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Abstract Background Twist is a basic helix-loop-helix (bHLH) transcriptional factor that has been identified to play an important role in epithelial-mesenchymal transition (EMT)-mediated metastasis through the regulation of E-cadherin expression. However, few authors have examined the expression of Twist and E-cadherin and their prognostic value in patients with esophageal squamous cell carcinoma (ESCC). The purpose of this study is to evaluate the clinical significance of Twist and E-cadherin expression in ESCC. Methods We immunohistochemically investigated the relationship between their expression and clinicopathological factors including prognosis in surgical specimens of primary tumors in 166 patients with ESCC. Results The expression rate of high Twist was 42.0% and that of preserved E-cadherin was 40.4%. The expression of high Twist and reduced E-cadherin was significantly associated with depth of tumor invasion, lymph node metastasis, distant nodal metastasis, stage and lymphatic invasion, and poor prognosis. High Twist expression significantly correlated with reduced E-cadherin expression. In the preserved E-cadherin group, the 5-year survival rate was better for patients who were low for Twist expression than for those who were high for Twist expression. Multivariate analysis indicated that the combination of low Twist and preserved E-cadherin expression was an independent prognostic factor along with tumor depth, distant nodal metastasis and E-cadherin expression. Conclusions Evaluation of Twist and E-cadherin expressions should be useful for determining tumor properties, including prognosis, in patients with ESCC.

Background: The proliferation of cancer-associated fibroblasts (CAFs) hampers drug delivery and anti-tumor immunity, inducing tumor resistance to immune checkpoint blockade (ICB) therapy. However, it has remained a challenge to develop therapeutics that specifically target or modulate CAFs., Methods: We investigated the involvement of Meflin + cancer-restraining CAFs (rCAFs) in ICB efficacy in patients with clear cell renal cell carcinoma (ccRCC) and urothelial carcinoma (UC). We examined the effects of Am80 (a synthetic retinoid) administration on CAF phenotype, the tumor immune microenvironment, and ICB efficacy in cancer mouse models., Results: High infiltration of Meflin + CAFs correlated with ICB efficacy in patients with ccRCC and UC. Meflin + CAF induction by Am80 administration improved ICB efficacy in the mouse models of cancer. Am80 exerted this effect when administered prior to, but not concomitant with, ICB therapy in wild-type but not Meflin-deficient mice. Am80-mediated induction of Meflin + CAFs was associated with increases in antibody delivery and M1-like tumor-associated macrophage (TAM) infiltration. Finally, we showed the role of Chemerin produced from CAFs after Am80 administration in the induction of M1-like TAMs., Conclusion: Our data suggested that Am80 administration prior to ICB therapy increases the number of Meflin + rCAFs and ICB efficacy by inducing changes in TAM phenotype., (© 2024. The Author(s).)

Aims: To predict preterm birth (PTB) accurately, we conducted a comprehensive cytokine assay using cervicovaginal fluid (CVF) and evaluated the additive effects of cytokine levels on the fetal fibronectin (fFN) test., Methods: A total of 645 CVF samples were collected from 256 asymptomatic pregnant women between 24 and 35 weeks gestation, exhibiting short cervix. After selection based on specific criteria, 17 cytokines in 105 CVF samples were simultaneously measured using multiplex assay. Multivariate logistic regression analysis was performed to evaluate the association between cytokine levels and impending PTB, which is defined as PTB within 2 weeks after CVF collection. Moreover, receiver operating characteristic (ROC) analysis was performed in women with positive fFN results, which was validated using another set of 65 CVF samples., Results: In positive fFN women, the CCL2 level was significantly higher in the impending PTB group than the other group (p < 0.01) and a predictor of impending PTB (adjusted odds ratio 1.020, 95% confidence interval [95% CI] 1.003-1.038, p = 0.020). The cutoff value of CCL2 was 64.8 pg/mL (are under the curve 0.726, p = 0.004, 95% CI 0.593-0.859, sensitivity 45.2%, specificity 91.7%). Additionally, the reliable classification performance of proposed ROC model could be validated. However, measuring cytokine levels could not help in predicting impending PTB in women with negative fFN or normal labor onset in healthy-term women., Conclusion: Comprehensive analysis of CVF cytokines revealed that the CCL2 level significantly improves the prediction of impending PTB in asymptomatic fFN-positive women with a short cervix, which may contribute to better clinical management., (© 2024 Japan Society of Obstetrics and Gynecology.)

Background: Microporous polysaccharide hemospheres (MPH) are hydrophilic particles administered to reduce the incidence of seroma after mastectomy, but their clinical effectiveness remains controversial. Because a previous randomized, controlled study in a small cohort could not demonstrate the effectiveness of MPH in breast surgery, we evaluated their effectiveness in surgery for breast cancer in a larger cohort., Methods: Medical records of 352 patients who underwent total mastectomy for breast cancer were retrospectively reviewed. Clinical data were compared between 126 patients who received MPH during surgery (MPH group) and 226 who did not (control group) according to surgical procedures. Patients were significantly older in the MPH group than in the control group because of selection bias, but other factors, such as body mass index and number of dissected lymph nodes, did not differ between groups., Results: When analyzed by use of axillary manipulation, the drain placement period and drainage volume were significantly less in the MPH group than in the control group for patients with mastectomy and sentinel lymph node biopsy. Only drainage volume was significantly less in the MPH group for patients with mastectomy and axillary lymph node dissection. The frequency of total postoperative complications, such as seroma requiring puncture, did not differ between groups., Conclusions: Use of MPH may decrease the postoperative drainage volume and drain placement period in mastectomy for patients with breast cancer., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-23-297/coif). The authors have no conflicts of interest to declare., (2024 Gland Surgery. All rights reserved.)

Background: Insulin-like growth factor-1 (IGF-1) is involved in the pathology of non-alcoholic fatty liver disease (NAFLD) and ameliorates fatty infiltration in the liver. It is activated by growth hormone (GH); however, the role of GH-IGF-1 axis in NAFLD developmental phase has not been well identified. Therefore, in this study, we focused on the effect of IGF-1 in NAFLD pathology and GH excretion activation from the pituitary gland by peripheral autonomic neural pathways relaying liver-brain-gut pathway and by central neuropeptides., Methods: GH and IGF-1 levels were assessed in wild-type and melanocortin-4 receptor knockout mice upon the development of diet-induced NAFLD. The contribution of the peripheral autonomic nervous system connecting the liver-brain-gut axis was assessed by its blockade using capsaicin and that of the central nervous system was assessed by the expression of hypothalamic brain-derived neurotrophic factor (BDNF) and corticotropin-releasing factor (CRH), which activates GH release from the pituitary gland., Results: In the NAFLD mouse models, the levels of GH and IGF-1 increased (p < .05). Further, hepatic fatty infiltration was suppressed even under peripheral autonomic nervous system blockade (p < .001), which inhibited gastric ghrelin expression. In mice with peripheral autonomic nervous blockade, hypothalamic BDNF and CRH were inhibited (p < .05), resulting in GH and IGF-1 excretion, whereas other neuropeptides of somatostatin and cortistatin showed no changes. These complementary effects were canceled in melanocortin-4 receptor knockout mice, which diminished BDNF and CRH release control., Conclusions: Our study demonstrates that the release of IGF-1 by the nervous system is a key factor in maintaining the pathological homeostasis of NAFLD, suggesting its therapeutic potential., (© 2023. Asian Pacific Association for the Study of the Liver.)

Higher consumption of broccoli (Brassica oleracea var. italica) is associated with a reduced risk of cardiometabolic diseases, neurological disorders, diabetes, and cancer. Broccoli is rich in various phytochemicals, including glucosinolates, and isothiocyanates. Moreover, it has recently reported the endogenous production of polysulfides, such as cysteine hydropersulfide (CysS2H) and glutathione hydropersulfide (GS2H), in mammals including humans, and that these bioactive substances function as potent antioxidants and important regulators of redox signaling in vivo. However, few studies have focused on the endogenous polysulfide content of broccoli and the impact of germination on the polysulfide content and composition in broccoli. In this study, we investigated the alternations in polysulfide biosynthesis in broccoli during germination by performing untargeted polysulfide omics analysis and quantitative targeted polysulfide metabolomics through liquid chromatography-electrospray ionization-tandem mass spectrometry. We also performed 2,2-diphenyl-1-picrylhydrazyl radical-scavenging assay to determine the antioxidant properties of the polysulfides. The results revealed that the total polysulfide content of broccoli sprouts significantly increased during germination and growth; CysS2H and cysteine hydrotrisulfide were the predominant organic polysulfide metabolites. Furthermore, we determined that novel sulforaphane (SFN) derivatives conjugated with CysS2H and GS2H were endogenously produced in the broccoli sprouts, and the novel SFN conjugated with CysS2H exhibited a greater radical scavenging capacity than SFN and cysteine. These results suggest that the abundance of polysulfides in broccoli sprouts contribute to their health-promoting properties. Our findings have important biological implications for the development of novel pharmacological targets for the health-promoting effects of broccoli sprouts in humans., Competing Interests: Declaration of competing interest The authors have nothing to disclose., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Delays in breast cancer diagnosis can allow the disease to progress to an incurable stage. However, factors that cause patients to delay seeking treatment are unclear. In this study, we aimed to identify behavioral economic factors and personality characteristics of patients with breast cancer who had a delayed diagnosis., Methods: We analyzed questionnaires completed by 41 patients with breast cancer. A delayed diagnosis was defined if the time between the first symptom and the medical visit was more than 6 months., Results: We found 11 patients who had a delayed diagnosis. The significant characteristics associated with patients with breast cancer who had delayed diagnosis were: (i) less experience with breast cancer screening; (ii) progressive disease stage; and (iii) low time and future time preference. We found no significant behavioral economic factors other than time preference, and personality that differed between patients with breast cancer who did and did not have a delayed diagnosis., Conclusion: Low time preference rate is a characteristic of patients with breast cancer who had a delayed diagnosis.

Introduction: Solid and sensitive infectious disease surveillance systems need to be developed and implemented to prevent and control epidemics. Although statutory national infectious disease surveillance systems have been developed in many countries, some challenges remain, such as their limited timeliness, representativeness, and sensitivity, as well as the fact that they cannot capture all local outbreaks that occur in small communities. To overcome these limitations, local community-based infectious disease surveillance systems that meet local needs and can operate with constrained resources need to be developed, especially in remote and rural low-resource areas. This study aimed to develop, implement, and evaluate a voluntary and unique local community-based ophthalmology sentinel surveillance system in Isa city (OSSS-Isa), a remote rural area in Japan., Methods: For the development of OSSS-Isa, one hospital in Isa city assumed a leading role and developed a network with all medical institutions - 20 hospitals and clinics in the local community, including two ophthalmology clinics - as sentinel reporting sites. Surveillance was conducted on a weekly basis from Monday to Sunday. The collection, aggregation, and reporting of the surveillance data were implemented promptly on the same day, Monday, using a paper-based form and fax. For the evaluation of OSSS-Isa, the study followed the updated guidelines for evaluating public health surveillance systems proposed by the Centers for Disease Control and Prevention to select the evaluation criteria and develop a questionnaire. The questionnaires were then distributed to 20 hospitals and clinics, with the responses evaluated on a five-point Likert scale., Results: For the implementation of OSSS-Isa, the system issued alerts twice to the networked hospitals and clinics when signs of an increase in the prevalence of a target infectious eye disease appeared in Isa city. After the alerts, the number of cases decreased in the community. Regarding the evaluation survey, physicians from 18 hospitals and clinics responded to the questionnaire (response rate 90%). In contrast to flexibility, more than 75% of the respondents gave high ratings to simplicity, data quality, acceptability, timeliness, and stability in evaluating OSSS-Isa, with the mean score for these evaluation criteria higher than 3.67., Conclusion: The present results indicate that OSSS-Isa has high simplicity, data quality, acceptability, timeliness, and stability, which is highly embedded with the local healthcare providers in Isa city. OSSS-Isa contributed to the early and accurate detection of signs of infectious eye disease outbreaks emerging in a small remote rural local community. The success factors seem to include its simple well-designed implementation methods, good external factors, and active human factors suited to the characteristics of the small remote rural community. The OSSS-Isa initiative appears to be a meaningful practical example of successful health advocacy by healthcare providers by developing a system at the local social level while going beyond the boundaries of routine medical practice. If voluntary small-scale surveillance systems can complement statutory large-scale ones and work together locally, nationally, and internationally, it might be possible to detect small, unusual happenings that occur in the community, such as emerging infectious diseases, and thereby help avert global outbreaks.