The role of CK2 in the regulation of mitochondrial autophagy induced by rotenone.

CK2 regulates receptor-mediated mitophagy that removes damaged mitochondria. The PINK1/Parkin pathways also involve mitochondrial clearance through mitophagy. However, it is not clear whether CK2 regulates PINK1/Parkin-dependent mitophagy in response to stress. Rotenone treatment showed a decrease of FUNDC1 expression in the mitochondrial fraction of SH-SY5Y and HeLa cells, but an increase of PINK1/Parkin expression only in SH-SY5Y cells. Interestingly, CK2 inhibition increased mitochondrial LC3II expression in rotenone-treated HeLa cells, whereas it decreased in SH-SY5Y cells, indicating that CK2 mediates rotenone-induced mitophagy in dopaminergic neurons. Furthermore, FUNDC1 expression increased in rotenone-treated SH-SY5Y cells by CK2 inhibition, whereas it decreased in HeLa cells. CK2 inhibition also blocked the increase of Drp1, PINK1 and Parkin translocation into mitochondria and decrease of PGAM5 expression in rotenone-treated SH-SY5Y cells. As expected, rotenone treatment in PGAM5-knockdown cells reduced the expression of PINK1 and Parkin and decrease of LC3II expression. Interestingly, we observed that knockdown of CK2α or PGAM5 induced a further increase in caspase-3 expression. These results suggest that PINK1/Parkin-dependent mitophagy was dominant over FUNDC1 receptor-mediated mitophagy. Collectively, our findings suggest that CK2 can positively induce PINK1/Parkin-dependent mitophagy, and that mitophagy regulates cytoprotective effects by CK2 signaling in dopaminergic neurons. DATA AVAILABILITY STATEMENT: All data generated or analyzed during this study are available upon request.

Reliable screening and classification of phosphodiesterase type 5 inhibitors in dietary supplements using gas chromatography / mass spectrometry combined with specific common ions.

Illegal dietary supplements adulterated with phosphodiesterase type 5 inhibitors (PDE-5i) are increasingly widely distributed through internet markets and underground routes. For this reason, it demands development of reliable screening methods to determine a wide range of PDE-5i drugs in various types of dietary supplements. Herein, we developed a screening method using gas chromatography-mass spectrometry (GC-MS) for simultaneous detection of 53 PDE-5i drugs in supplements. Common formulations (such as capsule, powder, pill, and tablet) of supplements with complicated matrices were treated by simple liquid-liquid extraction and trimethylsilyl (TMS) derivatization. With the aid of TMS derivatization, 53 PDE-5i drugs could be successfully separated and detected within 15 min, using a short microbore GC column (15 m). Moreover, owing to enhanced detection sensitivity and selectivity of PDE-5i TMS derivatives, 0.5 mg of sample was sufficient to screen and confirm targeted PDE-5i drugs. In this study, specific common ions according to structural characteristics of PDE-5i drugs were found under the electron ionization (EI) of their TMS derivatives. These specific common fragments could reflect the common pharmacophores for 4 classes of PDE-5i drugs (sildenafil, other sildenafil, vardenafil, and tadalafil analogues). Based on characteristic EI fragment ions, extracted common ion chromatograms (ECICs) and discriminant analysis (DA) were effectively used for reliable screening and classification of various types of PDE-5i drugs. Specific ECICs and DA using characteristic EI fragments here will aid in identification of newly emerging PDE-5i counterfeits in supplements. This study will be helpful to supervise illegal adulteration of PDE-5i drugs in dietary supplements to protect public health and consumer safety.

Surveillance Rate and its Impact on Survival of Hepatocellular Carcinoma Patients in South Korea: A Cohort Study.

PURPOSE: Though regular surveillance of hepatocellular carcinoma (HCC) for high-risk patients is widely recommended, its rate and effectiveness are not clear. The aim of this study is to investigate the actual rate of HCC surveillance and its related factors and to clarify its impact on survival in a Korean HCC cohort. MATERIALS AND METHODS: From 2012 to 2015, 319 newly diagnosed HCC patients were prospectively enrolled at a tertiary hospital. Patient interviews based on a structured questionnaire survey were conducted. Surveillance was defined as liver imaging test ≥ 2 times with at least 3-month interval within 2 years prior to HCC diagnosis. RESULTS: Surveillance rate was 39.8%. Of the HCC patients with high-risk factors, only 182 (57.1%) had knowledge for the need for regular surveillance, and 141 (44.2%) had the accurate information about the method (ultrasound-based study). Surveillance group showed a higher proportion of early HCC (p < 0.001) and a longer overall survival (p < 0.001) compared to non-surveillance group. The multivariable Cox regression analysis indicated Child-Pugh class A, history of anti-viral therapy, low serum α-fetoprotein level, non-advanced Barcelona Clinic Liver Cancer stage as independent predictors of overall survival, while regular surveillance was not (p=0.436). CONCLUSION: Less than half of the newly diagnosed Korean HCC patients were under surveillance and the accurate perception for the need of HCC surveillance was insufficient. Of those under surveillance, most patients were diagnosed with early stage HCC, which led to the improved survival. Comprehensive efforts to optimize the surveillance program for the target population are warranted.

[Anisakiasis Induced Segmental Jejunum Obstruction].

Human anisakiasis is a disease caused by an infestation of the third stage larvae of family anisakidae. The ingested larvae invade the gastrointestinal wall, causing clinical symptoms that include abdomen pain, nausea, and vomiting. Although enteric anisakiasis is extremely rare, it can induce intestinal obstruction. We report a case in which emergency surgery was needed due to intestinal obstruction that coincided with symptoms related to anisakiasis, along with a brief literature review.

Liver volume-based prediction model stratifies risks for hepatocellular carcinoma in chronic hepatitis B patients on surveillance.

BACKGROUND AND AIM: The aim of this study was to determine whether dynamic computed tomography (CT)-measured liver volume predicts the risk of hepatocellular carcinoma (HCC) when the CT scans do not reveal evidence of HCC in chronic hepatitis B (CHB) patients on surveillance. METHODS: This retrospective multicentre cohort study included 1,246 patients who received entecavir and regular HCC surveillance in three tertiary referral centres in South Korea. Liver volumes were measured on portal venous phase CT images. A nomogram was developed based on Cox independent predictors and externally validated. Time-dependent receiver operating characteristic (ROC) analysis was performed for comparison with previous prediction models. RESULTS: Patients who received dynamic CT studies during surveillance had significantly higher risk for HCC compared to patients without CT studies (hazard ratio [HR] = 3.1; p < 0.001). Expected/measured liver volume ratio was an independent predictor of HCC (HR = 4.2; p = 0.002) in addition to age, sex and cirrhosis. The nomogram based on the four predictors discriminated risks for HCC (HR = 4.1 and 6.0 in derivation and validation cohort, respectively, for volume score > 150; p < 0.001). Time-dependent ROC analysis confirmed better performance of the volume score compared to HCC prediction models with conventional predictors (integrated area under curve = 0.758 vs. 0.661-0.712; p < 0.05). CONCLUSIONS: CT-measured liver volume is an independent predictor of future HCC, and nomogram-based liver volume score may stratify the risks of HCC in CHB patients who showed negative CT findings for HCC during surveillance.

Optimizing Surveillance Performance of Alpha-Fetoprotein by Selection of Proper Target Population in Chronic Hepatitis B.

Although alpha-fetoprotein (AFP) is the most widely used biomarker in hepatocellular carcinoma (HCC) surveillance, disease activity may also increase AFP levels in chronic hepatitis B (CHB). Since nucleos(t)ide analog (NA) therapy may reduce not only HBV viral loads and transaminase levels but also the falsely elevated AFP levels in CHB, we tried to determine whether exposure to NA therapy influences AFP performance and whether selective application can optimize the performance of AFP testing in CHB during HCC surveillance. A retrospective cohort of 6,453 CHB patients who received HCC surveillance was constructed from the electronic clinical data warehouse. Covariates of AFP elevation were determined from 53,137 AFP measurements, and covariate-specific receiver operating characteristics regression analysis revealed that albumin levels and exposure to NA therapy were independent determinants of AFP performance. C statistics were largest in patients with albumin levels ≥ 3.7 g/dL who were followed without NA therapy during study period, whereas AFP performance was poorest when tested in patients with NA therapy during study and albumin levels were < 3.7 g/dL (difference in C statics = 0.35, p < 0.0001). Contrary to expectation, CHB patients with current or recent exposure to NA therapy showed poorer performance of AFP during HCC surveillance. Combination of concomitant albumin levels and status of NA therapy can identify subgroup of CHB patients who will show optimized AFP performance.

A case of spontaneous esophagopleural fistula successfully treated by endoscopic stent insertion.

The most common cause of esophagorespiratory fistulas (ERFs) is associated with malignancy. The use of self-expandable metal stents is effective for the treatment of malignant ERFs, but benign ERF is rare, which is why its optimal treatment is not defined yet. There have been few reports describing benign esophagopleural fistula and its treatments in South Korea. Here, we report a rare case of spontaneous esophagopleural fistula, which was successfully treated by endoscopic placement of a membrane covered metal stent.

Is endoscopic mucosal resection a sufficient treatment for low-grade gastric epithelial dysplasia?

BACKGROUND/AIMS: The rate of diagnosis of gastric adenoma has increased because esophagogastroduodenoscopy is being performed at an increasingly greater frequency. However, there are no treatment guidelines for low-grade dysplasia (LGD). To determine the appropriate treatment for LGD, we evaluated the risk factors associated with the categorical upgrade from LGD to high grade dysplasia (HGD)/early gastric cancer (EGC) and the risk factors for recurrence after endoscopic treatment. METHODS: We compared the complication rates, recurrence rates, and remnant lesions in 196 and 56 patients treated with endoscopic submucosal dissection (ESD) and endoscopic mucosal resection (EMR), respectively, by histologically confi rming low-grade gastric epithelial dysplasia. RESULTS: The en bloc resection rate was significantly lower in the EMR group (31.1%) compared with the ESD group (75.0%) (p<0.001). However, no significant difference was observed in the prevalence of remnant lesions or recurrence rate (p=0.911) of gastric adenoma. The progression of LGD to HGD or EGC caused an increase in the incidence of tumor lesions >1 cm with surface redness and depressions. CONCLUSIONS: For the treatment of LGD, EMR resulted in a higher incidence of uncertain resection margins and a lower en bloc resection rate than ESD. However, there was no signifi cant difference in recurrence rate.