The role of lactoferrin in atherosclerosis.

Atherosclerosis (AS) is a common pathological basis for many cardiovascular diseases (CVDs) and result in high mortality and immense health and economic burdens worldwide. Early prevention, diagnosis, and treatment are promising approaches for stemming the development and progression of AS. Lactoferrin (Lf) is an iron-binding glycoprotein belonging to the transferrin family. It is widely found in body fluids such as digestive tract fluids, tears, and milk. Lf possesses anti-inflammatory, antibacterial, immunoregulatory, antioxidant and many other physiological functions. The serum Lf level is reportedly associated with the risk of AS and AS-related CVDs. Lf administration is closely involved in several mechanisms, including cholesterol metabolism, foam cell formation, ICAM-1 expression, homocysteine and leptin levels, anti-inflammatory and antioxidant function. Moreover, Lf has also been applied in the sythesis of magnetic resonance imaging (MRI) contrast agents to detect AS. Lf plays an important role in AS and may therefore be used in its diagnosis and treatment. Thus, this article aims to review the association between Lf and the risk of AS and AS-related CVDs, the mechanisms of Lf administration on AS, and its potential application in AS diagnosis.

The association between meat consumption and the metabolic syndrome: a cross-sectional study and meta-analysis.

The findings regarding the associations between red meat, fish and poultry consumption, and the metabolic syndrome (Mets) have been inconclusive, and evidence from Chinese populations is scarce. A cross-sectional study was performed to investigate the associations between red meat, fish and poultry consumption, and the prevalence of the Mets and its components among the residents of Suzhou Industrial Park, Suzhou, China. A total of 4424 participants were eligible for the analysis. A logistic regression model was used to estimate the OR and 95 % CI for the prevalence of the Mets and its components according to red meat, fish and poultry consumption. In addition, the data of our cross-sectional study were meta-analysed under a random effects model along with those of published observational studies to generate the summary relative risks (RR) of the associations between the highest v. lowest categories of red meat, fish and poultry consumption and the Mets and its components. In the cross-sectional study, the multivariable-adjusted OR for the highest v. lowest quartiles of consumption was 1·23 (95 % CI 1·02, 1·48) for red meat, 0·83 (95 % CI 0·72, 0·97) for fish and 0·93 (95 % CI 0·74, 1·18) for poultry. In the meta-analysis, the pooled RR for the highest v. lowest categories of consumption was 1·20 (95 % CI 1·06, 1·35) for red meat, 0·88 (95 % CI 0·81, 0·96) for fish and 0·97 (95 % CI 0·85, 1·10) for poultry. The findings of both cross-sectional studies and meta-analyses indicated that the association between fish consumption and the Mets may be partly driven by the inverse association of fish consumption with elevated TAG and reduced HDL-cholesterol and, to a lesser extent, fasting plasma glucose. No clear pattern of associations was observed between red meat or poultry consumption and the components of the Mets. The current findings add weight to the evidence that the Mets may be positively associated with red meat consumption, inversely associated with fish consumption and neutrally associated with poultry consumption.

Lactoferrin ameliorated obesity-induced endothelial dysfunction by inhibiting the Tak1/IL-18/eNOS pathway between PVAT and vascular endothelium.

Vascular endothelial dysfunction (ED) is one of the mechanisms underlying obesity-related hypertension. Perivascular adipose tissue (PVAT) surrounds blood vessels and influences the vascular endothelium function. Previous studies have demonstrated the antihypertensive effects of lactoferrin (LF) and its hydrolysates through various mechanisms. However, the effect of LF on ED and PVAT has not yet been investigated. In this study, we examined the influence of LF on ED and PVAT using high-fat diet mice as well as MAEC cells and 3T3-L1 adipocytes. Finally, LF supplementation decreases the systolic blood pressure (SBP), serum adhesion molecule (ICAM-1 and VCAM-1), and aorta ROS levels, and improves endothelium-dependent relaxation function in high-fat diet mice. Moreover, LF supplementation down-regulates the Tak1/IL-18/eNOS pathway between PVAT and aorta and enhances the NO generation in high-fat diet mice. In addition, we observe that LF decreases the expression levels of IL-18 and p-Tak1 in 3T3-L1 adipocytes, but fails to influence the eNOS and p-eNOS expression levels in MAEC cells. Finally, the significant associations between LF and IL-18 and SBP and hypertension risk are also observed in obesity children only. These findings provide evidence that the Tak1/IL-18/eNOS pathway between the aorta and PVAT is important in obesity-related ED, and LF may improve ED or even hypertension by down-regulating this pathway.

The prevalence of hypertension and elevated blood pressure and its correlation with overweight/obesity among students aged 6-17 years in Suzhou.

OBJECTIVES: Lifestyle changes have led to an increase in the prevalence of hypertension in Chinese children and adolescents. The aim of this study was to analyze the prevalence of hypertension and its association with overweight and obesity among students aged 6-17 years in Suzhou. This retrospective analysis included physical examination data of primary and junior high school students in Suzhou Industrial Park from 2016 to 2019. METHODS: Elevated blood pressure and hypertension were defined using blood pressure criteria appropriate for age, sex, and height percentile. Overweight and obesity were defined using the 2007 diagnostic criteria proposed by the World Health Organization for school-age children. Logistic regression analysis was used to evaluate the association between hypertension and overweight and obesity. RESULTS: A total of 128,113 students were included. The prevalence of elevated BP and hypertension was 9.92% and 13.56%, respectively. The incidence of high blood pressure was higher in boys than in girls and increased with an increase in body mass index (BMI). The prevalence of hypertension in obese boys and girls (27.07% and 27.49%, respectively) was 2.3-fold and 2.8-fold higher than that in normal-weight boys and girls (11.58% and 9.83%, respectively). CONCLUSIONS: Blood pressure was positively correlated with BMI, and the risk of high blood pressure due to overweight/obesity was 10.44%. Overweight and obesity significantly increased the risk of hypertension in students aged 6-17 years in Suzhou. Targeted weight-loss programs during childhood and adolescence may reduce the risk of hypertension in adulthood.

Slowly Digestible Carbohydrate Diet Ameliorates Hyperglycemia and Hyperlipidemia in High-Fat Diet/Streptozocin-Induced Diabetic Mice.

Objective: Given that the prevalence rate of type 2 diabetes mellitus (T2DM) continues to increase, it is important to find an effective method to prevent or treat this disease. Previous studies have shown that dietary intervention with a slowly digestible carbohydrate (SDC) diet can improve T2DM with almost no side effects. However, the underlying mechanisms of SDC protect against T2DM remains to be elucidated. Methods: The T2DM mice model was established with a high-fat diet and streptozocin injection. Then, SDC was administered for 6 weeks. Bodyweight, food intake, organ indices, fasting blood glucose (FBG), oral glucose tolerance test (OGTT), homeostasis model assessment for insulin resistance (HOMA-IR), and other biochemical parameters were measured. Histopathological and lipid accumulation analyses were performed, and the glucose metabolism-related gene expressions in the liver and skeletal muscle were determined. Lastly, colonic microbiota was also analyzed. Results: SDC intervention alleviated the weight loss in the pancreas, lowered blood glucose and glycosylated hemoglobin levels, and improved glucose tolerance and HOMA-IR. SDC intervention improved serum lipid profile, adipocytokines levels, and lowered the lipid accumulation in the liver, subcutaneous adipose tissue, and epididymal visceral adipose tissue. In addition, SDC intervention increased the expression levels of IRS-2 and GLUT-2 in liver tissues and elevated GLUT-4 expression levels in skeletal muscle tissues. Notably, SDC intervention decreased the Bacteroidetes/Firmicutes ratio, increased Desulfovibrio and Lachnospiraceae genus levels, and inhibited the relative abundance of potentially pathogenic bacteria. Conclusions: SDC intervention can improve hyperglycemia and hyperlipidemia status in diabetic mice, suggesting that this intervention might be beneficial for T2DM.

Holo-lactoferrin: the link between ferroptosis and radiotherapy in triple-negative breast cancer.

Rationale: Iron-saturated Lf (Holo-Lactoferrin, Holo-Lf) exhibits a superior anticancer property than low iron-saturated Lf (Apo-Lf). Ferroptosis is an iron-dependent cell death characterized by the accumulation of lipid peroxidation products and lethal reactive oxygen species (ROS). Radiotherapy also exerts its therapeutic effect through ROS. Methods: The effect of different iron-saturated Lf on ferroptosis and radiotherapy were tested on triple-negative breast cancer (TNBC) cell line MDA-MB-231 and non-TNBC cell line MCF-7. Results: Holo-Lf significantly increased the total iron content, promoted ROS generation, increased lipid peroxidation end product, malondialdehyde (MDA), and enhanced ferroptosis of MDA-MB-231 cells. By contrast, Apo-Lf upregulated SLC7a11 expression, increased GSH generation and inhibited ferroptosis of MDA-MB-231 cells. However, non-TNBC MCF-7 cells were resistant to Holo-Lf-induced ferroptosis because MCF-7 cells have a higher redox balance capacity than MDA-MB-231 cells. More importantly, Holo-Lf downregulated HIF-1α expression, ameliorated the hypoxia microenvironment in subcutaneous MDA-MB-231 tumors, and promoted radiation-induced DNA damage to hypoxic MDA-MB-231 cells. Finally, the efficacy of radiotherapy to MDA-MB-231 tumors was enhanced by Holo-Lf. Conclusion: Holo-Lf could induce ferroptosis in MDA-MB-231 cells and sensitize MDA-MB-231 tumors to radiotherapy.