ADH4-a potential prognostic marker for hepatocellular carcinoma with possible immune-related implications.

OBJECTIVE: This study aims to explore ADH4 expression in hepatocellular carcinoma (HCC), its prognostic impact, and its immune correlation to provide novel insights into HCC prognostication and treatment. METHODS: HCC prognostic marker genes were rigorously selected using GEO database, Lasso regression, GEPIA, Kaplan-Meier and pROC analyses. The expression of interested markers (ADH4, DNASE1L3, RDH16, LCAT, HGFAC) in HCC and adjacent tissues was assessed by Immunohistochemistry (IHC). We observed that ADH4 exhibited low expression levels in liver cancer tissues and high expression levels in normal liver tissues. However, the remaining four genes did not manifest any statistically significant differences between hepatocellular carcinoma (HCC) tissue and adjacent non-cancerous tissue. Consequently, ADH4 became the primary focus of our research. ADH4 expression was validated by signed-rank tests and unpaired Wilcoxon rank sum tests across pan-cancer and HCC datasets. Clinical significance and associations with clinicopathological variables were determined using Kaplan-Meier, logistic regression and Cox analyses on TCGA data. The ADH4-related immune responses were explored by Spearman correlation analysis using TIMER2 data. CD68, CD4, and CD19 protein levels were confirmed by IHC in HCC and non-cancerous tissues. RESULTS: ADH4 showed significant downregulation in various cancers, particularly in HCC. Moreover, low ADH4 expression was associated with clinicopathological variables and served as an independent prognostic marker for HCC patients. Additionally, ADH4 affects a variety of biochemical functions and may influence cancer development, prognosis, and treatment by binding to immune cells. Furthermore, at the immune level, the low expression pattern of ADH4 is TME-specific, indicating that ADH4 has the potential to be used as a target for cancer immunotherapy. CONCLUSION: This study highlights the diagnostic, prognostic and immunomodulatory roles of ADH4 in HCC. ADH4 could serve as a valuable biomarker for HCC diagnosis and prognosis, as well as a potential target for immunotherapeutic interventions.

Reticular framework materials for photocatalytic organic reactions.

Photocatalytic organic reactions, harvesting solar energy to produce high value-added organic chemicals, have attracted increasing attention as a sustainable approach to address the global energy crisis and environmental issues. Reticular framework materials, including metal-organic frameworks (MOFs) and covalent organic frameworks (COFs), are widely considered as promising candidates for photocatalysis owing to their high crystallinity, tailorable pore environment and extensive structural diversity. Although the design and synthesis of MOFs and COFs have been intensively developed in the last 20 years, their applications in photocatalytic organic transformations are still in the preliminary stage, making their systematic summary necessary. Thus, this review aims to provide a comprehensive understanding and useful guidelines for the exploration of suitable MOF and COF photocatalysts towards appropriate photocatalytic organic reactions. The commonly used reactions are categorized to facilitate the identification of suitable reaction types. From a practical viewpoint, the fundamentals of experimental design, including active species, performance evaluation and external reaction conditions, are discussed in detail for easy experimentation. Furthermore, the latest advances in photocatalytic organic reactions of MOFs and COFs, including their composites, are comprehensively summarized according to the actual active sites, together with the discussion of their structure-property relationship. We believe that this study will be helpful for researchers to design novel reticular framework photocatalysts for various organic synthetic applications.

Crystal Engineering of MOF-Derived Bimetallic Oxide Solid Solution Anchored with Au Nanoparticles for Photocatalytic CO2 Reduction to Syngas and C2 Hydrocarbons.

Considering that CO2 reduction is mostly a multielectron reaction, it is necessary for the photocatalysts to integrate multiple catalytic sites and cooperate synergistically to achieve efficient photocatalytic CO2 reduction to various products, such as C2 hydrocarbons. Herein, through crystal engineering, we designed and constructed a metal-organic framework-derived Zr/Ti bimetallic oxide solid solution support, which was confirmed by X-ray diffraction, electron microscopy and X-ray absorption spectroscopy. After anchoring Au nanoparticles, the composite photocatalyst exhibited excellent performances toward photocatalytic CO2 reduction to syngas (H2 and CO production rates of 271.6 and 260.6 µmol g-1 h-1) and even C2 hydrocarbons (C2H4 and C2H6 production rates of 6.80 and 4.05 µmol g-1 h-1). According to the control experiments and theoretical calculations, the strong interaction between bimetallic oxide solid solution support and Au nanoparticles was found to be beneficial for binding intermediates and reducing CO2 reduction, highlighting the synergy effect of the catalytic system with multiple active sites.

Induction of Chirality in Boron Imidazolate Frameworks: The Structure-Directing Effects of Substituents.

By enhancing steric hindrance of substituents on the imidazole ring, the fan-shaped molecule of a tridentate boron imidazolate ligand (KBH(2-ipim)3, 2-ipim = 2-isopropylimidazolate) with racemic chirality was obtained. Then, seven novel boron imidazolate frameworks (BIFs) were prepared by mixing KBH(2-ipim)3 ligands with various derivatives of benzene carboxylic acid under solvothermal conditions. All of these seven materials contain a ladder-like zinc-boron-imidazolate chain as a basic building block, and the ligand BH(2-ipim)3- exists in the same handedness in one chain. The structural variations are associated with the position of substituents of the auxiliary ligand. Of particular interest is the spontaneous resolution of BH(2-ipim)3- ligands into two independent enantiomorphous homochiral structures, BIF-131-S and BIF-131-R, which contain both a chiral chain and an absolute helix embedded in the nets.

Peony seed oil decreases plasma cholesterol and favorably modulates gut microbiota in hypercholesterolemic hamsters.

PURPOSE: Peony (Paeonia spp.) seed oil (PSO) contains a high amount of α-linolenic acid. The effects of PSO on hypercholesterolemia and gut microbiota remains unclear. The present study was to investigate effects of PSO supplementation on cholesterol metabolism and modulation of the gut microbiota. METHODS: Male Golden Syrian hamsters (n = 40) were randomly divided into five groups (n = 8, each) fed one of the following diets namely low-cholesterol diet (LCD); high cholesterol diet (HCD); HCD with PSO substituting 50% lard (LPSO), PSO substituting 100% lard (HPSO) and HCD with addition of 0.5% cholestyramine (PCD), respectively, for 6 weeks. RESULTS: PSO supplementation dose-dependently reduced plasma total cholesterol (TC) by 9-14%, non-high-density lipoprotein cholesterol (non-HDL-C) by 7-18% and triacylglycerols (TG) by 14-34% (p < 0.05). In addition, feeding PSO diets reduced the formation of plaque lesions by 49-61% and hepatic lipids by 9-19% compared with feeding HCD diet (p < 0.01). PSO also altered relative genus abundance of unclassified_f__Coriobacteriaceae, unclassified_f__Erysipelotrichaceae, Peptococcus, unclassified_f__Ruminococcaceae, norank_o__Mollicutes_RF9 and Christensenellaceae_R-7_group. CONCLUSIONS: It was concluded that PSO was effective in reducing plasma cholesterol and hepatic lipids and favorably modulating gut microbiota associated with cholesterol metabolism.

[Protective effect of oleanolic acid liposomes on cisplatin-induced oligoasthenospermia in mice].

OBJECTIVE: To study the protective effect of oleanolic acid liposomes (OA-Lips) on cisplatin-induced oligoasthenospermia (COAS) in mice. METHODS: Sixty ICR mice were randomly divided into a normal control, a COAS model control, a positive control and a low-, a medium- and a high-dose OA-Lips group. The animals in the low-, medium- and high-dose OA-Lips and positive control groups were given intragastrically OA-Lips solution at 25, 50, and 100 mg/kg/d and vitamin E at 50 mg/kg/d, respectively. On the 28th day, the mice in the COAS model control, positive control and OA-Lips groups were injected intraperitoneally with cisplatin solution at 10 mg/kg, while those in the normal control group with the same dose of normal saline. Three days after administration, all the mice were sacrificed and their testis tissues collected for detection of the semen parameters and observation of the testicular morphology. RESULTS: Both the percentage of motile sperm and sperm concentration were significantly increased in the high-dose OA-Lips group (P < 0.05). HE staining showed that OA-Lips remarkably improved the damaged testis tissue (P < 0.05) and protected the seminiferous tubules and interstitial cells. The percentage of progressively motile sperm (PMS) and the curvilinear velocity (VCL), straight line velocity (VSL), average path velocity (VAP), linearity (LIN), straightness (STR), wobble (WOB), amplitude of lateral head displacement (ALH) and beat-cross frequency (BCF) of sperm were gradually increased in a dose-dependent manner in the OA-Lips groups. The serum T level was significantly higher (P < 0.05) in the OA-Lips-treated mice than in the COAS model controls while the percentage of morphologically abnormal sperm (MAS) markedly lower in the high-dose OA-Lips group than in the model control, positive control and low-dose OA-Lips groups (P < 0.05). CONCLUSION: OA-Lips can relieve oligoaspermia and improve the productive ability of mice.

Blueberry and cranberry anthocyanin extracts reduce bodyweight and modulate gut microbiota in C57BL/6 J mice fed with a high-fat diet.

PURPOSE: Blueberry and cranberry are rich in anthocyanins. The present study was to investigate the effects of anthocyanin extracts from blueberry and cranberry on body weight and gut microbiota. METHODS: C57BL/6 J Mice were divided into six groups (n = 9 each) fed one of six diets namely low-fat diet (LFD), high-fat diet (HFD), HFD with the addition of 1% blueberry extract (BL), 2% blueberry extract (BH), 1% cranberry extract (CL), and 2% cranberry extract (CH), respectively. RESULTS: Feeding BL and BH diets significantly decreased body weight gain by 20-23%, total adipose tissue weight by 18-20%, and total liver lipids by 16-18% compared with feeding HFD. Feeding CH diet but not CL diet reduced the body weight by 27%, accompanied by a significant reduction of total plasma cholesterol by 25% and tumor necrosis factor alpha (TNF-α) by 38%. The metagenomic analysis showed that the supplementation of blueberry and cranberry anthocyanin extracts reduced plasma lipopolysaccharide concentration, accompanied by a reduction in the relative abundance of Rikenella and Rikenellaceae. Dietary supplementation of berry anthocyanin extracts promoted the growth of Lachnoclostridium, Roseburia, and Clostridium_innocuum_group in genus level, leading to a greater production of fecal short-chain fatty acids (SCFA). CONCLUSIONS: It was concluded that both berry anthocyanins could manage the body weight and favorably modulate the gut microbiota at least in mice.

Potential of crocodile blood as a medication and dietary supplement: A systemic review.

Crocodile blood has long been used as a traditional medicine in many Asian countries to treat diseases such as asthma, allergies, and many others. Yet, only recently has the safety and effectiveness of using crocodile blood as a medicine been examined using modern scientific methods; with both conserved and novel active components identified from crocodile blood. Further in vitro and in vivo investigations found that crocodile blood can have a wide range of beneficial effects, including antimicrobial, antiviral, anti-oxidative, anti-inflammatory, antitumour effects, anti-anaemia, and enhancement of wound healing. A systematic research of literature published in English-language journals up to April 2020 was conducted in PubMed, Google Scholar, and Web of Science. Based on the biological and chemical knowledge of crocodile immunity and crocodile blood, this article aims to: provide a critical review on the proposed properties of crocodile blood, identify the knowledge gap and offer some insights for future investigations regarding the use of crocodile blood as a medication or dietary supplement.

Rutin and Quercetin Decrease Cholesterol in HepG2 Cells but Not Plasma Cholesterol in Hamsters by Oral Administration.

Rutin (R) and quercetin (Q) are two widespread dietary flavonoids. Previous studies regarding the plasma cholesterol-lowering activity of R and Q generated inconsistent results. The present study was therefore carried out to investigate the effects of R and Q on cholesterol metabolism in both HepG2 cells and hypercholesterolemia hamsters. Results from HepG2 cell experiments demonstrate that both R and Q decreased cholesterol at doses of 5 and 10 µM. R and Q up-regulated both the mRNA and protein expression of sterol regulatory element binding protein 2 (SREBP2), low-density lipoprotein receptor (LDLR), and liver X receptor alpha (LXRα). The immunofluorescence study revealed that R and Q increased the LDLR expression, while only Q improved LDL-C uptake in HepG2 cells. Results from hypercholesterolemia hamsters fed diets containing R (5.5 g/kg diet) and Q (2.5 g/kg diet) for 8 weeks demonstrate that both R and Q had no effect on plasma total cholesterol. In the liver, only Q reduced cholesterol significantly. The discrepancy between the in vitro and in vivo studies was probably due to a poor bioavailability of flavonoids in the intestine. It was therefore concluded that R and Q were effective in reducing cholesterol in HepG2 cells in vitro, whereas in vivo, the oral administration of the two flavonoids had little effect on plasma cholesterol in hamsters.

Antimicrobial activities of Asian ginseng, American ginseng, and notoginseng.

Asian ginseng (Panax ginseng C.A. Meyer), American ginseng (Panax quinquefolius) and notoginseng (Panax notoginseng) are the three most commonly used ginseng botanicals in the world. With the increasing interests on antimicrobial properties of plants, the antimicrobial activities of ginseng species have been investigated by a number of researchers worldwide. This overview interprets our present knowledge of the antimicrobial activities of the three ginseng species and some of their bioactive components against pathogenic bacteria (Pseudomonas aeruginosa, Helicobacter pylori, Staphylococcus aureus, Escherichia coli, Propionibacterium acnes, et al.) and fungi (Candida albicans, Fusarium oxysporum, et al). Ginsenosides, polysaccharides, essential oil, proteins, and panaxytriol are all might responsible for the antimicrobial activities of ginseng. The antimicrobial mechanisms of ginseng components could be summarized to the following points: (a) inhibit the microbial motility and quorum-sensing ability; (b) affect the formation of biofilms and destroy the mature biofilms, which can weaken the infection ability of the microbes; (c) perturb membrane lipid bilayers, thus causing the formation of pores, leakages of cell constituents and eventually cell death; (d) stimulate of the immune system and attenuate microbes induced apoptosis, inflammation, and DNA damages, which can protect or help the host fight against microbial infections; and (e) inhibit the efflux of antibiotics that can descend the drug resistance of the microbial. The collected information might facilitate and guide further studies needed to optimize the use of ginseng and their components to improve microbial food safety and prevent or treat animal and human infections.

Standing-type magnetically guided capsule endoscopy versus gastroscopy for gastric examination: multicenter blinded comparative trial.

AIM: To compare feasibility and safety after gastrointestinal checkup by standing-type magnetically controlled capsule endoscopy (SMCE) and conventional gastroscopy. METHODS: This was a prospective multicenter, blinded study that compared SMCE with gastroscopy in patients from April 2018 to July 2018. All patients first underwent SMCE and then subsequently had gastroscopy with i.v. anesthesia. We calculated the compliance rates of gastric lesion detection by SMCE using gastroscopy as the standard. Capsule retention rate, incidence of adverse events, and patient satisfaction were documented throughout the study. RESULTS: One hundred and sixty-one patients who completed SMCE and gastroscopy were included in the analysis. Positive compliance rate among SMCE and gastroscopy was 92.0% (95% CI: 80.77%-97.78%). Negative compliance rate was 95.5% (89.80%, 98.52%). Moreover, overall compliance rate was 94.41% (89.65%, 97.41%). Sixty-four pathological outcomes were identified. Of these 64 outcomes, 50 were detected by both procedures. The gastroscopy method neglected seven findings (such as five erosions, one polyp, and one ulcer). Furthermore, SMCE also overlooked seven lesions (i.e. one erosion, two polyps, one atrophy, and three submucosal tumors). Capsule retention or related adverse events were not reported. CONCLUSION: Standing-type magnetically controlled capsule endoscopy provides equivalent agreement with gastroscopy and may be useful for screening of gastric illnesses without any anesthesia.

Impact of capsule endoscopy on prevention of postoperative recurrence of Crohn's disease.

BACKGROUND AND AIMS: Capsule endoscopy (CE) can detect lesions outside the scope of ileocolonoscopy in postoperative patients with Crohn's disease (CD). However, the impact of such findings on patient outcomes remains unknown. This study is intended to evaluate the impact of CE findings on clinical management and outcomes in asymptomatic patients with CD without pharmacologic prophylaxis after ileocolonic resection. METHODS: In this retrospective cohort study, 37 patients (group 1) received ileocolonoscopy together with CE within 1 year after surgery, whereas 46 patients (group 2) only received ileocolonoscopy. Patients with endoscopic recurrence detected by either ileocolonoscopy or CE received pharmacologic therapy with azathioprine or infliximab. One year later, disease activity was re-evaluated. RESULTS: In group 1, all patients with ileocolonoscopy-identified recurrence also had CE-identified recurrence. In addition, CE detected endoscopic recurrence in 11 patients missed by ileocolonoscopy. Endoscopic remission identified by ileocolonoscopy was confirmed by CE in 13 patients. One year later, endoscopic remission identified by ileocolonoscopy was maintained in all 24 patients, and none had clinical recurrence. Conversely, in group 2, of those with ileocolonoscopy-identified remission, both ileocolonoscopy-identified recurrence and clinical recurrence occurred in 9 of 31 patients 1 year later. The total clinical recurrence rate was 2.7% (1/37) in group 1 versus 21.7% (10/46) in group 2 (P = .019). CONCLUSIONS: If endoscopic remission identified by ileocolonoscopy was confirmed by CE, patients could remain free of pharmacologic prophylaxis. If recurrence outside the scope of ileocolonoscopy was detected by CE, initiation of active pharmacologic therapy would be needed.

Bone Morphogenic Protein 4-Smad-Induced Upregulation of Platelet-Derived Growth Factor AA Impairs Endothelial Function.

OBJECTIVE: Bone morphogenic protein 4 (BMP4) is an important mediator of endothelial dysfunction in cardio-metabolic diseases, whereas platelet-derived growth factors (PDGFs) are major angiogenic and proinflammatory mediator, although the functional link between these 2 factors is unknown. The present study investigated whether PDGF mediates BMP4-induced endothelial dysfunction in diabetes mellitus. APPROACH AND RESULTS: We generated Ad-Bmp4 to overexpress Bmp4 and Ad-Pdgfa-shRNA to knockdown Pdgfa in mice through tail intravenous injection. SMAD4-shRNA lentivirus, SMAD1-shRNA, and SMAD5 shRNA adenovirus were used for knockdown in human and mouse endothelial cells. We found that PDGF-AA impaired endothelium-dependent vasodilation in aortas and mesenteric resistance arteries. BMP4 upregulated PDGF-AA in human and mouse endothelial cells, which was abolished by BMP4 antagonist noggin or knockdown of SMAD1/5 or SMAD4. BMP4-impared relaxation in mouse aorta was also ameliorated by PDGF-AA neutralizing antibody. Tail injection of Ad-Pdgfa-shRNA ameliorates endothelial dysfunction induced by Bmp4 overexpression (Ad-Bmp4) in vivo. Serum PDGF-AA was elevated in both diabetic patients and diabetic db/db mice compared with nondiabetic controls. Pdgfa-shRNA or Bmp4-shRNA adenovirus reduced serum PDGF-AA concentration in db/db mice. PDGF-AA neutralizing antibody or tail injection with Pdgfa-shRNA adenovirus improved endothelial function in aortas and mesenteric resistance arteries from db/db mice. The effect of PDGF-AA on endothelial function in mouse aorta was also inhibited by Ad-Pdgfra-shRNA to inhibit PDGFRα. CONCLUSIONS: The present study provides novel evidences to show that PDGF-AA impairs endothelium-dependent vasodilation and PDGF-AA mediates BMP4-induced adverse effect on endothelial cell function through SMAD1/5- and SMAD4-dependent mechanisms. Inhibition of PGDF-AA ameliorates vascular dysfunction in diabetic mice.

Surface tuning laser desorption/ionization mass spectrometry (STLDI-MS) for the analysis of small molecules using quantum dots.

In most applications of quantum dots (QDs) for surface-assisted laser desorption/ionization mass spectrometry (SALDI-MS), one side of QDs is supported by a solid substrate (stainless - steel plate), whereas the other side is in contact with the target analytes. Therefore, the surface capping agent of QDs is a key parameter for laser desorption/ionization mass spectrometry (LDI-MS). Cadmium telluride quantum dots (CdTe QDs) modified with different capping agents are synthesized, characterized, and applied for surface tuning laser desorption/ionization mass spectrometry (STLDI-MS). Data shows that CdTe quantum dot modified cysteine (cys@CdTe QDs) has an absorption that matches with the wavelength of the N2 laser (337 nm). The synergistic effect of large surface area and absorption of the laser irradiation of cys@CdTe QDs enhances the LDI-MS process for small - molecule analysis, including α-, ß-, and γ-cyclodextrin, gramicidin D, perylene, pyrene, and triphenylphosphine. Cys@CdTe QDs are also applied using Al foils as substrates. Aluminum foil combined with cys@CdTe QDs enhances the ionization efficiency and is cheap compared to traditional matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) with a stainless - steel plate.

Effect of surface capping of quantum dots (CdTe) on proteomics.

RATIONALE: Investigation of nanoparticles for laser desorption/ionization mass spectrometry (LDI-MS) is routinely reported. However, the effect of surface capping of nanomaterials for LDI-MS is not well studied. METHODS: Different capping agents of quantum dots (CdTe) affect the spectra quality and sensitivity of protein analysis and protein digestion using trypsin enzyme assisted by microwave. Surface modification of CdTe quantum dots with different capping agents, namely 3-mercaptopropionic acid (3-MPA), 4-aminothiophenol (4-ATP), 4-mercaptobenzoic acid (4-MBA), 11-mercaptoundecanoic acid (11-MUA), cysteine (Cys) and thioglycolic acid (TG), were investigated for quantum dots (QDs)-assisted trypsin protease followed by analysis using mass spectrometry. RESULTS: CdTe QDs were used as a surface to assist trypsin protease and laser desorption/ionization mass spectrometry (surface-assisted laser desorption/ionization mass spectrometry, SALDI-MS). The MS profiles for the investigated analytes (bovine serum albumin (BSA), lysozyme, cytochrome c, α-casein, transferrin and myoglobin) revealed almost the absence of degradation that implies the softness of the present technique. QDs-assisted LDI-MS offered high sensitivity and high resolution. QDs showed significant enhancement of microwave-assisted trypsin digestion of the investigated proteins and these improvements boosted the identifications of fragments with a database. CONCLUSIONS: A capping agent of quantum dots affects the analysis of proteins and peptides using LDI-MS. CdTe QDs offer sensitive, high-resolution and simple analysis of proteins. QDs improved the protein digestion using the microwave-assisted trypsin digestion. Copyright © 2016 John Wiley & Sons, Ltd.

Comparison of the diagnostic efficacy of white light endoscopy and magnifying endoscopy with narrow band imaging for early gastric cancer: a meta-analysis.

OBJECTIVE: Magnifying endoscopy with narrow band imaging (ME-NBI) is widely used in gastroscopy, especially in the diagnosis of early gastric cancer. The purpose of this meta-analysis is to compare the diagnostic efficacy of white light imaging (WLI) and that of ME-NBI for early gastric cancer. METHODS: PubMed/MEDLINE, EMBASE, and the Cochrane Library were searched to identify studies which met the inclusion criteria. A random-effects model was used to calculate overall sensitivity, specificity, and the area under the receiver operating characteristic curve (AUC) to assess the diagnostic efficacy of WLI and ME-NBI in early gastric cancer. Sensitivity analysis was performed to assess the stability of the results. RESULTS: Ten studies met the inclusion criteria, and included 1724 patients and 2153 lesions. The pooled sensitivity, specificity, and AUC for the diagnosis of early gastric cancer using WLI were 0.48 [95 % confidence interval (CI) 0.39-0.57; I (2) = 78.6 %], 0.67 (95 % CI 0.62-0.71; I (2) = 81.9 %), and 0.62, respectively. The pooled sensitivity, specificity, and AUC using ME-NBI were 0.83 (95 % CI 0.79-0.87; I (2) = 79.8 %), 0.96 (95 % CI 0.95-0.97; I (2) = 89.3 %), and 0.96, respectively. The studies showed a high degree of heterogeneity. Further sensitivity analysis was mainly performed for the studies of small lesions (mean size 10 mm or less) and the studies with a the score of 12 points or greater in the literature quality assessment, and the AUCs for ME-NBI for diagnosis of early gastric cancer were between 0.93 and 0.98, which suggested that the diagnostic value was still high and stable. CONCLUSION: Compared with WLI, ME-NBI can effectively diagnose early gastric cancer.

Chronic black tea extract consumption improves endothelial function in ovariectomized rats.

PURPOSE: Menopause escalates the risk of cardiovascular diseases in women. There is an unmet need for better treatment strategy for estrogen-deficiency-related cardiovascular complications. Here we investigated the impact of chronic black tea extract (BT) consumption on cardiovascular function and lipid metabolism using a rat model of estrogen deficiency. METHODS: Female Sprague-Dawley rats were ovariectomized (OVX) and treated with BT (15 mg/kg/day, 4 weeks; active ingredients: theaflavins) or estrogen (E2) treatment for 4 weeks. Serum was collected for measuring cholesterol, triacylglycerol and estradiol levels. Changes in vascular reactivity were examined. The protein levels of NADPH oxidases were assessed by Western blotting. Reactive oxygen species (ROS) level was measured using dihydroethidium fluorescence imaging. The concentrations of cGMP were measured using ELISA kit. RESULTS: Aortic rings from control, BT-treated and E2-treated OVX rats exhibited a greater increase in Phe-induced contraction after inhibition of NO synthase compared with those from OVX rats. ACh-induced endothelium-dependent relaxations were augmented in aortae and renal arteries in BT/E2-treated OVX rats than in OVX rats. BT/E2 treatment improved flow-mediated dilatation in small mesenteric resistance arteries of OVX rats. BT/E2 treatment restored the eNOS phosphorylation level and reversed the up-regulation of NADPH oxidases and ROS overproduction in OVX rat aortae. ACh-stimulated cGMP production was significantly elevated in the aortae from BT- and E2-treated rats compared with those from OVX rats. BT/E2 treatment reduced circulating levels of total cholesterol. CONCLUSIONS: The present study reveals the novel benefits of chronic BT consumption to reverse endothelial dysfunction and favorably modifying cholesterol profile in a rat model of estrogen deficiency and provides insights into developing BT as beneficial dietary supplements for postmenopausal women.

Metformin protects endothelial function in diet-induced obese mice by inhibition of endoplasmic reticulum stress through 5' adenosine monophosphate-activated protein kinase-peroxisome proliferator-activated receptor δ pathway.

OBJECTIVE: 5' Adenosine monophosphate-activated protein kinase (AMPK) interacts with peroxisome proliferator-activated receptor δ (PPARδ) to induce gene expression synergistically, whereas the activation of AMPK inhibits endoplasmic reticulum (ER) stress. Whether the vascular benefits of antidiabetic drug metformin (AMPK activator) in diabetes mellitus and obesity is mediated by PPARδ remains unknown. We aim to investigate whether PPARδ is crucial for metformin in ameliorating ER stress and endothelial dysfunction induced by high-fat diet. APPROACH AND RESULTS: Acetylcholine-induced endothelium-dependent relaxation in aortae was measured on wire myograph. ER stress markers were determined by Western blotting. Superoxide production in mouse aortae and NO generation in mouse aortic endothelial cells were assessed by fluorescence imaging. Endothelium-dependent relaxation was impaired and ER stress markers and superoxide level were elevated in aortae from high-fat diet-induced obese mice compared with lean mice. These effects of high-fat diet were reversed by oral treatment with metformin in diet-induced obese PPARδ wild-type mice but not in diet-induced obese PPARδ knockout littermates. Metformin and PPARδ agonist GW1516 reversed tunicamycin (ER stress inducer)-induced ER stress, oxidative stress, and impairment of endothelium-dependent relaxation in mouse aortae as well as NO production in mouse aortic endothelial cells. Effects of metformin were abolished by cotreatment of GSK0660 (PPARδ antagonist), whereas effects of GW1516 were unaffected by compound C (AMPK inhibitor). CONCLUSIONS: Metformin restores endothelial function through inhibiting ER stress and oxidative stress and increasing NO bioavailability on activation of AMPK/PPARδ pathway in obese diabetic mice.

Additional mechanism for selective absorption of cholesterol and Phytosterols.

Phytosterols are structurally similar to cholesterol but they are much less absorbed (<2%) than cholesterol (>50%) in the intestine. We hypothesize that phytosterols are poor substrates of intestinal acyl-CoA: cholesterol acyltransferase 2 (ACAT2), and thus minimal phytosterol esters are formed and packed into chylomicrons, leading to their low absorption. Two isotope tracing models, including a radioactive hamster microsomal ACAT2 reaction model and a differentiated Caco-2 cell model, were established to examine the specificity of ACAT2 to various sterols, including cholesterol, sitosterol, stigmasterol, and campesterol. Both models consistently demonstrated that only cholesterol but not phytosterols could be efficiently esterified by ACAT2 in a time- and dose-dependent manner. Molecular docking further suggested that unfavorable interactions existed between ACAT2 and phytosterols. In conclusion, phytosterols are poor substrates of ACAT2 and thus minimally absorbed. This work provides a theoretical basis for the use of phytosterol-based supplements in treating dyslipidemia and preventing heart diseases.

Dietary supplementation with capsaicinoids alleviates obesity in mice fed a high-fat-high-fructose diet.

Capsaicinoids are the pungent compounds in chili peppers. The present study investigated the effect of capsaicinoids on obesity in mice induced by a high-fat-high-fructose diet. Thirty-two male C57BL/6J mice were randomly divided into four groups (n = 8) and fed one of the following diets, namely, a low-fat diet (LFD), a high-fat-high-fructose diet (HFF), an HFF + 0.015% capsaicinoids (LCP), and an HFF + 0.045% capsaicinoids (HCP), for 12 weeks. Results showed that capsaicinoids significantly reversed HFF-induced obesity. Supplementation with capsaicinoids improved glucose tolerance, reduced plasma lipids, and attenuated inflammation. Capsaicinoids also reduced hepatic lipid accumulation by upregulating the expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). In addition, capsaicinoids enhanced the production of fecal short-chain fatty acids (SCFAs) and increased the fecal excretion of lipids. Gut microbiota analysis revealed that capsaicinoids decreased the Firmicutes/Bacteroidetes ratio and beneficially reconstructed the microbial community. However, the effects of capsaicinoids on intestinal villus length and lipid tolerance were negligible. In conclusion, capsaicinoids effectively attenuated HFF-induced obesity and metabolic syndrome by favorably modulating lipid metabolism, improving SCFA production, and reshaping gut microbial structure.