Background: Cholelithiasis poses significant health and economic burdens, necessitating novel pharmacological targets to enhance treatment efficacy.
Method: Based on genome-wide association analysis (GWAS) studies, we performed two-sample Mendelian randomization (MR) analysis based on plasma proteomics to explore potential drug targets in European (nCase=40,191 and nControl=361,641) and Asian (nCase=9,305 and nControl=168,253) populations. We confirmed the directionality and robust correlation of the drug targets with the results through reverse MR analysis, Steiger filtering, Bayesian colocalization, phenotype scanning and replication in multiple databases.
Background: The gut microbiota can be influenced by lipid metabolism. We aimed to evaluate the impact of lipid-lowering medications, such as proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, Niemann-Pick C1-Like 1 protein (NPC1L1) inhibitors, and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) inhibitors, on gut microbiota through drug target Mendelian randomization (MR) investigation.
Methods: We used genetic variants that were associated with low-density lipoprotein cholesterol (LDL-C) in genome-wide association studies and located within or near drug target genes as proxies for lipid-lowering drug exposure.
J Transl Int Med
February 2024
Gastric cancer (GC) ranks third among cancers in terms of mortality rate worldwide. A clear understanding of the mechanisms underlying the genesis and progression of GC will contribute to clinical decision making. N-methyladenosine (mA) is the most abundant among diverse mRNA modification types and regulates multiple facets of RNA metabolism.
View Article and Find Full Text PDFBackground: The causal relationship between gut microbiota and cerebral cortex development remains unclear. We aimed to scrutinize the plausible causal impact of gut microbiota on cortical thickness via Mendelian randomization (MR) study.
Methods: Genome-wide association study (GWAS) data for 196 gut microbiota phenotypes (N = 18,340) were obtained as exposures, and GWAS data for cortical thickness-related traits (N = 51,665) were selected as outcomes.
Bacterial-derived extracellular vesicles (EVs) have emerged as crucial mediators in the cross-talk between hosts and pathogens, playing a significant role in infectious diseases and cancers. Among these pathogens, Helicobacter pylori (H. pylori) is a particularly important bacterium implicated in various gastrointestinal disorders, gastric cancers, and systemic illnesses.
View Article and Find Full Text PDFThe surface of the small bowel mucosa is covered more than any other section of the digestive canal; however, the overall prevalence of small bowel tumors of the whole gastrointestinal tract is evidently low. Owing to the improvement in endoscopic techniques, the prevalence of small bowel tumors has increased across multiple countries, which is mainly due to an increase in duodenal tumors. Superficial non-ampullary duodenal epithelial tumors (SNADETs) are defined as tumors originating from the non-ampullary region in the duodenum that share similarities and discrepancies with their gastric and colorectal counterparts in the pathogenesis and clinicopathologic characteristics.
View Article and Find Full Text PDFBackground: Dengue virus (DENV) infection during pregnancy increases the risk of adverse fetal outcomes, which has become a new clinical challenge. However, the underlying mechanism remains unknown.
Methods: The effect of DENV-2 infection on fetuses was investigated using pregnant interferon α/β receptor-deficient (Ifnar1) mice.
Glycosylphosphatidylinositol-specific phospholipase D (GPLD1) is a specific enzyme for glycosylphosphatidylinositol (GPI) anchors, thereby exerting its biological functions by cleaving membrane-associated GPI molecules. GPLD1 is abundant in serum, with a concentration of approximately 5-10 µg/mL. Previous studies have demonstrated that GPLD1 plays a crucial role in the pathogenesis of numerous chronic diseases including disorders of lipid and glucose metabolism, cancer, and neurological disorders.
View Article and Find Full Text PDFThe importance of mRNA N6-methyladenosine (m A) modification during tumor metastasis is controversial as it plays distinct roles in different biological contexts. Moreover, how cancer cell plasticity is shaped by m A modification is interesting but remains uncharacterized. Here, this work shows that m A reader insulin like growth factor 2 mRNA binding protein 3 (IGF2BP3) is remarkably upregulated in metastatic lung adenocarcinoma (LUAD) and indicates worse prognosis of patients.
View Article and Find Full Text PDFBackground: There is evidence supporting the association between infection and colorectal cancer (CRC), but whether eradication reduces the risk of CRC is still unknown.
Objectives: To compare the incidence of CRC in subjects who had received eradication therapy with general population.
Design: A population-based retrospective cohort study.
Esophageal tuberculosis (ET) is a rare infectious disease of the gastrointestinal tract. Awareness of ET is deficient due to its low incidence. Unexplained dysphagia and upper gastrointestinal bleeding are the most common symptoms of ET.
View Article and Find Full Text PDFCell Oncol (Dordr)
February 2023
Purpose: AKT hyperactivation drives malignant phenotypes in lung cancer via promoting tumor cell proliferation and survival. However, the relationship between dysregulation of cell cycle progression and AKT1 kinase activity is still not clear.
Methods: Following the expression level of PKMYT1 in lung cancer, we performed cell proliferation, migration, invasion, and xenograft assays to determine the function of PKMYT1.
Helicobacter pylori infection is a leading cause of gastric cancer (GC). However, the underlying mechanisms have not yet been fully elucidated. We aimed to identify microRNAs (miRNAs) regulated by H.
View Article and Find Full Text PDFRho GTPases are molecular switches that play an important role in regulating the behavior of a variety of tumor cells. RhoA GTPase-activating protein 26 (ARHGAP26) is a GTPase-activating protein and inhibits the activity of Rho GTPases by promoting the hydrolytic ability of Rho GTPases. It also affects tumorigenesis and progression of various tumors through several methods, including formation of abnormal fusion genes and circular RNA.
View Article and Find Full Text PDFIEEE/ACM Trans Comput Biol Bioinform
April 2023
Sepsis is a major public concern due to its high mortality, morbidity, and financial cost. There are many existing works of early sepsis prediction using different machine learning models to mitigate the outcomes brought by sepsis. In the practical scenario, the dataset grows dynamically as new patients visit the hospital.
View Article and Find Full Text PDFEsophageal squamous cell carcinoma (ESCC) persists among the most lethal and broad-spreading malignancies in China. The exosome is a kind of extracellular vesicle (EV) from about 30 to 200 nm in diameter, contributing to the transfer of specific functional molecules, such as metabolites, proteins, lipids, and nucleic acids. The paramount role of exosomes in the formation and development of ESCC, which relies on promoting intercellular communication in the tumor microenvironment (TME), is manifested with immense amounts.
View Article and Find Full Text PDFBackground: Endoscopic ultrasound (EUS)-guided transmural drainage for pancreatic fluid collections (PFCs) has become the first-line treatment with quicker recovery and more minor injury compared with surgery and percutaneous drainage. The efficacy of stents implantation and drainage for different PFCs remains controversial, especially lumen-apposing metal stents (LAMS). This study aimed to compare the efficacy and safety of LAMS drainage for pancreatic pseudocysts (PPC) and walled-off necrosis (WON).
View Article and Find Full Text PDFGastric cancer (GC) is one of the most common malignancies in the world. Exosomes, a subset of extracellular vesicles with an average diameter of 100 nm, contain and transfer a variety of functional macromolecules such as proteins, lipids, and nucleic acids. A large number of studies indicated that exosomes can play a significant role in the initiation and development of GC via facilitating intercellular communication between gastric cancer cells and microenvironment.
View Article and Find Full Text PDFFront Cell Infect Microbiol
June 2021
() infection is closely associated with the occurrence and development of gastric diseases. Therefore, eliminating infection should help to prevent gastric diseases. Vitamin D3 (VitD3, 1,25(OH)D) was previously observed to exhibit anti- infection activity in clinic, but these results were reported in heterogeneous studies without elucidation of the underlying mechanisms.
View Article and Find Full Text PDFFront Biosci (Landmark Ed)
January 2021
Ovarian serous adenocarcinoma is one of the most common and fatal malignancies among women worldwide. The tumor microenvironment plays a critical role in tumor initiation, proliferation, and metastasis. Immune scores and stromal scores of the tumor microenvironment were determined using the ESTIMATE.
View Article and Find Full Text PDFEsophageal squamous cell carcinoma (ESCC) is one of the most common and aggressive malignancies in China. Cancer-associated fibroblasts (CAFs) can actively communicate with and stimulate tumor cells, thereby contributing to the development and progression of tumors. Yet, whether CAFs-derived exosomes have a role in the progression of ESCC is largely unknown.
View Article and Find Full Text PDFNeuropeptide S (NPS) has been associated with a number of complex brain functions, including anxiety-like behaviors, arousal, sleep-wakefulness regulation, drug-seeking behaviors, and learning and memory. In order to better understand how NPS influences these functions in a neuronal network context, it is critical to identify transmitter systems that control NPS release and transmitters that are co-released with NPS. For this purpose, we generated several lines of transgenic mice that express enhanced green-fluorescent protein (EGFP) under control of the endogenous NPS precursor promoter.
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