Comparative analysis of leukemia and risk estimation in working age population between provinces of Ecuador.

Leukemia is associated with exposure to radiation, benzene derivatives, and pesticides. Previous research has documented an increase in work-related leukemia in the Latin American Andean region. To date, there are only few studies in Ecuador on the impact of oil exploitation on adjacent indigenous communities.

State of the Art in CAR-T Cell Therapy for Solid Tumors: Is There a Sweeter Future?

Chimeric antigen receptor (CAR)-T cell therapy has proven to be a powerful treatment for hematological malignancies. The situation is very different in the case of solid tumors, for which no CAR-T-based therapy has yet been approved. There are many factors contributing to the absence of response in solid tumors to CAR-T cells, such as the immunosuppressive tumor microenvironment (TME), T cell exhaustion, or the lack of suitable antigen targets, which should have a stable and specific expression on tumor cells.

Neuroblastoma RAS viral oncogene homolog (N-RAS) deficiency aggravates liver injury and fibrosis.

Progressive hepatic damage and fibrosis are major features of chronic liver diseases of different etiology, yet the underlying molecular mechanisms remain to be fully defined. N-RAS, a member of the RAS family of small guanine nucleotide-binding proteins also encompassing the highly homologous H-RAS and K-RAS isoforms, was previously reported to modulate cell death and renal fibrosis; however, its role in liver damage and fibrogenesis remains unknown. Here, we approached this question by using N-RAS deficient (N-RAS) mice and two experimental models of liver injury and fibrosis, namely carbon tetrachloride (CCl) intoxication and bile duct ligation (BDL).

Expression of HMGCS2 in intestinal epithelial cells is downregulated in inflammatory bowel disease associated with endoplasmic reticulum stress.

Introduction: The Unfolded Protein Response, a mechanism triggered by the cell in response to Endoplasmic reticulum stress, is linked to inflammatory responses. Our aim was to identify novel Unfolded Protein Response-mechanisms that might be involved in triggering or perpetuating the inflammatory response carried out by the Intestinal Epithelial Cells in the context of Inflammatory Bowel Disease.

Methods: We analyzed the transcriptional profile of human Intestinal Epithelial Cell lines treated with an Endoplasmic Reticulum stress inducer (thapsigargin) and/or proinflammatory stimuli.

Manufacture of Mesoporous Silicon Microparticles (MSMPs) as Adjuvants for Vaccine Delivery.

The advent of computational approaches has accelerated the identification of vaccine candidates like epitope peptides. However, epitope peptides are usually very poorly immunogenic and adequate platforms are required with adjuvant capacity to verity immunogenicity and antigenicity of vaccine subunits in vivo. Silicon microparticles are being developed as potential new adjuvants for vaccine delivery due to their physicochemical properties.

Role of mTOR inhibitor in the cellular and humoral immune response to a booster dose of SARS-CoV-2 mRNA-1273 vaccine in kidney transplant recipients.

Background: Immunocompromised patients have an increased risk of developing severe COVID disease, as well as a tendency to suboptimal responses to vaccines. The objective of this study was to evaluate the specific cellular and humoral adaptive immune responses of a cohort of kidney transplant recipients (KTR) after 3 doses of mRNA-1273 vaccine and to determinate the main factors involved.

Methods: Prospective observational study in 221 KTR (149 non infected), 55 healthy volunteers (HV) and 23 dialysis patients (DP).

A Shortcut from Metabolic-Associated Fatty Liver Disease (MAFLD) to Hepatocellular Carcinoma (HCC): c-MYC a Promising Target for Preventative Strategies and Individualized Therapy.

Background: Metabolic-associated fatty liver disease (MAFLD) has risen as one of the leading etiologies for hepatocellular carcinoma (HCC). Oncogenes have been suggested to be responsible for the high risk of MAFLD-related HCC. We analyzed the impact of the proto-oncogene c-MYC in the development of human and murine MAFLD and MAFLD-associated HCC.

An Experimental DUAL Model of Advanced Liver Damage.

Individuals exhibiting an intermediate alcohol drinking pattern in conjunction with signs of metabolic risk present clinical features of both alcohol-associated and metabolic-associated fatty liver diseases. However, such combination remains an unexplored area of great interest, given the increasing number of patients affected. In the present study, we aimed to develop a preclinical DUAL (alcohol-associated liver disease plus metabolic-associated fatty liver disease) model in mice.

Intestinal Epithelial Cell-Derived Extracellular Vesicles Modulate Hepatic Injury via the Gut-Liver Axis During Acute Alcohol Injury.

Binge drinking, i.e., heavy episodic drinking in a short time, has recently become an alarming societal problem with negative health impact.

Alcoholic liver disease: Utility of animal models.

Alcoholic liver disease (ALD) is a major cause of acute and chronic liver injury. Extensive evidence has been accumulated on the pathological process of ALD during the past decades. However, effective treatment options for ALD are very limited due to the lack of suitable models that recapitulate the full spectrum of ALD.

Monocyte-Derived Dendritic Cells Differentiated in the Presence of Lenalidomide Display a Semi-Mature Phenotype, Enhanced Phagocytic Capacity, and Th1 Polarization Capability.

Lenalidomide is an analog of thalidomide, with potent anticancer activity demonstrated in several hematological malignancies. It has immunomodulatory properties, being able to enhance the activation of different types of immune cells, which results in antitumor activities. Dendritic cells (DCs) are pivotal in the immune response, and different immunotherapeutic approaches targeting these cells are being developed.

Dissecting the molecular pathophysiology of drug-induced liver injury.

Drug-induced liver injury (DILI) has become a major topic in the field of Hepatology and Gastroenterology. DILI can be clinically divided into three phenotypes: hepatocytic, cholestatic and mixed. Although the clinical manifestations of DILI are variable and the pathogenesis complicated, recent insights using improved preclinical models, have allowed a better understanding of the mechanisms that trigger liver damage.

Intestinal epithelial cell endoplasmic reticulum stress promotes MULT1 up-regulation and NKG2D-mediated inflammation.

Endoplasmic reticulum (ER) stress is commonly observed in intestinal epithelial cells (IECs) and can, if excessive, cause spontaneous intestinal inflammation as shown by mice with IEC-specific deletion of X-box-binding protein 1 (), an unfolded protein response-related transcription factor. In this study, deletion in the epithelium ( ) is shown to cause increased expression of natural killer group 2 member D (NKG2D) ligand (NKG2DL) mouse UL16-binding protein (ULBP)-like transcript 1 and its human orthologue cytomegalovirus ULBP via ER stress-related transcription factor C/EBP homology protein. Increased NKG2DL expression on mouse IECs is associated with increased numbers of intraepithelial NKG2D-expressing group 1 innate lymphoid cells (ILCs; NK cells or ILC1).

The Role of Lipids in Development of Allergic Responses.

Most allergic diseases are caused by activation of Th2 type immune responses resulting in the production of specific IgE against proteins found in normally harmless substances such as pollen, mites, epithelia or food. Allergenic substances are composed, in addition to proteins, of other compounds such as carbohydrates and lipids. Those lipids are able to promote the development of Th2-type responses associated with allergy.

Human MR1 expression on the cell surface is acid sensitive, proteasome independent and increases after culturing at 26°C.

Mucosal-associated invariant T (MAIT) cells are a population of non-conventional T-lymphocytes which are restricted by the MHC-related 1 (MR1) molecule. MR1 is a non-classical member of the MHC class I family of proteins, it is unknown if MR1 presents any kind of antigens to MAIT cells. In the present manuscript we describe that detection of MR1 on the cell surface by conformation-dependent monoclonal antibodies is enhanced upon culture the cells at 26°C; we also show that detection of MR1 on the cell surface is lost after treating the cells at pH 3.

The MHC-related protein 1 (MR1) is expressed by a subpopulation of CD38+, IgA+ cells in the human intestinal mucosa.

MHC-related 1 (MR1) molecule is a non-classical member of the MHC class I family of proteins. The sequence homology between classical MHC class I molecules and MR1 is very high, although the MR1 gene is not polymorphic and is highly conserved between species. MR1 is the restriction molecule of a sub-population of T lymphocytes, which are CD4-,CD8- and display conserved TCR alpha chain.

Expression of adhesion molecules and RANTES in kidney transplant from nonheart-beating donors.

The main difference between cadaveric kidneys from donors with a heartbeat (HBD) and kidneys from nonheart-beating donors (NHBD) is related to warm ischemia/reperfusion time which constitutes an acute inflammatory process. On the contrary, brain death induces in HBD expression of pro-inflammatory adhesion molecules, making it important to evaluate this kind of molecules in both types of donors. Human renal biopsies from NHBD, HBD and normal kidneys (ischemia time = 0) were taken and frozen just before transplant.

Characterization of a novel activation antigen on porcine lymphocytes recognized by monoclonal antibody 5A6/8.

In this report, we describe the characterization of a novel activation antigen on porcine lymphocytes recognized by mAb 5A6/8. This antigen was detected on B and T cells 24 h after treatment with various stimuli. It was also found on alveolar macrophages, and at low levels on untreated monocytes.

Expression of human CD1d molecules protects target cells from NK cell-mediated cytolysis.

The cytotoxic activity of NK cells can be inhibited by classical and nonclassical MHC molecules. The CD1 system is formed by a family of glycoproteins that are related to classical MHC. CD1a, b, and c molecules present lipids or glycolipids to T cells and are involved in defense against microbial infections, especially mycobacteria.