Background: Atherosclerosis (AS) is the primary pathological basis for cardiovascular and cerebrovascular events, with its development closely linked to dyslipidemia and chronic inflammation. The gut-liver axis, serving as a core bridge connecting gut microbiota, hepatic metabolism, and systemic inflammation, has gained increasing prominence in AS pathogenesis. Phytochemicals exhibit multifaceted biological activities, yet their mechanisms for preventing and treating AS via the gut-liver axis remain to be systematically summarized. This review aims to summarize the potential mechanisms of phytochemicals interventions in AS from an intestinal-hepatic axis perspective. Methods: A systematic literature search was conducted using PubMed, Web of Science, and Embase, focusing on previously published articles, reviews, and meta-analyses. Keywords included "phytochemicals", "flavonoids", "atherosclerosis", "AS", "gut-liver axis", "gut axis", "intestinal axis", "gut microbiota" and "TMAO". This narrative review synthesizes current research evidence on the interactions among phytochemicals, the gut-liver axis, and atherosclerosis, summarizing their action pathways and molecular mechanisms. Results: Phytochemicals (such as polyphenols, carotenoids, saponins, etc.) have low bioavailability but can be metabolized and transformed by gut microbiota. Through multiple mechanisms-including modulating gut microbiota composition, enhancing intestinal barrier function, regulating bile acid metabolism, and exerting anti-inflammatory and antioxidant effects-they positively influence gut-liver axis function. This alleviates lipid metabolism disorders, suppresses systemic inflammation, and thereby combats the onset and progression of atherosclerosis at multiple stages. Conclusions: Phytochemicals can intervene in the progression of atherosclerosis through the gut-liver axis. Future studies should further investigate dose-response relationships and conduct clinical validation to determine optimal usage strategies.

Bioactive food compounds have attracted growing attention for their ability to influence human health beyond basic nutritional functions [...]

BackgroundAllergic diseases have become one of the major public health problems to be addressed in the world today. As a tissue resident cell, mast cells are crucial in the pathogenesis of allergic diseases. Vitamin A is an important fat-soluble vitamin with immunomodulatory functions. Vitamin A deficiency has been shown to be associated with allergic disease states, including asthma; however, no studies have been reported on whether vitamin A deficiency has an effect on the activation of mast cells in allergic reactions. ObjectiveTo explore whether blocking retinoic acid receptors has an effect on mast cell degranulation. Methods Flow cytometry was used to analyze the expression of FCεRIα and CD117 on the cell surface, toluidine blue staining was used to visualize cellular features and morphological changes. ELISA was used to detect histamine release. High-throughput transcriptome sequencing and qRT-PCR were used to detect the expression of relevant signaling pathways and cytokine genes. Western blot was used to detect the expression of relevant signaling pathway proteins. ResultsIn the present study, we found that antagonism of the retinoic acid receptor (RAR) resulted in overactive mast cells and increased their degranulation. Furthermore, inflammatory signaling pathways such as MyD88-IKK-NF-κB and PI3K-Akt-m-TOR were involved in the effect of retinoic acid (RA) on the activation state of mast cells. ConclusionsIn this paper, we demonstrated that blocking RAR can exacerbate its activation state in IgE-mediated mast cells. This study provided new insights into the possibility that vitamin A deficiency exacerbated mast cell activation and thus affectd allergic diseases and their mechanisms.

Background: The triglyceride glucose (TyG) index has been correlated with all kinds of diseases. However, its association with hyperuricemia is still a subject of controversy. Methods: This meta-analysis encompassed relevant studies on the TyG index and hyperuricemia obtained from electronic databases, from the launch date until March 2025. The effect sizes and corresponding 95% confidence intervals (CIs) were obtained using a random effects model. Results: Twenty-six trials with 637,954 subjects were incorporated in this study. It was revealed that the TyG index was linked to hyperuricemia (OR = 2.67; 95% CI: 2.34, 3.04; p < 0.001). A dose-response analysis demonstrated that with each 1 mg/dL rise in the TyG index, the risk of being diagnosed with hyperuricemia increased by 2.07 times (OR = 2.07; 95% CI: 1.89, 2.25; p < 0.001). Conclusions: The TyG index has an association with hyperuricemia. Given the constraints identified in our meta-analysis, further cohort studies will be essential to confirm this correlation.

AIMS:As a result of the withdrawal of lorcaserin and the approval of tirzepatide and semaglutide, we conducted a new network meta-analysis to assess the overall and comparative effects of six US Food and Drug Administration (FDA)-approved weight-loss medications on the cardiometabolic risk profile of obese adults, and to find out which of these medications is best in improving cardiometabolic risk factors. MATERIALS AND METHODS:We searched our databases for randomised clinical trials of the effects of weight-loss drugs approved by the FDA as of April 2024 in obese adults taking them for 1 year or more, compared with placebo or between the agents. We performed pairwise and network meta-analyses, and the results were reported as weighted and standardised mean differences. RESULTS:A total of 31 trials with 24 792 participants were included in this network meta-analysis. The quality of evidence was rated as moderate in most cases using the GRADE. Compared with placebo, the weight-loss drugs resulted in moderate reductions in fasting glucose of 11.12 mg/dL (95% CI, -13.70, -8.53), glycosylated haemoglobin of 0.60% (95% CI, -0.75, -0.45) and waist circumference of 5.28 cm (95% CI, -6.57, -4.00), with minimal or modest benefits of clinical relevance in blood pressure and cholesterol profile. In addition, we found tirzepatide to be relatively good overall in comparisons between drugs. CONCLUSIONS:This study found that six FDA-approved weight-loss drugs had a moderately beneficial effect on the cardiometabolic risk profile. In general, tirzepatide was more effective than other pharmacological agents in improving cardiometabolic risk factors.

Most studies suggest that B vitamins can reduce the risk of colorectal cancer (CRC), and research in this field has been growing. Focusing on 2617 articles in the field, this study used CiteSpace and VOSviewer software to evaluate the contributions of various countries/regions, institutions, authors, and journals. The United States and Harvard University were identified as the most productive nation and institution, respectively, with Edward L. Giovannucci (Harvard) being the top contributor. Cancer Epidemiology Biomarkers & Prevention was recognized as the leading journal. Through the analysis of keywords and citations, we found that the potential of B vitamins (B1, B2, B6, B9, and B12) in the prevention and treatment of CRC and their mechanisms including regulation of gene expression, anti-inflammatory and antioxidant, and modulation of gut microenvironment are hot topics of research in this field. Burst detection analysis further revealed that the application of nanoparticle-based targeted drug delivery systems (such as folate-conjugated nanocarriers) in the treatment of CRC represents both a current hotspot and a future trend. This study offers a comprehensive overview of the field, highlights research hotspots and trends, and offers valuable information for researchers to further grasp the research direction.

BACKGROUND:The association between dietary intake of live microbes and mortality remains unclear. OBJECTIVE:This study aims to investigate the relationship between dietary live microbial intake and all-cause and cause-specific mortality among adults in the United States. DESIGN:This is a cross-sectional study of adults aged 20 years or older who participated in the 1999-2018 National Health and Nutrition Examination Survey. PARTICIPANTS AND SETTING:The study utilized data from adults aged 20 years and older with complete dietary and mortality data from the National Health and Nutrition Examination Survey from 1999 to 2018. MAIN OUTCOME MEASURES:Deaths from any cause are defined as all-cause mortality. The International Statistical Classification of Diseases, 10th Revision, and the National Center for Health Statistics classifications of heart disease (054-064) and malignant neoplasms (019-043) were used to identify disease-specific causes of death. STATISTICAL ANALYSES PERFORMED:Cox proportional hazard regression was utilized to examine the associations between the consumption of dietary live microbes and all-cause and cause-specific mortality. Restricted cubic spline regression modeling was used to assess potential linear associations between dietary live microorganism intake and mortality. In addition, stratified analyses and sensitivity analyses of the association of dietary live microorganism intake with all-cause and cardiovascular deaths were performed to validate the robustness of the results. RESULTS:The study included 31 836 participants, of whom 4160 died, including 1109 cardiovascular deaths and 915 cancer deaths. The study found that consuming live microbes from the diet was linked to a lower rate of all-cause and cardiovascular mortality, respectively (hazard ratio 0.80, 95% CI 0.72 to 0.89; P < .001; hazard ratio 0.79, 95% CI 0.65 to 0.95; P = .014). However, there was no significant association observed between microbial intake and cancer mortality (hazard ratio 0.93, 95% CI 0.75 to 1.17; P = .545). Restricted cubic spline demonstrates a linear association between dietary live microorganism intake and all-cause and cardiovascular mortality (P < .001). Furthermore, sensitivity analyses indicated that a high intake of live dietary microorganisms was associated with a lower risk of all-cause mortality and cardiovascular mortality (P < .05). CONCLUSIONS:The study found that consuming live microbes through diet was linked to a lower rate of all-cause and cardiovascular mortality but not cancer mortality.

Given the ongoing controversy regarding the relationship between serum retinol levels and asthma, this study aims to clarify their association in adults through an integrated analysis of National Health and Nutrition Examination Survey (NHANES) data and a two-sample Mendelian randomization (MR) study. Cross-sectional analysis of 10,136 participants from NHANES (1999-2006 and 2017-2018), using weighted multivariate logistic regression, revealed that serum retinol levels were negatively associated with adult asthma (OR = 0.89, 95% CI: 0.74-0.99, p = 0.044). Subsequent two-sample MR analysis with genome-wide association study (GWAS) statistics (serum retinol: ukb-b-17406, N = 62,991; asthma: ebi-a-GCST006862, N = 127,669) employed Inverse Variance Weighted method (instrument selection threshold: p < 1x10(-5), F-statistic > 10), confirming a causal effect in which genetically predicted higher retinol levels reduced asthma risk (OR = 0.62, 95% CI: 0.41-0.93, p = 0.021). Sensitivity analyses (MR-Egger/MR-PRESSO) detected no significant pleiotropy (p > 0.05 in both tests). This study suggests a potential causal link between higher serum retinol levels and a reduced prevalence of adult asthma.

BACKGROUND:Many studies have evaluated possible associations between the SII, NLR, SIRI, AISI, NLPR with depression, but the results remain controversial. OBJECTIVE:To determine the association between levels of the systemic inflammatory markers and the prevalence of depression. METHODS:Databases like Web of Science, PubMed, Cochrane Library, and EMBASE were searched for relevant studies. Differences in SII, NLR, SIRI, AISI, and NLPR levels between depressed patients and controls were assessed using OR, SMD, and 95 % CI. Subgroup and sensitivity analyses explored heterogeneity based on diagnostic criteria, region, study design, gender, and underlying disease. A meta-analysis was also performed to evaluate the diagnostic effectiveness of inflammatory markers for depression. RESULTS:A total of 41 studies with 205,438 participants were analyzed. Depressed subjects showed significantly higher NLR (SMD = 0.35, 95 % CI [0.17, 0.53], P < 0.001) and SII (OR = 1.38, 95 % CI [1.15, 1.65], P < 0.001) than controls. Subgroup analyses suggested that diagnostic criteria, study design, and country influence the association. Meta-analysis showed that NLR was effective in diagnosing depression (AUC = 0.70, 95 % CI [0.66, 0.74]), whereas SII was less effective (AUC = 0.37, 95 % CI [0.33, 0.41]). CONCLUSIONS:This study supports the hypothesis that inflammation is associated with depression and that NLR and SII can be a potential predictor, but there are fewer studies related to SIRI, AISI, and NLPR, and further research is needed.

Background: Chronic obstructive pulmonary disease (COPD) is a common respiratory disease, and its development and prognosis are influenced by many nutrients. However, the relationship between polyunsaturated fatty acids (PUFAs) and COPD remains unclear. Methods: This study searched all literature reports on PUFAs and COPD based on electronic databases from their inception up to October 2023. Meta-analysis was conducted to evaluate the differences in PUFAs between COPD patients and controls, the risk of COPD in subjects with different levels of PUFA concentrations, and the effect of PUFA supplementation on COPD. Results: A total of nineteen studies met our inclusion criteria, which included 155 636 subjects. Our meta-analysis results showed that the daily dietary intake of PUFAs was lower in COPD patients than in controls (SMD = -0.80 g, 95% CI: -1.28, -0.31 g, I-2 = 98.6%, P < 0.001). Meanwhile, the lower n-3 PUFA levels and higher n-6 PUFA levels were associated with an increased risk of COPD (effect size n-3 = 0.87, 95% CI: 0.77, 0.98, I-2 = 52.2%, P = 0.018; effect size n-6 = 1.23, 95% CI: 1.05, 1.43, I-2 = 75.2%, P < 0.001). Furthermore, the content of low-density lipoprotein cholesterol in the PUFA supplementation group was higher than that in the control group (SMD = 0.63 mg dL(-1), 95% CI: 0.15, 1.12 mg dL(-1), I-2 = 0.0%, P = 0.697). Conclusions: Our meta-analysis indicated a potential relationship between PUFAs and COPD. More large-scale prospective cohort studies and clinical trials are necessary to validate this relationship.

Background Food allergy (FA) has become a growing public health issue globally, with a steady increase in prevalence over recent decades. Despite this, effective treatment strategies remain elusive. Modulating the composition and function of gut microbiota through probiotic intervention has gained attention as a promising strategy for the prevention and management of FA. Results M-16V alleviated infants’ clinical symptoms such as crying, reflux, and abnormal stool patterns, which were accompanied by improvements in biochemical parameters. M-16V significantly attenuated mice OVA-induced allergic responses, suppressed the production of OVA-sIgE and OVA-sIgG1, elevated OVA-sIgA levels, and downregulated the expression of allergy-related mRNA. In both mice and infants, microbial metabolic pathways were pivotal in modulating immune cell function. Notably, M-16V enhanced the abundance and diversity of the gut microbiota. Conclusion Our results highlight the therapeutic efficacy of M-16V in mitigating FA and provide valuable insights for developing of novel microbiota-targeted interventions aimed at the prevention and treatment of FA.

Studies have reported an association among systemic immune inflammation index (SII), all-cause and cause-specific mortality, but the results are inconsistent. To comprehensively explore the association between Systemic Immune Inflammation (SII) and the risk of all-cause mortality, cardiovascular disease (CVD), and cancer mortality. A meta-analysis was conducted by reviewing existing literature. The search encompassed prominent databases including PubMed, Embase, Cochrane, and the Web of Science, with the cutoff date set at March 1, 2024. Furthermore, subgroup analyses and dose-response assessments were undertaken to provide a nuanced exploration of mortality risk factors. A total of 33 articles were included (427,819 participants). In the study, SII was associated with an increased risk of all-cause mortality (HR = 1.45, 95

BACKGROUND:The Energy-Adjusted Dietary Inflammatory Index (E-DII) is related to both body mass index (BMI) and hyperuricemia. However, the association among BMI, hyperuricemia and DII is yet to be fully elucidated. The purpose of this study is to explore the role of BMI in the relationship between E-DII and hyperuricemia in the American population. METHODS:A cross-sectional study was conducted using data from the National Health and Nutrition Examination Survey (NHANES) spanning from 2007 to 2016, with a sample size of 10,571 participants. The study used a weighted logistic regression model and a generalized additive model (GAM) to explore the associations among BMI, hyperuricemia and E-DII. Furthermore, mediation analysis was utilized to illustrate the mediating relationships among these variables. RESULTS:The results of the study indicated that a higher E-DII was related to an increased risk of hyperuricemia. The association between E-DII and hyperuricemia was partially mediated by BMI. CONCLUSIONS:E-DII is associated with hyperuricemia. BMI mediates the relationship between E-DII and hyperuricemia among Americans, which provides crucial information for the prevention of hyperuricemia.

SCOPE:Lactoferrin (LF) is an iron-bound protein with a molecular weight of about 80 kDa. LF has many biological functions such as antibacterial, antiviral, immunomodulatory, and anticancer. The purpose of this study is to explore the research trend of LF through bibliometric analysis. METHODS AND RESULTS:The search is conducted in the Web of Science Core Collection database, and then the publications information of LF related literature is exported. Based on CiteSpace and VOSviewer software, countries, institutions, authors, journals, keywords, and so on are analyzed. Since 1987, a total of 9382 literature have been included, and the number of papers related to LF has increased year by year. These publications come mainly from 124 countries and 725 institutions. Of the 1256 authors analyzed, Valenti Piera is the one with the most publications. The burst strength of gut microbiota, antioxidant, nanoparticles, and in vitro digestion are 21.3, 15.63, 23.03, and 13.51, respectively. They represent the frontier of research in this field and are developing rapidly. CONCLUSION:This study shows that LF has important research value. The study of LF nanoparticles and the effects of LF on the gut microbiota are an emerging field that helps to explore new research directions.

The global rise in prediabetes and diabetes, with type 2 diabetes (T2DM) being predominant, highlights the association between T2DM and hypertriglyceridemia (HTG). Patients with both abnormal glucose levels and HTG require increased attention due to higher risks of complications and mortality. Therefore, this study aimed to find the key long non-coding RNA (lncRNA) of HTG in the abnormal glucose metabolism patients. We collected blood samples for RNA sequencing experiments and blood samples for validation in population. We have conducted RNA sequencing, weighted gene co-expression network analysis (WGCNA), quantitative real-time polymerase chain reaction (qRT-PCR) in a 82-vs-82-sample-size population and insulin induced HepG2, RNA- Fluorescence in situ hybridization (FISH) and Cell Counting Kit-8 (CCK-8). We also explored lipid metabolism related transcription factor and the related protein expression and processed key lncRNA by both interference expression and overexpression, and the related consequences were rescued by its target mRNA. ENST00000540317.5 (LINC317.5) was lower in HTG with abnormal glucose metabolism and was found in both cytoplasm and nucleus in HepG2, inversely regulating the accumulation of TG and its target mRNA TKFC. Relative expression of peroxisome proliferator-activated receptor alpha (PPARα) and peroxisome proliferator-activated receptor gamma (PPARγ) were decreasing, and SREBP-1c (sterol regulatory element-binding protein-1c) was increasing of the interference expression of LINC317.5. Interference expression of LINC317.5 significantly decreased the protein expression of ACADM and CPT1A, whereas increased the protein expression of FAS and ACC1. TKFC partly reduced the triglyceride (TG) accumulation of LINC317.5. In conclusion, we suggested LINC317.5-TKFC as a key for TG accumulation in the HepG2-insulin resistant (IR). These might provide information of non-invasive biomarkers for the HTG with abnormal glucose.

Compared with diabetic patients with normal blood lipid, diabetic patients with dyslipidemia such as high triglycerides have a higher risk of clinical complications, and the disease is also more serious. For the subjects with hypertriglyceridemia, the lncRNAs affecting type 2 diabetes mellitus (T2DM) and the specific mechanisms remain unclear. Transcriptome sequencing was performed on peripheral blood samples of new-onset T2DM (six subjects) and normal blood control (six subjects) in hypertriglyceridemia patients using gene chip technology, and differentially expressed lncRNA profiles were constructed. Validated by the GEO database and RT-qPCR, lncRNA ENST00000462455.1 was selected. Subsequently, fluorescence in situ hybridization (FISH), real-time quantitative polymerase chain reaction (RT-qPCR), CCK-8 assay, flow cytometry, and enzyme-linked immunosorbent assay (ELISA) were used to observe the effect of ENST00000462455.1 on MIN6. When silencing the ENST00000462455.1 for MIN6 in high glucose and high fat, the relative cell survival rate and insulin secretion decreased, the apoptosis rate increased, and the expression of the transcription factors Ins1, Pdx-1, Glut2, FoxO1, and ETS1 that maintained the function and activity of pancreatic β cells decreased (p < 0.05). In addition, we found that ENST00000462455.1/miR-204-3p/CACNA1C could be the core regulatory axis by using bioinformatics methods. Therefore, ENST00000462455.1 was a potential biomarker for hypertriglyceridemia patients with T2DM.

Data is limited on intestinal microbiota and metabolites in healthy residents exposed to cadmium (Cd), a population uniquely susceptible to Cd toxicity through contaminated foods. In this study, the 16 S rRNA gene sequencing, serum metabolomics and urine metabolomics were performed to examine the alterations of gut microbiota and metabolomics profile of wistar rats exposed to Cd. These findings indicated that Cd exposure markedly altered the structure of gut microbial community, reduced significantly microbiome diversity, and identified 5 phyla and 6 genera with significant changes. Specifically, the levels of Pseudoxanthomonas and Anaerovibrio upregulated and that of Akkermansia, Brachyspira, Aggregatibacter and SMB53 reduced in rats treated with Cd. Metabolomics profiles of the urine and serum of Cd-treated rats revealed that the abundance of glycerophospholipid metabolites and their derivatives were markedly altered. Glycerophospholipid metabolic pathways that were markedly enriched in metabolomics in both samples was also significantly predicted in gut microbiota analysis. Further, interaction analysis predicted that there might be a relationship between the differential glycerophospholipid metabolites and affected bacteria genera induced by Cd. These results suggested that subacute Cd could disrupt the intestinal microecologica equilibrium and glycerophospholipid metabolic homeostasis, and also provided potential differential microbiota and glycerophospholipid biomarkers between subacute Cd-exposed rats and healthy rats.

Food allergy (FA) is one of the global human health problems, affecting about 1 in 12 children and 1 in 10 adults worldwide. Probiotics have alleviating effects on FA, but the mechanisms have not been fully understood. We sought to explore the therapeutic potential of probiotics Bifidobacterium longum CECT7894 (B. longum CECT7894) on anaphylaxis in the ovalbumin (OVA)-induced FA model using an integrated multiomics approaches. The results revealed treatment with B. longum CECT7894 relieved OVA-induced allergic symptoms such as patho-logical changes in small intestine to some extent. Furthermore, probiotics utilization also reduced IgE levels. The transcriptomic data demonstrated that the expressions of genes associated with sphingolipid metabolism were altered in the group received B. longum CECT7894 compared to the sensitized group, including Sgpl1, Trpc1 and Prss8. In addition, the abundances of Sphingobacterium at the genus level, Sphingobacterium sp. 21 and B. longum at the species level, which might related with sphingolipid metabolism, were significantly altered by B. longum CECT7894 when compared to the OVA group. Employed the metabolomics analysis, phytosphingosine, C16 sphinganine, sphinganine and sphingosine were identified as significantly changed metabolites and sphingolipid metabolism pathway was significantly enriched by pathway enrichment analysis. The Spearman's correlation analysis further demonstrated that there were strong correlations between serum biochemical indicators, tran-scripts, gut microbiota and metabolites. Based on the findings described above, from the perspective of genes, gut flora and metabolites changes, it can be concluded that B. longum CECT7894 might suppress OVA-induced FA by regulating the sphingolipid metabolism pathway.

Background: The dietary inflammatory index (DII) is thought to be related to many healthy events. However, the association between the DII and sarcopenia remains unclear. Methods: The meta-analysis was conducted to evaluate the effects of the DII on the risk of sarcopenia utilizing available studies. Up to September 2022, Cochrane, PubMed, Web of Science, Medline, and EMBASE databases were searched to evaluate the relationships between the DII and sarcopenia. A random‒effects model was used to calculate the effect size and 95% confidence intervals (CIs). Result: Eleven studies with 19,954 participants were included in our meta-analysis. The results indicated that a high DII increased the risk of sarcopenia (OR = 1.16, 95%CI [1.06, 1.27], p < 0.05). The result of the dose–response analysis showed that the risk of sarcopenia increased by 1.22 times for each 1-point increase in the DII score (OR = 1.22, 95%CI [1.12, 1.33], p < 0.05). Conclusion: The meta-analysis demonstrated that the DII is associated with sarcopenia. Considering some limitations in this study, more studies are needed to verify this relationship.