Oral Administration of PLGA Nanoparticles to Deliver Antisense Oligonucleotides to Inflammatory Lesions in the Gastrointestinal Tract
In this study, we prepared antisense oligonucleotide (ASO)-encapsulated nanoparticles (NPs) with a suitable profile for oral administration for the treatment of inflammatory bowel disease (IBD). We chose a water-in-oil-in-water (w/o/w) method to prepare the NPs using poly(lactide-co-glycolide) as a matrix and Pluronic as a stabilizer. The obtained NPs had a suitable diameter (158 nm) for the penetration of the mucus layer, endocytic uptake by enterocytes, and accumulation in inflammatory lesions in the intestine. The amount of ASOs in the NPs was relatively large (6.41% (w/w)). When the NPs were stably dispersed in solutio...
Source: Biological and Pharmaceutical Bulletin - April 14, 2024 Category: Drugs & Pharmacology Authors: Yuta Yagi Yiwei Liu Jinting Li Shunsuke Shimada Munetaka Ohkouchi Yasushi Taguchi Teruki Nii Takeshi Mori Yoshiki Katayama Source Type: research

Metabolic Regulation of the Th17/Treg Balance in Inflammatory Bowel Disease
Pharmacol Res. 2024 Apr 12:107184. doi: 10.1016/j.phrs.2024.107184. Online ahead of print.ABSTRACTInflammatory bowel disease (IBD) is a long-lasting and inflammatory autoimmune condition affecting the gastrointestinal tract, impacting millions of individuals globally. The balance between T helper 17 (Th17) cells and regulatory T cells (Tregs) is pivotal in the pathogenesis and progression of IBD. This review summarizes the pivotal role of Th17/Treg equilibrium in maintaining intestinal homeostasis, elucidating how its dysregulation contributes to the development and exacerbation of IBD. It comprehensively synthesizes the c...
Source: Cell Research - April 14, 2024 Category: Cytology Authors: Shunfen Zhang Ruqing Zhong Shanlong Tang Liang Chen Hongfu Zhang Source Type: research

GSE216371 A single-cell atlas of chromatin accessibility in mouse organogenesis
Contributors : Keyong Sun ; Xun LanSeries Type : Genome binding/occupancy profiling by high throughput sequencingOrganism : Mus musculusRecent surveys of mouse organogenesis cell atlas (MOCA) with single cell transcriptomics have uncovered hundreds of cell types, but the cell-type-specific transcriptional regulatory programs responsible for the unique identity and function of each cell type have yet to be elucidated. We applied a four-level combinatorial indexing assay, SPATAC-seq, to profile the chromatin accessibility in>350,000 cells derived from 13 embryos staged between embryonic day (E) 10.5 and 13.5 in a single e...
Source: GEO: Gene Expression Omnibus - April 14, 2024 Category: Genetics & Stem Cells Tags: Genome binding/occupancy profiling by high throughput sequencing Mus musculus Source Type: research

Organizational and Implementation Factors Associated with Cirrhosis Care in the Veterans Health Administration
ConclusionsResources, barriers, and care processes varied across diverse VAMCs. Smaller VAMCs without specialty care achieved HCC and EVST surveillance rates nearly as high as more complex and resourced VAMCs if they used a population management tool to identify the patients due for cirrhosis care. (Source: Digestive Diseases and Sciences)
Source: Digestive Diseases and Sciences - April 14, 2024 Category: Gastroenterology Source Type: research

Incidence and molecular characteristics of deficient mismatch repair conditions across nine different tumors and identification of germline variants involved in Lynch-like syndrome
ConclusionsOur data regarding the LS to LLS ratio would be useful for genetic counseling in patients who are suspected to have LS, though the genetic backgrounds for the pathogenesis of LLS need further investigation. (Source: International Journal of Clinical Oncology)
Source: International Journal of Clinical Oncology - April 14, 2024 Category: Cancer & Oncology Source Type: research

Coarse-grained modeling and dynamics tracking of nanoparticles diffusion in human gut mucus
Int J Biol Macromol. 2024 Apr 11:131434. doi: 10.1016/j.ijbiomac.2024.131434. Online ahead of print.ABSTRACTThe gastrointestinal (GI) tract's mucus layer serves as a critical barrier and a mediator in drug nanoparticle delivery. The mucus layer's diverse molecular structures and spatial complexity complicates the mechanistic study of the diffusion dynamics of particulate materials. In response, we developed a bi-component coarse-grained mucus model, specifically tailored for the colorectal cancer environment, that contained the two most abundant glycoproteins in GI mucus: Muc2 and Muc5AC. This model demonstrated the effect...
Source: International Journal of Biological Macromolecules - April 13, 2024 Category: Biochemistry Authors: Liming Zhao Sandra L Arias Warren Zipfel Ilana L Brito Jingjie Yeo Source Type: research

Hypovitaminosis D and hyperparathyroidism: a 5-year postoperative follow-up of 30,458 gastric bypass and sleeve gastrectomy patients
CONCLUSIONS: Previous studies alongside these results suggest that RYGB, more so than SG, may cause hypovitaminosis D and thereby hyperparathyroidism, which could lead to osteopenia. The threshold for 25-OH-D should be >75 nmol/L, and despite higher levels, current vitamin D supplementation may not be sufficient. Follow-up should include screening for hyperparathyroidism and hypovitaminosis D.PMID:38614927 | DOI:10.1016/j.soard.2024.02.004 (Source: Surgery for Obesity and Related Diseases : official journal of the American Society for Bariatric Surgery)
Source: Surgery for Obesity and Related Diseases : official journal of the American Society for Bariatric Surgery - April 13, 2024 Category: Surgery Authors: Katharina Stevens Hella Hultin Magnus Sundbom Source Type: research

Ketohexokinase-A deficiency attenuates the proliferation via reducing β-catenin in gastric cancer cells
Exp Cell Res. 2024 Apr 11:114038. doi: 10.1016/j.yexcr.2024.114038. Online ahead of print.ABSTRACTOverconsumption of fructose is closely related to cancer. Ketohexokinase (KHK) catalyzes the conversion from fructose to fructose-1-phosphate (F1P), which is the first and committed step of fructose metabolism. Recently, aberrant KHK activation has been identified in multiple malignancies. However, the roles of KHK in gastric cancer (GC) cells are largely unclear. Herein, we reveal that the expression of ketohexokinase-A (KHK-A), one alternatively spliced KHK isoform that possesses low affinity for fructose, was markedly incre...
Source: Cell Research - April 13, 2024 Category: Cytology Authors: Gang Ma Siya Liu Fenglin Cai Han Liang Jingyu Deng Rupeng Zhang Mingzhi Cai Source Type: research

Machine learning for identifying tumor stemness genes and developing prognostic model in gastric cancer
Aging (Albany NY). 2024 Apr 12;16. doi: 10.18632/aging.205715. Online ahead of print.ABSTRACTGastric cancer presents a formidable challenge, marked by its debilitating nature and often dire prognosis. Emerging evidence underscores the pivotal role of tumor stem cells in exacerbating treatment resistance and fueling disease recurrence in gastric cancer. Thus, the identification of genes contributing to tumor stemness assumes paramount importance. Employing a comprehensive approach encompassing ssGSEA, WGCNA, and various machine learning algorithms, this study endeavors to delineate tumor stemness key genes (TSKGs). Subseque...
Source: Aging - April 13, 2024 Category: Biomedical Science Authors: Guo-Xing Li Yun-Peng Chen You-Yang Hu Wen-Jing Zhao Yun-Yan Lu Fu-Jian Wan Zhi-Jun Wu Xiang-Qian Wang Qi-Ying Yu Source Type: research

Mobocertinib in Patients with EGFR Exon 20 Insertion-Positive Non-Small Cell Lung Cancer (MOON): An International Real-World Safety and Efficacy Analysis
Int J Mol Sci. 2024 Apr 3;25(7):3992. doi: 10.3390/ijms25073992.ABSTRACTEGFR exon 20 (EGFR Ex20) insertion mutations in non-small cell lung cancer (NSCLC) are insensitive to traditional EGFR tyrosine kinase inhibitors (TKIs). Mobocertinib is the only approved TKI specifically designed to target EGFR Ex20. We performed an international, real-world safety and efficacy analysis on patients with EGFR Ex20-positive NSCLC enrolled in a mobocertinib early access program. We explored the mechanisms of resistance by analyzing postprogression biopsies, as well as cross-resistance to amivantamab. Data from 86 patients with a median a...
Source: Molecular Medicine - April 13, 2024 Category: Molecular Biology Authors: Oliver Illini Felix Carl Saalfeld Petros Christopoulos Micha ël Duruisseaux Anders Vikstr öm Nir Peled Ingel Demedts Elizabeth Dudnik Anna Eisert Sayed M S Hashemi Urska Janzic Waleed Kian Katja Mohorcic Saara Mohammed Maria Silvoniemi Sacha I Rothschil Source Type: research

Hypovitaminosis D and hyperparathyroidism: a 5-year postoperative follow-up of 30,458 gastric bypass and sleeve gastrectomy patients
CONCLUSIONS: Previous studies alongside these results suggest that RYGB, more so than SG, may cause hypovitaminosis D and thereby hyperparathyroidism, which could lead to osteopenia. The threshold for 25-OH-D should be >75 nmol/L, and despite higher levels, current vitamin D supplementation may not be sufficient. Follow-up should include screening for hyperparathyroidism and hypovitaminosis D.PMID:38614927 | DOI:10.1016/j.soard.2024.02.004 (Source: Surgery for Obesity and Related Diseases : official journal of the American Society for Bariatric Surgery)
Source: Surgery for Obesity and Related Diseases : official journal of the American Society for Bariatric Surgery - April 13, 2024 Category: Surgery Authors: Katharina Stevens Hella Hultin Magnus Sundbom Source Type: research

Lonidamine Induced Selective Acidification and De-Energization of Prostate Cancer Xenografts: Enhanced Tumor Response to Radiation Therapy
Cancers (Basel). 2024 Mar 31;16(7):1384. doi: 10.3390/cancers16071384.ABSTRACTProstate cancer is a multi-focal disease that can be treated using surgery, radiation, androgen deprivation, and chemotherapy, depending on its presentation. Standard dose-escalated radiation therapy (RT) in the range of 70-80 Gray (GY) is a standard treatment option for prostate cancer. It could be used at different phases of the disease (e.g., as the only primary treatment when the cancer is confined to the prostate gland, combined with other therapies, or as an adjuvant treatment after surgery). Unfortunately, RT for prostate cancer is associa...
Source: Cancer Control - April 13, 2024 Category: Cancer & Oncology Authors: Stepan Orlovskiy Pradeep Kumar Gupta Jeffrey Roman Fernando Arias-Mendoza David S Nelson Cameron J Koch Vivek Narayan Mary E Putt Kavindra Nath Source Type: research

Reducing State Conflicts between Network Motifs Synergistically Enhances Cancer Drug Effects and Overcomes Adaptive Resistance
Cancers (Basel). 2024 Mar 29;16(7):1337. doi: 10.3390/cancers16071337.ABSTRACTInducing apoptosis in cancer cells is a primary goal in anti-cancer therapy, but curing cancer with a single drug is unattainable due to drug resistance. The complex molecular network in cancer cells causes heterogeneous responses to single-target drugs, thereby inducing an adaptive drug response. Here, we showed that targeted drug perturbations can trigger state conflicts between multi-stable motifs within a molecular regulatory network, resulting in heterogeneous drug responses. However, we revealed that properly regulating an interconnecting m...
Source: Cancer Control - April 13, 2024 Category: Cancer & Oncology Authors: Yunseong Kim Sea Rom Choi Kwang-Hyun Cho Source Type: research

Proton Pump Inhibitors and Cancer Risk: A Comprehensive Review of Epidemiological and Mechanistic Evidence
Conclusions: Despite the well-established cancer risk associated with PPIs, it is notable that these medications continue to be widely prescribed for periods longer than 3 months. Thus, it is of paramount importance for clinicians and patients to thoughtfully evaluate the potential risks and benefits of long-term PPI usage and explore alternative treatments before making informed decisions regarding their medical management.PMID:38610738 | DOI:10.3390/jcm13071970 (Source: Clinical Colorectal Cancer)
Source: Clinical Colorectal Cancer - April 13, 2024 Category: Cancer & Oncology Authors: Ibrahim O Sawaid Abraham O Samson Source Type: research

Neuropsychiatric disorder as early clinical presentation of marantic endocarditis in patient with newly diagnosed poorly differentiated esophago ‐gastric junction adenocarcinoma: A case report
Transesophageal cardiac echocolor-Doppler: large package of endocardial vegetations encompassing the posterior mitral leaflet, especially at P2-P3 level; similar lesions also at the free edge of the anterior mitral flap in A2. Key Clinical MessageNeuropsychiatric symptoms, depression, and progressive mental confusion should not be overlooked as onset symptoms of multiple cerebral ischemic lesions due to cardiac embolization. Comprehensive clinical evaluation due to progressive anemia led to the diagnosis of poorly differentiated adenocarcinoma of the esophagogastric junction as cause of embolizing nonbacterial mitral endoc...
Source: Clinical Case Reports - April 13, 2024 Category: General Medicine Authors: Filomena Ferrentino, Sara Campana, Marco Torri, Carlo Rostagno Tags: CASE REPORT Source Type: research