Dietary isothiocyanates and anticancer agents: exploring synergism for improved cancer management.

Human studies have shown the anticancer effects of dietary isothiocyanates (ITCs), but there are some inconsistencies, and more evidence supports that such anticancer effect is from higher doses of ITCs. The inconsistencies found in epidemiological studies may be due to many factors, including the biphasic dose-response (so called hormetic effect) of ITCs, which was found to be more profound under hypoxia conditions. In this comprehensive review, we aim to shed light on the intriguing synergistic interactions between dietary ITCs, focusing on sulforaphane (SFN) and various anticancer drugs.

Supplementation of Silymarin Alone or in Combination with Salvianolic Acids B and Puerarin Regulates Gut Microbiota and Its Metabolism to Improve High-Fat Diet-Induced NAFLD in Mice.

Silymarin, salvianolic acids B, and puerarin were considered healthy food agents with tremendous potential to ameliorate non-alcoholic fatty liver disease (NAFLD). However, the mechanisms by which they interact with gut microbiota to exert benefits are largely unknown. After 8 weeks of NAFLD modeling, C57BL/6J mice were randomly divided into five groups and fed a normal diet, high-fat diet (HFD), or HFD supplemented with a medium or high dose of Silybum marianum extract contained silymarin or polyherbal extract contained silymarin, salvianolic acids B, and puerarin for 16 weeks, respectively.

Dietary Achievable Dose of Protocatechuic Acid, a Metabolite of Flavonoids, Inhibits High-Fat Diet-Induced Obesity in Mice.

Scope: Protocatechuic acid (PCA), a gut microbiota metabolite of flavonoids, inhibits dietary obesity and increases uncoupling protein 1 (UCP1), a critical regulator responsible for adipose thermogenesis; however, these effects are achieved at dietary unachievable (pharmacological) dose. It evaluates whether dietary achievable dose of PCA inhibits adiposity by activating adipose thermogenesis.

Methods And Results: Six-week-old male C57BL/6J mice are fed a high-fat diet (HFD) alone (control) or supplemented with 0.

Protocatechuic acid boosts continual efferocytosis in macrophages by derepressing KLF4 to transcriptionally activate MerTK.

Macrophages clear apoptotic cells through a process called continual efferocytosis. We found that protocatechuic acid (PCA), a polyphenolic compound abundant in fruits and vegetables, increased the continual efferocytic capacity of macrophages and inhibited the progression of advanced atherosclerosis. PCA reduced the intracellular amounts of microRNA-10b (miR-10b) by promoting its secretion in extracellular vesicles, which led to an increase in the abundance of the miR-10b target Krüppel-like factor 4 (KLF4).

Cardamonin targets KEAP1/NRF2 signaling for protection against atherosclerosis.

Atherosclerosis (AS)-induced cardiovascular disease is a leading cause of death worldwide. To date, there is still a lack of effective approaches for AS intervention. Cardamonin (CAD) is a bioactive food component, but its effect on AS is unknown.

Re-Visiting Antioxidant Therapy in Murine Advanced Atherosclerosis with Brussels Chicory, a Typical Vegetable in Mediterranean Diets.

Brussels chicory, a typical vegetable in Mediterranean diets, has been recently reported to stabilize advanced atherosclerotic plaques in the brachiocephalic artery of apoE-deficient () mice. Herein, we investigated whether Brussels chicory can stabilize advanced plaques in the aorta via improving oxidative stress. Thirty week old mice were fed the AIN-93G diet or supplemented with 0.

Alterations of NMR-Based Lipoprotein Profile Distinguish Unstable Angina Patients with Different Severity of Coronary Lesions.

Non-invasive detection of unstable angina (UA) patients with different severity of coronary lesions remains challenging. This study aimed to identify plasma lipoproteins (LPs) that can be used as potential biomarkers for assessing the severity of coronary lesions, determined by the Gensini score (GS), in UA patients. We collected blood plasma from 67 inpatients with angiographically normal coronary arteries (NCA) and 230 UA patients, 155 of them with lowGS (GS ≤ 25.

Association of MAFLD with end-stage kidney disease: a prospective study of 337,783 UK Biobank participants.

Introduction: Metabolic dysfunction-associated fatty liver (MAFLD) has been found to be associated with the prevalence of chronic kidney disease (CKD). However, it is unknown whether MAFLD is associated with CKD development and the incidence of end-stage kidney disease (ESKD). We aimed to clarify the association between MAFLD and incident ESKD in the prospective UK Biobank cohort.

Protects Against Elevated Arterial Stiffness.

Background: Dysbiosis of gut microbiota plays a pivotal role in vascular dysfunction and microbial diversity was reported to be inversely correlated with arterial stiffness. However, the causal role of gut microbiota in the progression of arterial stiffness and the specific species along with the molecular mechanisms underlying this change remain largely unknown.

Methods: Participants with elevated arterial stiffness and normal controls free of medication were matched for age and sex.

Extraction, Characterization, and Platelet Inhibitory Effects of Two Polysaccharides from the Cs-4 Fungus.

Cardiovascular diseases are associated with platelet hyperactivity, and downregulating platelet activation is one of the promising antithrombotic strategies. This study newly extracted two polysaccharides (purified exopolysaccharides, EPSp and purified intercellular exopolysaccharides, IPSp) from Cs-4 mycelial fermentation powder, and investigated the effects of the two polysaccharides and their gut bacterial metabolites on platelet functions and thrombus formation. EPSp and IPSp are majorly composed of galactose, mannose, glucose, and arabinose.

Global burden of nonalcoholic steatohepatitis-related liver cancer, 1990-2019: a systematic analysis for the GBD 2019.

With the pandemic of metabolic diseases, nonalcoholic fatty liver disease (NAFLD) prevalence has dramatically elevated. NAFLD encompasses a spectrum of diseases including simple steatosis and nonalcoholic steatohepatitis (NASH), which can further progress to cirrhosis or liver cancer (LC). However, data are lacking on the burden and trend of NASH-related LC.

Gut Microbially Produced Indole-3-Propionic Acid Inhibits Atherosclerosis by Promoting Reverse Cholesterol Transport and Its Deficiency Is Causally Related to Atherosclerotic Cardiovascular Disease.

Background: Accumulating evidence has shown that disorders in the gut microbiota and derived metabolites affect the development of atherosclerotic cardiovascular disease (ASCVD). However, which and how specific gut microbial metabolites contribute to the progression of atherosclerosis and the clinical relevance of their alterations remain unclear.

Methods: We performed integrated microbiome-metabolome analysis of 30 patients with coronary artery disease (CAD) and 30 age- and sex-matched healthy controls to identify CAD-associated microbial metabolites, which were then assessed in an independent population of patients with ASCVD and controls (n=256).

Cyanidin-3-O-Glucoside Ameliorates Palmitic-Acid-Induced Pancreatic Beta Cell Dysfunction by Modulating CHOP-Mediated Endoplasmic Reticulum Stress Pathways.

Cyanidin-3-O-glucoside (C3G) is a natural colorant with anti-diabetic properties, while its underlying mechanisms remain far from clear. Here, we investigated the protective role of C3G on palmitic acid (PA)-induced pancreatic beta cell dysfunction and further decipher its possible molecular mechanisms. Both primary isolated mouse islets and the INS-1E cell were used, and treated with a mixture of PA (0.

Protective effects of konjac glucomannan on gut microbiome with antibiotic perturbation in mice.

This study assessed the protective effects of konjac glucomannan (KGM) on gut microbiome against the antibiotic perturbation in C57BL/6J mice. The native KGM (1.82 × 10) was partially hydrolyzed by endo-1,4-β-mannanase, and two hydrolyzed fractions (KGM-eM with 3.

Brussels Chicory Stabilizes Unstable Atherosclerotic Plaques and Reshapes the Gut Microbiota in Apoe-/- Mice.

Background: Adherence to a Mediterranean dietary pattern can protect against atherosclerosis in part by reducing intestinal permeability and gut microbial LPS production. Brussels chicory, a typical Mediterranean vegetable, has been shown to inhibit the formation of early-stage atherosclerosis in mice.

Objectives: We evaluated whether Brussels chicory affects advanced atherosclerosis progression, intestinal permeability, and gut microbial LPS production.

Biphasic effect of sulforaphane on angiogenesis in hypoxia modulation of both Nrf2 and mitochondrial dynamics.

Sulforaphane (SFN) is an isothiocyanate (ITC) derived from a glucosinolate, glucoraphinin found in cruciferous vegetables. There are few studies that focus on the role of SFN in angiogenesis under hypoxic conditions. The effect of SFN on angiogenesis and the underlying mechanisms including the roles of Nrf2 and mitochondrial dynamics were investigated using cultured human umbilical vein endothelial cells (HUVECs) in hypoxia.

Terpene Lactucopicrin Limits Macrophage Foam Cell Formation by a Reduction of Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 in Lipid Rafts.

Scope: Sustained inflammation promotes macrophage foam cell formation by promoting cholesterol influx and impairing cholesterol efflux. Terpene lactucopicrin, affluent in vegetables of the Asteraceae family (e.g.

Cyanidin-3-O-Glucoside Supplementation Ameliorates Metabolic Insulin Resistance via Restoration of Nitric Oxide-Mediated Endothelial Insulin Transport.

Scope: Anthocyanin cyanidin-3-O-glucoside (Cy3G) possesses a great potential in prevention of diabetes and its vascular complications while the underlying mechanisms are still far from clear. Accumulating evidence suggests that endothelial insulin transport plays a critical role in regulating metabolic insulin sensitivity. Whether Cy3G can modulate metabolic insulin resistance via regulating endothelial insulin transport is not reported yet.

Inverse Association of Serum Adipsin with the Remission of Nonalcoholic Fatty-Liver Disease: A 3-Year Community-Based Cohort Study.

Purposes: Adipokine alterations contribute to the development and remission of nonalcoholic fatty-liver disease (NAFLD). Adipsin is one of the most abundant adipokines and is almost exclusively produced by adipocytes. However, data on adipsin in human NAFLD are limited and controversial.

Prevalence and risk factors of metabolic associated fatty liver disease in the contemporary South China population.

Background: As a newly proposed diagnosis, data on the prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) is rare. We aimed to assess the prevalence and risk factors of MAFLD using new definition in the contemporary South China population.

Methods: In this population based, cross sectional study, a total of 5377 participants aged 30-79 years old were recruited from the South China between 2018 and 2019.

Natural lactucopicrin alleviates importin-α3-mediated NF-κB activation in inflammated endothelial cells and improves sepsis in mice.

Lactucopicrin, a bitter sesquiterpene lactone of leafy vegetables, such as chicory, curly escarole, and lettuce, possesses anti-malarial, anti-cancer and analgesic properties. However, it remains unknown whether lactucopicrin could inhibit vascular endothelial nuclear factor-κB (NF-κB) activation, a hallmark of vascular inflammatory diseases including sepsis. In tumor necrosis factor-α-stimulated human or mouse aortic endothelial cells, lactucopicrin dose-dependently inhibited NF-κB activation, and concomitantly repressed both vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1)-mediated monocyte adhesion.

Lactucopicrin Inhibits Cytoplasmic Dynein-Mediated NF-κB Activation in Inflammated Macrophages and Alleviates Atherogenesis in Apolipoprotein E-Deficient Mice.

Scope: Nuclear factor-κB (NF-κB) activation in macrophages aggravates atherosclerosis. Dietary plant secondary metabolites including sesquiterpene lactone lactucopicrin target multiple organs. This study is focused on the impact of lactucopicrin on NF-κB activation in inflammed macrophages and atherogenesis in a mouse model of atherosclerosis.

Low Oral Bioavailability and Partial Gut Microbiotic and Phase II Metabolism of Brussels/Witloof Chicory Sesquiterpene Lactones in Healthy Humans.

Free and glycosylated sesquiterpene lactones (SLs), which are abundant in leafy vegetables including Brussels/witloof chicory, possess health-promoting effects in vivo. However, the pharmacokinetics of dietary source of SLs remain largely unknown. In this open-label and single-dose trial, sixteen healthy volunteers consumed 150 g of Brussels/witloof chicory juice containing 48.

Retinol-Binding Protein 4 Activates STRA6, Provoking Pancreatic β-Cell Dysfunction in Type 2 Diabetes.

Pancreatic β-cell dysfunction plays a decisive role in the progression of type 2 diabetes. Retinol-binding protein 4 (RBP4) is a prominent adipokine in type 2 diabetes, although its effect on β-cell function remains elusive, and the underlying mechanisms are unknown. Here, we found that elevated circulating RBP4 levels were inversely correlated with pancreatic β-cell function in mice across different glycemic stages.

Intermittent Fasting Improves Cardiometabolic Risk Factors and Alters Gut Microbiota in Metabolic Syndrome Patients.

Context: Intermittent fasting (IF) is an effective strategy to improve cardiometabolic health.

Objective: The objective of this work is to examine the effects of IF on cardiometabolic risk factors and the gut microbiota in patients with metabolic syndrome (MS).

Design And Setting: A randomized clinical trial was conducted at a community health service center.