Withering is a critical step that influences the formation of tea quality. The dehydration stress during withering induced considerable losses of lipids, which are crucial tea aroma precursors. However, the lipid metabolism and transformation during withering and their impact on tea aroma formation have not been systematically characterized. Herein, through lipidomics and gas chromatography-mass spectrometry (GC-MS) analysis, we found the significant loss of total lipids during withering, primarily driven by the degradation of glycerophospholipids, bis(monoacylglycero)phosphates (BMPs), sphingomyelins (SMs) and monogalactosyldiacylglycerols (MGDGs) containing (18:3) fatty acyl residues, while triacylglycerols (TAGs) and free fatty acids (FFAs) accumulation were activated. The lipid metabolism was remodeled with changes in the unsaturation degree and chain length of acyl chains. Total 271 lipids and 38 volatiles were identified as withering dynamic lipids and withering different volatile compounds, respectively. Through co-expression analysis of lipids and volatile compounds, certain C52/C54 TAGs, FFAs, LPC(16:0), LPE(16:0), and LPG(16:0) were the key lipids or lipid biomarkers for tea aroma formation during withering. Furthermore, withering could promote lipid-aroma formation by activating the expression of CsPLA/CsPLC/CsPLD, CsLOXs, CsHPL1, CsADHs and CsAAT. These findings offer lipid-centric reference data for the improvement of tea quality and the development of standardized tea processing.
Salting treatment can compromise the stable emulsification system of egg yolks, resulting in lipid oxidation and decomposition. This study investigated the effects of CaCl2 on the primary and secondary oxidation products of lipids, fatty acid content, alterations in lipid structure, and lipidomic analysis. These results demonstrated that adding CaCl2 promoted the lipid oxidation reaction, which led to an increase in polyunsaturated fatty acid reduction in the eggs salted with CaCl2 (CSEY group). The 1H NMR and Raman spectra indicated that the addition of CaCl2 disrupts the microstructure of lipoproteins, releases internal oils, and activates molecular oxygen, accelerating the free radical chain reaction and enhancing the oxidative degradation of egg yolk lipids, resulting in the cleavage of carbon-carbon double bonds and changes in fatty acid unsaturation. Lipidomic analysis revealed 830 types of lipids, with 156 exhibiting significant differences between the CSEY group and the salted eggs without CaCl2 (SEY group). The differential lipids predominantly exhibited high unsaturation (double bond numbers 4-9) and ultralong carbon chains (C56-C60), and easily oxidized phospholipids were consumed in considerable amounts, while structurally stable ultralong-chain high-unsaturated triglycerides (TGs) were relatively enriched. Moreover, KEGG enrichment analysis revealed that different lipids are mostly associated with neutral lipid storage and droplet formation.
Fatty acid-acylated cholines, a recently identified class of endogenous compounds, have been de tected in both human and animal organisms. Our prior work established that oleoylcholine (Ol-Chol), and other acylcholines, at micromolar levels, modulate the cholinergic system and are suitable as cationic lipids for introducing nucleic acids into human and animal cells. The present research examines the interaction with the nicotinic acetylcholine receptors (nAChR) of two ionic forms of Ol-Chol and two synthesized cat ionic lipids, each featuring a quaternary ammonium moiety and two oleic acid chains. A radioligand bind ing assay revealed that the affinity of acylcholines and synthetic cationic lipids for the muscle-type nAChR surpasses that for the human neuronal α7 nAChR by a factor of 2-5.5. Oleoylcholine iodide demonstrated a two-fold higher efficacy of mesylate in binding to the orthosteric site of muscle and α7 nAChR. In a func tional calcium imaging assay, both compounds exhibited superior inhibition of α7 nAChR by several orders of magnitude, suggesting potential interaction with allosteric binding sites. Compared to oleoylcholine, syn thetic cationic lipids demonstrated markedly reduced efficacy in binding to α7 nAChRs and, in contrast to oleoylcholine, induced a substantial cytotoxic impact on SH-SY5Y neuroblastoma cells, a phenomenon unaf fected by specific nAChR ligands. As a result, the nAChR-inhibitory properties are attributed to the quater nary ammonium group present in all studied compounds. However, the modification of the lipophilic moiety with two oleic acid residues curbs these properties but enhances cytotoxic activity through an alternative mechanism independent of nAChR.
To comprehensively evaluate the oxidation stability of specialty nut oils from Northeast China, this study examined hazelnut oil (HO), almond oil (AO), shiny-leaved yellowhorn oil (SYO), walnut oil (WO), and pine nut oil (PO). Using the Schaal oven accelerated oxidation method, we dynamically monitored changes in their oxidation indicators and antioxidant capacity, and conducted an evaluation through principal component analysis. The results indicated that HO exhibited excellent oxidation stability. Further analysis of fatty acid changes revealed that HO maintained a monounsaturated/polyunsaturated fatty acid (MUFA/PUFA) ratio as high as 7.66. In contrast, the PUFA in the other four oils degraded significantly faster during oxidation, further validating its superior stability. Based on untargeted lipidomics technology utilizing ultra-high-performance liquid chromatography-Quadrupole-Exactive Orbitrap mass spectrometry (UHPLC-QE-Orbitrap/MS/MS), a total of 789 lipid molecules from 23 subclasses were identified. Among these, triacylglycerol (TG) was the most abundant lipid subclass (relative abundance > 90%). 176 significantly differential lipids were successfully identified through chemometrics, serving as potential biomarkers for distinguishing between each other. Unsaturation analysis of differential lipids revealed that the content of polyunsaturated lipids in HO was significantly lower than in other oils, intrinsically explaining the origin of its superior stability. This study employs multidimensional analysis to not only provide comprehensive information on the lipid composition of Northeast China's specialty nuts but also systematically reveal the differences in their oxidative stability and underlying causes. It lays a solid scientific foundation for the high-value development, quality control, and industrial application of specialty oilseed resources.
Medium-chain triglycerides (MCTs) have garnered considerable attention in the food and health industries due to their rapid absorption, efficient metabolism, and nutritional benefits compared to long-chain triglycerides. In this study, the integral stereoselectivities of both native and recombinant forms of an MCT-selective lipase, Cordyceps militaris lipase (CML), toward tricaprylin (TC) were determined to evaluate their potential applications to MCTs. Lipase assays revealed that catalytic activities were markedly enhanced in the presence of 30 mM sodium cholate, with 6.9-fold and 1.9-fold increases for native and recombinant CML, respectively. To accurately monitor hydrolysis of TC, an optimized HPLC system was established, enabling efficient separation and quantification of TC and its hydrolysates. Kinetic modeling indicated that native and recombinant CML showed a preference for the sn-3 position over all other sn positions of TC by 98% and 70%, respectively. To further validate these findings, covalent docking of TC into CML, which mimics its tetrahedral intermediate, was simulated, confirming the sn-3 selectivity of CML to TC. Overall results indicated the industrial potential of CML as a biocatalyst for producing structured lipids, such as low-calorie lipids, from MCTs, highlighting its potential application in food processing.
Soybeans are a high-quality plant-based food with both nutritional value and physiological activity, widely used in various fields such as food and feed. The quality evolution during soybean storage is a complex biological process regulated by multiple factors, but the mechanism of quality deterioration during long-term soybean storage is not yet fully understood. To reveal the underlying mechanism of soybean deterioration, this study constructed an accelerated storage simulation system under normal temperature and humidity conditions (20 °C, 65% RH) for 0-3 years, and explored the changes in the metabolic network during soybean storage and its intrinsic relationship with quality deterioration through non-targeted metabolomics. The results showed that with prolonged storage time, the brightness of soybeans significantly decreased, while the accumulation of free fatty acids (FFA) and formaldehyde (MDA) in the oil significantly increased, increasing by 364% and 134%, respectively. Metabolomics analysis identified a total of 903 differential metabolites, with lipids and lipid molecules accounting for the highest proportion. Compared with the control group, after storage, a total of 5 KEGG pathways were significantly enriched (p < 0.01), among which the linoleic acid metabolic pathway played an important regulatory role in soybean storage. The study on the correlation between significantly enriched lipid differential substances and lipid metabolites in this pathway found that there was a significant positive correlation between the relevant metabolites, with an overall correlation coefficient above 0.74, fully demonstrating the key regulatory role of linoleic acid metabolism in soybean oil oxidation. Lipoxygenase and cytochrome P450 have been found to play key regulatory roles in the linoleic acid metabolism pathway, with their key metabolites Linoleate, 13-HPODE, 13-KODE, 9-KODE, and 12,13-DHOME significantly accumulating during storage. Further analysis of the correlation between metabolites and soybean oxidation products, FFA, and malondialdehyde revealed a positive correlation, with a correlation coefficient above 0.83, providing potential evidence for early warning of quality deterioration. This study systematically analyzed the dynamic relationship between storage time and metabolic network, not only elucidating the key metabolic pathways of soybean quality deterioration during storage, but also providing a theoretical basis for establishing quality maintenance technology based on lipid metabolism regulation.
Exosomes, nanosized extracellular vesicles secreted by diverse cell types, have emerged as promising natural nanocarriers for therapeutic delivery. Their intrinsic ability to cross the Blood-Brain Barrier (BBB) positions them as valuable tools for treating neurodegenerative diseases. This review critically examines exosome biology, transport mechanisms, engineering strategies, and their clinical potential as drug-delivery platforms for the Central Nervous System (CNS). We analyzed recent experimental, translational, and clinical studies on exosomes and engineered derivatives, focusing on BBB penetration, therapeutic cargo delivery, and applications in brain disorders. Key advances and landmark preclinical studies were synthesized to provide a comprehensive perspective. Exosomes cross the BBB through receptor-mediated transcytosis, lipid raft-associated uptake, and macropinocytosis, enabling bidirectional transport between circulation and brain. Their intrinsic cargo, including proteins, nucleic acids, and lipids, can reflect disease states and serve as predictive biomarkers. Engineered exosomes further enhance delivery potential, as surface functionalization and optimized cargo loading improve brain specificity and therapeutic efficacy in preclinical models. Collectively, both native and engineered exosomes surpass many synthetic carriers in stability, targeting, and BBB penetration. Versus previous reviews, this manuscript integrates exosome composition, engineering, isolation technologies, and administration routes, while also addressing patent and clinical translation challenges. Importantly, it highlights quantitative and mechanistic insights into BBB transport, offering a distinct framework for advancing exosome-based CNS therapies. Exosomes constitute a versatile platform for BBB-crossing drug delivery. By consolidating mechanistic, preclinical, and translational evidence, this review highlights their transformative potential in neurodegenerative disease therapy while outlining limitations and future directions.
Extracellular vesicles (EVs), encompassing exosomes, microvesicles, and apoptotic bodies, are pivotal mediators of intercellular communication, facilitating the transfer of nucleic acids, proteins, and lipids between cells and thereby influencing a wide range of physiological and pathological processes. Their inherent biocompatibility, nanoscale size, and ability to reflect the molecular signatures of their parental cells have positioned EVs as promising therapeutic agents for various diseases, including neurological, cardiovascular, hepatic, and pulmonary disorders, for which conventional therapies often provide limited or nonspecific benefits. Notably, EVs can traverse biological barriers such as the blood-brain barrier, enhancing their clinical applicability by enabling drug delivery to anatomically protected sites. Furthermore, patient-derived EVs exhibit distinct molecular profiles compared with healthy controls, underscoring their potential as diagnostic biomarkers and modulators of disease pathogenesis, with growing evidence demonstrating their ability to distinguish disease subtypes, predict prognosis, and monitor therapeutic responses. Accumulating evidence also indicates that EVs regulate immune responses, angiogenesis, and tissue remodeling, thereby contributing to both physiological homeostasis and pathological processes. Engineered EVs further offer innovative drug delivery solutions by improving therapeutic precision while minimizing adverse effects associated with conventional systems, and they hold considerable promise for future personalized- medicine strategies. This review summarizes current knowledge on the diverse roles of EVs across major organ diseases, highlights their translational potential as both therapeutic agents and biomarkers, and discusses emerging challenges that must be addressed for successful clinical translation. By providing a comprehensive overview, this study aims to advance the clinical translation of EVs in precision medicine.
A curcumin (Cur)-sensitized food-grade titanium dioxide (TiO2) composite photocatalyst, TiO2@Cur, was successfully constructed via rotary evaporation. Spectral analyses revealed that curcumin sensitization extended the light absorption range of TiO2@Cur from the ultraviolet to the visible region and markedly reduced its band gap to 2.42 eV. Fourier transform infrared spectroscopy (FTIR) and scanning electron microscope/energy dispersive spectrometer (SEM/EDS) analyses confirmed the uniform loading of curcumin into the porous structure of TiO2. Furthermore, TiO2@Cur exhibited a high aqueous solubility of 3700.10 ± 141.42 μg/mL (∼10-fold that of free curcumin), and its aqueous solution remained stable without noticeable precipitation. Notably, TiO2@Cur demonstrated a strong capacity to generate singlet oxygen (1O2) and hydroxyl radicals (•OH). In the 4 °C preservation application, refrigerated red shrimp treated with TiO2@Cur-mediated photocatalytic preservation received the highest sensory evaluation scores and color protection effect. Moreover, TiO2@Cur could effectively control the increase of freshness indicators, including total volatile basic nitrogen (TVC-N) content, pH value, total viable bacteria count (TVC), and malondialdehyde (MDA) content, which were 24.04 ± 0.67 mg/100 g, 7.44 ± 0.02, and 5.72 ± 0.06 lg CFU/g on the 6th day of storage respectively. Additionally, TiO2@Cur significantly suppressed the oxidation of proteins and lipids, with a total protein content of 5.49 ± 0.07 g/L. Meanwhile, it could effectively inhibit the water loss of refrigerated shrimp. Therefore, TiO2@Cur-mediated photocatalytic preservation treatment significantly extended the refrigerated shelf life to 6 days, demonstrating its potential as a novel seafood preservative with promising applications.
Multidrug-resistant bacteria (MDRB) have become a global health crisis that challenges the effectiveness of conventional antibiotics. Bacterial extracellular vesicles (BEVs) are nanoscale bilayered membrane vesicles secreted by both Gram-positive and Gram-negative bacteria. They can encapsulate proteins, lipids, and nucleic acids, and transfer these molecules between bacteria and host cells without direct contact. Owing to their natural ability to transport bioactive molecules, BEVs have recently gained attention as potential anti-infective platforms. They can deliver antimicrobial agents directly to resistant pathogens and act as vaccine carriers by triggering innate and adaptive immunity. Advances in BEV isolation, drug loading, and bioengineering have expanded their therapeutic potential. However, challenges such as large-scale manufacturing, immunogenicity control, and regulatory standardization still hinder clinical translation. This review summarizes the mechanisms, engineering strategies, and biomedical applications of BEVs against MDRB and discusses future perspectives for their safe and effective clinical use as antimicrobial nanoplatforms.
Research on Solid Lipid Nanoparticles has increased significantly due to their ability to improve drug delivery and control drug release from lipids. This bibliometric study illustrated SLN's evolution, co-authored networks between researchers, and research trends. We analyzed 5,063 'Article' type publications obtained from the Web of Science Core Collection using the multi-tools VOSviewer, CiteSpace, and HistCite. Solid Lipid Nanoparticles' journal growth for publications and citations highlighted continued scientific interest in this area. India was the most productive country (1,003 publications). At the same time, the Free University of Berlin was the most productive institution, and the most productive authors, Souto, Eliana B. (98 publications, 16 collaborative links), and Mueller, R.H. (82 publications, 7 collaborative links), formed the core of the co-authorship network. Keywords associated and emerging frontiers indicated an innovative field evolving from formulation studies to one focused on application data. We traced the trajectory from the lowest-hanging fruit to use cases in grand challenges, but coverage of database bias remains a concern. The past twenty years have witnessed an increase in publications and citations, as evidenced by active contributions from numerous countries, institutions, and authors. Keyword analysis and emerging frontiers marked their hot topics and research directions.
To our knowledge, a systematic comparison of nutrients contribution to mortality in large scale cohort of middle-aged to elderly individuals has not yet been done. We aim to investigate the associations between most of the available nutrients and all-cause and disease-specific mortality, and explored their joint effect on mortality risk. A total of 208,312 participants from the UK Biobank (UKB) with baseline 24-hour dietary recall data were enrolled. Cox proportional hazards models were used for a nutrients-wide association analysis of all-cause mortality and disease-specific mortality. Mixed-effects analyses were further conducted to evaluate the combined effects of nutrients significantly associated with mortality risk by Bayesian kernel machine regression (BKMR) and Quantile G-Computation (Qgcomp) regression models. No significant associations were found between total energy, total protein, total lipid, or total carbohydrate intake and all-cause mortality risk. However, energy density was moderately and positively associated with all-cause mortality (HR=1.017, 95%CI: 1.004-1.030). Nutrient type and quality exhibited significant impacts: plant-derived protein (HR=0.995, 95%CI: 0.992-0.998), plant-derived lipids (HR=0.997, 95%CI: 0.995-0.999), were negatively associated with all-cause mortality. Among carbohydrates, starch, lactose, and intrinsic/milk sugars showed protective effects, while free sugars, non-milk extrinsic sugars, sucrose, and maltose were positively associated with increased mortality risk. For minerals and vitamins, copper, manganese, total iron, non-haem iron, vitamin E, riboflavin, biotin, and pantothenic acid exhibited inverse associations with all-cause mortality. Mixed-effects analyses revealed cumulative inverse trends of beneficial nutrients and positive trends of harmful nutrients on mortality risk, with manganese, maltose, biotin, and niacin being key contributors. Disease-specific analysis showed that energy density and certain sugars were positively associated with neoplasms mortality; multiple sugars were linked to nervous system disease mortality; and alcohol, maltose were positively associated with digestive system disease mortality, while most macronutrients, minerals, vitamins, and fibre had protective effects. Sodium and chloride were positively associated with circulatory system disease mortality. Total intake of major macronutrients was not significantly associated with mortality risk, but nutrient type and quality played critical roles. Plant-derived nutrients, specific minerals, vitamins, dietary fibre, and natural carbohydrates were protective against mortality, whereas refined sugars and high energy density were detrimental. These findings highlight the importance of dietary quality in reducing mortality risk and provide evidence for developing targeted dietary recommendations.
ABHD12 is linked to cancer and neurodegeneration; we systematically characterized its pan-cancer role and validated its oncogenic function in breast cancer (BRCA) to guide mechanistic studies. We integrated multi-omics data from TCGA, GTEx, and various public platforms to analyze expression, prognosis, genetic variations, methylation, immune infiltration, and drug resistance. In qRT-PCR, Western blot, functional assays (CCK-8, wound healing, colony formation), and a nude mouse xenograft model, were conducted to validate ABHD12's role in BRCA. ABHD12 was significantly upregulated at both mRNA and protein levels across multiple cancers. High expression correlated with poorer overall survival in BRCA, GBM, LGG, LIHC, and UVM. It demonstrated strong to moderate diagnostic value. ABHD12 expression was associated with copy number variations (CNVs) across 23 cancers, but not with methylation. It also correlated with immune cell infiltration (especially with macrophage), tumor mutational burden, neoantigens, microsatellite instability, and immune-related genes in certain cancers, and was potentially linked to resistance to multiple chemotherapeutics. KEGG analysis indicated that ABHD12 may play a potential role in the AMPK pathway. In BRCA, ABHD12 was higher in tumors than normal tissues. Functional studies showed ABHD12 enhanced proliferation, invasion, and migration, while silencing suppressed these traits. In vivo, ABHD12-overexpressing cells formed larger tumors, confirming its tumor-promoting role. ABHD12 may act as an oncogene across multiple cancers, linked to poor prognosis, diagnostic potential, chemotherapy resistance, and immunotherapy response. Its dysregulation is driven by CNVs rather than promoter methylation. ABHD12 might modulate macrophage polarization via the AMPK signaling pathway, leading to the remodeling of the tumor immune microenvironment. In vitro and vivo studies confirm its pro-tumorigenic role in BRCA, highlighting ABHD12 as a multifunctional biomarker and a molecular nexus linking lipid metabolism, immunity, and treatment resistance-warranting further study.
Viral infections might trigger systemic inflammatory responses characterised by inflammasome activation and cytokine release, driven by immune complex (IC) formation, but the precise mechanism remains unknown. The NLRP3 inflammasome is a vital component of innate immunity that plays a significant role in inflammatory responses. The involvement of the non-receptor spleen tyrosine kinase (SYK) in the activation of the NLRP3 inflammasome has been demonstrated. SYK plays a critical role in signal transduction pathways of immunoreceptors and regulates NLRP3 inflammasome activation. Our previous study showed that viral antigens and their IC with specific antibodies trigger NLRP3 inflammasome activation in macrophages. Therefore, we studied the role of SYK in IC-induced NLRP3 inflammasome activation pathway using primary mouse microglia as a macrophage model. The inflammasome activation was analysed by measuring cytokine secretion, ASC speck formation, and NLRP3 expression. To link SYK activation to NLRP3 inflammasome activation and other macrophage functional properties, we employed a specific SYK inhibitor, R406. We demonstrated SYK involvement in NLRP3 inflammasome activation by viral IC and in SYK-dependent antigen presentation in microglia after IC phagocytosis. Our findings also revealed lipid raft clustering upstream of SYK activation. These results may explain the mechanisms behind severe inflammation caused by viral IC.
Our previous studies have demonstrated that the activated pancreatic stellate cell (PSC) could induce islet damage in type 2 diabetes mellitus (T2DM). While tissue-type plasminogen activator (tPA) is significantly reduced in T2DM, its subsequent effects are unclear. The purpose of this experiment was to observe the impact of tPA on PSC activation, with the aim to better understand the potential role of tPA in T2DM. 50 type 2 diabetic patients and 50 healthy persons were included in the diabetic group and the control group, respectively. Fasting blood was collected separately, and the tPA-level was detected by ELISA. Rat PSCs were isolated from pancreatic tissue using standard explant techniques. The PSCs were then characterized by staining them with Oil Red O to visualize lipid droplets and using immunofluorescent markers (α-smooth muscle actin (α-SMA), vimentin, and glial fibrillary acidic protein (GFAP)). After characterization, the PSCs were treated with tPA, then the proliferation of PSCs was measured using the cell counting kit-8 (CCK-8), the apoptosis was observed by the caspase-3 fluorometric assay kit, and the migration ability was assessed using the wound-healing assay and the transwell migration assay. Finally, a Western blot was used to identify the extracellular matrix (ECM) component synthesized by PSCs. The diabetic patients had significantly lower levels of tPA compared to the controls. Rat PSCs treated with tPA exhibited more lipid droplet accumulation, and their ability of proliferation, migration, and ECM synthesis were significantly inhibited. This study demonstrated that tPA can play a crucial role in significantly inhibiting the activation, proliferation, migration, and ECM synthesis of PSC. Therefore, we speculate that the significant reduction of tPA in T2DM may exacerbate the detrimental effect of PSC on β-cell function.
Glucosylated-sterols can be synthetized endogenously, absorbed through the diet or derive from bacterial infection. Their clinical relevance is currently underestimated, even though their imbalance has been associated with an increased risk of neurodegeneration over the lifespan. We studied the detrimental effects elicited by dietary consumption of the plant-derived β-sitosterol β-D-glucoside (BSSG), known to be associated with the occurrence of ALS-PDC, to elucidate its potential mechanism of action. Zebrafish larvae and adults, as well as mice, were treated with BSSG administered directly in the water or via customized food pellet, respectively. Since the intestine was identified as the primary target tissue, its morphological and functional characteristics were assessed, together with transcriptional profiling and gut microbiota sequencing. Ex vivo analysis of zebrafish gut contractility was applied to evaluate intestinal neuromuscular responses. Mutant and transgenic zebrafish lines were used to explore a potential BSSG mechanism of action. BSSG induced intestinal inflammation in both zebrafish and mouse models. This previously unknown effect was evidenced by gut dysmotility and inflammatory response. Transcriptomic analyses revealed increased expression of inflammation-related genes in the intestine of both zebrafish and mice, while preliminary gut microbiota analyses suggested the onset of dysbiosis. Transgenic and mutant zebrafish lines, depleted of genes involved in glucocorticoids synthesis and activity, evidenced that BSSG likely interacts with the glucocorticoid receptor, potentially impairing its canonical anti-inflammatory activity. We identified novel pathways altered by dietary BSSG exposure. This molecule appears to initially induce gut inflammation, leading to changes in intestinal morphology and function, and may contribute to neurodegeneration through disruption of the well-known gut-brain axis.
Appetite dysregulation and obesity have become major global health challenges, closely linked to metabolic disorders and reduced quality of life. Dietary polyphenols, particularly tea polyphenols, have attracted increasing attention due to their beneficial effects on appetite control and metabolic homeostasis. A growing body of evidence suggests that tea polyphenols suppress food intake through multiple mechanisms, including inhibition of digestive enzymes, modulation of enteroendocrine hormone secretion, and attenuation of low-grade inflammation. Meanwhile, alterations in gut microbiota composition and microbial metabolites have been increasingly recognized as critical contributors to appetite regulation and energy balance. This review summarizes the role of tea polyphenols in reshaping gut microbial composition and metabolic output, with particular emphasis on microbiota-derived 5-hydroxytryptamine (5-HT) and short-chain fatty acids (SCFAs). How these microbial signals engage transient receptor potential vanilloid 1 (TRPV1)-dependent calcium ion (Ca2+) signaling in enteroendocrine cells (EECs) and gut-innervating sensory afferents is further discussed, thereby linking microbial metabolism to gut-brain communication and central appetite regulation. It provides theoretical basis for the development of dietary interventions targeting appetite regulation and metabolic disorders.
Internal carotid artery fenestration is a rare vascular anomaly that may present with transient ischemic attack symptoms due to localized flow disturbances. It is important to report such cases, as they present unique diagnostic challenges and clinical implications, particularly when associated with systemic vascular risk factors such as diabetes and hypertension. Differentiating internal carotid artery fenestration from other conditions, such as internal carotid artery dissection, is crucial for appropriate management and patient outcomes. A 78-year-old Iranian female patient with a medical history of uncontrolled diabetes mellitus and hypertension presented to the emergency department with sudden-onset double vision, dizziness, and weakness in her left limbs. Symptoms lasted for 15 minutes and fully resolved. Neurological examination revealed mild weakness in the left upper and lower limbs but no sensory deficits. A bruit was detected over the left carotid artery, raising suspicion for carotid artery disease. Blood tests showed elevated blood glucose, and imaging studies, including carotid Doppler ultrasound, revealed irregularities and increased intima-media thickness, suggesting early vascular changes. Brain computed tomography scan was normal, and computed tomographic angiography of the head and neck revealed an incidental finding of internal carotid artery fenestration at the cervical segment. The fenestration appeared as a mild fusiform dilation of internal carotid artery with no signs of dissection or thrombosis. The patient was started on dual antiplatelet therapy (aspirin and clopidogrel) and optimized for blood pressure and lipid control. She was discharged with no residual neurological deficits, and follow-up was arranged for continued management of her cardiovascular risk factors. This case highlights the diagnostic challenges and clinical relevance of internal carotid artery fenestration, particularly in patients with systemic vascular risk factors. Although internal carotid artery fenestration is often asymptomatic, it can be associated with cerebrovascular complications, such as ischemic events. In this case, the transient symptoms likely resulted from localized hemodynamic disturbances due to the fenestrated artery. While there is no established consensus on the management of asymptomatic internal carotid artery fenestration, dual antiplatelet therapy and risk factor optimization remain key strategies. Further research is needed to better understand the implications of internal carotid artery fenestration and to refine diagnostic and management protocols for these rare vascular anomalies.
Differences in the interfacial composition and structure of fat globules between infant formula (IF) and human milk (HM) limit lipid digestion. To address this issue, this study incorporated milk fat globule membrane protein (MFGMP) into liposomes (Lip) to form MFGMP-Lip complexes for stabilizing model infant formula emulsions (MIFEs). The interaction between MFGMP and Lip was characterized, and its influence on the stability, interfacial properties, and in vitro lipid digestion of MIFEs was investigated. The MFGMP-Lip interaction was spontaneous and exothermic, driven by hydrogen bonds, van der Waals forces, and hydrophobic interactions. Lip promoted the exposure of hydrophobic groups in MFGMP. The complex at a 1:1 MFGMP-to-lipid mass ratio showed the lowest surface tension (8.26 mN/m) and the highest emulsifying capacity, which resulted in the emulsion (MIFE3) with the smallest particle size (427.57 nm) and highest physical stability. Microstructural and interfacial chemical composition analysis confirmed the co-localization of MFGMP, phospholipids, and cholesterol on the lipid droplet surfaces in MIFEs, exhibiting HM fat globule-like interfacial characteristics. This improvement led to higher lipid digestibility in MIFEs during in vitro digestion. The lipolysis degree of MIFE3 (83.97%) and MIFE4 (82.51%) was similar to that of HM (83.64%) and significantly higher than that of commercial IF (77.51%). Modulating lipid droplet interfacial properties based on MFGMP-Lip complexes could be an effective strategy to improve the lipid digestion of infant foods.
Exosomes are small, nanoscale extracellular vesicles that facilitate intercellular communication through the transport of proteins, lipids, and nucleic acids. Recent advances in utilizing exosomes as promising vehicles for targeted delivery have opened up numerous opportunities for establishing next-generation exosome-based nanocarriers and therapeutics for multiple biomedical domains. Their inherent biocompatibility, low immunogenicity, nanoscale size and ability to naturally cross biological barriers make them promising alternatives to traditional synthetic drug-delivery systems such as liposomes and polymeric nanoparticles. In this review, we analyzed existing literature and provided an overview of biogenesis, molecular composition, and functional diversity of exosomes followed by a review of recent reports on their application in regenerative therapies and immunomodulation. First, we outlined the role of exosomes in angiogenesis, tissue repair, and immunomodulation. Next, we critically evaluated existing engineering solutions, including isolation techniques, cargo-loading approaches, genetic programming of donor cells, and surface functionalization strategies. Furthermore, we provided a comprehensive overview of recent research on engineered systems that enable controlled release, stability, and multifunctional design of therapeutics, such as exosome-biomaterial hybrids, synthetic exosome mimics, and exosome-nanoparticle platforms. Finally, we highlighted the significant barriers, such as vesicle heterogeneity, optimized production and standardization, and other regulatory challenges in translating exosomal therapeutics from basic research to clinical practice.