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International Journal of Molecular... Jun 2024A family of bifunctional dihetarylmethanes and dibenzoxanthenes is assembled via a reaction of acetals containing a 2-chloroacetamide moiety with phenols and related...
A family of bifunctional dihetarylmethanes and dibenzoxanthenes is assembled via a reaction of acetals containing a 2-chloroacetamide moiety with phenols and related oxygen-containing heterocycles. These compounds demonstrated selective antitumor activity associated with the induction of cell apoptosis and inhibition of the process of glycolysis. In particular, bis(heteroaryl)methane containing two 4-hydroxy-6-methyl-2-pyran-2-one moieties combine excellent in vitro antitumor efficacy with an IC of 1.7 µM in HuTu-80 human duodenal adenocarcinoma models with a high selectivity index of 73. Overall, this work highlights the therapeutic potential of dimeric compounds assembled from functionalized acetals and builds a starting point for the development of a new family of anticancer agents.
Topics: Humans; Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Methane; Cell Proliferation; Xanthenes
PubMed: 38928428
DOI: 10.3390/ijms25126724 -
Journal of Clinical and Experimental... 2024Duodenal type follicular lymphoma (DFL), a rare entity of follicular lymphoma (FL), is clinically indolent and is characterized by a low histological grade compared with...
Duodenal type follicular lymphoma (DFL), a rare entity of follicular lymphoma (FL), is clinically indolent and is characterized by a low histological grade compared with nodal follicular lymphoma (NFL). Our previous reports revealed that DFL shares characteristics of both NFL and mucosa-associated lymphoid tissue (MALT) lymphoma in terms of clinical and biological aspects, suggesting its pathogenesis may involve antigenic stimulation. In contrast to NFL, the genomic methylation status of DFL is still challenging. Here, we determined the methylation profiles of DNAs from patients with DFL (n = 12), NFL (n = 10), duodenal reactive lymphoid hyperplasia (D-RLH) (n = 7), nodal reactive lymphoid hyperplasia (N-RLH) (n = 5), and duodenal samples from normal subjects (NDU) (n = 5) using methylation specific PCR of targets previously identified in MALT lymphoma (CDKN2B/P15, CDKN2A/P16, CDKN2C/P18, MGMT, hMLH-1, TP73, DAPK, HCAD). DAPK1 was frequently methylated in DFL (9/12; 75%), NFL (9/10; 90%), and D-RLH (5/7; 71%). CDKN2B/P15 sequences were methylated in six DFL samples and in only one NFL sample. Immunohistochemical analysis showed that p15 expression inversely correlated with methylation status. Genes encoding other cyclin-dependent kinase inhibitors (CDKN2A/P16, CDKN2C/P18) were not methylated in DFL samples. Methylation of the genes of interest was not detected in DNAs from D-RLH, except for DAPK1, and the difference in the extent of methylation between NDU and D-RLH was statistically significant (P = 0.013). Our results suggest that D-RLH serves as a reservoir for the development of DFL and that methylation of CDKN2B/P15 plays an important role in this process.
Topics: Humans; Lymphoma, Follicular; Death-Associated Protein Kinases; DNA Methylation; Male; Pseudolymphoma; Female; Middle Aged; Cyclin-Dependent Kinase Inhibitor p15; Aged; Duodenal Neoplasms; Adult
PubMed: 38925973
DOI: 10.3960/jslrt.24020 -
Biological & Pharmaceutical Bulletin 2024A major site for the absorption of orally administered drugs is the intestinal tract, where the mucosal epithelium functions as a barrier separating the inside body from...
A major site for the absorption of orally administered drugs is the intestinal tract, where the mucosal epithelium functions as a barrier separating the inside body from the outer environment. The intercellular spaces between adjacent epithelial cells are sealed by bicellular and tricellular tight junctions (TJs). Although one strategy for enhancing intestinal drug absorption is to modulate these TJs, comprehensive gene (mRNA) expression analysis of the TJs components has never been fully carried out in humans. In this study, we used human biopsy samples of normal-appearing mucosa showing no endoscopically visible inflammation collected from the duodenum, jejunum, ileum, colon, and rectum to examine the mRNA expression profiles of TJ components, including occludin and tricellulin and members of the claudin family, zonula occludens family, junctional adhesion molecule (JAM) family, and angulin family. Levels of claudin-3, -4, -7, -8, and -23 expression became more elevated in each segment along the intestinal tract from the upper segments to the lower segments, as did levels of angulin-1 and -2 expression. In contrast, expression of claudin-2 and -15 was decreased in the large intestine compared to the small intestine. Levels of occludin, tricellulin, and JAM-B and -C expression were unchanged throughout the intestine. Considering their segment specificity, claudin-8, claudin-15, and angulin-2 appear to be targets for the development of permeation enhancers in the rectum, small intestine, and large intestine, respectively. These data on heterogenous expression profiles of intestinal TJ components will be useful for the development of safe and efficient intestinal permeation enhancers.
Topics: Humans; Tight Junctions; Intestinal Mucosa; MARVEL Domain Containing 2 Protein; Claudins; Occludin; Male; Adult; Middle Aged; Female; RNA, Messenger; Gene Expression; Aged
PubMed: 38925921
DOI: 10.1248/bpb.b23-00927 -
Journal of Advanced Research Jun 2024During lactation, dairy cattle's digestive tract requires significant adaptations to meet the increased nutrient demands for milk production. As we attempt to improve...
During lactation, dairy cattle's digestive tract requires significant adaptations to meet the increased nutrient demands for milk production. As we attempt to improve milk-related traits through selective pressure, it is crucial to understand the biological functions of the epithelia of the rumen, small intestine, and colonic tissues in response to changes in physiological state driven by changes in nutrient demands for milk synthesis. In this study, we obtained a total of 108 transcriptome profiles from three tissues (epithelia of the colon, duodenum, and rumen) of five Holstein cows, spanning eight time points from the early, mid, late lactation periods to the dry period. On average 97.06% of reads were successfully mapped to the reference genome assembly ARS-UCD1.2. We analyzed 27,607 gene expression patterns at multiple periods, enabling direct comparisons within and among tissues during different lactation stages, including early and peak lactation. We identified 1645, 813, and 2187 stage-specific genes in the colon, duodenum, and rumen, respectively, which were enriched for common or specific biological functions among different tissues. Time series analysis categorized the expressed genes within each tissue into four clusters. Furthermore, when the three tissues were analyzed collectively, 36 clusters of similarly expressed genes were identified. By integrating other comprehensive approaches such as gene co-expression analyses, functional enrichment, and cell type deconvolution, we gained profound insights into cattle lactation, revealing tissue-specific characteristics of the gastrointestinal tract and shedding light on the intricate molecular adaptations involved in nutrient absorption, immune regulation, and cellular processes for milk synthesis during lactation.
PubMed: 38925453
DOI: 10.1016/j.jare.2024.06.020 -
Endoscopy Dec 2024
Topics: Humans; Hamartoma; Brunner Glands; Duodenal Diseases; Male; Female; Duodenoscopy; Middle Aged
PubMed: 38925166
DOI: 10.1055/a-2336-3268 -
Cureus Jun 2024Transarterial angiographic embolization using coils is an effective, common, and safe treatment for non-variceal upper gastrointestinal bleeding (UGIB) refractory to...
Transarterial angiographic embolization using coils is an effective, common, and safe treatment for non-variceal upper gastrointestinal bleeding (UGIB) refractory to endoscopic therapy/management. Coil migration is a complication that can lead to rebleeding. Our patient experienced UGIB due to a recurring duodenal ulcer with coil protrusion following previous embolization for a bleeding duodenal ulcer that was not responsive to endoscopic therapy. The ulceration was successfully managed with endoscopic partial coil removal and medical therapy to achieve hemostasis and ulcer healing. Endoscopists should be aware of coil embolization complications and consider endoscopic removal in the appropriate clinical setting.
PubMed: 38919859
DOI: 10.7759/cureus.62972 -
Clinical Endoscopy Jun 2024Dilation of the tract before stent deployment is a challenging step in endoscopic ultrasound-guided pancreatic duct drainage (EUS-PDD). In this study, we examined the...
BACKGROUND/AIMS
Dilation of the tract before stent deployment is a challenging step in endoscopic ultrasound-guided pancreatic duct drainage (EUS-PDD). In this study, we examined the effectiveness and safety of a novel spiral dilator, Tornus ES (Asahi Intec), for EUS-PDD.
METHODS
This was a retrospective, single-arm, observational study at Aichi Cancer Center Hospital. The punctured tract was dilated using a Tornus ES dilator in all EUS-PDD cases. Our primary endpoint was the technical success rate of initial tract dilation. Technical success was defined as successful fistula dilation using Tornus ES followed by successful stent insertion. Secondary endpoints were procedure times and early adverse events.
RESULTS
A total of 12 patients were included between December 2021 and March 2023. EUS-PDD was performed in 11 patients for post-pancreaticoduodenectomy anastomotic strictures and one patient with pancreatitis with duodenal perforation. The technical success rates of stent insertion and fistula dilation using Tornus ES dilator was 100%. The median procedure time was 24 minutes. No remarkable adverse events related to the procedure were observed, apart from fever, which occurred in 2 patients.
CONCLUSIONS
Tract dilation in EUS-PDD using Tornus ES is effective and safe.
PubMed: 38919059
DOI: 10.5946/ce.2023.272 -
Clinical Endoscopy May 2024With the alarmingly increasing prevalence of obesity in the Western world, it has become necessary to provide more acceptable treatment options for patients with... (Review)
Review
With the alarmingly increasing prevalence of obesity in the Western world, it has become necessary to provide more acceptable treatment options for patients with obesity. Minimally invasive endoscopic techniques are continuously evolving. Currently, metabolic and bariatric endoscopies encompass several different techniques that can offer significant weight loss and improvement in comorbidities with a favorable safety profile. Restrictive bariatric procedures include the use of intragastric balloons and gastric remodeling techniques with different suturing devices. Several studies have demonstrated the efficacy and safety of these techniques that are widely used in clinical practice. Small intestine-targeted metabolic endoscopy is an intriguing and rapidly evolving field of research, although it is not widespread in routine practice. These techniques include duodenal-jejunal bypass liners, duodenal mucosal resurfacing, and incisionless anastomoses. The aim of this review article is to provide a detailed update on the currently available bariatric endoscopy techniques in Western countries.
PubMed: 38919056
DOI: 10.5946/ce.2023.253 -
Cureus May 2024Periampullary cancers, which include pancreatic adenocarcinoma, ampullary cancer, distal cholangiocarcinoma, and duodenal cancer, present diagnostic and management...
Periampullary cancers, which include pancreatic adenocarcinoma, ampullary cancer, distal cholangiocarcinoma, and duodenal cancer, present diagnostic and management challenges due to their aggressive nature and nonspecific symptoms. We describe a case of a female patient, age 20, who had obstructive jaundice brought on by a periampullary tumor. Despite difficulties in diagnosis and treatment, including failed endoscopic retrograde cholangiopancreatography (ERCP), the patient underwent a successful pancreaticoduodenectomy (Whipple's resection), and subsequent immunohistochemistry revealed adenocarcinoma with a mixed immunophenotype expressing duodenal and pancreatic markers. This example emphasizes the significance of taking young patients' periampullary tumors into account, the difficulties in diagnosing them, and the possibility of effective surgical surgery throughout this age range.
PubMed: 38915985
DOI: 10.7759/cureus.61013 -
The Indian Journal of Radiology &... Jul 2024The aim of this study was to examine the imaging manifestations of post-endoscopic retrograde cholangiopancreatography (ERCP) specific complications by computed...
The aim of this study was to examine the imaging manifestations of post-endoscopic retrograde cholangiopancreatography (ERCP) specific complications by computed tomography to aid in its early and successful diagnosis and timely intervention. Forty-one cases of imaging having post-ERCP were complications were retrospectively collected and the spectrum of complications and their key imaging features and methods to improve their detection were analyzed. The most common complication detected in computed tomography (CT) post-ERCP was the presence of intra-abdominal collections seen in 21 patients (51.2%). Pancreatitis was seen in 20 of 41 patients (48.7%), while bowel perforation was present in 9 patients (21%). Pleural effusion was present in 8 patients (19.5%), liver abscess in 6 patients (14.6%), cholangitis in 4 patients (9.7%), gallbladder perforation in 4 patients (9.7%), displaced common bile duct stent in 3 patients (7.3%), possibility of main pancreatic duct cannulation in 2 patients (4.8%), vascular injury resulting in right hepatic artery pseudoaneurysm in 1 patient (2.4%), thrombosis of portal vein or its branches in 2 patients (4.8%), superior mesenteric vein thrombosis in 1 patient (2.4%), right hepatic vein thrombosis in 1 patient (2.4%), pulmonary thromboembolism in 2 patients (4.8%), duodenal inflammation in 1 patient (2.4%), bowel ileus in 4 patients (9.6%), and bowel obstruction in 1 patient (2.4%). Complications after ERCP can cause significant morbidity and mortality if not diagnosed early and treated appropriately. Familiarity with normal findings post-ERCP and knowledge of the imaging appearance of these complications are vital in the early management of these conditions.
PubMed: 38912237
DOI: 10.1055/s-0044-1779585