Characteristics and antioxidant activities of seed oil from okra (Abelmoschus esculentus L.).

To investigate the potential functional properties and added value of okra seed oil and provide a scientific basis for further industrial development and production of okra seed oil, its fatty acid profile, total phenolic, fat-soluble vitamin composition, mineral element composition, and antioxidant activities were examined in this study. Also, correlations between bioactive components and the antioxidant activities of okra seed oil were explored. The study results show that okra seed oil contains 12 types of fatty acids, 65.22% of which are unsaturated acids, and among these unsaturated acids, linoleic acid (43%) and oleic acid (20.16%) are two dominant acid types. Compared with walnut oil and peanut oil, okra seed oil contains relatively high total phenols, fat-soluble vitamins, and a variety of essential mineral nutrients, with a total phenolic content (TPC) of 959.65 µg/mL, a total tocopherol content of 742.71 µg/mL, a vitamin A content of 0.0017 µg/100 mL, a vitamin D content of 1.44 µg/100 mL, and a vitamin K1 content of 52.54 ng/100 mg. Also, okra seed oil exhibits better scavenging activities on hydroxyl (IC50 = 0.50 mg/mL) and ammonium salt (ABTS) free radicals (IC50 = 6.46 mg/mL) and certain reducing power (IC50 = 17.22 mg/mL) at the same concentration. The scavenging activities of okra seed oil on hydroxyl radicals and ABTS radicals, as well as its reducing power, are significantly correlated with its contents of total phenol, total tocopherol, α-tocopherol, and γ-tocopherol (p < .01). These results show that okra seed oil is rich in bioactive substances, thus presenting great nutritional potential.

Microtubule-Mediated Regulation of ß2AR Translation and Function in Failing Hearts.

BACKGROUND: ß1AR (beta-1 adrenergic receptor) and ß2AR (beta-2 adrenergic receptor)-mediated cyclic adenosine monophosphate signaling has distinct effects on cardiac function and heart failure progression. However, the mechanism regulating spatial localization and functional compartmentation of cardiac ß-ARs remains elusive. Emerging evidence suggests that microtubule-dependent trafficking of mRNP (messenger ribonucleoprotein) and localized protein translation modulates protein compartmentation in cardiomyocytes. We hypothesized that ß-AR compartmentation in cardiomyocytes is accomplished by selective trafficking of its mRNAs and localized translation. METHODS: The localization pattern of ß-AR mRNA was investigated using single molecule fluorescence in situ hybridization and subcellular nanobiopsy in rat cardiomyocytes. The role of microtubule on ß-AR mRNA localization was studied using vinblastine, and its effect on receptor localization and function was evaluated with immunofluorescent and high-throughput Förster resonance energy transfer microscopy. An mRNA protein co-detection assay identified plausible ß-AR translation sites in cardiomyocytes. The mechanism by which ß-AR mRNA is redistributed post-heart failure was elucidated by single molecule fluorescence in situ hybridization, nanobiopsy, and high-throughput Förster resonance energy transfer microscopy on 16 weeks post-myocardial infarction and detubulated cardiomyocytes. RESULTS: ß1AR and ß2AR mRNAs show differential localization in cardiomyocytes, with ß1AR found in the perinuclear region and ß2AR showing diffuse distribution throughout the cell. Disruption of microtubules induces a shift of ß2AR transcripts toward the perinuclear region. The close proximity between ß2AR transcripts and translated proteins suggests that the translation process occurs in specialized, precisely defined cellular compartments. Redistribution of ß2AR transcripts is microtubule-dependent, as microtubule depolymerization markedly reduces the number of functional receptors on the membrane. In failing hearts, both ß1AR and ß2AR mRNAs are redistributed toward the cell periphery, similar to what is seen in cardiomyocytes undergoing drug-induced detubulation. This suggests that t-tubule remodeling contributes to ß-AR mRNA redistribution and impaired ß2AR function in failing hearts. CONCLUSIONS: Asymmetrical microtubule-dependent trafficking dictates differential ß1AR and ß2AR localization in healthy cardiomyocyte microtubules, underlying the distinctive compartmentation of the 2 ß-ARs on the plasma membrane. The localization pattern is altered post-myocardial infarction, resulting from transverse tubule remodeling, leading to distorted ß2AR-mediated cyclic adenosine monophosphate signaling.

RANKL Is Independently Associated with Increased Risks of Non-Alcoholic Fatty Liver Disease in Chinese Women with PCOS: A Cross-Sectional Study.

Women with polycystic ovarian syndrome (PCOS) are more likely to have non-alcoholic fatty liver disease (NAFLD) than non-PCOS women; however, the exact mechanism underlying this trend is unknown. The receptor activator of NF-κB ligand (RANKL) is strongly involved in bone metabolism and has multiple functions. Recent studies suggest that RANKL is implicated in hepatic insulin resistance (IR), which is the highest risk factor for NAFLD. This study aimed to assess the role of RANKL in NAFLD in Chinese women with PCOS. A cross-sectional observational study was conducted on women newly diagnosed with PCOS, which included 146 patients with NAFLD and 142 patients without NAFLD. Sex hormones, glucose, insulin, and lipids were measured, and anthropometric data were collected. The concentration of serum total RANKL was measured using commercial ELISA kits. PCOS patients with NAFLD had a significantly higher mean age, body mass index (BMI), waist circumference (WC), and worsened metabolic profile than non-NAFLD subjects. The concentrations of high-sensitivity C-reactive protein, total cholesterol, and low-density lipoprotein cholesterol increased with the RANKL tertile (p for trend = 0.023, 0.026, and 0.035, respectively). A significantly positive association was found between RANKL (per SD change) and the risks of NAFLD (OR = 1.545, 95% CI = 1.086−2.199) after adjusting for confounders, including demographic factors, metabolic markers, and sex hormones. Subgroup multivariate logistic analyses stratified by age, BMI, and WC showed the same tendency. In addition, the positive association between RANKL and NAFLD seemed more prominent in lean patients with a BMI < 24 kg/m2 (OR = 1.70, 95% CI = 1.06−2.75) when compared to overweight/obesity subjects. Therefore, this study suggests that RANKL is positively associated with the increased risk of NAFLD in Chinese women with PCOS, independent of metabolic and reproductive factors.

Transthoracic echocardiographic assessment of cardiac valves in patients with Behçet's disease.

The main objectives of the current study are to investigate valvular involvement in patients with cardiac Behçet's disease (BD) and find out the risk factors of valvular involvement in cardiac BD. We retrospectively assessed the clinical and echocardiographic data in the medical records of 121 patients with BD admitted to Beijing Anzhen Hospital from January 2015 to January 2022. We evaluated the valvular structure and function mainly by echocardiography. A total of 77 BD patients (77/121, 63.64%) had cardiac valvular involvement. Valvular lesions occurred more frequently in males (p = 0.022). Aortic regurgitation (AR) (62/77, 80.52%) was the most common finding and severe AR occupied 80.65% (50/62). The most common manifestations of BD patients with severe AR was aortic valve prolapse (25/50, 50%), followed by echo-free spaces within the aortic annulus (11/50, 22%), vegetation-like lesions (10/50, 20%), and aortic root aneurysm (10/50, 20%). The incidence of paravalvular leaks (PVL) in BD patients was 14.29% (7/49). The diameter of the sinus of Valsalva and proximal ascending aorta, and total cholesterol (TCHO) were the independent risk factors of moderate-severe aortic valvular regurgitation (p < 0.01). Left ventricular end-diastolic dimension (LVEDD), left ventricular ejection fraction (LVEF) and brain natriuretic peptide (BNP) were significantly associated with moderate-severe mitral valvular regurgitation (p < 0.01). The most common valvular abnormality in BD is AR. Echocardiography has great value in the comprehensive evaluation and accurate diagnosis of valvular involvement in BD patients.

Exenatide, Metformin, or Both for Prediabetes in PCOS: A Randomized, Open-label, Parallel-group Controlled Study.

CONTEXT: Up to 40% of patients with polycystic ovary syndrome (PCOS) have prediabetes; an optimal pharmacotherapy regimen for diabetes prevention in PCOS is yet to be established. OBJECTIVE: To evaluate clinical efficacy of exenatide (EX), metformin (MET), or combination (COM) for prediabetes in PCOS. DESIGN: Randomized, open-label, parallel-group controlled trial. SETTING: Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine. PATIENTS: PCOS with prediabetes (fasting plasma glucose 5.6-6.9 mmol/L and/or 2 hour post glucose 7.8-11.0 mmol/L on oral glucose tolerance test [OGTT]). A total of 150 out of 183 eligible enrollees completed the study. INTERVENTION: EX (10-20µg daily), MET (1500-2000 mg daily), or COM (EX plus MET) for 12 weeks. MAIN OUTCOME MEASURES: Sustained remission rate of prediabetes (primary endpoint, a normal OGTT after 12 weeks of treatment followed by 12 weeks of washout on no drug treatment) along with anthropometric, hormonal, metabolic, and pancreatic ß-cell function parameters (secondary endpoints) and potential mechanisms were assessed. RESULTS: Impaired glucose tolerance was found the dominant prediabetes phenotype. Overall sustained prediabetes remission rate was 50.7%. Remission rate of COM group (64%, 32/50) or EX group (56%, 28/50) was significantly higher than that of the MET group (32%, 16/50) (P = .003 and .027, respectively). EX was associated with superior suppression of 2-hour glucose increment in OGTT. A 2-step hyperglycemic clamp study revealed that EX had led to higher postprandial insulin secretion than MET, potentially explaining the higher remission rate. CONCLUSIONS: Compared with MET monotherapy, EX or COM achieved higher rate of remission of prediabetes among PCOS patients by improving postprandial insulin secretion.

ß-Adrenoceptor blockade prevents carotid body hyperactivity and elevated vascular sympathetic nerve density induced by chronic intermittent hypoxia.

Carotid body (CB) hyperactivity promotes hypertension in response to chronic intermittent hypoxia (CIH). The plasma concentration of adrenaline is reported to be elevated in CIH and our previous work suggests that adrenaline directly activates the CB. However, a role for chronic adrenergic stimulation in mediating CB hyperactivity is currently unknown. This study evaluated whether beta-blocker treatment with propranolol (Prop) prevented the development of CB hyperactivity, vascular sympathetic nerve growth and hypertension caused by CIH. Adult male Wistar rats were assigned into 1 of 4 groups: Control (N), N + Prop, CIH and CIH + Prop. The CIH paradigm consisted of 8 cycles h-1, 8 h day-1, for 3 weeks. Propranolol was administered via drinking water to achieve a dose of 40 mg kg-1 day-1. Immunohistochemistry revealed the presence of both ß1 and ß2-adrenoceptor subtypes on the CB type I cell. CIH caused a 2-3-fold elevation in basal CB single-fibre chemoafferent activity and this was prevented by chronic propranolol treatment. Chemoafferent responses to hypoxia and mitochondrial inhibitors were attenuated by propranolol, an effect that was greater in CIH animals. Propranolol decreased respiratory frequency in normoxia and hypoxia in N and CIH. Propranolol also abolished the CIH mediated increase in vascular sympathetic nerve density. Arterial blood pressure was reduced in propranolol groups during hypoxia. Propranolol exaggerated the fall in blood pressure in most (6/7) CIH animals during hypoxia, suggestive of reduced sympathetic tone. These findings therefore identify new roles for ß-adrenergic stimulation in evoking CB hyperactivity, sympathetic vascular hyperinnervation and altered blood pressure control in response to CIH.

Endosulfan induces endothelial inflammation and dysfunction via IRE1α/NF-κB signaling pathway.

Cardiovascular diseases are related to vascular endothelial cell injury; our previous studies showed that endosulfan could cause hypercoagulation of blood by inducing endothelial cell injury. To clarify the mechanism of it, we treated human umbilical vein endothelial cells (HUVECs) with 0, 1, 5, and 10 µg/mL endosulfan, while in the inhibition groups, reactive oxygen species (ROS) inhibitor N-acetylcysteine (NAC, 3 mmol) and endoplasmic reticulum (ER) stress inhibitor (STF-083010, 10 µmol) were incubated prior to endosulfan. The results showed that endosulfan could induce inflammatory response and dysfunction by increasing the release of inflammatory cytokines such as interleukin-1ß (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and adhesion molecules such as vascular cell adhesion molecule 1 (VCAM-1) and endothelin-1 (ET-1), and inducing ROS production in HUVECs. We also found that endosulfan could cause ER damage, remarkably increase the expressions of inositol-requiring enzyme 1α (IRE1α), phosphorylated IRE1α (p-IRE1α), GRP78, XBP1, nuclear factor-kappa B (NF-κB), and phosphorylated NF-κB (p-NF-κB) in HUVECs. The presence of NAC antagonized the ROS production, expressions of IRE1α and p-IRE1α; however, STF-083010 could decrease the expression levels of GRP78, XBP1, NF-κB, and p-NF-κB and attenuate IL-1ß, IL-6, TNF-α, VCAM-1, and ET-1 release induced by endosulfan. These results demonstrated that endosulfan-induced endothelial inflammation and dysfunction through the IRE1α/NF-κB signaling pathway may be triggered by oxidative stress. The study provided experimental basis for the correlation between environmental pollutants (endosulfan) and cardiovascular diseases.

BDE-209 induces autophagy and apoptosis via IRE1α/Akt/mTOR signaling pathway in human umbilical vein endothelial cells.

Recently, the essentiality and fatalness of cardiovascular diseases is attracting much attention. Polybrominated diphenyl ethers (PBDEs) are persistent environmental pollutants, which could induce the toxic effect and have been implicated in the occurrence and development of cardiovascular diseases. However, it is unclear how autophagy and apoptosis induced by BDE-209 in endothelial cells are regulated. The aim of the present study was to investigate the effects of BDE-209 on human umbilical vein endothelial cells (HUVECs) and elucidate the mechanisms involved. HUVECs were treated with a wide range concentration of BDE-209 for 24 h. The appearance of autophagy was tested by the testing index such as outcomes of monodansylcadaverine (MDC) staining and lysotracker staining, observation of autophagosomes and conversion between autophagy marker light chain 3 (LC3)-I and LC3-II. Besides, the apoptotic cell rate was detected with flow cytometry. In addition, BDE-209 induced endoplasmic reticulum (ER) stress was detected by transmission electron microscopy (TEM). Our data suggest that the exposure of BDE-209 could induce autophagy, which was confirmed by MDC staining, transmission electron microscopy observation, lysotracker staining and LC3-I/LC3-II conversion. Besides, the ER stress-related inositol-requiring enzyme 1α (IRE1α)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway could be activated by reactive oxygen species (ROS) to regulate autophagy. Moreover, the apoptosis of endothelial cells was alleviated when autophagy was blocked by 3-Methyladenine (3-MA). The results demonstrated that BDE-209 could induce the production of ROS and ER stress, activate autophagy through IRE1α/AKT/mTOR signaling pathway and ultimately induce apoptosis of vascular endothelial cells. These findings indicate that exposure to PBDE is possible to be a potential risk factor for cardiovascular diseases.