Metformin Prolongs Survival in Type 2 Diabetes Lung Cancer Patients With EGFR-TKIs.

Background: Metformin use reportedly reduces cancer risk and improves survival in lung cancer patients. This study aimed to investigate the effect of metformin use in patients with diabetes mellitus (DM) and lung cancer receiving epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy. Methods: A nationwide, population-based cohort study was conducted using the Taiwan National Health Insurance Research Database. From January 1, 2004, to December 31, 2012, a total of 373 metformin and 1260 non-metformin lung cancer cohorts with type 2 DM and EGFR-TKI treatment were studied. Results: Metformin use was significantly associated with a reduced risk of death (hazard ratio: 0.73, 95% confidence interval [CI]: 0.62-0.85, P < .001), as well as a significantly longer median progression-free survival (9.2 months, 95% CI: 8.6-11.7, vs 6.4 months, 95% CI: 5.9-7.2 months, P < .001) and median overall survival (33.4 months, 95% CI: 29.4-40.2, vs 25.4 months, 95% CI: 23.7-27.2 months, P < 0.001). Conclusions: In conclusion, metformin may potentially enhance the therapeutic effect and increase survival in type 2 DM patients with lung cancer receiving EGFR-TKI therapy.

Asatone Prevents Acute Lung Injury by Reducing Expressions of NF-[Formula: see text]B, MAPK and Inflammatory Cytokines.

Asatone is an active component extracted from the Chinese herb Radix et Rhizoma Asari. Our preliminary studies have indicated that asatone has an anti-inflammatory effect on RAW 264.7 culture cells challenged with lipopolysaccharide (LPS). Acute lung injury (ALI) has high morbidity and mortality rates due to the onset of serious lung inflammation and edema. Whether asatone prevents ALI LPS-induced requires further investigation. In vitro studies revealed that asatone at concentrations of 2.5-20[Formula: see text][Formula: see text]g/mL drastically prevented cytotoxicity and concentration-dependently reduced NO production in the LPS-challenged macrophages. In an in vivo study, the intratracheal administration of LPS increased the lung wet/dry ratio, myeloperoxidase activity, total cell counts, white blood cell counts, NO, iNOS, COX, TNF-[Formula: see text], IL-1[Formula: see text], and IL-6 in the bronchoalveolar lavage fluid as well as mitogen-activated protein kinases in the lung tissues. Pretreatment with asatone could reverse all of these effects. Asatone markedly reduced the levels of TNF-[Formula: see text] and IL-6 in the lung and liver, but not in the kidney of mice. By contrast, LPS reduced anti-oxidative enzymes and inhibited NF-[Formula: see text]B activations, whereas asatone increased anti-oxidative enzymes in the bronchoalveolar lavage fluid and NF-[Formula: see text]B activations in the lung tissues. Conclusively, asatone can prevent ALI through various anti-inflammatory modalities, including the major anti-inflammatory pathways of NF-[Formula: see text]B and mitogen-activated protein kinases. These findings suggest that asatone can be applied in the treatment of ALI.

Obesity, hyperhomocysteinaemia and risk of chronic kidney disease: a population-based study.

Background: Obesity is associated with increased risk of cardiovascular disease and chronic kidney disease (CKD). Hyperhomocysteinaemia refers to increased oxidative stress and has been associated with the risk of CKD. Objectives: We investigated the association among body mass index (BMI), homocysteine level and impaired renal function in a Taiwanese adult population. Methods: This was a retrospective cross-sectional study involving 24826 subjects who underwent a health check-up from January 2013 to December 2015. A multivariate linear regression model was developed to analyse the relationship among BMI, serum homocysteine and estimated glomerular filtration rate (eGFR). A multivariate logistic regression model was used to assess the relationship among weight categories, hyperhomocysteinaemia and CKD. Results: The prevalence of CKD in the quartile groups of homocysteine were 2.5%, 2.7%, 3.4% and 5.2% (P < 0.01). For every one-unit increase in BMI (kg/m2), the eGFR decreased by 0.50 ml/min/1.73 m2. Overweight/obese subjects with high homocysteine levels had a higher odds ratio (OR) for CKD, as compared with normal weight subjects (1.84 versus 1.38, respectively; P < 0.01 versus P = 0.02, respectively). Overweight/obese female subjects with hyperhomocysteinaemia had an OR of 3.40 [P < 0.01; 95% confidence interval (CI): 2.06-5.61] for CKD; in males, the OR was 1.66 (P < 0.01; 95% CI: 1.38-1.99). Conclusions: Patients who are overweight/obese with higher homocysteine levels have an increased risk of CKD, especially females. Additional studies exploring whether the effect of weight loss or homocysteine-lowering therapies such as folic acid, vitamin B12 supplements that may prevent or slow the progression of declining renal function, is warranted.

Ethanol extract of Phellinus merrillii protects against diethylnitrosamine- and 2-acetylaminofluorene-induced hepatocarcinogenesis in rats.

OBJECTIVE: To study whether the ethanol extract of Phellinus merrillii (EPM) has chemopreventive potential against liver carcinogenesis. METHODS: Thirty male Spraque-Dawley rats were randomly divided into control group, EPM control group, hepatocarcinoma control group, low-dose EPM group and high-dose EPM group, 6 in each group. Using the Solt and Farber protocol in a rat model of hepatocarcinogenesis, the chemopreventive effect of EPM on diethylnitrosamine (DEN)-initiated, 2-acetylaminofluorene (2-AAF) and partial hepatectomy (PH)-promoted liver carcinogenesis in rats was evaluated. Basic pathophysiological and histological examinations, together with the serum levels of glutamic oxaloacetic transaminase (sGOT), glutamic pyruvic transaminase (sGPT) and gamma-glutamyl transpeptidase (γ-GT) were measured. RESULTS: Treatment of EPM at the concentration of 2 g/kg body weight in the diet for 8 weeks clearly prevented the development of carcinogenesis and reduced the levels of sGOT, sGPT, and serum γ-GT of rats as compared with the hepatocarcinoma control group (P<0.05 or P<0.01). These phenotypes were accompanied by a significant increase in natural killer cell activity. CONCLUSION: EPM showed a strong liver preventive effect against DEN+2-AAF+PH-induced hepatocarcinogenesis in a rat model.

Hispolon from Phellinus linteus induces G0/G1 cell cycle arrest and apoptosis in NB4 human leukaemia cells.

Hispolon (a phenolic compound isolated from Phellinus linteus) has been shown to possess strong antioxidant, anti-inflammatory, anticancer, and antidiabetic properties. In this study, we investigated the antiproliferative effect of hispolon on human hepatocellular carcinoma NB4 cells using the MTT assay, DNA fragmentation, DAPI (4, 6-diamidino-2-phenylindole dihydrochloride) staining, and flow cytometric analysis. Hispolon inhibited the cellular growth of NB4 cells in a dose-dependent manner through the induction of cell cycle arrest at G0/G1 phase measured using flow cytometric analysis and apoptotic cell death, as demonstrated by DNA laddering. Exposure of NB4 cells to hispolon-induced apoptosis-related protein expressions, such as the cleavage form of caspase 3, caspase 8, caspase 9, poly (ADP ribose) polymerase, and the proapoptotic Bax protein. Western blot analysis showed that the protein levels of extrinsic apoptotic proteins (Fas and FasL), intrinsic related proteins (cytochrome c), and the ratio of Bax/Bcl-2 were increased in NB4 cells after hispolon treatment. Hispolon-induced G0/G1-phase arrest was associated with a marked decrease in the protein expression of p53, cyclins D1, and cyclins E, and cyclin-dependent kinases (CDKs) 2, and 4, with concomitant induction of p21waf1/Cip1 and p27Kip1. We conclude that hispolon induces both of extrinsic and intrinsic apoptotic pathways in NB4 human leukemia cells in vitro.

Antioxidant and anti-inflammatory properties of Taiwanese yam (Dioscorea japonica Thunb. var. pseudojaponica (Hayata) Yamam.) and its reference compounds.

Dioscorea japonica Thunb. var. pseudojaponica (DP) is consumed as food and widely used in traditional Chinese medicine in Taiwan. The aims of this study are to investigate the antioxidant and anti-inflammatory effects of ethanol extract of DP (EDP) and its reference compounds. Fingerprint chromatogram from HPLC indicated that EDP contains gallic acid and vanillic acid. EDP was evaluated for its antioxidant effects and LPS-induced nitrite oxide (NO) production in RAW264.7 cells. EDP decreased the LPS-induced NO production and expressions of iNOS and COX-2 in RAW264.7 cells. In-vivo anti-inflammatory activities of EDP were assessed in mouse paw oedema induced by λ-carrageenan (Carr). We investigated the antioxidant mechanism of EDP via studies of the activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) and the levels of malondialdehyde (MDA) in the oedematous paw. The results showed that EDP might be a natural antioxidant and anti-inflammatory agent.

The crossmodal facilitation of visual object representations by sound: evidence from the backward masking paradigm.

We report a series of experiments designed to demonstrate that the presentation of a sound can facilitate the identification of a concomitantly presented visual target letter in the backward masking paradigm. Two visual letters, serving as the target and its mask, were presented successively at various interstimulus intervals (ISIs). The results demonstrate that the crossmodal facilitation of participants' visual identification performance elicited by the presentation of a simultaneous sound occurs over a very narrow range of ISIs. This critical time-window lies just beyond the interval needed for participants to differentiate the target and mask as constituting two distinct perceptual events (Experiment 1) and can be dissociated from any facilitation elicited by making the visual target physically brighter (Experiment 2). When the sound is presented at the same time as the mask, a facilitatory, rather than an inhibitory effect on visual target identification performance is still observed (Experiment 3). We further demonstrate that the crossmodal facilitation of the visual target by the sound depends on the establishment of a reliable temporally coincident relationship between the two stimuli (Experiment 4); however, by contrast, spatial coincidence is not necessary (Experiment 5). We suggest that when visual and auditory stimuli are always presented synchronously, a better-consolidated object representation is likely to be constructed (than that resulting from unimodal visual stimulation).

Catch the moment: multisensory enhancement of rapid visual events by sound.

Repetition blindness (RB) is a visual deficit, wherein observers fail to perceive the second occurrence of a repeated item in a rapid serial visual presentation stream. Chen and Yeh (Psychon Bull Rev 15:404-408, 2008) recently observed a reduction of the RB effect when the repeated items were accompanied by two sounds. The current study further manipulated the pitch of the two sounds (same versus different) in order to examine whether this cross-modal facilitation effect is caused by the multisensory enhancement of the visual event by sound, or multisensory Gestalt (perceptual grouping) of a new representation formed by combining the visual and auditory inputs. The results showed robust facilitatory effects of sound on RB regardless of the pitch of the sounds (Experiment 1), despite an effort to further increase the difference in pitch (Experiment 2). Experiment 3 revealed a close link between participants' awareness of pitch and the effect of pitch on the RB effect. We conclude that the facilitatory effect of sound on RB results from multisensory enhancement of the perception of visual events by auditory signals.

Konjac supplement alleviated hypercholesterolemia and hyperglycemia in type 2 diabetic subjects--a randomized double-blind trial.

OBJECTIVES: The present study was designed to evaluate effects of konjac glucomannan (KGM) supplement (3.6 g/day) for 28 days on blood lipid and glucose levels in hyperlipidemic type 2 diabetic patients and the possible mechanism for the reductions in blood lipid levels. METHODS: Twenty-two diabetic subjects (age 64.2 + 8.4 years, BMI 25.5 + 3.2 kg/m(2)) with elevated blood cholesterol levels (fasting glucose between 6.7-14.4 mmol/L), but currently not taking lipid-lowering medication, were recruited to participate in a two 28-day period, randomized, double-blind, crossover clinical trial. Fasting blood samples drawn on the initial and final days of each period were determined for plasma lipids and glucose levels. Feces collected at the end of each experimental period were analyzed for neutral sterol and bile acid contents. RESULTS: Compared with placebo, KGM effectively reduced plasma cholesterol (11.1%, p = 0.0001, adjusted alpha = 0.006), LDL-cholesterol (20.7%, p = 0.0004, adjusted alpha = 0.006), total/HDL cholesterol ratio (15.6%, p = 0.0005, adjusted alpha = 0.007), ApoB (12.9%, p = 0.0001, adjusted alpha = 0.006) and fasting glucose (23.2%, p = 0.002, adjusted alpha = 0.008). Plasma triglyceride, HDL-cholesterol, LDL/HDL cholesterol, postprandial glucose and body weight were not significant after adjustment by the Bonferroni-Hochberg procedure. Fecal neutral sterol and bile acid concentrations were increased by 18.0% (p = 0.004) and 75.4% (p < 0.001), respectively, with KGM supplement. CONCLUSIONS: The KGM supplement improved blood lipid levels by enhancing fecal excretion of neutral sterol and bile acid and alleviated the elevated glucose levels in diabetic subjects. KGM could be an adjunct for the treatment of hyperlipidemic diabetic subjects.