-citrulline (~13.5-fold higher than stipe, p < 0.01) and urea, while the stipe accumulates sulfur-derived and oxidized metabolites such as L-homocystine (~3.5-fold higher, p < 0.01) and methionine sulfoxide. Lipid profiles further distinguished the two tissues: the pileus featured high levels of linoleic acid-derived oxylipins, including 13(S)-HODE and 12(13)-DiHOME (~9.7-fold and ~303-fold enrichment, respectively, p < 0.01), suggesting a role in signaling and redox buffering. In contrast, the stipe preferentially accumulated oxidized eicosanoids (e.g., 5-oxoETE) and thromboxane B1, indicative of a stress-responsive lipid network. Together, these metabolite-level observations support a tentative “pileus-synthesis/stipe-defense” dual-hub model. This work provides a quantitative metabolic framework for understanding tissue specialization in a symbiotic fungus and offers practical entry points for cultivation optimization and quality control of Termitomyces. Full article

Clutch persistence, defined as the ability to sustain consecutive egg-laying cycles, is a pivotal determinant of profitability in the poultry industry, particularly for aging laying hens (≥65 weeks). However, the molecular mechanisms governing this trait remain elusive, largely due to the traditional “ovary-centric” paradigm that overlooks systemic regulation by the gut microbiota. To address this knowledge gap, the present study aimed to dissect the comprehensive regulatory network governing clutch persistence using integrated multi-omics analyses. A total of 20 sixty-five-week-old Rhode Island Red (RIR) laying hens with cumulative egg production exceeding 300 eggs but distinct clutch persistence were stratified into a high-clutch persistence group (HCP, ≥25 clutches, n = 10) and a low-clutch persistence group (LCPLCP, ≤15 clutches, n = 10). Multi-omics profiling, including ovarian transcriptomics, proteomics, and metabolomics; serum metabolomics; and cecal microbiota 16S rRNA sequencing was performed. Data integration and association mining were conducted via Spearman correlation analysis with stringent thresholds (r > 0.6, p < 0.01). Integrated analyses revealed a “gut–ovary axis” regulatory model mediated by a lipid mediator network, operating through a three-tiered mechanism: (1) Gut Initiation: The HCP group exhibited enriched cecal γ-Proteobacteria, which promoted biosynthesis of lipid precursors. (2) Serum Transport: Key serum lipid mediators, most notably LysoPC (22:6) (VIP = 4.5) and cholesterol ester CE (20:4), served as critical carriers transducing gut-derived signals to the ovary. (3) Ovarian Execution: These lipid signals activated a core ovarian metabolic pathway centered on the PLA2G6-ALOX15B-AGPAT3 axis, which coordinated follicular development and ovulation by supplying steroid hormone synthesis substrates, exerting anti-inflammatory effects, and stabilizing membrane structures. Collectively, this study demonstrates that gut microbiota modulates clutch persistence in aging laying hens via lipid mediators, orchestrating a systemic “gut–serum–ovary” regulatory cascade. These findings provide a novel molecular framework for extending the economic egg-laying cycle through the targeted manipulation of intestinal microbiota or serum lipid metabolism. Full article

Ovotransferrin (OVT), a major iron binding glycoprotein in egg white, is increasingly studied as a multifunctional ingredient for food preservation, mineral delivery, and colloidal design. This review critically evaluates how native structure, iron saturation, thermal history, glycation, phosphorylation, fibrillation, and interactions with proteins, polysaccharides, polyphenols, and lipid interfaces influence or determine OVT behavior during processing and gastrointestinal digestion. Rather than defining digestive stability simply as resistance to proteolysis, the review compares how processing routes reshape protease accessibility, peptide release, residual allergenic risk, and the persistence of antimicrobial or antioxidant functions. Particular emphasis is placed on cross-matrix interactions because OVT rarely acts as an isolated purified protein in practical formulations; its performance depends on pH, ionic strength, competing ligands, and the architecture of emulsified, coated, or liquid food systems. The available literature indicates that the most mature application space is multifunctional food system design, including preservation-oriented coatings, Pickering-type emulsions, oleogel-associated systems, and liquid food delivery platforms. Broader industrial applications will require standardized reporting of apo/holo state, processing history, digestion models, real food validation, sensory consequences, and allergenicity. To reduce overinterpretation, the present synthesis prioritizes primary studies and weighs model food or real food validation more heavily than mechanistic or preclinical evidence when discussing application readiness. Overall, OVT should be regarded as a promising but context-dependent protein platform whose value lies in coupling bioactivity with techno-functionality rather than in any single universal health claim. Methodological transparency is further supported by explicit database sources, reproducible search blocks, inclusion/exclusion rules, and a structured quality-appraisal and evidence tiering framework. Full article