Search Results (141)

Chatuphalatika is a traditional Thai polyherbal formulation whose metabolically active fraction has not been identified. This study fractionated the aqueous extract (CPT) by sequential liquid–liquid partitioning to obtain solvent fractions. The ethyl acetate fraction (CPTX) had the highest total phenolic content and was enriched in hydrolyzable tannins, particularly chebulagic acid. CPTX showed the strongest inhibitory activity against HMG-CoA reductase in vitro. In vivo, C57BL/6 mice were fed a high-fat diet for 12 weeks, then treated with CPT, CPTX, or silymarin for 8 weeks while high-fat diet feeding continued. Both CPT and CPTX improved serum lipid profiles. High-dose CPTX (500 mg/kg) additionally reduced fasting blood glucose, serum ALT, and relative liver weight, without affecting body weight or adipose tissue weights. These findings indicate that phenolic enrichment concentrates the hepatic and lipid-lowering activity of Chatuphalatika. HMG-CoA reductase inhibition was used as a screening criterion to identify CPTX as the active fraction; the in vivo hepatometabolic improvements are consistent with, but do not directly confirm, modulation of cholesterol biosynthesis and hepatic lipid metabolism. Full article

Background/Objectives: Metabolic syndrome (MetS) is a pressing global health challenge comprising obesity, hyperglycemia, hypertension, and hyperlipidemia. Conventional polypharmacy often presents long-term compliance issues and side effects. Eucommia ulmoides Oliv., a traditional medicinal and edible plant rich in iridoids, lignans, flavonoids, and polysaccharides, has emerged as a promising natural intervention. This review aims to systematically summarize the bioavailability and multifaceted pharmacological mechanisms of E. ulmoides and its bioactive components in alleviating MetS. Methods: We comprehensively reviewed the recent in vitro and in vivo literature to map the functional evidence, specific signaling pathways, and gut microbiota–host interactions associated with E. ulmoides extracts and its key phytochemicals (e.g., asperuloside) against various metabolic dysfunctions. Results: Current evidence indicates that E. ulmoides operates through a “multi-component, multi-target, and multi-pathway” paradigm. For hyperlipidemia and obesity, it activates hepatic lipid metabolism (PPARα/CPT1A, FXR/CYP7A1) and mitigates oxidative stress (Nrf2/ARE). Furthermore, it dose-dependently reshapes the gut microbiota by enriching beneficial bacteria like Akkermansia and increasing butyrate production, exerting profound gut–liver axis regulation. It also ameliorates hypertension by activating the ACE2-Ang-(1–7)-Mas axis, improves insulin resistance via the AMPK/PI3K/Akt cascade, and manages hyperuricemia by modulating XOD and renal transporters. Notably, the low oral bioavailability of its glycosides highlights the crucial role of gut microbial hydrolysis in its efficacy. Conclusions: E. ulmoides holds substantial therapeutic potential as a multi-target natural supplement for MetS. However, future translational applications necessitate large-scale randomized clinical trials, multi-omics studies to further clarify host–microbiome interactions, and the development of standardized formulations to ensure clinical efficacy. Full article

Heat stress leads to excessive hepatic lipid deposition and oxidative imbalance in laying hens, especially during peak laying period. Chlorogenic acid (CGA), a dietary polyphenol with antioxidant and lipid-modulating properties, may improve hepatic lipid homeostasis, yet its effects under heat-stress conditions remain unclear. In this study, 240 Hy-Line Brown laying hens at 36 weeks of age were randomly assigned to one of two treatments (120 hens per treatment, with six replicates of 20 hens each): a basal diet or a basal diet supplemented with 300 mg/kg CGA and subjected to heat-stress conditions for 8 weeks. CGA supplementation significantly reduced liver weight (25.3%), liver index (14.4%), hepatic triglyceride content (29.1%), and serum triglyceride level (61.7%) (p < 0.05). Histological assessment revealed lower steatosis and inflammation scores, alongside increased hepatic SOD activity (13.6%) and decreased MDA content (58.7%) (p < 0.05). RNA-seq analysis identified 420 differentially expressed genes that were significantly enriched in PPAR signaling and fatty acid β-oxidation pathways. CGA upregulated fatty acid oxidation-related genes (ACSL1, CPT1A, ACOX1, ACAA1) and downregulated lipogenic markers (FASN, ACACA). Serum metabolomics revealed coordinated changes in lipid and carbon metabolism. These results indicate that dietary CGA alleviates hepatic lipid accumulation and oxidative stress in heat-stressed peak-laying hens, potentially via PPARα-mediated enhancement of fatty acid oxidation and inhibition of de novo lipogenesis. Full article

The role of the catechol-O-methyltransferase (COMT) Val158Met rs4680 polymorphism in altered pain processing in headaches is controversial. The aim of this study was to investigate the influence of the Val158Met rs4680 polymorphism in conditioned pain modulation (CPM) in women with migraine. A case-control study including 70 women with chronic migraine, 70 with episodic migraine and 70 pain-free women was conducted. Pressure pain thresholds (PPTs) at the temporalis muscle, lateral epicondyle, and tibialis anterior were bilaterally assessed. Heat (HPT) and cold (CPT) pain thresholds at the frontalis muscle were also assessed. Subsequently, CPM was evaluated immediately after a one-minute cold-pressor test paradigm on changes obtained in PPTs, HPT and CPT. Thus, after amplifying Val158Met polymorphism by polymerase chain reaction, genotype frequencies (Val/Val, Val/Met, or Met/Met) and allele distributions were identified. The distribution of Val158Met genotypes (p = 0.097) was not significantly different among women with episodic migraine, chronic migraine and pain-free controls. The results revealed significant group*time*Val 158Met interactions for PPTs at the temporalis (Wilk’s λ = 0.917, F [4, 193] = 4.377, p = 0.002, n²p = 0.083, 1 − β = 0.930) and lateral epicondyle (Wilk’s λ = 0.892, F [4, 193] = 5.870, p < 0.001, n²p = 0.108, 1 − β = 0.982), as well as CPT (Wilk’s λ = 0.872, F [4, 193] = 7.111, p < 0.001, n²p = 0.128, 1 − β = 0.995) or HPT (Wilk’s λ = 0.921, F [4, 193] = 4.133, p = 0.003, n²p = 0.079, β − 1 = 0.914), but not for the PPT at tibialis anterior (Wilk’s λ = 0.983, F [4, 193] = 0.834, p = 0.505, n²p = 0.017, 1 − β = 0.263). Women with chronic migraine with the Met/Met genotype exhibited reduced CPM indexes for PPT, CPT, or HPT at the temporalis (trigeminal area) than those with the Val/Val genotype. This study showed that CPM deficit is higher in women with migraine with the Met/Met genotype, but this association is mostly present in the symptomatic (trigeminal) area in the chronic form of the disease. No association of the Met/Met genotype with CPM was seen in healthy controls. Full article

Rare-disease diagnosis is difficult because clinicians must identify plausible conditions from a large, severely imbalanced disease space using evidence distributed across clinical narratives, structured findings, and image-linked descriptions. This paper presents a hybrid pipeline with caption-mediated multimodal fusion for ranked rare-disease diagnosis and grounded explanation, developed and evaluated on the ZebraMap multimodal case-report dataset (69,146 structured cases; 1727 diseases). Grouped train–validation–test splitting by source article was applied to prevent leakage, and a sequential pipeline was constructed combining BM25 lexical retrieval, a class-balanced TF–IDF classifier, MedCPT dense retrieval and cross-encoder reranking, caption-based image-aware late fusion, and post hoc grounded explanation generation. The final pipeline achieved test MRR 0.3905 and Recall@10 0.5507 (nDCG@10 0.4273), while the strongest individual component, the class-balanced TF–IDF classifier, reached MRR 0.4200 and Recall@10 0.6279; the hybrid pipeline therefore integrates ranking with grounded explanation rather than maximizing single-metric diagnostic accuracy. On 256 explained cases, the explanation module achieved citation coverage 0.7334 and usefulness 3.8734, exposing a tradeoff between diagnostic accuracy and explanation richness. These results indicate that a hybrid retrieval-and-classification approach can support ranked rare-disease differential diagnosis and that grounded explanation quality can be evaluated quantitatively, extending computational support for the prolonged rare-disease diagnostic process. Full article

Patients with liver cancer frequently exhibit abnormal liver function and disorders in lipid metabolism. This study investigates the effects of Oleanolic acid (OA) on hepatocellular carcinoma (HCC) through the regulation of lipid metabolism. Computational simulations identified six core targets of OA, including PPARα, HMGCR, and ESR1, with stable binding confirmed through molecular docking and dynamics analyses. The experiments demonstrated that OA reduced intracellular lipid accumulation, suppressed cell migration (p < 0.05), and promoted apoptosis. The levels of lipid droplets and triglycerides (TG) were significantly decreased (p < 0.05). The expression levels of lipid metabolism-related genes, including PPARA, CPT1A, FASN, and HMGCR, were assessed using qRT-PCR (p < 0.05). Additionally, protein expression levels were analyzed through Western blotting (p < 0.05). Furthermore, the combination of OA with the antagonist GW6471 enhanced tumor suppression, while the combination with the agonist Pemafibrate reversed the effects of OA. Compared to OA alone, the antagonist combination significantly reduced PPARα and CPT1A protein expression (p < 0.05), whereas Pemafibrate upregulated these proteins (p < 0.05). In conclusion, OA exerts its anti-lipid metabolism effects in HCC by modulating the PPARα-CPT1A axis, indicating its potential therapeutic value in liver cancer treatment. Full article

Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by abnormal hepatic lipid accumulation and is frequently driven by factors such as a high-fat diet (HFD). Total flavonoids of Apocynum venetum (TFAV), the bioactive constituents of a traditional medicinal plant, have demonstrated antioxidant and lipid-modulating properties. However, their therapeutic potential against MASLD and the underlying mechanisms are not explored. This study aims to evaluate the ameliorative effects of TFAV on HFD-induced MASLD utilizing both in vivo animal and in vitro cellular models. Methods: C57BL/6J were allocated to control, high-fat diet (HFD), TFAV (100 mg/kg/day), and TFAV intervention groups (25, 50, and 100 mg/kg/day). In vitro, WRL68 hepatocytes were stimulated with free fatty acids (FFAs) to establish a cellular model of steatosis. Liver function, serum lipid profiles, hepatic histopathology, and the AMPK signaling pathway were assessed. Results: TFAV intervention significantly improved serum biochemical profiles in the animal models; for instance, co-treatment with 100 mg/kg/day TFAV and HFD reduced TC, TG, and LDL-C levels by 20.59%, 45.26%, and 38.24% respectively (p < 0.05), and effectively alleviated hepatic steatosis and hepatocyte ballooning. Furthermore, TFAV markedly inhibited intracellular reactive oxygen species (ROS) levels and activated the AMPK signaling pathway (p < 0.05). This was accompanied by the downregulation of SREBP-1c and ACC expression (p < 0.05), as well as the upregulation of ATGL and CPT1α expression (p < 0.05). Conclusions: These results demonstrates that TFAV remodel hepatic lipid homeostasis by activating the AMPK signaling pathway, and exerting significant preventive and protective effects against the progression of HFD-induced MASLD in vivo. Full article

The SHI-related sequence (SRS) transcription factors are vital plant regulators involved in development and stress responses. Given that biosynthesis of the valuable anticancer drug camptothecin (CPT) in Camptotheca acuminata is influenced by developmental and environmental cues, we hypothesized that SRS genes play key regulatory roles in the CPT biosynthetic pathway. To test this hypothesis and characterize the SRS family in this medicinally crucial plant, we performed a genome-wide identification of CaSRS genes and focused our analysis on their potential functional link to CPT biosynthesis. Eight distinct CaSRS genes were identified and classified into three phylogenetic subgroups. Comprehensive characterization—including phylogenetic relationships, gene structures, conserved motifs, chromosomal distribution, and synteny with Arabidopsis thaliana, Catharanthus roseus, and Ophiorrhiza pumila—provided foundational insights into the family. Crucially, integrated analysis of multi-tissue expression profiles revealed significant correlations between specific CaSRS genes (CaSRS2, CaSRS3, and CaSRS5) and key CPT biosynthetic genes. Promoter cis-regulatory element analysis further indicated that these CaSRS genes possess binding sites associated with stress and hormone responses known to modulate CPT production. These convergent lines of evidence strongly implicate CaSRS2, CaSRS3, and CaSRS5 as potential regulators of CPT biosynthesis. Collectively, this study first identifies specific CaSRS gene candidates for functional validation and provides a crucial foundation for understanding the role of the CaSRS family in regulating CPT biosynthesis in C. acuminata. Full article

The clinical utility of the anticancer drug camptothecin (CPT) is limited by its poor aqueous solubility and instability in the bloodstream, hindering bioavailability and efficacy. This study explores the complexation of CPT with carboxymethyl-beta-cyclodextrin (cmβCD) to overcome these limitations. Fluorescence spectroscopy and molecular modeling demonstrated 1:1 inclusion complexes, with stability constants governed by electrostatic interactions that were inversely correlated with pH. To validate this effect, a cationic amino-beta-cyclodextrin (amβCD) was used as a mechanistic control, revealing that Coulombic forces significantly modulate binding strength and stoichiometry. Crucially, cmβCD enhanced CPT solubility by up to 11-fold at 14 × 10⁻³ moldm⁻³, enabling a 385-fold increase in drug loading into liposomal carriers compared to the cyclodextrin-free system. Fluorescence-based release studies indicated high liposomal stability at physiological pH and partial CPT release under acidic conditions. Furthermore, CPT-loaded liposomes demonstrated cytotoxicity against cancer cell lines, particularly BT-474, with IC₅₀ values generally comparable to or slightly higher than those of free CPT and the CPT:cmβCD complex, likely due to the distinct lysosomal cellular uptake pathway. This work highlights cmβCD complexation as a promising strategy to enhance CPT solubility and liposomal loading for improved drug delivery. Full article

Bone formation requires a substantial energy supply to sustain extracellular matrix production and mineralization, yet the temporal contribution of lipid metabolism during osteoblast maturation remains incompletely characterized. This study investigated the molecular and transcriptional remodeling of lipid metabolism. Intracellular lipid distribution was analyzed by confocal microscopy using Nile Red staining. Transcriptional modulation of lipid synthesis, storage, lipolysis, genes associated with mitochondrial fatty acid oxidation, and osteogenic markers were assessed by quantitative real-time PCR, and the biochemical composition was evaluated by Raman spectroscopy. Early stages of spheroid development showed higher expression of genes involved in lipid synthesis and storage (FASN, DGAT2, and PLIN2) together with intracellular lipid accumulation, whereas later stages displayed increased expression of lipolytic and β-oxidation markers (PNPLA2/ATGL, CPT1A, and HADHA), accompanied by the redistribution of lipid droplets. The Raman analysis revealed a time-dependent variation of lipid-associated CH₂/CH₃ bands and modulation of protein-related Amide I–III signals, consistent with biochemical remodeling during maturation. Overall, the data indicate a coordinated transcriptional shift from lipid accumulation-associated pathways toward lipid mobilization during osteogenic progression in a 3D culture. This model provides a controlled experimental platform for investigating metabolic regulation during bone formation and for studying metabolic alterations associated with skeletal disorders. Full article

This experiment investigated the effects of dietary Artemisia ordosica Krasch. (AOK) supplementation on the n3-polyunsaturated fatty acid (n3-PUFA) profile of subcutaneous adipose tissue (SADT) in Arbas cashmere goats and explored the underlying transcriptional mechanisms. Forty healthy, weaned kids (120 ± 10 days of age; similar body weight) were randomly allocated to two groups (n = 20): a control group (CON, basal diet) and an AOK group (AOK, basal diet with 3% of the roughage replaced by AOK). The feeding trial spanned 104 days, consisting of a 14-day adaptation period and 90 days of data acquisition. Compared with the CON group, AOK significantly reduced the content of saturated fatty acids (SFAs) and n6-polyunsaturated fatty acids (n6-PUFAs)/n3-PUFAs (n6/n3). In contrast, the levels of n3-PUFAs in the SADT of cashmere goats increased markedly (p < 0.05). Compared with the CON group, AOK exhibited significantly higher activities of hormone-sensitive lipase (HSL) (p = 0.027), adenylyl cyclase 2 (ADCY2) (p = 0.010), adenylyl cyclase 5 (ADCY5) (p = 0.046), cluster of differentiation 36 (CD36) (p = 0.013), solute carrier family 27 member 4 (SLC27A4) (p = 0.021), and fatty acid binding protein 4 (FABP4) (p = 0.040), along with significantly lower activities of fatty acid synthase (FAS) (p = 0.002), lipoprotein lipase (LPL) (p = 0.048), and stearoyl-coa desaturase (SCD) (p = 0.026) in SADT. Compared with the CON group, the activities of superoxide dismutase (SOD) (p = 0.032), catalase (CAT) (p = 0.010), glutathione peroxidase (GSH-PX) (p = 0.029), and total antioxidant capacity (T-AOC) (p = 0.002) were significantly increased in the AOK group. Transcriptomic profiling revealed that AOK supplementation downregulated mRNA levels of ADCY2, ADCY5, LPL, FAS, SCD, stearoyl-CoA desaturase 1 (SCD1), stearoyl-CoA desaturase 2 (SCD2), glycogen synthase 1 (GYS1), acyl-CoA oxidase 1 (ACOX1), acetyl-CoA carboxylase (ACC), diacylglycerol acyltransferase 1 (DGAT1), fatty acid desaturase 1 (FADS1), solute carrier family 27 member 2 (SLC27A2), erythroblastic leukemia viral oncogene homolog 4 (ERBB4), and carnitine palmitoyltransferase 1B (CPT1B) (p < 0.05). It also markedly induced acyl-CoA synthetase long-chain family member 4 (ACSL4) (p < 0.01) in SADT. Genes significantly enriched in the adenosine-monophosphate-activated protein kinase (AMPK) signaling pathway included LPL, SCD1, CPT1B, and GYS1 (p = 0.010). Genes significantly enriched in the phosphatidylinositol 3-kinase-akt (PI3K-Akt) signaling pathway included GYS1 and ERBB4 (p = 0.015). CPT1B, ADCY2, and GYS1 were identified as the genes significantly enriched in the insulin resistance signaling pathway (p = 0.048). LPL was the only gene significantly enriched in the cholesterol metabolism pathway (p = 0.049). Genes showing a tendency toward significant enrichment in the peroxisome-proliferator-activated receptor (PPAR) signaling pathway included ACSL4, CPT1B, SCD1, and LPL (p = 0.051). These interconnected cascades improve insulin sensitivity, stimulate triglyceride (TG) hydrolysis, and modulate n3-PUFA levels. Supplementation with AOK enhances n3-PUFA content by accelerating TG breakdown while simultaneously restraining FA oxidation in SADT. Consequently, AOK supplementation can be effectively used to enhance the nutritional value of cashmere goat meat through improved n3-PUFA deposition in SADT. Full article

Tributyrin (TB), as a novel feed additive, holds broad market prospects and is crucial for promoting fish growth and maintaining intestinal health. We first identified the fatty acid metabolism-related gene cpt1b in the intestines of mandarin fish (Siniperca chuatsi) from the TB-supplemented group. A total of 600 mandarin fish (200.0 ± 5.0 g) were evenly allocated into three groups. The control group (C) received only the standard extruded feed, while the experimental groups were supplemented with tributyrin (TB) at concentrations of 500 mg/kg (T1 group) and 1000 mg/kg (T2 group), respectively. Cloning yielded a 2364 bp open reading frame (ORF) encoding 787 amino acids, with the gene possessing two conserved transmembrane domains. Phylogenetic analysis further indicated a close phylogenetic relationship between largemouth blackbass (Micropterus salmoides) and mandarin fish. Tissue distribution and intestinal enzyme activity analyses revealed that supplementation with varying concentrations of TB upregulates cpt1b gene expression in different tissues, while modulating intestinal digestive enzyme and antioxidant enzyme activities. Our findings suggest a potential mechanism involving enhanced intestinal enzyme activity, reduced fat accumulation, increased expression of lipid oxidation-related genes, and accelerated TB degradation in the intestine. Full article

Capacitive Power Transfer (CPT) technology, as an emerging wireless power supply solution, exhibits great potential in areas such as electric vehicle charging, underwater equipment power supply, biomedical implants, and consumer electronics due to its advantages of low cost, light weight, insensitivity to metals, and potential high power density. However, the coupling capacitance is susceptible to the influence of transmission distance, misalignment, and changes in environmental media, leading to fluctuations in system output characteristics and becoming a key challenge restricting its application. This report aims to systematically review the key technological advancements proposed in recent years to achieve constant voltage/current/power output and enhance system robustness. Firstly, this study categorically reviews the CPT system topologies for constant voltage output, constant current output, and constant power output, analyzing the principles, advantages, and disadvantages of achieving load-independent or coupling-independent output. Secondly, it sorts out various active and passive control strategies, including frequency regulation, impedance matching, adaptive parameter switching, and pulse modulation, which are used to manage dynamic changes. Next, it summarizes innovative design and optimization methods for couplers tailored to specific application scenarios, such as large-gap electric vehicle charging, underwater, and rotating mechanisms. Finally, based on existing research, this review describes the challenges that CPT technology still faces in achieving efficient, high-power, and highly robust constant output, and looks forward to future research directions. Full article

Malonyl-CoA decarboxylase (MCD) is an enzyme that controls malonyl-CoA levels and regulates fatty acid synthesis and oxidation. Although its physiological relevance in peripheral tissues is well known, the role of MCD in the central nervous system remains poorly understood. MCD is expressed in mitochondria, cytosol, and peroxisomes and may be regulated by PPAR-α, AMPK, and SIRT4 in tissues such as muscle, liver and kidney. In the brain, MCD expression varies during development and can respond to nutritional states. Inherited MCD deficiency (malonic aciduria) leads to the toxic accumulation of malonic acid and predominantly affects the central nervous system. The underlying mechanisms leading to brain damage in MCD patients remain unclear. Conversely, pharmacological modulation of MCD activity has been studied in obesity, diabetes, and ischemic injury, highlighting its therapeutic potential. There are still major gaps regarding MCD cellular distribution, regulatory pathways, and metabolic interaction with CPT1c (carnitine palmitoyltransferase 1c) in neural metabolism. A deeper understanding of the role of MCD in brain physiology and pathology may indicate novel therapeutic strategies targeting metabolic disorders that involve altered malonyl-CoA dynamics. Here, we discuss the current knowns and unknowns regarding MCD physiology, regulation, and pathophysiology, emphasizing brain aspects. Full article

Precision nutrition has emerged as a promising strategy for the prevention of type 2 diabetes mellitus (T2DM) by targeting molecular pathways underlying insulin resistance and impaired glucose metabolism. Accumulating evidence indicates that dietary patterns, caloric intake, and specific nutrients can modulate gene expression and epigenetic mechanisms involved in insulin signaling, inflammation, and energy homeostasis. This narrative review synthesizes recent human and experimental studies (2025–2026) examining how dietary components influence transcriptional and epigenetic regulation of insulin signaling and glucose metabolism in the context of T2DM prevention. A total of 29 peer-reviewed studies were included, encompassing dietary patterns, macronutrient manipulation, micronutrient and bioactive supplementation, and gene–diet interactions. Very-low-calorie diets consistently induced coordinated modulation of key metabolic genes, including downregulation of glucose transporter type 4 (GLUT4) and upregulation of PDK4, CPT1, and AMPK, reflecting a metabolic shift toward enhanced fatty acid oxidation and improved insulin sensitivity. In contrast, high-fat and fructose-rich diets promoted proinflammatory gene expression and immune activation, contributing to insulin resistance. Plant-based and vegan dietary patterns were associated with reduced epigenetic aging and improved insulin sensitivity through DNA methylation changes. Targeted interventions, including vitamin D combined with probiotics, dietary fiber, nucleotides, and trace elements such as copper, further demonstrated favorable transcriptional and epigenetic effects linked to improved glycemic control. Collectively, these findings highlight diet-driven modulation of insulin signaling and glucose metabolism at the molecular level and support nutrigenomics-guided precision nutrition as a viable preventive approach for T2DM. Integrating genetic and epigenetic insights into dietary strategies may enable more personalized and effective interventions to curb the growing global burden of type 2 diabetes. Full article