Background/Aims: Nonalcoholic fatty liver disease (NAFLD) is closely related to gut-microbiome. There is a paucity of research on which strains of gut microbiota affect the progression of NAFLD. This study explored the NAFLD-associated microbiome in humans and the role of Lactobacillus in the progression of NAFLD in mice. Methods: The gut microbiome was analyzed via next-generation sequencing in healthy people (n=37) and NAFLD patients with elevated liver enzymes (n=57). Six-week-old male C57BL/6J mice were separated into six groups (n=10 per group; normal, Western, and four Western diet + strains [109 colony-forming units/g for 8 weeks; L. acidophilus, L. fermentum, L. paracasei, and L. plantarum]). Liver/body weight ratio, liver pathology, serum analysis, and metagenomics in the mice were examined. Results: Compared to healthy subjects (1.6±4.3), NAFLD patients showed an elevated Firmicutes/Bacteroidetes ratio (25.0±29.0) and a reduced composition of Akkermansia and L. murinus (P<0.05). In the animal experiment, L. acidophilus group was associated with a significant reduction in liver/body weight ratio (5.5±0.4) compared to the Western group (6.2±0.6) (P<0.05). L. acidophilus (41.0±8.6), L. fermentum (44.3±12.6), and L. plantarum (39.0±7.6) groups showed decreased cholesterol levels compared to the Western group (85.7±8.6) (P<0.05). In comparison of steatosis, L. acidophilus (1.9±0.6), L. plantarum (2.4±0.7), and L. paracasei (2.0±0.9) groups showed significant improvement of steatosis compared to the Western group (2.6±0.5) (P<0.05). Conclusions Ingestion of Lactobacillus, such as L. acidophilus, L. fermentum, and L. plantarum, ameliorates the progression of nonalcoholic steatosis by lowering cholesterol. The use of Lactobacillus can be considered as a useful strategy for the treatment of NAFLD.

Oxidative stress plays a crucial role in the development of neuronal disorders including brain ischemic injury. Thioredoxin 1 (Trx1), a 12 kDa oxidoreductase, has anti-oxidant and anti-apoptotic functions in various cells. It has been highly implicated in brain ischemic injury. However, the protective mechanism of Trx1 against hippocampal neuronal cell death is not identified yet. Using a cell permeable Tat-Trx1 protein, protective mechanism of Trx1 against hydrogen peroxide-induced cell death was examined using HT-22 cells and an ischemic animal model. Transduced Tat-Trx1 markedly inhibited intracellular ROS levels, DNA fragmentation, and cell death in H 2O 2-treatment HT-22 cells. Tat-Trx1 also significantly inhibited phosphorylation of ASK1 and MAPKs in signaling pathways of HT-22 cells. In addition, Tat-Trx1 regulated expression levels of Akt, NF-κB, and apoptosis related proteins. In an ischemia animal model, Tat-Trx1 markedly protected hippocampal neuronal cell death and reduced astrocytes and microglia activation. These findings indicate that transduced Tat-Trx1 might be a potential therapeutic agent for treating ischemic injury.

Oxidative stress plays a crucial role in the development of neuronal disorders including brain ischemic injury. Thioredoxin 1 (Trx1), a 12 kDa oxidoreductase, has anti-oxidant and anti-apoptotic functions in various cells. It has been highly implicated in brain ischemic injury. However, the protective mechanism of Trx1 against hippocampal neuronal cell death is not identified yet. Using a cell permeable Tat-Trx1 protein, protective mechanism of Trx1 against hydrogen peroxide-induced cell death was examined using HT-22 cells and an ischemic animal model. Transduced Tat-Trx1 markedly inhibited intracellular ROS levels, DNA fragmentation, and cell death in H 2O 2-treatment HT-22 cells. Tat-Trx1 also significantly inhibited phosphorylation of ASK1 and MAPKs in signaling pathways of HT-22 cells. In addition, Tat-Trx1 regulated expression levels of Akt, NF-κB, and apoptosis related proteins. In an ischemia animal model, Tat-Trx1 markedly protected hippocampal neuronal cell death and reduced astrocytes and microglia activation. These findings indicate that transduced Tat-Trx1 might be a potential therapeutic agent for treating ischemic injury.

Aldose reductase (AR) protein, a member of the NADPH-dependent aldo-keto reductase family, reduces a wide range of aldehydes and enhances cell survival by inhibition of oxidative stress. Oxidative stress is known as one of the major pathological factor in ischemia. Since the precise function of AR protein in ischemic injury is fully unclear, we examined the function of AR protein in hippocampal neuronal (HT-22) cells and in an animal model of ischemia in this study. Cell permeable Tat-AR protein was produced by fusion of protein transduction domain in Tat for delivery into the cells. Tat-AR protein transduced into HT-22 cells and significantly inhibited cell death and regulated the mitogen-activate protein kinases (MAPKs), Bcl-2, Bax, and Caspase-3 under oxidative stress condition. In an ischemic animal model, Tat-AR protein transduced into the brain tissues through the blood-brain barrier (BBB) and drastically decreased neuronal cell death in hippocampal CA1 region. These results indicate that transduced Tat-AR protein has protective effects against oxidative stress-induced neuronal cell death in vitro and in vivo, suggesting that Tat-AR protein could be used as potential therapeutic agent in ischemic injury.
Aldehyde Reductase ; Aldehydes ; Blood-Brain Barrier ; Brain ; CA1 Region, Hippocampal ; Caspase 3 ; Cell Death ; Cell Survival ; Humans ; In Vitro Techniques ; Ischemia ; Models, Animal ; Neurons ; Oxidative Stress ; Oxidoreductases ; Protein Kinases

BACKGROUND AND OBJECTIVES: The mechanism responsible for lethal ventricular arrhythmia (LVA) after acute myocardial infarction (AMI) remains unclear. SUBJECTS AND METHODS: The corrected QT interval (QTc) and interval from the peak to the end of the T wave (TpTe) were measured, which indicated myocardial transmural dispersion of repolarization (TDR) in 72 patients with AMI. TpTe was also expressed as a corrected value, [TpTe/QTe]x100% and TpTe/√RR. These parameters were obtained from all the 12-leads of electrocardiography after arrival at the hospital, just before and after percutaneous coronary intervention (PCI), and at 4, 24, and 48 hours and 5 days after PCI. RESULTS: Analyzing with repeated measures analysis of variance, the TpTe, [TpTe/QTe]x100% and TpTe/√RR after AMI showed significant changes in time variance. The patients were divided into LVA (17 patients, 24%) and non-LVA group (55 patients, 76%). The [TpTe/ QTe]×100% (V₂: 25±7% vs. 22±5%, p=0.036) and TpTe/√RR (V₂: 109 ± 42 ms vs. 88 ± 22 ms, p=0.05, V₃: 108±39 ms vs. 91±27 ms, p=0.048) in V₂ and V₃ leads were prolonged in the LVA group after PCI. The [TpTe/QTe]×100% (28±9 % vs. 22±5%, p=0.025) and TpTe/√RR (129±53 ms vs. 99±41 ms, p=0.05) in V₃ lead were prolonged in the LVA group 24 hours after PCI. CONCLUSION: The mechanisms responsible for LVA after AMI may be associated with increased TDR, and PCI may have an important role in reducing LVA.
Arrhythmias, Cardiac ; Electrocardiography* ; Humans ; Myocardial Infarction* ; Percutaneous Coronary Intervention

BACKGROUND AND OBJECTIVES: Microvascular function is a useful predictor of left ventricular functional changes in patients with ST-segment elevation myocardial infarction (STEMI). We evaluated the usefulness of the hyperemic microvascular resistance index (hMVRI) for predicting long-term major adverse cardiovascular events (MACEs) in patients with STEMI assessed immediately after primary percutaneous coronary intervention (PCI). SUBJECTS AND METHODS: hMVRI were evaluated in 145 patients with first acute STEMI treated with primary PCI using an intracoronary Doppler wire. hMVRI was defined as the ratio of mean aortic pressure over hyperemic averaged peak velocity of infarct-related artery. Major adverse cardiovascular events (MACEs) included cardiac death and re-hospitalization for congestive heart failure. RESULTS: During the mean follow-up of 85+/-43 months, MACEs occurred in 17.2% of patients. Using a receiver-operating characteristics analysis, hMVRI >2.82 mm Hg.cm-1.sec (sensitivity: 87%; specificity: 69%; and area under curve: 0.818) was the best cut-off values for predicting future cardiac events. The Cox proportional hazard analysis showed that hMVRI was an independent predictor for long-term MACEs (hazard ratio 1.741, 95% confidence interval 1.348-2.264, p<0.001). The Kaplan-Meier survival analysis showed a higher incidence of MACEs in patients with hMVRI >2.82 mm Hg.cm-1.sec (p<0.001). CONCLUSION: hMVRI was a strong predictor of long-term MACEs in patients with STEMI treated with primary PCI.
Area Under Curve ; Arterial Pressure ; Arteries ; Death ; Follow-Up Studies ; Heart Failure ; Humans ; Incidence ; Microcirculation ; Myocardial Infarction* ; Percutaneous Coronary Intervention ; Sensitivity and Specificity

PURPOSE: To investigate the differences in the cancer detection rate and pathological findings on a second prostate biopsy according to benign diagnosis, high-grade prostatic intraepithelial neoplasia (HGPIN), and atypical small acinar proliferation (ASAP) on first biopsy. MATERIALS AND METHODS: We retrospectively reviewed the records of 1,323 patients who underwent a second prostate biopsy between March 1995 and November 2012. We divided the patients into three groups according to the pathologic findings on the first biopsy (benign diagnosis, HGPIN, and ASAP). We compared the cancer detection rate and Gleason scores on second biopsy and the unfavorable disease rate after radical prostatectomy among the three groups. RESULTS: A total of 214 patients (16.2%) were diagnosed with prostate cancer on a second biopsy. The rate of cancer detection was 14.6% in the benign diagnosis group, 22.1% in the HGPIN group, and 32.1% in the ASAP group, respectively (p<0.001). When patients were divided into subgroups according to the number of positive cores, the rate of cancer detection was 16.7%, 30.5%, 31.0%, and 36.4% in patients with a single core of HGPIN, more than one core of HGPIN, a single core of ASAP, and more than one core of ASAP, respectively. There were no significant differences in Gleason scores on second biopsy (p=0.324) or in the unfavorable disease rate after radical prostatectomy among the three groups (benign diagnosis vs. HGPIN, p=0.857, and benign diagnosis vs. ASAP, p=0.957, respectively). CONCLUSIONS: Patients with multiple cores of HGPIN or any core number of ASAP on a first biopsy had a significantly higher cancer detection rate on a second biopsy. Repeat biopsy should be considered and not be delayed in those patients.
Aged ; Biopsy, Needle/methods ; Humans ; Kallikreins/blood ; Male ; Middle Aged ; Neoplasm Grading ; Precancerous Conditions/*pathology/surgery ; Predictive Value of Tests ; Prostate-Specific Antigen/blood ; Prostatectomy ; Prostatic Intraepithelial Neoplasia/*pathology/surgery ; Prostatic Neoplasms/*pathology/surgery ; Retrospective Studies

PURPOSE: Partial nephrectomy has a similar oncologic outcome to radical nephrectomy while reducing cardiac and metabolic morbidity. However, previous studies reported that partial nephrectomy had been underutilized. The purpose of this study is to analyze trends in the use of partial nephrectomy in Korea and evaluate which individual factors and hospital factor influenced the operative approach. MATERIALS AND METHODS: Using URO-PDS database, 11560 patients underwent nephrectomy for renal cell carcinoma between 2006 and 2010 were identified. International Classification of Disease (ICD-9) diagnosis codes were applied to target subject of interest. Logistic regression was applied to identify determinants of partial nephrectomy. RESULTS: Over the study period, the proportion of partial nephrectomies has steadily increased from 9.4% in 2006 to 30.4% in 2010 (p<0.001). Deviation of utilization in partial nephrectomy has been observed based on the area (p<0.001) and type of surgery (p<0.001). Individual of younger age, as well as male, were more likely to be treated with partial nephrectomy (p<0.001 for each). Furthermore, Patient treated at hospitals with higher nephrectomy volume were more prone to be treated with partial nephrectomy (p<0.001 for each). CONCLUSIONS: Partial nephrectomies have been increasingly performed over the study period but are still underutilized.
Carcinoma, Renal Cell* ; Classification ; Diagnosis ; Humans ; Korea* ; Logistic Models ; Male ; Nephrectomy*