The role of exosomal lncRNAs in acetaminophen-induced induced liver injury in SD rats.

Background: Drug-induced liver injury (DILI) is a leading cause of drug development failures during clinical trials and post-market introduction. Current biomarkers, such as ALT and AST, lack the necessary specificity and sensitivity needed for accurate detection. Exosomes, which protect LncRNAs from RNase degradation, could provide reliable and easily accessible options for biomarkers. Materials and methods: RNA-sequencing was used to identify differentially expressed LncRNAs (DE-LncRNAs), followed by isolation of LncRNAs from plasma exosomes in this study. Exosome characterization was conducted by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blot (WB). Bioinformatics analysis included functional enrichment and co-expression network analysis. Five rat models were established, and quantitative real-time PCR was used to verify the specificity and sensitivity of two candidate exosomal LncRNAs. Results: The APAP-induced hepatocellular injury model was successfully established for RNA-sequencing, leading to the identification of several differentially expressed exosomal LncRNAs. Eight upregulated exosomal DE-LncRNAs were selected for validation. Among them, NONRATT018001.2 (p < 0.05) and MSTRG.73954.4 (p < 0.05) exhibited a more than 2-fold increase in expression levels. In hepatocellular injury and intrahepatic cholestasis models, both NONRATT018001.2 and MSTRG.73954.4 showed earlier increases compared to serum biomarkers ALT and AST. However, no histological changes were observed until the final time point. In the fatty liver model, NONRATT018001.2 and MSTRG.73954.4 increased earlier than ALT and AST at 21 days. By the 7th day, minor steatosis was evident in liver tissue, while the expression levels of the two candidate exosomal LncRNAs exceeded 2 and 4 times, respectively. In the hepatic fibrosis model, NONRATT018001.2 and MSTRG.73954.4 showed increases at every time point. By the 49th day, hepatocellular necrosis and fibrosis were observed in the liver tissue, with NONRATT018001.2 showing an increase of more than 8 times. The specificity of the identified exosomal DE-LncRNAs was verified using a myocardial injury model and they showed no significant differences between the case and control groups. Conclusion: NONRATT018001.2 and MSTRG.73954.4 hold potential as biomarkers for distinguishing different types of organ injury induced by drugs, particularly enabling early prediction of liver injury. Further experiments, such as siRNA interference or gene knockout, are warranted to explore the underlying mechanisms of these LncRNAs.

Effect of plasma exosome lncRNA on isoproterenol hydrochloride-induced cardiotoxicity in rats.

Isoprenaline hydrochloride (IH) is a ß-adrenergic receptor agonist commonly used in the treatment of hypotension, shock, asthma, and other diseases. However, IH-induced cardiotoxicity limits its application. A large number of studies have shown that long noncoding RNA (lncRNA) regulates the occurrence and development of cardiovascular diseases. This study aimed to investigate whether abnormal lncRNA expression is involved in IH-mediated cardiotoxicity. First, the Sprague-Dawley (SD) rat myocardial injury model was established. Circulating exosomes were extracted from the plasma of rats and identified. In total, 108 differentially expressed (DE) lncRNAs and 150 DE mRNAs were identified by sequencing. These results indicate that these lncRNAs and mRNAs are substantially involved in chemical cardiotoxicity. Further signaling pathway and functional studies indicated that lncRNAs and mRNAs regulate several biological processes, such as selective mRNA splicing through spliceosomes, participate in sphingolipid metabolic pathways, and play a certain role in the circulatory system. Finally, we obtained 3 upregulated lncRNAs through reverse transcription-quantitative PCR (RT-qPCR) verification and selected target lncRNA-mRNA pairs according to the regulatory relationship of lncRNA/mRNA, some of which were associated with myocardial injury. This study provides valuable insights into the role of lncRNAs as novel biomarkers of chemical-induced cardiotoxicity.

Exosomal Long Noncoding RNAs Serve as Biomarkers for Liver Disease.

Exosomes are tiny vesicles secreted by cells, with a diameter of 40-160 nm, which contain proteins, DNA, mRNA, long noncoding RNA, etc. Because of the low sensitivity and specificity of the conventional biomarkers for liver diseases, it is of utmost importance to discover novel, sensitive, specific, and non-invasive biomarkers. Exosomal long noncoding RNAs have been considered as potential diagnostic, prognostic, or predictive biomarkers in a wide range of liver pathologies. In this review, we discuss the recent progress on exosomal long noncoding RNAs that serve as potential diagnostic, prognostic, or predictive markers and molecular targets in patients with hepatocellular carcinoma, cholestatic liver injury, viral hepatitis, and alcohol-related liver diseases.

Preclinical safety profile of RC88-ADC：a novel mesothelin-targeted antibody conjugated with Monomethyl auristatin E.

Mesothelin (MSLN) is an attractive therapeutic target for antibody drug conjugates (ADC) because of significant differences in expression pattern between diseased and normal tissues. RC88-ADC is a novel ADC, targeting MSLN, and inhibits tumor growth significantly in mice xenograft models. We performed an 11-week repeated dose toxicity study of RC88-ADC via intravenous injection in Cynomolgus Monkeys with an 8-Week recovery period according to International Conference on Harmonization (ICH) S9 and S6(R1). RC88-ADC was administered to groups of 5 male and 5 female monkeys at dose levels of 2.5, 5, and 10 mg/kg/2 weeks, meanwhile vehicle, naked antibody, small molecule groups were set up as the control. 4 animals died in 10 mg/kg group of RC88-ADC. The clinical symptoms mainly included ocular toxicity, weight loss and food intake decrease in the middle and high dose groups of RC88-ADC. RC88-ADC caused dose-related reversible myelosuppression, manifested as hematologic toxicity, which was consistent with the small molecule toxicity profile of its coupling. The highest non-severely toxic dose of RC88-ADC was 5 mg/kg in monkeys after repeated dosing. Nonetheless, the integrated analysis showed that RC88-ADC demonstrated an acceptable safety profile and provided an improved treatment window. These results pave the way for further investigation of RC88-ADC in humans.

A 90-day Sub-chronic Oral Toxicity Assessment of Mulberry Extract in Sprague Dawley Rats.

Mulberry extract from Fructus Mori contains an anthocyanin pigment and has been widely used as a food additive in China and other Eastern Asian countries. Only few research has been done on toxicological profiling of mulberry extract for its safety evaluation; however, the data is inconclusive. In the current study, mulberry extract of 4200, 1400, or 466 mg/kg were orally administrated to Sprague Dawley rats for 90 consecutive days followed by a recovery period of 28 days. No abnormalities were detected in body weights, food intake, ophthalmological, hematological, coagulation, clinical chemistry, and organ weights parameters. Discoloration of urine (red, purple, and brown) and feces (black), along with bedding material (purple) were observed in the 4200 mg/kg group. Further, microscopic examination revealed brown granules in the renal tubular cells for rats in 4200 and 1400 mg/kg groups. Since these changes were associated with excretory effect of the extract, the No Observed Adverse Effect Level was determined to be 4200 mg/kg, which was equivalent to the 1058.5 mg/kg of anthocyanin.

Safety reassessment of cinobufotalin injection: new findings into cardiotoxicity.

Cinobufotalin injection, a traditional Chinese medicine preparation, successfully used for several years, might induce cardiotoxicity. The aim of the study was to evaluate the cardiotoxicity of cinobufotalin injection and the cardiotoxicity-preventive effect of sodium phenytoin in vivo. According to the 4 × 4 Latin square design, four Beagle dogs were allocated into four dose levels of 0, 0.3, 1, and 3 g/kg in treatment phases I-IV (cinobufotalin injection) and 3 g/kg in treatment phase V (cardiotoxicity antidote). The following parameters and endpoints were assessed: clinical observations, body weight, indicators of myocardial injury, and electrocardiogram (ECG) parameters. The cinobufotalin injection-related changes were observed in clinical observations (rapid breathing pattern), indicators of myocardial injury (increased cardiac troponin I, creatine kinase isoenzymes, and aspartate aminotransferase), and ECG graphics (arrhythmia) at 3 g/kg concentration in treatment phases I-IV. The cardiotoxicity of cinobufotalin injection was attenuated by sodium phenytoin in treatment phase V. The results confirmed the cardiotoxicity of cinobufotalin injection, and they might bring information about the appropriate monitoring time points and cardiotoxicity parameters in clinical practices and shed light on the treatment of cardiovascular adverse reactions.

Effects of miR-503-5p on apoptosis of human pulmonary microvascular endothelial cells in simulated microgravity.

Recent studies have shown that microRNA (miRNAs) can play important roles in the regulation of endothelial cell (EC) function. However, the expression profile of miRNAs and their effects on the apoptosis of ECs under microgravity conditions remains unclear. In this study, the apoptosis of human pulmonary microvascular endothelial cells (HPMECs) under simulated microgravity was identified by Annexin V and propidium iodide double staining and transmission electron microscopy. miRNA microarray assay was used to screen the differentially expressed miRNAs in HPMECs under simulated microgravity, and eight differentially expressed miRNAs were identified. Specifically, miR-503-5p, which was found to be most significantly upregulated in both microarray and quantitative reverse-transcription polymerase chain reaction assays, was selected for further functional investigation. Overexpression of miR-503-5p induced apoptosis of HPMECs under normal gravity and aggravated the negative effects of simulated microgravity on HPMECs. Furthermore, silencing of miR-503-5p expression effectively attenuated the negative effects of simulated microgravity on HPMECs. Further experiments showed that the mRNA and protein expression of anti-apoptotic factor B-cell lymphoma-2 (Bcl-2), which has been confirmed as a direct target of miR-503-5p, was inhibited by the upregulation of miR-503-5p and increased by the downregulation of miR-503-5p. Taken together, our findings demonstrate, for the first time, that miR-503-5p can induce apoptosis of HPMECs under simulated microgravity through, at least in part, inhibiting the expression of Bcl-2.

Risk/benefit profile of panitumumab-based therapy in patients with metastatic colorectal cancer: evidence from five randomized controlled trials.

This study aims to evaluate the risk and benefit profiles of panitumumab-based therapy (PBT) in patients with metastatic colorectal cancer (mCRC). Relevant randomized controlled trials were identified by searching PubMed, Medline, EMBASE and Cochrane Library. Data on progression-free survival (PFS), overall survival (OS), all grade and severe (grade ≥3) adverse events were extracted and pooled to calculate hazard ratios (HRs) and risk ratios (RRs) with 95 % confidence intervals (CIs). Number needed to treat (NNT) for PFS and number needed to harm (NNH) for significantly changed toxicities were calculated. A total of 4,155 patients were included in the analysis. PBT significantly improved PFS (HRrandom = 0.66, 95 % CI = 0.45-0.95) but not OS (HRfixed = 0.93, 95 % CI = 0.83-1.04) when used in the subsequent-line setting. The effect on PFS was more evident in patients with wild-type KRAS (HRrandom = 0.64, 95 % CI = 0.47-0.87) and the NNT for PFS is 11 to 23at 1 year. PBT did not benefit patients when used in the first-line setting. In addition, PBT significantly increased the risk of skin toxicity, infections, diarrhea, dehydration, mucositis, hypokalemia, fatigue, hypomagnesemia, pulmonary embolism and paronychia. The NNHs for skin toxicity, diarrhea, infection, hypokalemia and mucositis are less than 23. In conclusion, when used in the subsequent-line setting, PBT can improve the disease progression, especially in mCRC patients with wild-type KRAS. Regarding the adverse events associated with the PBT, close monitoring and necessary preparations are recommended during the therapy.

Time-series pattern of gene expression profile in gentamycin-induced nephrotoxicity.

There have been many studies investigating the genomic biomarker and/or molecular mechanism of nephrotoxicity using microarray. However, most of these researches were carried out by studying gene expression changes at one specific time point. As gene expression varies with time and disease stage, the current study investigated the time-series pattern of gene expression in a rat model using a typical nephrotoxic compound. Rats were administrated with 80 mg/kg gentamycin or saline by intramuscular injection for 14 consecutive days followed by a 28-d recovery. Rats were scarified on D2, D4, D8, D15 and Recovery Day (R29), when kidneys were obtained for whole-genome microarray analysis and histological examination. Urine was collected at each necropsy for kidney injury molecular-1 (KIM-1) analysis. The KIM-1 detection and histological examination confirmed the nephrotoxicity. After differentially expression genes (DEGs) identification, there were 4360 and 4323 regulated genes for females and males, respectively. However, few overlapping expression genes co-regluated at each time point were found. By principle component analysis (PCA) and hierarchical cluster, the gene expression patterns were observed to be apparently associated with the disease stage. GO Annotation showed (1) immune response and related process, response to wounding, cell locomotion on D2; (2) cell death and apoptosis was also noted on D4; (3) processes of organic acid or carboxylic acid, apoptosis or cell death on D8 and D15; (4) processes of cell cycle, mitosis, division cell cycle on R29. In conclusion, the authors mapped the time-series gene expression patterns at the initiation, development and recovery stage of gentamycin-induced nephrotoxicity.

[The effects of microgravity on blood vessels and vascular endothelial cells].

The dysfunction of vascular system is one of the main causes of orthostatic intolerance induced by microgravity. Vascular endothelial cell is a single layer on the inner wall of the blood vessel and is the important component of the blood vessel wall. Vascular endothelial cell plays a pivotal role in the regulation of vascular functions, such as serving as a permeability barrier, regulating vasoconstriction and vasodilatation. Recent studies have demonstrated that microgravity may have different effects on vascular sys- tem and vascular endothelial cells in different parts of the body, such as increasing vasoconstrictor reactivity and decreasing vasodilator reactivity of cerebral arteries, decreasing vasoconstrictor and vasodilator reactivity of carotid and abdominal aortic arteries, decreasing vasoconstrictor reactivity and increasing vasodilator reactivity of pulmonary arteries, decreasing vasoconstrictor reactivity of mesenteric arteries and veins and lower extremity arteries. In addition, microgravity can promote the growth of vascular endothelial cells in the large vessels and inhibit the growth of microvascular endothelial cells. This paper summarized the research progress in the effects of microgravity on blood vessels and vascular endothelial cells.

Identification of endogenous reference genes for RT-qPCR analysis of plasma microRNAs levels in rats with acetaminophen-induced hepatotoxicity.

Circulating microRNA (miRNA) expression profiles have been reported to be promising biomarkers for drug-induced liver injury in preclinical and clinical practice. Proper normalization is critical for accurate miRNAs expression analysis. Herein, using SYBR green quantitative real-time PCR (RT-qPCR), we evaluated the expression stability of six candidate reference genes including two commonly used small RNAs (U6, 5S) and four miRNAs (let-7a, miR-92a, miR-103 and miR-16) in plasma of rats with acetaminophen-induced hepatotoxicity. Data were analysed using geNorm, Normfinder, BestKeeper and comparative delta-Ct statistical models, and the results consistently show that miR-103 is the most stably expressed reference gene. Whereas the commonly used housekeeping genes 5S or U6 are all not suitable normalizers, because 5S exhibits extensive variability in expression and U6 has a low expression level across the plasma samples. Then the effect of reference genes on normalization of plasma miR-122 was assessed; when normalized to the most stable reference gene there were significant differences between the acetaminophen-treated group and the vehicle group. However, when the data were normalized to a less stably expressed gene, miR-16, a biased result was obtained. Therefore, we recommend that miR-103 as suitable reference gene for plasma miRNAs analysis for acetaminophen-induced liver injury. Data presented in this paper are crucial to successful biomarker discovery and validation for the diagnosis of the early stage of acetaminophen hepatotoxicity.

Myeloperoxidase G-463A polymorphism and susceptibility to coronary artery disease: a meta-analysis.

Published data on the association between the myeloperoxidase (MPO) G-463A polymorphism and coronary artery disease (CAD) are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis on this topic was performed. PubMed, EMBASE and Chinese national knowledge infrastructure were searched for studies regarding the association between the MPO G-463A polymorphism and CAD. A logistic regression analysis was used to estimate the genetic effect and the possible genetic model of action. Summary odds ratios (ORs) with their corresponding 95% confidence intervals (CIs) were calculated. There was strong evidence for an association between the MPO G-463A polymorphism and CAD. The genetic model of action was most likely to be co-dominant. Overall, the data showed that AA and GA genotypes were significantly associated with reduced risk of CAD (AA vs. GG: OR=0.37, 95% CI=0.17-0.78; GA vs. GG: OR=0.73, 95% CI=0.57-0.92). In subgroup analyses by study population and sources of controls, statistically significant results were observed in the Chinese population (AA vs. GG: OR=0.21, 95% CI=0.10-0.43; GA vs. GG: OR=0.57, 95% CI=0.44-0.74) and in hospital-based control studies (AA vs. GG: OR=0.20, 95% CI=0.10-0.39; GA vs. GG: OR=0.61, 95% CI=0.48-0.77). This meta-analysis suggests that the MPO G-463A variant genotypes may be associated with decreased risk of CAD. However, given the limited number of studies and the potential biases, the influence of this polymorphism on CAD risk needs further investigation.

A polymorphism in the visfatin gene promoter is related to decreased plasma levels of inflammatory markers in patients with coronary artery disease.

Visfatin, a newly identified proinflammatory adipokine, has been linked to coronary artery disease (CAD). The -1535C>T polymorphism (rs61330082) located in the visfatin gene promoter is reportedly associated with proinflammatory status. However, it is unclear whether this polymorphism correlates with plasma levels of inflammatory markers including visfatin, hs-CRP, IL-6 and TNF-α in CAD patients. The present study was to investigate the potential association of the -1535C>T polymorphism with plasma levels of visfatin, IL-6, C reactive protein (hs-CRP) and TNF-α in patients with CAD. We conducted a hospital based study with 171 CAD patients to examine the association between the -1535C>T polymorphism and plasma levels of visfatin, hs-CRP, IL-6 and TNF-α. Plasma visfatin levels were markedly different between patients with stable angina pectoris (SAP, 11.91 ± 0.70 ng/l) and those with unstable angina pectoris (UAP, 17.49 ± 0.20 ng/l) or acute myocardial infarction (AMI, 16.63 ± 0.22 ng/l; SAP versus UAP or AMI, P < 0.05). Compared with the CC genotype, variant genotypes CT and TT correlated with significantly lower levels of visfatin, hs-CRP, IL-6 and TNF-α in the SAP group (P < 0.05), with lower levels of hs-CRP and IL-6 in the UAP group (P < 0.05), and with lower levels of visfatin in the AMI group (P < 0.05) after adjustment for age, gender, smoking, hypertension, diabetes, dyslipidemia and medication. Our results suggest that the -1535C>T polymorphism is associated with decreased plasma levels of inflammatory markers in CAD patients, reflecting that this polymorphism might provide a useful marker for predicting the development of CAD events.

Coffee consumption and risk of lung cancer: a meta-analysis.

Epidemiologic studies have evaluated the potential association between coffee consumption and lung cancer risk. However, results were inconsistent. To clarify the role of coffee in lung cancer, we conducted a meta-analysis on this topic. We searched PubMed and EMBASE databases (from 1966 to January 2009) and the reference lists of retrieved articles. Study-specific risk estimates were pooled using random-effects model. Five prospective studies and 8 case-control studies involving 5347 lung cancer cases and 104,911 non-cases were included in this meta-analysis. The combined results indicated a significant positive association between highest coffee intake and lung cancer [relative risk (RR)=1.27, 95% confidence interval (CI)=1.04-1.54). Furthermore, an increase in coffee consumption of 2 cups/day was associated with a 14% increased risk of developing lung cancer (RR=1.14, 95% CI=1.04-1.26). In stratified analyses, the highest coffee consumption was significantly associated with increased risk of lung cancer in prospective studies, studies conducted in America and Japan, but borderline significantly associated with decreased risk of lung cancer in non-smokers. In addition, decaffeinated coffee drinking was associated with decreased lung cancer risk, although the number of studies on this topic was relative small. In conclusion, results from this meta-analysis indicate that high or an increased consumption of coffee may increase the risk of lung cancer. Because the residual confounding effects of smoking or other factors may still exist, these results should be interpreted with caution.

Genetic variant in visfatin gene promoter is associated with decreased risk of coronary artery disease in a Chinese population.

BACKGROUND: Visfatin is a newly identified pro-inflammatory adipokine expressed predominantly in visceral fat. Previous studies have suggested a role for visfatin in low-grade inflammation and regulation of lipid metabolism. Most recently, a genetic polymorphism -1535C>T located in the visfatin gene promoter has been identified, and suggested to be associated with the regulation of visfatin expression, lipid levels. However, it is unclear whether this polymorphism has a linkage with CAD. METHODS: We conducted a hospital-based case-control study with 257 CAD patients and 292 controls to examine the potential association of the Visfatin -1535C>T polymorphism with CAD. RESULTS: The frequencies of the CC, CT, and TT genotypes in cases were significantly different from those of controls (chi2=6.223, P=0.045). Subjects with the variant genotypes (CT+TT) had a 40% decreased risk of CAD relative to CC carriers (adjusted OR=0.60, 95%CI=0.40-0.89). Furthermore, the adjusted OR of a TT genotype for CAD was 0.52 (95%CI=0.31-0.87). There was a significant association between Visfatin -1535C>T polymorphism and triglyceride levels in both CAD patients and controls (P=0.003, 0.018, respectively). In stratified analyses, the T allele was significantly associated with reduced risk of CAD in males, subjects with age <59years, and non-smokers. Moreover, a borderline statistical significance (P=0.058 for trend) was observed between the variant genotypes and severity of CAD. CONCLUSION: Our results suggested that Visfatin -1535C>T polymorphism might be associated with reduced risk of CAD in a Chinese population.

Tea consumption and risk of endometrial cancer: a metaanalysis.

OBJECTIVE: The objective of the study was to assess the association between tea consumption and endometrial cancer. STUDY DESIGN: Studies were identified by searching PubMed and EMBASE databases and screening the references of retrieved articles. The summary relative risk (RR) with 95% confidence interval (CI) was calculated. RESULTS: The combined RR for ever drinkers vs non/lowest drinkers was 0.85 (95% CI, 0.77-0.94). Compared with non/lowest drinkers, the summary RR was 0.88 (95% CI, 0.78-0.98) for low to moderate drinkers and 0.75 (95% CI, 0.64-0.88) for high drinkers. An increase in tea intake of 2 cups/day was associated with a 25% decreased risk of endometrial cancer. In subgroup analyses, tea consumption was significantly associated with reduced endometrial cancer risk in Asian studies and studies using interviewing techniques. Furthermore, the protective effect of green tea on endometrial cancer seemed more evident than that of black tea. CONCLUSION: Findings from this metaanalysis suggest that tea consumption may reduce the risk of endometrial cancer. Because of the limited number of studies, further prospective studies are needed to explore the protective effect of tea on endometrial cancer.

HTRA1 promoter polymorphism and risk of age-related macular degeneration: a meta-analysis.

PURPOSE: To clarify the role of human high-temperature requirement A-1 (HTRA1) gene promoter polymorphism (-512G>A) in age-related macular degeneration (AMD). METHODS: Relevant studies were identified by searching PubMed and EMBASE database. A logistic regression analysis proposed for molecular association studies was carried out to estimate the genetic effect and the possible genetic model of action. RESULTS: Fourteen case-control studies were included in this meta-analysis. There was strong evidence for an association between HTRA1 -512G>A polymorphism and AMD (p < 0.001). The genetic model test indicated that the genetic model was most likely to be co-dominant. Overall, our meta-analysis showed that AA and GA genotypes were associated with increased risk of AMD (AA vs. GG: odds ratio(1) [OR(1)] = 7.46; 95% confidence interval [CI] = 6.16-9.04; GA vs. GG: OR(2) = 2.27, 95% CI = 2.02-2.55). In stratified analysis by ethnicity and age, the genetic effect seemed to be stronger in Caucasians and subjects > or =73 years of age than in Asians and subjects <73 years of age. When subgroup analysis was conducted by AMD type, significant association was noted for wet AMD but not for dry AMD. CONCLUSIONS: This meta-analysis summarizes the strong evidence for an association between HTRA1 -512G>A polymorphism and AMD and indicates a co-dominant model of action.

Flavonoids intake and risk of lung cancer: a meta-analysis.

OBJECTIVE: A number of studies have evaluated the association between flavonoids intake and lung cancer risk. However, results were inconsistent. To clarify the role of flavonoids in lung cancer, we conducted a meta-analysis on this topic. METHODS: Two authors independently searched PubMed and EMBASE for studies regarding the association of flavonoids intake with lung cancer risk. Summary relative risks (RRs) with their corresponding 95% confidence intervals (CIs) were calculated by using random-effects model. RESULTS: Eight prospective studies and four case-control studies involving 5073 lung cancer cases and 237 981 non-cases were included in this meta-analysis. The combined results indicated a statistically significant association between highest flavonoids intake and reduced risk of developing lung cancer (RR = 0.76, 95% CI = 0.63-0.92). Furthermore, an increase in flavonoids intake of 20 mg/day was associated with a 10% decreased risk of developing lung cancer (RR = 0.90, 95% CI = 0.83-0.97). In stratified analyses, the highest flavonoids intake was significantly associated with decreased lung cancer risk in prospective studies, studies conducted in Finnish population, studies without adjustment for fruits and vegetables or vitamins, males, smokers and studies using dietary history interview for flavonoids intake estimation. Most subclasses of flavonoids were inversely associated with lung cancer except for hesperetin. CONCLUSIONS: Our data indicate that high or an increased intake of flavonoids is associated with reduced risk of lung cancer in some population but not in other population.

Green tea, black tea consumption and risk of lung cancer: a meta-analysis.

Studies investigating the association of green tea and black tea consumption with lung cancer risk have reported inconsistent findings. To provide a quantitative assessment of this association, we conducted a meta-analysis on the topic. Studies were identified by a literature search in PubMed from 1966 to November 2008 and by searching the reference lists of relevant studies. Summary relative risk (RR) estimates and their corresponding 95% confidence intervals (CIs) were calculated based on random-effects model. Our meta-analysis included 22 studies provided data on consumption of green tea or black tea, or both related to lung cancer risk. For green tea, the summary RR indicated a borderline significant association between highest green tea consumption and reduced risk of lung cancer (RR=0.78, 95% CI=0.61-1.00). Furthermore, an increase in green tea consumption of two cups/day was associated with an 18% decreased risk of developing lung cancer (RR=0.82, 95% CI=0.71-0.96). For black tea, no statistically significant association was observe through the meta-analysis (highest versus non/lowest, RR=0.86, 95% CI=0.70-1.05; an increment of two cups/day, RR=0.82, 95% CI=0.65-1.03). In conclusion, our data suggest that high or an increase in consumption of green tea but not black tea may be related to the reduction of lung cancer risk.

Coffee consumption and risk of breast cancer: a metaanalysis.

OBJECTIVE: This metaanalysis was conducted to assess the association between coffee consumption and breast cancer risk. STUDY DESIGN: Relevant studies were identified by searching Medline (1966-May 2008) and the reference lists of retrieved articles. The summary relative risk (RR) with 95% confidence interval (CI) was calculated using a random-effects model. RESULTS: Nine cohort and 9 case-control studies met the inclusion criteria. The combined RR showed a borderline significant influence of highest coffee consumption (RR, 0.95; 95% CI, 0.90-1.00) or an increment of 2 cups/day of coffee consumption (RR, 0.98; 95% CI, 0.96-1.00) on the risk of breast cancer. In stratified analysis, borderline significant associations were observed among cohort and case-control studies and studies conducted in Europe and the United States. However, no significant association was noted among studies conducted in Asia. CONCLUSION: Our findings suggest a possible influence of high coffee consumption or an increased coffee consumption on the risk of breast cancer.