Coffeeberry Activates the CaMKII/CREB/BDNF Pathway, Normalizes Autophagy and Apoptosis Signaling in Nonalcoholic Fatty Liver Rodent Model.

Nonalcoholic fatty liver disease (NAFLD) shows extensive liver cell destruction with lipid accumulation, which is frequently accompanied by metabolic comorbidities and increases mortality. This study aimed to investigate the effects of coffeeberry (CB) on regulating the redox status, the CaMKII/CREB/BDNF pathway, autophagy, and apoptosis signaling by a NAFLD rodent model senescence-accelerated mice prone 8 (SAMP8). Three-month-old male SAMP8 mice were divided into a control group and three CB groups (50, 100, and 200 mg/kg BW), and fed for 12 weeks. The results show that CB reduced hepatic malondialdehyde and carbonyl protein levels. CB significantly enhanced Ca2+/calmodulin-dependent protein kinase II (CaMKII) and brain-derived neurotrophic factor (BDNF) and reduced the phospho-cAMP response element-binding protein (p-CREB)/CREB ratio. In addition, CB increased the silent information regulator T1 level, promoted Beclin 1 and microtubule-associated protein light chain 3 II expressions, and reduced phosphorylated mammalian target of rapamycin and its downstream p-p70s6k levels. CB also inhibited the expressions of apoptosis-related factors poly (ADP-ribose) polymerase-1 and the apoptosis-inducing factor. In conclusion, CB might protect the liver by reducing oxidative stress, activating the CaMKII/CREB/BDNF pathway, and improving autophagic and apoptotic expressions in a dose-dependent manner.

Effect of Oligomeric Proanthocyanidin on the Antioxidant Status and Lung Function of Patients with Chronic Obstructive Pulmonary Disease.

BACKGROUND/AIM: Evidence exists that oxidative stress and oxidative damage play a pivotal role in chronic obstructive pulmonary disease (COPD). Oligomeric proanthocyanidins (OPCs) extracted from grape seeds have been shown to exhibit antioxidant capabilities greater than those of vitamin C and E. The objective of this study was to evaluate the effects of OPCs on antioxidant status and lung function in patients with COPD. PATIENTS AND METHODS: Patients were supplemented with 150 mg/day OPC (n=13) orally or with a placebo (n=14) for 8 weeks in a randomized double-blind clinical design. Changes in anthropometric values, lung function, oxidative state, and lipid profiles were assessed after OPC or placebo treatment for 8 weeks. RESULTS: The results showed that OPC supplementation significantly reduced the concentration of malondialdehyde, superoxide dismutase, and total cholesterol (TC)/high-density lipoprotein cholesterol (HDL-C) ratio. The concentration of HDL-C significantly increased in the OPC-treated group. The plasma triglyceride, TC and low-density lipoprotein cholesterol values and the activities of catalase and glutathione peroxidase also decreased, but did not significantly differ between the OPC- and placebo-treated groups. Lung function was not significantly different between the two groups after 8 weeks. CONCLUSION: OPC supplementation was effective in increasing the antioxidant capacity, in addition to improving the lipid profiles in patients with COPD.

Effects of Nutritional Intervention on the Survival of Patients with Cardiopulmonary Failure Undergoing Extracorporeal Membrane Oxygenation Therapy.

BACKGROUND/AIM: This study aimed to examine the effects of nutritional intervention on the prognosis of patients with cardiopulmonary failure undergoing extracorporeal membrane oxygenation (ECMO) therapy in Taiwan. MATERIALS AND METHODS: An institutional review board-approved retrospective study was conducted on patients receiving ECMO therapy in the intensive care unit of the China Medical University Hospital, Taiwan, from January 2013 to December 2013. The study included 102 patients with cardiopulmonary failure receiving ECMO therapy. RESULTS: The data indicated that higher survival rates were closely related to lower age and APACHE II scores among the patients. In addition, compared to patients who deceased, those who survived had a higher total calorie intake. Most patients could tolerate bolus feeding and polymeric formulas. Furthermore, patients who underwent nutritional therapy with nutritional goals greater than 80% achieved a better outcome and lower mortality than other patients. CONCLUSION: Early nutritional intervention could benefit patients undergoing ECMO, and those who reached the delivery goal of 80% had significantly better outcomes than other patients. Enteral feeding can begin early and was well tolerated by patients receiving ECMO therapy. Following individual nutrition goals is critical for better outcomes, and this analysis might be useful in establishing individualized nutrition goals for oriental population when caring for critically ill patients.

Contribution of matrix metalloproteinases-1 genotypes to gastric cancer susceptibility in Taiwan.

Expression of matrix metalloproteinase-1 (MMP1), an interstitial collagenase regulating the extracellular matrix, plays a major role in carcinogenesis of gastric cancer, a leading cause of death worldwide. In literature, the single-nucleotide polymorphism (SNP) promoter -1607 1G/2G (rs1799750) at the MMP1 gene promoter has been reported to alter its own transcription level. While the importance's of the genotype of MMP1 promoter -1607 has not yet been studied in gastric cancer in Taiwan, our aim was to investigate MMP1 promoter -1607 genotypes and gastric cancer (GC) susceptibility in central Taiwan population. In the current hospital-based case-control study, the contribution of MMP1 promoter -1607 genotypes to GC risk was investigated among 121 GC patients and 363 gender- and age-matched healthy controls recruited and genotyped by the polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) methodology. We found that the genotypic and allelic frequencies were not differentially distributed between GC patient and control groups. The variant 1G containing genotypes have interactions with cigarrete smoking behaviors and Helicobacter pylori infection status, but not alcoholism on GC susceptibility determination. Our findings suggest that the variant 1G allele on MMP1 promoter -1607 may contribute to GC carcinogenesis and may be useful for GC early detection and prevention when combined with cigarrete smoking behaviors and Helicobacter pylori infection status.

Inhibitory Effects of AVEMAR on Proliferation and Metastasis of Oral Cancer Cells.

Oral cancer is keeping its 4th rank on the death causing cancers among Taiwan males, and its metastatic and recurrent rates remain high and a life-threatening issue to the citizens. Fermented wheat germ extract (AVEMAR) is used in clinical cancer nutritional therapy in gastrointestinal cancers but not in oral cancer yet. In this study, the potential of AVEMAR to inhibit tumor proliferation and metastasis of oral cancer was first investigated. Antiproliferative activity of AVEMAR was determined in human oral squamous carcinoma SCC-4 cells by MTT methodology. Wound-healing migration, transwell invasion, and Western blotting assays were carried out to examine the in vitro antimetastatic effects and involved signaling molecules for AVEMAR in oral cancer cells. AVEMAR at 0.2-1.6 mg/ml significantly inhibited the cell viability with IC50 values of 1.19 and 0.98 mg/ml for 24-h and 48-h treatment. Furthermore, AVEMAR could induce cell apoptosis and inhibit the migration and invasion of metastatic SCC-4 cells at a similar dose range. Notably, AVEMAR suppressed the expression of matrix metalloproteinase (MMP)-2 and urokinase plasminogen activator (u-PA), but not MMP-1 or MMP-9, in SCC-4 cells. These results strongly support the antiproliferation and in vitro antimetastatic capacity of AVEMAR which may extend its contributions from cancer nutrition supplements to preventive agent for oral cancer.

The contribution of XRCC6/Ku70 to hepatocellular carcinoma in Taiwan.

BACKGROUND: Hepatocellular carcinoma (HCC) is a neoplasm for which the prevalence and mortality rates are very high in Taiwan. The DNA non-homologous end-joining repair gene XRCC6/Ku70 plays an important role in the repair of DNA double-strand breaks (DSBs) induced by both exogenous and endogenous DNA-damaging agents. Defects in overall DSB repair capacity can lead to genomic instability and carcinogenesis. In this study, we investigated the contribution of variant XRCC6 in relation to the risk of HCC, from the levels of DNA, RNA and protein. MATERIALS AND METHODS: In this hospital-based case-control study, we collected 298 patients with HCC and 298 cancer-free controls, with frequency matched by age and gender. Firstly, the associations of XRCC6 promoter T-991C (rs5751129), promoter G-57C (rs2267437), promoter A-31G (rs132770), and intron-3 (rs132774) polymorphisms with HCC risk in this Taiwanese population were evaluated. Secondly, 30 HCC tissue samples with variant genotypes were tested to estimate the XRCC6 mRNA expression by real-time quantitative reverse transcription. Finally, the HCC tissue samples of variant genotypes were examined by immunohistochemistry and western blotting to estimate their XRCC6 protein expression levels. RESULTS: Compared with the TT genotype, the TC and CC genotypes conferred a significantly increased risk of HCC [adjusted odds ratio (aOR)=2.43 and 3.52, 95% confidence interval (CI)=1.52-4.03 and 1.18-13.36, p=0.0003 and 0.0385, respectively]. The mRNA and protein expression levels in HCC tissues revealed statistically significantly lower XRCC6 mRNA and protein expressions in the HCC samples with TC/CC genotypes compared with those with the TT genotype (p=0.0037 and 0.0003, respectively). CONCLUSION: Our multi-approach findings at the DNA, RNA and protein levels suggested that XRCC6 may play an important role in HCC carcinogenesis in the Taiwanese population.