Synthesis and biological profile of 2,3-dihydro[1,3]thiazolo[4,5-b]pyridines, a novel class of acyl-ACP thioesterase inhibitors.

The present work covers novel herbicidal lead structures that contain a 2,3-dihydro[1,3]thiazolo[4,5-b]pyridine scaffold as structural key feature carrying a substituted phenyl side chain. These new compounds show good acyl-ACP thioesterase inhibition in line with strong herbicidal activity against commercially important weeds in broadacre crops, e.g., wheat and corn. The desired substituted 2,3-dihydro[1,3]thiazolo[4,5-b]pyridines were prepared via an optimized BH3-mediated reduction involving tris(pentafluorophenyl)borane as a strong Lewis acid. Remarkably, greenhouse trials showed that some of the target compounds outlined herein display promising control of grass weed species in preemergence application, combined with a dose response window that enables partial selectivity in certain crops.

Discovery and optimization of spirocyclic lactams that inhibit acyl-ACP thioesterase.

BACKGROUND: There are various methods to control weeds, that represent considerable challenges for farmers around the globe, although applying small molecular compounds is still the most effective and versatile technology to date. In the search for novel chemical entities with new modes-of-action that can control weeds displaying resistance, we have investigated two spirocyclic classes of acyl-ACP thioesterase inhibitors based on X-ray co-crystal structures and subsequent modelling studies. RESULTS: By exploiting scaffold-hopping and isostere concepts, we were able to identify new spirolactam-based lead structures showing promising activity in vivo against commercially important grass weeds in line with strong target affinity. CONCLUSION: The present work covers a series of novel herbicidal lead structures that contain a spirocyclic lactam as a structural key feature carrying ortho-substituted benzyl or heteroarylmethylene side chains. These new compounds show good acyl-ACP thioesterase inhibition in line with strong herbicidal activity. Glasshouse trials showed that the spirolactams outlined herein display promising control of grass-weed species in pre-emergence application combined with dose-response windows that enable partial selectivity in wheat and corn. Remarkably, some of the novel acyl-ACP thioesterase-inhibitors showed efficacy against resistant grass weeds such as Alopecurus myosuroides and Lolium spp. on competitive levels compared with commercial standards. © 2024 Society of Chemical Industry.

Discordance in Secular Trends of Bone Mineral Density Measurements in Different Ages of Postmenopausal Women.

BACKGROUND: Age-adjusted bone mineral density (BMD) in postmenopausal women decreases in developed countries whereas incidence of osteoporotic fracture decreases or remains stable. We investigated secular trends of bone density from 2008 to 2017 among different age groups of postmenopausal women. METHODS: We analyzed BMD data obtained from health check-ups of 4,905 postmenopausal women during three survey cycles from 2008 to 2017. We divided them into 3 groups by age (50-59 years, 60-69 years, and 70 years or more) and observed the transition of lumbar and femoral BMD in each group, before and after adjusting for variables that may affect BMD. RESULTS: Age-adjusted BMD, bone mineral content (BMC), and T-score demonstrated a declining trend over the survey period at lumbar spine (-2.8%), femur neck (-3.5%) and total femur (-4.3%), respectively. In the analysis for the age groups, the BMD, BMC, and T-score presented linear declining trend (-6.1%) in younger postmenopausal women while women aged over 70 or more showed linear increasing trends (+6.3%) at lumbar spine during the survey period. Femoral neck and total femur BMD demonstrated a declining linear trend only in the 50-59 and 60-69 years groups (-5.5%, -5.2%, respectively), but not in the 70 years or more group. CONCLUSION: BMD in younger postmenopausal women has decreased considerably but has increased or plateaued in elderly women. This discordance of BMD trends among different age groups may contribute to decreased incidence of osteoporotic fracture despite a recent declining BMD trend in postmenopausal women.

Analysis of the Outcomes of Immediate Recurrent Laryngeal Nerve Reconstruction During Thyroid Surgery for Prevention of Vocal Fold Paralysis.

BACKGROUND: Recurrent laryngeal nerve (RLN) injury and the resulting paralysis is the most common and known complication of thyroid surgery. Several surgical techniques, such as medialization thyroplasty with or without arytenoid adduction and injection laryngoplasty, have been developed to treat RLN injury, but these procedures have specific limitations and complications. In this study, we present the outcomes for our patients who underwent immediate RLN reconstruction during thyroid surgery by analyzing both subjective and objective outcomes. METHODS: A retrospective study was conducted for patients who underwent total or subtotal thyroidectomy between May 2012 and March 2020. Among them, patients who underwent immediate RLN reconstruction due to unilateral RLN injury were followed for at least 12 months. The voice perceptual evaluation, acoustic analysis, voice range profile, and Voice Handicap Index (VHI) scores were obtained preoperatively, 1 month, 6 months, and 12 months after surgery. RESULTS: Among the 11 patients, 6 patients (54.5%) underwent direct anastomosis, and 5 patients (45.5%) underwent nerve grafts using ansa cervicalis and great auricular nerve. The grade and breathiness in the GRBAS (grade, roughness, breathiness, asthenia, and strain) scale and jitter item showed significant improvement at 12 months postoperatively, and although not statistically significant, the rest of the items also tended to improve. The total, functional, and physical scores on VHI improved significantly at 12 months postoperatively. Moreover, when comparing the voice analysis of the direct anastomosis group and the nerve graft group, there was no significant difference between the groups in objective and subjective results. CONCLUSION: Immediate RLN reconstruction demonstrated significant voice improvement postoperatively, and reconstructing the nerve immediately and combining follow-up treatment in the event of RLN injury will greatly help patients improve their long-term voice outcomes.

Software reliability model for open-source software that considers the number of finite faults and dependent faults.

Software has become a vital factor in the fourth industrial revolution. Owing to the increase in demand for software products in various fields (big data, artificial intelligence, the Internet of Things, etc.), the software industry has expanded more than ever before. Therefore, software reliability has become very important, and efforts are being made to increase it. One of these efforts is the development of software reliability models (SRMs). SRMs have been studied for a long time as a model that predicts software reliability by using the number of software faults. Software failures can occur for several reasons, including independent software faults such as code errors and software hangs, as well as dependent cases where code errors lead to other software faults. Recently, due to the diversity of software operating environments, software faults are more likely to occur in a dependent manner, and, for this reason, they are likely to increase rapidly from the beginning and progress slowly to the maximum number thereafter. In addition, many large companies have focused on open-source software (OSS) development, and OSS is being developed by many users. In this study, we propose a new SRM that considers the number of finite faults and dependent faults, and examine the goodness-of-fit of a new SRM and other existing non-homogeneous Poisson process models based on the OSS datasets. Through numerical examples, the proposed model demonstrated a significantly better goodness-of-fit when compared to other existing models, and it also exhibited better results on the newly proposed integrated criteria.

A new histopathological location of parathyroid gland with high possibility of unintended parathyroidectomy.

Background: Unintended parathyroidectomy occasionally happens despite meticulous capsular dissection and the histopathological location of removed parathyroid glands were traditionally classified as extracapsular, subcapsular, and intrathyroidal location. This study aimed to investigate the new histopathological location of parathyroid gland with high possibility of unintended parathyroidectomy that was difficult to be found with naked eye despite capsular dissection. Methods: This study investigated unintended parathyroidectomy that occurred in 743 patients who received thyroid surgery by reviewing pathology reports and slides. The histopathological location of unintentionally removed parathyroid glands was classified as intracapsule and extracapsule, and the intracapsular glands were further classified as completely buried in the thyroid parenchyme, partially buried, and subcapsular locations. Results: The incidence of unintended parathyroidectomy was 12.8%. Among the 103 unintentionally removed parathyroid glands, 74 (71.8%) were found intracapsular and 29 were extracapsular. Among the intracapsular glands, 57 (55.4%) parathyroid glands were found in difficult locations such as completely buried (40.8%) and partially buried (14.6%). Conclusions: The partially buried parathyroid gland can act as a risk factor for unintended parathyroidectomy comparable to intrathyroidal parathyroid gland despite the surgeon's best effort with meticulous capsular dissection. However, continued advances in visualizing technique such as autofluorescence imaging may lower the chance of incidentally removed partially buried parathyroid glands in the future.

Discordance in Secular Trends of Bone Mineral Density Measurements in Different Ages of Postmenopausal Women

Background@#Age-adjusted bone mineral density (BMD) in postmenopausal women decreases in developed countries whereas incidence of osteoporotic fracture decreases or remains stable. We investigated secular trends of bone density from 2008 to 2017 among different age groups of postmenopausal women. @*Methods@#We analyzed BMD data obtained from health check-ups of 4,905 postmenopausal women during three survey cycles from 2008 to 2017. We divided them into 3 groups by age (50–59 years, 60–69 years, and 70 years or more) and observed the transition of lumbar and femoral BMD in each group, before and after adjusting for variables that may affect BMD. @*Results@#Age-adjusted BMD, bone mineral content (BMC), and T-score demonstrated a declining trend over the survey period at lumbar spine (−2.8%), femur neck (−3.5%) and total femur (−4.3%), respectively. In the analysis for the age groups, the BMD, BMC, and T-score presented linear declining trend (−6.1%) in younger postmenopausal women while women aged over 70 or more showed linear increasing trends (+6.3%) at lumbar spine during the survey period. Femoral neck and total femur BMD demonstrated a declining linear trend only in the 50–59 and 60–69 years groups (−5.5%, −5.2%, respectively), but not in the 70 years or more group. @*Conclusion@#BMD in younger postmenopausal women has decreased considerably but has increased or plateaued in elderly women. This discordance of BMD trends among different age groups may contribute to decreased incidence of osteoporotic fracture despite a recent declining BMD trend in postmenopausal women.

Matrix metalloproteinase-7 induces E-cadherin cleavage in acid-exposed primary human pharyngeal epithelial cells via the ROS/ERK/c-Jun pathway.

Laryngopharyngeal reflux disease (LPRD) is caused by pharyngeal mucosal damage due to the reflux of gastric contents, including acid, pepsin, and bile juice. Our previous study has demonstrated that LPRD is associated with the cleavage of E-cadherin, which is facilitated by the acid-activated matrix metalloproteinase-7 (MMP-7); however, the mechanism by which the acid activates MMP-7 remains unclear. The purpose of this study was to investigate the mechanism by which MMP-7 is activated in the pharyngeal epithelial cells that are exposed to acid. The levels of reactive oxygen species (ROS) were measured in the epithelial cells exposed to acid. To investigate the signaling mechanism of ROS in the expression of MMP-7, the mechanism of action of the mitogen-activated protein kinase was examined. The expression of various signaling factors was determined, according to the presence or absence of each inhibitor in the acid-exposed pharyngeal epithelial cells. To identify changes in the cleavage of E-cadherin, the integrity of the mucosal membrane was assessed using a transepithelial permeability test. We found that acid exposure increased the levels of ROS, phosphorylated-extracellular signal-regulated kinase (p-ERK) 1/2, and phosphorylated-c-Jun (p-c-Jun) in pharyngeal epithelial cells. The ROS inhibitor reduced the expression of p-ERK and MMP-7, while the ERK inhibitor reduced the expression of p-c-Jun and MMP-7. Moreover, the c-Jun inhibitor reduced the expression of MMP-7 and blocked the degradation of E-cadherin. In addition, decrease in the levels of immunostained E-cadherin and increase in transepithelial permeability after acid exposure were collectively alleviated by the inhibitors of ROS, ERK, and c-Jun. The degradation of E-cadherin that occurs after human mucosal cells are exposed to acid appears to be caused by an increase in the expression of MMP-7 via the ROS/ERK/c-Jun pathway, which is thought to be an important mechanism associated with the development of LPRD. KEY MESSAGES: • ROS is triggered when reflux occurs. • ROS regulates the transcription factor c-Jun via the ERK pathway. • The increase in MMP-7 that induces LPRD is induced via the ROS/ERK/c-Jun pathway. • This study revealed for the first time the expression mechanism of MMP-7, which is one of the causes of LPRD.

The Utility of Gastrointestinal Endoscopic Examination Versus Positron Emission Tomography-Computed Tomography in the Detection of Second Primary Lesions in Korean Patients With Head and Neck Cancer.

OBJECTIVE: Head and neck cancer often accompany a synchronous secondary primary lesion in the digestive tract. The aim of this study was to compare detection rates between positron emission tomography-computed tomography (PET-CT) and esophagogastroduodenoscopy (G-fiber) or colonoscopy (C-fiber) in the initial staging and to analyze risk factors for premalignant, malignant, and total synchronous secondary primary lesions. METHODS: A total of 739 patients with head and neck cancer who underwent PET-CT, G-fiber, or C-fiber were analyzed retrospectively. RESULTS: Positron emission tomography-CT did not definitely detect any premalignant synchronous secondary primary lesions (0 [0%] of 739) but definitely detected 10 malignant synchronous secondary primary lesions (10 [1.35%] of 739). Esophagogastroduodenoscopy or C-fiber detected all 20 premalignant synchronous secondary primary lesions (20 [2.71%] of 739) and all 37 malignant synchronous secondary primary lesions (37 [5.00%] of 739). The patients with nasopharynx cancer tended to have premalignant synchronous secondary primary lesions (odds ratio [OR]: 3.793; 95% CI: 1.414-10.171; P = .008). Those with distant metastasis tended to have premalignant (OR: 4.743; 95% CI: 1.508-14.916; P = .009), malignant (OR: 3.803; 95% CI: 1.486-9.731; P = .005), and total synchronous secondary primary lesions (OR: 2.753; 95% CI: 1.159-6.538; P = .022). CONCLUSIONS: Premalignant or malignant synchronous secondary primary lesions that were not definitely detected by PET-CT could be found in the endoscopic examination.

Association between oral health and thyroid disorders: A population-based cross-sectional study.

OBJECTIVES: In this study, we aimed to determine the relationship between oral health status and thyroid dysfunction. METHODS: A population-based cross-sectional analysis using data from the Korean National Health and Nutrition Examination Survey (KNHNES) was performed. We investigated the association between oral health-related parameters and the prevalence of thyroid diseases. In addition, the relationship between oral health status and thyroid function test (TFT) results was analyzed. One-way analysis of variances or chi-square test was used for comparisons between oral health-related parameters and presence of thyroid diseases. Univariable and multivariable logistic regression analyses were conducted to evaluate the associations between participants' characteristics including oral health-related parameters and the abnormal results of TFTs. RESULTS: A total of 18,034 adults were surveyed. Histories of thyroid diseases were found to be more common in people who brushed their teeth frequently or used oral hygiene products. However, histories of periodontitis and community periodontal index (CPI) did not show significant associations with histories of thyroid diseases. Among 14,860 participants without history of thyroid disorders, people having higher CPI values demonstrated higher probabilities of abnormal TFTs (OR 1.381, 95% CI 1.241-1.537, p < .0001); however, statistical significance was not found after adjusting for the other variables. CONCLUSIONS: Our study demonstrated that good oral health-related behavior was associated with more frequent thyroid disease history. High CPI showed a significant association with TFT abnormalities; however, the significance of this association became lower when other variables such as age and sex were adjusted. Further studies will be needed to determine how the control of oral health-related conditions actually has a causal relationship with thyroid disease/dysfunction through prospective cohort studies.

Effectiveness of a combination therapy using non-ablative fractional laser and intralesional triamcinolone injection for thyroidectomy scar treatment: a prospective, randomized, blinded pilot study.

BACKGROUND: The occurrence of thyroid cancer has increased dramatically, and postoperative scars are placed at easily visible locations. Many patients show stronger desire for scar prevention. So far, numerous approaches have been discussed for the treatment of scars; this study is conducted to verify whether the early application of combined therapy contributes to minimal scar formation. METHODS: Between March 2019 and December 2019, total of 64 patients with thyroidectomy scars of a size greater than 4.5 cm located on the anterior neck were enrolled in this prospective pilot study. Subjective and objective evaluation were carried out using the Patient and Observer Scar Assessment Scale (POSAS) at one, two, and six months after operation. Results were compared between a treatment group and a non-treatment group. RESULTS: In PSAS score, the mean values of pain, itching sensation, pliability, thickness, and relief were significantly higher in the laser and steroid treatment group (p = 0.009, p = 0.000, p = 0.013, p = 0.002, and p = 0.007). The value of color of the scars showed no significant differences (p = 0.504). In OSAS score, parameter of thickness, relief, and surface area score was significantly higher score in the combination group (p = 0.029, 0.035, and 0.020), while vascularity, pigmentation, and pliability were not significantly different between two groups (p = 0.548, p = 0.983, and p = 0.128). CONCLUSION: This study demonstrates that early combination therapy contributes to scar improvement to a meaningful extent based on POSAS. We believe that the combined therapy has a synergy effect on scar management, which improves the patients' quality of life in relation to their postoperative scars.

Genome-wide association of individual vulnerability with alcohol-associated liver disease: A Korean genome and epidemiology study.

BACKGROUND AND AIMS: The quantity of alcohol leading to alcohol-associated liver disease (ALD) varies individually. Genetic backgrounds contributing to the divergence in individual susceptibility to alcohol-induced liver damage have not been elucidated in detail. APPROACH AND RESULTS: Based on the Korean Genome and Epidemiology Study Health Examination (KoGES_HEXA) cohort data, 21,919 participants (40-79 years old) were included and divided into cases and controls based on the ALD diagnostic criteria proposed by the American College of Gastroenterology. Data generated by a genome wide-association study were analyzed using logistic regression to assess the risk of ALD development in nondrinkers, light drinkers, and heavy drinkers. We detected three loci, gamma-glutamyltransferase 1 (GGT1), zinc protein finger 827 (ZNF827) and HNF1 homeobox A (HNF1A), which were significantly associated with ALD risk. The GGT1 rs2006227 minor allele was strongly associated with all groups. Among the minor alleles of single nucleotide polymorphisms (SNPs) in HNF1A, rs1183910 had the strongest association with a protective effect from ALD in light drinkers. However, this association was not observed in heavy drinkers. Five SNPs on chromosome 11 showed suggestive significance in protective effects against ALD. CONCLUSIONS: SNPs, including HNF1A rs1183910 minor allele, are the most promising genetic candidates for protection against ALD. The expression of genes contributing to ALD development may be altered by the amount of alcohol consumed.

Preoperative Balloon Occlusion Test of the Carotid Artery and Preoperative Tumor Embolization on Paraganglioma of Carotid Body: 20-Year Experience in a Single Institute and Literature Review / 대한이비인후과학회지

Background and Objectives@#Carotid body paraganglioma is the common type of carotid body tumor for which angiography, carotid artery balloon occlusion test (BOT) and tumor embolization could be considered before the surgery. We analyzed cases in a single institute and reviewed related literature to investigate the necessity of these preoperative examinations.Subjects and Method Medical records of patients who were diagnosed with paraganglioma were retrospectively analyzed from 2000 to 2019. @*Results@#Sixteen patients were identified. Of the total, 14 patients underwent surgery at this institute, and 13 underwent angiography. Of the 13 patients who underwent angiography, 6 patients underwent carotid artery BOT, and 12 patients underwent tumor embolization. The average tumor size of 6 patients who underwent carotid artery BOT was 28.7 mm, and 8 patients who did not undergo carotid artery BOT was 30.1 mm. The average tumor size of 12 patients who underwent tumor embolization was 29.4 mm. Two patients did not undergo tumor embolization, and their average tumor size was 30 mm. In 1 patient, both preoperative angiography and carotid artery BOT were performed, but tumor embolization was not performed due to spasm of tumor vessels. @*Conclusion@#Preoperative carotid artery BOT can be performed to reduce side effects in patients with the potential for carotid resection. In addition, tumor embolization is performed regardless of tumor size. By reducing the amount of bleeding during surgery and reducing the size of the tumor, it is possible to secure an appropriate surgical field of view to facilitate operation during surgery; however, its effectiveness needs to be clearly identified.

Comparison of the Voice Outcome After Injection Laryngoplasty: Unilateral Vocal Fold Paralysis Due to Cancer Nerve Invasion and Iatrogenic Injury

Background and Objectives@#Injection laryngoplasty is a common method for treatment of unilateral vocal fold paralysis. Unilateral vocal fold paralysis has various causes, including idiopathic, infection, stroke, neurologic condition, surgery and nerve invasion by cancer. To the knowledge of the authors, there was no study on the relationship between the causes of vocal cord paralysis and the outcome of injection laryngoplasty. Therefore, we tried to investigate the difference in the outcomes of injection laryngoplasty between vocal cord paralysis after surgery group and nerve invasion by cancer group.Materials and Method A retrospective analysis was performed for 24 patients who underwent vocal cord injection due to unilateral vocal cord paralysis caused by surgery or nerve invasion by cancer. The objective quality of the voice was assessed by acoustic voice analysis with the Multi-Dimensional Voice Program. @*Results@#Both group showed an improvement of fundamental frequemcy (F0), jitter percent, shimmer (percent), and noise to hearmonic ratio (NHR) after injection laryngoplasty. The vocal cord paralysis due to nerve invasion group showed more improvement in both the mean and median value of F0, shimmer percent and NHR than the vocal cord paralysis due to surgery group, but there was not statistically significant. @*Conclusion@#Our study did not show a statistically significant difference in outcome between vocal cord paralysis due to cancer invasion group and surgery group, but statistically tendency was suggested. The vocal cord paralysis due to nerve invasion group showed more improvement in both the mean and median value of acoustic voice analysis than surgery group.

Usefulness of matrix metalloproteinase-7 in saliva as a diagnostic biomarker for laryngopharyngeal reflux disease.

Several diagnostic methods are currently being used to diagnose LPRD (laryngopharyngeal reflux disease), but have the disadvantage of being invasive, subjective, or expensive. Our purpose in this study was to investigate the correlation between pepsin and MMP-7 (Matrix Metalloproteinase-7) in pharyngeal secretions of subjects according to RSI (Reflux Symptom Index) score to find out the diagnostic value of MMP-7. We recruited 173 subjects aged between 19 and 85 years who completed the RSI scale. All samples were taken after waking up, and the amount of the pepsin and MMP-7 in saliva were measured by means of an enzyme activity assay. There was a significant increase of pepsin and MMP-7 activity in the study group with an RSI score of 13 or higher. The sensitivity and specificity of MMP-7 for predicting the possibility of an RSI of 13 or more was higher than that of pepsin. When MMP-7 and pepsin were combined, this sensitivity and specificity increased. An enzyme assay of MMP-7 in saliva may be a noninvasive and easy technique for diagnosing LPRD.

Application of M1 macrophage as a live vector in delivering nanoparticles for in vivo photothermal treatment.

Introduction: To enhance photothermal treatment (PTT) efficiency, a delivery method that uses cell vector for nanoparticles (NPs) delivery has drawn attention and studied widely in recent years. Objectives: In this study, we demonstrated the feasibility of M1 activated macrophage as a live vector for delivering NPs and investigated the effect of NPs loaded M1 stimulated by Lipopolysaccharide on PTT efficiency in vivo. Methods: M1 was used as a live vector for delivering NPs and further to investigate the effect of NPs loaded M1 on PTT efficiency. Non-activated macrophage (MФ) was stimulated by lipopolysaccharide (LPS) into M1 and assessed for tumor cell phagocytic capacity towards NPs. Results: We found M1 exhibited a 20-fold higher uptake capacity of NPs per cell volume and 2.9-fold more active infiltration into the tumor site, compared with non-activated macrophage MФ. We injected M1 cells peritumorally and observed that these cells penetrated into the tumor mass within 12 h. Then, we conducted PTT using irradiation of a near-infrared laser for 1 min at 1 W/cm2. As a result, we confirmed that using M1 as an active live vector led to a more rapid reduction in tumor size within 1 day indicating that the efficacy of PTT with NPs-loaded M1 is higher than that with NPs-loaded MФ. Conclusion: Our study demonstrated the potential role of M1 as a live vector for enhancing the feasibility of PTT in cancer treatment.

Forecasting COVID-19 Confirmed Cases Using Empirical Data Analysis in Korea.

From November to December 2020, the third wave of COVID-19 cases in Korea is ongoing. The government increased Seoul's social distancing to the 2.5 level, and the number of confirmed cases is increasing daily. Due to a shortage of hospital beds, treatment is difficult. Furthermore, gatherings at the end of the year and the beginning of next year are expected to worsen the effects. The purpose of this paper is to emphasize the importance of prediction timing rather than prediction of the number of confirmed cases. Thus, in this study, five groups were set according to minimum, maximum, and high variability. Through empirical data analysis, the groups were subdivided into a total of 19 cases. The cumulative number of COVID-19 confirmed cases is predicted using the auto regressive integrated moving average (ARIMA) model and compared with the actual number of confirmed cases. Through group and case-by-case prediction, forecasts can accurately determine decreasing and increasing trends. To prevent further spread of COVID-19, urgent and strong government restrictions are needed. This study will help the government and the Korea Disease Control and Prevention Agency (KDCA) to respond systematically to a future surge in confirmed cases.

Non-surgical animal model of gastroesophageal reflux disease by overeating induced in mice.

Previous animal models of gastroesophageal reflux disease (GERD) were not physiological and required a variety of surgical procedures. Therefore, the animal model developed by conditions that are similar to the pathogenesis of GERD is necessary. The aim is to establish a non-surgical animal model with GERD caused by overeating induced in mice. To induce mice to overeat, we designed dietary control protocols including repetitive fasting and feeding. The esophageal tissues were evaluated with GERD markers to prove the establishment of a GERD animal model. Mice fasted every other day (group 2) showed more pronounced overeating feature and demonstrated evident changes similar to the macroscopic and microscopic findings of GERD, the expressions of inducible nitric oxide synthase and substance P were stronger. The higher frequency of fasting and overeating could cause GERD effectively. The dietary control can make mice overeat, which elicits the change of lower esophageal mucosa similar to GERD. Thus, the overeating-induced mouse may be used as a GERD mouse model.