Protective effect of genistein on radiation-induced intestinal injury in tumor bearing mice

BACKGROUND: Radiation therapy is the most widely used treatment for cancer, but it causes the side effect of mucositis due to intestinal damage. We examined the protective effect of genistein in tumor-bearing mice after abdominal irradiation by evaluation of apoptosis and intestinal morphological changes. METHODS: Mouse colon cancer CT26 cells were subcutaneously injected at the flank of BALB/c mice to generate tumors. The tumor-bearing mice were treated with abdominal radiation at 5 and 10 Gy, and with genistein at 200 mg/kg body weight per day for 1 d before radiation. The changes in intestinal histology were evaluated 12 h and 3.5 d after irradiation. To assess the effect of the combination treatment on the cancer growth, the tumor volume was determined at sacrifice before tumor overgrowth occurred. RESULTS: Genistein significantly decreased the number of apoptotic nuclei compared with that in the irradiation group 12 h after 5 Gy irradiation. Evaluation of histological changes showed that genistein ameliorated intestinal morphological changes such as decreased crypt survival, villus shortening, and increased length of the basal lamina 3.5 d after 10 Gy irradiation. Moreover, the genistein-treated group exhibited more Ki-67-positive proliferating cells in the jejunum than the irradiated control group, and crypt depths were greater in the genistein-treated group than in the irradiated control group. The mean weight of the CT26 tumors was reduced in the group treated with genistein and radiation compared with the control group. CONCLUSION: Genistein had a protective effect on intestinal damage induced by irradiation and delayed tumor growth. These results suggest that genistein is a useful candidate for preventing radiotherapy-induced intestinal damage in cancer patients

Attenuated Age-Related Thinning of Peripapillary Retinal Nerve Fiber Layer in Long Eyes

PURPOSE: To assess the impact of axial length on the age-related peripapillary retinal nerve fiber layer (RNFL) thinning. METHODS: This cross-sectional observational comparative case series included 172 eyes from 172 healthy Korean subjects. Peripapillary RNFL thickness was measured using an Optic Disc Cube 200 x 200 scan of spectral domain Cirrus HD OCT and the axial length was measured using IOL Master Advanced Technology. In age groups based on decade, the normal ranges of peripapillary RNFL thickness for average, quadrant, and clock-hour sectors were determined with 95% confidence intervals. After dividing the eyes into two groups according to axial length (cut-off, 24.50 mm), the degrees of age-related RNFL thinning were compared. RESULTS: Among the eyes included in the study, 53 (30.81%) were considered to be long eyes (axial length, 25.04 +/- 0.48 microm) and 119 (69.19%) were short-to-normal length eyes (axial length, 23.57 +/- 0.60 microm). The decrease in average RNFL thickness with age was less in long eyes (negative slope, -0.12 microm/yr) than in short-to-normal length eyes (negative slope, -0.32 microm/yr) (p < 0.001). CONCLUSIONS: Age-related thinning of peripapillary RNFL thickness is attenuated in long eyes compared to short-to-normal length eyes.ope

Prevalence and Characteristics of Glaucoma among Korean Adults

PURPOSE: The purpose of this study was to investigate the prevalence and characteristics of glaucoma in the population of the rural Korean town, Sangju. METHODS: Residents of Sangju aged greater than 50 years old were included in this study. Participants completed an interview examining their medical and ophthalmic history Information was collected on the participants' uncorrected and best corrected vision scores, slit lamp examination results, angle width measurements using the Van Herick technique, gonioscopy if the angle width was less than 1 / 4 angle, intraocular pressure (IOP) assessed with the Goldmann applanation tonometry, optic disc examination results, and a visual field test results using frequency-doubling perimetry in cases in which glaucoma was suspected. Glaucoma was diagnosed according to the criteria described by the International Society for Geographic and Epidemiological Ophthalmology. RESULTS: 1,118 residents aged greater than 50 years were examined initially from a population of 2,984 people. Of these, 671 subjects (60%) participated in this study. The prevalence of glaucoma was determined to be 3.4% (95% confidence interval [CI], 2.1-4.8). Open-angle glaucoma with low IOP was determined to be the most common form with a prevalence rate as high as 2.5% (95% CI, 1.8-3.7). Additionally, primary angle closure glaucoma was determined to have a prevalence rate of 0.3% (95% CI, 0.1-0.9). Open-angle glaucoma with low IOP accounted for 94.4% of the open-angle glaucoma cases. CONCLUSIONS: The prevalence of glaucoma among the population of rural Sangju was 3.4%, and open-angle glaucoma with low IOP was the most common form accounting for 94.4% of the total number of cases.ope

Intelligent Chiral Sensing Based on Supramolecular and Interfacial Concepts

Of the known intelligently-operating systems, the majority can undoubtedly be classed as being of biological origin. One of the notable differences between biological and artificial systems is the important fact that biological materials consist mostly of chiral molecules. While most biochemical processes routinely discriminate chiral molecules, differentiation between chiral molecules in artificial systems is currently one of the challenging subjects in the field of molecular recognition. Therefore, one of the important challenges for intelligent man-made sensors is to prepare a sensing system that can discriminate chiral molecules. Because intermolecular interactions and detection at surfaces are respectively parts of supramolecular chemistry and interfacial science, chiral sensing based on supramolecular and interfacial concepts is a significant topic. In this review, we briefly summarize recent advances in these fields, including supramolecular hosts for color detection on chiral sensing, indicator-displacement assays, kinetic resolution in supramolecular reactions with analyses by mass spectrometry, use of chiral shape-defined polymers, such as dynamic helical polymers, molecular imprinting, thin films on surfaces of devices such as QCM, functional electrodes, FET, and SPR, the combined technique of magnetic resonance imaging and immunoassay, and chiral detection using scanning tunneling microscopy and cantilever technology. In addition, we will discuss novel concepts in recent research including the use of achiral reagents for chiral sensing with NMR, and mechanical control of chiral sensing. The importance of integration of chiral sensing systems with rapidly developing nanotechnology and nanomaterials is also emphasized

Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

Minimal Symptom Expression' in Patients With Acetylcholine Receptor Antibody-Positive Refractory Generalized Myasthenia Gravis Treated With Eculizumab

The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension

Replication Fork Stability Confers Chemoresistance in BRCA-deficient Cells

Brca1- and Brca2-deficient cells have reduced capacity to repair DNA double-strand breaks (DSBs) by homologous recombination (HR) and consequently are hypersensitive to DNA damaging agents, including cisplatin and poly(ADP-ribose) polymerase (PARP) inhibitors. Here we show that loss of the MLL3/4 complex protein, PTIP, protects Brca1/2-deficient cells from DNA damage and rescues the lethality of Brca2-deficient embryonic stem cells. However, PTIP deficiency does not restore HR activity at DSBs. Instead, its absence inhibits the recruitment of the MRE11 nuclease to stalled replication forks, which in turn protects nascent DNA strands from extensive degradation. More generally, acquisition of PARPi and cisplatin resistance is associated with replication fork (RF) protection in Brca2-deficient tumor cells that do not develop Brca2 reversion mutations. Disruption of multiple proteins, including PARP1 and CHD4, leads to the same end point of RF protection, highlighting the complexities by which tumor cells evade chemotherapeutic interventions and acquire drug resistance

Genome-wide association study of lung adenocarcinoma in East Asia and comparison with a European population

Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset (n = 115) identified novel candidate genes, including FADS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European studies, four loci were identified at 2p11, 4q32, 16q23, and 18q12. At the same time, most of our findings in East Asian populations showed no evidence of association in European populations. In our studies drawn from East Asian populations, a polygenic risk score based on the 25 loci had a stronger association in never-smokers vs. individuals with a history of smoking (P interaction  = 0.0058). These findings provide new insights into the etiology of lung adenocarcinoma in individuals from East Asian populations, which could be important in developing translational applications

Genome-wide association study of lung adenocarcinoma in East Asia and comparison with a European population.

Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset (n = 115) identified novel candidate genes, including FADS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European studies, four loci were identified at 2p11, 4q32, 16q23, and 18q12. At the same time, most of our findings in East Asian populations showed no evidence of association in European populations. In our studies drawn from East Asian populations, a polygenic risk score based on the 25 loci had a stronger association in never-smokers vs. individuals with a history of smoking (Pinteraction = 0.0058). These findings provide new insights into the etiology of lung adenocarcinoma in individuals from East Asian populations, which could be important in developing translational applications

Antimicrobial Resistance of Helicobacter pylori Isolates in Korea

Antimicrobial resistance is a growing problem in the eradication of Helicobacter pylori. A combination therapy with proton pump inhibitor, clarithromycin, and amoxicillin is recommended as the first-line treatment regimen in Korea. However, the eradication rate with a standard triple therapy has been unsatisfactory in the last decade, and one of the main reasons for treatment failure is the increasing prevalence of strains resistant to antimicrobials. Therefore, comprehensive and detailed information on antimicrobial resistance is mandatory to optimize the strategy of eradication treatment. The antimicrobial resistance of H. pylori is reported to vary according to study population, geographical region, and test methods. In this review, the prevalence of antimicrobial resistance of H. pylori isolates in Korea is summarized on the basis of recent studies