Inhibition of α-glucosidase activity and intestinal glucose transport to assess the in vivo anti-hyperglycemic potential of dodecyl-acylated phlorizin and polydatin derivatives.

A diet containing natural active compounds that can inhibit the hydrolytic activity of α-glucosidase on carbohydrates and intestinal glucose absorption is an effective means of controlling postprandial hyperglycemia. Phlorizin and polydatin as phenolic glycosides have a high affinity for the catalytic site of α-glucosidase, but exhibited unsatisfactory competitive inhibitory capacity, with an IC50 of 0.97 and >2 mM, respectively. However, dodecyl-acylated derivatives of phlorizin and polydatin exerted α-glucosidase inhibitory capacity, with an IC50 of 55.10 and 70.95 µM, respectively, which were greatly enhanced and much stronger than that of acarbose with an IC50 of 2.46 mM. The SPR assay suggested the high affinity of dodecyl phlorizin and dodecyl polydatin to α-glucosidase with equilibrium dissociation constant (KD) values of 12.0 and 7.9 µM, respectively. Both dodecyl phlorizin and dodecyl polydatin reduced the catalytic ability of α-glucosidase by reversible noncompetitive and uncompetitive mixed inhibition, which bind noncovalently to the allosteric site 2 through hydrogen bonds and hydrophobic interactions, thereby inducing the secondary structure unfolding and intrinsic fluorescence quenching of α-glucosidase. Confocal microscopy detection visually showed significant inhibitory effects on FITC-labeled glucose uptake in intestinal Caco-2 cells by phlorizin, polydatin, dodecyl phlorizin and dodecyl polydatin. In addition, based on the differentiated Caco-2 cell monolayer model, dodecyl phlorizin and dodecyl polydatin suppressed intestinal glucose transport more effectively than phlorizin and polydatin, suggesting that they were promising in vivo hypoglycemic active compounds.

Chondroitin sulfate and chitosan-coated liposomes as a novel delivery system for betanin: Preparation, characterization and in vitro digestion behavior.

Betanin, a water-soluble pigment known for its high bioactivity, is hindered by pH and temperature sensitivity, weak ionic strength, and low bioavailability. In this study, nanoliposome (NPS), chitosan-coated NPS (CNPS), and chondroitin sulfate-chitosan bilayer-modified nanoliposomes (SCNPS) were prepared based on a layer-by-layer electrostatic interaction method for betanin encapsulation. The increase of polymer layers from NPS to SCNPS led to a monotonic increment from 223.57 to 522.33 nm in size, from -27.73 to 16.70 mV in negative charge and from 0.22 to 0.35 in polydispersity index. The chemical stability against pH (ranging from 2 to 10), ionic type (KCl, CaCl2, ALCl3) and ionic strength (100, 500 mM) significantly impacted the appearance and particle size of the double-layered nanoliposome. In vitro digestion experiment showed that SCNPS displayed higher stability and slower betanin release compared to NPS and CNPS. This study demonstrates that betanin can be efficiently encapsulated by SCNPS with improved stability and bioavailability.

Remote guidance of percutaneous coronary intervention: A pilot study.

The safety and effectiveness of remote guidance of percutaneous coronary interventions (PCI) have not been fully appraised in controlled studies. We hereby presented the results of a study on remote guidance (vs on-site guidance) of PCI to explore its feasibility, safety, and effectiveness. Patients were recruited from those who received PCI procedures from January 2018 to June 2019 in a secondary hospital (Jincheng, Shanxi, China), in collaboration with a tertiary medical center (Beijing, China) approximately 680 km away. According to the type of guidance during the procedure, the patients were assigned to two groups: the remote guidance group and the on-site guidance group. Remote guidance was assisted with an advanced commercial telemedicine system. Interventional strategies, procedural success rate, peri-procedural complications, procedural duration, radiation doses, and the amount of contrast medium were compared between the two groups. A total of 352 patients were included in this study, with a total of 411 PCI procedures and 446 target lesions. The baseline clinical characteristics, as well as the distribution and characteristics of coronary artery lesions, did not differ significantly between the two groups. No significant differences were noticed in procedural success rate, peri-procedural complications, procedural duration, radiation dose, and in-hospital major adverse cardiovascular events. However, the amount of contrast medium was slightly higher in the remote guidance group. The results of the present pilot study showed the feasibility of remotely guided PCI, with safety and effectiveness measures at acceptable levels comparable to the traditional on-site guidance. Randomized studies with long-term follow-up are warranted to further confirm our findings.

Green-Efficient Enzymatic Synthesis and Characterization of Liposoluble 6'/6″-O-Lauryl Phenolic Glycosides with Enhanced Intestinal Permeability.

Arbutin, salidroside, polydatin, and phlorizin are typically natural bioactive phenolic glycosides. To improve the liposolubility and bioavailability, highly liposoluble derivatives including 6'-O-lauryl arbutin, 6'-O-lauryl salidroside, 6″-O-lauryl polydatin, and 6″-O-lauryl phlorizin were efficiently synthesized by enzymatic acylation in a green solvent 2-MeTHF. Their reaction conversions reached 84.4, 99.5, 99.8, and 89.1%, respectively, when catalyzed by Lipozyme 435 at 20 mg/mL at 50 °C. As expected, the derivatives had high log P (1.66-2.37) and retained good antioxidant activity, making them potential alternatives to butylated hydroxytoluene (BHT) and tert-butyl-hydroquinone (TBHQ) in lipid systems. Then, the intestinal permeability characteristics and metabolism of phenolic glycosides and their derivatives were investigated based on Caco-2 monolayers. The permeability of polydatin and phlorizin was mainly through active transport, but that of arbutin and salidroside involved both passive diffusion and active uptake. The acylated derivatives suffered from severe CES-mediated hydrolysis but exhibited a larger transported amount than phenolic glycosides.

CHA2DS2-VASc score as a prognostic indicator in patients with atrial fibrillation undergoing coronary stenting.

BACKGROUND: Patients with atrial fibrillation (AF) and coronary stenting had a poor prognosis. This study aimed to assess the accuracy of CHA2DS2-VASc score for predicting and grading adverse clinical outcomes in this population. METHODS: We reviewed the clinical data of all patients with previously documented nonvalvular AF who underwent coronary stenting between January 2010 and June 2015 in 12 hospitals of Beijing, China. The study population was divided into three groups: 1) Low CHA2DS2-VASc score, ≦ 2 points, 2) Intermediate score, 3-4 points, and 3) High score, ≧ 5 points. Major adverse cardiac/cerebrovascular events (MACCE) were defined as a composite of all-cause death, nonfatal myocardial infarction, repeat revascularization and ischemic stroke/systemic thromboembolism (IS/SE). RESULTS: A total of 2394 patients (men: 72.3% vs. women: 27.7%, median age: 67 years) were included, with the CHA2 DS2-VASc score of 3.6 ± 1.6. The median follow-up duration was 36.2 months. All-cause mortality increased 3 folds from the low score (4.8%) to the high score group (15.8%). The high score group had more IS/SE (7.4%) and MACCE (26.3%). The CHA2 DS2-VASc score ≧ 5 points was independently associated with all-cause death (hazard ratio [HR]: 2.303, 95% confidence interval [CI]: 1.492- 3.555), IS/SE (HR: 4.169, 95% CI: 2.216-7.845) and MACCE (HR: 1.468, 95% CI: 1.113-1.936) on multivariate Cox proportional hazards regression. The area under the receiver operating characteristic curve of the CHA2DS2-VASc score was 0.644 (95% CI: 0.624-0.663) for all-cause death, 0.647 (95% CI: 0.627-0.666) for IS/SE, and 0.592 (95% CI: 0.572-0.611) for MACCE. DISCUSSION: CHA2DS2-VASc score was a reliable prognostic indicator in patients with AF and coronary stenting.

Long-term outcomes of high-risk percutaneous coronary interventions under extracorporeal membrane oxygenation support: An observational study.

BACKGROUND: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) offers hemodynamic support for patients undergoing high-risk percutaneous coronary interventions (PCIs). However, long-term outcomes associated with VA-ECMO have not previously been studied. AIM: To explore long-term outcomes in high-risk cases undergoing PCI supported by VA-ECMO. METHODS: In the present observational cohort study, 61 patients who received VA-ECMO-supported high-risk PCI between April 2012 and January 2020 at the Sixth Medical Center of Chinese People's Liberation Army General Hospital were enrolled. The endpoint characteristics such as all-cause mortality, repeated cardiovascular diseases, and cardiac death were examined. RESULTS: Among 61 patients, three failed stent implantation due to chronic total occlusions with severely calcified lesions. One patient showed VA-ECMO intolerance because of high left ventricular afterload. PCI was successfully performed in 57 patients (93.4%). The in-hospital mortality was 23.0%, and the overall survival was 45.9%, with a median follow-up period of 38.6 (8.6-62.1) mo. CONCLUSION: VA-ECMO can be used as a support in patients undergoing high-risk PCI as it is associated with favorable long-term patient survival.

Predictive models for adverse clinical outcomes in Chinese patients with atrial fibrillation undergoing percutaneous coronary intervention with stenting.

OBJECTIVE: This study aimed to evaluate predictors for adverse cardiovascular outcomes in patients with atrial fibrillation (AF) undergoing coronary stenting. METHODS: We retrospectively recruited consecutive patients with previously documented non-valvular AF who underwent coronary stenting between January 2010 and June 2015 in 12 hospitals of Beijing, China. Major adverse cardiac/cerebrovascular events (MACCE) were a composite of all-cause death, non-fatal myocardial infarction, repeat revascularization, and ischaemic stroke/systemic thromboembolism (IS/STE). Major bleeding referred to grade 2 or higher of Bleeding Academic Research Consortium criteria. RESULTS: A total of 2394 patients (men: 72.3% vs. women: 27.7%, median age: 67 years) were included. The CHA2DS2-VASc and HAS-BLED were 3.6 ± 1.6 and 1.9 ± 0.7, respectively. The median follow-up duration was 36.2 months. There were 230 (9.6%) deaths, 96 (4.0%) IS/STE, 426 (17.8%) MACCE, and 72 (3.0%) major bleeding. Multivariate Cox regression yielded predictive models for (1) all-cause death: diabetes, prior myocardial infarction, chronic kidney disease (CKD), ST-segment elevation myocardial infarction (STEMI) at presentation, heart failure, no use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and statins; (2) IS/STE: advanced age, prior history of ischaemic stroke and intracranial haemorrhage; (3) MACCE: prior history of myocardial infarction and ischaemic stroke, CKD, STEMI, heart failure, and no statin use; (4) major bleeding: prior major bleeding, prior myocardial infarction, CKD and use of oral anticoagulants. CONCLUSION: Chinese patients with AF and coronary stenting had high mortality and incidence of MACCE. We compiled separate predictive models for all-cause death, IS/STE, MACCE, and major bleeding.

Influence of phenolic acids/aldehydes on color intensification of cyanidin-3-O-glucoside, the main anthocyanin in sugarcane (Saccharum officinarum L.).

Sugarcane contains various anthocyanins, which are responsible for the colors present in sugarcane. In this study, the color intensification of the major anthocyanin, cyanidin-3-O-glucoside, by phenolic acids/aldehydes (ferulic acid, vanillic acid, p-coumaric acid, syringic aldehyde and vanillic aldehyde) was investigated. The color enhancement of cyanidin-3-O-glucoside (hyperchromic effect and bathochromic shift) was affected by the temperature and concentration of phenolic acids/aldehydes present. Reactions were spontaneous and exothermic, as determined using different thermodynamic parameters (ΔG0, ΔH0, ΔS0). Quantum chemical calculations demonstrated their intermolecular interaction differences, and AIM analysis indicated that hydrogen bonds and van der Waals force interactions contributed to color. Pyranoanthocyanins derived from cyanidin-3-O-glucoside and ferulic/p-coumaric acids during storage were recognized as cyanidin-3-O-glucoside-vinylphenol and cyanidin-3-O-glucoside-vinylguaiacol, respectively, by UPLC-ESI-QTOF-MS/MS. The electron-donating substituents on the aromatic ring of ferulic/p-coumaric acids stabilized the intermediately formed carbenium ion. Decarboxylation and further oxidation of the pyran moieties to the aromatic heterocycles resulted in the final products.

High removal performance of a magnetic FPA90-Cl anion resin for bromate and coexisting precursors: kinetics, thermodynamics, and equilibrium studies.

In this study, the FPA90-Cl resin was magnetized with supported Fe3O4 particles using a chemical co-precipitation method and its removal performance of bromate and coexisting precursors was explored. The magnetized FPA90-Cl resin was structurally characterized by SEM, FT-IR, and XRD. The effects of the initial concentrations, temperature, and resin dosage on bromate and bromide ion removal in drinking water were investigated using batch experiments. The magnetized FPA90-Cl resin exhibited a high removal efficiency for bromate and bromide ions at three initial concentrations, and the residual bromate concentrations were under the maximum contaminant level (MCL) of 10 µg L-1 after 80 min. The adsorption data of bromate and bromide ion could be well described by a pseudo-first-order kinetic model (R2 Ëƒ 0.98). The bromate removal alone was further studied by varying the initial solution pH, temperature, and competitive anions. The results showed that the magnetized FPA90-Cl resin could be used over a wide pH range (4.0-9.0). The maximum sorption capacity of the magnetized FPA90-Cl resin for bromate reached 132.83 mg g-1 at 298 K. The Freundlich and Redlich-Peterson isotherm models fit the bromate adsorption equilibrium better (R2 Ëƒ 0.99) than the Langmuir isotherm model (R2 Ëƒ 0.98). The thermodynamic analysis showed that the bromate adsorption process was endothermic. The negative ΔG and positive ΔS indicated that the process was spontaneous and that randomness increased after adsorption, respectively. The competition of coexisting anions with bromate was in the order of SO42- > CO32- > Cl- > NO3- > HCO3- > PO43-. Additionally, the magnetized FPA90-Cl resin could maintain a high bromate and bromide ion adsorption capacity after five cycles of regeneration by a 0.1 M NaCl solution. Graphical abstract ᅟ.

Recycling metals from lithium ion battery by mechanical separation and vacuum metallurgy.

The large-batch application of lithium ion batteries leads to the mass production of spent batteries. So the enhancement of disposal ability of spent lithium ion batteries is becoming very urgent. This study proposes an integrated process to handle bulk spent lithium manganese (LiMn2O4) batteries to in situ recycle high value-added products without any additives. By mechanical separation, the mixed electrode materials mainly including binder, graphite and LiMn2O4 are firstly obtained from spent batteries. Then, the reaction characteristics for the oxygen-free roasting of mixed electrode materials are analyzed. And the results show that mixed electrode materials can be in situ converted into manganese oxide (MnO) and lithium carbonate (Li2CO3) at 1073K for 45min. In this process, the binder is evaporated and decomposed into gaseous products which can be collected to avoid disposal cost. Finally, 91.30% of Li resource as Li2CO3 is leached from roasted powders by water and then high value-added Li2CO3 crystals are further gained by evaporating the filter liquid. The filter residues are burned in air to remove the graphite and the final residues as manganous-manganic oxide (Mn3O4) is obtained.

Multicolor ELISA based on alkaline phosphatase-triggered growth of Au nanorods.

Seed-mediated synthesis of gold nanorods (AuNRs) has been widely used for diverse applications in the past decade. In this work, this synthetic process is demonstrated for multicolor biosensing for the first time. Our investigation reveals that ascorbic acid acts as a key factor to mediate the growth of AuNRs. This phenomenon is incorporated into the alkaline phosphatase (ALP)-enzyme-linked immunosorbent assay (ELISA) system based on the fact that ALP can catalyze the conversion of ascorbic acid-phosphate into ascorbic acid with high efficiency. This allows us to develop a multicolor ELISA approach for sensitive detection of disease biomarkers with the naked eye. We show the proof-of-concept multicolor ELISA for the detection of prostate-specific antigen (PSA) in human serum. The results show that different colors are presented in response to different concentrations of PSA, and a detection limit of 3 × 10(-15) g mL(-1) in human serum was achieved. The proposed multicolor ELISA could be a good supplement to conventional ELISA for POC diagnostics.

Anomalous left coronary artery arising from the pulmonary artery discovered beyond infancy.

Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is a congenital heart defect rarely diagnosed beyond infancy. We present a 9-year-old girl who had once been diagnosed as congenital coronary artery fistula. Echogenic mitral chordae tendineae, multiple coronary collaterals within the ventricular septum and free ventricular wall, and a shunting flow from the left coronary artery into the pulmonary artery were prominent echocardiographic features of ALCAPA. Reimplantation of the left coronary artery directly onto the aorta achieved a favorable outcome with regression of left ventricular size and alleviation of mitral regurgitation.

Resveratrol inhibits hydrogen peroxide-induced apoptosis in endothelial cells via the activation of PI3K/Akt by miR-126.

AIM: Resveratrol(RSV) is an edible polyphenolic phytoalexin present in different plant species that plays an important role in improving endothelial dysfunction. However, the molecular mechanisms underlying these effects are unknown. In the present study, the mechanism underlying the protection of CRL-1730 cells by RSV against oxidative stress was examined. METHODS: We first assessed the effects of RSV on the cell viability and apoptosis of CRL-1730 cells exposed to hydrogen peroxide(H2O2). Real-time PCR was used to determine the microRNA-126(miR-126) expression in cells treated with RSV and/or H2O2. We also evaluated the PI3K/Akt signaling pathway in CRL-1730 cells following upregulation of the miR-126 expression. Finally, we determined the effects of miR-126 on RSV against oxidative injury using an miR-126 inhibitor. RESULTS: Treatment with RSV resulted in a significant increase in survival and a decrease in the apoptosis of CRL-1730 cells exposed to H2O2. We also found that H2O2 significantly suppressed the expression of miR-126, which was reversed by RSV in a dose-dependent manner. The overexpression of miR-126 decreased PIK3R2(p85-ß) and enhanced Akt phosphorylation, which resulted in an increase in the survival of CRL-1730 cells exposed to H2O2. More importantly, the downregulation of the miR-126 expression reversed the effects of RSV on the survival and apoptosis of CRL-1730 cells exposed to H2O2. In addition, the knockdown of Ets-1 reversed the effects of RSV on the miR-126 expression in CRL-1730 cells exposed to H2O2. CONCLUSIONS: In this study, we demonstrated that the protection of endothelial cells by RSV against oxidative injury is due to the activation of PI3K/Akt by miR-126.

Mineralocorticoid receptor, CYP11B2 mRNA expression, and atrial matrix remodelling in patients with atrial fibrillation.

OBJECTIVE: Atrial fibrillation is associated with the activation of the renin-angiotensin-aldosterone system in the atria. It is not clear whether the expression of mineralocorticoid receptor (MR) and aldosterone synthase CYPII B2 in patients with atrial fibrillation is altered. This study aimed to investigate the mRNA expression of MR and CYPIIB2 and to reveal the correlation between CYPIIB2 mRNA and matrix remodelling in patients with atrial fibrillation. METHODS: Twenty-five patients with rheumatic heart valve disease, 12 in sinus rhythm and 13 in atrial fibrillation (> or = 6 months), underwent a valve replacement operation and right and left atrial lateral wall tissue samples were obtained. The MR and CYPI IB2 expressions were analysed at the mRNA level and collagen volume fraction was determined by Van Gieson's staining. Results - Collagen volume fraction was found to be increased significantly in atrial fibrillation groups compared with sinus rhythm groups (P < 0.001). Both the mRNA of MR and CYPIIB2 were significantly increased in the fibrillation group compared with the group in sinus rhythm (P < 0.01). Collagen volume fraction significantly and positively correlated with left atrial dimension (r = 0.845, P < 0.001).There was a positive correlation between CYPI I B2 mRNA and collagen volume fraction (r = 0.757, P < 0.001). CONCLUSION: Increased expression of MR and CYPIIB2 in the atria is one of the molecular mechanisms for the development of atrial interstitial fibrosis in patients with atrial fibrillation.

Chemoprevention of colorectal cancer by targeting APC-deficient cells for apoptosis.

Cancer chemoprevention uses natural, synthetic, or biological substances to reverse, suppress, or prevent either the initial phase of carcinogenesis or the progression of neoplastic cells to cancer. It holds promise for overcoming problems associated with the treatment of late-stage cancers. However, the broad application of chemoprevention is compromised at present by limited effectiveness and potential toxicity. To overcome these challenges, here we developed a new chemoprevention approach that specifically targets premalignant tumour cells for apoptosis. We show that a deficiency in the adenomatous polyposis coli (APC) gene and subsequent activation of beta-catenin lead to the repression of cellular caspase-8 inhibitor c-FLIP (also known as CFLAR) expression through activation of c-Myc, and that all-trans-retinyl acetate (RAc) independently upregulates tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) death receptors and suppresses decoy receptors. Thus, the combination of TRAIL and RAc induces apoptosis in APC-deficient premalignant cells without affecting normal cells in vitro. In addition, we show that short-term and non-continuous TRAIL and RAc treatment induce apoptosis specifically in intestinal polyps, strongly inhibit tumour growth, and prolong survival in multiple intestinal neoplasms C57BL/6J-Apc(Min)/J (Apc(Min)) mice. With our approach, we further demonstrate that TRAIL and RAc induce significant cell death in human colon polyps, providing a potentially selective approach for colorectal cancer chemoprevention by targeting APC-deficient cells for apoptosis.

[Atrial 11beta-hydroxysteroid dehydrogenase type 2 expression in rheumatic heart disease patients with or without atrial fibrillation].

OBJECTIVE: To investigate the mRNA and protein expressions of 11beta-Hydroxysteroid dehydrogenase type 2 (11betaHSD2) in patients with atrial fibrillation. METHODS: Right and left atrial lateral wall tissue samples were obtained during mitral/aortic valve replacement operation from 25 patients with rheumatic heart valve disease (12 in sinus rhythm and 13 in chronic atrial fibrillation). Realtime quantitative PCR and Western blot were used to determine the mRNA and protein expressions of 11betaHSD2 in atria specimens. The distribution of 11betaHSD2 in human atrial tissue was analyzed by specific immunohistochemical staining. Echocardiography examination was performed before operation. RESULTS: The left atrial diameters were significantly higher in the atrial fibrillation group as compared to sinus rhythm group (P < 0.01). Similarly, mRNA expression of 11betaHSD2 (0.86 +/- 0.14 vs 0.33 +/- 0.12 in right atria, 0.95 +/- 0.15 vs 0.37 +/- 0.10 in left atria, all P < 0.01) and protein expression of 11betaHSD2 (1.18 +/- 0.64 vs 0.71 +/- 0.21 in right atria, P < 0.01; and 1.36 +/- 0.58 vs 0.85 +/- 0.15 in left atria, P < 0.05) were also significantly upregulated in atrial fibrillation groups than those in sinus rhythm groups. The mRNA and protein expressions of 11betaHSD2 were similar between left atria and right atria both in fibrillation and sinus groups (all P > 0.05). The special immunohistochemical staining demonstrated that 11betaHSD2 was abundant in the human atrial myocardium and located mainly in the cytoplasm. CONCLUSION: These findings suggested that upregulated 11betaHSD2 might be associated to the development and persistence of atrial fibrillation.

Bypass NFkappaB-mediated survival pathways by TRAIL and Smac.

Activation of NFkappaB is frequently associated with human malignancies. The involvement of NFkappaB is in part attributed to its ability to activate various genes promoting cell survival. This property contributes to aggressive tumor growth and resistance to chemotherapy and radiation in cancer treatment. Various reports have shown that inhibition of NFkappaB promotes apoptosis and suppress tumor growth. However, NFkappaB has many important cellular functions and targeting NFkappaB directly may lead to severe side effects. Thus, developing strategies with low cytotoxicity to overcome NKkappaB-mediated cell survival is critical to improve cancer therapy. In this report, we described an approach using TRAIL/ Apo2L (TNF-related apoptosis-inducing ligand TRAIL or Apo2 ligand) and a Smac analog to overcome and bypass NFkappaB activation in cancer treatment. We have shown that a panel of head and neck squamous cell carcinoma (HNSCC) cell lines are highly resistant to TRAIL-induced apoptosis due to activation of NFkappaB-mediated cell survival pathways, and that inhibition of NFkappaB renders HNSCC cells sensitive to TRAIL. We further show that TRAIL and a small molecule mimic of Smac overcome and bypass NFkappaB activation in inducing cancer cell death. Since this treatment has no effect on NFkappaB activation and TRAIL offers tumor selectivity, cotreatment of TRAIL and Smac provides a strategy with potentially low toxicity to overcome NFkappaB activation in cancer cells, which has potential therapeutic benefit.