Association of alprazolam with major cardiovascular events in patients with hypertension.

RATIONALE: Anxiety is a mediator for emotional reactivity and acute blood pressure elevations, which are associated with an increased risk of cardiovascular death. Alprazolam is a common medication for anxiolysis. We hypothesized that alprazolam usage can reduce the risk of major adverse cardiovascular events (MACEs) in patients with hypertension. METHODS: A retrospective cohort study was performed using datasets from Taiwanese Health and Welfare Data. Patients with hypertension were divided into exposed (Alprazolam-exposed) and control groups (non-Alprazolam-exposed) with 1:1 propensity score matching. The study endpoint was the occurrence of MACE. Adjusted hazard ratio (aHR) of MACE risk was estimated using the multiple Cox proportional hazard model. Age-stratified analysis was performed to evaluate the interaction of age and alprazolam use with MACEs. RESULTS: The study cohort consisted of 335 517 alprazolam-exposed patients and 1:1 PSM controls. The mean age was 63.62 ± 12.71 years in the Alprazolam-exposed population. Alprazolam exposure was significantly associated with reduced risk of MACEs (aHR = 0.965, 95% CI = 0.954-0.977), including ischemic stroke (aHR = 0.958, 95% CI = 0.940-0.976), hemorrhagic stroke (aHR = 0.856, 95% CI = 0.821-0.892), myocardial infarction (aHR = 0.933, 95% CI = 0.900-0.968), sudden cardiac death (aHR = 0.955, 95% CI = 0.916-0.996), and all-cause mortality (aHR = 0.921, 95% CI = 0.909-0.932). In the age-subgroup analysis, alprazolam showed the greatest risk reduction effect in hemorrhagic stroke for patients aged <65 years (aHR = 0.779, 95% CI = 0.727-0.835). CONCLUSION: Alprazolam usage in patients with hypertension was associated with a slightly reduced risk of MACEs and all-cause mortality, and up to 22% reduced risk of hemorrhagic stroke was observed in alprazolam users aged <65 years.

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.

Risk of pneumonia in patients with burn injury: a population-based cohort study.

BACKGROUND: Burns are the main cause of accidental injury, and pneumonia is a common respiratory disease in humans. AIM: The purpose of this study was to investigate the relationship between burn injury and pneumonia. PATIENTS AND METHODS: A nationwide population-based cohort study was conducted using data from the National Health Insurance Research Database in Taiwan. We identified and enrolled 2,893 subjects with burn injury, who were individually matched to 2,893 subjects in the comparison group by using the propensity score. Furthermore, we used a self-controlled case-series design to estimate the temporal association between burn injury and pneumonia. RESULTS: Exposure to burn injury revealed a higher risk of pneumonia than that to non-burn injury within 1 year. The Cox proportional hazards model revealed that, compared with the non-burn injury, burn injury yielded a 2.39-fold (95% CI=1.44-3.96) increase in risk of pneumonia. The exposure period of burn injury within 30 days showed 2.76-fold increase in risk of pneumonia (95% CI=1.44-3.96) compared with that in the baseline period. CONCLUSION: Burn injury was associated with a significant increased risk of pneumonia, especially occurring within 30 days.

Association between Proton Pump Inhibitor Use and CNS Infection Risk: A Retrospective Cohort Study.

This study investigated the incidence of central nervous system (CNS) infection following the use of proton pump inhibitors (PPIs). A retrospective cohort study was conducted in Taiwan by using data from the National Health Insurance Research Database. We identified and enrolled 16,241 patients with CNS infection who used PPIs (PPI users). The patients were individually propensity score matched (1:1) according to age, sex, hypertension, hyperlipidemia, Charlson comorbidity index (CCI), H2 blocker, non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroid, and immunosuppressant use with 16,241 controls (PPI nonusers). A Cox proportional hazards model was used to estimate adjusted hazard ratio (aHR) for CNS infection in the PPI users and nonusers. After adjustment for other confounding factors, the incidence of CNS infection in the PPI users was 2.23-fold higher than that in the PPI nonusers (95% CI = 1.27⁻3.94). In addition, the PPI users exhibited a higher risk of CNS infection than the nonusers in the hypertension and CCI = 1 groups (aHR = 3.80, 95% CI = 1.40⁻10.32; aHR = 2.47, 95% CI = 1.07⁻5.70 in the PPI users and nonusers, respectively). In conclusions, according to these results, we concluded that the incidence of CNS infection was higher in the PPI users than in the nonusers.

FUT2 genetic variants as predictors of tumor development with hepatocellular carcinoma.

Lewis antigens related to the ABO blood group are fucosylated oligosaccharides and are synthesized by specific glycosyltransferases (FUTs). FUTs are involved in various biological processes including cell adhesion and tumor progression. The fucosyltransferase-2 gene (FUT2) encodes alpha (1,2) fucosyltransferase, which is responsible for the addition of the alpha (1,2)-linkage of fucose to glycans. Aberrant fucosylation occurs frequently during the development and progression of hepatocellular carcinoma (HCC). However, the association of FUT2 polymorphisms with HCC development has not been studied. Therefore, we aimed to investigate the association of FUT2 polymorphisms with demographic, etiological, and clinical characteristics and with susceptibility to HCC. In this study, a total of 339 patients and 720 controls were recruited. The genotypes of FUT2 at four single-nucleotide polymorphisms (SNPs; rs281377, rs1047781, rs601338, and rs602662) were detected by real-time polymerase chain reaction from these samples. Compared with the wild-type genotype at SNP rs1047781, which is homozygous for nucleotides AA, at least one polymorphic T allele (AT or TT) displayed significant association with clinical stage (p = 0.048) and tumor size (p = 0.022). Our study strongly implicates the polymorphic locus rs1047781 of FUT2 as being associated with HCC development.

Tricetin suppresses human oral cancer cell migration by reducing matrix metalloproteinase-9 expression through the mitogen-activated protein kinase signaling pathway.

Tricetin is a flavonoid derivative and a potent anti-inflammatory and anticancer agent. However, the molecular mechanism underlying the effects of tricetin on human oral cancer cell migration remains unclear. The cell migration and invasion abilities of three oral cancer cell lines (SCC-9, HSC-3, and OECM-1) were analyzed using Boyden chamber migration assays. Our results demonstrated that tricetin attenuates 12-O-tetradecanoylphorbol-13-acetate-induced SCC-9, HSC-3, and OECM-1 cell invasiveness and migration by reducing matrix metalloproteinase (MMP)-9 enzyme activity. The reverse transcription polymerase chain reaction and luciferase reporter assay revealed that tricetin downregulates the mRNA expression and promoter activity of MMP-9. In addition, Western blot analysis revealed that tricetin significantly reduced the levels of phosphorylated c-Jun N-terminal kinase (JNK) 1/2 and p38 levels but not those of extracellular signal-regulated kinase 1/2. In conclusion, this study demonstrated that tricetin suppresses MMP-9 enzymatic activity by downregulating the p38/JNK1/2 pathway and might be a beneficial chemopreventive agent.

ß-mangostin suppresses human hepatocellular carcinoma cell invasion through inhibition of MMP-2 and MMP-9 expression and activating the ERK and JNK pathways.

ß-mangostin is a dietary xanthone that has been reported to have the anticancer properties in some human cancer cell types. However, the antimetastatic effect and molecular mechanism of ß-mangostin action in human hepatocellular carcinoma (HCC) cells remain unknown. In this study, we found that ß-mangostin did not induce cytotoxicity in human HCC cells (SK-Hep-1, Huh-7 and HA22T/VGH cells). ß-mangostin could inhibit migration and invasion of human HCC cells. Meanwhile, ß-mangostin significantly decreased the protein activities and expression of matrix metalloproteinase (MMP)-2 and MMP-9 via increasing the activation of MEK1/2, ERK1/2, MEK4 and JNK1/2 signaling pathways. Furthermore, using specific inhibitor for ERK1/2 (PD98059) and JNK1/2 (JNKII) significantly restored the expression of MMP-2/-9 and invasion by ß-mangostin treatment in Huh-7 cells. In addition, ß-mangostin effectively restored the protein levels and transcription activity of MMP-2 and MMP-9 in siERK or siJNK-transfected Huh-7 cells, concomitantly with promotion on cell migration and invasion. Taken together, these findings are the first to demonstrate the antimetastatic activity of ß-mangostin against human HCC cells, which may act as a promising therapeutic agent for the treatment of HCC.

Pneumonia is an independent risk factor for pyogenic liver abscess: A population-based, nested, case-control study.

BACKGROUND: Bacteremic pneumonia is considered a potential cause of distal organ abscess formation. Therefore, we hypothesize that pneumonia is a risk factor for pyogenic liver abscess (PLA).The aim of this study is to explore the association between pneumonia and PLA. METHODOLOGY/PRINCIPAL FINDINGS: A nationwide, population-based, nested, case-control study was conducted using data from the Taiwan National Health Insurance Research Database. In total, 494 patients with PLA and 1,976 propensity score matched controls were enrolled. Conditional logistic regression was used to estimate adjusted odds ratios (aORs) in patients with exposure to pneumonia before PLA. After matched and adjusted for confounding factors including age, sex, urbanization, income, chronic liver disease, alcohol-related disease, biliary stone, chronic kidney disease, diabetes mellitus, chronic liver disease, and cancer, hospitalization for pneumonia remained an independent risk factor for PLA with an aORs of 2.104 [95% confidence interval (CI) = 1.309-3.379, p = 0.0021]. Moreover, the aORs were significantly higher among patients hospitalized for pneumonia within 30 days (aORs = 10.73, 95% CI = 3.381-34.054), 30-90 days (aORs = 4.698, 95% CI = 1.541-14.327) and 90-180 (aORs = 4.000, 95% CI = 1.158-13.817) days before PLA diagnosis. CONCLUSION: Pneumonia is an independent risk factor for subsequent PLA. Moreover, hospitalization for pneumonia within 180 days before PLA diagnosis was associated with an increased risk of PLA.

Association of Proton Pump Inhibitors Usage with Risk of Pneumonia in Dementia Patients.

OBJECTIVES: To determine the association between usages of proton pump inhibitors (PPIs) and subsequent risk of pneumonia in dementia patients. DESIGN: Retrospective cohort study. SETTING: Taiwanese National Health Insurance Research Database. PARTICIPANTS: The study cohort consisted of 786 dementia patients with new PPI usage and 786 matched dementia patients without PPI usage. MEASUREMENTS: The study endpoint was defined as the occurrence of pneumonia. The Cox proportional hazard model was used to estimate the pneumonia risk. Defined daily dose methodology was applied to evaluate the cumulative and dose-response relationships of PPI. RESULTS: Incidence of pneumonia was higher among patients with PPI usage (adjusted hazard ratio (HR) = 1.89; 95% CI = 1.51-2.37). Cox model analysis also demonstrated that age (adjusted HR = 1.05; 95% CI = 1.03-1.06), male gender (adjusted HR = 1.57; 95% CI = 1.25-1.98), underlying cerebrovascular disease (adjusted HR = 1.30; 95% CI = 1.04-1.62), chronic pulmonary disease (adjusted HR = 1.39; 95% CI = 1.09-1.76), congestive heart failure (adjusted HR = 1.54; 95% CI = 1.11-2.13), diabetes mellitus (adjusted HR = 1.54; 95% CI = 1.22-1.95), and usage of antipsychotics (adjusted HR = 1.29; 95% CI = 1.03-1.61) were independent risk factors for pneumonia. However, usage of cholinesterase inhibitors and histamine receptor-2 antagonists were shown to decrease pneumonia risk. CONCLUSION: PPI usage in dementia patients is associated with an 89% increased risk of pneumonia.

Risk of pneumonia in patients with isolated minor rib fractures: a nationwide cohort study.

OBJECTIVES: Isolated minor rib fractures (IMRFs) after blunt chest traumas are commonly observed in emergency departments. However, the relationship between IMRFs and subsequent pneumonia remains controversial. This nationwide cohort study investigated the association between IMRFs and the risk of pneumonia in patients with blunt chest traumas. DESIGN: Nationwide population-based cohort study. SETTING: Patients with IMRFs were identified between 2010 and 2011 from the Taiwan National Health Insurance Research Database. PARTICIPANTS: Non-traumatic patients were matched through 1:8 propensity-score matching according to age, sex, and comorbidities (namely diabetes, hypertension, cardiovascular disease, asthma and chronic obstructive pulmonary disease (COPD)) with the comparison cohort. We estimated the adjusted HRs (aHRs) by using the Cox proportional hazard model. A total of 709 patients with IMRFs and 5672 non-traumatic patients were included. MAIN OUTCOME MEASURE: The primary end point was the occurrence of pneumonia within 30 days. RESULTS: The incidence of pneumonia following IMRFs was 1.6% (11/709). The aHR for the risk of pneumonia after IMRFs was 8.94 (95% CI=3.79 to 21.09, p<0.001). Furthermore, old age (≥65 years; aHR=5.60, 95% CI 1.97 to 15.89, p<0.001) and COPD (aHR=5.41, 95% CI 1.02 to 3.59, p<0.001) were risk factors for pneumonia following IMRFs. In the IMRF group, presence of single or two isolated rib fractures was associated with an increased risk of pneumonia with aHRs of 3.97 (95% CI 1.09 to 14.44, p<0.001) and 17.13 (95% CI 6.66 to 44.04, p<0.001), respectively. CONCLUSIONS: Although the incidence of pneumonia following IMRFs is low, patients with two isolated rib fractures were particularly susceptible to pneumonia. Physicians should focus on this complication, particularly in elderly patients and those with COPD.

Practice Variations between Emergency Physicians and Pediatricians in Treating Acute Bronchiolitis in the Emergency Department: A Nationwide Study.

BACKGROUND: Although supportive care is the mainstay management for acute bronchiolitis, non-evidence-based diagnostic testing and medications remain common in emergency departments (EDs). OBJECTIVE: Our aim was to compare emergency physicians (EPs) and pediatricians practice patterns in the management of acute bronchiolitis in the ED. METHODS: A cross-sectional study was conducted by using registration and claims datasets from 2008 to 2011. Patients with acute bronchiolitis were divided into EP group and pediatrician group. RESULTS: A total of 2174 patients were enrolled. The diagnostic tests used, including chest x-ray (63.7% vs. 46%; adjusted odds ratio [OR] = 2.27; 95% CI 1.77-2.91), complete blood count (33.2% vs. 21.8%; adjusted OR = 1.74; 95% CI 1.33-2.26), C-reactive protein (35.1% vs. 22.6%; adjusted OR = 1.79; 95% CI 1.38-2.33), blood culture (23.9% vs. 14.3%; adjusted OR = 1.79; 95% CI 1.33-2.39), and arterial blood gas (3.7% vs. 1.8%, adjusted OR = 2.38; 95% CI 1.21-4.67), were higher in the EP group than in the pediatrician group. Intravenous fluid administration was also higher in the EP group (20.8% vs. 3.5%; adjusted OR = 7.49; 95% CI 5.12-10.8). In addition, EPs more frequently arranged for hospital admissions (36% vs. 19.5%; adjusted OR = 2.51; 95% CI 1.15-3.26). CONCLUSIONS: Both EPs and pediatricians had high rates of ordering diagnostic testing for acute bronchiolitis patients in ED. Compared with pediatricians, EPs used more diagnostic tests for the patients with acute bronchiolitis in ED.

Population-based cohort study on the risk of pneumonia in patients with non-traumatic intracranial haemorrhage who use proton pump inhibitors.

OBJECTIVES: This nationwide cohort study investigated the association between proton pump inhibitor (PPI) usage and the risk of pneumonia in patients with non-traumatic intracranial haemorrhage (ICH). DESIGN: Nationwide population-based cohort study. SETTING: Longitudinal Health Insurance Database 2010 (LHID2010) sampled from the Taiwan National Health Insurance Research Database. PARTICIPANTS: 4644 patients with non-traumatic ICH from 2010 to 2011 were identified. Patients aged <18 years and newly diagnosed with non-traumatic ICH complicated with pneumonia during the same admission period were excluded. A total of 2170 participants were eligible for the final analysis. MAIN OUTCOME MEASURE: Patients using PPIs or not during the study period were tracked to identify the occurrence of any type of pneumonia. RESULTS: The adjusted HR of the risk of pneumonia for ICH patients who used PPIs was 1.61 (95% CI 1.32 to 1.97, p<0.001). The risk of pneumonia was positively associated with the administration of PPIs. We observed a greater risk of pneumonia in patients who used PPIs than in those who did not. Moreover, we observed that the risk of pneumonia in patients who used PPIs was 2.60 and 2.04 (95% CI 2.01 to 3.38, p<0.001; 95% CI 1.34 to 3.10, p<0.001) greater than that in patients who did not use PPIs when the defined daily dose was <30 and 30-60, respectively. CONCLUSIONS: The results of this study indicate that the use of PPIs in patients with non-traumatic ICH is associated with an increased risk of pneumonia, and the severity of this risk depends on the defined daily dose. Physicians should exercise caution when prescribing PPIs for patients with non-traumatic ICH.

Determinants of emergency medical utilization among the elderly population in Taiwan: a national longitudinal cohort study.

The aim of this study was to evaluate the potential determinants for emergency medical utilization by elderly patients in Taiwan. The data were drawn from the 'Survey of Health and Living Status of the Elderly in Taiwan', a population-based, longitudinal study of a nationally representative random sample of older adults aged 60 years and older, which was conducted from 1989 to 2007. Face-to-face interviews were conducted at the respondents' homes by trained interviewers accompanied by local health workers. The Andersen Behavioral Model helped us to evaluate the potential determinants for emergency medical utilization that included predisposing factors, enabling factors, and need factors. The measurements of determinants were repeated five times in the period of this study, and the longitudinal data were analyzed through the generalized estimating equation (GEE) by SPSS 17.0 software. The eligibility criteria were that respondents had to be more than 65 years old at baseline in 1993, and then they had to be enrolled in a 14-year follow-up period from 1993 to 2007. At the beginning of this study in 1993, there were 2961 eligible respondents in total, and in 2007, there were 1136 survivors. The loss in follow-up was mainly due to death. The results demonstrated that the significant determinants of emergency medical utilization by the elderly population were gender, age, education, self-ranked health status, chronic disease, and medical accessibility. The GEE model provides a suitable method to predict the long-term trend of emergency medical utilization by the elderly.

Macrophage migration inhibitory factor induces ICAM-1and thrombomobulin expression in vitro.

Macrophage migration inhibitory factor (MIF) is an important cytokine in the modulation of inflammatory and immune responses, but its role in coagulation remains to be elucidated. In this study, we investigated the potential role of MIF in coagulation through its influence on two factors, thrombomodulin (TM) and intercellular adhesion molecule-1 (ICAM-1). Recombinant human MIF was added to human microvascular endothelial cell line (HMEC-1) to investigate its influence on the expression of TM and ICAM-1. The results showed that both TM and ICAM-1 were induced with MIF addition in a dose-dependent and time-dependent manner. The expression of ICAM-1 and TM was increased as MIF doses were increased, with the highest expression seen at 12 hr after 400 ng/ml of MIF treatment. Besides, anti-MIF antibody treatment reduced the TM expression in HMEC-1 cells. In conclusion, our data support a role of MIF as an important factor in the regulation of coagulation.

Curcumin alleviates eosinophilic meningitis through reduction of eosinophil count following albendazole treatment against Angiostrongylus cantonensis in mice.

Angiostrongylus cantonensis (A. cantonensis) is the most common cause of parasitic eosinophilic meningitis worldwide. By using an animal model of BALB/c mice infected with A. cantonensis, previous studies indicated that the anthelmintic drug, albendazole, could kill A. cantonensis larvae and prevent further infection. However, the dead larvae will induce severe immune responses targeting at brain tissues. To alleviate the detrimental effects caused by the dead larvae, we administered curcumin, a traditional anti-inflammatory agent, as a complementary treatment in addition to albendazole therapy, to determine whether curcumin could be beneficial for treatment. The results showed that although curcumin treatment alone did not reduce worm number, combined treatment by albendazole and curcumin helped to reduce eosinophil count in the cerebrospinal fluid, better than using albendazole alone. This alleviating effect did not affect albendazole treatment alone, since histological analysis showed similar worm eradication with or without addition of curcumin. Nevertheless, curcumin treatment alone and combined albendazole-curcumin treatment did not inhibit MMP-9 expression in the brain tissue. In conclusion, curcumin, when used as a complementary treatment to albendazole, could help to alleviate eosinophilic meningitis through suppression of eosinophil count in the cerebrospinal fluid.

Comamonas testosteroni infection in Taiwan: Reported two cases and literature review.

Comamonas testosteroni is a widely distributed aerobic gram-negative bacillus. Infection by C testosteroni is infrequent, and no such cases have been reported in Taiwan. Here, we would like to present a 54-year-old alcoholic patient from Taiwan, and his left leg was injured during a fishing trip, resulting in left leg cellulitis and C testosteroni bacteremia. The patient's fever subsided after initial treatment with extended-spectrum cephalosporin, whereas his erythematous swelling did not resolve until switched to ciprofloxacin. The second patient is a 73-year-old Taiwanese male with chronic hepatitis B infection, liver cirrhosis, and hepatocellular carcinoma. Comamonas testosteroni bacteremia was found after transarterial embolization. Further studies are necessary to determine the best antibiotic(s) for patients infected with C testosteroni.

SLC34A2 as a novel marker for diagnosis and targeted therapy of breast cancer.

The purpose of this study was to estimate the role of the SLC34A2 gene in breast cancer. A total of 146 samples were collected from breast cancer tissues and their adjacent normal breast tissues. Reverse transcription and real-time polymerase chain reaction were used to estimate gene expression levels. There was a significantly increased gene expression of SLC34A2 (normal tissues: 6.71±0.77; tumour tissues: 10.29±0.80) among breast cancer tissues compared with normal tissues. However, there was no significant association between overall survival and the gene expression level of SLC34A2. Moreover, a significant overexpression of CA125 (normal tissues: 7.26±0.62; tumour tissues: 10.51±0.58) in breast cancer tissues and a significant correlation between SLC34A2 and CA125 gene expressions were found. Our results suggested SLC34A2 to be involved in the development of breast cancer; this gene may therefore be a novel marker for the detection of breast cancer and act as a target gene in therapeutic strategies.

Quercetin-mediated cell cycle arrest and apoptosis involving activation of a caspase cascade through the mitochondrial pathway in human breast cancer MCF-7 cells.

Dietary polyphenols have been correlated with a reduced risk of developing cancer. Quercetin (a natural polyphenolic compound) induced apoptosis in many human cancer cell lines, including breast cancer MCF-7 cells. However, the involvement of possible signaling pathways and the roles of quercetin in apoptosis are still undefined. The purpose of this study was to investigate the effects of quercetin on the induction of the apoptotic pathway in human breast cancer MCF-7 cells. When MCF-7 cells were treated with quercetin for 24 and 48 h and at various doses (10-175 microM), cell viability decreased significantly in time- and dose-dependent manners. Exposure of MCF-7 cells to 10-175 microM quercetin resulted in an approximate 90.25% decrease in viable cells. To explicate the mechanism underlying the antiproliferative effect of quercetin, cell cycle distribution and apoptosis in MCF-7 cells was investigated after exposure to 150 microM quercetin for 6-48 h. Quercetin caused a remarkable increase in the number of S phase (14.56% to 61.35%) and sub-G1 phase cells (0.1% to 8.32%) in a dose- and time-dependent manner. Quercetin caused S phase arrest by decreasing the protein expression of CDK2, cyclins A and B while increasing the p53 and p57 proteins. Following incubation with quercetin for 48 h, MCF-7 cells showed apoptotic cell death by the decreased levels of Bcl-2 protein and DeltaPsi(m) and increased activations of caspase-6, -8 and -9. Moreover, quercetin increased the AIF protein released from mitochondria to nuclei and the GADD153 protein translocation from endoplasmic reticulum to the nuclei. These data suggested that quercetin may induce apoptosis by direct activation of the caspase cascade through the mitochondrial pathway in MCF-7 cells.