Insulin resistance, coronary artery lesion complexity and adverse cardiovascular outcomes in patients with acute coronary syndrome.

BACKGROUND: Insulin resistance (IR) is linked to both the complexity of coronary artery lesions and the prognosis of acute coronary syndrome (ACS). However, the precise extent of this correlation and its impact on adverse cardiovascular outcomes in ACS patients remain unclear. Therefore, this study aims to investigate the intricate relationship between IR, coronary artery lesion complexity, and the prognosis of ACS through a cohort design analysis. METHOD: A total of 986 patients with ACS who underwent percutaneous coronary intervention (PCI) were included in this analysis. IR was assessed using the triglyceride-glucose (TyG) index, while coronary artery lesion complexity was evaluated using the SYNTAX score. Pearson's correlation coefficients were utilized to analyze the correlations between variables. The association of the TyG index and SYNTAX score with major adverse cardiovascular events (MACEs) in ACS was investigated using the Kaplan-Meier method, restricted cubic splines (RCS), and adjusted Cox regression. Additionally, a novel 2-stage regression method for survival data was employed in mediation analysis to explore the mediating impact of the SYNTAX score on the association between the TyG index and adverse cardiovascular outcomes, including MACEs and unplanned revascularization. RESULTS: During a median follow-up of 30.72 months, 167 cases of MACEs were documented, including 66 all-cause deaths (6.69%), 26 nonfatal myocardial infarctions (MIs) (2.64%), and 99 unplanned revascularizations (10.04%). The incidence of MACEs, all-cause death, and unplanned revascularization increased with elevated TyG index and SYNTAX score. Both the TyG index (non-linear, P = 0.119) and SYNTAX score (non-linear, P = 0.004) displayed a positive dose-response relationship with MACEs, as illustrated by the RCS curve. Following adjustment for multiple factors, both the TyG index and SYNTAX score emerged as significant predictors of MACEs across the total population and various subgroups. Mediation analysis indicated that the SYNTAX score mediated 25.03%, 18.00%, 14.93%, and 11.53% of the correlation between the TyG index and MACEs in different adjusted models, respectively. Similar mediating effects were observed when endpoint was defined as unplanned revascularization. CONCLUSION: Elevated baseline TyG index and SYNTAX score were associated with a higher risk of MACEs in ACS. Furthermore, the SYNTAX score partially mediated the relationship between the TyG index and adverse cardiovascular outcomes.

The additive effect of the triglyceride-glucose index and estimated glucose disposal rate on long-term mortality among individuals with and without diabetes: a population-based study.

BACKGROUND: The triglyceride-glucose (TyG) index and estimated glucose disposal rate (eGDR), which are calculated using different parameters, are widely used as markers of insulin resistance and are associated with cardiovascular diseases and prognosis. However, whether they have an additive effect on the risk of mortality remains unclear. This study aimed to explore whether the combined assessment of the TyG index and eGDR improved the prediction of long-term mortality in individuals with and without diabetes. METHODS: In this cross-sectional and cohort study, data were derived from the National Health and Nutrition Examination Survey (NHANES) 2001-2018, and death record information was obtained from the National Death Index. The associations of the TyG index and eGDR with all-cause and cardiovascular mortality were determined by multivariate Cox regression analysis and restricted cubic splines. RESULTS: Among the 17,787 individuals included in the analysis, there were 1946 (10.9%) all-cause deaths and 649 (3.6%) cardiovascular deaths during a median follow-up of 8.92 years. In individuals with diabetes, the restricted cubic spline curves for the associations of the TyG index and eGDR with mortality followed a J-shape and an L-shape, respectively. The risk of mortality significantly increased after the TyG index was > 9.04 (all-cause mortality) or > 9.30 (cardiovascular mortality), and after eGDR was < 4 mg/kg/min (both all-cause and cardiovascular mortality). In individuals without diabetes, the association between eGDR and mortality followed a negative linear relationship. However, there was no association between the TyG index and mortality. Compared with individuals in the low TyG and high eGDR group, those in the high TyG and low eGDR group (TyG > 9.04 and eGDR < 4) showed the highest risk for all-cause mortality (hazard ratio [HR] = 1.592, 95% confidence interval [CI] 1.284-1.975) and cardiovascular mortality (HR = 1.683, 95% CI 1.179-2.400) in the overall population. Similar results were observed in individuals with and without diabetes. CONCLUSIONS: There was a potential additive effect of the TyG index and eGDR on the risk of long-term mortality in individuals with and without diabetes, which provided additional information for prognostic prediction and contributed to improving risk stratification.

Predictive value of stress hyperglycemia ratio on one-year mortality in chronic kidney disease patients admitted to intensive care unit.

BACKGROUND: Stress Hyperglycemia Ratio (SHR) reflects the acute blood glucose variation in critically ill conditions. However, its prognostic value in chronic kidney disease (CKD) remains understudied. This study aimed to investigate the association between SHR and one-year mortality in CKD patients hospitalized in the Intensive Care Unit (ICU). METHODS: Patients with diagnosis of CKD in the Medical Information Mart for Intensive Care IV (MIMIC-IV) database were enrolled. Incidence of all-cause mortality within one-year follow-up was used as the primary endpoint. RESULTS: 1825 CKD patients were included in the study. A "U-shaped" relationship between SHR and one-year mortality as identified using multivariate restricted cubic spline (RCS) analysis. Then study population were categorized into three groups: Group 1 (SHR < 0.70), Group 2 (0.70 ≤ SHR ≤ 0.95) and Group 3 (SHR > 0.95). Group 2 showed significantly better one-year outcomes compared to the other two groups (p = 0.0031). This survival benefit persisted across subgroup analyses stratified by age, sex, CKD stage, anemia and various clinical conditions. CONCLUSION: SHR proved to be a meaningful biomarker for predicting one-year mortality in ICU-admitted CKD patients, with a "U-shaped" correlation. The identification of the optimal SHR range (0.70-0.95) provided clinicians with a valuable tool for detecting high-risk populations.

Predictive value of the stress hyperglycemia ratio in dialysis patients with acute coronary syndrome: insights from a multi-center observational study.

BACKGROUND: Various studies have indicated that stress hyperglycemia ratio (SHR) can reflect true acute hyperglycemic status and is associated with poor outcomes in patients with acute coronary syndrome (ACS). However, data on dialysis patients with ACS are limited. The Global Registry of Acute Coronary Events (GRACE) risk score is a well-validated risk prediction tool for ACS patients, yet it underestimates the risk of major events in patients receiving dialysis. This study aimed to evaluate the association between SHR and adverse cardiovascular events in dialysis patients with ACS and explore the potential incremental prognostic value of incorporating SHR into the GRACE risk score. METHODS: This study enrolled 714 dialysis patients with ACS from January 2015 to June 2021 at 30 tertiary medical centers in China. Patients were stratified into three groups based on the tertiles of SHR. The primary outcome was major adverse cardiovascular events (MACE), and the secondary outcomes were all-cause mortality and cardiovascular mortality. RESULTS: After a median follow-up of 20.9 months, 345 (48.3%) MACE and 280 (39.2%) all-cause mortality occurred, comprising 205 cases of cardiovascular death. When the highest SHR tertile was compared to the second SHR tertile, a significantly increased risk of MACE (adjusted hazard ratio, 1.92; 95% CI, 1.48-2.49), all-cause mortality (adjusted hazard ratio, 2.19; 95% CI, 1.64-2.93), and cardiovascular mortality (adjusted hazard ratio, 2.70; 95% CI, 1.90-3.83) was identified in the multivariable Cox regression model. A similar association was observed in both diabetic and nondiabetic patients. Further restricted cubic spline analysis identified a J-shaped association between the SHR and primary and secondary outcomes, with hazard ratios for MACE and mortality significantly increasing when SHR was > 1.08. Furthermore, adding SHR to the GRACE score led to a significant improvement in its predictive accuracy for MACE and mortality, as measured by the C-statistic, net reclassification improvement, and integrated discrimination improvement, especially for those with diabetes. CONCLUSIONS: In dialysis patients with ACS, SHR was independently associated with increased risks of MACE and mortality. Furthermore, SHR may aid in improving the predictive efficiency of the GRACE score, especially for those with diabetes. These results indicated that SHR might be a valuable tool for risk stratification and management of dialysis patients with ACS.

The triglyceride-glucose index predicts 1-year major adverse cardiovascular events in end-stage renal disease patients with coronary artery disease.

BACKGROUND: The triglyceride-glucose (TyG) index has been suggested as a dependable indicator for predicting major adverse cardiovascular events (MACE) in individuals with cardiovascular conditions. Nevertheless, there is insufficient data on the predictive significance of the TyG index in end-stage renal disease (ESRD) patients with coronary artery disease (CAD). METHODS: This study, conducted at multiple centers in China, included 959 patients diagnosed with dialysis and CAD from January 2015 to June 2021. Based on the TyG index, the participants were categorized into three distinct groups. The study's primary endpoint was the combination of MACE occurring within one year of follow-up, including death from any cause, non-fatal myocardial infarction, and non-fatal stroke. We assessed the association between the TyG index and MACE using Cox proportional hazard models and restricted cubic spline analysis. The TyG index value was evaluated for prediction incrementally using C-statistics, continuous net reclassification improvement (NRI), and integrated discrimination improvement (IDI). RESULTS: The three groups showed notable variations in the risk of MACE (16.3% in tertile 1, 23.5% in tertile 2, and 27.2% in tertile 3; log-rank P = 0.003). Following complete adjustment, patients with the highest TyG index exhibited a notably elevated risk of MACE in comparison to those in the lowest tertile (hazard ratio [HR] 1.63, 95% confidence interval [CI] 1.14-2.35, P = 0.007). Likewise, each unit increase in the TyG index correlated with a 1.37-fold higher risk of MACE (HR 1.37, 95% CI 1.13-1.66, P = 0.001). Restricted cubic spline analysis revealed a connection between the TyG index and MACE (P for nonlinearity > 0.05). Furthermore, incorporating the TyG index to the Global Registry of Acute Coronary Events risk score or baseline risk model with fully adjusted factors considerably enhanced the forecast of MACE, as demonstrated by the C-statistic, continuous NRI, and IDI. CONCLUSIONS: The TyG index might serve as a valuable and dependable indicator of MACE risk in individuals with dialysis and CAD, indicating its potential significance in enhancing risk categorization in clinical settings.

Association between the triglyceride glucose index and in-hospital and 1-year mortality in patients with chronic kidney disease and coronary artery disease in the intensive care unit.

OBJECTIVE: This study aimed to explore the association between the triglyceride glucose index (TyG) and the risk of in-hospital and one-year mortality in patients with chronic kidney disease (CKD) and cardiovascular disease (CAD) admitted to the intensive care unit (ICU). METHODS: The data for the study were taken from the Medical Information Mart for Intensive Care-IV database which contained over 50,000 ICU admissions from 2008 to 2019. The Boruta algorithm was used for feature selection. The study used univariable and multivariable logistic regression analysis, Cox regression analysis, and 3-knotted multivariate restricted cubic spline regression to evaluate the association between the TyG index and mortality risk. RESULTS: After applying inclusion and exclusion criteria, 639 CKD patients with CAD were included in the study with a median TyG index of 9.1 [8.6,9.5]. The TyG index was nonlinearly associated with in-hospital and one-year mortality risk in populations within the specified range. CONCLUSION: This study shows that TyG is a predictor of one-year mortality and in-hospital mortality in ICU patients with CAD and CKD and inform the development of new interventions to improve outcomes. In the high-risk group, TyG might be a valuable tool for risk categorization and management. Further research is required to confirm these results and identify the mechanisms behind the link between TyG and mortality in CAD and CKD patients.

Ischemia preconditioning alleviates ischemia/reperfusion injury-induced coronary no-reflow and contraction of microvascular pericytes in rats.

BACKGROUND: Ischemia preconditioning (IPC) ameliorates coronary no-reflow induced by ischemia/reperfusion (I/R) injury, and pericytes play an important role in microvascular function. However, it is unclear whether IPC exerts a protective effect on coronary microcirculation and regulates the pericytes. OBJECTIVE: The purpose of this study was to assess whether IPC improves coronary microvascular perfusion and reduces pericyte constriction after myocardial I/R injury. METHODS: Rats were randomly divided into three groups: the sham group, the I/R group, and the IPC + I/R group. The left anterior descending artery (LAD) of rats in the I/R group were ligated for 45 min, and the rats in the IPC + I/R group received 4 episodes of 6min occlusion followed by 6min reperfusion before the LAD was ligated. After 24 h of reperfusion, the area of no-reflow, and area at risk were evaluated with thioflavin-S and Evens blue staining, and infarct size with triphenyl tetrazolium chloride staining, respectively. Besides, fluorescent microspheres were perfused to enable visualization of the non-obstructed coronary vessels. Cardiac pericytes and microvascular were observed by immunofluorescence, and the diameter of microvascular at the site of the pericyte somata was analyzed. RESULTS: The infarct size, and area of no-reflow in the IPC + I/R group were significantly reduced compared with the I/R group (infarct size, 33.5% ± 11.9% vs. 49.2% ± 9.4%, p = 0.021；no-reflow, 12.7% ± 5.2% vs. 26.6% ± 5.0%, p < 0.001). IPC improved microvascular perfusion and reduced the percentage of the blocked coronary capillary. Moreover, we found that cardiac pericytes were widely distributed around the microvascular in various regions of the heart, and expressed the contractile protein α-smooth muscle actin. The microvascular lumen diameter at pericyte somata was reduced after I/R (4.3 ± 1.0 µm vs. 6.5 ± 1.2 µm, p < 0.001), which was relieved in IPC + I/R group compared with the I/R group (5.2 ± 1.0 µm vs. 4.3 ± 1.0 µm, p < 0.001). Besides, IPC could reduce the proportion of apoptotic pericytes compared to the I/R group (22.1% ± 8.4% vs. 38.5% ± 7.5%, p < 0.001). CONCLUSION: IPC reduced no-reflow and inhibited the contraction of microvascular pericytes induced by cardiac I/R injury, suggesting that IPC might play a protective role by regulating the pericyte function.

The triglyceride glucose index is associated with future cardiovascular disease nonlinearly in middle-aged and elderly Chinese adults.

OBJECTIVE: We aimed to investigate the association between triglyceride glucose index and cardiovascular disease (CVD) development in the Chinese middle-aged and elderly population using the China Health and Retirement Longitudinal Study dataset 2011-2018. METHODS: Basic characteristics of participants, including sociodemographic information, and health conditions, were acquired. Logistic regression analyses and restricted cubic spline regression analyses were conducted to investigate the association between the triglyceride glucose index and future CVD risks. Subgroup analyses were performed to evaluate potential interaction. RESULTS: Seven hundred fifty-three of 6114 (12.3%) participants have developed CVD in 2018 over an approximately 7-year follow-up. The logistic regression analysis exhibited that compared to the lowest triglyceride glucose index group, the multivariable OR for future CVD was 0.985 (95%CI 0.811-1.198) in the T2 triglyceride glucose index group and 1.288 (95%CI 1.068-1.555) in the T3 TyG index (P for trend 0.006). The restricted cubic spline regression analysis showed the nonlinear association between triglyceride glucose index and CVD incidence; the cut-off values were 8.07 and 8.57, respectively, after total adjustment. Gender, fast blood glucose, and triglycerides interacted with triglyceride glucose index and CVD except for BMI. CONCLUSION: The triglyceride glucose index was nonlinearly related to the risk of future cardiovascular disease in the middle-aged and elderly Chinese population.

Triglyceride glucose index exacerbates the risk of future cardiovascular disease due to diabetes: evidence from the China Health and Retirement Longitudinal Survey (CHARLS).

OBJECTIVE: We aimed to investigate the effect of the triglyceride glucose (TyG) index on the association between diabetes and cardiovascular disease (CVD). METHODS: Data from 6,114 individuals were extracted and analyzed from the China Health and Retirement Longitudinal Survey (CHARLS) from 2011 to 2018. Logistic regression analyses were conducted to assess the relationship between diabetes and CVD across the various TyG index groups. The statistical method of subgroup analysis was used to determine the correlation between diabetes and CVD for each TyG index group by sex, history of hypertension and dyslipidemia, smoking, and drinking. RESULTS: Diabetes was positively associated with CVD risk after adjustment in 2011(odds ratio (OR) 1.475, 95% CI 1.243-1.752, P < 0.001). There was a gradient increase in the OR for new-onset CVD in 2018 due to diabetes at baseline across the value of the TyG index based on a fully adjusted model (P for trend < 0.05). The ORs of diabetes at baseline for CVD in 2018 were 1.657 (95% CI 0.928-2.983, P = 0.098), 1.834(95% CI 1.064-3.188, P = 0.037) and 2.234(95% CI 1.349-3.673, P = 0.006) for T1, T2 and T3 of the TyG index respectively. The gradient of increasing risk of CVD still existed among those with hypertension and nondrinkers in the subgroup analysis. CONCLUSION: Elevated TyG index strengthens the correlation between diabetes mellitus and CVD in middle-aged and elderly Chinese adults.

Maillard and Hydrolytic Reactions in Subcritical Water Extraction of Bioactive Compounds from Licorice.

Nowadays, subcritical water extraction (SWE) techniques are extensively investigated worldwide, while the thermal reactions that inevitably occur under subcritical water conditions are rarely studied. In order to investigate the behaviors of the different reactions during SWE of bioactive compounds from licorice, the Maillard reaction process was accessed via their products and the hydrolytic reaction was analyzed according to the kinetic parameters. In addition, the contents of total phenolics and flavonoids in the extracts obtained at the different temperatures were determined and total antioxidant capacities were evaluated by HPLC-ABTS+. The results showed that flavonoids and phenolics from licorice as well as new compounds generated via the Maillard reaction contributed to the antioxidant activity of the extracts. The fluorescence, color and absorbance of the extracts showed that the degree of the Maillard reaction increased with the rise of the extraction temperature. The kinetics of extraction for glycyrrhizic acid showed that it was firstly extracted by diffusion, and then was hydrolyzed into glycyrrhetinic acid 3-O-mono-ß-D-glucuronide and glycyrrhetinic acid following a first-order mechanism. These findings could provide deep insights into the SWE process and a new method for producing glycyrrhetinic acid 3-O-mono-ß-D-glucuronide and glycyrrhetinic acid.

Design of gel structures in water and oil phases for improved delivery of bioactive food ingredients.

Gels are viscoelastic systems built up with a liquid phase entrapped in a three-dimensional network, which can behave as carriers for bioactive food ingredients. Many attempts have been made to design gel structures in the water phase (hydrogels, emulsion gels, bigels) or oil phase (organogels, bigels) in order to improve their delivery performances. Hydrogels are originated from proteins or polysaccharides, which are suitable for the delivery of hydrophilic ingredients. Organogels are mainly built up with the self-assembling of gelator molecules in the oil phase, and they offer good carriers for lipophilic ingredients. Emulsion gels and bigels, containing both aqueous and oil domains, can provide accommodations for lipophilic and hydrophilic ingredients simultaneously. Gel structures (e.g. rheology, texture, water holding capacity, swelling ratio) can be modulated by choosing different gelators, modifying gelation techniques, and the involvement of other ingredients (e.g. oils, emulsifiers, minerals, acids), which then alter the diffusion and release of the bioactive ingredients incorporated. Various studies have proved that gel-based delivery systems are able to improve the stability and bioavailability of many bioactive food ingredients. This review provides a state-to-art overview of different gel-based delivery systems, highlighting the significance of structure-functionality relationship, to provide advanced knowledge for the design of novel functional foods.

Smooth Muscle Sirtuin 1 Blocks Thoracic Aortic Aneurysm/Dissection Development in Mice.

PURPOSE: Advancing age is the major risk factor for thoracic aortic aneurysm/dissection (TAAD). However, the causative link between age-related molecules and TAAD remains elusive. Here, we investigated the role of Sirtuin 1 (SIRT1, also known as class III histone deacetylase), the best studied member of the longevity-related Sirtuin family, in TAAD development in vivo. METHODS: We used male smooth muscle-specific SIRT1 transgenic (ST-Tg) mice, smooth muscle-specific SIRT1 knockout (ST-KO) mice, and their wild-type (WT) littermates on a C57BL/6J background to establish a TAAD model induced by oral administration of 3-aminopropionitrile fumarate (BAPN). We analyzed the incidence and fatality rates of TAAD in the groups. We examined matrix metallopeptidase 2 (MMP2) and MMP9 expression in aortas or cultured A7r5 cells via western blotting and real-time polymerase chain reaction (PCR). We performed chromatin immunoprecipitation (ChIP) to clarify the epigenetic mechanism of SIRT1-regulated MMP2 expression in vascular smooth muscle cells (VSMCs). RESULTS: BAPN treatment markedly increased the incidence of TAAD in WT mice but caused less disease in ST-Tg mice. Moreover, ST-KO mice had the highest BAPN-induced TAAD fatality rate of all the groups. Mechanistically, SIRT1 overexpression resulted in lower MMP2 and MMP9 expression after BAPN treatment in both mouse aortas and cultured A7r5 cells. The downregulation of BAPN-induced MMP2 expression by SIRT1 was mediated by deacetylation of histone H3 lysine 9 (H3K9) on the Mmp2 promoter in the A7r5 cells. CONCLUSION: Our findings suggest that SIRT1 expression in SMCs protects against TAAD and could be a novel therapeutic target for TAAD management.

Effects of MTNR1B Genetic Variants on Individual Susceptibility to Gestational Diabetes Mellitus: A Meta-Analysis.

OBJECTIVE: Whether melatonin receptor 1B (MTNR1B) variants are implicated in gestational diabetes mellitus (GDM) remains unclear. Therefore, we performed this meta-analysis to obtain a more conclusive result on associations between MTNR1B variants and GDM. STUDY DESIGN: Literature research was performed in PubMed, Web of Science, Embase, and China National Knowledge Infrastructure. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. RESULTS: A total of 17 studies were eligible for analyses. Pooled overall analyses showed that rs1387153 (dominant model: p = 0.0002, OR = 0.78, 95% CI: 0.68-0.89; recessive model: p < 0.0001, OR = 1.46, 95% CI: 1.24-1.73; allele model: p < 0.0001, OR = 0.78, 95% CI: 0.72-0.84), rs4753426 (recessive model: p = 0.01, OR = 1.75, 95% CI: 1.14-2.68; allele model: p = 0.01, OR = 0.69, 95% CI: 0.51-0.93), and rs10830963 (dominant model: p < 0.0001, OR = 0.72, 95% CI: 0.65-0.78; recessive model: p < 0.0001, OR = 1.56, 95% CI: 1.40-1.74; allele model: p < 0.0001, OR = 0.73, 95% CI: 0.69-0.78) variants were all significantly associated with the susceptibility to GDM. Further subgroup analyses by ethnicity of participants yielded similar positive results. CONCLUSION: Our findings indicated that MTNR1B rs1387153, rs4753426, and rs10830963 variants might serve as genetic biomarkers of GDM.

Melatonin attenuates nicotine-induced autophagy and neurological changes by decreasing the production of reactive oxygen species.

Purpose: The aim of this study was to explore the mechanism of neurological changes underlying the toxicity of nicotine.Materials and methods: Rat pheochromocytoma 12 (PC12) cells and human neuroglia (HM) cells were used. The ROS levels of the cells were detected by the FACScan. Autophagy flux was monitored by a tandem monomeric RFP-GFP-tagged LC3 lentivirus. The autophagic proteins LC3, SQSTM1/p62 and Beclin1 were detected by western blot assay. In order to evaluate the effects of nicotine and melatonin on the morphological changes of neurons, primary cortical neurons were obtained and immunocytochemistry of TUBB3 tubulin were conducted.Results: Nicotine increased the levels of reactive oxygen species (ROS) in PC12 and HM cells in a concentration-dependent manner. Microscopy showed increased autophagic flux in nicotine-treated PC12 cells. Subsequent western blotting results showed that nicotine induced increase in the levels of LC3B-II and Beclin1, and decreased SQSTM1/p62 in a concentration-dependent manner. Finally, nicotine treatment reduced the length of TUBB3-positive axons and dendrites. Melatonin, a mitochondrially targeted antioxidant, reduced the ROS level, and blocked autophagy activation and the morphologic structural changes induced by nicotine.Conclusions: Our results suggested that the role of nicotine in neuronal toxicity maybe through the induction of ROS and the subsequent activation of autophagy. These effects could be restored by melatonin.

Naringenin Ameliorates Renovascular Hypertensive Renal Damage by Normalizing the Balance of Renin-Angiotensin System Components in Rats.

Background: Naringenin, a member of the dihydroflavone family, has been shown to have a protective function in multiple diseases. We previously demonstrated that naringenin played a protective role in hypertensive myocardial hypertrophy by decreasing angiotensin-converting enzyme (ACE) expression. The kidney is a primary target organ of hypertension. The present study tested the effect of naringenin on renovascular hypertensive kidney damage and explored the underlying mechanism. Methods and Results: An animal model of renovascular hypertension was established by performing 2-kidney, 1-clip (2K1C) surgery in Sprague Dawley rats. Naringenin (200 mg/kg/day) or vehicle was administered for 10 weeks. Blood pressure and urinary protein were continuously monitored. Plasma parameters, renal pathology and gene expression of nonclipped kidneys were evaluated by enzyme-linked immunosorbent assay, histology, immunohistochemistry, real-time polymerase chain reaction, and Western blot at the end of the study. Rats that underwent 2K1C surgery exhibited marked elevations of blood pressure and plasma Ang II levels and renal damage, including mesangial expansion, interstitial fibrosis, and arteriolar thickening in the nonclipped kidneys. Naringenin significantly ameliorated hypertensive nephropathy and retarded the rise of Ang II levels in peripheral blood but had no effect on blood pressure. 2K1C rats exhibited increases in the ACE/ACE2 protein ratio and AT1R/AT2R protein ratio in the nonclipped kidney compared with sham rats, and these increases were significantly suppressed by naringenin treatment. Conclusions: Naringenin attenuated renal damage in a rat model of renovascular hypertension by normalizing the imbalance of renin-angiotensin system activation. Our results suggest a potential treatment strategy for hypertensive nephropathy.

Postnatal deficiency of ADAMTS1 ameliorates thoracic aortic aneurysm and dissection in mice.

NEW FINDINGS: What is the central question of this study? Thoracic aortic aneurysm and dissection (TAAD) is characterized by extracellular matrix remodelling and an inflammatory response. Evidence suggests that ADAMTS1 is closely associated with TAAD development, but whether it contributes to the pathophysiology of TAAD remains unknown. What is the main finding and its importance? We generated inducible postnatal ADAMTS1 knockout mice and found that ADAMTS1 deficiency attenuated ß-aminopropionitrile-dependent TAAD formation and rupture. Furthermore, ADAMTS1 deficiency suppressed neutrophil and macrophage infiltration by inhibiting inflammatory cytokine levels and macrophage migration during the early stage of ß-aminopropionitrile-induced TAAD. ADAMTS1 could be a new therapeutic target for TAAD. ABSTRACT: Thoracic aortic aneurysm and dissection (TAAD), as a life-threatening cardiovascular disease, is characterized by extracellular matrix remodelling and an inflammatory response. A disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1) is an inflammation-related protein that is able to degrade extracellular matrix proteins in arteries. Herein, we investigated whether ADAMTS1 contributes to the pathophysiology of TAAD in mice. Using the mouse model of ß-aminopropionitrile (BAPN)-induced TAAD, we found that ADAMTS1 expression was upregulated beginning in the early stage of TAAD development and localized predominantly in the aortic adventitia. ADAMTS1-floxed mice and whole-body tamoxifen-inducible ADAMTS1 knockout mice (ADAMTS1flox/flox Ubc-CreERT2+ , ADAMTS1 KO) were generated to investigate the direct causal role of ADAMTS1 in TAAD development. The incidence and rupture rates of BAPN-induced TAAD in ADAMTS1 KO mice were significantly lower than those in ADAMTS1flox/flox mice (45.5 versus 81.8% and 18.2 versus 42.4%, respectively). Aortas from BAPN-treated ADAMTS1flox/flox mice displayed profound destruction of the elastic lamellae, abundant neutrophil and macrophage accumulation in the adventitia, obviously increased neutrophil proportions in peripheral blood and significantly increased expression of inflammatory factors in the early stage of TAAD induction, all of which were markedly suppressed in ADAMTS1 KO mice. Furthermore, ADAMTS1-deficient macrophages exhibited abrogated migration capacity both in vivo and in vitro. In conclusion, ADAMTS1 plays a crucial role in postnatal TAAD formation and rupture by regulating inflammatory responses, suggesting that ADAMTS1 might be a new therapeutic target for TAAD.

Properties of Ternary Biopolymer Nanocomplexes of Zein, Sodium Caseinate, and Propylene Glycol Alginate and Their Functions of Stabilizing High Internal Phase Pickering Emulsions.

A pH-cycle method based on preparing an alkaline solution of zein followed by neutralization with an acid can be used to prepare zein nanoparticles. In the present work, partial alkaline hydrolysis of propylene glycol alginate (PGA) to a lower pH was studied to prepare binary zein-PGA nanocomplexes and ternary complexes with additional sodium caseinate (NaCas). 0.5% or more PGA was sufficient to reduce the pH to 7.5 or lower, eliminating the need for titration, and resulted in simultaneous nanocomplex formation. The addition of NaCas into alkaline zein-PGA solution resulted in smaller complexes with all biopolymers, whereas adsorption on binary zein-PGA complexes was observed when NaCas was added into the neutral zein-PGA dispersions. The formation of nanocomplexes involved with hydrophobic and electrostatic attractions and hydrogen bonds and was further affected by the amount of NaCas. The ternary nanocomplexes with equal masses of zein and NaCas had an excellent capacity to prepare gel-like Pickering emulsions with as much as 80% v/v oil with characteristics suitable for texture modification and delivery systems of bioactive compounds in food and consumer products. Therefore, PGA can be used to possibly scale-up the pH-cycle method to produce zein-based nanoparticles with unique functional properties.

Emulsion design for the delivery of ß-carotene in complex food systems.

ß-Carotene has been widely investigated both in the industry and academia, due to its unique bioactive attributes as an antioxidant and pro-vitamin A. Many attempts were made to design delivery systems for ß-carotene to improve its dispersant state and chemical stability, and finally to enhance the functionality. Different types of oil-in-water emulsions were proved to be effective delivery systems for lipophilic bioactive ingredients, and intensive studies were performed on ß-carotene emulsions in the last decade. Emulsions are thermodynamically unstable, and emulsions with intact structures are preferable in delivering ß-carotene during processing and storage. ß-Carotene in emulsions with smaller particle size has poor stability, and protein-type emulsifiers and additional antioxidants are effective in protecting ß-carotene from degradation. Recent development in the design of protein-polyphenol conjugates has provided a novel approach to improve the stability of ß-carotene emulsions. When ß-carotene is consumed, its bioaccessibility is highly influenced by the digestion of lipids, and ß-carotene in smaller oil droplets containing long-chain fatty acids has a higher bioaccessibility. In order to better deliver ß-carotene in complex food products, some novel emulsions with tailor-made structures have been developed, e.g., multilayer emulsions, solid lipid particles, Pickering emulsions. This review summarizes the updated understanding of emulsion-based delivery systems for ß-carotene, and how emulsions can be better designed to fulfill the benefits of ß-carotene in functional foods.

Physicochemical and in vitro antioxidant properties of pectin extracted from hot pepper (Capsicum annuum L. var. acuminatum (Fingerh.)) residues with hydrochloric and sulfuric acids.

BACKGROUND: Transformation of hot pepper residues to value-added products with concomitant benefits on environmental pollution would be of great value to capsicum oleoresin manufacturers. Pectin, a soluble dietary fiber with multiple functions, from hot pepper residues was investigated in this study. RESULTS: The extraction of hot pepper pectin using hydrochloric acid was first optimized using response surface methodology (RSM). The most efficient parameters for maximum hot pepper pectin yield (14.63%, dry basis) were a pH of 1.0, a temperature of 90 °C, an extraction time of 2 h and a liquid-to-solid ratio of 20 L g-1 . The pectin was mainly composed of uronic acids, and the major neutral sugars were galactose and glucose. The structure of hot pepper pectin was characterized by homogalacturonan and rhamnogalacturonan I elements. The physicochemical properties of hot pepper pectin extracted by sulfuric acid and hydrochloric acid were further investigated. The content of protein and degree of esterification in hot pepper pectin extracted with sulfuric acid solution (SP) were higher (P < 0.05) than those in that extracted with hydrochloric acid solution (HP), while the mean molecular weight of SP was lower than that of HP. Compared with HP, SP exhibited higher viscosity and better emulsifying property. CONCLUSION: Based on the yield and physicochemical properties of hot pepper pectin, hot pepper residues would be a new source to obtain pectin, and SP would be more preferred than HP. © 2017 Society of Chemical Industry.

Food-Grade Covalent Complexes and Their Application as Nutraceutical Delivery Systems: A Review.

Food proteins, polysaccharides, and polyphenols are 3 major food constituents with distinctly different functional attributes. Many proteins and polysaccharides are capable of stabilizing emulsions and foams, thickening solutions, and forming gels, although they differ considerably in their abilities to provide these functional attributes. Many plant polyphenols exhibit beneficial physiological functions, such as antitumor, antioxidant, antibacterial, and antiviral properties. Proteins, polysaccharides, and polyphenols can form complexes with each other, which leads to changes in the functional and nutritional properties of the combined systems. Recently, there has been considerable interest in understanding and utilizing covalent interactions between polyphenols and biopolymers (proteins and polysaccharides). The binary or tertiary conjugates formed may be designed to have physicochemical properties and functional attributes that cannot be achieved using the individual components. This article provides a review of the formation, characterization, and utilization of conjugates prepared using proteins, polysaccharides, and polyphenols. It also discusses the relationship between the structural properties and functionality of the conjugates, and it highlights the bioavailability of bioactive compounds loaded in conjugate-based delivery systems. In addition, it highlights the main challenges to be considered when preparing and analyzing conjugates. This article provides an improved understanding of the chemical reactions that occur between major food ingredients and how they can be utilized to develop biopolymer-based delivery systems with enhanced functional attributes.