Background/Aims: Potassium channel tetramerization domain containing 17 (KCTD17) protein, an adaptor for the cullin3 (Cul3) ubiquitin ligase complex, has been implicated in various human diseases; however, its role in hepatocellular carcinoma (HCC) remains elusive. Here, we aimed to elucidate the clinical features of KCTD17, and investigate the mechanisms by which KCTD17 affects HCC progression. Methods: We analyzed transcriptomic data from patients with HCC. Hepatocyte-specific KCTD17 deficient mice were treated with diethylnitrosamine (DEN) to assess its effect on HCC progression. Additionally, we tested KCTD17-directed antisense oligonucleotides for their therapeutic potential in vivo. Results: Our investigation revealed the upregulation of KCTD17 expression in both tumors from patients with HCC and mouse models of HCC, in comparison to non-tumor controls. We identified the leucine zipper-like transcriptional regulator 1 (Lztr1) protein, a previously identified Ras destabilizer, as a substrate for KCTD17-Cul3 complex. KCTD17-mediated Lztr1 degradation led to Ras stabilization, resulting in increased proliferation, migration, and wound healing in liver cancer cells. Hepatocyte-specific KCTD17 deficient mice or liver cancer xenograft models were less susceptible to carcinogenesis or tumor growth. Similarly, treatment with KCTD17-directed antisense oligonucleotides (ASO) in a mouse model of HCC markedly lowered tumor volume as well as Ras protein levels, compared to those in control ASO-treated mice. Conclusions KCTD17 induces the stabilization of Ras and downstream signaling pathways and HCC progression and may represent a novel therapeutic target for HCC.

Background: Reactive oxygen species (ROS) and inflammation are reported to have a fundamental role in the pathogenesis of ischemia-reperfusion (IR) injury, a leading cause of acute kidney injury. The present study investigated the role of pyruvate dehydrogenase kinase 4 (PDK4) in ROS production and inflammation following IR injury. Methods: We used a streptozotocin-induced diabetic C57BL6/J mouse model, which was subjected to IR by clamping both renal pedicles. Cellular apoptosis and inflammatory markers were evaluated in NRK-52E cells and mouse primary tubular cells after hypoxia and reoxygenation using a hypoxia work station. Results: Following IR injury in diabetic mice, the expression of PDK4, rather than the other PDK isoforms, was induced with a marked increase in pyruvate dehydrogenase E1α (PDHE1α) phosphorylation. This was accompanied by a pronounced ROS activation, as well as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), and monocyte chemoattractant protein-1 (MCP-1) production. Notably, sodium dichloroacetate (DCA) attenuated renal IR injury-induced apoptosis which can be attributed to reducing PDK4 expression and PDHE1α phosphorylation levels. DCA or shPdk4 treatment reduced oxidative stress and decreased TNF-α, IL-6, IL-1β, and MCP-1 production after IR or hypoxia-reoxygenation injury. Conclusion PDK4 inhibition alleviated renal injury with decreased ROS production and inflammation, supporting a critical role for PDK4 in IR mediated damage. This result indicates another potential target for reno-protection during IR injury; accordingly, the role of PDK4 inhibition needs to be comprehensively elucidated in terms of mitochondrial function during renal IR injury.

Mitochondrial reactive oxygen species (mROS) that are overproduced by mitochondrial dysfunction are linked to pathological conditions including sensory abnormalities. Here, we explored whether mROS overproduction induces itch through transient receptor potential canonical 3 (TRPC3), which is sensitive to ROS. Intradermal injection of antimycin A (AA), a selective inhibitor of mitochondrial electron transport chain complex III for mROS overproduction, produced robust scratching behavior in naïve mice, which was suppressed by MitoTEMPO, a mitochondria-selective ROS scavenger, and Pyr10, a TRPC3-specific blocker, but not by blockers of TRPA1 or TRPV1. AA activated subsets of trigeminal ganglion neurons and also induced inward currents, which were blocked by MitoTEMPO and Pyr10. Besides, dry skin-induced chronic scratching was relieved by MitoTEMPO and Pyr10, and also by resveratrol, an antioxidant. Taken together, our results suggest that mROS elicit itch through TRPC3, which may underlie chronic itch, representing a potential therapeutic target for chronic itch.
Animals ; Antioxidants/pharmacology* ; Mice ; Mitochondria ; Pruritus/chemically induced* ; Reactive Oxygen Species/metabolism* ; TRPA1 Cation Channel

BACKGROUND/AIMS: An incomplete virological response has been observed to tenofovir dipivoxil fumarate (TDF) in nucleos(t)ide analogue (NA)-experienced chronic hepatitis B (CHB) patients. This study investigated the efficacy of TDF in NA-naïve CHB patients 96 weeks after treatment. METHODS: CHB patients treated with TDF were enrolled retrospectively between November 2012 and January 2016. We assessed virological and biochemical parameters. RESULTS: The study enrolled 179 NA-naïve patients with a median follow-up duration of 59.6 weeks. The serum hepatitis B virus (HBV) DNA level decreased significantly during treatment. The complete virological response (CVR) rate was 83.21% at week 96. In univariate analyses, the predictors of a CVR at 96 weeks were the baseline HBV DNA level (CVR vs. no-CVR, HBV DNA log10 mean value 7.34 vs. 7.86, 95% confidential interval [CI]: -7.89 to -7.37; p < 0.001) and male sex (CVR vs. no-CVR, 49.1% vs. 81.3%, odds ratio [OR] 0.22, 95% CI: 0.06 to 0.87; p = 0.025). In the multivariate analysis, male sex predicted a CVR at week 96. The CVR was significantly lower in males than in females (OR 0.12, 95% CI: 0.02 to 0.96; p = 0.046). CONCLUSIONS: TDF was effective for treating CHB for more than 2 years in NA-naïve patients.
DNA ; Female ; Follow-Up Studies ; Hepatitis B ; Hepatitis B virus ; Hepatitis B, Chronic* ; Hepatitis, Chronic* ; Humans ; Male ; Multivariate Analysis ; Odds Ratio ; Retrospective Studies ; Tenofovir*

BACKGROUND: Rheumatoid arthritis (RA) and metabolic syndrome (Mets) are considered to be diseases with common traits that can increase the risk of cardiovascular disease incidence; studies in other countries examined the relationship between these diseases. However, existing studies did not show consistent results. In the present study, the relationship between RA and Mets in Koreans was examined using the data of the 4th and 5th Korea National Health and Nutrition Examination Survey (KNHANES). METHODS: The present study used the data of the 4th and 5th KNHANES, conducted between 2007 and 2012. Among 25,812 adults aged over 40, 19,893 were selected as study subjects, excluding 5,919 who did not have variable information needed for the analysis. T-test and chi-square test were used for the analysis of related variables. To determine the relationship between diagnostic status of RA and Mets, multivariate logistic regression analysis was performed by controlling confounding variables, which were selected through literature review and statistical analysis. RESULTS: Multivariate logistic regression analysis was conducted to examine the relationship between diagnostic status of RA and Mets. When age, education level, average monthly household income, smoking, alcohol consumption, and level of physical activity were adjusted, the prevalence of Mets was lower in RA patients (adjusted odds ratio [aOR], 0.79; 95% confidence interval [CI], 0.65 to 0.96). Multivariate logistic regression analysis was performed to examine the relationship between treatment status of RA and Mets. When age, education level, average monthly household income, smoking, alcohol consumption, and level of physical activity were adjusted, there was a significant negative correlation in women (aOR, 0.65; 95% CI, 0.44 to 0.96). CONCLUSION: The relationship between RA and Mets showed a significantly negative correlation in Korean women. The group that received RA treatment showed significantly lower prevalence of the Mets as compared to the untreated group in Korean RA women.
Adult ; Alcohol Drinking ; Arthritis, Rheumatoid* ; Cardiovascular Diseases ; Confounding Factors (Epidemiology) ; Education ; Family Characteristics ; Female ; Humans ; Incidence ; Korea ; Logistic Models ; Motor Activity ; Nutrition Surveys ; Odds Ratio ; Prevalence ; Smoke ; Smoking

BACKGROUND: A nasogastric tube (NGT) is commonly inserted into patients undergoing abdominal surgery to decompress the stomach during or after surgery. However, for anatomic reasons, the insertion of NGTs into anesthetized and intubated patients may be challenging. We hypothesized that the use of a tube exchanger for NGT insertion could increase the success rate and reduce complications. METHODS: One hundred adult patients, aged 20–70 years, who were scheduled for gastrointestinal surgeries with general anesthesia and NGT insertion were enrolled in our study. The patients were randomly allocated to the tube-exchanger group or the control group. The number of attempts, the time required for successful NGT insertion, and the complications were noted for each patient. RESULTS: In the tube-exchanger group, the success rate of NGT insertion on the first attempt was 92%, which is significantly higher than 68%, the rate in the control group (P = 0.007). The time required for successful NGT insertion in the tube-exchanger group was 18.5 ± 8.2 seconds, which is significantly shorter than the control group, 75.1 ± 9.8 seconds (P < 0.001). Complications such as laryngeal bleeding and the kinking and knotting of the NGT occurred less often in the tube-exchanger group. CONCLUSIONS: There were many advantages in using a tube-exchanger as a guide to inserting NGTs in anesthetized and intubated patients. Compared to the conventional technique, the use of a tube-exchanger resulted in a higher the success rate of insertion on the first attempt, a shorter procedure time, and fewer complications.
Adult ; Anesthesia, General ; Digestive System Surgical Procedures ; Hemorrhage ; Humans ; Intubation, Gastrointestinal ; Preoperative Care ; Stomach

BACKGROUND/AIMS: Pyogenic liver abscess (PLA) is a life-threatening condition, despite advances in diagnostic technology and strategies for treatment. A strong predictor of mortality in this condition is septic shock. This study describes clinical, biochemical, and radiologic features in patients with PLA with or without septic shock, with the intent of describing risk factors for septic shock. METHODS: Of 358 patients with PLA enrolled, 30 suffered septic shock and the remaining 328 did not. We reviewed the medical records including etiologies, underlying diseases, laboratory, radiologic and microbiologic findings, methods of treatment and treatment outcomes. RESULTS: The case fatality rate was 6.1%. In univariate analysis, the presence of general weakness, mental change, low platelet level, prolonged PT, high BUN level, high creatinine level, low albumin level, high AST level, high CRP level, abscess size >6 cm, the presence of gas-forming abscess, APACHE II score ≥20, and the presence of Klebsiella pneumoniae infection were significantly associated with septic shock. Multivariate analysis showed the presence of mental change (p=0.004), gas-forming abscess (p=0.012), and K. pneumoniae infection (p=0.027) were independent predictors for septic shock. CONCLUSIONS: The presence of mental change, gas-forming abscess, and K. pneumoniae infection were independent predictors for septic shock in patients with PLA.
Abscess ; APACHE ; Blood Platelets ; Creatinine ; Humans ; Klebsiella pneumoniae ; Liver Abscess, Pyogenic* ; Medical Records ; Mortality ; Multivariate Analysis ; Pneumonia ; Risk Factors ; Shock, Septic*

OBJECTIVE: To evaluate the performance of Momguard, non-invasive prenatal test (NIPT) for detecting trisomy (T) 21, T18, T13, and sex-chromosome abnormalities recently developed in Korea. METHODS: This preliminary study formed part of a large prospective cohort study conducted at Asan Medical Center, Seoul, Korea. Only pregnant women who underwent both NIPT and confirmatory karyotyping were included in this study. NIPT results were compared with those of karyotype analyses. RESULTS: Among 93 eligible cases, NIPT results could not be obtained in one case due to a low fetal cell-free DNA fraction. Based on NIPT, eight cases of fetal aneuploidies, including T21 (n=5), T18 (n=2), and T13 (n=1), were identified. For T21 and T18, the sensitivity and specificity of NIPT were both 100%, with a false-positive and false-negative rate of 0% and a positive-predictive value of 100%. One patient classified as having intermediate risk for T13 by NIPT was confirmed to have T13 by karyotyping, and there were no false-negative cases. No cases of sex-chromosome anomalies were detected by NIPT or karyotyping during the study period. CONCLUSION: Momguard is a reliable screening tool for detecting T21 and T18. For T13 and sex-chromosome anomalies, further prospective studies are necessary to confirm its utility.
Aneuploidy ; Chungcheongnam-do ; Cohort Studies ; DNA ; Down Syndrome ; Female ; Humans ; Karyotype ; Karyotyping ; Korea* ; Mass Screening ; Pregnant Women ; Prenatal Diagnosis ; Prospective Studies ; Sensitivity and Specificity ; Seoul ; Trisomy

BACKGROUND: Proper physical activities are known to be helpful in the prevention and management of chronic diseases. However, the physical activity level of patients with chronic diseases is low. Therefore, this study aimed to investigate the physical activity compliance of patients with hypertension, diabetes, and dyslipidemia in Korea. METHODS: This study analyzed the 2010-2012 Fifth Korean National Health and Nutrition Examination Survey data. We included 13,873 individuals in the analysis. The level of physical activity compliance was measured by performing multivariate logistic regression analyses. RESULTS: In the univariate analysis, the subjects with hypertension or diabetes tended to comply with the physical activity guidelines less faithfully than their healthy counterparts. The proportion of subjects with hypertension who were insufficiently physically active was 65.4% among the men and 75.8% among the women. For diabetes, the proportions were 66.7% and 76.8%, respectively. No significant difference was found between the subjects with dyslipidemia and their healthy counterparts. In the multivariate logistic regression analysis, no significant difference in physical activity compliance was observed between the subjects with hypertension, diabetes, or dyslipidemia and their healthy counterparts for both sexes. CONCLUSION: The patients with hypertension or diabetes tended to have lower physical activity prevlaence than their healthy counterparts. However, for dyslipidemia, no significant difference was found between the two groups. Given the significance of physical activities in the management of chronic diseases, the physical activities of these patients need to be improved.
Adult* ; Chronic Disease* ; Compliance ; Dyslipidemias ; Female ; Humans ; Hypertension ; Korea ; Logistic Models ; Male ; Motor Activity* ; Nutrition Surveys

We found an title error in our published article.