Advanced glycation end products (AGEs) are the unwanted by-products of excessive sugar intake, and their generation and accumulation promote aging and disease occurrence. However, the lack of robust biology model and platform for fast evaluating AGE generation and accumulation under intervention of drugs hampers AGEs-targeted therapeutic development. This work described a novel biological high AGEs recombinant extracellular matrix 3D human hepatocellular spheres model was built, under the same cell numbers, this 3D hepatocellular spheres expressed more AGEs over an order of magnitude than monolayer culture cells. Combined with UV curable gelatin methacryloyl (GelMA), biological 3D human hepatocellular sphere were made into a extruded type bio-ink with high AGEs, simply encapsulated in a hepatic lobule shaped micro array polymethyl methacrylate (PMMA) microfluidic chip successfully. Due to this biomimetic fluid microreactor environment, our biological microfluidic chip enables effectively determine the inhibition capacity of compounds on endogenous AGE accumulation with a high sensitivity and in a short time, total determination workflow less than 2.5 h, it takes 1/200 of the time required by mainstream methods. The evaluation results showed that alisol B 23-monoacetate and chlorogenic acid were potential natural AGEs inhibitors. Moreover, the integration of high AGEs bio-ink and microfluidic chip provides a promising tool for AGE-related drug discovery and liver disease research.

Blue light (BL) is a known risk factor for age-related macular degeneration (AMD), a retinal pathology where damage to the retinal pigment epithelium (RPE) is one of the earliest events. While the endocannabinoid system (ECS) is implicated in various physio-pathological conditions of the retina, its role in BL-injured RPE has not yet been addressed. To fill this gap, we developed an in vitro model of BL-induced human RPE damage showing key features of AMD: cytotoxicity, cell cycle arrest, oxidative stress, inflammation, and cellular senescence. Notably, our model demonstrates modulation of gene and protein expression of specific ECS elements, particularly cannabinoid receptors 1 and 2 (CB1 and CB2), thus providing unprecedented evidence of ECS dysregulation in RPE cells upon BL exposure.

Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, has emerged as a critical player in cancer pathogenesis. Concurrently, inflammation, a key biological response to tissue injury or infection, significantly influences cancer development and progression. The interplay between ferroptosis and inflammation represents a promising yet underexplored area of research. This review synthesizes recent advances in understanding the molecular mechanisms governing their interaction, emphasizing how ferroptosis triggers inflammatory responses and how inflammatory mediators, such as TNF-α, regulate ferroptosis through iron metabolism and lipid peroxidation pathways. Key molecular targets within the ferroptosis-inflammation axis, including GPX4, ACSL4, and the NF-κB signaling pathway, offer therapeutic potential for cancer treatment. By modulating these targets, it may be possible to enhance ferroptosis and fine-tune inflammatory responses, thereby improving therapeutic outcomes. Additionally, this review explores the broader implications of targeting the ferroptosis-inflammation interplay in disease treatment, highlighting opportunities for developing innovative strategies to combat cancer. By bridging the gap in current knowledge, this review provides a comprehensive resource for researchers and clinicians, offering insights into the therapeutic potential of this intricate biological relationship.

While lipids and inflammation are recognized as key modulators of tumor progression, their causal interplay in endometrial carcinoma in situ (ECIS)-the precursor of endometrial cancer-remains mechanistically undefined. Despite broad associations between lipid metabolism and cancer, the specific pathways driving ECIS initiation through inflammatory mediators are unknown.

We pioneer an integrative Mendelian randomization (MR) framework combining multivariable MR, Bayesian weighted MR (BWMR), and sensitivity analyses to address pleiotropy. This approach was systematically applied to 179 lipids and 91 inflammatory factors. Methodological novelty further includes mediation analysis quantifying inflammatory factors' role in lipid-ECIS pathways.

First evidence reveals a phosphatidylcholine (O-18:0_16:1)-TNFSF12-ECIS axis: TNFSF12 mediates 4.894 % of phosphatidylcholine's effect (OR: 2.925; beta: 1.073; 95 % CI: 1.752-4.884; p = 4.032E-05), attenuating the direct lipid-ECIS association. This represents the inaugural demonstration of an inflammation-mediated lipid pathway in ECIS pathogenesis.

As the first MR study decoding lipid-ECIS causality, we establish the following.

Isatis tinctoria L. (Isatidis Radix) is a type of Chinese medicine used to treat various inflammations. Lignans are the main active ingredients of Isatidis Radix, which exhibit potent anti-inflammatory properties. However, the targets underlying the anti-inflammatory effects of Isatidis Radix remain unclear.

The objective of this research was to investigate the active constituents of Isatidis Radix and the molecular mechanisms behind its anti-inflammatory properties.

Firstly, Liquid Chromatography-Mass Spectrometry (LC-MS), network pharmacology, and molecular docking were employed to identify the active ingredients and key targets of Isatidis Radix lignans and predict their underlying anti-inflammatory mechanisms. Secondly, the enzyme-linked immunosorbent assay (ELISA) and the LPS-induced cell model were employed to verify the selective inhibitory effect of the active ingredients on the key target COX-2. Finally, the analgesic and anti-inflammatory effects were evaluated using the hot-plate test, acetic acid-induced writhing, complete Freund's adjuvant-induced paw edema, and xylene-induced ear edema assays.

A total of 24 compounds were found to be absorbed into the bloodstream, including 15 prototype components and 9 metabolites, as determined by LC-MS analysis. Furthermore, Network pharmacology analysis revealed that COX-2 served as the central target in the anti-inflammatory mechanism of Isatidis Radix lignans. Lariciresinol, a class of lignans derived from Isatidis Radix, selectively inhibited COX-2 and reduced inflammatory marker production in vitro and in vivo. It significantly increased the incubation period of heat pain, reduced writhing frequency, and decreased the severity of ear and foot swelling. Moreover, lariciresinol had no obvious gastrointestinal side effects and was not toxic to cardiomyocytes.

Our study indicates that Isatidis Radix lignans exert their anti-inflammatory effect by selectively inhibiting the COX-2 enzyme and confirms lariciresinol as a natural selective COX-2 inhibitor.

Ether-glycerophospholipids (ether-GPs), the ether bond- (- O -) containing glycerophospholipids are major components of brain lipidome. Ether-GPs play a crucial role in regulating neuronal function, and their deficiency has been implicated in many neurodegenerative diseases. However, how they are affected after traumatic brain injury (TBI) is not known. Our data demonstrate a significant decrease in ether-GPs abundance in the mouse cortex following controlled cortical impact (CCI) induced TBI. This is at least in part due to the impairment of peroxisomal ether-GP synthesis in the mouse brain after TBI. We detected dysregulation of peroxisomal ether-GPs synthesizing enzymes - glyceronephosphate-O-acyltransferase (GNPAT) and alkylglycerone phosphate synthase (AGPS) in the injured mouse brains. Our data demonstrate a significant decline in GNPAT level in the peroxisomal fraction and a marked accumulation of AGPS in the cytosol of mouse cortices after TBI. To restore ether-GPs level in the injured brain, we treated TBI mice with an ether-GP precursor - 1-O-octadecylglycerol (OAG) to bypass peroxisomal ether-GPs synthesizing steps. OAG partially restored the levels of several ether-GPs, attenuated inflammatory cytokine expression and improved their functional recovery after TBI. Taken together, our data demonstrate that decline in ether-GPs abundance after TBI is at least in part due to the impairment in peroxisomal ether-GPs synthesis and that restoration of ether-GPs by OAG treatment can improve TBI outcomes.

POI is a highly heterogeneous, multifactorial condition, and dysregulated lipid metabolism has been implicated in its inflammatory pathogenesis This study is the first to systematically investigate causal relationships between 179 lipid species, 91 inflammatory factors, and POI using Two-Sample Mendelian Randomization (TSMR) and Multivariable Mendelian Randomization (MVMR). By integrating lipidomics and inflammatories data with POI from Genome-wide association study (GWAS) and FinnGen, we identified 18 causally significant lipids, including risk-elevating phosphatidylcholines and sphingomyelins, and protective triglycerides. Methodologically, we innovatively applied Bayesian Weighted Mendelian Randomization (BWMR) to confirm the robustness of causal estimates, addressing limitations of conventional MR in pleiotropy-prone metabolic networks. Biologically, we discovered IL-10 mediates 7.02-9.03 % of the effects of sphingomyelin (d40:2) and (d42:2) on POI, reconciling lipid-driven inflammation with ovarian aging-a mechanism previously unreported. Sensitivity analyses confirmed no horizontal pleiotropy (p > 0.05). This work establishes three advances: (1) First MR evidence linking specific lipid subclasses (not just broad categories) to POI; (2) Identification of IL-10 as a novel inflammatory mediator bridging sphingolipids and POI pathogenesis; (3) A validated framework combining MVMR and mediation analysis to disentangle direct/indirect effects in reproductive aging. Our findings provide clinically actionable insights: IL-10 emerge as potential biomarkers, while triglycerides highlight dietary/therapeutic targets. This mechanistic clarity advances POI research beyond prior observational associations into causal biology.

20-carbon fatty acid-derived eicosanoids are versatile signaling oxylipins in mammals. In particular, a group of eicosanoids termed prostanoids are involved in multiple physiological processes, such as reproduction and immune responses. Although some eicosanoids such as prostaglandin E2 (PGE2) have been detected in some insect species, molecular mechanisms of eicosanoid synthesis and signal transduction in insects have not been thoroughly investigated. Our phylogenetic analysis indicated that, in clear contrast to the presence of numerous receptors for oxylipins and other lipid mediators in humans, the Drosophila genome only possesses a single ortholog of such receptors, which is homologous to human prostanoid receptors. This G protein-coupled receptor, named Prostaglandin Receptor or PGR, is activated by PGE2 and its isomer PGD2 in Drosophila S2 cells. PGR mutant flies die as pharate adults with insufficient tracheal development, which can be rescued by supplying high oxygen. Consistent with this, through a comprehensive mutagenesis approach, we identified a Drosophila PGE synthase whose mutants show similar pharate adult lethality with hypoxia responses. Drosophila thus has a highly simplified eicosanoid signaling pathway as compared to humans, and it may provide an ideal model system for investigating evolutionarily conserved aspects of eicosanoid signaling.

The remnant cholesterol inflammatory index (RCII) is a novel metric that combines remnant cholesterol and high-sensitivity C-reactive protein, reflecting the metabolic and inflammatory risk. This study investigates the association between RCII and long-term risks of all-cause and cause-specific mortality in middle-aged and elderly populations in the US and China.

We analyzed data from the National Health and Nutrition Examination Survey (NHANES) and the China Health and Retirement Longitudinal Study (CHARLS), including 7,565 and 12,932 participants aged 45 years and older, respectively. The participants were categorized into quartiles based on natural log-transformed RCII (lnRCII) values. Kaplan-Meier survival analysis, Cox proportional hazards models, restricted cubic splines (RCS) and mediation analysis were used to examine the relationship between lnRCII and mortality outcomes, adjusting for potential covariates.

The mean age of the participants was 59.90 ± 10.44 years (NHANES) and 58.64 ± 9.78 years (CHARLS), with 53.28% and 52.50% female, respectively. Kaplan-Meier survival analysis showed that higher lnRCII quartiles (≥ 0.79 in NHANES, ≥ -0.13 in CHARLS) were significantly associated with increased all-cause mortality risk (p < 0.001). Each standard deviation (SD) increase in lnRCII corresponded to a higher risk of all-cause mortality, and the hazard ratios (HRs) and 95% confidence interval (CI) were 1.29 (95% CI: 1.21-1.36) in NHANES and 1.26 (95% CI: 1.15-1.38) in CHARLS. In NHANES, lnRCII was also associated with elevated risks of cardiovascular mortality (HR = 1.21, 95% CI: 1.08-1.35) and cancer mortality (HR = 1.30, 95% CI: 1.09-1.55). RCS analysis indicated a J-shaped relationship between lnRCII and both all-cause and cardiovascular mortality, and a linear association with cancer mortality. Mediation analysis showed that systolic blood pressure and fasting plasma glucose partially mediated these associations. Subgroup analyses suggested a stronger association between lnRCII and all-cause mortality in middle-aged US participants (p for interaction = 0.010).

Elevated RCII levels are significantly associated with increased all-cause mortality risk middle-aged and elderly populations in both the US and China. In the US population, RCII is also associated with increased risks of cardiovascular and cancer mortality. By integrating metabolic and inflammatory risk factors, RCII may serve as a valuable tool for mortality risk stratification and clinical decision-making.

Hyperactivation of osteoclasts has been identified as a significant etiological factor in several bone resorption-related disorders, including osteoporosis, periodontitis, arthritis, and bone metastasis of tumors. It has been demonstrated that the severity of these diseases is influenced by lipids that regulate osteoclast differentiation and activity through specific signaling pathways and cytokine levels. The regulatory mechanisms of different types of lipids on osteoclastogenesis vary across diverse disease contexts in bone resorption regulated by osteoclasts. This review presents an overview of the mechanisms underlying osteoclast formation and summarizes the pathways through which various lipids regulate osteoclastogenesis in different pathological contexts. We also discuss effective therapeutic strategies for osteolytic diseases based on modulation of lipid metabolism.

T cells play pivotal roles in inflammation's initiation and progression. Exploring natural compounds that regulate T cell function is crucial for preventing and treating inflammation. Herein, we report that Alternariol (AOH), a marine-derived secondary metabolite, exerts an anti-inflammatory activity by targeting T cell function. Using an ovalbumin (OVA)-induced OT-II CD4+ T cell activation model, we demonstrated that AOH potently suppresses T cell proliferation and cytokine secretion, mildly promotes T cell apoptosis, and spares antigen presentation processes. Mechanistically, AOH controlled early T cell activation by inhibiting the expression of activation markers (CD69, CD25, CD44) and transcription factors (T-bet, Eomes), leading to impaired Th1 cytokine production. In vivo experiments revealed that AOH attenuated OVA-induced lung injury in mice by reducing immune cell infiltration in pulmonary tissues and draining lymph nodes. Notably, AOH dramatically suppressed OVA-specific T cells migrating to the inflammatory lung while impairing T-cell-mediated other immune cell infiltration. Collectively, AOH exhibited potent anti-inflammatory effects by modulating T cell proliferation, function, and migration, offering a promising therapeutic strategy for T-cell-mediated inflammatory diseases.

20-carbon fatty acid-derived eicosanoids are versatile signaling oxylipins in mammals. In particular, a group of eicosanoids termed prostanoids are involved in multiple physiological processes, such as reproduction and immune responses. Although some eicosanoids such as prostaglandin E2 (PGE2) have been detected in some insect species, molecular mechanisms of eicosanoid synthesis and signal transduction in insects have not been thoroughly investigated. Our phylogenetic analysis indicated that, in clear contrast to the presence of numerous receptors for oxylipins and other lipid mediators in humans, the Drosophila genome only possesses a single ortholog of such receptors, which is homologous to human prostanoid receptors. This G protein-coupled receptor, named Prostaglandin Receptor or PGR, is activated by PGE2 and its isomer PGD2 in Drosophila S2 cells. PGR mutant flies die as pharate adults with insufficient tracheal development, which can be rescued by supplying high oxygen. Consistent with this, through a comprehensive mutagenesis approach, we identified a Drosophila PGE synthase whose mutants show similar pharate adult lethality with hypoxia responses. Drosophila thus has a highly simplified eicosanoid signaling pathway as compared to humans, and it may provide an ideal model system for investigating evolutionarily conserved aspects of eicosanoid signaling.

This study aimed to explore the association between lipid-based Cardiovascular Event Risk Tests (CERT1 and CERT2), including ceramides (Cer) and phosphatidylcholine (PC) lipid species, and rheumatoid arthritis (RA), an inflammatory disease that can increase the risk of cardiovascular diseases.

Prospective population-based cohort study.

Primary care centres across five geographical areas in Finland.

The study included 7702 individuals (selected from the FINRISK cohort) who were assessed for the prevalence and incidence of RA. At baseline, the cohort included 7518 RA-free individuals, among whom 329 developed RA during the study, and 184 had a history of RA at baseline. Serum levels of ceramides and PC were measured using mass spectrometry, and CERT scores were calculated.

Prevalence and incidence of RA, CERT scores, and serum lipid levels.

CERT scores were associated with prevalent RA but not with incident RA in the full cohort. Adjusted ORs and 95% CI for prevalent RA were 1.24 (95% CI 1.05 to 1.46) for CERT1 and 1.42 (95% CI 1.20 to 1.68) for CERT2. Stratified analyses showed that these associations were consistent among individuals over 50 years of age and across both sexes. The Cer (d18:1/16:0)/PC (16:0/22:5) ratio was significantly associated with RA in younger individuals (OR 1.66; 95% CI (1.26 to 2.18)). Overall, the association between lipids and RA was stronger in women than men.

The study shows a significant association between prevalent RA and bioactive lipid species used for cardiovascular risk assessment. These findings emphasise the importance of considering residual inflammatory risks, such as RA, in cardiovascular risk evaluations in clinical settings.

This systematic review explores the hypothesis that various lipid categories and lipid metabolism-related genomic variations link to mental disorders, seeking potential clinically useful markers.

We searched PubMed, Scopus, and PsycInfo databases until October 12th, 2024, using terms related to lipidomics, lipid-related genomics, and different mental disorders, i.e., Major Depressive Disorder (MDD), Bipolar Disorder (BD), Schizophrenia (SCZ), and Obsessive-Compulsive Disorder (OCD). Eligible studies were assessed. Extracted data included author, year, methodology, outcomes, genes, and lipids linked to disorders. Bias and evidence certainty were evaluated. The systematic review adhered to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and a registered protocol (PROSPERO: CRD42023438862).

A total of 27 studies were included. SCZ showed alterations in 77 lipids, including triglycerides (TG), ceramides, and phosphatidylcholine, while MDD and BD exhibited 97 and 47 altered lipids, respectively, with overlap among disorders. Shared genes, such as ABCA13, DGKZ, and FADS, and pathways involving inflammation, lipid metabolism, and mitochondrial function were identified. OCD was associated with sphingolipid signaling and peroxisomal metabolism.

Lipid signatures in MDD, BD, and SCZ shed light on underlying processes. Further research is needed to validate biomarkers and refine their clinical applications in precision psychiatry.

Existing studies on the association between the composite dietary antioxidant index (CDAI) and all-cause mortality are controversial. We aimed to analyze the association of CDAI with all-cause mortality, and determine the influence of gender on this association.

The data of adult participants (age ≥ 18) from the National Health and Nutrition Examination Survey (NHANES) cycles spanning 2001 to 2018 were analyzed. The NHANES-issued identifiers for participants enabled the linkage of data from the NHANES Public Use Linked Mortality File.

The study encompassed a sample of 15,651 individuals. The mean CDAI was 0.52 ± 6.06. The restricted cubic spline revealed that the hazard ratio (HR) of all-cause mortality decreased significantly with increasing CDAI. However, this negative association existed only when the CDAI was less than 5. Multivariate Cox regression analysis showed that compared to the first CDAI quartile, the HR of all-cause mortality was significantly decreased in the third and fourth quartiles (both p < 0.001), and the p-value of the trend test was <0.001. In the subgroup analysis, a notably strong negative association between CDAI and the risk of all-cause mortality was only observed in men (p for interaction <0.001).

Higher CDAI is associated with a reduced risk of all-cause mortality exclusively in adult males, underscoring the substantial influence of gender on this relationship.

The condition of cellular senescence has specific features, including an altered lipid metabolism. Delta-9 desaturase (Δ9) catalyzes the conversion of saturated fatty acids, such as palmitic acid and stearic acid, into their monounsaturated forms, palmitoleic and oleic acid, respectively. Δ9 activity is important for most lipid functions, such as membrane fluidity, lipoprotein metabolism and energy storage. The present study aimed to investigate differences in the expression of Δ9 in senescence-induced pancreatic (MIA-PaCa-2 and PANC-1) and hepatic (Hepa-RG and HLF) cancer cell lines. Cellular senescence was induced by growing cells in the presence of the chemotherapic drug doxorubicin. Senescence status was determined by the senescence-associated beta-galactosidase activity assay kit combined with the p21 and senescence associated secretory phenotype protein assay. Δ9 was downregulated in all senescence-induced cell lines compared to control cells, in both the lipidomic analysis and when measuring protein levels via western blotting. Hence, our findings demonstrate that the study of membrane lipid composition and the expression levels of Δ9 could potentially form the basis for future applications investigating the state of cellular senescence.

As a synthetic rubber antioxidant, the environmental monitoring concentrations of N-(1,3-Dimethylbutyl)-N'-phenyl-p-phenylenediamine (6-PPD) have exceeded the risk threshold, attracting widespread attention. Although investigations into the harmful effects on zebrafish have commenced, a comprehensive exploration of its toxicological impacts and underlying molecular mechanisms remains to be conducted. By using zebrafish as a model, this study systematically evaluated 6-PPD-induced lipid metabolism disorders and inflammation response following environmental exposure. Bioinformatics analysis revealed that 6-PPD target genes enriched in the hepatitis B pathway, indicating potential hepatic toxicity via inflammatory pathways. Therefore, we hypothesize that 6-PPD could trigger hepatotoxicity through the crosstalk between lipid metabolism and inflammation. Further experiments substantiated this hypothesis by showing lipid accumulation in the liver following 6-PPD exposure, along with elevated triglyceride (TG) and total cholesterol (TC) levels, and imbalanced expression of lipid metabolism-related marker genes. Additionally, 6-PPD exposure induced the accumulation of reactive oxygen species (ROS) and inhibited the differentiation and maturation of immune cells, resulting in immune evasion. Most of these abnormalities were exacerbated in a dose-dependent manner with increasing concentrations of 6-PPD. The addition of the PPARγ pathway agonist puerarin (PUE) or NF-κB pathway inhibitor quinazoline (QNZ) to 6-PPD exposure group mitigated these toxic effects, validating our conjecture that lipid metabolism disorder and inflammatory responses may result from the regulation of the PPARγ/NF-κB pathway.

Conventional dendritic cells (cDCs) are crucial antigen-presenting cells that initiate and regulate T cell responses, thereby shaping immunity against pathogens, innocuous antigens, tumors, and self-antigens. The migration of cDCs from peripheral tissues to draining lymph nodes (dLNs) is essential for their function in immune surveillance. This migration allows cDCs to convey the conditions of peripheral tissues to antigen-specific T cells in the dLNs, facilitating effective immune responses. Migration is primarily mediated by chemokine receptor CCR7, which is upregulated in response to homeostatic and inflammatory cues, guiding cDCs to dLNs. However, during type 2 immune responses, such as those triggered by parasites or allergens, a paradox arises-cDCs exhibit robust migration to dLNs despite low CCR7 expression. This review discusses how type 2 inflammation relies on additional signaling pathways, including those induced by membrane-derived bioactive lipid mediators like eicosanoids, sphingolipids, and oxysterols, which cooperate with CCR7 to enhance cDC migration and T helper 2 (Th2) differentiation. We explore the potential regulatory mechanisms of cDC migration in type 2 immunity, offering insights into the differential control of cDC trafficking in diverse immune contexts and its impact on immune responses.

Lipid metabolism is a well-regulated process essential for maintaining cellular functions and energy homeostasis. Dysregulation of lipid metabolism is associated with various conditions, including cardiovascular diseases, neurodegenerative disorders, and metabolic syndromes. This review explores the mechanisms underlying lipid metabolism, emphasizing the roles of key lipid species such as triglycerides, phospholipids, sphingolipids, and sterols in cellular physiology and pathophysiology. It also examines the genetic and environmental factors contributing to lipid dysregulation and the challenges of diagnosing and managing lipid-related disorders. Recent advancements in lipid-lowering therapies, including PCSK9 inhibitors, ezetimibe, bempedoic acid, and olpasiran, provide promising treatment options. However, these advancements are accompanied by challenges related to cost, accessibility, and patient adherence. The review highlights the need for personalized medicine approaches to address the interplay between genetics and environmental factors in lipid metabolism. As lipidomics and advanced diagnostic tools continue to progress, a deeper understanding of lipid-related disorders could pave the way for more effective therapeutic strategies.

Inflammation underlies a wide variety of physiological and pathological processes, the Lipopolysaccharide (LPS)-induced inflammation model is widely recognized as a classical inflammatory paradigm, while Transforming growth factor-β (TGF-β) serves as a potent immunosuppressant capable of inhibiting immune responses and mitigating inflammation. However, its in vivo instability and the high cost associated with purification have imposed limitations on its clinical application. Therefore, we propose a therapeutic strategy for genetically modifying extracellular vesicles (HEVs) derived from HEK-293 T cells to incorporate TGF-β which holds potential for mitigating LPS-induced inflammation. In this study, we engineered a TGF-β lentivirus that specific incorporates TGF-β into HEVs and efficiently produces highly expressed TGF-β HEVs (HEVTs) through infection of HEK293 cells. Our data demonstrated that, compared to the LPS group, HEVTs internalized by immune cells significantly regulated pro-inflammatory cytokine expression in RAW 264.7 cells, such as IL-1β (p < 01), TNF-α (p < 001). Moreover, HEVTs were found to effectively reach the lesion area, compared to the LPS group, resulting in a remarkable inhibition in the activation of macrophages (p < 0.0001), dendritic cells (p < 0.0001), and neutrophils (p < 0.0001) in the peripheral immune system as well as microglia in the central nervous system of LPS-induced inflammation model mice. The utilization of this endogenous loading technique may present a promising strategy for the protein-based pharmacotherapy of inflammatory disorders.

The aim of this study was to investigate the joint association of systemic inflammatory response index (SIRI) and sarcopenia with cancer-specific and all-cause mortality in individuals with self-reported cancer.

The study cohort comprised individuals with a self-reported cancer diagnosis from the NHANES database, with data collected between 1999 and 2006 and 2011-2018. The researchers tracked deaths up to 31 December 2019 by linking the relevant records to those held by the (NDI). A weighted sampling design was employed, with participants stratified according to the median value of the SIRI. Cox regression models were employed to assess the association between SIRI, sarcopenia, all-cause mortality, and cancer-specific mortality.

The study cohort comprised 1316 individuals with self-reported cancer. Over a median follow-up period of 9.21 years, 523 all-cause deaths were recorded, including 163 cancer-specific and 360 non-cancer deaths. Adjusting for multiple confounders, elevated SIRI levels were significantly associated with increased risks of all-cause (HR = 1.90 [1.58-2.28]), cancer (HR = 1.88 [1.26-2.78]), and non-cancer mortality (HR = 1.93 [1.54-2.41]). Sarcopenia also emerged as a significant predictor of mortality. Individuals with sarcopenia faced a 50% higher risk of all-cause mortality (HR = 1.50 [1.18-1.91]) and a 54% higher risk of non-cancer mortality (HR = 1.54 [1.11-2.12]). However, the association with cancer mortality was not significant in the fully adjusted model. When both sarcopenia and elevated SIRI were present, the risk was the highest for all-cause (HR = 2.54 [1.92-3.37]), cancer (HR = 2.29 [1.19-4.40]), and non-cancer mortality (HR = 2.63 [1.78-3.89]). Elevated SIRI alone was linked to significant risks for all-cause (HR = 1.91 [1.51-2.42]), cancer (HR = 1.95 [1.28-2.97]), and non-cancer mortality (HR = 1.92 [1.46-2.53]). Sarcopenia alone significantly increased the risk of all-cause mortality (HR = 1.63 [1.01-2.56]) but not cancer mortality.

Our study is the first to demonstrate the joint association between the SIRI and sarcopenia with mortality among individuals with self-reported cancer. These findings underscore the importance of assessing and managing these two factors in individuals with self-reported cancer to reduce the risk of death and improve survival outcomes.

Macrophages, crucial innate immune cells, defend against pathogens and resolve inflammation, maintaining tissue balance. They perform phagocytosis, present antigens to T cells, and bond innate and adaptive immunity through various activation states. Classical activation is associated with Th1 responses and interferon γ production, while alternative activation, induced by interleukin 4, is characterized by increased endocytosis, reduced secretion of pro-inflammatory cytokines, and roles in immunoregulation and tissue remodeling. Although these represent opposite extremes observed in vitro, the remarkable plasticity of macrophages allows for a wide spectrum of activation phenotypes that are complex to characterize experimentally. While the application of omics techniques has resulted in significant advances in the characterization of macrophage polarization, lipidomic studies have received lesser attention. Beyond their role as structural components and energy sources, lipids function as signaling molecules that regulate macrophage activation and polarization, thereby shaping immune responses. This work reviews the interaction between lipid signaling and macrophage polarization, exploring how lipid metabolism influences macrophage phenotype and function. These insights offer potential therapeutic strategies for immune-mediated diseases and inflammation-related disorders, including inflammaging.

Acute kidney injury (AKI) can progress to chronic kidney disease (CKD) and subsequently to renal fibrosis. Poor repair of renal tubular epithelial cells (TECs) after injury is the main cause of renal fibrosis. Studies have shown that restoring damaged fatty acid β-oxidation (FAO) can reduce renal fibrosis. Adipose triglyceride lipase (ATGL) is a key enzyme that regulates lipid hydrolysis. This study, for the first time, demonstrated that ATGL was downregulated in the renal TEC in the AKI-CKD transition mouse model. Moreover, treatment with the ATGL inhibitor atglistatin exacerbated lipid accumulation and downregulated the FAO level and mitochondrial function, while it increased the level of oxidative stress injury and apoptosis, resulting in aggravated renal fibrosis. In contrast, ATGL overexpression suppressed lipid accumulation, improved the FAO level and mitochondrial function, and attenuated oxidative stress and apoptosis, thereby ameliorating fibrosis in vitro and in vivo. In summary, ATGL regulates renal fibrosis by reprogramming lipid metabolism in renal TECs. This study provided new avenues and targets for treating CKD.

Cellular aging is a multifactorial and intricately regulated physiological process with profound implications. The interaction between cellular senescence and cancer is complex and multifaceted, senescence can both promote and inhibit tumor progression through various mechanisms. M6A methylation modification regulates the aging process of cells and tissues by modulating senescence-related genes. In this review, we comprehensively discuss the characteristics of cellular senescence, the signaling pathways regulating senescence, the biomarkers of senescence, and the mechanisms of anti-senescence drugs. Notably, this review also delves into the complex interactions between senescence and cancer, emphasizing the dual role of the senescent microenvironment in tumor initiation, progression, and treatment. Finally, we thoroughly explore the function and mechanism of m6A methylation modification in cellular senescence, revealing its critical role in regulating gene expression and maintaining cellular homeostasis. In conclusion, this review provides a comprehensive perspective on the molecular mechanisms and biological significance of cellular senescence and offers new insights for the development of anti-senescence strategies.

Extra-cerebral manifestations of Alzheimer's disease (AD) develop in the retina, which is, therefore, considered a "window to the brain". Recent studies demonstrated the dysregulation of the endocannabinoid (eCB) system (ECS) in AD brain. Here, we explored the possible alterations of ECS and the onset of gliosis in the retina of AD-like mice. Tg2576 (TG) mice overexpressing the amyloid precursor protein (APP) were used at the age of 12 months, when hippocampal β-amyloid plaques had not been developed yet. Analysis of retinal gliosis showed a significant increase in the number of IBA1 (+) microglia cells in TG versus wild type (WT). Gliosis was not associated with retinal β-amyloid plaques, evident retinal degenerative signatures, or excitotoxicity; instead, oxidative stress burden was observed as increased acrolein levels. Analysis of the ECS (receptors/metabolic enzymes) through western blotting (WB) revealed the up-regulation of cannabinoid receptor 2 (CB2) and monoacylglycerol lipase (MAGL), the enzyme responsible for the degradation of 2-arachidonoylglycerol (2-AG), in TG retinas. Fluorescence intensity analysis of anti-CB2 and anti-MAGL immuno-stained cryosections was consistent with WB, showing their up-regulation throughout the retinal layers. No statistically significant differences were found for the other enzymes/receptors of the ECS under study. However, linear regression analysis for individual animals showed a significant correlation between CB2 and fatty acid amide hydrolase (FAAH), diacylglycerol lipase α/β (DAGLα/β), and APP; instead, a significant negative correlation was found between MAGL and APP. Finally, ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) demonstrated a significant reduction of 2-AG in TG retinas (~0.34 ng/mg) compared to WT (~1.70 ng/mg), while a trend toward increase was found for the other eCB anandamide (AEA). Overall, our data indicate that gliosis and ECS dysregulation-in particular of CB2, MAGL and 2-AG-occur in the retina of AD-like mice before retinal degeneration and development of hippocampal β-amyloid plaques.

Here, a high molecular weight polysaccharide preparation from Ophiocordyceps gracilis was utilized as a stabilizer and dispersant to create nanocomposites based on selenium nanoparticles (GSP-1a-SeNPs). The NPs showed the highest stability at a selenium/polysaccharide mass ratio of 1:1, with no significant change after 28 days of storage at 4 °C. The NPs exhibited a symmetrical spheroid structure with an average diameter of 85.4 nm. Next, the anti-inflammatory properties and mechanisms of the GSP-1a-SeNPs were examined in LPS-induced RAW264.7 cells, which efficiently internalized the NPs. In the anti-inflammatory assays, GSP-1a-SeNPs significantly reduced the production of pro-inflammatory cytokines, including TNF-α and IL-6, and lowered ROS levels by activating the Nrf2-Keap1 pathway. This pathway regulates selenoprotein expression, thereby balancing the immune microenvironment of RAW264.7 cells and mitigating inflammation. These results suggest that GSP-1a-SeNPs could serve as potential therapeutic agents or adjuvants for treating LPS-induced inflammation.

A high-fat diet (HFD) is often associated with hepatic lipid metabolism disorders, leading to dysfunction in multiple body systems. Ginsenosides derived from Panax ginseng have been reported to possess potential effects in ameliorating lipid metabolism disorders; however, their underlying mechanisms remain insufficiently explored. This study aims to investigate the bioactivities of ginsenosides in combating lipid metabolism disorders and obesity, with a focus on their mechanisms involving the cholesterol metabolism signaling pathway and gut microbiota. Our results demonstrated that ginsenoside treatment significantly reduced overall body weight, body weight changes, liver weight, and eWAT weight, as well as alleviated hepatic steatosis and dyslipidemia in HFD-fed rats, without affecting food intake. These effects were dose-dependent. Furthermore, 16S rRNA sequencing revealed that ginsenosides significantly increased the relative abundance of Akkermansia muciniphila, Blautia, Eisenbergiella, Clostridium clusters XI, XVIII, and III, while decreasing the relative abundance of Clostridium subcluster XIVa and Dorea. In addition, ginsenoside treatment significantly regulated the expression of hepatic genes and proteins involved in the cholesterol metabolism signaling pathway (FXR, CYP7A1, CYP7B1, CYP27A1, ABCG5, ABCG8, Insig2, and Dhcr7), potentially inhibiting hepatic cholesterol biosynthesis while promoting cholesterol transport to HDL and its excretion via bile and feces. Notably, levels of 7-dehydrocholesterol (7-DHC) and 27-hydroxycholesterol (27-OHC) were reduced, while 5β,6β-epoxycholesterol (5,6β-epoxy) levels were elevated following ginsenoside treatment, indicating significant modulation of oxysterols by ginsenosides. Moreover, bile acid enterohepatic circulation was regulated through the enhancement of hepatic FXR-CYP7A1 signaling and intestinal FXR-FGF15 signaling in HFD-fed rats treated with ginsenosides, which was closely linked to gut microbiota composition. Collectively, our findings suggest that ginsenosides alleviate hepatic lipid metabolism disorders by modulating gut microbiota and the cholesterol metabolism signaling pathway in HFD-fed rats.

Major depressive disorder (MDD) is a widespread and severe mental health condition characterized by persistent low mood and loss of interest. Emerging evidence suggests that ferroptosis, an iron-dependent form of cell death, and epigenetic dysregulation contribute to the pathogenesis of MDD. This study investigates the role of RNA demethylase FTO and autophagy regulator BECN1 in ferroptosis and their regulation by the active compound ginsenoside Rb1 (GRb1) as a potential antidepressant strategy. Hippocampal tissues from postmortem MDD patient brains and mice with chronic restraint stress (CRS)-induced depression were analyzed. Ferroptosis was evaluated by analyzing the levels of markers such as glutathione (GSH) and malondialdehyde (MDA). GRb1 was administered to CRS model mice by gavage to explore its effects on ferroptosis-related pathways. The results showed that FTO and BECN1 expression was reduced in the hippocampal tissues of MDD patients and CRS model mice, promoting ferroptosis via disruption of the antioxidant system. Moreover, GRb1 treatment increased FTO and BECN1 expression, modulated m6A methylation, restored the antioxidant balance, and inhibited ferroptosis in CRS model mice. These findings reveal a novel epigenetic mechanism of ferroptosis in MDD and highlight GRb1 as a promising agent for treating depression through the targeting of ferroptosis pathways.

Cancer patients are commonly affected by fatigue. Herein, we sought to examine epigenetic modifications (i.e., DNA methylation) related to fatigue in peripheral blood among patients during and after treatment for head and neck cancer (HNC). Further, we determined whether these modifications were associated with gene expression and inflammatory protein markers, which we have previously linked to fatigue in HNC. This prospective, longitudinal study enrolled eligible patients with data collected at pre-radiotherapy, end of radiotherapy, and six months and one-year post-radiotherapy. Fatigue data were reported by patients using the Multidimensional Fatigue Inventory (MFI)-20. DNA methylation (Illumina MethylationEPIC) and gene expression (Applied Biosystems Clariom S) arrays and assays for seven inflammatory markers (R&D Systems multiplex) were performed. Mixed models and enrichment analyses were applied to establish the associations. A total of 386 methylation loci were associated with fatigue among 145 patients (False Discovery Rate [FDR] < 0.05). Enrichment analyses showed the involvement of genes related to immune and inflammatory responses, insulin and lipid metabolism, neuropsychological disorders, and tumors. We further identified 16 methylation-gene expression pairs (FDR < 0.05), which were linked to immune and inflammatory responses and lipid metabolism. Ninety-one percent (351) of the 386 methylation loci were also significantly associated with inflammatory markers (e.g., interleukin 6, c-reactive protein; FDR < 0.05), which further mediated the association between methylation and fatigue (FDR < 0.05). These data suggest that epigenetic modifications associated with inflammation and immunometabolism, in conjunction with relevant gene expression and protein markers, are potential targets for treating fatigue in HNC patients. The findings also merit future prospective studies in other cancer populations as well as interventional investigations.

It remains difficult to evaluate the risk factors for concomitant carotid artery as well as coronary artery diseases in elderly patients. The aim of this research was to determine the TNF-α/IL-1β/IL-1α/IL-12 axes-TLR1/TLR3/TLR5/MYD88 immune signaling pathway interactions in coexistent carotid artery occlusion and coronary artery occlusion in elderly patients.

Elderly patients, who underwent carotid ultrasonography and coronary computed tomography angiography, were consecutively included in this research. The analyzed groups consisted of those with coexistent carotid artery occlusion and coronary artery occlusion as well as healthy individuals were enrolled as control group. The circulating levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-1α (IL-1α), interleukin-12 (IL-12), toll-like receptor 1 (TLR1), toll-like receptor 3 (TLR3), toll-like receptor 5 (TLR5) and myeloid differentiation factor 88 (MYD88) were measured.

The biomarkers (TNF-α, IL-1β, IL-1α, IL-12, TLR1, TLR3, TLR5 and MYD88) were significantly increased in carotid artery occlusion + left circumflex coronary artery occlusion group when compared with control group and carotid artery occlusion + right coronary artery occlusion group, respectively (P < 0.001), and were further elevated in carotid artery occlusion + left anterior descending coronary artery occlusion group when compared to carotid artery occlusion + right coronary artery occlusion group and carotid artery occlusion + left circumflex coronary artery occlusion group, respectively (P < 0.001).

This research demonstrated that the TNF-α/IL-1β/IL-1α/IL-12 axes and TLR1/TLR3/TLR5/MYD88 immune signaling pathway implicated in the pathogenesis of carotid artery occlusion with coronary artery occlusion in elderly patients.

Myocardial infarction (MI) is considered an inflammatory disease and among the leading causes of death globally. An essential indicator of inflammation, high-sensitivity C-reactive protein (hs-CRP), is linked with the acute MI prognosis. We aimed to examine the impact of omega-3 polyunsaturated fatty acids (PUFAs) as an anti-inflammatory supplement on hs-CRP levels in acute MI patients. Sixty patients with acute MI participated in this randomized, placebo-controlled trial. For 30 days, patients were randomized to receive omega-3 PUFAs (2 g/day, N = 30) or placebo (N = 30) on top of guideline-directed medical therapy. An initial and endpoint measurement of hs-CRP was performed. We found that the hs-CRP levels in both omega-3 PUFAs and placebo groups remarkably decreased following 30 days of treatment (decreasing from 1.84 (2.3) and 1.3 (2.6) to 0.38 (0.54) and 0.63 (1.12) mg/dL, respectively; P < 0.001). Following the 30 days of treatment, the reducing impact of omega-3 PUFAs (↓ 1.54 (1.98) mg/dL) on hs-CRP was more robust than the placebo group (↓ 0.92 (1.57) mg/dL, P = 0.008). Furthermore, the WBC, cholesterol, LDL, and triglyceride levels were markedly decreased in omega-3 and placebo groups after 30 days of therapy (P < 0.001 for all). However, no remarkable differences were reported in the level of these parameters after 30 days of therapy between both studied groups. Our findings showed that omega-3 PUFAs decrease hs-CRP amounts in patients with acute MI. Omega-3 PUFA supplementation may be an appropriate candidate in patients with early-stage acute MI for inhibiting inflammation.

Inflammation and apoptosis are interrelated biological processes that have a significant impact on the advancement and growth of certain chronic diseases, such as cardiovascular problems, neurological conditions, and osteoarthritis. Recent research has emphasized that focusing on these mechanisms could result in novel therapeutic approaches that aim to decrease the severity of diseases and enhance patient outcomes. Hydroxytyrosol (HT), which is well-known for its ability to prevent oxidation, has been identified as a possible candidate for regulating both inflammation and apoptosis. In this review, we will highlight the multifaceted benefits of HT as a therapeutic agent in mitigating inflammation, apoptosis, and associated conditions. This review provides a comprehensive overview of the latest in vitro and in vivo research on the anti-inflammatory and antiapoptotic effects of HT and the mechanisms by which it works. Based on these studies, it is strongly advised to use HT as a bioactive ingredient in pharmaceutical products intended for mitigating inflammation, as well as those with apoptosis applications.

Inflammation is the physiological response of the immune system to injury or infection, typically manifested by local tissue congestion, swelling, heat, and pain. Prolonged or excessive inflammation can lead to tissue damage and the development of many diseases. The anti-inflammatory effects of natural ingredients have been extensively researched and confirmed. This study investigated the effects of Chlorogenic acid (CGA) isomers -- 3-Caffeolyquninic acid (3-CQA), 4-Caffeolyquninic acid (4-CQA), and 5-Caffeolyquninic acid (5-CQA) -- on the inflammatory response and oxidative stress reaction induced by LPS in RAW264.7 cells. Overall, 3-CQA exhibited the most significant reduction in levels of TNF-α, IL-6, NO, and ROS. 4-CQA showed superior inhibition of TNF-α compared to 5-CQA (p < 0.05), while no significant difference in other parameters. We further used DARTS and CETSA to demonstrate that CGA isomers have stable affinity with AKR1B1. As a positive control, the AKR1B1 antagonist epalrestat exhibited similar effects to the CGA isomers. 3-CQA having the smallest half-inhibitory concentration (IC50) for AKR1B1, while 4-CQA and 5-CQA have similar values. AutoDock simulations of the docking conformations revealed minimal differences in the average binding energies of the CGA isomers. The main differences were that VAL47 formed a hydrogen bond with 3-CQA, whereas GLN49 formed hydrogen bonds with 4-CQA and 5-CQA. Additionally, the number of hydrophobic bonds involving PHE122 and LEU300 varies. Our conclusion is that differences in non-covalent interactions result in the varying inhibitory abilities of CGA isomers on AKR1B1, which further affect the anti-inflammatory and antioxidant effects of CGA isomers.

Erectile dysfunction (ED) is a common issue among adult males. The Composite Dietary Antioxidant Index (CDAI) reflects anti-inflammatory levels and has been linked to various diseases, but its relationship with ED is unclear.

This cross-sectional study utilised comprehensive data on clinical factors from the 2001-2004 National Health and Nutrition Examination Survey (NHANES). To investigate the link between variables and ED, we used multivariate regression analysis, univariate analysis, and subgroup analysis. The linear relationship between CDAI and ED was investigated by dose-response curve analysis. For sensitivity analysis, propensity score matching (PSM) was utilised to exclude the influence of potential confounders. Finally, we investigated the association between CDAI and ED using threshold effects analysis.

We included in our research a total of 2896 persons with data on CDAI from NHANES 2001-2004. Among these, 2,098 participants were thought to be free of ED, whereas 798 participants had ED. We found that compared to the ED group, men in the non-ED group had higher levels of CDAI (p < 0.0001 before PSM and p = 0.0145 after PSM). Additionally, after adjusting for covariates, it was found that an elevated CDAI was associated with a reduced incidence of ED [OR = 0.65(p = 0.001) before PSM and OR = 0.62(p = 0.002) after PSM]. Subgroup analysis indicated stronger associations in high-risk groups, and dose-response curves confirmed a linear negative correlation between CDAI and ED.

This study revealed a negative linear relationship between CDAI and the incidence of ED. The CDAI can be used as an indicator for assessing ED risk and for ED prevention.

Diesel Particulate Matter (DPM) is a very small particulate matter originating from cities, factories, and the use of fossil fuels in diesel vehicles. When DPM permeates the skin, it causes inflammation, leading to severe atopic dermatitis. Hibiscus cannabinus L. (Kenaf) seeds and leaves possess various beneficial properties, including anti-coagulation, antioxidant, and anti-inflammation effects. In this study, we investigated the anti-inflammatory effects of an ethanol extract of Hibiscus cannabinus L. flower (HCFE) in HaCaT cells stimulated with 100 μg/mL of DPM.

The anthocyanin content of HCFE was analyzed, and its antioxidant capacity was investigated using the DPPH assay. After inducing inflammation with 100 ug/mL of DPM, the cytotoxicity of HCFE 25, 50, and 100 ug/mL was measured, and the inhibitory effect of HCFE on inflammatory mediators was evaluated.

Anthocyanin and myricetin-3-O-glucoside were present in HCFE and showed high antioxidant capacity. In addition, HCFE decreased the mRNA expression of inflammatory cytokines and chemokines such as IL-1β, IL-4, IL-6, IL-8, IL-13, and MCP-1, and significantly reduced the gene expression of CXCL10, CCL5, CCL17, and CCL22, which are known to increase in atopic dermatitis lesions. Furthermore, HCFE reduced intracellular reactive oxygen species (ROS) production, and down-regulated the activation of NF-κB, MAPKs. Inhibition of the NLRP-3 inflammasome was observed in DPM-stimulated HaCaT cells. In addition, the restoration of filaggrin and involucrin, skin barrier proteins destroyed by DPM exposure, was confirmed.

These data suggest that HCFE could be used to prevent and improve skin inflammation and atopic dermatitis through the regulation of inflammatory mediators and the inhibition of skin water loss.

With the imbalance of intestinal microbiota, the body will then face an inflammatory response, which has serious implications for human health. Bodily allergies, injury or pathogens infections can trigger or promote inflammation and alter the intestinal environment. Meanwhile, excessive changes in the intestinal environment cause the imbalance of microbial homeostasis, which leads to the proliferation and colonization of opportunistic pathogens, invasion of the body's immune system, and the intensification of inflammation. Some natural compounds and gut microbiota and metabolites can reduce inflammation; however, the details of how they interact with the gut immune system and reduce the gut inflammatory response still need to be fully understood. The review focuses on inflammation and intestinal microbiota imbalance caused by pathogens. The body reacts differently to different types of pathogenic bacteria, and the ingestion of pathogens leads to inflamed gastrointestinal tract disorders or intestinal inflammation. In this paper, unraveling the interactions between the inflammation, pathogenic bacteria, and intestinal microbiota based on inflammation caused by several common pathogens. Finally, we summarize the effects of intestinal metabolites and natural anti-inflammatory substances on inflammation to provide help for related research of intestinal inflammation caused by pathogenic bacteria.

Alzheimer's disease (AD) and Parkinson's disease (PD) are neurodegenerative disorders that significantly impact well-being. Hyperoside (HYP), a flavonoid found in various plant species, particularly within the genus Hypericin, exhibits diverse pharmacological properties. However, the precise mechanisms underlying the anti-AD and anti-PD effects of HYP remain unclear. This systematic review consolidated existing preclinical research on HYP by conducting a comprehensive literature survey and analysis. The objective was to corroborate the therapeutic efficacy of HYP in AD and PD models and to synthesize its potential therapeutic mechanisms. Searches were conducted in the PubMed, CNKI, and Web of Science databases. Reliability assessment of the 17 included studies confirmed the credibility of the mechanisms of action of HYP against AD and PD. We systematically assessed the neuroprotective potential of HYP in in vivo and in vitro models of AD and PD. Our findings indicated that HYP can mitigate, intervene in, and treat AD and PD animal models and associated cells through various mechanisms, including anti-oxidative, anti-inflammatory, anti-apoptotic, anti-Aβ aggregation, and cholinesterase inhibitory activities. Therefore, HYP potentially exerts anti-AD and anti-PD effects through diverse mechanisms, making it a promising candidate for therapeutic intervention in both AD and PD.