Anti-hyperlipidemic and hepatoprotective properties of wheat bran with different particle sizes.

BACKGROUND: Wheat bran has been shown to have health-promoting benefits in relation to diabetes, colorectal cancer, cardiovascular disease, constipation, irritable bowel syndrome, diverticulitis, and gastrointestinal disease. However, its effects on obesity, hyperglycemia, hepatotoxicity, and hyperlipidemia are not yet clear. The effects of the consumption of wheat bran of different particle sizes (coarse, 427.55 µm versus ultra-fine, 11.63 µm) on body weight, serum glucose, liver, and blood lipid metabolism levels in high-fat-diet induced rats fed for 5 weeks were investigated. RESULTS: The high-fat diet significantly increased body weight, serum glucose, serum and liver lipids, and malondialdehyde levels. However, addition of coarse and ultra-fine wheat bran to a high-fat diet decreased weight gain, reduced the levels of serum and liver total cholesterol, triglycerides, malondialdehyde, serum low-density lipoprotein, and serum glucose, and improved serum high-density lipoprotein. Moreover, when two particle sizes were compared, the highest impact was exhibited by the wheat bran containing the larger particle size. CONCLUSIONS: The results suggest that micronized wheat bran significantly improves anti-hyperlipidemic and hepatoprotective properties that might provide a safeguard to protect humans against metabolic syndrome abnormalities and other acute, recurrent, or chronic diseases. © 2018 Society of Chemical Industry.

Multi-scale structural changes in lintnerized starches from three coloured potatoes.

Three kinds of potato starch were treated with 2.2 N HCl at 35 °C for 40 days, and their susceptibility to acid hydrolysis and the resulting structural changes were evaluated. Red potato starch was more susceptible to acid hydrolysis and presented highest rate of hydrolysis. Lintnerized starches had relatively low average molecular weights and z-average radius of gyration. HPAEC analyses showed three lintners presented different molecular size distributions. Lintnerized yellow potato starch had few chains of DP ≤ 12 (2.58 mol%) and more chains of DP ≥ 37 (8.16 mol%). Furthermore, the similarities of the branch-chain length distributions before and after debranching indicated the lintners consisted primarily of linear molecules. After lintnerization, most starch granules were degraded, and the birefringence disappeared from some granules. X-ray diffraction patterns revealed that the relative crystallinity significantly increased after lintnerization. DSC analyses showed that lintners displayed broader thermal-transitions.

Volume-sensitive outwardly rectifying chloride channel blockers protect against high glucose-induced apoptosis of cardiomyocytes via autophagy activation.

Hyperglycemia is a well-characterized contributing factor for cardiac dysfunction and heart failure among diabetic patients. Apoptosis of cardiomyocytes plays a major role during the onset and pathogenesis of diabetic cardiomyopathy (DCM). Nonetheless, the molecular machinery underlying hyperglycemia-induced cardiac damage and cell death remains elusive. In the present study, we found that chloride channel blockers, 4,4'-diisothiocya-natostilbene-2,2'- disulfonic acid (DIDS) and 4-(2-butyl-6,7-dichlor-2-cyclopentyl-indan-1-on-5-yl) oxybutyric acid (DCPIB), inhibited high glucose-activated volume-sensitive outwardly rectifying (VSOR) Cl- channel and improved the viability of cardiomyocytes. High glucose induced cardiomyocyte apoptosis by suppressing the autophagic stress, which can be reversed via blockade of VSOR Cl- channel. VSOR activation in high glucose-treated cardiomyocytes was attributed to increased intracellular levels of reactive oxygen species (ROS). Taken together, our study unraveled a role of VSOR chloride currents in impaired autophagy and increased apoptosis of high glucose-exposed cardiomyocyte, and has implications for a therapeutic potential of VSOR chloride channel blockers in DCM.

Activation of volume-sensitive Cl- channel mediates autophagy-related cell death in myocardial ischaemia/reperfusion injury.

Excessive reactive oxygen species (ROS) plays an important role in myocardial ischemia/reperfusion (I/R) injury, which triggers not only myocardial cellular apoptosis but also autophagy-related cell death, in which volume-sensitive outwardly rectifying (VSOR) Cl- channel-activated by ROS contributes to cell apoptotic volume decrease, playing an incipient incident of cellular apoptosis. However, whether VSOR Cl- channel concurrently participates in autophagy-related cell death regulation remains unclear. To illuminate the issue, studies underwent in myocardial vitro and vivo I/R model. Rats were performed to ischemia 30 minutes and subsequent reperfusion 24-96 hours, ROS scavenger (NAC), VSOR Cl- channel blocker (DCPIB) and autophagy inhibitor (3MA) were administered respectively. Results showed that oxidative stress, LC3-II stain and inflammation in myocardial tissue were markedly increased, lysosome associated membrane protein-2 (LAMP2) were significantly reduced with I/R group as compared with sham group, reperfusion significantly led to damage in myocardial tissue and heart function, whereas the disorder could be rescued through these agents. Moreover, primary neonatal rat cardiomyocytes hypoxia/reoxygenation model were administered, results showed that VSOR Cl- channel-activated by reoxygenation could cause both cell volume decrease and intracellular acidification, which further increased LC3 and depleted of LAMP2, resulting in autophagy-related cell death. Interestingly, VSOR Cl- channel-blocked by DCPIB could stably maintain the cell volume, intracellular pH, abundant LAMP2 and autophagic intensity regardless of ROS intension derived from reoxygenation injury or adding H2O2. These results first demonstrate that VSOR Cl- channel-activated is a pivotal event to trigger autophagy-related death, which reveals a novel therapeutic target to decrease myocardial I/R injury.

Notch3 Ameliorates Cardiac Fibrosis After Myocardial Infarction by Inhibiting the TGF-ß1/Smad3 Pathway.

Notch3 and TGF-ß1 signaling play a key role in the pathogenesis and progression of chronic cardiovascular disease. However, whether Notch3 protects against myocardial infarction (MI) and the underlying mechanisms remains unknown. C57BL/6 mice were randomized to be treated with Notch3 siRNA (siNotch3) or lentivirus carrying Notch3 cDNA (Notch3) before coronary artery ligation. Four weeks after constructing MI model, cardiac function and fibrosis were compared between groups. The cardiac fibroblast cells (CFs) were isolated from newborn C57BL/6 mice (1-3 days old) and transfected with lentivirus carrying Notch3 cDNA. TGF-ß1 (5 ng/ml), a well-known pro-fibrotic factor, was administered 72 h after Notch3 cDNA administration in CFs. The related proteins of fibrosis such as a-smooth muscle actin (a-SMA), Type I collagen, metalloprotease (MMP)-9 and the tissue inhibitor of metalloproteinases (TIMP)-2 were examined by western blot analysis. Notch3 cDNA treatment attenuated cardiac damage and inhibited fibrosis in mice with MI. Meanwhile, Notch3 siRNA administration aggravated cardiac function damage and markedly enhanced cardiac fibrosis in mice with MI. Overexpression of Notch3 inhibited TGF-ß1-induced fibroblast-myofibroblast transition of mouse cardiac fibroblast cells, as evidenced by down-regulating a-SMA and Type I collagen expression. Notch3 cDNA treatment also increased MMP-9 expression and decreased TIMP-2 expression in the TGF-ß1-stimulated cells. This study indicates that Notch3 is an important protective factor for cardiac fibrosis in a MI model, and the protective effect of Notch3 is attributable to its action on TGF-ß1/Smad3 signaling.

DIDS reduces ischemia/reperfusion-induced myocardial injury in rats.

BACKGROUND/AIMS: Anion channels such as chloride channel are known to participate in the regulation of a wide variety of cellular processes including development, differentiation, proliferation, apoptosis and regeneration. This study was designed to examine the effect of the non-selective anion channel blocker 4,4'-Diisothiocyanostilbene-2, 2'-disulfonic acid (DIDS) on cardiac function and apoptosis using a rat model of ischemia/reperfusion (I/R). METHODS: Fifty male SD rats were randomly divided into the following groups including sham, I/R and I/R+DIDS (7, 14 or 28 mg/kg). In DIDS group, rats received DIDS treatment (4 ml/kg/hr) at the beginning of reperfusion for 2 hrs using a programmed micro-pump. Cardiac function was evaluated including left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP) as well as positive and negative maximal derivatives of left ventricular pressure (± dP/dt(max)). Myocardial infarct size was detected using the double staining with 2, 3, 5-triphenyl-2H-tetra-zolium chloride (TTC) and Evan's blue dye. DNA ladder, TUNEL assay, Bax and Bcl-2 protein levels were evaluated. Levels of ROS and Akt phosphorylation were detected. RESULTS: I/R injury compromised cardiac function as manifested by reduced LVSP and ± dP/dt(max) as well as pronounced apoptosis. I/R-induced cardiac anomalies were markedly ameliorated by DIDS. DIDS retarded I/R-induced myocardial infarct and apoptosis. In addition, DIDS ameliorated I/R-induced ROS production and Akt dephosphorylation in the heart. CONCLUSION: Taken together, our data revealed that DIDS may protect cardiomyocytes against I/R injury as evidenced by improved cardiac function, Bcl-2, Akt phosphorylation, and reduced myocardial apoptosis, Bax expression, ROS production and myocardial infarct size.

Baicalin protects the cardiomyocytes from ER stress-induced apoptosis: inhibition of CHOP through induction of endothelial nitric oxide synthase.

Baicalin, the main active ingredient of the Scutellaria root, exerts anti-oxidant and anti-apoptotic effects in cardiovascular diseases. However, the therapeutic mechanism of baicalin remains unknown. Cultured neonatal rat cardiomyocytes were pre-treated with baicalin (0-50 µM) for 24 h, and subsequently treated with tunicamycin (100 ng/ml). Cell viability was detected by MTT assay, and cell damage was determined by LDH release and TUNEL assay. The expression of CHOP, JNK, caspase-3, eNOS was analyzed by western blot. NO was measured by DAF-FM staining. As a result, treatment with baicalin significantly reduced apoptosis induced by ER stress inducer tunicamycin in cardiomyocytes. Molecularly, baicalin ameliorated tunicamycin-induced ER stress by downregulation of CHOP. In addition, baicalin inverted tunicamycin-induced decreases of eNOS mRNA and protein levels, phospho eNOS and NO production through CHOP pathway. However, the protective effects of baicalin were significantly decreased in cardiomyocytes treated with L-NAME, which suppressed activation of nitric oxide synthase. In conclusion, our results implicate that baicalin could protect cardiomyocytes from ER stress-induced apoptosis via CHOP/eNOS/NO pathway, and suggest the therapeutic values of baicalin against ER stress-associated cardiomyocyte apoptosis.

Adjuvant chemotherapy and radiotherapy in triple-negative breast carcinoma: a prospective randomized controlled multi-center trial.

BACKGROUND AND PURPOSE: Triple-negative breast cancer (TNBC) presents a high risk breast cancer that lacks the benefit from hormone treatment, chemotherapy is the main strategy even though it exists in poor prognosis. Use of adjuvant radiation therapy, which significantly decreases breast cancer mortality, has not been well described among poor TNBC women. The aim of this study was to evaluate whether the combination of chemotherapy and radiotherapy could significantly increase survival outcomes in TNBC women after mastectomy. PATIENTS AND METHODS: A prospective randomized controlled multi-center study was performed between February 2001 and February 2006 and comprised 681 women with triple-negative stage I-II breast cancer received mastectomy, of them, 315 cases received systemic chemotherapy alone, 366 patients received radiation after the course of chemotherapy. Recurrence-free survival (RFS) and overall survival (OS) were estimated. Simultaneously local and systemic toxicity were observed. RESULTS: After a median follow-up of 86.5 months, five-year RFS rates were 88.3% and 74.6% for adjuvant chemotherapy plus radiation and adjuvant chemotherapy alone, respectively, with significant difference between the two groups (HR 0.77 [95% CI 0.72, 0.98]; P=0.02). Five-year OS significantly improved in adjuvant chemotherapy plus radiation group compared with chemotherapy alone (90.4% and 78.7%) (HR 0.79 [95% CI 0.74, 0.97]; P=0.03). No severe toxicity was reported. CONCLUSIONS: Patients received standard adjuvant chemotherapy plus radiation therapy was more effective than chemotherapy alone in women with triple-negative early-stage breast cancer after mastectomy.

Three-dimensional conformal radiation therapy for refractory laryngeal granuloma.

AIMS AND BACKGROUND: The etiology of laryngeal granulomas is often multifactorial and the benefit of pharmacological therapy remains unclear. Anti-reflux treatment is only effective in granulomas definitely induced by gastroesophageal reflux. Steroid inhalation has shown favorable results but it is unclear whether it shortens the healing process. Surgical excision is associated with high recurrence rates. The aim of this study was to evaluate the role of 3-dimensional conformal radiation therapy (3DCRT) in the treatment of refractory laryngeal granuloma. METHODS AND STUDY DESIGN: The study was a retrospective review including all patients presenting to the Department of Radiation Oncology at Xijing Hospital from January 2004 to March 2007. We studied a total of 15 cases of refractory laryngeal granuloma that had recurred ≥2 times. Patients had previously been managed with voice rest, corticosteroids, antibiotics, antacids, surgery and botulinum toxin. All patients accepted surgical excision and immediate adjuvant 3DCRT at a total dose of 15 Gy over 5 days. RESULTS: All patients were successfully treated with surgery and 3DCRT. There has been no granuloma recurrence in 3 years of follow-up. CONCLUSIONS: 3DCRT is a safe and effective therapy for refractory laryngeal granulomas, especially when other methods have failed.

Bidirectional function of shenghe powder on repair of radiation-induced DNA damage in glioma and astrocyte.

The study assessed the effect of Chinese herbs of Shenghe Powder (SHP) on the repair capacity of gamma-radiation-induced DNA damage in rat glioma cells (C6) compared with normal human astrocytes (NHA). C6 and NHA Cells treated with SHP and irradiated with 2Gy of gamma radiation. Cells growth inhibition were analysed by MTT assay, DNA damage and repair were evaluated using phosphorylated histone H2AX (γH2AX) at the appointed time. Apoptosis was observed by flow cytometry, and the expression of DNA-dependent protein kinase (DNA-PK) and surviving proteins were assessed by Western blot analysis. SHP depressed the radiation-induced DNA double-strand break and enhanced the DNA repair capacity in NHA, which correlated with promotion of DNA-PK phosphorylation. In contrast, SHP enhanced radiosensitivity of C6 cells, the pre-treatment with SHP resulted in reduced numbers of γH2AX foci in irradiated C6 cells, and decreased the expression of DNA-PK and survivn(P<0.005). It significant effect on inhibition of C6 cell proliferation and induced C6 cells apoptosis in a time-depdendent manner than radiation alone (P<0.001). SHP showed a novel bidirectional function to improve the radioresistance of NHA and enhanced radiosensitivity of C6 cells. This implies that SHP can protect the NHA from radiant damage and enhanced the sensitivity of C6 cells to radiation, which could be attributed to the alteration of survivin DNA-PK in DNA repair processes.

Chinese herbs of Shenghe Powder reverse multidrug resistance of gastric carcinoma SGC-7901.

The objective of this study was to investigate the reversal effect of Chinese herbs of Shenghe Powder on the multidrug resistance of the human SGC-7901 gastric carcinoma cell line and vincristine-resistant cell line (SGC-7901/vincristine) and the possible mechanism. SGC-7901 and SGC-7901/ vincristine were cultured in liquid medium RMPI 1640, with the addition of vincristine to the vincristine-resistant line. The reversal effect of Shenghe Powder (using verapamil as control) on the multidrug resistance of SGC-7901/vincristine cells was observed using the 3-4,5-dimethylthiazol-2yl) -2,5-diphenylterazolium bromide method. The expression rate of P-glycoprotein (P-gp), lymphoma/leukemia-2 (Bcl-2), and apoptosis ratio of SGC-7901 and SGC-7901/vincristine with added Shenghe Powder, verapamil, or verapamil plus Shenghe Powder was observed by flow cytometry. Shenghe Powder and verapamil decreased the multidrug resistance of SGC-7901/vincristine. The effect of Shenghe Powder (10 mg/L) was significantly higher than verapamil (P< .05). The intracellular concentration of vincristine was increased by Shenghe Powder and verapamil. The vincristine concentration of SGC-7901/vincristine treated with Shenghe Powder was significantly higher (P< .05). Shenghe Powder reduced the expression level of P-gp and Bcl-2 in SGC-7901/ vincristine and increased the apoptotic percentage of tumor cells; Shenghe Powder had the more significant effect on apoptosis (P< .05). In conclusion, Shenghe Powder increases the intracellular concentration of vincristine, consistent with the down-regulation of the expression of P-gp and Bcl-2. The reversal effect of Shenghe Powder was stronger than that of verapamil.