MicroRNAs (miRNAs) are believed to have fundamental roles in tumorigenesis and have great potential for the diagnosis and treatment of cancer. However, the roles of miRNAs in hepatocellular ...carcinogenesis are still not fully elucidated. We investigated the aberrantly expressed miRNAs involved in hepatoma by comparison of miRNA expression profiles in cancerous hepatocytes with normal primary human hepatocytes, and 37 dysregulated miRNAs were screened out by twofold change with a significant difference (P<0.05). Clustering analysis based on 13 miRNAs with changes over 15-folds showed that the miRNA expression patterns between the cancerous and normal hepatocytes were clearly different. Among the 13 miRNAs, we found that miR-375 was significantly downregulated in hepatocellular carcinoma (HCC) tissues and cell lines. Overexpression of miR-375 in liver cancer cells decreased cell proliferation, clonogenicity, migration/invasion and also induced G1 arrest and apoptosis. To unveil the molecular mechanism of miR-375-mediated phenotype in hepatoma cells described above, we examined the putative targets using bioinformatics tools and found that astrocyte elevated gene-1 (AEG-1) was a potential target of miR-375. Then we demonstrated that miR-375 bound directly to the 3'-untranslated region of AEG-1 and inhibited the expression of AEG-1. TaqMan quantitative reverse transcriptase-PCR and western blot analysis showed that miR-375 expression was inversely correlated with AEG-1 expression in HCC tissues. Knockdown of AEG-1 by RNAi in HCC cells, similar to miR-375 overexpression, suppressed tumor properties. Ectopic expression of AEG-1, conversely, could partially reverse the antitumor effects of miR-375. In a mouse model, therapeutic administration of cholesterol-conjugated 2'-O-methyl-modified miR-375 mimics (Chol-miR-375) could significantly suppress the growth of hepatoma xenografts in nude mice. In conclusion, our findings indicate that miR-375 targets AEG-1 in HCC and suppresses liver cancer cell growth in vitro and in vivo, and highlight the therapeutic potential of miR-375 in HCC treatment.
Summary
Background
Peptic ulcer bleeding remains a major healthcare problem despite decreasing prevalence of peptic ulcer disease. The role of chronic obstructive pulmonary disease (COPD) in the risk ...of peptic ulcer bleeding has not yet been established.
Aim
To determine if COPD patients have a higher risk of peptic ulcer bleeding than the general population and to identify the risk factors of peptic ulcer bleeding in COPD patients.
Methods
From Taiwan's National Health Insurance research database, 62 876 patients, including 32 682 COPD and 30 194 age‐gender‐matched non‐COPD controls, were recruited. Cox proportional hazard regression was performed to evaluate independent risk factors for ulcer bleeding in all patients and to identify risk factors in COPD patients.
Results
During the 8‐year follow‐up, COPD patients had a significant higher rate of peptic ulcer bleeding than the control group (P < 0.001, by log‐rank test). By Cox proportional hazard regression analysis, COPD hazard ratio (HR) 1.93, 95% CI 1.73–2.17 was an independent risk factor after adjusting for age, gender, underlying comorbidities and ulcerogenic medication. Age > 65 years, male, comorbidities of hypertension, diabetes, heart failure, history of peptic ulcer disease, and chronic renal disease and use of nonsteroidal anti‐inflammatory drugs were risk factors of ulcer bleeding in COPD patients.
Conclusion
Patients with chronic obstructive pulmonary disease have a higher risk of peptic ulcer bleeding after adjustments for possible confounding factors like underlying comorbidities and ulcerogenic medication.
Summary
Background
Few large population‐based studies have compared the occurrence of peptic ulcer bleeding (PUB) in cirrhotic and noncirrhotic patients.
Aims
To investigate if cirrhotic patients ...have higher risk of PUB than the general population and to identify possible risk factors of PUB in cirrhotic patients.
Methods
Using the National Health Insurance Research Database, a nationwide population‐based dataset in Taiwan and matching age, gender, comorbidities and ulcerogenic medication by propensity score, 4013 cirrhotic patients, 8013 chronic hepatitis patients and 7793 normal controls were compared. The log‐rank test was used to analyse differences in accumulated PUB‐free survival rates between the groups. Cox proportional hazard regressions were performed to evaluate independent risk factors for PUB in all patients and identified risk factors of PUB in cirrhotic patients.
Results
During the 7‐year follow‐up, cirrhotic patients had significantly higher incidences of PUB than chronic hepatitis patients and controls, respectively (P < 0.001 by log‐rank test). By Cox proportional hazard regression analysis, cirrhosis was independently associated with increased risk of PUB (hazard ratio: 4.22; 95% CI 3.37–5.29, P < 0.001) after adjusting for age, gender, economic status, underlying comorbidities and ulcerogenic medication. Age, male, diabetes, chronic renal disease, history of gastro‐oesophageal variceal bleeding and use of nonsteroidal anti‐inflammatory drugs were risk factors for PUB in cirrhotic patients.
Conclusion
Cirrhotic patients have a significantly higher risk of peptic ulcer bleeding after adjustments for possible confounding factors like age, gender, economic status, underlying comorbidities and ulcerogenic medication.
Summary
Background
The risk factors for gastrointestinal bleeding (GIB) in clopidogrel users have not been identified.
Aim
To clarify whether clopidogrel use is a risk factor for upper GIB (UGIB) and ...lower GIB (LGIB) and identify the risk factors in clopidogrel users.
Methods
Using the National Health Insurance Research Database of Taiwan, 3238 clopidogrel users and 12 952 age‐, sex‐, and enrolment time‐matched controls in a 1:4 ratio were extracted for comparison from a cohort dataset of 1 000 000 randomly sampled subjects. Cox proportional hazard regression models were used to identify the independent risk factors for UGIB and LGIB in all enrollees and clopidogrel users after adjustments for age, gender, comorbidity i.e., coronary artery disease, hypertension, diabetes, chronic obstructive pulmonary disease, chronic kidney disease (CKD), cirrhosis, uncomplicated peptic ulcer disease, and peptic ulcer bleeding (PUB), and medications e.g., nonsteroidal anti‐inflammatory drugs (NSAIDs), cyclooxygenase‐2 inhibitors, aspirin, steroids, selective serotonin reuptake inhibitors (SSRIs), warfarin and alendronate.
Results
Cox proportional hazard regression analysis showed that use of clopidogrel increased the risk of UGIB hazard ratio (HR): 3.66; 95% confidence interval (CI): 2.96–4.51 and LGIB HR: 3.52, 95% CI: 2.74–4.52. Age, CKD, PUB history, use of aspirin and NSAIDs were independent risk factors for UGIB in the clopidogrel users. Age, CKD, PUB history, use of aspirin and SSRIs were independent risk factors for LGIB.
Conclusions
In clopidogrel users, age, CKD, PUB history, use of aspirin and NSAIDs are independent risk factors for UGIB; age, CKD, PUB history, use of aspirin and SSRIs are independent risk factors for LGIB.
BACKGROUND: Neutrophil gelatinase–associated lipocalin (NGAL) is released from renal tubular cells after injury and serves in humans as a real‐time indicator of active kidney damage, including acute ...kidney injury (AKI) and chronic kidney disease (CKD). However, NGAL concentrations in dogs with naturally occurring AKI or CKD rarely have been explored in detail. HYPOTHESIS/OBJECTIVES: The goal of this study was to evaluate whether NGAL can serve as a useful biomarker in dogs with naturally occurring renal disease. ANIMALS: Client‐owned dogs with renal disease (57) and control dogs without any disease (12) were examined. METHODS: Serum NGAL (sNGAL) and urine NGAL (uNGAL) concentrations were measured in each animal by a newly developed ELISA system. Demographic, hematologic, and serum biochemical data were recorded. Survival attributable to AKI and CKD was evaluated at 30 days and 90 days, respectively. RESULTS: Serum and urine NGAL concentrations in azotemic dogs were significantly higher than in nonazotemic dogs and were highly correlated with serum creatinine concentration (P < .05). Among CKD dogs, death was associated with significantly higher sNGAL and uNGAL concentrations compared with survivors. Receiver‐operating characteristic curve (ROC) analysis showed that sNGAL was better than serum creatinine concentration when predicting clinical outcomes for CKD dogs (P < .05). The best cutoff point for sNGAL was 50.6 ng/mL, which gave a sensitivity and a specificity of 76.9 and 100%, respectively. Furthermore, dogs that had higher concentrations of sNGAL survived for a significantly shorter time. CONCLUSION: sNGAL is a useful prognostic marker when evaluating dogs with CKD.
Conventionally, acute myeloid leukemia (AML) patients are categorized into good-, intermediate- and poor-risk groups according to cytogenetic changes. However, patients with intermediate-risk ...cytogenetics represent a largely heterogeneous population regarding treatment response and clinical outcome. In this study, we integrated cytogenetics and molecular mutations in the analysis of 318 patients with de novo non-M3 AML who received standard chemotherapy. According to the mutation status of eight genes, including NPM1, CEBPA, IDH2, RUNX1, WT1, ASXL1, DNMT3A and FLT3, that had prognostic significance, 229 patients with intermediate-risk cytogenetics could be refinedly stratified into three groups with distinct prognosis (P<0.001); patients with good-risk genotypes had a favorable outcome (overall survival, OS, not reached) similar to those with good-risk cytogenetics, whereas those with poor-risk genotypes had an unfavorable prognosis (OS, 10 months) similar to those with poor-risk cytogenetics (OS, 13.5 months), and the remaining patients with other genotypes had an intermediate outcome (OS, 25 months). Integration of cytogenetic and molecular profiling could thus reduce the number of intermediate-risk AML patients from around three-fourth to one-fourth. In conclusion, integration of cytogenetic and molecular changes improves the prognostic stratification of AML patients, especially those with intermediate-risk cytogenetics, and may lead to better decision on therapeutic strategy.
Background
Childhood asthma comprises different phenotypes with complex pathophysiology. Different asthma phenotypes evoke various clinical symptoms and vary in their responses to treatments.
Methods
...We applied k‐means clustering algorithm of twelve objective laboratory tests among 351 asthmatic children enrolled in the Taiwanese Consortium of Childhood Asthma Study (TCCAS). We constructed gene expression profiles of peripheral blood mononuclear cells (PBMC) from children with different asthma phenotypes.
Results
Five distinct phenotypes of childhood asthma were identified and can be characterized by either eosinophil‐predominant or neutrophil‐predominant inflammatory characteristics. In the gene expression profile analysis, significant differences were noted for neutrophil‐predominant asthma, compared with samples from all the other asthma phenotypes. The vast majority of the differentially expressed genes in neutrophil‐predominant asthma was associated with corticosteroid response. From an independent inhaled corticosteroid (ICS) response cohort, we also found neutrophils could be activated in this severe asthma phenotype and neutrophil‐predominant asthma may be associated with corticosteroid nonresponsiveness.
Conclusion
Phenotype clustering of childhood asthma can be helpful to identify clinically relevant patients and reveal different inflammatory characteristics in asthmatic children. Neutrophil‐predominant asthma is the most severe asthma phenotype with poor corticosteroid response. Gene expression profile of different asthma phenotypes not only improve our knowledge of childhood asthma, but also can guide asthma precision medicine.
Neutrophil‐predominant asthma is the most severe asthma phenotype with poor corticosteroid response. Five distinct phenotypes of childhood asthma identified in this study with differences in lung function, symptom frequency, healthcare utilization, percentages of eosinophils and neutrophils in peripheral blood, and serum IgE. Gene expression signature in PBMC constitutes an easier way to objectively identify corticosteroid‐resistant asthma in clinical settings.
Aim
The study aimed to determine whether nonalcoholic fatty liver disease (NAFLD) is an independent risk factor of adenoma after negative baseline colonoscopy.
Method
A retrospective cohort study was ...conducted on 1522 health‐check individuals who underwent two consecutive colonoscopies at Taipei Veterans General Hospital between 2003 and 2010. Those developing an adenoma after an initial negative baseline colonoscopy (adenoma group) were compared with those in whom the second colonoscopy was negative (nonadenoma group). Anthropometric measurements, biochemical tests and the presence of NAFLD were compared between the two groups.
Results
The adenoma group had a higher prevalence of NAFLD than the nonadenoma group (55.6% vs 38.8%; P < 0.05). On multivariate logistic regression analysis, NAFLD was an independent risk factor (OR = 1.45, 95% CI: 1.07–1.98) for adenoma formation after a negative baseline colonoscopy. The risk of colorectal adenoma increased when NAFLD patients had other morbidities including metabolic syndrome, hypertension or smoking (OR = 2.85, 4.03 and 4.17).
Conclusion
NAFLD is an independent risk factor for colorectal adenoma formation after a negative baseline colonoscopy. The risk is higher in individuals with NAFLD and other comorbidities, such as hypertension, smoking or metabolic syndrome.
Inflammatory markers such as interleukin (IL)-6 and tumour necrosis factor-alpha (TNF-α) are elevated in dialysis patients and can predict cardiovascular events and all-cause mortality. Endotoxin is ...an important source and also another marker of inflammation in patients with chronic kidney disease. The aim of this study was to evaluate the impact of oral probiotics on serum levels of endotoxemia and cytokines in peritoneal dialysis (PD) patients. The decline of residual renal function, peritonitis episodes, and cardiovascular events were also recorded. From July 2011 to June 2012, a randomised, double-blind, placebo-controlled trial was conducted in PD patients. The intervention group received one capsule of probiotics containing 10(9) cfu Bifobacterium bifidum A218, 10(9) cfu Bifidobacterium catenulatum A302, 10(9) cfu Bifidobacterium longum A101, and 10(9) cfu Lactobacillus plantarum A87 daily for six months, while the placebo group received similar capsules containing maltodextrin for the same duration. Levels of serum TNF-α, interferon gamma, IL-5, IL-6, IL-10, IL-17, and endotoxin were measured before and six months after intervention. 39 patients completed the study (21 in the probiotics group and 18 in the placebo group). In patients receiving probiotics, levels of serum TNF-α, IL-5, IL-6, and endotoxin significantly decreased after six months of treatment, while levels of serum IL-10 significantly increased. In contrast, there were no significant changes in levels of serum cytokines and endotoxin in the placebo group after six months. In addition, the residual renal function was preserved in patients receiving probiotics. In conclusion, probiotics could significantly reduce the serum levels of endotoxin, pro-inflammatory cytokines (TNF-α and IL-6), IL-5, increase the serum levels of anti-inflammatory cytokine (IL-10), and preserve residual renal function in PD patients.
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