Background: Disruptions of the intestinal epithelial barrier (IEB) are frequently observed in various digestive diseases, including irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). This study assessed the improvement in the IEB during the laxative activity of phlorotannin (Pt) harvested from Ecklonia cava in constipation by examining the changes in the expression of the regulatory proteins for the tight junction (TJ) and adherens junction (AJ), and inflammatory cytokines in Sprague Dawley (SD) rats with loperamide (Lm)-induced constipation after a Pt treatment. Results: The Pt treatment induced laxative activity, including the improvement of feces-related parameters, gastrointestinal transit rate, and histological structure of the mid colon in Lm-treated SD rats. In addition, significant recovery effects were detected in the histology of IEB, including the mucus layer, epithelial cells, and lamina propria in the midcolon of Lm + Pt treated SD rats. The expression levels of E-cadherin and p120-catenin for AJ and the ZO-1, occludin, and Claudin-1 genes for TJ in epithelial cells were improved remarkably after the Pt treatment, but the rate of increase was different. Furthermore, the Pt treatment increased the expression level of several inflammatory cytokines, such asTNF-α, IL-6, IL-1β, IL-13, and IL-4 in Lm + Pt treated SD rats. Conclusions These results provide the first evidence that the laxative activity of Pt in SD rats with Lm-induced constipation phenotypes involve improvements in the IEB.

Background: To evaluate the chemosensitivity to doxorubicin (DOX) in two primary cells derived from a tumor of FVB/N-Trp53tm1Hw1 knockout (KO) mice with TALEN-mediated Trp53 mutant gene, we evaluated the cell survivability, cell cycle distribution, apoptotic cell numbers and apoptotic protein expression in solid tumor cells and ascetic tumor cells treated with DOX. Results: The primary tumor cells showed a significant (P < 0.05) defect for UV-induced upregulation of the Trp53 pro-tein, and consisted of different ratios of leukocytes, fibroblasts, epithelial cells and mesenchymal cells. The ­ IC50 level to DOX was lower in both primary cells ­(IC50 = 0.12 μM and 0.20 μM) as compared to the CT26 cells ­(IC50 = 0.32  μM), although the solid tumor was more sensitive. Also, the number of cells arrested at the G0/G1 stage was significantly decreased (24.7–23.1% in primary tumor cells treated with DOX, P < 0.05) while arrest at the G2 stage was enhanced to 296.8–254.3% in DOX-treated primary tumor cells compared with DOX-treated CT26 cells. Furthermore, apoptotic cells of early and late stage were greatly increased in the two primary cell-lines treated with DOX when compared to same conditions for CT26 cells. However, the Bax/Bcl-2 expression level was maintained constant in the primary tumor and CT26 cells. Conclusions To the best of our knowledge, these results are the first to successfully detect an alteration in chemosensitivity to DOX in solid tumor cells and ascetic tumor cells derived from tumor of FVB/N-Trp53tm1Hw1 mice TALENmediated Trp53 mutant gene.

OBJECTIVES: Studies evaluating weight changes during the coronavirus disease 2019 (COVID-19) pandemic have yielded inconsistent results, and most of those studies were based on self-reported anthropometric measures. We investigated changes in body mass index (BMI), professionally measured waist circumference (WC), and metabolic syndrome components from before to during the pandemic in a sample of the adult population in Korea. METHODS: This retrospective study included 1,118 male and female (age≥18 years) who underwent health checkups at a university medical center between January 1, 2016 and March 31, 2022. Changes in BMI, lifestyles, and metabolic syndrome components during the pandemic were analyzed using the paired t-test, McNemar test, generalized estimating equations, and repeated-measures analysis of variance. RESULTS: Changes in body weight, BMI, and body fat percentage during the pandemic were not clinically significant. However, statistically significant results were found for decreased physical activity (p<0.001) and WC (p<0.001), and exacerbation of all metabolic syndrome components (except serum triglyceride levels). Moreover, the metabolic syndrome prevalence increased significantly from 20.2% to 31.2% during the pandemic (p<0.001). The prevalence of abdominal obesity and high fasting blood glucose levels also significantly increased from 2019 to 2021. CONCLUSIONS Metabolic syndrome, its components, and fat distribution worsened significantly after the implementation of social distancing and lockdowns, despite no clinically significant changes in body weight and BMI. Further studies on the post- pandemic period should investigate the long-term impact of social lockdowns on BMI and the prevalence of metabolic syndrome.

Purpose: The KNOG-1101 study showed improved 2-year PFS with temozolomide during and after radiotherapy compared to radiotherapy alone for patients with anaplastic gliomas. This trial investigates the effect of concurrent and adjuvant temozolomide on health-related quality of life (HRQoL). Materials and Methods: In this randomized, open-label, phase II trial, 90 patients with World Health Organization grade III glioma were enrolled across multiple centers in South Korea between March 2012 to February 2015 and followed up through 2017. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30 (EORTC QLQ-C30) and 20-item EORTC QLQ-Brain Neoplasm (QLQ-BN20) were used to compare HRQoL between patients assigned to concurrent chemoradiotherapy with temozolomide followed by 6 cycles of adjuvant temozolomide (arm A) and radiotherapy (RT) alone (arm B). Results: Of the 90 patients in the study, 84 patients (93.3%) completed the baseline HRQoL questionnaire. Emotional functioning, fatigue, nausea and vomiting, dyspnea, constipation, appetite loss, diarrhea, seizures, itchy skin, drowsiness, hair loss, and bladder control were not affected by the addition of temozolomide. All other items did not differ significantly between arm A and arm B throughout treatment. Global health status particularly stayed consistent at the end of adjuvant temozolomide (p=0.47) and at the end of RT (p=0.33). Conclusion The addition of concurrent and adjuvant temozolomide did not show negative influence on HRQoL with improvement of progression-free survival for patients with anaplastic gliomas. The absence of systematic and clinically relevant changes in HRQoL suggests that an overall long-term net clinical benefit exists for concurrent and adjuvant temozolomide.

The purpose of this study was to evaluate the structural characteristics of the thread length of orthodontic mini-screws and the effects of insertion and removal torques according to the formation of the cutting flute. Two types of mini-screws were made, with a thread length of 6.0 mm and a thread length of 3.3 mm. In order to examine the effect of flute formation, the experiment group was divided into a miniscrew test group with flute formation and an experiment group without flute formation. To evaluate the effect of flute formation, two flutes were formed at 180°on the circumference, and at the tip of the mini screw, up to 4 mm for thread length of 6.0 mm and 2.4 mm for thread length of 3.3 mm. A biomechanical test block formed of 2 mm cortical bone and 10 mm cancellous bone was used to eliminate the influence of the difference in cortical bone thickness and bone density according to the insertion site. 1 mm diameter guide hole was drilled on the test block and the mini-screw was placed vertically. Using a 0.1 N·cm precision digital torque gauge, the maximum torque value was recorded at this time by embedding it to the top of the screw under a static load of 1.2 kg and the value when it was removed in the opposite direction. The insertion torque values for the 6.0 mm and 3.3 mm length mini screws were (29.53±1.84) N·cm and (26.84±2.15) N·cm, and the removal torque values are (14.50±1.37) N·cm and (13.15±2.89) N·cm, respectively.There were no statistically significant differences (P>0.05). The flute of 6.0 mm mini-screws had no statistically significant difference in both insertion and removal torque values and increased to (30.13±1.97) N·cm and (18.65±1.10) N·cm (P>0.05). In experiments with 3.3 mm mini-screws, the insertion and removal torque values decreased to (20.99±3.94) N·cm and (11.32±2.03) N·cm, respectively, showing a statistically significant decrease only in the insertion torque values (P<0.05). The insertion and removal torque values of the mini-screw were not significantly increased even when the screw length was doubled, and the flute formation effect was different with the screw length.

The purpose of this study was to evaluate the structural characteristics of the thread length of orthodontic mini-screws and the effects of insertion and removal torques according to the formation of the cutting flute. Two types of mini-screws were made, with a thread length of 6.0 mm and a thread length of 3.3 mm. In order to examine the effect of flute formation, the experiment group was divided into a miniscrew test group with flute formation and an experiment group without flute formation. To evaluate the effect of flute formation, two flutes were formed at 180°on the circumference, and at the tip of the mini screw, up to 4 mm for thread length of 6.0 mm and 2.4 mm for thread length of 3.3 mm. A biomechanical test block formed of 2 mm cortical bone and 10 mm cancellous bone was used to eliminate the influence of the difference in cortical bone thickness and bone density according to the insertion site. 1 mm diameter guide hole was drilled on the test block and the mini-screw was placed vertically. Using a 0.1 N·cm precision digital torque gauge, the maximum torque value was recorded at this time by embedding it to the top of the screw under a static load of 1.2 kg and the value when it was removed in the opposite direction. The insertion torque values for the 6.0 mm and 3.3 mm length mini screws were (29.53±1.84) N·cm and (26.84±2.15) N·cm, and the removal torque values are (14.50±1.37) N·cm and (13.15±2.89) N·cm, respectively.There were no statistically significant differences (P>0.05). The flute of 6.0 mm mini-screws had no statistically significant difference in both insertion and removal torque values and increased to (30.13±1.97) N·cm and (18.65±1.10) N·cm (P>0.05). In experiments with 3.3 mm mini-screws, the insertion and removal torque values decreased to (20.99±3.94) N·cm and (11.32±2.03) N·cm, respectively, showing a statistically significant decrease only in the insertion torque values (P<0.05). The insertion and removal torque values of the mini-screw were not significantly increased even when the screw length was doubled, and the flute formation effect was different with the screw length.

Background: To determine whether the background of BALB/c substrains affects the response to anti-tumor drugs, we measured for alterations in tumor growth, histopathological structure of the tumor, and expressions of tumorrelated proteins in three BALB/c substrains derived from different sources (BALB/cKorl, BALB/cA and BALB/cB), after exposure to varying concentrations of cisplatin (0.1, 1 and 5 mg/kg). Results: Cisplatin treatment induced similar responses for body and organ weights, serum analyzing factors, and blood analyzing factors in all BALB/c substrains with CT26 syngeneic tumor. Few differences were detected in the volume and histopathological structure of the CT26 tumor. Growth inhibition of CT26 tumors after exposure to cisplatin was greater in the BALB/cB substrain than BALB/cKorl and BALB/cA substrains, and a similar pattern was observed in the histopathological structure of tumors. However, the expression levels of other tumor-related factors, including Ki67, p27, p53, Bcl-2-associated X protein (Bax), B-cell lymphoma 2 (Bcl-2), caspase-3 (Cas-3), matrix metallopeptidase 2 (MMP2) and vascular endothelial growth factor (VEGF) proteins, were constantly maintained in the tumors of all three substrains after cisplatin treatment. A similar decrease pattern was observed for the expressions of inflammatory cytokines, including interleukin (IL)-1β, IL-6 and IL-10, in the CT26 tumors of the three BALB/c substrains. Conclusions Taken together, results of the present study indicate that the genetic background of the three BALB/c substrains has no major effect on the therapeutic responsiveness of cisplatin, except growth and histopathology of the CT26 syngeneic tumor.

Purpose: We investigated the efficacy of temozolomide during and after radiotherapy in Korean adultswith anaplastic gliomas without 1p/19q co-deletion. Materials and Methods: This was a randomized, open-label, phase 2 study and notably the first multicenter trial forKorean grade III glioma patients. Eligible patients were aged 18 years or older and hadnewly diagnosed non-co-deleted anaplastic glioma with an Eastern Cooperative OncologyGroup performance status of 0-2. Patients were randomized 1:1 to receive radiotherapyalone (60 Gy in 30 fractions of 2 Gy) (control group, n=44) or to receive radiotherapy withconcurrent temozolomide (75 mg/m2/day) followed by adjuvant temozolomide (150-200mg/m2/day for 5 days during six 28-day cycles) (treatment group, n=40). The primary endpointwas 2-year progression-free survival (PFS). Seventy patients (83.3%) were availablefor the analysis of the isocitrate dehydrogenase 1 gene (IDH1) mutation status. Results: The two-year PFS was 42.2% in the treatment group and 37.2% in the control group. Overallsurvival (OS) did not reach to significant difference between the groups. In multivariableanalysis, age was a significant risk factor for PFS (hazard ratio [HR], 2.08; 95% confidenceinterval [CI], 1.04 to 4.16). The IDH1mutation was the only significant prognostic factor forPFS (HR, 0.28; 95% CI, 0.13 to 0.59) and OS (HR, 0.19; 95% CI, 0.07 to 0.50). Adverseevents over grade 3 were seen in 16 patients (40.0%) in the treatment group and werereversible. Conclusion Concurrent and adjuvant temozolomide in Korean adults with newly diagnosed nonco-deleted anaplastic gliomas showed improved 2-year PFS. The survival benefit of this regimenneeds further analysis with long-term follow-up at least more than 10 years.

BACKGROUND/OBJECTIVES: Inflammatory Bowel Disease (IBD) has rapidly escalated in Asia (including Korea) due to increasing westernized diet patterns subsequent to industrialization. Factors associated with endoplasmic reticulum (ER) stress are demonstrated to be one of the major causes of IBD. This study was conducted to investigate the effect of Lycium barbarum (L. barbarum) on ER stress. MATERIALS/METHODS: Mouse embryonic fibroblast (MEF) cell line and polarized Caco-2 human intestinal epithelial cells were treated with crude extract of the L. chinense fruit (LF). Paracellular permeability was measured to examine the effect of tight junction (TJ) integrity. The regulatory pathways of ER stress were evaluated in MEF knockout (KO) cell lines by qPCR for interleukin (IL) 6, IL8 and XBP1 spliced form (XBP1s). Immunoglobulin binding protein (BiP), XBP1s and CCAAT/enhancer-binding homologous protein (CHOP) expressions were measured by RT-PCR. Scanning Ion Conductance Microscopy (SICM) at high resolution was applied to observe morphological changes after treatments. RESULTS: Exposure to LF extract strengthened the TJ, both in the presence and absence of inflammation. In polarized Caco-2 pretreated with LF, induction in the expression of proinflammatory marker IL8 was not significant, whereas ER stress marker XBP1s expression was significantly increased. In wild type (wt) MEF cells, IL6, CHOP and XBP1 spliced form were dose-dependently induced when exposed to 12.5–50 µg/mL extract. However, absence of XBP1 or IRE1α in MEF cells abolished this effect. CONCLUSION: Results of this study show that LF treatment enhances the barrier function and reduces inflammation and ER stress in an IRE1α-XBP1-dependent manner. These results suggest the preventive effect of LF on healthy intestine, and the possibility of reducing the degree of inflammatory symptoms in IBD patients.
Animals ; Asia ; Carrier Proteins ; Cell Line ; Diet ; Endoplasmic Reticulum ; Epithelial Cells ; Fibroblasts ; Fruit ; Humans ; Immunoglobulins ; Inflammation ; Inflammatory Bowel Diseases ; Interleukin-6 ; Interleukin-8 ; Interleukins ; Intestines ; Lycium ; Mice ; Microscopy ; Permeability ; Tight Junctions

In the brain, a reduction in extracellular osmolality causes water-influx and swelling, which subsequently triggers Cl⁻- and osmolytes-efflux via volume-regulated anion channel (VRAC). Although LRRC8 family has been recently proposed as the pore-forming VRAC which is activated by low cytoplasmic ionic strength but not by swelling, the molecular identity of the pore-forming swelling-dependent VRAC (VRAC(swell)) remains unclear. Here we identify and characterize Tweety-homologs (TTYH1, TTYH2, TTYH3) as the major VRAC(swell) in astrocytes. Gene-silencing of all Ttyh1/2/3 eliminated hypo-osmotic-solution-induced Cl⁻ conductance (I(Cl,swell)) in cultured and hippocampal astrocytes. When heterologously expressed in HEK293T or CHO-K1 cells, each TTYH isoform showed a significant I(Cl,swell) with similar aquaporin-4 dependency, pharmacological properties and glutamate permeability as I(Cl,swell) observed in native astrocytes. Mutagenesis-based structure-activity analysis revealed that positively charged arginine residue at 165 in TTYH1 and 164 in TTYH2 is critical for the formation of the channel-pore. Our results demonstrate that TTYH family confers the bona fide VRAC(swell) in the brain.
Arginine ; Astrocytes ; Brain ; Cytoplasm ; Glutamic Acid ; Humans ; Osmolar Concentration ; Permeability