Sulforaphane Ameliorates High-Fat-Diet-Induced Metabolic Abnormalities in Young and Middle-Aged Obese Male Mice.

Type 2 diabetes (T2D) is still a fast-growing health problem globally. It is evident that chronic insulin resistance (IR) and progressive loss of ß-cell mass and function are key features of T2D etiology. Obesity is a leading pathogenic factor for developing IR. The aim of the present study was to determine whether sulforaphane (SFN), a natural compound derived from cruciferous vegetables, can prevent (prevention approach) or treat (treatment approach) obesity and IR in mouse models. We show that dietary intake of SFN (0.5 g/kg of HFD) for 20 weeks suppressed high-fat diet (HFD)-induced fat accumulation by 6.04% and improved insulin sensitivity by 23.66% in young male mice. Similarly, dietary provision of SFN (0.25 g/kg) significantly improved blood lipid profile, glucose tolerance, and insulin sensitivity of the middle-aged male mice while it had little effects on body composition as compared with the HFD group. In the treatment study, oral administration of SFN (40 mg/kg) induced weight loss and improved insulin sensitivity and plasma lipid profile in the diet-induced-obesity (DIO) male mice. In all three studies, the metabolic effects of SFN administration were not associated with changes in food intake. In vitro, SFN increased glucose uptake in C2C12 myotubes and increased fatty acid and pyruvate oxidation in primary human skeletal muscle cells. Our results suggest that SFN may be a naturally occurring insulin-sensitizing agent that is capable of improving the metabolic processes in HFD-induced obesity and IR and thereby may be a promising compound for T2D prevention.

Pachymic acid (PA) inhibits ferroptosis of cardiomyocytes via activation of the AMPK in mice with ischemia/reperfusion-induced myocardial injury.

Pachymic acid (PA) is a lanostane-type triterpenoid with various pharmacological effects. However, little is known about the effect of PA on myocardial infarction (MI) induced by ischemia/reperfusion (I/R). In this study, we aimed to investigate the protective effect of PA and its underlying mechanism. A cellular MI model was established by oxygen-glucose deprivation and reperfusion (OGD/R) treatment in HL-1 cardiomyocytes, and we found that OGD/R treatment decreased cell viability and glutathione peroxide (GSH-Px) activity, increased Fe2+ concentration and lactate dehydrogenase (LDH) activity, promoted malondialdehyde (MDA) and reactive oxygen species (ROS) production, and inhibited the expression of ferroptosis marker proteins SLC7A11 and GPX4 in a time-dependent manner. OGD/R-induced HL-1 cells were pretreated with different concentrations of PA (0, 20, 40, 60 µg/mL) for 24 h, and toxicological experiments showed that 150 µg/mL PA decreased cell viability, while low concentrations of PA had no toxic effect on cells. 20 µg/mL PA reversed the inhibitory effect of OGD/R on cell viability, reduced MDA and ROS production, and Fe2+ accumulation, increased GSH-Px activity and the expression of SLC7A11 and GPX4, and decreased LDH activity, especially at 60 µg/mL PA. Meanwhile, PA promoted the phosphorylation of IRS-1, AKT, and AMPK proteins in a dose-dependent manner. AICAR, an AMPK activator, inhibited ferroptosis, while STO-609, an AMPK inhibitor, largely abolished the effect of PA on OGD/R-induced ferroptosis of HL-1 cells. In addition, PA inhibited ferroptosis and myocardial I/R injury in wild-type mice and AMPK knockout (AMPK-/- ) mice. Collectively, PA inhibited ferroptosis of cardiomyocytes through activating of the AMPK pathway, thereby alleviating myocardial I/R injury in mice.

Date (Phoenix dactylifera L.) seed oil is an agro-industrial waste with biopreservative effects and antimicrobial activity.

Antimicrobial resistant (AMR) infections are a leading health threat globally. Previous literature has underscored the farm-to-fork continuum as a potential focal point for the emergence and spread of AMR. In the present study, date (Phoenix dactylifera L.) seed oil was investigated for its chemical composition and antimicrobial activity against common foodborne pathogens including Escherichia coli O157:H7, Salmonella enteritidis, Salmonella typhimurium, Listeria monocytogenes, and Staphylococcus aureus in vitro, and in ultra-high-temperature (UHT) milk as a food model at storage temperatures of 37 °C (24 h) and 10 °C (7 days). GC-MS analysis of the seed oil revealed 20 compounds, with octadecane (52.2-55.4%) as the major constituent, and the fatty acid analysis revealed 17 fatty acids, with oleic acid (42.3-43.1%) as the main constituent, followed by lauric acid (19.8-20.3%). The antimicrobial activity of date seed oil was determined using the microdilution method. A significant inhibition against gram-negative bacteria was noted in microbiological media and UHT milk, with a log reduction ranging from 4.3 to 6.7 (at 37 °C/24 h) and 5.7 to 7.2 (at 10 °C/7 days), respectively, at oil concentrations ranging between 10 and 15 µl/ml. The oil showed a similar significant inhibitory effect against St. aureus in the microbiological media (2.0-6.0 log reduction), whereas the inhibitory effect against L. monocytogenes was not statistically significant, with a maximum log reduction of 0.64 achieved at a concentration of 10 µl/ml. AFM imaging of the bacteria showed that oil treatment led to morphological changes in the bacteria including the formation of distorted shapes, surface blebs, indentations, stiffness, and swelling. Present findings suggest that date seed oil can be a promising by-product with potential antimicrobial activity and a food preservative.

Low-dose of phenolic rich extract from Annona squamosa Linn leaves ameliorates insulin sensitivity and reduces body weight gain in HF diet-induced obesity.

Obesity is associated with metabolic abnormalities that increase the risk and severity of several diseases. This study aimed to explore whether the aqueous extract of Annona squamosa Linn leaves (ASE) can ameliorate metabolic abnormalities associated with high fat (HF) diet-induced obesity. Forty-eight male Wistar rats were distributed among four treatment groups: a standard low-fat diet group, a HF diet group, and two HF diet groups with a daily oral dose of ASE (100 or 200 mg/kg body weights) administered for 9 weeks. Daily energy intake, body weight, blood glucose levels and glucose tolerance, and insulin tolerance were evaluated. At the end of the study, organs, and tissues were collected and weighed for analysis, and blood samples were collected to determine the serum insulin levels and serum liver enzymes. Total phenolic and flavonoid contents and 2,2-Diphenyl-1-picrylhydrazyl free radical antioxidant activity of the ASE were evaluated. Oral administration of the low dose of ASE to HF diet-fed rats significantly reduced the long-term food intake and body weight gain without altering adiposity compared with untreated HF diet-fed rats. This outcome was accompanied by a significant improvement in insulin sensitivity and a reduction in fasting blood glucose (FBG) levels measured at weeks 6 and 9 of the study. The high dose of ASE had a short-term effect on body weight gain and food and caloric intake, and in the long-term, it improved FBG levels measured at weeks 6 and 9 of the study. The high dose of ASE resulted in hyperinsulinemia and high homeostatic model assessment for insulin resistance (HOMA-IR) value compared to healthy rats. Total phenolic and flavonoid contents were 74.9 ± 0.491 mg of gallic acid equivalent and 20.0 ± 0.091 mg quercetin equivalent per g of ASE, respectively. The antioxidant activity of ASE expressed as half-maximal inhibitory concentration (IC50) value was 8.43 ± 0.825 mg/mL. These data suggest that ASE can safely and potently reduce the development of insulin resistance induced by HF diet feeding and lowering body weight gain in a dose-dependent manner.

Fuzhuan brick tea ameliorates hepatic steatosis and steatohepatitis through gut microbiota-derived aryl hydrocarbon receptor ligands in high-fat diet-induced obese mice.

High-fat diet (HFD) induced obesity and its associated conditions, such as hepatic steatosis and steatohepatitis, are major health concerns worldwide. Previous studies have reported the excellent efficiency of Fuzhuan brick tea (FBT) in attenuating HFD-induced obesity and metabolic disorders. In this study, we investigated the effects of FBT on hepatic steatosis and simple steatohepatitis in HFD-induced obese mice, as well as the metabolic function of the gut microbiome using metagenomics and metabolomics. The results showed that FBT ameliorated dyslipidemia, hepatic steatosis and steatohepatitis in HFD-induced obese mice by normalizing the gut microbiota structure and tryptophan metabolism. FBT increased the cecal abundance of aryl hydrocarbon receptor (AhR)-ligand producing bacteria such as Lactobacillus_reuteri and Lactobacillus_johnsonii, at the expense of AhR-ligand consuming bacteria, such as Faecalibaculum_rodentium and Escherichia_coli, and elevated the cecal contents of AhR-ligands such as IAA, IPA, and KYNA. Furthermore, FBT regulated the expressions of AhR and its targeted lipometabolic genes such as Pemt, Fasn, and SREBP-1c, as well as other inflammatory genes including TNF-α, IL-6, and IL-1ß in the liver of mice. Overall, these findings highlight the beneficial effects of FBT on obesity-related hepatic steatosis and steatohepatitis via microbiota-derived AhR signaling.

Efficacy and Interpretability Analysis of Noninvasive Imaging Based on Computed Tomography in Patients with Hepatocellular Carcinoma After Initial Transarterial Chemoembolization.

RATIONALE AND OBJECTIVES: The objective of this study is to accurately and timely assess the efficacy of patients with hepatocellular carcinoma (HCC) after the initial transarterial chemoembolization (TACE). MATERIALS AND METHODS: This retrospective study consisted of 279 patients with HCC in Center 1, who were split into training and validation cohorts in the ratio of 4:1, and 72 patients in Center 2 as an external testing cohort. Radiomics signatures both in the arterial phase and venous phase of contrast-enhanced computed tomography images were selected by univariate analysis, correlation analysis, and least absolute shrinkage and selection operator regression to build the predicting models. The clinical model and combined model were constructed by independent risk factors after univariate and multivariate logistic regression analysis. The biological interpretability of radiomics signatures correlating transcriptome sequencing data was explored using publicly available data sets. RESULTS: A total of 31 radiomics signatures in the arterial phase and 13 radiomics signatures in the venous phase were selected to construct Radscore_arterial and Radscore_venous, respectively, which were independent risk factors. After constructing the combined model, the area under the receiver operating characteristic curve in three cohorts was 0.865, 0.800, and 0.745, respectively. Through correlation analysis, 11 radiomics signatures in the arterial phase and 4 radiomics signatures in the venous phase were associated with 8 and 5 gene modules, respectively (All P < .05), which enriched some pathways closely related to tumor development and proliferation. CONCLUSION: Noninvasive imaging has considerable value in predicting the efficacy of patients with HCC after initial TACE. The biological interpretability of the radiological signatures can be mapped at the micro level.

Identification of Genipin as a Potential Treatment for Type 2 Diabetes.

The prevalence of type 2 diabetes (T2D) has been rising dramatically in many countries around the world. The main signatures of T2D are insulin resistance and dysfunction of ß-cells. While there are several pharmaceutical therapies for T2D, no effective treatment is available for reversing the functional decline of pancreatic ß-cells in T2D patients. It has been well recognized that glucagon-like peptide-1 (GLP-1), which is an incretin hormone secreted from intestinal L-cells, plays a vital role in regulating glycemic homeostasis via potentiating glucose-stimulated insulin secretion and promoting ß-cell function. We found that genipin, a natural compound from Elli, can directly target intestinal L-cells, leading to the secretion of GLP-1. Incubation of the cells with genipin elicited a rapid increase in intracellular Ca2+. Inhibition of PLC ablated genipin-stimulated Ca2+ increase and GLP-1 secretion, suggesting that genipin-induced GLP-1 release from cells is dependent on the PLC/Ca2+ pathway. In vivo, acute administration of genipin stimulated GLP-1 secretion in mice. Chronically, treatment with genipin via oral gavage at 50 mg/kg/day for 6 weeks reversed hyperglycemia and insulin resistance in high-fat-diet (HFD)-induced obese mice. Moreover, genipin alleviated the impaired lipid metabolism and decreased lipid accumulation in the liver of obese mice. These results suggest that naturally occurring genipin might potentially be a novel agent for the treatment of T2D and diet-induced fatty liver disease.

Assessing metabolic syndrome prediction quality using seven anthropometric indices among Jordanian adults: a cross-sectional study.

Metabolic syndrome (MSyn) is a considerable health concern in developing and developed countries, and it is a critical predictor of all-cause mortality. Obesity, specifically central obesity, is highly associated with MSyn incidence and development. In this study, seven anthropometric indices (Body Mass Index (BMI), Waist circumference (WC), Waist-to-Height Ratio (WHtR), A Body Shape Index (ABSI), Body Roundness Index (BRI), conicity index (CI), and the Visceral Adiposity Index (VAI)) were used to identify individuals with MSyn among the Jordanian population. These indices were assessed to identify their superiority in predicting the risk of MSyn. A total of 756 subjects (410 were male and 346 were female) were met between May 2018 and September 2019 and enrolled in this study. Height, weight, and waist circumferences were measured and BMI, WHtR, ABSI, BRI, CI, and VAI were calculated. Fasting plasma glucose level, lipid profile, and blood pressure were measured. Receiver-operating characteristic (ROC) curve was used to determine the discriminatory power of the anthropometric indices as classifiers for MSyn presence using the Third Adult Treatment Panel III (ATP III) definition. MSyn prevalence was 42.5%, and obese women and men have a significantly higher prevalence. BRI and WHtR showed the highest ability to predict MSyn (AUC = 0.83 for both indices). The optimal cutoff point for an early diagnosis of MSyn was > 28.4 kg/m2 for BMI, > 98.5 cm for WC, > 5.13 for BRI, > 0.09 m11/6 kg-2/3 for ABSI, > 5.55 cm2 for AVI, > 1.33 m3/2 kg-1/2 for CI, and > 0.59 for WHtR with males having higher cutoff points for MSyn early detection than females. In conclusion, we found that WHtR and BRI may be the best-suggested indices for MSyn prediction among Jordanian adults. These indices are affordable and might result in better early detection for MSyn and thereby may be helpful in the prevention of MSyn and its complications.

An olive-derived elenolic acid stimulates hormone release from L-cells and exerts potent beneficial metabolic effects in obese diabetic mice.

Insulin resistance and progressive decline in functional ß-cell mass are two key factors for developing type 2 diabetes (T2D), which is largely driven by overweight and obesity, a significant obstacle for effective metabolic control in many patients with T2D. Thus, agents that simultaneously ameliorate obesity and act on multiple pathophysiological components could be more effective for treating T2D. Here, we report that elenolic acid (EA), a phytochemical, is such a dual-action agent. we show that EA dose-dependently stimulates GLP-1 secretion in mouse clonal L-cells and isolated mouse ileum crypts. In addition, EA induces L-cells to secrete peptide YY (PYY). EA induces a rapid increase in intracellular [Ca2+]i and the production of inositol trisphosphate in L-cells, indicating that EA activates phospholipase C (PLC)-mediated signaling. Consistently, inhibition of (PLC) or Gαq ablates EA-stimulated increase of [Ca2+]i and GLP-1 secretion. In vivo, a single dose of EA acutely stimulates GLP-1 and PYY secretion in mice, accompanied with an improved glucose tolerance and insulin levels. Oral administration of EA at a dose of 50 mg/kg/day for 2 weeks normalized the fasting blood glucose and restored glucose tolerance in high-fat diet-induced obese (DIO) mice to levels that were comparable to chow-fed mice. In addition, EA suppresses appetite, reduces food intake, promotes weight loss, and reverses perturbated metabolic variables in obese mice. These results suggest that EA could be a dual-action agent as an alternative or adjuvant treatment for both T2D and obesity.

Research Hotspots and Trends Analysis of TFEB: A Bibliometric and Scientometric Analysis.

Objective: To explore the development context, research hotspots and frontiers of Transcription factor EB (TFEB) from 1991 to 2021 by bibliometric analysis. Methods: Publications about TFEB research from 1991 to 2021 were retrieved from the Web of Science Core Collection (WoSCC). Excel 2007 was used to collect basic information, including publications, research areas. VOSviewer 1.6.17 was used to analyze co-authorship of countries, institutes and authors. Co-citation of cited authors, cited references were analyzed by CiteSpace V.5.8.R3. In addition, CiteSpace was used to analyze keywords cluster and forecast research frontiers. Results: A total of 1,059 literatures were retrieved, including 1,340 research institutes and 393 academic journals. The main area of research related to TFEB is biology (340), the most published country and institutes were the United States (487) and Baylor College of Medicine (70). Settembre C owned the highest co-citations (663). Trending keywords may indicate frontier topics, including "Alzheimer's disease," "Parkinson's disease," "(p21; q12)," "melanoma," "pancreatic cancer," "breast cancer," "calcineurin," "TFE3," "trehalose," and "curcumin." Conclusion: This research provides valuable information for the study of TFEB. Disease research focuses more on neurodegenerative diseases (NDs) and tumors. Trehalose and curcumin are novel agents acting on TFEB. Rap-TRPML1-Calcineurin-TFEB and TFE3 are increasing signal pathway researches, similarly, the molecular biological mechanism of TFEB needs further exploration.

Dietary Flavonoids as Modulators of Lipid Metabolism in Poultry.

Flavonoids, naturally-occurring compounds with multiple phenolic structures, are the most widely distributed phytochemicals in the plant kingdom, and are mainly found in vegetables, fruits, grains, roots, herbs, and tea and red wine products. Flavonoids have health-promoting effects and are indispensable compounds in nutritional and pharmaceutical (i.e., nutraceutical) applications. Among the demonstrated bioactive effects of flavonoids are anti-oxidant, anti-inflammatory, and anti-microbial in a range of research models. Through dietary formulation strategies, numerous flavonoids provide the ability to support bird health while improving the nutritional quality of poultry meat and eggs by changing the profile of fatty acids and reducing cholesterol content. A number of such compounds have been shown to inhibit adipogenesis, and promote lipolysis and apoptosis in adipose tissue cells, and thereby have the potential to affect fat accretion in poultry at various ages and stages of production. Antioxidant and anti-inflammatory properties contribute to animal health by preventing free radical damage in tissues and ameliorating inflammation in adipose tissue, which are concerns in broiler breeders and laying hens. In this review, we summarize the progress in understanding the effects of dietary flavonoids on lipid metabolism and fat deposition in poultry, and discuss the associated physiological mechanisms.

Deletion of GPR30 Drives the Activation of Mitochondrial Uncoupling Respiration to Induce Adipose Thermogenesis in Female Mice.

Thermogenic adipocytes possess a promising approach to combat obesity with its capability promoting energy metabolism. We previously discovered that deletion of GPR30 (GPRKO), a presumably membrane-associated estrogen receptor, protected female mice from developing obesity, glucose intolerance, and insulin resistance when challenged with a high-fat diet (HFD). In vivo, the metabolic phenotype of wild type (WT) and GPRKO female mice were measured weekly. Acute cold tolerance test was performed. Ex vivo, mitochondrial respiration of brown adipose tissue (BAT) was analyzed from diet-induced obese female mice of both genotypes. In vitro, stromal vascular fractions (SVF) were isolated for beige adipocyte differentiation to investigate the role of GPR30 in thermogenic adipocyte. Deletion of GPR30 protects female mice from hypothermia and the mitochondria in BAT are highly energetic in GPRKO animals while the WT mitochondria remain in a relatively quiescent stage. Consistently, GPR30 deficiency enhances beige adipocyte differentiation in white adipose tissue (WAT) and activates the thermogenic browning of subcutaneous WAT due to up-regulation of UCP-1, which thereby protects female mice from HFD-induced obesity. GPR30 is a negative regulator of thermogenesis, which at least partially contributes to the reduced adiposity in the GPRKO female mice. Our findings provide insight into the mechanism by which GPR30 regulates fat metabolism and adiposity in female mice exposed to excess calories, which may be instrumental in the development of new therapeutic strategies for obesity.

Noninvasive Imaging Evaluation Based on Computed Tomography of the Efficacy of Initial Transarterial Chemoembolization to Predict Outcome in Patients with Hepatocellular Carcinoma.

Purpose: This study aims to develop a new model to more comprehensively and accurately predict the survival of patients with HCC after initial TACE. Patients and Methods: The whole cohort (n = 102) was randomly divided into a training cohort and a validation cohort in the ratio of 8:2. The optimal radiomics signatures were screened using the least absolute shrinkage and selection operator algorithm (LASSO) regression for constructing the radscore to predict overall survival (OS). The C-index (95% confidence interval, CI), calibration curve, and decision curve analysis (DCA) were used to evaluate the performance of the models. The independent risk factors (hazard ratio, HR) for predicting OS were stratified by Kaplan-Meier (K-M) analysis and the Log rank test. Results: The median OS was 439 days (95% CI: 215.795-662.205) in whole cohort, and in the training cohort and validation cohort, the median OS was 552 days (95% CI: 171.172-932.828), 395 days (95% CI: 309.415-480.585), respectively (P = 0.889). After multivariate cox regression, the combined radscore-clinical model was consisted of radscore (HR: 2.065, 95% CI: 1.285-3.316; P = 0.0029) and post-response (HR: 1.880, 95% CI: 1.310-2.697; P = 0.0007), both of which were independent risk factors for the OS. In the validation cohort, the efficacy of both the radscore (C-index: 0.769, 95% CI: 0.496-1.000) and combined model (C-index: 0.770, 95% CI: 0.581-0.806) were higher than that of the clinical model (C-index: 0.655, 95% CI: 0.508-0.802). The calibration curve of the combined model for predicting OS presented good consistency between observations and predictions in both the training cohort and validation cohort. Conclusion: Noninvasive imaging has a good prediction performance of survival after initial TACE in patients with HCC. The combined model consisting of post-response and radscore may be able to better predict outcome.

The metabolic regulation of Fuzhuan brick tea in high-fat diet-induced obese mice and the potential contribution of gut microbiota.

This study investigated the metabolic effects of Fuzhuan brick tea (FBT) in high-fat diet (HFD)-induced obese mice and the potential contribution of gut microbiota. The results showed that FBT ameliorated the HFD-induced glycerophospholipid metabolic aberrance, specifically increased the serum levels of phosphatidylcholines (PCs), lysophosphatidylcholines (LysoPCs), and the ratio of PC to phosphatidylethanolamines (PE). Besides, FBT increased the serum level of gut microbiota-derived aryl hydrocarbon receptor (AhR) ligand, 3-indole propionic acid, as well as the relative abundance of intestinal AhR-ligand producing bacteria such as Clostridiaceae, Bacteroidales_S24-7_group, and Lactobacillaceae. However, the metabolic benefits of FBT were weakened when the gut microbiota were depleted by antibiotic treatment, thereby suggesting that gut microbiota was required for FBT to regulate glycerophospholipid metabolism. Indeed, the metabolites regulated by FBT were significantly correlated with the AhR-ligand producing bacteria. The KEGG pathway enrichment analysis and expressions of AhR target genes indicated that FBT would improve the glycerophospholipid metabolism via the AhR-Pemt signal axis, in which the gut microbiota and their metabolites played pivotal mediators. Overall, FBT could be a functional beverage to improve HFD-induced metabolic disorders in a gut microbiota dependent manner.

Obesity Measures as Predictors of Type 2 Diabetes and Cardiovascular Diseases among the Jordanian Population: A Cross-Sectional Study.

Obesity is strongly associated with cardiovascular diseases (CVD) and type 2 diabetes (T2D). This study aimed to use obesity measures, body mass index (BMI) and waist circumference (WC) to predict the CVD and T2D risk and to determine the best predictor of these diseases among Jordanian adults. A cross-sectional study was conducted at the governmental and military hospitals across Jordan. The study participants were healthy or previously diagnosed with CVD or T2D. The continuous variables were compared using ANOVA, and the categorical variables were compared using the X2 test. The multivariate logistic regression was used to predict CVD and T2D risk through their association with BMI and WC. The final sample consisted of 6000 Jordanian adults with a mean age of 41.5 ± 14.7 years, 73.6% females. The BMI (OR = 1.7, CI: 1.30-2.30, p < 0.001) was associated with a higher risk of T2D compared to WC (OR = 1.3, CI: 1.04-1.52, p = 0.016). However, our results showed that BMI was not associated with CVD risk, while the WC was significantly and positively associated with CVD risk (OR = 1.9, CI: 1.47-2.47, p < 0.001). In conclusion, an elevated BMI predicts a higher risk of T2D, while WC is more efficient in predicting CVD risk. Our results can be used to construct a population-specific intervention to reduce the risk of CVD and T2D among adults in Jordan and other countries with similar backgrounds.

Natural Compound Resveratrol Attenuates TNF-Alpha-Induced Vascular Dysfunction in Mice and Human Endothelial Cells: The Involvement of the NF-κB Signaling Pathway.

Resveratrol, a natural compound in grapes and red wine, has drawn attention due to potential cardiovascular-related health benefits. However, its effect on vascular inflammation at physiologically achievable concentrations is largely unknown. In this study, resveratrol in concentrations as low as 1 µm suppressed TNF-α-induced monocyte adhesion to human EA.hy926 endothelial cells (ECs), a key event in the initiation and development of atherosclerosis. Low concentrations of resveratrol (0.25-2 µm) also significantly attenuated TNF-α-stimulated mRNA expressions of MCP-1/CCL2 and ICAM-1, which are vital mediators of EC-monocyte adhesion molecules and cytokines for cardiovascular plaque formation. Additionally, resveratrol diminished TNF-α-induced IκB-α degradation and subsequent nuclear translocation of NF-κB p65 in ECs. In the animal study, resveratrol supplementation in diet significantly diminished TNF-α-induced increases in circulating levels of adhesion molecules and cytokines, monocyte adhesion to mouse aortic ECs, F4/80-positive macrophages and VCAM-1 expression in mice aortas and restored the disruption in aortic elastin fiber caused by TNF-α treatment. The animal study also confirmed that resveratrol blocks the activation of NF-κB In Vivo. In conclusion, resveratrol at physiologically achievable concentrations displayed protective effects against TNF-α-induced vascular endothelial inflammation in vitro and In Vivo. The ability of resveratrol in reducing inflammation may be associated with its role as a down-regulator of the NF-κB pathway.

A monoclonal antibody neutralizes pesudorabies virus by blocking gD binding to the receptor nectin-1.

Pseudorabies virus (PRV) was isolated from some human cases recently and the infected patients manifested respiratory dysfunction and acute neurological symptoms. However, no effective drug or vaccine, preventing the progression of PRV infection, is available. Nectin-1 was the only reported receptor for PRV cell entry both swine and human origin, representing an excellent target to block PRV infection, and especially its transmission from pigs to humans. A PRV-gD specific mAbs (10B6) was isolated from hybridomas and its neutralizing activities in vitro and in vivo were determined. 10B6 exhibited effective neutralizing activities in vitro with IC50 = 2.514 µg/ml and 4.297 µg/ml in the presence and absence of complement. And in vivo, 10B6 provided 100% protection against PRV lethal challenge with a dose of 15 mg/kg. Further, 10B6 could bind to a conserved epitope, 316QPAEPFP322, locating in gD pro-fusion domain, and finally blocks the binding of PRV-gD to nectin-1. Moreover, 10B6 showed an effective inhibition on PRV cell-attachment in a cell type-independent manner and could also block the virus spreading among cells. 10B6 exhibited effectively neutralizing activities to Chinese PRV variant strain in vitro and in vivo by blocking gD binding to nectin-1, implied both prophylactic and therapeutic interventions against PRV infections.

Rosmarinic Acid Potently Detoxifies Amylin Amyloid and Ameliorates Diabetic Pathology in a Transgenic Rat Model of Type 2 Diabetes.

Protein aggregation is associated with a large number of human protein-misfolding diseases, yet FDA-approved drugs are currently not available. Amylin amyloid and plaque depositions in the pancreas are hallmark features of type 2 diabetes. Moreover, these amyloid deposits are implicated in the pathogenesis of diabetic complications such as neurodegeneration. We recently discovered that catechols and redox-related quinones/anthraquinones represent a broad class of protein aggregation inhibitors. Further screening of a targeted library of natural compounds in complementary medicine that were enriched with catechol-containing compounds identified rosmarinic acid (RA) as a potent inhibitor of amylin aggregation (estimated inhibitory concentration IC50 = 200-300 nM). Structure-function relationship analysis of RA showed the additive effects of the two catechol-containing components of the RA molecule. We further showed that RA does not reverse fibrillation back to monomeric amylin but rather lead to nontoxic, remodeled protein aggregates. RA has significant ex vivo efficacy in reducing human amylin oligomer levels in HIP rat sera as well as in sera from diabetic patients. In vivo efficacy studies of RA treatment with the diabetic HIP rat model demonstrated significant reduction in amyloid islet deposition and strong mitigation of diabetic pathology. Our work provides new in vitro molecular mechanisms and in vivo efficacy insights for a model nutraceutical agent against type 2 diabetes and other aging-related protein-misfolding diseases.

Dietary Supplementation of Baicalein Affects Gene Expression in Broiler Adipose Tissue During the First Week Post-hatch.

Dietary supplementation of baicalein, a flavonoid, has anti-obesity effects in mammals and broiler chickens. The aim of this study was to determine the effect of dietary baicalein supplementation on broiler growth and adipose tissue and breast muscle deposition. Fifty Hubbard × Cobb-500 day-of-hatch broiler chicks were assigned to a control starter diet or control diet supplemented with 125, 250, or 500 mg/kg baicalein and diets were fed for the first 6 days post-hatch. Body weight, average daily body weight gain, and average daily food intake were all reduced by 500 mg/kg baicalein. Breast muscle and subcutaneous and abdominal fat weights were also reduced in chicks that consumed the baicalein-supplemented diets. mRNAs for genes encoding factors involved in adipogenesis and fat storage, 1-acylglycerol-3-phosphate-O-acyltransferase 2, CCAAT/enhancer-binding protein ß, perilipin-1, and sterol regulatory element-binding transcription factor 1, were more highly expressed in the adipose tissue of broilers supplemented with baicalein than the controls, independent of depot. Diacylglycerol acyltransferase and peroxisome proliferator-activated receptor gamma mRNAs, involved in triacylglycerol synthesis and adipogenesis, respectively, were greater in subcutaneous than abdominal fat, which may contribute to differences in expansion rates of these depots. Results demonstrate effects of dietary supplementation of baicalein on growth performance in broilers during the early post-hatch stage and molecular effects in major adipose tissue depots. The mild reduction in food intake coupled to slowed rate of breast muscle and adipose tissue accumulation may serve as a strategy to modulate broiler growth and body composition to prevent metabolic and skeletal disorders later in life.