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OBJECTIVE: This study aimed to investigate the obstetric outcomes of transabdominal cerclage (TAC) in Japan. METHODS: Questionnaires on TAC were sent to 183 institutions performing high-quality perinatal management in Japan. As a first-step questionnaire, we asked whether TAC was performed between January 1, 2011, and December 31, 2022. In the second step of the questionnaire, the characteristics of all cases were asked from all institutions in which TAC was performed. RESULTS: The response rate for the first survey was 59% (108/183). Of the 108 institutions, 27 performed TAC (25%) in 133 pregnancies. Of these 27 institutions, 19 responded to the second survey. One hundred twenty-five pregnancies were included in this study, five of which were aborted (gestational weeks <22 weeks), and 69 babies were born after 37 gestational weeks (55%). Eighty-two open abdominal cerclages were performed at 17 institutions and 43 laparoscopic TACs at three institutions. There were no differences in the age at TAC, gestational weeks at TAC, operative time of TAC, gestational weeks at delivery, incidence rate of second-trimester loss, or preterm delivery (before 37 gestational weeks) rate between the two groups. However, blood loss during open TAC was greater than that during laparoscopic TAC. CONCLUSION: TAC is a rare surgery for cervical insufficiency in Japan. TAC may be a safe and useful method for preventing second-trimester loss and preterm delivery in high-risk patients. TAC may also be a key option in Japan to improve perinatal outcomes in patients with cervical insufficiency.
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BACKGROUND: BRAF mutation has been recognized as a negative prognostic marker for metastatic colorectal cancer (mCRC), but these data are from common BRAF V600E-mutated mCRC. Combination therapy of BRAF inhibitor and anti-epidermal growth factor receptor (EGFR) antibody has been approved for BRAF V600E-mutated mCRC. However, BRAF non-V600 mutations are rare mutations, and their clinical behavior is not understood. Moreover, the BRAF K601E mutation is extremely rare in mCRC, and there have been no reports on its specific treatment. CASE SUMMARY: Herein, we report the case of a 59-year-old female with super aggressive mCRC with multiple metastases, which extended to whole body including mediastinal to abdominal lymph nodes, bones, pleura, and peritoneum. The companion diagnostics of tumor tissues showed RAS/BRAF wild-type without microsatellite instability. She received chemotherapy with mFOLFOX6 (oxaliplatin plus infusional 5-fluorouracil [5-FU] and leucovorin) plus panitumumab, following FOLFIRI (irinotecan plus infusional 5-FU and leucovorin) plus ramucirumab. For the next regimen selection, a comprehensive genomic profiling panel was performed and revealed a BRAF K601E mutation, which was not covered in the initial companion diagnostics. After disease progression, a combination of encorafenib, binimetinib, and cetuximab was selected as third-line chemotherapy. The serum levels of tumor markers were immediately decreased accompanied by improvements in pleural effusion and ascites. However, the disease progressed again, and best supportive care was done instead. CONCLUSION: This case offers novel insights into the clinical behaviors of BRAF non-V600E-mCRC, potentially advancing personalized therapy for rare and aggressive cases.
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(1) Background: Proglucagon-derived peptides (PDGPs) including glucagon (Gcg), GLP-1, and GLP-2 regulate lipid metabolism in the liver, adipocytes, and intestine. However, the mechanism by which PGDPs participate in alterations in lipid metabolism induced by high-fat diet (HFD) feeding has not been elucidated. (2) Methods: Mice deficient in PGDP (GCGKO) and control mice were fed HFD for 7 days and analyzed, and differences in lipid metabolism in the liver, adipose tissue, and duodenum were investigated. (3) Results: GCGKO mice under HFD showed lower expression levels of the genes involved in free fatty acid (FFA) oxidation such as Hsl, Atgl, Cpt1a, Acox1 (p < 0.05), and Pparα (p = 0.05) mRNA in the liver than in control mice, and both FFA and triglycerides content in liver and adipose tissue weight were lower in the GCGKO mice. On the other hand, phosphorylation of hormone-sensitive lipase (HSL) in white adipose tissue did not differ between the two groups. GCGKO mice under HFD exhibited lower expression levels of Pparα and Cd36 mRNA in the duodenum as well as increased fecal cholesterol contents compared to HFD-controls. (4) Conclusions: GCGKO mice fed HFD exhibit a lesser increase in hepatic FFA and triglyceride contents and adipose tissue weight, despite reduced ß-oxidation in the liver, than in control mice. Thus, the absence of PGDP prevents dietary-induced fatty liver development due to decreased lipid uptake in the intestinal tract.
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Antígenos CD36 , Dieta Alta en Grasa , Absorción Intestinal , Metabolismo de los Lípidos , Hígado , Ratones Noqueados , PPAR alfa , Proglucagón , Animales , Masculino , Dieta Alta en Grasa/efectos adversos , PPAR alfa/metabolismo , PPAR alfa/genética , Hígado/metabolismo , Proglucagón/metabolismo , Proglucagón/genética , Antígenos CD36/metabolismo , Antígenos CD36/genética , Ratones , Esterol Esterasa/metabolismo , Esterol Esterasa/genética , Triglicéridos/metabolismo , Ratones Endogámicos C57BL , Ácidos Grasos no Esterificados/metabolismo , Péptido 1 Similar al Glucagón/metabolismo , Duodeno/metabolismo , Carnitina O-Palmitoiltransferasa/metabolismo , Carnitina O-Palmitoiltransferasa/genética , Tejido Adiposo/metabolismo , Grasas de la Dieta , Péptido 2 Similar al Glucagón/metabolismo , Aciltransferasas , LipasaRESUMEN
To evaluate perinatal outcomes and risk factors for large for gestational age (LGA; birth weight over 90 percentile) in gestational diabetes diagnosed before 24 gestational weeks and treated with diet therapy alone until delivery (Diet Early gestational diabetes mellitus (Diet Early GDM)), we assessed the maternal characteristics and perinatal outcomes of patients with early GDM (n = 309) and normal glucose tolerance (NGT; n = 309) at Keio University Hospital. The gestational weight gain (GWG) expected at 40 weeks was significantly lower in the Diet Early GDM group than in the NGT group. The Diet Early GDM group exhibited a significantly lower incidence of low birth weight (<2500 g) and higher Apgar score at 5 min than the NGT group. Multiple logistic regression analysis revealed that the pre-pregnancy body mass index and GWG expected at 40 weeks were significantly associated with LGA for Diet Early GDM. No differences were observed in random plasma glucose levels in the first trimester, 75 g oral glucose tolerance test values, and initial increase or subsequent decrease between the two groups. Dietary early GDM did not exhibit a worse prognosis than NGT. To prevent LGA, it might be important to control maternal body weight not only during pregnancy but also before conception.
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Diabetes Gestacional , Humanos , Embarazo , Diabetes Gestacional/dietoterapia , Femenino , Adulto , Resultado del Embarazo , Recién Nacido , Ganancia de Peso Gestacional , Peso al Nacer , Prueba de Tolerancia a la Glucosa , Edad Gestacional , Glucemia/metabolismo , Factores de Riesgo , Índice de Masa Corporal , Macrosomía Fetal/epidemiología , Macrosomía Fetal/etiología , Macrosomía Fetal/prevención & control , Dietoterapia/métodos , Recién Nacido de Bajo PesoRESUMEN
This study aims to investigate the antiallergic effects of Shiikuwasha (Citrus depressa Hayata) leaf and peel extracts by examining the regulation of degranulation and inflammatory cytokine production from rat basophilic leukemia (RBL-2H3) cells and antigen-specific antibody production in sensitized mouse spleen lymphocytes. In vivo antiallergic activity was evaluated using the passive cutaneous anaphylaxis (PCA) reaction model. Extracts of Shiikuwasha leaves and peel were prepared using 80% methanol and dissolved in dimethylsulfoxide. The dinitrophenyl-human serum albumin-induced ß-hexosaminidase levels in immunoglobulin (Ig) E-sensitized RBL-2H3 cells were assessed using enzymatic assays. Cytokine production was measured by enzyme-linked immunosorbent assay. Antibody production capacity was evaluated using lymphocytes isolated from spleens of type I allergy model mice. Lymphocytes were cultured for 72 h with Shiikuwasha extracts, and ovalbumin-specific IgE, IgG1, and IgG2a levels were measured. Shiikuwasha leaf and peel extract significantly reduced ß-hexosaminidase release and suppressed interleukin-4 and tumor necrosis factor-α production from RBL-2H3 cells. Ovalbumin-specific IgE and IgG1 production decreased in Shiikuwasha extract-treated lymphocytes. These extracts also significantly suppressed the PCA reaction. Shiikuwasha leaf and peel extract reduce degranulation in RBL-2H3 cells and antibody production in spleen-derived lymphocytes and therefore exhibit antiallergic effects.
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Antialérgicos , Degranulación de la Célula , Inmunoglobulina E , Extractos Vegetales , Hojas de la Planta , Bazo , Animales , Extractos Vegetales/farmacología , Ratas , Bazo/efectos de los fármacos , Bazo/inmunología , Bazo/citología , Hojas de la Planta/química , Ratones , Línea Celular Tumoral , Degranulación de la Célula/efectos de los fármacos , Inmunoglobulina E/sangre , Antialérgicos/farmacología , Antialérgicos/uso terapéutico , Linfocitos/efectos de los fármacos , Linfocitos/inmunología , Linfocitos/metabolismo , beta-N-Acetilhexosaminidasas/metabolismo , Anafilaxis Cutánea Pasiva/efectos de los fármacos , Ratones Endogámicos BALB C , Leucemia Basofílica Aguda/inmunología , Citocinas/metabolismo , Modelos Animales de Enfermedad , Inmunoglobulina G , Masculino , Interleucina-4/metabolismoRESUMEN
OBJECTIVES: Linking information on Japanese pharmaceutical products to global knowledge bases (KBs) would enhance international collaborative research and yield valuable insights. However, public access to mappings of Japanese pharmaceutical products that use international controlled vocabularies remains limited. This study mapped YJ codes to RxNorm ingredient classes, providing new insights by comparing Japanese and international drug-drug interaction (DDI) information using a case study methodology. MATERIALS AND METHODS: Tables linking YJ codes to RxNorm concepts were created using the application programming interfaces of the Kyoto Encyclopedia of Genes and Genomes and the National Library of Medicine. A comparative analysis of Japanese and international DDI information was thus performed by linking to an international DDI KB. RESULTS: There was limited agreement between the Japanese and international DDI severity classifications. Cross-tabulation of Japanese and international DDIs by severity showed that 213 combinations classified as serious DDIs by an international KB were missing from the Japanese DDI information. DISCUSSION: It is desirable that efforts be undertaken to standardize international criteria for DDIs to ensure consistency in the classification of their severity. CONCLUSION: The classification of DDI severity remains highly variable. It is imperative to augment the repository of critical DDI information, which would revalidate the utility of fostering collaborations with global KBs.
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Interacciones Farmacológicas , Bases del Conocimiento , RxNorm , Japón , Humanos , Vocabulario Controlado , Pueblos del Este de AsiaRESUMEN
BACKGROUND: The standard treatment for colorectal cancer consists of surgery and chemotherapy, which can be combined to improve outcomes. Immune checkpoint inhibitors (ICI) are a significant advancement in the standard treatment of metastatic, unresectable colorectal cancer with deficient mismatch repair (dMMR). However, limited data are available about the use of ICI in the neoadjuvant and conversion settings. Here, we present two cases treated with ICI. CASE PRESENTATION: Case 1: A 75-year-old male with a large, borderline resectable rectal cancer diagnosed as cT4bN1bM0 who underwent neoadjuvant chemotherapy, followed by combination ICI consisting of ipilimumab and nivolumab. After four courses of ICI, the tumor significantly shrank, but positron emission tomography still showed a positive result and R0 resection was performed. Pathological analysis revealed no residual cancer cells. The patient has been monitored without adjuvant chemotherapy, and no recurrences have occurred after one year. Case 2: A 60-year-old male with locally advanced sigmoid colon cancer who received neoadjuvant treatment with pembrolizumab. The tumor partially shrank after three courses, and continued pembrolizumab monotherapy resulted in further tumor shrinkage which still showed positive positron emission tomography. Curative sigmoidectomy with partial resection of the ileum and bladder was performed, and the pathological outcome was pCR. There was no viable tumor in the specimen. The patient has been monitored without adjuvant chemotherapy for six months, and no recurrence has been observed. CONCLUSIONS: The present study reports two cases, including a large, borderline resectable rectal cancer after failure of chemotherapy followed by combination treatment with nivolumab and ipilimumab and one case of sigmoid colon cancer after pembrolizumab treatment, which resulted in pathological complete response. However, it remains unknown whether ICI therapy can replace surgery or diminish the optimal extent of resection, or whether adjuvant chemotherapy is needed after surgery in the case of achieving pCR after ICI therapy. Overall, this case report suggests that ICI before colorectal surgery can be effective and potentially a 'watch-and-wait" strategy could be used for cases in which ICI is effective.
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Background and Objectives: Despite the fact that biologic drugs have transformed inflammatory bowel disease (IBD) treatment, addressing fibrosis-related strictures remains a research gap. This study explored the roles of cytokines, macrophages, and Krüppel-like factors (KLFs), specifically KLF4, in intestinal fibrosis, as well as the interplay of KLF4 with various gut components. Materials and Methods: This study examined macrophage subtypes, their KLF4 expression, and the effects of KLF4 knockdown on macrophage polarization and cytokine expression using THP-1 monocyte models. Co-culture experiments with stromal myofibroblasts and a conditioned medium from macrophage subtype cultures were conducted to study the role of these cells in intestinal fibrosis. Human-induced pluripotent stem cell-derived small intestinal organoids were used to confirm inflammatory and fibrotic responses in the human small intestinal epithelium. Results: Each macrophage subtype exhibited distinct phenotypes and KLF4 expression. Knockdown of KLF4 induced inflammatory cytokine expression in M0, M2a, and M2c cells. M2b exerted anti-fibrotic effects via interleukin (IL)-10. M0 and M2b cells showed a high migratory capacity toward activated stromal myofibroblasts. M0 cells interacting with activated stromal myofibroblasts transformed into inflammatory macrophages, thereby increasing pro-inflammatory cytokine expression. The expression of IL-36α, linked to fibrosis, was upregulated. Conclusions: This study elucidated the role of KLF4 in macrophage polarization and the intricate interactions between macrophages, stromal myofibroblasts, and cytokines in experimental in vitro models of intestinal fibrosis. The obtained results may suggest the mechanism of fibrosis formation in clinical IBD.
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Fibrosis , Factor 4 Similar a Kruppel , Macrófagos , Humanos , Citocinas/metabolismo , Enfermedades Inflamatorias del Intestino , Macrófagos/metabolismo , Monocitos/metabolismo , Fenotipo , Células THP-1RESUMEN
The aim of this study was to elucidate the anti-allergic effects of polymethoxyflavonoids in combination with milk proteins and the mechanism of inhibition. Three polymethoxyflavonoids and two milk proteins were exposed to the rat basophilic leukemia cell line RBL-2H3. ß-hexosaminidase was used as an indicator of degranulation inhibition. The mechanism of inhibition was examined by measuring intracellular Ca2+ levels and western blot method. In the degranulation inhibition test with polymethoxyflavonoids and milk proteins alone, nobiletin was the strongest inhibitor in the polymethoxyflavonoid group and lactoferrin in the milk protein group. Next, co-stimulation with nobiletin and lactoferrin showed stronger synergistic degranulation inhibition than treatment with nobiletin or lactoferrin alone. Western blot analysis showed that co-stimulation with nobiletin and lactoferrin significantly downregulated the induction of phospholipase Cγ 1 phosphorylation. The degranulation response in RBL-2H3 cells was synergistically suppressed by co-stimulation of nobiletin and lactoferrin acting on both Ca2+-dependent and Ca2+-independent pathways.
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Midazolam (MDZ) is clinically used for its sedative and anticonvulsant properties. However, its prolonged or potentiated effects are sometimes concerning. The main binding protein of MDZ is albumin, and reduced serum albumin levels could lead to MDZ accumulation, thereby potentiating or prolonging its effects. Previous investigations have not thoroughly examined these phenomena from a behavioral pharmacology standpoint. Consequently, this study aimed to evaluate both the prolonged and potentiated effects of MDZ, as well as the effects of serum albumin levels on the action of MDZ in low-albumin rats. Male Wistar rats were classified into control (20% protein diet), low-protein (5% protein), and non-protein groups (0% protein diet) and were fed the protein-controlled diets for 30 d to obtain low-albumin rats. The locomotor activity and muscle relaxant effects of MDZ were evaluated using the rotarod, grip strength, and open-field tests conducted 10, 60, and 120 min after MDZ administration. Serum albumin levels decreased significantly in the low-protein and non-protein diet groups compared with those in the control group. Compared with the control rats, low-albumin rats demonstrated a significantly shorter time to fall, decreased muscle strength, and a significant decrease in the distance traveled after MDZ administration in the rotarod, grip strength, and open-field tests, respectively. Decreased serum albumin levels potentiated and prolonged the effects of MDZ. Hence, serum albumin level is a critical parameter associated with MDZ administration, which should be monitored, and any side effects related to decreased albumin levels should be investigated.
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Hipoalbuminemia , Midazolam , Ratas , Masculino , Animales , Midazolam/farmacología , Ratas Wistar , Hipnóticos y Sedantes/farmacología , Albúmina SéricaRESUMEN
Lung cancer (LC) is currently the leading cause of cancer deaths in Japan. Early detection through lung cancer screening (LCS) is important for reducing mortality. Therefore, exploring the factors affecting willingness to undergo LCS, particularly among young people, is important. This study aimed to elucidate the inclination toward LCS and its determining factors among Japanese university students. This cross-sectional study, involving 10,969 Japanese university students, was conducted in April 2023. A Pearson's chi-square test and a binomial logistic regression analysis were used to analyze factors related to the dependent variable, willingness to undergo LCS in the future. Out of the 6779 participants (61.8%) involved in this study, 6504 (95.9%) provided valid responses, and 4609 (70.9%) expressed a willingness to undergo LCS in the future. Analysis revealed current smoking as a barrier to future willingness to undergo LCS. Other barriers included postponing the age of screening, anxiety about the screening content, and concerns about the possibility of having cancer after screening. Addressing barriers, such as current smoking and anxiety about screening, that prevent young people from undergoing LCS in the future is crucial. Therefore, universities should provide opportunities to educate students about LCS and explore various educational methods.
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BACKGROUND: Maternal obesity influences birth weight and newborn adiposity. Fetal fractional limb volume has recently been introduced as a useful parameter for the proxy of fetal adiposity. However, the association between maternal adiposity and the growth of fetal fractional limb volume has not been examined. AIMS: To investigate the association of maternal pre-pregnancy BMI with the growth of fetal fractional limb volume. STUDY DESIGN: Prospective cohort study. SUBJECTS: Women with singleton uncomplicated pregnancies enrolled between July 2017 and June 2020. OUTCOME MEASURES: Fetal fractional limb volume was assessed between 20 and 40 weeks' gestation, measured as cylindrical limb volume based on 50 % of the total diaphysis length. The measured fractional limb volume at each gestational week were converted to z-scores based on a previous report. The association between pre-pregnancy BMI and fetal fractional limb volume was examined. Maternal age, parity, gestational weight gain and fetal sex were considered as potential confounding variables. RESULTS: Ultrasound scans of 455 fractional arm volume and thigh volume were obtained. Fractional limb volume increased linearly until the second trimester of gestation, then increased exponentially in the third trimester. Maternal pre-pregnancy BMI was significantly correlated with z-scores of fractional arm volume and thigh volume across gestation. The post-hoc analysis showed the association between pre-pregnancy BMI and fractional arm volume was significant especially between 34 and 40 weeks. CONCLUSIONS: Maternal obesity influences the growth pattern of fetal fractional limb volume. Fractional arm volume may potentially provide a useful surrogate marker of fetal nutritional status in late gestation.
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Obesidad Materna , Recién Nacido , Embarazo , Femenino , Humanos , Estudios Prospectivos , Ultrasonografía Prenatal , Peso al Nacer , Tercer Trimestre del Embarazo , Edad Gestacional , Obesidad/epidemiologíaRESUMEN
BACKGROUND/AIM: Photodynamic therapy (PDT) is a relatively non-invasive anti-cancer therapy that employs a photosensitizer with a specific wavelength of light, causing a photochemical reaction that releases free radicals, thereby inducing tumor cell necrosis via oxidative stress. The oxygen molecule reaches the singlet excited state through efficient energy transfer from an excited triplet state of the photosensitizer. Heavy atoms are frequently introduced in photosensitizers for efficiently generating reactive oxygen species (ROS) in PDT, known as the heavy atom effect. However, metal-complexed photosensitizers often show low water-solubility. To overcome this limitation and produce ROS effectively, we focused on the better solubility of photosensitizers with heavy metals bound within the chlorin skeleton and conjugated with glucose in this study. MATERIALS AND METHODS: We established maltotriose (Mal3)-conjugation with heavy metallochlorins [M (Mal3-chlorin), M=Pt or Pd)] and evaluated its anti-tumor effect. RESULTS: M (Mal3-chlorin) showed effective ROS production and singlet oxygen induction. Consequently, these cytotoxic factors caused effective anti-tumor effects and induced morphological changes, followed by cell death in vitro. In a xenograft tumor mouse model, PDT with M (Mal3-chlorin) showed tumor growth suppression. CONCLUSION: M (Mal3-Chlorin) might be an excellent glucose-conjugated chlorin because of its strong anti-tumor PDT effect.
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Fotoquimioterapia , Porfirinas , Trisacáridos , Humanos , Animales , Ratones , Fármacos Fotosensibilizantes/farmacología , Especies Reactivas de Oxígeno , Metales , Porfirinas/farmacología , Modelos Animales de Enfermedad , GlucosaRESUMEN
Exertional heatstroke (EHS), a severe form of exertional heat illness (EHI), is the third leading cause of death in athletes; thus, early detection and prevention of EHI can help prevent EHS, which is a life-threatening condition. This study aimed to clarify the association between the cognizance of experiencing EHI and living conditions and specific EHI symptoms among collegiate athletes. This study was conducted in October 2022 by administering a questionnaire to 237 male collegiate athletes. Of the 215 (90.7%) respondents, 197 (91.6%) provided valid responses; among them, 88 (44.7%) responded they had experienced EHI, while 109 (55.3%) had not. A history of medical examinations due to EHI, having experienced headaches during summer activities, and having read the EHI manual were factors indicating cognizance of EHI. The number of times meals containing a staple food, main dish, and side dish were eaten in a day was a factor in preventing EHI. Early detection of EHI is important for its prevention, and it is important that athletes themselves have knowledge of symptoms and can correctly self-diagnose EHI. Emphasizing the potential of a well-balanced dietary intake has the potential to prevent EHI is crucial.
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Trastornos de Estrés por Calor , Condiciones Sociales , Humanos , Masculino , Calor , Trastornos de Estrés por Calor/diagnóstico , Trastornos de Estrés por Calor/epidemiología , Trastornos de Estrés por Calor/prevención & control , Atletas , EstudiantesRESUMEN
Edible canna rhizomes contain extremely high levels of resistant starch among cereals and potatoes. We previously showed that feeding canna rhizome starch to mice may increase intestinal barrier function and improve the intestinal environment. Here, we investigated the effects of canna starch intake in a murine food allergy model. Five-week-old female BALB/c mice were divided into four groups: Control and OVA groups fed on the control diet (AIN-93G) ad libitum and Canna and OVA-Canna groups fed on the canna diet (AIN-93G with 10% replaced with canna starch). The OVA and OVA-Canna groups were sensitized to ovalbumin (OVA), and the anaphylactic response was assessed by measuring body temperature. Body temperature was significantly lower in the OVA group than in the non-sensitized group, but no decrease was observed in the OVA-Canna group. Fecal weight, fecal mucin content, and goblet cells of colorectal tissue were significantly increased in the Canna and OVA-Canna groups compared with those in the Control and OVA groups. Allergen uptake into the liver was also increased in the OVA group and decreased in the OVA-Canna group to the same level as in the non-sensitized group. These results indicate that canna starch supplementation in a murine food allergy model suppresses anaphylactic symptoms by improving the intestinal environment and reducing allergen uptake by increasing intestinal barrier function.
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Anafilaxia , Hipersensibilidad a los Alimentos , Ratones , Femenino , Animales , Ovalbúmina , Alérgenos , Funcion de la Barrera Intestinal , Almidón/farmacologíaRESUMEN
INTRODUCTION: Endoscopic diagnosis is essential for predicting the curability of early gastric cancer (EGC; R0 resection) before treatment, but the relationship between ulcerative lesions and clinical outcomes remains unclear. We aimed to investigate the effect of proton pump inhibitor (PPI) or potassium-competitive acid blocker (P-CAB) on the morphological changes of ulcerative EGCs and its relevance to the clinical outcomes. METHODS: Altogether, 143 patients with differentiated ulcerative EGC that were resected by endoscopic submucosal dissection were retrospectively identified and divided into the following two cohorts depending on their PPI/P-CAB administration status: PPI/P-CAB (n = 76) and non-PPI/P-CAB (n = 67) cohorts. Furthermore, in each cohort, the patients were further divided into the improved and unimproved subgroups based on the ulcerative changes. RESULTS: In the PPI/P-CAB cohort, the deep submucosal invasion and lymphovascular invasion rates were significantly higher in the unimproved subgroup than in the improved subgroup, resulting in a significantly lower R0 resection rate. Contrarily, no significant differences were found between the two subgroups in the non-PPI/P-CAB cohort. The significance of PPI/P-CAB administration was observed only in the ulcerative EGCs with open-type atrophy (R0 resection rate; improved vs. unimproved, 90.9% vs. 48.0%, p = 0.001). When the finding of improved ulcer with PPI/P-CAB administration was used as the indication of endoscopic resection in ulcerative EGCs with open-type atrophy, high sensitivity (78.9%) and accuracy (76.3%) rates for the curability were observed, which were higher than those of conventional endoscopic diagnosis alone (p = 0.021). CONCLUSION: PPI or P-CAB administration might contribute to the potential selection of ulcerative EGCs, enabling endoscopic curative resection.
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Resección Endoscópica de la Mucosa , Inhibidores de la Bomba de Protones , Neoplasias Gástricas , Úlcera Gástrica , Humanos , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/patología , Neoplasias Gástricas/tratamiento farmacológico , Inhibidores de la Bomba de Protones/uso terapéutico , Inhibidores de la Bomba de Protones/administración & dosificación , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Resección Endoscópica de la Mucosa/métodos , Úlcera Gástrica/tratamiento farmacológico , Úlcera Gástrica/etiología , Úlcera Gástrica/patología , Úlcera Gástrica/diagnóstico , Mucosa Gástrica/patología , Mucosa Gástrica/cirugía , Mucosa Gástrica/diagnóstico por imagen , Resultado del Tratamiento , Gastroscopía/métodos , Adulto , Invasividad Neoplásica , Anciano de 80 o más Años , Detección Precoz del Cáncer/métodosRESUMEN
OBJECTIVE: The authors aimed to investigate the prevalence of pregnancy and obstetric outcomes in patients who underwent radical trachelectomy (RT) for early-stage cervical cancer in the Kanto area, Japan. METHOD: A survey among 113 perinatal centers affiliated with the Kanto Society of Obstetrics and Gynecology was conducted to investigate their experience in managing pregnancies following RT, between 2010 and 2020. The association between preterm delivery (before 34 gestational weeks) and a midtrimester short cervix (<13 mm) was evaluated. RESULTS: The authors retrospectively collected maternal and perinatal data from 13 hospitals. There were 135 pregnancies among 115 women following RT. Of the 135 pregnancies, 32 were miscarriages (<12 gestational weeks: n = 22; >12 gestational weeks: n = 10), and 103 were delivered after 22 gestational weeks. The incidences of preterm delivery before 28 and 34 gestational weeks were 8.7% and 30.1%, respectively. A midtrimester short residual cervix was associated with preterm delivery (P = 0.046). CONCLUSION: Since more than 100 pregnancies were recorded after RT in the Kanto area, many physicians had more opportunities to manage pregnancy after RT. Pregnancy following RT is associated with increased risk of preterm delivery, and midtrimester short residual cervix is a good predictor of preterm delivery.
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Nacimiento Prematuro , Traquelectomía , Neoplasias del Cuello Uterino , Embarazo , Recién Nacido , Femenino , Humanos , Resultado del Embarazo , Cuello del Útero/cirugía , Traquelectomía/efectos adversos , Nacimiento Prematuro/epidemiología , Nacimiento Prematuro/etiología , Neoplasias del Cuello Uterino/cirugía , Neoplasias del Cuello Uterino/etiología , Estudios Retrospectivos , Japón/epidemiologíaRESUMEN
BACKGROUND: Photodynamic therapy (PDT) is an effective tumor treatment that involves the administration of a photosensitizer to generate cytotoxic 1O2 [reactive oxygen species (ROS)] from molecular oxygen that is produced from energy absorption following tumor irradiation at specific wavelengths. Ferroptosis is induced by the disruption of the glutathione peroxidase 4 (GPX4) antioxidant system, leading to lipid peroxidation. We hypothesized that talaporfin sodium-photodynamic therapy (TS-PDT)-generated ROS would lead to ferroptosis via accumulation of lipid peroxidation. METHODS: Cell viability assay in TS-PDT-treated cells in combination with a ferroptosis inhibitor (ferrostatin-1: Fer-1) or ferroptosis inducers (imidazole ketone erastin: IKE, Ras-selective lethal 3: RSL3) was performed. Accumulation of lipid peroxidation, GPX4 antioxidant system and cystine/glutamate antiporter (system xc-) activity in TS-PDT-treated cells was investigated. In xenograft mice, the antitumor effect of TS-PDT in combination with ferroptosis inducers (IKE or sorafenib) was examined. RESULTS: TS-PDT-induced cell death was partly suppressed by Fer-1 and accompanied by lipid peroxidation. TS-PDT combined with IKE or RSL3 enhanced the induction of cell death. TS-PDT inhibited cystine uptake activity via system xc-. In vivo, the combination of TS-PDT and ferroptosis inducers (IKE or sorafenib) reduced tumor volume. CONCLUSION: This study found that the mechanism underlying TS-PDT-induced ferroptosis constitutes direct lipid peroxidation by the generated ROS, and the inhibition of system xc-, and that the combination of a ferroptosis inducer with TS-PDT enhances the antitumor effect of TS-PDT. Our findings suggest that ferroptosis-inducing therapies combined with PDT may benefit cancer patients.
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Ferroptosis , Neoplasias , Fotoquimioterapia , Humanos , Animales , Ratones , Antioxidantes , Especies Reactivas de Oxígeno/metabolismo , Sorafenib/farmacología , Cistina/farmacologíaRESUMEN
While plastics are classified by size as microplastics (<5 mm), mesoplastics (5-25 mm), and macroplastics (>25 mm), research in rivers has centered on microplastics, followed by macroplastics, with limited research on mesoplastics (research gap). This study aims to clarify the concentration, shape, and polymer composition of microplastics and mesoplastics in Japanese river water. We conducted field surveys for microplastics and mesoplastics in 147 rivers and at 185 measurement stations. The novelty of this study is in the use of a large number of field data to minimize the effect of the spatial difference in the microplastics and mesoplastics on the data analysis. Microplastics and mesoplastics were found at 183 (99 %) and 136 (74 %) stations, respectively. The difference between the concentration of microplastics and mesoplastics increased significantly with the increase in the concentration of microplastics, showing that the concentration of both microplastics and mesoplastics should be monitored to prevent an underestimation of plastic pollution in rivers with the appropriate sampling. A 2-stage size classification with microplastics (<5 mm) and macroplastics (>5 mm) is not suitable because the mesoplastics may be substantially overlooked. The regression slopes between microplastics and mesoplastics concentrations significant decrease in variance with increasing data number, suggesting the necessity of the large number of samples used in this study. The predominant shapes and polymer types of microplastics and mesoplastics were found to be fragment and fiber and polyethylene and polyethylene terephthalate (PET), respectively, which were affected appreciably by many fiber clusters. The fiber and PET ratios were dominant at stations with small population densities and urban ratios and can be attributed to atmospheric deposition and the underdeveloped rate of wastewater treatment plants (WWTPs). Therefore, it is necessary to monitor the dynamics and fate of fiber clusters inside and outside the basin.
Asunto(s)
Microplásticos , Contaminantes Químicos del Agua , Plásticos/análisis , Polímeros , Ríos , Japón , Contaminantes Químicos del Agua/análisis , Monitoreo del AmbienteRESUMEN
PURPOSE: Obesity is a risk factor and poor prognostic factor for pancreatic ductal adenocarcinoma (PDAC), but the underlying mechanisms remain unclear. METHODS: PDAC cells and obese visceral adipocytes (O-Ad) derived from mice and humans were used to analyze interactions between the two cell types, and human microvascular endothelial cells were used for angiogenesis assay. A xenograft mouse model with subcutaneously injected PDAC cells was used for animal studies. The relationship between visceral fat and prognosis was analyzed using resected tissues from PDAC patients with and without obesity. RESULTS: Conditioned media (CM) from O-Ad significantly increased PDAC cell growth and migration and angiogenic capacity in both human and mice cells, and blocking osteopontin (OPN) in O-Ad canceled O-Ad-induced effects in both mouse and human cells. In addition, O-Ad directly increased the migratory and tube-forming capacities of endothelial cells, while blocking OPN canceled these effects. O-Ad increased AKT phosphorylation and VEGFA expression in both PDAC and endothelial cells, and OPN inhibition in O-Ad canceled those O-Ad-induced effects. In the xenograft model, PDAC tumor volume was significantly increased in obese mice compared with lean mice, whereas blocking OPN significantly inhibited obesity-accelerated tumor growth. OPN expression in adipose tissues adjacent to human PDAC tumor was significantly higher in obese patients than in non-obese patients. In PDAC patients with obesity, high OPN expression in adipose tissues was significantly associated with poor prognosis. CONCLUSION: Obese adipocytes trigger aggressive transformation in PDAC cells to induce PDAC progression and accelerate angiogenesis via OPN secretion.