Atherosclerosis is the primary cause of cardiovascular and cerebrovascular diseases. However, current anti-atherosclerosis drugs have shown conflicting therapeutic outcomes, thereby spurring the search for novel and effective treatments. Recent research indicates the crucial involvement of oral and gastrointestinal microbiota in atherosclerosis. While gut microbiota metabolites, such as choline derivatives, have been extensively studied and reviewed, emerging evidence suggests that bacterial extracellular vesicles (BEVs), which are membrane-derived lipid bilayers secreted by bacteria, also play a significant role in this process. However, the role of BEVs in host-microbiota interactions remains insufficiently explored. This review aims to elucidate the complex communication mediated by BEVs along the gut-heart axis. In this review, we summarize current knowledge on BEVs, with a specific focus on how pathogen-derived BEVs contribute to the promotion of atherosclerosis, as well as how BEVs from gut symbionts and probiotics may mitigate its progression. We also explore the potential and challenges associated with engineered BEVs in the prevention and treatment of atherosclerosis. Finally, we discuss the benefits and challenges of using BEVs in atherosclerosis diagnosis and treatment, and propose future research directions to address these issues.

Helicobacter pylori (H. pylori), a globally widespread pathogen affecting half of the global population, has been increasingly implicated in metabolic disorders, including obesity, dyslipidemia, and metabolic dysfunction-associated steatotic liver disease (MASLD). MASLD is a common condition, impacting nearly one in four adults globally. It also shares significant pathophysiological links with metabolic syndrome. Despite the fact that mechanistic hypotheses (such as oxidative stress and inflammation) have been proposed to explain these relationships, large-scale studies comprehensively assessing multifactorial metabolic associations are lacking. We proposed that H. pylori infection may independently correlate with unfavorable metabolic profiles and the presence of MASLD among adults in a large cohort.

To investigate the associations of H. pylori infection with obesity, glucose, lipids, blood pressure, and MASLD in Chinese adults.

This study included 28624 adults recruited from the Physical Examination Center at Nanchang University's Second Affiliated Hospital. The 13C-urea breath test was used to identify H. pylori infection, while abdominal ultrasound was employed for MASLD diagnosis. The relationships between H. pylori infection and metabolic factors were analyzed via multivariate logistic regression.

The overall H. pylori infection incidence was 26.8%, with higher rates observed in older adults (≥ 70 years: 26.1% vs 18-29 years: 24.6%, P < 0.001) and obese individuals [body mass index (BMI) ≥ 28 kg/m²: 30.0% vs normal BMI: 25.3%, P < 0.001]. H. pylori-positive individuals exhibited elevated blood glucose (5.43 ± 1.55 mmol/L vs 5.27 ± 1.23 mmol/L, P < 0.001), low-density lipoprotein cholesterol (2.97 ± 0.76 mmol/L vs 2.94 ± 0.75 mmol/L, P < 0.001), and blood pressure (systolic: 123.49 ± 19.06 mmHg vs 122.85 ± 18.33 mmHg, P = 0.009; diastolic: 75.48 ± 12.37 vs 74.9 mmHg ± 11.9 mmHg, P < 0.001) levels. Among MASLD patients, infection was associated with increased glucose (5.82 ± 1.95 mmol/L vs 5.60 ± 1.60 mmol/L, P < 0.001), total cholesterol (5.05 ± 1.03 mmol/L vs 5.00 ± 1.00 mmol/L, P = 0.039), BMI (26.23 ± 3.00 kg/m² vs 26.04 ± 2.96 kg/m², P = 0.004), and blood pressure (systolic: 129.5 ± 20.00 mmHg vs 128.49 ± 17.62 mmHg, P = 0.009; diastolic: 79.87 ± 12.07 mmHg vs 79.04 ± 11.76 mmHg, P = 0.002) levels. Multivariate analysis demonstrated elevated glucose [odds ratio (OR) = 1.079, P < 0.001], BMI (OR = 1.016, P = 0.002), and diastolic pressure (OR = 1.003, P = 0.048) levels as independent risk factors, with high-density lipoprotein (HDL) being observed as a protective factor (OR = 0.837, P < 0.001).

H. pylori infection correlates with older age, obesity, elevated glucose levels, and elevated diastolic blood pressure, whereas HDL protects against H. pylori infection, thus underscoring its role in metabolic disturbances and MASLD.

Helicobacter pylori (H. pylori) is known to induce chronic inflammatory conditions, and interactions between the host immune system and pathogen have diverted attention toward investigating its correlation with extra-gastrointestinal disorders.

The present study aimed to assess the rate of H. pylori infection in cardiovascular disease (CVD) through a systematic review and meta-analysis.

We conducted a large-scale meta-analysis to determine the prevalence rates of H. pylori infection in vascular diseases. Articles from PubMed/Medline, Web of Science, and Embase databases published between 2000 and 2023 were included for analysis. We used multiple independent observers to extract data, calculated the pooled frequency of H. pylori in vascular diseases using a random effect model, and reported the results as a weighted average based on the study population. The main outcome measures were presented with 95% confidence intervals (CI).

In 87 included studies, the prevalence of H. pylori infection in vascular diseases was 56.7% worldwide. 14.25% of H. pylori isolates harbored the cagA gene. The predominant vascular complication was coronary artery disease (CAD) (31.07%), primarily documented in Europe. This meta-analysis revealed a declining emphasis on studying the association of H. pylori infection with vascular disease in recent times.

According to this meta-analysis, H. pylori infection has a high frequency in CVD and may increase the risk of vascular diseases. However, further research is required, particularly in nations with limited data.

Hypertriglyceridemia (HTG) is a prevalent metabolic disorder closely linked to cardiovascular diseases, diabetes, and other metabolic conditions. However, research examining the relationship between Helicobacter pylori (H. pylori) and HTG is limited. This study aimed to investigate the influence of H. pylori on HTG.

The study participants were individuals who underwent health examinations at Taizhou Hospital between 2017 and 2024. The subjects underwent hematological tests, anthropometric measurements, and urea breath tests. Logistic regression analysis was used to assess the relationship between H. pylori and HTG. Kaplan-Meier curves were utilized to compare HTG incidence between groups, and Cox regression models were applied to calculate associated hazard ratios.

Logistic regression confirmed that H. pylori was a risk factor for HTG. Further cohort study indicated that prolonged H. pylori infection increased the risk of HTG, whereas H. pylori eradication led to a decrease in HTG incidence. Subgroup analyses demonstrated that the impact of H. pylori on HTG did not exhibit heterogeneity.

H. pylori was associated with an increased risk of HTG, and its eradication was crucial for reducing this risk.

Although Helicobacter pylori (H. pylori) infections are widespread throughout the world, it is yet unknown whether they are linked to systemic illnesses like dyslipidemia. The purpose of this systematic review and meta-analysis was to examine the connection between lipid metabolism and H. pylori infection, with a particular emphasis on how it affects dyslipidemia.

We conducted a thorough search up until October 10, 2024, across databases such as PubMed, Web of Science, and Embase. Studies that reported lipid profiles in both H. pylori-infected and non-infected patients were considered eligible. The primary outcomes were triglyceride, LDL-C, HDL-C, and total cholesterol levels, which were examined using a random-effects model in R software version 4.4.

There were 17 studies with more than 150,000 participants from 681 screened publications. Higher levels of LDL (MD: 5.32 mg/dL; 95% CI: 1.315 to 9.319) and total cholesterol (MD: 6.28 mg/dL; 95% CI: 0.718 to 11.842), as well as lower levels of HDL (MD: -2.06 mg/dL; 95% CI: -3.212 to -0.915), were the results of the meta-analysis. Among those infected, triglyceride levels were likewise higher (MD: 7.93 mg/dL; 95% CI: 0.413 to 15.436), but the odds ratio (OR) did not show a significant increase in risk (OR: 1.002; 95% CI: 0.995 to 1.010).

H. pylori infection is associated with significant dyslipidemia, suggesting a potential link between chronic bacterial infection and lipid metabolism. The findings emphasize the need for further research to explore the mechanisms and potential therapeutic interventions.

Helicobacter pylori (H. pylori) infection have been closely associated with several extra-gastrointestinal disorders. Outer membrane vesicles (OMVs), as lipid-membrane-bounded nanoparticles, are usually shed from Gram-negative both in vitro and in vivo. H. pylori is also capable of producing OMVs, which can enter the systemic circulation and be delivered to various cells, tissues or organs, eliciting a range of inflammatory and immune modulation responses. In this current review, we summarize the biogenesis and functions of H. pylori OMVs, describe the contribution of H. pylori OMVs to the generation and progression of extra-gastrointestinal diseases, such as neuronal damage, Alzheimer disease, hepatic fibrosis and atherosclerosis. We also explored the effect of H. pylori OMVs in inflammatory and immune modulation of diverse immune cells, including macrophages, mononuclear cells and dendritic cells. By elucidating the molecular mechanism of H. pylori OMVs-mediated extra-gastrointestinal diseases and immunomodulatory effect, it may promote the development of efficient treatments and vaccinations against H. pylori.

Extracellular vesicles (EVs) are relevant elements for cell-to-cell communication and are considered crucial in host-pathogen interactions by transferring molecules between the pathogen and the host during infections. These structures participate in various physiological and pathological processes and are considered promising candidates as disease markers, therapeutic reagents, and drug carriers. Both H. pylori and the host epithelial cells infected by H. pylori secrete EVs, which contribute to inflammation and the development of disease phenotypes. However, many aspects of the cellular and molecular biology of EV functions remain incompletely understood due to methodological challenges in studying these small structures. This review also highlights the roles of EVs derived from H. pylori-infected cells in the pathogenesis of gastric and extragastric diseases. Understanding the specific functions of these EVs during H. pylori infections, whether are advantageous to the host or the pathogen, may help the development new therapeutic approaches to prevent disease.

The Triglyceride-glucose (TyG) index is a marker for insulin resistance and metabolic syndrome, while Helicobacter pylori is linked to gastrointestinal diseases and may affect metabolic risks. This study examined the association between the TyG index and H. pylori infection in adults.

Data from 3797 participants in the NHANES 1999-2000 cycle were analyzed. The relationship between the TyG index and H. pylori infection was assessed using multivariate logistic regression and a two-piecewise logistic model to explore non-linear effects. Subgroup analyses were conducted based on age, sex, glucose levels, BMI, and CKD.

A linear association between the TyG index and H. pylori infection was found. Subgroup analyses revealed significant interactions with a few variables.

This study indicates a linear relationship between the TyG index and H. pylori infection, suggesting metabolic influences on H. pylori infection and potential for targeted interventions in at-risk groups.

Hypertension is a major harbinger of cardiovascular morbidity and mortality. It predisposes to higher rates of myocardial infarction, chronic kidney failure, stroke, and heart failure than most other risk factors. By 2025, the prevalence of hypertension is projected to reach 1.5 billion people. The pathophysiology of this disease is multifaceted, as it involves nitric oxide and endothelin dysregulation, reactive oxygen species, vascular smooth muscle proliferation, and vessel wall calcification, among others. With the advent of new biomolecular techniques, various studies have elucidated a gaping hole in the etiology and mechanisms of hypertension. Indeed, epigenetics, DNA methylation, histone modification, and microRNA-mediated translational silencing appear to play crucial roles in altering the molecular phenotype into a hypertensive profile. Here, we critically review the experimentally determined associations between microRNA (miRNA) molecules and hypertension pharmacotherapy. Particular attention is given to the epigenetic mechanisms underlying the physiological responses to antihypertensive drugs like candesartan, and other relevant drugs like clopidogrel, aspirin, and statins among others. Furthermore, how miRNA affects the pharmaco-epigenetics of hypertension is especially highlighted.

Given sparse relevant data, the aim of this study was to determine whether Helicobacter pylori infection, including cytotoxin-associated gene-A (CagA) producing strains, is associated with dementia in type 2 diabetes (T2DM).

Longitudinal data from 1115 participants in the community-based Fremantle Diabetes Study Phase I (mean age 64.0 years, 48.0 % males; 38.0 % H. pylori seronegative, 24.3 % H. pylori seropositive/CagA seronegative, and 37.7 % H. pylori/CagA seropositive at baseline) were analyzed.

During up to 19 years of follow-up, 50.3 % and 83.5 % of participants without and with incident dementia, respectively, died. In Cox proportional hazards models, H. pylori/CagA seropositivity (hazard ratio (95 % CI) 1.68 (1.15, 2.46), P = 0.008), but not H. pylori seropositivity/CagA seronegativity (P = 0.541) was an independent predictor of incident dementia, but neither H. pylori seropositivity/CagA seronegativity nor H. pylori/CagA seropositivity were significant predictors in competing risks models (P ≥ 0.280).

Although CagA seropositivity in T2DM may have a contributory etiologic role in the risk of dementia, this may be through its association with reduced cardiovascular/all-cause mortality.

Cardiovascular disease (CVD) remains the leading cause of global morbidity and mortality. Extensive efforts have been invested to explicate mechanisms implicated in the onset and progression of CVD. Besides the usual suspects as risk factors (obesity, diabetes, and others), the gut microbiome has emerged as a prominent and essential factor in the pathogenesis of CVD. With its endocrine-like effects, the microbiome modulates many physiologic processes. As such, it is not surprising that dysbiosis-by generating metabolites, inciting inflammation, and altering secondary bile acid signaling- could predispose to or aggravate CVD. Nevertheless, various natural and synthetic compounds have been shown to modulate the microbiome. Prime among these molecules are flavonoids, which are natural polyphenols mainly present in fruits and vegetables. Accumulating evidence supports the potential of flavonoids in attenuating the development of CVD. The ascribed mechanisms of these compounds appear to involve mitigation of inflammation, alteration of the microbiome composition, enhancement of barrier integrity, induction of reverse cholesterol transport, and activation of farnesoid X receptor signaling. In this review, we critically appraise the methods by which the gut microbiome, despite being essential to the human body, predisposes to CVD. Moreover, we dissect the mechanisms and pathways underlying the cardioprotective effects of flavonoids.

Inflammation plays a crucial role in the development of metabolic syndrome (MetS). However, the roles of pepsinogens (PGs) and gastrin, known biomarkers linked to gastric inflammation, in MetS and the transition of MetS status are unclear. This research aimed to explore the relationship between MetS, the transition of MetS status, and levels of gastric biomarkers.

This large-scale cross-sectional study included 19162 participants aged 18-80 years between August 2021 and March 2024. Serum levels of the gastric biomarkers PGI, PGII, and gastrin-17 were analyzed using enzyme-linked immunosorbent assay. In addition, the relationship between transitions of MetS status based on 1032 MetS-negative participants from baseline to the second health exam after 2 years was considered. The association between MetS and the transitions of MetS status and gastric biomarkers was analyzed using logistic regression models.

The prevalence of MetS in the study population was 31.4%, with higher rates in males (35.2%) than females (24.6%). Gastrin-17 levels were markedly elevated in participants with MetS, a trend observed in both genders. In the logistic regression analysis, after adjusting for confounding factors, gastrin-17 levels were strongly and positively correlated with MetS in the entire cohort and in males but not in females. Male participants with MetS had lower levels of PGI and PGII than those without MetS, whereas the opposite trend was observed in females. Logistic regression analysis indicated that PGI and PGII were not independently associated with MetS. During the follow-up of 2 years, 199 (19.28%) of the 1032 MetS-negative participants transitioned to MetS-positive status. As compared to the stable MetS-negative subjects, transition from MetS-negative to MetS-positive was associated with higher levels of gastrin-17, especially in males, but not in females.

Gastrin-17 is a promising biomarker for MetS, exhibiting potential utility in monitoring the transition of MetS status and revealing gender difference.

Local wisdom food ingredients in North Sumatra, Indonesia, are a source of phenolics which have antioxidant, antihyperlipidemia, neuronal survival, and growth. Administering products with antioxidant properties can provide a supporting effect in preventing inflammation and neurodegenerative process.

The main objective of this study was to analyze the formulation of red palm oil (Elaeis guineensis Jacq), koja bay leaves (Murraya koenigii L Spreng), and passion fruit seeds (Passiflora edulis Sims) to improve lipid profile, antioxidant activity, Brain-Derived Neurotrophic Factor (BDNF), and lipase enzyme activity of Sprague-Dawley rats.

This study was an in vivo and pre-post experimental study, starting with analyzing flavonoid of the three extract ingredients, then tested by giving it to rats for 14 days and ending with induction administration of lipopolysaccharide (LPS) for two days. This pre-post study on animals involved 36 rats divided into 6 groups. At the end of the study, termination and examination of malondialdehyde, lipid profile, glucose, BDNF, lipase enzyme activity and histopathological examination were carried out.

The study results showed that there were significant values in several parameters, which were body weight, LDL, LDL/HDL ratio, BDNF, and lipase enzyme activity especially in the group of rats given LPS and the group with high calories-fat-protein. This study showed that there were significant differences in body weight, LDL levels, and LDL/HDL ratio in each group of rats, especially in the group given the formulation of the three extract ingredients, the significant dose showed in 300mg/kg body weight (p < 0.001).

The formulation of red palm oil, koja bay leaves, and passion fruit seeds showed significant reduction in LDL levels, LDL/HDL ratio, BDNF, and lipase enzyme activity.

Helicobacter pylori, a type of gram-negative bacterium, infects roughly half of the global population. It is strongly associated with gastrointestinal disorders like gastric cancer, peptic ulcers, and chronic gastritis. Moreover, numerous studies have linked this bacterium to various extra-gastric conditions, including hematologic, cardiovascular, and neurological issues. Specifically, research has shown that Helicobacter pylori interacts with the brain through the microbiota-gut-brain axis, thereby increasing the risk of neurological disorders. The inflammatory mediators released by Helicobacter pylori-induced chronic gastritis may disrupt the function of the blood-brain barrier by interfering with the transmission or direct action of neurotransmitters. This article examines the correlation between Helicobacter pylori and a range of conditions, such as hyperhomocysteinemia, schizophrenia, Alzheimer's disease, Parkinson's disease, ischemic stroke, multiple sclerosis, migraine, and Guillain-Barré syndrome.

Helicobacter pylori, the causative agent of peptic ulcer, gastritis, and gastric cancer encodes two carbonic anhydrases (CA, EC 4.2.1.1) belonging to the α- and β-class (HpCAα/β), which have been validated as antibacterial drug targets. Acetazolamide and ethoxzolamide were also clinically used for the management of peptic ulcer.

Sulfonamides were the most investigated HpCAα/β compounds, with several low nanomolar inhibitors identified, some of which also crystallized as adducts with HpCAα, allowing for the rationalization of the structure-activity relationship. Few data are available for other classes of inhibitors, such as phenols, sulfamides, sulfamates, dithiocarbamates, arylboronic acids, some of which showed effective in vitro inhibition and for phenols, also inhibition of planktonic growth, biofilm formation, and outer membrane vesicles spawning.

Several recent drug design studies reported selenazoles incorporating seleno/telluro-ethers attached to benzenesulfonamides, hybrids incorporating the EGFR inhibitor erlotinib and benzenesulfonamides, showing KIs < 100 nM against HpCAα and MICs in the range of 8-16 µg/mL for the most active derivatives. Few drug design studies for non-sulfonamide inhibitors were performed to date, although inhibition of these enzymes may help the fight of multidrug resistance to classical antibiotics which emerged in the last decades also for this bacterium.

1,3,6-Trigalloylglucose is a natural compound that can be extracted from the aqueous extracts of ripe fruit of Terminalia chebula Retz, commonly known as "Haritaki". The potential anti-Helicobacter pylori (HP) activity of this compound has not been extensively studied or confirmed in scientific research. This compound was isolated using a semi-preparative liquid chromatography (LC) system and identified through Ultra-high-performance liquid chromatography-MS/MS (UPLC-MS/MS) and Nuclear Magnetic Resonance (NMR). Its role was evaluated using Minimum inhibitory concentration (MIC) assay and minimum bactericidal concentration (MBC) assay, scanning electron microscope (SEM), inhibiting kinetics curves, urea fast test, Cell Counting Kit-8 (CCK-8) assay, Western blot, and Griess Reagent System. Results showed that this compound effectively inhibits the growth of HP strain ATCC 700392, damages the HP structure, and suppresses the Cytotoxin-associated gene A (Cag A) protein, a crucial factor in HP infection. Importantly, it exhibits selective antimicrobial activity without impacting normal epithelial cells GES-1. In vitro studies have revealed that 1,3,6-Trigalloylglucose acts as an anti-adhesive agent, disrupting the adhesion of HP to host cells, a critical step in HP infection. These findings underscore the potential of 1,3,6-Trigalloylglucose as a targeted therapeutic agent against HP infections.