Childhood obesity and risk of inflammatory bowel disease in adulthood: A Mendelian randomization study.

It is well-known that childhood obesity is associated with various adult gastrointestinal diseases, inflammatory bowel disease (IBD) being no exception. However, previous epidemiological observational studies, while reporting a correlation between the 2, have left the question of a causal relationship inconclusive. This study aims to use a 2-sample Mendelian randomization (MR) analysis to assess the causal relationship between childhood obesity and IBD as well as its subtypes (ulcerative colitis [UC] and Crohn disease [CD]).

A metagenomics study reveals the gut microbiome as a sex-specific modulator of healthy aging in Hainan centenarians.

Background: Sex differences in health status and life expectancy are widely accepted to exist. The mechanisms underlying it are still poorly understood. In this study, we aimed to clarify the influences and contributions of sex on the gut microbiome in healthy centenarians and to explore the different roles played by the gut microbiome in healthy aging between the sexes.

Hereditary hemorrhagic telangiectasia involving portal venous system: A case report and review of the literature.

Background: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant genetic disorder with an incidence of approximately 1 in 5000 in the general population. It is characterized by vasodilation, which affects specific organs, such as the skin, mucous membranes, brain, lungs, gastrointestinal tract, liver, and others. However, HHT rarely involves the portal venous system to cause serious clinical complications.

Clinical characteristics of patients with early-onset diabetes mellitus: a single-center retrospective study.

Background: The prevalence of diabetes mellitus (DM) is dramatically increasing around the world, and patients are getting younger with changes in living standards and lifestyle. This study summarized and analyzed the clinical characteristics of different types of newly diagnosed diabetes mellitus patients with an onset age between 18 and 40 years to provide clinical evidence for the early diagnosis and treatment of diabetes, reduce short-term and long-term complications and offer scientific and personalized management strategies.

Methods: A total of 655 patients newly diagnosed with early-onset diabetes mellitus in the Department of Endocrinology, the First Medical Center of PLA General Hospital from January 2012 to December 2022 were retrospectively enrolled in this study, with an onset age of 18-40 years.

Efficacy and safety of Oral LL-37 against the Omicron BA.5.1.3 variant of SARS-COV-2: A randomized trial.

Recombinant LL-37 Lactococcus lactis (Oral LL-37) was designed to prevent progression of COVID-19 by targeting virus envelope, however, effectiveness and safety of Oral LL-37 in clinical application was unclear. A total of 238 adult inpatients, open-labelled, randomized, placebo-controlled, single-center study was conducted to investigate the primary end points, including negative conversion time (NCT) of SARS-CoV-2 RNA and adverse events (AEs). As early as intervened on 6th day of case confirmed, Oral LL-37 could significantly shorten NCT (LL-37 9.

Lactobacillus oris improves non-alcoholic fatty liver in mice and inhibits endogenous cholesterol biosynthesis.

We previously confirmed that a strain of Lactobacillus oris isolated from the fecal samples of healthy Hainan centenarian having potent lipid-lowering ability in HepG2 cells; and this study was to investigate the effect of the stain on non-alcoholic fatty liver in mice in vivio. The Lactobacillus oris strain isolated from Hainan centenarian fecal samples were frozen stored in our laboratory. Thirty ob/ob mice (10 in each group) were orally gavaged with Lactobacillus oris (Lactobacillus, 5 × 10 cfu), mixed probiotics (Mixed, 5 × 10 cfu, a mixture with known lipid-lowering ability), or culture medium (Control) respectively.

RNA-Seq Analysis Reveals Altered Expression of Cell Adhesion-Related Genes Following PZR Knockout in Lung Cancer Cells.

Protein zero related (PZR) serves as a substrate and anchor protein for SHP-2, the product of the proto-oncogene PTPN11 that is frequently mutated in cancers. The expression level of PZR is elevated in various cancers, which is correlated with an unfavorable prognosis. The role of PZR in lung cancer is not fully studied.

miR-221/222 induce instability of p53 By downregulating deubiquitinase YOD1 in acute myeloid leukemia.

Acute myeloid leukemia (AML) is a hematological malignancy characterized by the impaired differentiation and uncontrolled proliferation of myeloid blasts. Tumor suppressor p53 is often downregulated in AML cells via ubiquitination-mediated degradation. While the role of E3 ligase MDM2 in p53 ubiquitination is well-accepted, little is known about the involvement of deubiquitinases (DUBs).

PZR promotes tumorigenicity of lung cancer cells by regulating cell migration and invasion via modulating oxidative stress and cell adhesion.

PZR is a transmembrane glycoprotein encoded by the gene. It serves as a specific binding protein and substrate of tyrosine phosphatase SHP-2 whose mutations cause developmental diseases and cancers. Bioinformatic analyses of cancer gene databases revealed that PZR is overexpressed in lung cancer and correlated with unfavorable prognosis.

Sunitinib selectively targets leukemogenic signaling of mutant SHP2 in juvenile myelomonocytic leukemia.

Leukemogenic SHP2 mutations occur in 35% of patients with juvenile myelomonocytic leukemia (JMML), a hematopoietic malignancy with poor response to cytotoxic chemotherapy. Novel therapeutic strategies are urgently needed for patients with JMML. Previously, we established a novel cell model of JMML with HCD-57, a murine erythroleukemia cell line that depends on EPO for survival.

SHP2 participates in decidualization by activating ERK to maintain normal nuclear localization of progesterone receptor.

In Brief: The establishment and maintenance of embryo implantation and pregnancy require decidualization of endometrial stromal cells. This paper reveals that SHP2 ensures the correct subcellular localization of progesterone receptor, thereby safeguarding the process of decidualization.

Abstract: Decidualization is the process of conversion of endometrial stromal cells into decidual stromal cells, which is caused by progesterone production that begins during the luteal phase of the menstrual cycle and then increases throughout pregnancy dedicated to support embryonic development.

Knockdown of phosphatases of regenerating liver-1 prolongs the lifespan of Caenorhabditis elegans via activating DAF-16/FOXO.

Phosphatases of regenerating liver (PRLs) are dual-specificity protein phosphatases. The aberrant expression of PRLs threatens human health, but their biological functions and pathogenic mechanisms are unclear yet. Herein, the structure and biological functions of PRLs were investigated using the Caenorhabditis elegans (C.

Leukemogenic SHP2 mutations lead to erythropoietin independency of HCD-57 cells: a novel model for preclinical research of SHP2-mutant JMML.

Leukemogenic SHP2 mutations occur in 35% of patients with juvenile myelomonocytic leukemia (JMML), a rare but fatal hematopoietic malignancy without representative cell models, which are urgently needed to investigate the pathogenesis and to develop novel therapeutic strategies. In this study, we established stable cell lines with aberrant signaling resembling SHP2-mutant JMML through retroviral expression of SHP2-D61Y/E76K in HCD-57 cells, a murine erythroleukemia cell line that depends on erythropoietin (EPO) for survival. SHP2-D61Y/E76K drives the survival and proliferation of HCD-57 cells in the absence of EPO, but not in Ba/F3 cells in the absence of IL-3.

Bioinformatics analyses of combined databases identify shared differentially expressed genes in cancer and autoimmune disease.

Background: Inadequate immunity caused by poor immune surveillance leads to tumorigenesis, while excessive immunity due to breakdown of immune tolerance causes autoimmune genesis. Although the function of immunity during the onset of these two processes appears to be distinct, the underlying mechanism is shared. To date, gene expression data for large bodies of clinical samples are available, but the resemblances of tumorigenesis and autoimmune genesis in terms of immune responses remains to be summed up.

Efficacy of SCF drug conjugate targeting c-KIT in gastrointestinal stromal tumor.

Background: Gastrointestinal stromal tumor (GIST) is a rare type of cancer that occurs in the gastrointestinal tract. The majority of GIST cases carry oncogenic forms of KIT, the receptor for stem cell factor (SCF). Small molecule kinase inhibitor imatinib is effective in prolonging the survival of GIST patients by targeting KIT.

HMGA1 chromatin regulators induce transcriptional networks involved in GATA2 and proliferation during MPN progression.

Myeloproliferative neoplasms (MPNs) transform to myelofibrosis (MF) and highly lethal acute myeloid leukemia (AML), although the actionable mechanisms driving progression remain elusive. Here, we elucidate the role of the high mobility group A1 (HMGA1) chromatin regulator as a novel driver of MPN progression. HMGA1 is upregulated in MPN, with highest levels after transformation to MF or AML.

Bidirectional Interaction Between Cancer Cells and Platelets Provides Potential Strategies for Cancer Therapies.

Platelets are essential components in the tumor microenvironment. For decades, clinical data have demonstrated that cancer patients have a high risk of thrombosis that is associated with adverse prognosis and decreased survival, indicating the involvement of platelets in cancer progression. Increasing evidence confirms that cancer cells are able to induce production and activation of platelets.

Phenylacetylglutamine is associated with the degree of coronary atherosclerotic severity assessed by coronary computed tomographic angiography in patients with suspected coronary artery disease.

Background And Aims: Phenylacetylglutamine (PAG), a gut microbiota metabolite, has recently been found to be associated with major adverse cardiovascular events. In this study, we analyzed the relationship between plasma PAG and coronary atherosclerotic severity assessed by coronary computed tomographic angiography (CCTA).

Methods: We enrolled consecutive patients with suspected coronary artery disease (CAD) who underwent CCTA.

Tyrosine Kinase ROR1 as a Target for Anti-Cancer Therapies.

Receptor tyrosine kinase ROR1 plays an essential role in embryogenesis and is overexpressed in many types of malignant tumors. Studies have demonstrated that it plays an important role in oncogenesis by activating cell survival signaling events, particularly the non-canonical WNT signaling pathway. Antibody-based immunotherapies targeting ROR1 have been developed and evaluated in preclinical and clinical studies with promising outcomes.

Association of -C1858T Polymorphism With Susceptibility to and Infection: A Meta-Analysis.

It was previously published that single-nucleotide polymorphism rs2476601 ( [protein tyrosine phosphatase non-receptor type 22]-C1858T) might be related to increased sensibility to and infection. However, the results were inconclusive despite a high degree of similarity between both parameters. Herein, we carried out this meta-analysis to systematically summarize and articulate the correlation between -C1858T polymorphism and mycobacterial infection.

Expression of a recombinant FLT3 ligand and its emtansine conjugate as a therapeutic candidate against acute myeloid leukemia cells with FLT3 expression.

Background: Most patients with acute myeloid leukemia (AML) remain uncurable and require novel therapeutic methods. Gain-of-function FMS-like tyrosine kinase 3 (FLT3) mutations are present in 30-40% of AML patients and serve as an attractive therapeutic target. In addition, FLT3 is aberrantly expressed on blasts in > 90% of patients with AML, making the FLT3 ligand-based drug conjugate a promising therapeutic strategy for the treatment of patients with AML.