The Inhibitory Effects of Plant Derivate Polyphenols on the Main Protease of SARS Coronavirus 2 and Their Structure-Activity Relationship.

The main protease (Mpro) is a major protease having an important role in viral replication of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the novel coronavirus that caused the pandemic of 2020. Here, active Mpro was obtained as a 34.5 kDa protein by overexpression in E. coli BL21 (DE3). The optimal pH and temperature of Mpro were 7.5 and 37 °C, respectively. Mpro displayed a Km value of 16 µM with Dabcyl-KTSAVLQ↓SGFRKME-Edans. Black garlic extract and 49 polyphenols were studied for their inhibitory effects on purified Mpro. The IC50 values were 137 µg/mL for black garlic extract and 9-197 µM for 15 polyphenols. The mixtures of tannic acid with puerarin, daidzein, and/or myricetin enhanced the inhibitory effects on Mpro. The structure-activity relationship of these polyphenols revealed that the hydroxyl group in C3', C4', C5' in the B-ring, C3 in the C-ring, C7 in A-ring, the double bond between C2 and C3 in the C-ring, and glycosylation at C8 in the A-ring contributed to inhibitory effects of flavonoids on Mpro.

How can we predict the presence of missed synchronous lesions after endoscopic submucosal dissection for early gastric cancers or gastric adenomas?

GOALS: To identify predictive factors associated with the presence of missed synchronous lesions after endoscopic submucosal dissection (ESD) for gastric adenoma or early gastric cancer (EGC). BACKGROUND: Secondary gastric neoplasms that develop during follow-up period after ESD for gastric adenoma or EGC are divided into metachronous lesions and missed synchronous lesions. METHODS: ESD was performed in 250 patients with EGC or gastric adenoma. The patients with endoscopic follow-ups of <1 year, patients without curative resection, and patients with additional surgery were excluded from the study. Missed synchronous lesions were defined as secondary gastric neoplasms detected within one year of ESD but initially missed. We compared clinicopathologic factors between patients with missed synchronous lesions and patients without missed synchronous lesions. RESULTS: Missed synchronous lesions were found in 11.6% of the patients (29/250). The occurrence of missed synchronous lesions had significant correlation with tumor number at the time of ESD and age in the univariate analysis. Tumor number at the time of ESD and age were significant independent predictive factors for presence of missed synchronous lesions by multivariate logistic regression analysis (odds ratio 5.302, P = 0.006; odds ratio 2.315, P = 0.040, respectively). Missed synchronous lesions tended to be smaller, often located in the same third of the stomach as the main lesions. CONCLUSIONS: Tumor number at the time of ESD and age could be predictive factors for the presence of missed synchronous lesions after ESD. Careful endoscopic surveillance should be performed after ESD for multiple lesions or for elderly patients.

A comparative study on the efficacy of covered metal stent and plastic stent in unresectable malignant biliary obstruction.

BACKGROUND/AIMS: The placement of self expandable metal stent (SEMS) is one of the palliative therapeutic options for patients with unresectable malignant biliary obstruction. The aim of this study was to compare the effectiveness of a covered SEMS versus the conventional plastic stent. METHODS: We retrospectively evaluated 44 patients with unresectable malignant biliary obstruction who were treated with a covered SEMS (21 patients) or a plastic stent (10 Fr, 23 patients). We analyzed the technical success rate, functional success rate, early complications, late complications, stent patency and survival rate. RESULTS: There was one case in the covered SEMS group that had failed technically, but was corrected successfully using lasso. Functional success rates were 90.5% in the covered SEMS group and 91.3% in the plastic stent group. There was no difference in early complications between the two groups. Median patency of the stent was significantly prolonged in patients who had a covered SEMS (233.6 days) compared with those who had a plastic stent (94.6 days) (p=0.006). During the follow-up period, stent occlusion occurred in 11 patients of the covered SEMS group. Mean survival showed no significant difference between the two groups (covered SEMS group, 236.9 days; plastic stent group, 222.3 days; p=0.182). CONCLUSIONS: The patency of the covered SEMS was longer than that of the plastic stent and the lasso of the covered SEMS was available for repositioning of the stent.

Risk factors for perforations associated with endoscopic submucosal dissection in gastric lesions: emphasis on perforation type.

BACKGROUND: Endoscopic submucosal dissection (ESD) enables en bloc resection of larger gastric neoplasms. However, the procedure is associated with a high incidence of perforation. Perforations during ESD are divided into macro- and microperforations. Although both types of perforations could cause widespread tissue injury and secondary sepsis, very little is known concerning the risk factors for perforations according to the type of perforation. Thus, this study was performed to evaluate the risk factors for macro-, micro-, and all perforations (both) during ESD. METHODS: 823 gastric lesions (gastric adenoma or early gastric cancer) in 729 patients treated by ESD were enrolled, and their records were reviewed retrospectively. Risk factors were evaluated, focusing on age, sex, gastric neoplasm-related factors (12 locations, resected size, gross type of lesions, presence of ulceration, presence of fibrosis, pathologic diagnosis, and depth of invasion), and ESD procedure-related factors (type of knife, immediate bleeding during ESD, en bloc resection, procedure time, and the number of ESD cases experienced by the endoscopist). RESULTS: Of the 823 gastric lesions, the rates of all perforation, macroperforation, and microperforation were 9.6%, 7.5%, and 2.1%, respectively. Risk factors for all perforations on multivariate analysis were location of tumor in upper portion, presence of fibrosis, and long procedure time (>2 h). Risk factors for macroperforations were the same as all perforations. Risk factors for microperforations on multivariate analysis were old age (≥81 years), depth of invasion (muscularis mucosa), and long procedure time (>2 h). CONCLUSIONS: The risk factors for perforations during ESD could differ according to the type of perforation. Therefore, although macroperforation did not develop during ESD, it would be necessary to consider the possibility of microperforation in case of old age, long procedure time, and (deep) depth of invasion.

Emergence of adefovir-resistant mutants after reversion to YMDD wild-type in lamivudine-resistant patients receiving adefovir monotherapy.

BACKGROUND: To evaluate the effect of reversion to YMDD wild-type on emergence of adefovir (ADV)-resistant mutation and antiviral activity of ADV in lamivudine (LAM)- resistant patients. METHODS: We determined YMDD mutations and ADV-resistant mutations before and every 3 months during ADV monotherapy in 33 LAM-resistant patients using the restriction fragment mass polymorphism (RFMP) method. RESULTS: Reversion to pure YMDD wild-type hepatitis B virus (HBV) occurred in 6% (2/33), 9% (3/33), 20% (4/20) and 35% (6/17) of patients after 12, 24, 36 and 48 weeks, respectively. Five (29%) patients were found to have pure YMDD mutants at 48 weeks of therapy. Among 33 patients, 4 (12%) patients developed ADV-resistant mutations at 48 weeks of therapy. Adefovir-resistant mutants emerged in all patients after reversion to YMDD wild-type HBV. The mean serum HBV reductions, evaluated at 24 weeks of therapy, were not different between patients with and without reversion to YMDD wild-type HBV (-3.1 log(10) copies/mL vs-3.4 log(10) copies/mL, P > 0.05). CONCLUSIONS: ADV-resistant mutations emerged after reversion to YMDD wild-type in LAM-resistant patients who received ADV monotherapy. Thus, ADV add-on therapy may be necessary to reduce the incidence of developing ADV resistance in patients with LAM resistance.