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1.
Dig Dis Sci ; 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38967903

RESUMEN

INTRODUCTION: Scissor-type knives are spreading as safe devises in endoscopic submucosal dissection (ESD). We evaluated the efficacy of two kinds of scissor-type knives (Clutch Cutter: CC, Fujifilm Co. and SB Knife Jr2: SB, SB-KAWASUMI Laboratories. Inc.) in colorectal ESD. METHODS: This single-center retrospective study analyzed 178 ESD cases treated with CC from January 2020 to August 2021 and 91 cases with SB from September 2021 to December 2023. The two groups were compared through propensity score matching. Therapeutic results, such as ESD procedure time, en bloc resection rate, perioperative bleeding frequency, and complications, were analyzed in each group. Risk factors for long ESD procedure time (≥ 90 min) were also examined. RESULTS: After matching, 87 cases in each group were analyzed. There was no significant difference in the ESD procedure time (min, median [interquartile range]) between the CC and SB groups (54.0 [36.0-72.0] vs. 53.0 [39.0-72.0], p = 0.99). Additionally, there were no differences in the en bloc resection (100% vs. 100%, p = 1.00), perioperative perforation (1.1% vs. 1.1%, p = 1.00), or delayed bleeding (1.1% vs. 0.0%, p = 1.00). There was a significant difference in perioperative bleeding frequency (mean ± standard deviation: 1.8 ± 2.6 vs. 3.0 ± 3.5, p < 0.01). The significant risk factors (odds ratio [95% confidence interval]) for long ESD procedure time in patients treated with CC or SB were antiplatelet (7.51 [1.82-31.00]), large lesion size (1.08 [1.05-1.12]), severe fibrosis (24.30 [7.60-77.90]), and perioperative bleeding frequency (1.34 [1.14-1.56]). CONCLUSIONS: CC and SB in colorectal ESD enabled high en bloc resection and low complication rates. CC showed significantly less perioperative bleeding than SB.

2.
Sci Rep ; 14(1): 15706, 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38977770

RESUMEN

Maintaining the mucus layer is crucial for the innate immune system. Urolithin A (Uro A) is a gut microbiota-derived metabolite; however, its effect on mucin production as a physical barrier remains unclear. This study aimed to elucidate the protective effects of Uro A on mucin production in the colon. In vivo experiments employing wild-type mice, NF-E2-related factor 2 (Nrf2)-deficient mice, and wild-type mice treated with an aryl hydrocarbon receptor (AhR) antagonist were conducted to investigate the physiological role of Uro A. Additionally, in vitro assays using mucin-producing cells (LS174T) were conducted to assess mucus production following Uro A treatment. We found that Uro A thickened murine colonic mucus via enhanced mucin 2 expression facilitated by Nrf2 and AhR signaling without altering tight junctions. Uro A reduced mucosal permeability in fluorescein isothiocyanate-dextran experiments and alleviated dextran sulfate sodium-induced colitis. Uro A treatment increased short-chain fatty acid-producing bacteria and propionic acid concentration. LS174T cell studies confirmed that Uro A promotes mucus production through the AhR and Nrf2 pathways. In conclusion, the enhanced intestinal mucus secretion induced by Uro A is mediated through the actions of Nrf-2 and AhR, which help maintain intestinal barrier function.


Asunto(s)
Colitis , Cumarinas , Mucosa Intestinal , Factor 2 Relacionado con NF-E2 , Receptores de Hidrocarburo de Aril , Animales , Factor 2 Relacionado con NF-E2/metabolismo , Receptores de Hidrocarburo de Aril/metabolismo , Ratones , Mucosa Intestinal/metabolismo , Cumarinas/farmacología , Colitis/metabolismo , Colitis/inducido químicamente , Mucina 2/metabolismo , Mucina 2/genética , Humanos , Colon/metabolismo , Ratones Endogámicos C57BL , Transducción de Señal/efectos de los fármacos , Masculino , Microbioma Gastrointestinal , Ratones Noqueados , Sulfato de Dextran , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Funcion de la Barrera Intestinal
3.
Oncol Lett ; 27(3): 116, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38312910

RESUMEN

Advanced gastric cancer is a highly aggressive malignancy. The available literature does not provide the prognostic value of ascites based on their degree, because most clinical trials exclude patients who present with massive ascites. Therefore, this study examined whether the presence or degree of ascites has a prognostic value in 124 patients with advanced gastric cancer. The degree of ascites was assessed using computed tomography and classified as none, small, moderate or massive. The overall survival (OS) was compared based on the presence or degree of ascites. Furthermore, a Cox proportional hazards analysis was performed to ascertain the predictors of OS. The cumulative 1-year and 2-year OS rates in patients without ascites were 43.5 and 20.2%, respectively, whereas those in patients with ascites were 29.1 and 13.6%, respectively (P=0.116). The cumulative 1-year and 2-year OS rates in patients without moderate or massive ascites were 39.5 and 20.9%, respectively; however, those in patients with moderate or massive ascites were 28.0 and 4.0%, respectively (P=0.027). Multivariate analysis showed that diffuse-type [hazard ratio (HR), 1.532; 95% confidence interval (CI), 1.002-2.343; P=0.049], moderate or massive ascites (HR, 2.153; 95% CI, 1.301-3.564; P=0.003) and chemotherapy (HR, 0.189; 95% CI, 0.101-0.352; P<0.001) were significant predictive factors of OS. In conclusion, the present study indicated that moderate or massive ascites may influence the OS of patients with advanced gastric cancer.

4.
Biol Pharm Bull ; 47(2): 373-382, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38325854

RESUMEN

Patients with diarrhea-predominant irritable bowel syndrome (IBS-D) show excessive peristalsis, and antispasmodic agents may be useful therapeutic agents. There are few reports on the use of Kampo medicines for the treatment of IBS-D. Shakuyakukanzoto (SKT) is a Kampo medicine that is effective against abdominal pain. We examined the relationship between SKT and intestinal peristalsis in an animal model and a prospective study. In the animal model, SKT and its components were administered from the serosal side of the colon and colonic peristalsis was evaluated using intraluminal pressure and spatiotemporal mapping before and after the administration of SKT and its components. In this clinical trial, we used abdominal ultrasonography (US) to obtain long-axis images of the sigmoid colon of 11 patients. The frequency of intestinal peristalsis was measured using US in five patients with SKT and six patients without medication after the ingestion of a test meal. The primary outcome was the frequency of peristalsis. The Clinical Trial Registry Website (Trial No. UMIN-CTR; UMIN000051547). In the animal model, peony did not suppress peristalsis frequency, but SKT (p = 0.005) and glycyrrhiza (p = 0.001) significantly suppressed peristalsis frequency compared with saline and peony. Among the glycyrrhiza components, glycycoumarin and isoliquiritigenin suppressed the peristalsis frequency compared to dimethyl sulfoxide (control) (p = 0.001, 0.01, respectively). In a clinical trial, peristalsis was significantly suppressed after oral administration in patients taking SKT (p = 0.03). Administration of SKT was found to inhibit colonic peristalsis, with glycicumarin and isoliquiritigenin being particularly relevant among its components.


Asunto(s)
Chalconas , Síndrome del Colon Irritable , Humanos , Animales , Peristaltismo , Estudios Prospectivos , Modelos Animales , Diarrea
5.
Clin J Gastroenterol ; 17(2): 253-257, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38190090

RESUMEN

Neuroendocrine tumors (NETs) of the ampulla of Vater are rare. Therefore, there is a lack of comprehensive information regarding their pathogenesis. We herein present the case of a patient with a 5-mm ampullary NET who demonstrated the presence of lymphatic invasion after undergoing endoscopic papillectomy. A 44-year-old woman was referred to our hospital for treatment of a grade 1 NET in the ampulla of Vater. Endoscopic ultrasonography revealed a hypoechoic mass within the submucosal layer without obvious infiltration into the common bile duct or the main pancreatic duct. We performed underwater endoscopic papillectomy (UEP) to remove the tumor with a negative margin. Pathological evaluation of the resected specimen showed a grade 1 NET with a negative margin. However, pancreaticoduodenectomy was subsequently performed because of the risk of lymph node metastasis, which was expected due to the significant number of NET cells infiltrating the endothelium of the lymphatic vessels. No lymph node metastasis or recurrence was observed during the 26-month follow-up period. UEP is a useful method to achieve complete resection for diagnostic and therapeutic purposes. UEP may be a novel option for endoscopic treatment of ampullary NET.


Asunto(s)
Ampolla Hepatopancreática , Neoplasias del Conducto Colédoco , Tumores Neuroendocrinos , Femenino , Humanos , Adulto , Tumores Neuroendocrinos/diagnóstico por imagen , Tumores Neuroendocrinos/cirugía , Tumores Neuroendocrinos/patología , Ampolla Hepatopancreática/cirugía , Ampolla Hepatopancreática/patología , Resultado del Tratamiento , Neoplasias del Conducto Colédoco/diagnóstico por imagen , Neoplasias del Conducto Colédoco/cirugía , Neoplasias del Conducto Colédoco/patología , Endoscopía , Estudios Retrospectivos
6.
Surg Endosc ; 38(4): 1784-1790, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38286838

RESUMEN

BACKGROUND AND AIMS: This retrospective study aimed to compare the short- and long-term outcomes of endoscopic submucosal dissection and laparoscopic and endoscopic cooperative surgery in patients with superficial non-ampullary duodenal epithelial tumors. PATIENTS AND METHODS: We investigated consecutive patients with SNADETs > 10 mm in size who underwent ESD (ESD group) or LECS (LECS group) between January 2015 and March 2021. The data was used to analyze the clinical course, management, survival status, and recurrence between the two groups. RESULTS: A total of 113 patients (100 and 13 in the ESD and LECS groups, respectively) were investigated. The rates of en bloc resection and curative resection were 100% vs. 100% and 93.0% vs. 77.0% in the ESD and LECS groups, respectively, with no significant difference. The ESD group had shorter resection and suturing times than the LECS group, but there were no significant difference after propensity score matching. There were also no differences in the rates of postoperative adverse event (7.0% vs. 23.1%; P = 0.161). The 3-year overall survival (OS) rate was high in both the ESD and LECS groups (97.6% vs. 100%; P = 0.334). One patient in the ESD group experienced recurrence due to liver metastasis; however, no deaths related to SNADETs were observed. CONCLUSION: ESD and LECS are both acceptable treatments for SNADETs in terms of a high OS rate and a low long-term recurrence rate, thereby achieving a comparable high rate of curative resection. Further studies are necessary to compare the outcomes of ESD and LECS for SNADETs once both techniques are developed further.


Asunto(s)
Resección Endoscópica de la Mucosa , Laparoscopía , Neoplasias Glandulares y Epiteliales , Humanos , Estudios Retrospectivos , Resección Endoscópica de la Mucosa/métodos , Resultado del Tratamiento , Laparoscopía/métodos
7.
Dig Endosc ; 36(2): 215-220, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37983598

RESUMEN

Conventional clip closure of mucosal defects after duodenal endoscopic submucosal dissection decreases the incidence of delayed adverse events, but may result in incomplete closure, depending on size or location. This study aimed to assess the effectiveness of the underwater clip closure method for complete duodenal defect closure without the difficulties associated with conventional closure methods. We investigated 19 patients with 20 lesions who underwent endoscopic submucosal dissection of the duodenum and subsequent mucosal defect closure in underwater conditions at our facility between February 2021 and January 2022. The success rate of the underwater clip closure method was defined as the complete endoscopic closure of the mucosal defect; a success rate of 100% was achieved. The median resected specimen size was 34.3 mm, the median procedure time for mucosal defect closure was 14 min, and the median number of clips used per patient was 12. No delayed adverse events were observed. The underwater clip closure method is a feasible option for complete closure of mucosal defects, regardless of the size or location of a duodenal endoscopic submucosal dissection.


Asunto(s)
Resección Endoscópica de la Mucosa , Humanos , Resección Endoscópica de la Mucosa/métodos , Duodeno/cirugía , Técnicas de Cierre de Heridas , Mucosa Intestinal/cirugía , Instrumentos Quirúrgicos , Resultado del Tratamiento , Estudios Retrospectivos
8.
J Gastroenterol ; 59(2): 145-156, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38006445

RESUMEN

BACKGROUND: Microsatellite instability high (MSI-H) and tumor mutational burden high (TMB-high) pancreatic cancer are rare, and information is lacking. Based on the C-CAT database, we analyzed the clinical and genomic characteristics of patients with these subtypes. METHODS: We retrospectively reviewed data on 2206 patients with unresectable pancreatic adenocarcinoma enrolled in C-CAT between July 2019 and January 2022. The clinical features, proportion of genomic variants classified as oncogenic/pathogenic in C-CAT, overall response rate (ORR), disease control rate (DCR), and time to treatment failure (TTF) of chemotherapy as first-line treatment were evaluated. RESULTS: Numbers of patients with MSI-H and TMB-high were 7 (0.3%) and 39 (1.8%), respectively. All MSI-H patients were TMB-high. MSI-H and TMB-high patients harbored more mismatch repair genes, such as MSH2, homologous recombination-related genes, such as ATR and BRCA2, and other genes including BRAF, KMT2D, and SMARCA4. None of the 6 MSI-H patients who received chemotherapy achieved a clinical response, including 4 patients treated with gemcitabine plus nab-paclitaxel (GnP) therapy, whose DCR was significantly lower than that of microsatellite stable (MSS) patients (0 vs. 67.0%, respectively, p = 0.01). Among the TMB-high and TMB-low groups, no significant differences were shown in ORR, DCR (17.1 vs. 23.1% and 57.1 vs. 63.1%, respectively), or median TTF (25.9 vs. 28.0 weeks, respectively) of overall first-line chemotherapy. CONCLUSIONS: MSI-H and TMB-high pancreatic cancers showed some distinct genomic and clinical features from our real-world data. These results suggest the importance of adapting optimal treatment strategies according to the genomic alterations.


Asunto(s)
Adenocarcinoma , Neoplasias Pancreáticas , Humanos , Inestabilidad de Microsatélites , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/genética , Mutación , Estudios Retrospectivos , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/genética , Biomarcadores de Tumor/genética , ADN Helicasas/genética , Proteínas Nucleares/genética , Factores de Transcripción/genética
9.
Jpn J Clin Oncol ; 54(2): 137-145, 2024 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-37869773

RESUMEN

BACKGROUND AND OBJECTIVE: Several endoscopic resection methods have been developed as less invasive treatments for superficial non-ampullary duodenal epithelial tumours. This study aimed to compare outcomes of conventional endoscopic mucosal resection and underwater endoscopic mucosal resection for superficial non-ampullary duodenal epithelial tumours, including resection depth and rate of the muscularis mucosa contained under the lesion. METHODS: This single-centre retrospective cohort study conducted from January 2009 to December 2021 enrolled patients who underwent conventional endoscopic mucosal resection and underwater endoscopic mucosal resection for superficial non-ampullary duodenal epithelial tumours and investigated their clinicopathological outcomes using propensity score matching. RESULTS: Of the 285 superficial non-ampullary duodenal epithelial tumours, 98 conventional endoscopic mucosal resections and 187 underwater endoscopic mucosal resections were included. After propensity score matching, 64 conventional endoscopic mucosal resections and 64 underwater endoscopic mucosal resections were analysed. The R0 resection rate was significantly higher in underwater endoscopic mucosal resection cases than in conventional endoscopic mucosal resection cases (70.3% vs. 50.0%; P = 0.030). In the multivariate analysis, a lesion diameter > 10 mm (odds ratio 7.246; P = 0.001), being in the 1st-50th treatment period (odds ratio 3.405; P = 0.008), and undergoing conventional endoscopic mucosal resection (odds ratio 3.617; P = 0.016) were associated with RX/R1 resection. Furthermore, in underwater endoscopic mucosal resection cases, the R0 rate was significantly higher for lesions diameter ≤10 mm than >10 mm, and was significantly higher in the 51st-treatment period than in the 1st-50th period. Conventional endoscopic mucosal resection and underwater endoscopic mucosal resection cases showed no significant difference in resection depth and muscularis mucosa containing rate. CONCLUSIONS: Underwater endoscopic mucosal resection may be more acceptable than conventional endoscopic mucosal resection for superficial non-ampullary duodenal epithelial tumours ≤ 10 mm. A steep early learning curve may be acquired for underwater endoscopic mucosal resection. Large multicentre prospective studies need to be conducted to confirm the effectiveness of underwater endoscopic mucosal resection.


Asunto(s)
Carcinoma , Neoplasias Duodenales , Humanos , Estudios Retrospectivos , Estudios Prospectivos , Resultado del Tratamiento , Endoscopía , Neoplasias Duodenales/patología
10.
Dig Dis Sci ; 68(12): 4398-4406, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37875607

RESUMEN

BACKGROUND: Helicobacter pylori (H. pylori) is widely recognized as a definite carcinogen in gastric cancer (GC). Although H. pylori eradication reduces the risk of GC, GC recurrence has been detected even after successful H. pylori eradication. Recently, the analysis of gut microbiota was reported. AIMS: This study aimed to evaluate the correlation between gastric mucosa-associated microbiota (G-MAM) and early gastric cancer (EGC) after successful H. pylori eradication. METHODS: In this pilot study, G-MAM were collected during the esophagogastroduodenoscopy of 17 patients, receiving H. pylori eradication therapy at least 5 years ago. The patients were divided into those with EGC (the EGC group, 8 patients) and those without EGC (the NGC group, 9 patients). Microbial samples in the greater curvature of the pyloric site were obtained using an endoscopic cytology brush, and the G-MAM profiles of each sample were analyzed using 16S rRNA V3-V4 gene sequencing. RESULTS: Between the two groups, there was no significant difference in the median age, sex, median period after successful eradication of H. pylori, the α diversity, and the average abundance at the phylum level. At the genus level, the average abundance of Unclassified Oxalobacteraceae, Capnocytophaga, and Haemophilus was significantly lower in the EGC group than in the NGC group (0.89 vs. 0.14%, P < 0.01, 0.28 vs. 0.00%, P < 0.01 and 5.84 vs. 2.16%, P = 0.034, respectively). CONCLUSIONS: We demonstrated alternations in the profiles of G-MAM between the two groups. Our results suggest that G-MAM may influence carcinogenesis after successful H. pylori eradication.


Asunto(s)
Microbioma Gastrointestinal , Infecciones por Helicobacter , Helicobacter pylori , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/complicaciones , Proyectos Piloto , ARN Ribosómico 16S/genética , Infecciones por Helicobacter/diagnóstico , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/complicaciones , Recurrencia Local de Neoplasia/tratamiento farmacológico , Mucosa Gástrica , Antibacterianos/uso terapéutico
11.
Inflamm Intest Dis ; 8(2): 84-90, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37901338

RESUMEN

Introduction: Although the efficacy of 5-aminosalicylic acid (ASA) suppositories for ulcerative colitis (UC) has been reported in many studies, many studies have also described poor adherence to 5-ASA suppository regimens. We aimed to identify the clinical background factors that influence adherence to 5-ASA suppositories to improve adherence and efficacy of the treatment. Methods: We conducted a retrospective cohort study of 61 patients with active UC who were using 5-ASA suppositories. All patients underwent endoscopy and rectal biopsy for histological diagnosis prior to 5-ASA suppository treatment. The efficacy of 5-ASA suppository treatment was compared in relation to clinical background factors (sex, age, disease duration, disease type, clinical activity, Ulcerative Colitis Endoscopic Index of Severity, histological activity, serum C-reactive protein level, concomitant use of immunomodulators, history of steroid use, and dose of oral 5-ASA). Results: The efficacy of 5-ASA suppositories was significantly related to low Lichtiger Colitis Activity Index (LCAI) scores and proctitis type prior to its use. In terms of sex, females tended to show higher efficacy. Multivariate logistic regression analysis using these three factors showed high predictive value for the efficacy of 5-ASA suppositories (AUC, 0.788; sensitivity, 87.2%; and specificity, 63.7%). Conclusion: This study is the first to extract clinical background factors for predicting the efficacy of 5-ASA suppositories. The use of 5-ASA suppositories in patients who are expected to show efficacy will be effective in improving patient co-operation.

12.
Digestion ; 104(6): 468-479, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37619533

RESUMEN

INTRODUCTION: Aortic stenosis (AS) is sometimes associated with gastrointestinal bleeding, and this phenomenon is known as Heyde's syndrome. Such bleeding is most often considered to originate from gastrointestinal angiodysplasias, but the frequency and endoscopic features of such bleeding remain unclear. This study aimed to determine the frequency and endoscopic features of gastrointestinal angiodysplasia in patients with severe AS. PATIENTS AND METHODS: In this multicenter, retrospective study, we evaluated consecutive patients who underwent transcatheter aortic valve implantation (TAVI) with severe AS from May 2016 to December 2019. We extracted the data on the clinicopathological features according to the status of anemia, the proportion of patients who underwent gastrointestinal endoscopic examinations and demonstrated gastrointestinal angiodysplasia, and identified the endoscopic features associated with such patients. RESULTS: In 325 patients, the rates of moderate/severe anemia (hemoglobin < 11 g/dL) were 52%. Regarding medicine, there were no significant differences between the patients with and without moderate/severe anemia. Patients were examined by esophagogastroduodenoscopy (21%), colonoscopy (12%), and balloon-assisted enteroscopy or small bowel capsule endoscopy (1.5%). Patients with moderate/severe anemia had significantly more angiodysplasia (38.3% vs. 7.7%; p < 0.0001) and active bleeding (23.4% vs. 0%; p < 0.01). Angiodysplasia was detected in 21 patients (stomach, n = 9; small intestine, n = 5, and colon, n = 10). CONCLUSIONS: The results suggest, for the first time, that patients with severe AS who underwent TAVI and moderate/severe anemia frequently had gastrointestinal angiodysplasia and active bleeding throughout the entire gastrointestinal tract.


Asunto(s)
Anemia , Angiodisplasia , Estenosis de la Válvula Aórtica , Endoscopía Capsular , Enfermedades del Colon , Humanos , Estudios Retrospectivos , Hemorragia Gastrointestinal/complicaciones , Estenosis de la Válvula Aórtica/complicaciones , Estenosis de la Válvula Aórtica/diagnóstico por imagen , Estenosis de la Válvula Aórtica/cirugía , Angiodisplasia/diagnóstico , Angiodisplasia/diagnóstico por imagen , Anemia/complicaciones
13.
J Gen Fam Med ; 24(3): 185-187, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37261040

RESUMEN

An 84-year-old woman who was admitted for protein-losing gastroenteropathy associated with radiation enteritis 10 years after pelvic radiotherapy developed pyelonephritis. She became anuric despite having an indwelling bladder catheter. Imaging studies revealed bladder wall thickening, bilateral hydroureter formation, and hydronephrosis. Autopsy findings led to a diagnosis of gangrenous cystitis (GC). Our case indicates that radiation-induced late effects may be an indirect cause of GC, not a direct cause as previously suggested, and that GC may induce bilateral vesicoureteral junction obstruction.

14.
Org Lett ; 25(26): 4913-4917, 2023 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-37358542

RESUMEN

A palladium-dihydroxyterphenylphosphine (DHTP) catalyst was successfully applied to the dearomative C3-arylation of tryptamine derivatives with aryl nonaflates. The intramolecular cyclization of the resulting 3,3-disubstituted indolenines afforded C3a-arylated pyrroloindolines in one pot. We postulate that the formation of complexes between the lithium salts of DHTP and the tryptamine derivative is the key to promoting selective arylation at the C3-position of the indole ring. Furthermore, reactions using homotryptamine derivatives successfully provided C4a-arylated pyridoindolines.

15.
J Gastroenterol ; 58(6): 575-585, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37029223

RESUMEN

BACKGROUND: Special subtypes of pancreatic cancer, such as acinar cell carcinoma (ACC), adenosquamous carcinoma (ASC), and anaplastic carcinoma of the pancreas (ACP), are rare, and so data on them are limited. Using the C-CAT database, we analyzed clinical and genomic characteristics of patients with these and evaluated differences on comparison with pancreatic ductal adenocarcinoma (PDAC) patients. METHODS: We retrospectively reviewed data on 2691 patients with unresectable pancreatic cancer: ACC, ASC, ACP, and PDAC, entered into C-CAT from June 2019 to December 2021. The clinical features, MSI/TMB status, genomic alterations, overall response rate (ORR), disease control rate (DCR), and time to treatment failure (TTF) on receiving FOLFIRINOX (FFX) or GEM + nab-PTX (GnP) therapy as first-line treatment were evaluated. RESULTS: Numbers of patients with ACC, ASC, ACP, and PDAC were 44 (1.6%), 54 (2.0%), 25 (0.9%), and 2,568 (95.4%), respectively. KRAS and TP53 mutations were prevalent in ASC, ACP, and PDAC (90.7/85.2, 76.0/68.0, and 85.1/69.1%, respectively), while their rates were both significantly lower in ACC (13.6/15.9%, respectively). Conversely, the rate of homologous recombination-related (HRR) genes, including ATM and BRCA1/2, was significantly higher in ACC (11.4/15.9%) than PDAC (2.5/3.7%). In ASC and ACP, no significant differences in ORR, DCR, or TTF between FFX and GnP were noted, while ACC patients showed a trend toward higher ORR with FFX than GnP (61.5 vs. 23.5%, p = 0.06) and significantly more favorable TTF (median 42.3 vs. 21.0 weeks, respectively, p = 0.004). CONCLUSIONS: ACC clearly harbors different genomics compared with PDAC, possibly accounting for differences in treatment efficacy.


Asunto(s)
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Proteína BRCA1 , Estudios Retrospectivos , Japón , Proteína BRCA2 , Carcinoma Ductal Pancreático/tratamiento farmacológico , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patología , Genómica , Neoplasias Pancreáticas
17.
NPJ Sci Food ; 7(1): 10, 2023 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-36977699

RESUMEN

Colonic mucus layers protect intestinal tissues against intestinal bacteria. We investigated the effects of dietary fiber and its metabolites on mucus production in the colonic mucosa. Mice were fed a partially hydrolyzed guar gum (PHGG)-containing diet and a fiber-free diet (FFD). The colon mucus layer, fecal short-chain fatty acid (SCFA) levels, and gut microbiota were evaluated. Mucin 2 (MUC2) expression was assessed in SCFA-treated LS174T cells. The role of AKT in MUC2 production was investigated. The mucus layer in the colonic epithelium was significantly increased in the PHGG group compared with that in the FFD group. In the PHGG group, an increase in Bacteroidetes in the stool was observed, and fecal acetate, butyrate, propionate, and succinate levels were significantly increased. However, MUC2 production was significantly increased only in succinate-stimulated LS174T cells. The succinate-induced MUC2 production was associated with AKT phosphorylation. Succinate mediated the PHGG-induced increase in the colon mucus layer.

18.
Microbiol Spectr ; : e0238122, 2023 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-36840603

RESUMEN

The environmental stability of human coronavirus OC43 (HCoV-OC43) on the surface of human skin and the effectiveness of disinfectant against HCoV-OC43, which are important to prevent contact transmission, have not been clarified in previous studies. Using previously generated models, we evaluated HCoV-OC43 stability and disinfection effectiveness. Then we compared the results with those for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The median survival time of HCoV-OC43 on the surface of human skin was 24.6 h (95% confidence interval, 19.7 to 29.6 h), which was higher than that of SARS-CoV-2 (10.8 h). Although the in vitro disinfectant effectiveness evaluation showed that HCoV-OC43 has a higher ethanol resistance than SARS-CoV-2, HCoV-OC43 on the skin surface was completely inactivated by a minimum of 50% ethanol within 5 s (the log reduction values were >4.0). Moreover, 1.0% chlorhexidine gluconate and 0.2% benzalkonium chloride showed relatively high disinfectant effectiveness, and the log reduction values when these disinfectants were applied for 15 s were >3.0. HCoV-OC43 is highly stable on the skin surface, which may increase the risk of contact transmission. Although HCoV-OC43 has relatively high ethanol resistance, appropriate hand hygiene practices with current alcohol-based disinfectants sufficiently reduce the risk of contact transmission. IMPORTANCE This study revealed the environmental stability of HCoV-OC43 and disinfectant effectiveness against HCoV-OC43, which had not been demonstrated in previous studies. HCoV-OC43 is highly stable on the surface of human skin, with a survival time of approximately 25 h. High stability of HCoV-OC43 may increase the risk of contact transmission. Furthermore, the in vitro disinfectant effectiveness evaluation showed that HCoV-OC43, which is classified as an envelope virus, has a relatively high ethanol resistance. This finding suggests that disinfectant effectiveness may vary greatly depending on the virus and that each virus targeted for infection control should be evaluated individually. HCoV-OC43 on the skin surface was rapidly inactivated by 50% ethanol, which suggests that appropriate hand hygiene practices with current alcohol-based disinfectants can sufficiently reduce the risk of HCoV-OC43 contact transmission.

19.
Chem Pharm Bull (Tokyo) ; 71(2): 175-182, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36724980

RESUMEN

Palladium-catalyzed, hydroxy-group-directed C-H arylation of [1,1'-biphenyl]-2-ols with chloroarenes was performed. The reaction showed a broad substrate scope and was successfully applied to pharmaceuticals containing a chloro group. Using 2-heteroarylphenols instead of [1,1'-biphenyl]-2-ols also yielded the desired products. The arylated product was further transformed into a triphenylene derivative.


Asunto(s)
Compuestos de Bifenilo , Paladio , Estructura Molecular , Catálisis
20.
Int J Vitam Nutr Res ; 93(5): 427-437, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35635517

RESUMEN

Gut microbiota and short-chain fatty acids (SCFAs) are recognized as key factors in the pathophysiology of irritable bowel syndrome. Astaxanthin is a carotenoid with strong antioxidant and anti-inflammatory activities. In this study, we examined the effects of astaxanthin on gut microbiota-, SCFAs-, and corticotropin-releasing factor (CRH)-induced intestinal hypermotility. Male Wistar rats (n=12 per group) were fed a diet with or without 0. 02% (w/w) astaxanthin for four weeks and CRH or saline was administered intravenously. The number of fecal pellets was counted 2 h after injection. Then the rats were sacrificed, and the cecal content were collected 3 h after injection. The number of feces was significantly increased by CRH injection in the control group (2.0 vs. 6.5; p=0.028), but not in the astaxanthin group (1.0 vs. 2.2; p=0.229) (n=6 per group). The cecal microbiota in the astaxanthin group was significantly altered compared with that in the control group. The concentrations of acetic acid (81.1 µmol/g vs. 103.9 µmol/g; p=0.015) and butyric acid (13.4 µmol/g vs. 39.2 µmol/g; p<0.001) in the astaxanthin group were significantly lower than that in the control group (n=12 per group). Astaxanthin attenuates CRH-induced intestinal hypermotility and alters the composition of gut microbiota and SCFAs.


Asunto(s)
Microbioma Gastrointestinal , Síndrome del Colon Irritable , Masculino , Ratas , Animales , Microbioma Gastrointestinal/fisiología , Ratas Wistar , Ácidos Grasos Volátiles/farmacología , Motilidad Gastrointestinal
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