Embryonic development through in vitro fertilization using high-quality bovine sperm separated in a biomimetic cervix environment.

This study is the first to identify bovine blastocysts through in vitro fertilization (IVF) of matured oocytes with a large quantity of high-quality sperm separated from a biomimetic cervix environment. We obtained high-quality sperm in large quantities using an IVF sperm sorting chip (SSC), which could mimic the viscous environment of the bovine cervix during ovulation and facilitates isolation of progressively motile sperm from semen. The viscous environment-on-a-chip was realized by formulating and implementing polyvinylpyrrolidone (PVP)-based solutions for the SSC medium. Sperm separated from the IVF-SSC containing PVP 1.5% showed high motility, normal morphology and high DNA integrity. As a result of IVF, a higher rate of hatching blastocysts, which is the pre-implantation stage, were observed, compared to the conventional swim-up method. Our results may significantly contribute to improving livestock with superior male and female genetic traits, thus overcoming the limitation of artificial insemination based on the superior genetic traits of existing males.

Ovotestis Isolation and Cryopreservation of Nesiohelix samarangae (Oriental Snail) as a Snail Model for Conserving Other Endangered Snail Species.

This study aimed to develop a cryopreservation system for the reproductive organs of Nesiohelix samarangae (oriental snail) to support the conservation of their species. The reproductive glands of N. samarangae are divided into numerous acini by acinar boundaries. Within each acinus, the presence of spermatogonia, spermatocytes, spermatids, and sperm were observed, indicating various stages of sperm development. The spermatocytes were irregular in shape and possessed large nuclei. Spermatids, on the other hand, were predominantly located within the lumen of the tissue and exhibited densely packed nuclei. Furthermore, sperm with tails attached were observed within the tissue. In order to preserve the oriental snail species, we utilized the vitrification method to freeze the reproductive organs. Comparing the two methods, it was observed that cryopreservation of ovotestis using 2% alginate encapsulation exhibited superior viability following thawing, surpassing the viability achieved with the non-encapsulated approach. In this study, the establishment of a cryopreservation system for the reproductive organs of the oriental snail not only contributes to the genetic conservation of the endangered snail species but also plays a role in maintaining genetic resources and diversity.

Impact of COVID-19 on ophthalmic medical access during successive waves: Demographics, disease factors, and wave locations.

BACKGROUND: The coronavirus disease (COVID-19) pandemic significantly impacted medical care, including ophthalmology. This study aimed to identify factors associated with reduced ophthalmic medical access during the pandemic. METHODS: This nationwide population-based cohort study analysed South Korean health insurance claims data from January 2019 to November 2021. Outpatient visits and surgeries for age-related macular degeneration, cataract, diabetic retinopathy, glaucoma, and retinal detachment during the two pandemic waves were compared with those in the non-pandemic period. Poisson regression was used to estimate incidence rate ratios and changes in outpatient visits and surgeries between waves concerning patient age, sex, residential location, and health insurance type. RESULTS: Outpatient visits for five eye diseases decreased in the first wave (0.733-0.985, P < 0.001). In the second wave, only outpatient visits for age-related macular degeneration, cataract, and glaucoma decreased (0.754, 0.878, and 0.874, respectively, all P < 0.001). Age-related macular degeneration, cataract, and glaucoma surgeries were significantly reduced in the first wave (0.829, P < 0.001; 0.836, P < 0.001; 0.904, P = 0.030, respectively). Age-related macular degeneration (0.852) and cataract (0.716) surgeries dropped in the second wave. Women and elderly (>65 years) patients curtailed outpatient visits and surgeries more throughout the pandemic and were less resilient during the second wave. Wave location was also related to outpatient visits and surgeries. CONCLUSIONS: The COVID-19 pandemic decreased outpatient visits and surgeries for eye diseases, with more significant impact on women, older patients, and those residing near wave locations. These findings can inform healthcare policies to minimise future pandemic impacts on healthcare delivery.

Control of the growth and development of murine preantral follicles in a biomimetic ovary using a decellularized porcine scaffold.

This study aimed to derive mature oocytes from murine preantral follicles cultured in a biomimetic ovary with a porcine scaffold using decellularization technology. We evaluated the DNA content and the presence of cell and extracellular matrix (ECM) components, including collagen, elastin, and glycosaminoglycans (GAGs), in decellularized (decell) porcine ovaries. The DNA content inthe decell ovarian tissues was approximately 94 % less than that in native tissues (66 ± 9.8 ng/mg vs. 1139 ± 269 ng/mg). Furthermore, the ECM component integrity was maintained in the decell ovarian tissue. The soluble collagen concentration of native ovarian tissue (native) was 195.34 ± 15.13 µg/mg (dry wt.), which was less than 878.6 ± 8.24 µg/mg for the decell ovarian tissue due to the loss of cellular mass. Hydrogels derived from decell porcine ovaries were prepared to develop an in vitro biomimetic ovary with appropriate ECM concentration (2-6 mg/mL). Scanning electron microscope (SEM) imagining revealed that the complex fiber network and porous structure were maintained in all groups treated with varying ECM concentration (2-6 mg/mL). Furthermore, rheometer analysis indicated that mechanical strength increased with ECM concentration in a dose-dependently. The preantral follicles cultured with 4 mg/mL ECM showed high rates of antral follicle (66 %) and mature oocyte (metaphase II) development (47 %). The preantral follicles cultured in a biomimetic ovary with a decell porcine scaffold showed a higher rate of antral follicle and mature oocytes than those cultured in other biomaterials such as collagen and Matrigel. In mature oocytes derived from antral follicles, meiotic spindles and nuclei were stained using a tubulin antibody and Hoechst, respectively. Two-cell embryos were developed from MII oocytes following parthenogenetic activation. Preantral follicles were cultured in a biomimetic ovary derived from the ECM of a decell porcine ovary, and embryos were generated from MII oocytes. This biomimetic ovary could contribute to restoring fertility in infertile women with reduced ovarian function, benefit mating efforts for endangered species, and maintain animals with valuable genetic traits.

Trends in treatment patterns and survival outcomes in pancreatic cancer: A nationwide population-based study in Korea.

BACKGROUND: The treatment of pancreatic cancer has evolved; however, real-world data on treatment trends remain scarce. This study investigated treatment patterns for pancreatic cancer and patient survival using a nationwide population-based study in Korea. METHODS: Using the National Health Insurance database, data from 78,920 patients diagnosed with pancreatic cancer in Korea between 2006 and 2019 were extracted. Treatment patterns and survival by age group and year of diagnosis were examined. RESULTS: Primary treatment was delivered as follows: 16,562 patients (21.0%) underwent surgery, 20,998 patients (26.6%) received chemotherapy, 1332 patients (1.7%) received chemoradiotherapy, and 40,040 patients (50.7%) received supportive care only. The proportion of patients undergoing surgery or chemotherapy increased gradually in all age groups over time. The commonly used anti-cancer drugs have changed from gemcitabine±erlotinib to gemcitabine+nab-paclitaxel and FOLFIRINOX. Survival improved mainly in patients who underwent surgery or chemotherapy. Median overall survival for all patients improved from 5.5 months in 2006-2008 to 9.8 months in 2018-2019, with greater improvement observed in younger age groups: 8.8-18.8 months, age ≤59 years, 6.8-14.6 months, age 60-69 years, 4.2-8.3 months, age 70-79 years and 2.4-3.4 months, age ≥80 years (all p < 0.0001). CONCLUSIONS: An increase in the rates of surgery and chemotherapy for pancreatic cancer was observed. Survival rates for pancreatic cancer have generally improved over the past decade and are greater in patients undergoing surgery or chemotherapy and in younger age groups.

Risk of pancreatic cancer after acute pancreatitis: A population-based matched cohort study.

BACKGROUND: We investigated the short- and long-term risks of pancreatic cancer after the diagnosis of acute pancreatitis. METHODS: This population-based matched-cohort study used data from the Korean National Health Insurance Service database. Patients with acute pancreatitis (n = 25,488) were matched with the control group (n = 127,440) based on age, sex, body mass index, smoking status, and diabetes. We estimated the hazard ratios for developing pancreatic cancer in both groups using Cox regression analysis. RESULTS: During a median follow-up of 5.4 years, pancreatic cancer developed in 479 patients (1.9%) in the acute pancreatitis group and 317 patients (0.2%) in the control group. Compared with the control group, the risk of pancreatic cancer in the acute pancreatitis group was very high within the first 2 years, which gradually decreased over time. The hazard ratio for the risk of developing pancreatitis was 8.46 (95% confidence interval, 5.57-12.84) at 1-2 years, and then decreased to 3.62 (95% confidence interval, 2.26-4.91) at 2-4 years. However, even after 8-10 years, the hazard ratio was still statistically significantly increased to 2.80 (95% confidence interval, 1.42-5.53). After 10 years, there was no significant difference in the risk of pancreatic cancer between the two groups. CONCLUSIONS: The risk of pancreatic cancer increases rapidly after acute pancreatitis diagnosis, gradually declines after 2 years, and remains elevated for up to 10 years. Further studies are needed to determine the long-term effects of acute pancreatitis on the risk of pancreatic cancer.

Germ Cell Isolation and Cryopreservation from Reproductive Organs of Brown Mealworm.

This study aimed to isolate and freeze germ cells from the superior brown mealworm. Styrofoam diet changes were observed for 20 days to determine whether mealworms were useful insects for decomposing Styrofoam. The average weight of mealworms before the Styrofoam diet was 500 mg, which decreased to 336 mg at D20 after their diet. To preserve mealworms with excellent Styrofoam-degrading ability, we first isolated the reproductive organs of mealworms, testes, ovaries, sperms, and ovarioles. Morphologically, male and female adult brown mealworms were distinguished according to the presence or absence of a protrusion at the tip of the fifth segment of the abdomen. Sperms and ovarioles were observed in anatomically isolated testes and ovaries. We compared mechanical and enzymatic (collagenase I) methods to effectively isolate ovarioles from adult female brown mealworms. For the enzymatic method, most were torn and burst as the membrane of the ovarioles was damaged by collagenase I, unlike the mechanical method. To preserve the superior genetic resources of mealworms, we cryopreserved the ovaries of female brown mealworms using slow-freezing and vitrification. Histological analysis showed that the yolk sac was completely damaged in the ovaries after slow-freezing. However, only partial damage was achieved in the vitrification group compared to the control group (no freezing). The newly developed vitrification method with alginate-encapsulated ovarioles maintained the yolk sac in the ovarioles but was evenly distributed. These results provide basic data for reproductive studies of other useful insects and contribute to the biobanking and fertility preservation of superior mealworm germ cells and endangered insects.

Impact of intensive rehabilitation on long-term prognosis after stroke: A Korean nationwide retrospective cohort study.

An increasing number of patients are receiving rehabilitation after stroke. But the impact of intensive rehabilitation on the long-term prognosis of patients with stroke remains to be elucidated. The purpose of this study was to identify the impact of intensive rehabilitation on the long-term prognosis of patients with stroke using data from the National Health Insurance Service database. This is a register-based, retrospective cohort study. Using data from the National Health Insurance Service database, we included the patients who received rehabilitation for stroke from 2006 to 2013. Of the 14,984 patients diagnosed with stroke, 2483 died within 1 year, and 2866 did not receive rehabilitation; hence, they were also excluded. The final sample included 9635 (49.2% men, 50.8% women) patients. After correcting for covariates, the Cox model was used to evaluate the effects of physical therapy (PT) and occupational therapy (OT) on survival. We estimated the independent contribution of each factor to the risk of death from the initiation of rehabilitation. Significant differences in mortality were observed according to age, Charlson comorbidity index (CCI), income level, and stroke type. Patients with stroke who received both PT and OT had a better long-term prognosis than those who received either treatment alone. Therapy performed by a physical therapist with more than 120 hours of training effectively improved the patients' long-term prognosis. Intensive PT and OT will help improve the long-term prognosis of patients with stroke. This study emphasizes the importance of intensive rehabilitation in these patients.

A Small Molecule Promoting Neural Differentiation Suppresses Cancer Stem Cells in Colorectal Cancer.

Cancer stem cells (CSCs) are a tumor cell subpopulation that drives tumor progression and metastasis, leading to a poor overall survival of patients. In colorectal cancer (CRC), the hyper-activation of Wnt/ß-catenin signaling by a mutation of both adenomatous polyposis coli (APC) and K-Ras increases the size of the CSC population. We previously showed that CPD0857 inactivates Wnt/ß-catenin signaling by promoting the ubiquitin-dependent proteasomal degradation of ß-catenin and Ras proteins, thereby decreasing proliferation and increasing the apoptosis of CRC lines. CPD0857 also decreased the growth and invasiveness of CRC cells harboring mutant K-Ras resistant to EGFR mAb therapy. Here, we show that CPD0857 treatment decreases proliferation and increases the neuronal differentiation of neural progenitor cells (NPCs). CDP0857 effectively reduced the expression of CSC markers and suppressed self-renewal capacity. CPD0857 treatment also inhibited the proliferation and expression of CSC markers in D-K-Ras MT cells carrying K-Ras, APC and PI3K mutations, indicating the inhibition of PI3K/AKT signaling. Moreover, CPD0857-treated xenograft mice showed a regression of tumor growth and decreased numbers of CSCs in tumors. We conclude that CPD0857 could serve as the basis of a drug development strategy targeting CSCs activated through Wnt/ß-catenin-Ras MAPK-PI3K/AKT signaling in CRCs.

Lifestyle, body mass index, diabetes, and the risk of pancreatic cancer in a nationwide population-based cohort study with 7.4 million Korean subjects.

BACKGROUND: Large-scale epidemiological studies on pancreatic cancer in non-Western populations are insufficient. We investigated the risk factors for pancreatic cancer. METHODS: Using the Korean National Health Insurance database, subjects who participated in the health examination program between 2005 and 2006 were identified and followed up until 2017. Adjusted hazard ratios (HRs) for pancreatic cancer risk were estimated using a Cox proportional hazards model. RESULTS: During 11.5 years follow-up, 22,543 of 7,445,947 participants were newly diagnosed with pancreatic cancer. Compared with normal-weight subjects, pancreatic cancer risk was increased in those with severe obesity (BMI ≥ 28 kg/m2) (HR = 1.16; 95% CI, 1.11-1.23). Subjects with diabetes had an increased risk compared with those without diabetes (HR = 1.48; 95% CI, 1.43-1.53). Current smokers had a higher risk than never smokers (HR = 1.43; 95% CI, 1.38-1.48). Current smoking combined with diabetes increased the risk compared with never smokers without diabetes (HR = 2.13; 95% CI, 2.00-2.28). Current smoking combined with BMI ≥ 25 kg/m2 had an increased risk compared with never smokers with BMI < 23 kg/m2 (HR = 1.55; 95% CI, 1.46-1.65). CONCLUSION: Smoking, obesity, and diabetes are significant risk factors for pancreatic cancer in Koreans. Lifestyle modifications for smoking and obesity would be beneficial for pancreatic cancer prevention.

A simple and efficient cryopreservation method for mouse small intestinal and colon organoids for regenerative medicine.

Organoid cryopreservation method is one of key step in the organoid culture. We aimed to establish a simple and efficient cryopreservation method for mouse small intestinal organoids (MIOs) and colon organoids (MCOs) using various concentrations of cryoprotectant. Based on the theoretical simulation, we optimized the dimethyl sulfoxide (DMSO) concentration by pretreating the organoids with 5, 7.5, and 10% DMSO for 30 min at 4 °C to allow penetration into the organoids and evaluated their viability, proliferation, and function after cryopreservation. Gene expression in the MIOs and staining of lineage markers were examined real-time PCR. The organoids in the DMSO-treated groups as well as the control, expressed ChrgA, Ecad, Muc2, Lyz, villin, and Lgr5, and there are no significant. A forskolin-induced swelling assay for MIOs was performed to confirm normal cystic fibrosis transmembrane conductance regulator (CFTR) activity. Similar forskolin-induced swelling was observed in the DMSO-treated groups and the control. In addition, MCOs were transplanted into mouse colon for confirmation of regeneration therapy efficacy. Thawing organoids were cultured for two and four sequential passages after cryopreservation with 5% DMSO to confirm any changes in the gene expression of lineage markers after subculture. We developed a simple and efficient organoid freezing method using 5% DMSO with low potential toxicity and validated our findings with theoretical simulation.

The Associations of Tonsillectomy with Adenoidectomy with Pneumonia and Appendicitis Based on National Sample Cohort Data from the Korean National Health Insurance Service.

Introduction The association between tonsillectomy with adenoidectomy (T&A) with appendicitis is controversial, and the association of T&A with pneumonia has not been investigated. Objective To investigate the associations of T&A with pneumonia and appendicitis using data from the Korean National Health Insurance Service National Sample Cohort. Methods We selected patients between the ages of 3 and 10 years who had undergone T&A in 2005 and were monitored since the performance of the T&A until 2013. The control group was established to have similar propensities for demographic characteristics compared to the T&A group. For eight years after the T&A, the number of patients with a diagnosis of pneumonia, patients who were admitted due to pneumonia, and those who underwent appendectomy were analyzed. The risk factors for pneumonia and appendectomy were analyzed. Results The number of pneumonia diagnoses was significantly higher in the T&A group than in the control group ( p = 0.023), but there were no significant differences in the number of admissions due to pneumonia between the 2 groups ( p = 0.155). Younger age and T&A were significant risk factors for the development of pneumonia. There were no significant differences in the number of appendectomies between the T&A and the control groups ( p = 0.425), neither were there significant risk factors for appendectomy. Conclusion Tonsillectomy with adenoidectomy was associated with an increase in pneumonia diagnoses, but it was not associated with the number of appendectomies. The associations of T&A with pneumonia and appendicitis were analyzed in this population-based study.

Improved conditions of a whole testis organ culture system in terms of spermatogonial proliferation levels in marine medaka (Oryzias dancena).

In vitro spermatogenesis can be performed for marine medaka (Oryzias dancena) via whole testis organ cultures, but spermatogenesis could only be maintained during the early phase of culturing, suggesting that the culture conditions can be further optimized. To improve the culture conditions, we examined the effects of culture temperature, basal media, and medium supplements on spermatogonial proliferation levels during whole testis organ culturing by BrdU incorporation assays. Our results show that a 30°C culture temperature negatively affected spermatogonial proliferation compared to 26°C and 28°C and that the use of Dulbecco's Modified Eagle Medium and Minimum Essential Medium α (α-MEM) was more effective for spermatogonial proliferation than the use of Leibovitz's L-15 Medium (L15). When fetal bovine serum (FBS) was replaced with KnockOut Serum Replacement (KSR), a significantly positive effect was observed for the maintenance of spermatogonial proliferation. However, supplementation of the medium with 17α, 20ß-dihydroxy-4-pregnen-3-one did not show any significant effect. Gene expression analyses of four genes, including Nanos2, SCP3, AMH, and StAR, indicated that the optimized culture conditions consisting of α-MEM and KSR had the most positive influence on the maintenance of spermatogonial proliferation levels in whole testis organ cultures compared to the original culture conditions consisting of L15 and FBS by maintaining the function of Sertoli and Leydig cells. The results from this study will provide useful information for the study of in vitro spermatogenesis in fish.

Viscous Cervical Environment-on-a-Chip for Selecting High-Quality Sperm from Human Semen.

When ejaculated sperm travels through the vagina to the uterus, mucus secreted by the cervical canal generally filters out sperm having low motility and poor morphology. To investigate this selection principle in vivo, we developed a microfluidic sperm-sorting chip with a viscous medium (polyvinylpyrrolidone: PVP) to imitate the biophysical environment mimic system of the human cervical canal. The material property of the PVP solution was tuned to the range of viscosities of cervical mucus using micro-viscometry. The selection of high-quality human sperm was experimentally evaluated in vitro and theoretically analyzed by the convection-diffusion mechanism. The convection flow is shown to be dominant at low viscosity of the medium used in the sperm-sorting chip when seeded with raw semen; hence, the raw semen containing sperm and debris convectively flow together with suppressed relative dispersions. Also, it was observed that the sperm selected via the chip not only had high motilities but also normal morphologies and high DNA integrity. Therefore, the biomimetic sperm-sorting chip with PVP medium is expected to improve male fertility by enabling the selection of high-quality sperm as well as uncovering pathways and regulatory mechanisms involved in sperm transport through the female reproductive tract for egg fertilization.

Association between Moving to a High-Volume Hospital in the Capital Area and the Mortality among Patients with Cancer: A Large Population-Based Cohort Study.

This study aimed to identify the association between moving to a high-volume hospital and the mortality of patients with cancer living in the district. The study population comprised participants diagnosed with cancer within the past nine years (2004-2012). The final sample included 8197 patients with cancer, 3939 were males (48.1%), and 4258 were females (51.9%). A Cox proportional hazard model was used to estimate the hazard ratio (HR) for death. Confounding variables including sex, age, type of social security, income level, disability, and utilization volume were incorporated into the model. Among patients with cancer living in the district, 2874 (35.1%) used healthcare services in Seoul. About 10% (n = 834) of patients died during the follow-up period. The HR for death in females (HR: 0.68, 95% CI: 0.58-0.81) was lower than that in males. Additionally, the HR for the death of patients using healthcare services in Seoul (HR: 1.30, 95% CI: 1.11-1.53) was higher than those patients who did not use healthcare services in Seoul. Among patients utilizing services in the province, wealthier patients' survival probability was significantly higher than that of others. The cause of income differences should be identified, and accessibility to medical use of low-income families should be enhanced to prevent mortality of patients from cancer disparities.

Pulmonary Metastasectomy in Colorectal Cancer: A Population-Based Retrospective Cohort Study Using the Korean National Health Insurance Database.

PURPOSE: The study aimed to investigate the current status and prognostic factors for overall survival in patients who had undergone pulmonary metastasectomy for colorectal cancer. MATERIALS AND METHODS: The data of 2,573 patients who had undergone pulmonary metastasectomy after surgery for colorectal cancer between January 2009 and December 2014 were extracted from the Korean National Health Insurance Service claims database. Patient-, colorectal cancer-, pulmonary metastasis-, and hospital-related factors were analyzed using the Kaplan-Meier method, log-rank test, and Cox proportional hazards analysis to identify prognostic factors for overall survival after pulmonary metastasectomy. RESULTS: The mean age of the patients was 60.9±10.5 years; 66.2% and 79.1% of the participants were male and had distally located colorectal cancer, respectively. Wedge resection (71.7%) was the most frequent extent of pulmonary resection; 21.8% of the patients underwent repeated pulmonary metastasectomies; 73% of pulmonary metastasectomy cases were performed in tertiary hospitals; 53.9% of patients were treated in Seoul area; 82% of patients received chemotherapy in conjunction with pulmonary metastasectomy. The median survival duration was 51.8 months. The 3- and 5-year overall survival rates were 67.7% and 39.4%, respectively. In multivariate analysis, female sex, distally located colorectal cancer, pulmonary metastasectomy-only treatment, and high hospital volume (> 10 pulmonary metastasectomy cases/yr) were positive prognostic factors for survival. CONCLUSION: Pulmonary metastasectomy seemed to provide long-term survival of patients with colorectal cancer. The female sex, presence of distally located colorectal cancer, and performance of pulmonary metastasectomy in high-volume centers were positive prognostic factors for survival.

The effect of tonsillectomy with adenoidectomy on medical services used in association with otitis media based on Korean national sample cohort data.

BACKGROUND: The effect of tonsillectomy with adenoidectomy (T&A) on otitis media has been investigated, but there have been no reports of the relationship between T&A and medical services used in association with otitis media. We investigated the effect of T&A on otitis media with regard to the number and cost of medical services used. METHODS: From the National Health Insurance Service National Sample Cohort data in Korea, we selected patients 7 years old or younger in 2002 who had T&A in 2005 while between the ages of three and ten. A control group was established matching the patient group with similar propensities of demographic characteristics. The number and cost of medical services used in association with otitis media were analyzed for 3 years before T&A through 8 years after T&A. RESULTS: The total number of patients was 1,338, with 227 in the T&A group and 1,111 in the non-T&A group. The number of medical services used was not significantly different between the T&A and non-T&A groups before and after surgery. The cost of medical services used was significantly higher in the T&A group than in the non-T&A group one year before surgery. The cost of medical services used was not significantly different between the two groups after surgery. CONCLUSIONS: There were no significant differences between the T&A and non-T&A groups in the number and cost of medical services used in association with otitis media after surgery.

Small Molecule Destabilizer of ß-Catenin and Ras Proteins Antagonizes Growth of K-Ras Mutation-Driven Colorectal Cancers Resistant to EGFR Inhibitors.

BACKGROUND: Oncogenic K-Ras mutations in colorectal cancer (CRC) combined with APC mutations worsen CRC prognosis and lower drug effectiveness. Thus, inhibition of both Wnt/ß-catenin and Ras-MAPK signaling may be a rational strategy to improve the treatment of this cancer. OBJECTIVE: To identify a novel compound inhibiting both Wnt/ß-catenin and Ras-MAPK signaling in CRC. METHODS AND PATIENTS: We developed a two-part screening system consisting of analysis of TOP flash reporter cells and then potential toxicity effects on primary neural stem cells (NSCs). We then screened 2000 chemical compounds and tested efficacy of candidates against isogenic colon cancer cells harboring wild-type or mutant K-Ras. We employed immunohistochemistry and immunocytochemistry to determine marker signatures associated with development of disease phenotypes. RESULTS: We identified CPD0857, a compound that inactivates Wnt/ß-catenin signaling and promotes ubiquitin-dependent proteasomal degradation of ß-catenin and Ras proteins. CPD0857 effectively decreased proliferation and increased apoptosis of CRC cell lines, and overcame resistance of CRC harboring APC and K-Ras mutations to treatment with an EGFR monoclonal antibody (mAb). Moreover, CPD0857 attenuated invasiveness of highly migratory CRC cells in vitro. Accordingly, xenograft mice treated with CPD0857 showed slower tumor growth and significant decreases in both ß-catenin and Ras protein expression. CONCLUSIONS: CPD0857 may be a potential drug for treating aggressive CRC carrying mutations that aberrantly activate Wnt/ß-catenin and Ras-ERK pathways.

Smoking cessation is related to change in metabolic syndrome onset: A rural cohort study.

INTRODUCTION: Relatively few, mainly cross-sectional, studies have examined the relationship between smoking cessation and metabolic syndrome (MetS). In particular, information on smoking cessation after MetS is limited. This study aimed to investigate the probability of smoking cessation after the onset of MetS. METHODS: In this study we used cohort data from a rural area of Korea and extracted the data of 1054 smokers who were identifiable at baseline and were followed up. Of these, 1041 individuals were selected. Descriptive statistical analyses were performed to identify the basic characteristics of smokers. Multiple logistic regression was performed to determine the association between changes in MetS and smoking cessation. RESULTS: The probability of smoking cessation was 1.84 times higher in the newly developed MetS cohort than in the reference group (without MetS at any time point), and it was 1.61 times higher in the persistent MetS cohort than in the reference group, with both probabilities being significant. CONCLUSIONS: We found that patients with MetS were more likely to quit smoking than those without MetS. However, intervention is still needed, as numerous patients with MetS continued to smoke. Interventions that actively involve medical institutions or organizations are among the most effective approaches to promote smoking cessation in patients with MetS. In particular, women, farmers and current drinkers should be prioritized.