Genetic and Non-Genetic Factor-Adjusted Association between Coffee Drinking and High-Density Lipoprotein Cholesterol in Taiwanese Adults: Stratification by Sex.

Low high-density lipoprotein cholesterol (HDL-C) is a major risk factor for cardiovascular diseases (CVDs), the leading cause of global mortality. We aimed to determine the effect of coffee drinking and sex and their interaction, as well as rs1800588 and rs1800775 polymorphisms on HDL-C levels in Taiwanese adults. Data of 4262 men and 4813 women, aged 30-70 years, were retrieved from Taiwan Biobank. The interaction between sex and coffee drinking on HDL-C was significant (p = 0.0452). Coffee consumption was significantly associated with higher HDL-C levels in only women (ß = 0.81679; p = 0.0246). However, rs1800588 and rs1800775 variants were significantly associated with HDL-C in both sexes. In women, ß-values were 0.99080; p = 0.0059 and 3.16277; p < 0.0001 for rs1800588 CT and TT genotypes, respectively and -1.80954; p < 0.0001 and -2.81512; p < 0.0001 for rs1800775 AC and CC genotypes, respectively. In men, ß-values were 1.32430; p < 0.0001 and 3.24976; p < 0.0001 for rs1800775 CT and TT genotypes, respectively and -1.96232; p < 0.0001 and -2.71536, p < 0.0001 for the AC and CC genotypes, respectively. In conclusion, coffee drinking was significantly associated with higher high-density lipoprotein (HDL) levels in women but not men after adjusting for confounders including rs1800588 (LIPC) and rs1800775 (CETP) variants.

Praeruptorin-B Inhibits 12-O-Tetradecanoylphorbol-13-Acetate-Induced Cell Invasion by Targeting AKT/NF-κB via Matrix Metalloproteinase-2/-9 Expression in Human Cervical Cancer Cells.

BACKGROUND/AIMS: Praeruptorins, a seselin-type coumarin, possess anti-inflammatory and antitumor promoting properties. However, molecular mechanisms through which Praeruptorin-B (Pra-B) exerts an antimetastatic effect on cervical cancer cells remain unclear. METHODS: Cell viability was examined using the MTT assay, whereas cell migration and invasion were examined using the Boyden chamber assay. Western blotting and RT-PCR were performed to investigate the inhibitory effect of Pra-B on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced matrix metalloproteinase-2/-9 (MMP-2/-9) expression in HeLa cells. The findings of the luciferase assay confirmed the inhibitory effect of Pra-B on TPA-induced transcriptional activity of MMP2/-9 in HeLa cells. RESULTS: Pra-B inhibited TPA-induced metastatic ability of human cervical cancer cells without any significant toxicity. Pra-B suppressed TPA-induced mRNA and protein expression and transcriptional activity of MMP-2/-9 in HeLa cells. Furthermore, Pra-B inhibited AKT phosphorylation but did not affect the MAPK pathway. Cotreatment of HeLa cells with TPA plus Pra-B or LY294002 (a PI3K inhibitor) reduced cell invasion and MMP-2/-9 expression and transcriptional activity. In addition, Pra-B attenuated TPA-induced nuclear translocation of NF-κB-p65/-p50, which reduced Ikk-α phosphorylation in HeLa cells. Cotreatment of HeLa cells with TPA plus Pra-B or LY294002 reduced NF-κB nuclear translocation. CONCLUSION: These results suggested that Pra-B-mediated inhibition of TPA-induced cell metastasis involved the suppression of p-AKT/NF-κB via MMP-2/-9 expression in HeLa cells. Pra-B can be a potential antimetastatic agent against cervical cancer.

Association of Consecutive Influenza Vaccinations and Pneumonia: A Population-Based Case-Control Study.

The purpose of this study was to investigate whether individuals receiving influenza vaccines have a lower risk of pneumonia. A nationwide population-based case-control study was conducted using data from the National Health Insurance Research Database in Taiwan. We enrolled 7565 patients each in pneumonia and non-pneumonia groups after diagnosis of patients with chronic pulmonary disease, and these patients were individually age and sex matched in a 1:1 ratio. Using conditional logistic regression analysis, adjusted odds ratios (aORs) were estimated in patients who received influenza vaccination and those who had not previously had pneumonia. Moreover, we also analyzed the interval between vaccination and the onset of pneumonia and the number of vaccinations received by patients. This was compared with patients who never received influenza vaccination. Patients who had received influenza vaccination and had been vaccinated for two consecutive years (aOR = 0.85, confidence interval (CI) = 0.79⁻0.93 and aOR = 0.75, CI = 0.67⁻0.85, respectively) showed lower rates of pneumonia occurrence by 15⁻25%. In conclusion, influenza vaccination significantly reduces the occurrence of pneumonia, especially in individuals who receive vaccination in consecutive years.

Noni (Morinda citrifolia L.) Fruit Extracts Improve Colon Microflora and Exert Anti-Inflammatory Activities in Caco-2 Cells.

Intestinal microflora and inflammation are associated with the risk of inflammatory bowel diseases. Noni (Morinda citrifolia L.) has various bioactivities, but its effect on colon health remains unknown. This study focused on the effects of fermented noni fruit extracts on colon microflora and inflammation of colon epithelial cells. The anti-inflammatory activities of ethanol and ethyl acetate extracts on Caco-2 cells were evaluated including interleukin-8 (IL-8) and cyclooxygenase-2 (COX-2). The growth of Lactobacillus and Bifidobacterium species was promoted by ethanol extract. Ethyl acetate extract decreased intracellular reactive oxygen species and significantly suppressed COX-2, IL-8, and prostaglandin E2 production and neutrophil chemotaxis by suppressing the translocation of the p65 subunit. Quercetin was the main contributor to the anti-inflammatory activity. The fermented noni fruit promoted probiotic growths and downregulated the intracellular oxidation and inflammation in Caco-2 cells. These results suggest that fermented noni fruit might protect against inflammatory diseases of the colon.

Dioscorin pre-treatment protects A549 human airway epithelial cells from hydrogen peroxide-induced oxidative stress.

Hydrogen peroxide (H(2)O(2)) is a highly reactive oxygen species involved in lung and bronchial epithelium injury. Increased H(2)O(2) levels have been reported in expired breath condensates of patients with inflammatory airway diseases such as chronic obstructive pulmonary disease. Protecting airway epithelial cells from oxidative stress is an important task in the prevention and management of airway diseases. Previous studies demonstrate that yam (Dioscorea batatas Decne) has antioxidant and anti-trypsin activities. This study evaluated the validity of dioscorin in vitro. The results showed that dioscorin attenuated the alteration of H(2)O(2) on G2/M cell cycle arrest. This might be associated with the activation of IκB and subsequent inactivation of NF-κB. Furthermore, dioscorin suppressed IL-8 secretion and reduced changes of adhesion molecule expressions in H(2)O(2)-injured A549 cells. These results help in understanding the potential of traditional Chinese herbal medicine as treatment for airway inflammatory diseases.

In vivo cytokine modulatory effects of cinnamaldehyde, the major constituent of leaf essential oil from Cinnamomum osmophloeum Kaneh.

The purpose of this study was to analyse the major compound in the leaf essential oil of Cinnamomum osmophloeum Kaneh. and to examine its in vivo toxicity and cytokine-modulatory effects. The HS-GC/MS and quantitative HPLC analyses showed the concentrations of the major compounds, cinnamaldehyde, benzaldehyde and 3-phenylpropionaldehyde, in the leaf essential oil of Cinnamomum osmophloeum to be 16.88, 1.28 and 1.70 mg/mL, respectively. Acute and sub-acute toxicity tests identified no significant changes in body weight, liver and kidney function indices, and pathology for the mice treated with up to 1 mL/kg body weight of Cinnamomum osmophloeum leaf essential oil or up to 4 mg/kg body weight of cinnamaldehyde. A murine model was established using ovalbumin (OVA)-primed Balb/C mice treated with various concentrations of Cinnamomum osmophloeum leaf essential oil or cinnamaldehyde daily for 4 weeks. The results of tests with commercial ELISA kits indicated no significant cytokine-modulatory effects in mice treated with Cinnamomum osmophloeum leaf essential oil; however, the serum concentrations of IL-2, IL-4 and IL-10, but not IFN-γ, significantly increased in animals treated with 1 mg/kg body weight of cinnamaldehyde during the 4-week period. The possibility that the other constituents act as antagonists of cinnamaldehyde cannot be excluded.

In vivo Th1 and Th2 cytokine modulation effects of Rhodiola rosea standardised solution and its major constituent, salidroside.

Although Rhodiola rosea (L.) is used widely and disseminated in Oriental medicine, its in vivo effects on cytokine modulation remain unclear. Among the biologically active components of Rhodiola rosea, salidroside was suggested to be the most active compound. The objectives of this study were to assess the toxicity and cytokine modulation effects of Rhodiola rosea standardised solution (RRSS) and salidroside. Quantitative high pressure liquid chromatography (HPLC) analysis determined the content of salidroside in RRSS to be 4.39% (w/v). Groups of Balb/c mice were fed daily with different doses of RRSS or salidroside, with CAPE or distilled water used as positive and negative controls, respectively. The acute and subacute toxicity tests did not reveal weight differences, pathological changes, or abnormalities in liver or kidney function indices among the treated groups. Ovalbumin-primed mouse cytokine assays demonstrated that both T helper (Th1) (IL-2 and IFN-γ) and Th2 (IL-4 and IL-10) cytokines were significantly increased by feeding with RRSS in a dose- and time-dependent manner (p < 0.05). Moreover, the cytokine modulation effects of salidroside were less prominent than that of RRSS treatment and not dose-dependent. These findings suggest that increased secretion of both Th1- and Th2-pattern cytokines can be achieved with RRSS and salidroside treatment.

Neuron Regeneration and Proliferation Effects of Danshen and Tanshinone IIA.

This study evaluates the proliferative effects of danshen and its monomer extract, tanshinone IIA, on Schwann cell proliferation. A piece of silicone rubber was guided across a 15-mm gap in the sciatic nerve of a rat. This nerve gap was then filled with different concentrations of danshen (0-100 mg/mL). The results showed that danshen increased the expressions of uPA, cyclin D1, E and ERK, JNK, and P38 MAP kinases via the FGF-2 signaling pathway in a dose-dependent manner. RSC96, Schwann cells were also administered with danshen (0, 20, 40, 60, 80, and 100 µg/mL) and tanshinone IIA (0, 2, 4, 6, 8, and 10 µg/mL). In lower concentrations, danshen and tanshinone IIA exhibited an apparent effect on Schwann cells. Similar effects were also demonstrated in the FGF-2-uPA regulating cascade and cell cycle proliferative protein results. Schwann cell migration was elevated as well. We used MAPK-signaling chemical inhibitors and identified the proliferative effects of danshen and tanshinone IIA as MAPK-signaling dependent. The results from the in vitro systems indicate that danshen and tanshinone IIA can be used to induce Schwann cell proliferation, and in vivo results potentially suggest that danshen and tanshinone IIA might enhance neuron regeneration.

Honokiol and magnolol as multifunctional antioxidative molecules for dermatologic disorders.

Chinese herbs have been and still are widely used as important remedies in Oriental medicine. Over the recent years, a variety of biologically active constituents have been isolated from these sources and confirmed to have multifunctional activity in experimental studies. Honokiol is a small-molecule polyphenol isolated from the genus Magnolia. It is accompanied by other related polyphenols, including magnolol, with which it shares certain biological properties. Recently, honokiol and magnolol have been found to have anti-oxidative, anti-inflammatory, anti-tumor, and anti-microbial properties in preclinical models, without appreciable toxicity. These findings have increased interest in bringing honokiol and magnolol to the clinic as novel therapeutic agents in dermatology. In this review, the findings concerning the major mechanisms of action of honokiol and magnolol are described. Knowledge of the multiple activities of honokiol and magnolol can assist with the development of honokiol and magnolol derivatives and the design of clinical trials that will maximize the potential benefit of honokiol and magnolol in the patient setting for dermatologic disorders.

Anti-herpes simplex virus effects of berberine from Coptidis rhizoma, a major component of a Chinese herbal medicine, Ching-Wei-San.

Berberine is an alkaloid extracted from Coptidis rhizome. Among the individual herbal components of a Chinese herb medicine, Ching-Wei-San, Coptidis Rhizoma has the most potent antimicrobial activity. By high-pressure liquid chromatography, the quantitative analysis of berberine from 6.25-mg/mL (w/v) Coptidis rhizome extract or 50.00-mg/mL (w/v) Ching-Wei-San was determined to be 0.26 mg/mL. To explore the potential use of Ching-Wei-San against herpes simplex virus (HSV) infection, the cytotoxicity, anti-HSV-1 and anti-HSV-2 activity in Vero cells were assayed. The selectivity index of berberine was about 1.2-1.5 times higher than that of Coptidis rhizome extract and Ching-Wei-San. Moreover, the antiviral activities correspond to the content of berberine in the aqueous solution. Berberine may interfere with the viral replication cycle after virus penetration and no later than the viral DNA synthesis step, and its activities were not affected by the preparation processes. Berberine, the natural plants that contain this component, including Coptidis rhizome, and Ching-Wei-San have all shown anti-HSV effects.

Effect of electroacupuncture on St. 36 (Zusanli) and LI. 10 (Shousanli) acupuncture points on heart rate variability.

Electrical stimulation of St. 36 (Zusanli) has been shown to enhance the regularity of gastric myoelectrical activity in healthy subjects. However, the underlying mechanism by which acupuncture alters gastric myoelectrical activity is still not clear. To elucidate the possible role of the autonomic nervous system in mediating the effect of acupuncture, we monitored heart rate variability (HRV), a widely used index of vagal discharge at the sinoatrial node of the heart before, during and after electroacupuncture. In this study, we applied two different frequencies (2 Hz and 100 Hz) of electrical stimulation at St. 36 (Zusanli) and LI. 10 (Shousanli) in 15 healthy volunteers. Low frequency (LF, sympathetic activity), high frequency (HF, vagal activity) and LF/HF ratio (sympathovagal balance) were analyzed and compared at the two different frequencies. The results showed an increase in the LF/HF ratio (indicating greater sympathetic activity) during the post-acupuncture period using 2 Hz of electrical stimulation at St. 36 (Zusanli). However, the overall change was not statistically significant. In addition, the power of LF and HF did not change significantly with electroacupuncture at St. 36 (Zusanli) and LI. 10 (Shousanli). In conclusion, applying 2 Hz or 100 Hz electroacupuncture at St. 36 (Zusanli) or LI. 10 (Shousanli) did not affect cardiovagal activity in normal volunteers. This phenomenon might be due to a difference in presentation in the autonomic nervous system between cardiac and abdominal vagal activity.

Oral antibiotics attenuate bowel segment reversal-induced systemic inflammatory response and body weight loss in massively bowel-resected rats.

BACKGROUND: Using a massively bowel-resected rat model, our previous study demonstrated that small bowel segment reversal stimulates jejunal hyperplasia but may also increase the possibility of bacterial translocation and the elevation of circulating white blood cells and serum interleukin-6 that may reduce the whole-body anabolism. The aim of this study is to investigate whether oral antibiotics might attenuate the inflammatory responses and might therefore facilitate the beneficial effects of bowel segment reversal. METHODS: Male Wistar rats (approximately 270 g) underwent a 70% small bowel resection with (REV group) or without (CON group) a 3-cm small bowel segment reversal, or underwent a sham operation (SHAM group). After surgeries, half of the animals in the REV group were given oral clindamycin plus amoxicillin (50 plus 50 mg/kg/d, ANT group) for 3 weeks. RESULTS: Oral antibiotics administration significantly attenuated the decreases in feeding efficiency (g of body weight/100 kcal diet) and increases in the circulation of white blood cells, serum nitric oxide, and interleukin-6 (1-way ANOVA, p < .05), which are associated with bowel segment reversal. In addition, antibiotics significantly increased serum concentrations of insulin-like growth factor-I, significantly decreased the total numbers of bacteria in the intestine, and tended to reduce the extent of jejunal hyperplasia in rats with bowel segment reversal. CONCLUSIONS: Our results suggest that oral antibiotics may be used as an adjuvant to attenuate the inflammatory responses and to enhance the anabolic responses in massively bowel-resected patients with bowel segment reversal.

Plasma homocysteine status in patients with ankylosing spondylitis.

Homocysteine (Hcy), a sulfur-containing amino acid, is eliminated through B vitamins-dependent pathways. Hyperhomocysteinemia has been found to be an independent risk factor for atherosclerotic cardiovascular, cerebrovascular, and peripheral vascular diseases. Recently, psoriasis, lupus, and rheumatoid arthritis were reported to be associated with hyperhomocysteinemia. This study was aimed to evaluate the changes of plasma Hcy level before and after sulfasalazine and MTX therapy in patients with ankylosing spondylitis (AS). One hundred and two patients with AS and ten normal controls were enrolled in the cross-sectional case-control study. Fasting plasma Hcy levels were determined by ELISA kits (IMX, Abbott). Hcy levels were compared to their Bath AS disease activity index (BASDAI) and the usage of sulfasalazine and/or MTX. Active disease was defined by BASDAI as more than 3 in a 10-cm scale with ESR >20 mm/h. For those patients with plasma Hcy >or=15 micromol/l, a perspective trial of daily supplement of vitamin B-12 0.5 mg, B-6 50 mg, and folic acid 5 mg for 2 weeks were also tested for the efficacy. Plasma Hcy level increased significantly in AS patients under sulfasalazine (10.4+/-3.8 micromol/l, p<0.05), MTX (11.9+/-4.7, p<0.05) and sulfasalazine/MTX combination treatment (11.2+/-2.6, p<0.05) compared with normal controls (8.6+/-1.2 micromol/l) and AS patients without DMARD(9.4+/- 2.6 micromol/l). No correlation between disease activity and plasma Hcy level was found. Daily supplement of vitamin B-12 0.5 mg, B-6 50 mg, and folic acid 5 mg can lower Hcy level in 2 weeks (32.3+/-24.0 vs 15.6+/-11.1 micromol/l, p=0.007). Plasma homocysteine level did significantly increase in AS patients under sulfasalazine or MTX treatment. B-vitamins should be considered as a routine supplementation for patients who underwent sulfasalazine and/or MTX treatment. Further longitudinal studies are required to confirm the conclusions.