A detailed quantitative analysis of circulating T peripheral and follicular helper lymphocytes in patients with rheumatoid arthritis and systemic lupus erythematosus.

Introduction And Objective: Peripheral and follicular helper T lymphocytes (Tph and Tfh, respectively) have an important role in B cell immune responses and the pathogenesis of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Although several studies on the number of Tph and Tfh cells in these conditions have been published, different phenotypes have been employed for their analysis. In this study, we assessed the levels and function of Tph and Tfh cells in blood samples from patients with RA and SLE by using an extended immunophenotype.

Function and expression of N-acetyltransferases 1 and 2 are altered in lymphocytes in type 2 diabetes and obesity.

The cytosolic enzymes N-Acetyl Transferases 1 and 2 (NATs) transfer an acetyl group from acetyl-CoA to a xenobiotic substrate. NATs are regulated at the genetic and epigenetic levels by deacetylase enzymes such as sirtuins. The enzymatic expression of NAT1, NAT2, and SIRT1 was evaluated by flow cytometry, as well as the enzymatic activity of NATs by cell culture and HPLC analysis.

Clinical Significance of the Lipid Profile Ratios and Triglyceride Glucose Index in the Diagnosis of Metabolic Syndrome.

Metabolic syndrome (MetS) is a pathophysiological condition defined by a set of metabolic alterations such as hypertriglyceridemia, hyperglycemia, hypertension, low HDL-c levels, and visceral obesity. Its presence identifies people with an increased risk of developing cardiovascular diseases and type 2 diabetes; however, the lack of practical and reliable methods for its diagnosis limits the identification of people with this condition. In this sense, the objective of this study was to analyze the diagnostic utility of markers derived from the lipid profile [triglyceride-glucose (TyG) index and the ratios total cholesterol (TC)/high-density lipoprotein cholesterol (HDL-c), triglyceride (TG)/HDL-c, low-density lipoprotein cholesterol/HDL-c, fasting blood glucose (FBG)/HDL-c, and white blood cell/HDL-c] in the determination of MetS.

Histone deacetylase (HDAC) inhibitors- based drugs are effective to control Mycobacterium tuberculosis infection and promote the sensibility for rifampicin in MDR strain.

Background: Tuberculosis (TB) is a major public health problem, which has been aggravated by the alarming growth of drug-resistant tuberculosis. Therefore, the development of a safer and more effective treatment is needed.

Objectives: The aim of this work was repositioning and evaluate histone deacetylases (HDAC) inhibitors- based drugs with potential antimycobacterial activity.

Nicotine promotes Mycobacterium tuberculosis H37Rv growth and overexpression of virulence genes.

Tobacco consumption increases the susceptibility to develop infectious diseases such as tuberculosis (TB). Nicotine (Nc) is the main component of cigarette smoke with immunomodulatory properties, however, its effect on Mycobacterium tuberculosis (Mtb) has been scarcely investigated. The present study evaluated the effect of nicotine on the growth of Mtb and on the induction of virulence-related genes.

Bioinformatic prediction of the molecular links between Alzheimer's disease and diabetes mellitus.

Background: Alzheimer's disease (AD) and type 2 diabetes mellitus (DM2) are chronic degenerative diseases with complex molecular processes that are potentially interconnected. The aim of this work was to predict the potential molecular links between AD and DM2 from different sources of biological information.

Materials And Methods: In this work, data mining of nine databases (DisGeNET, Ensembl, OMIM, Protein Data Bank, The Human Protein Atlas, UniProt, Gene Expression Omnibus, Human Cell Atlas, and PubMed) was performed to identify gene and protein information that was shared in AD and DM2.

The Purinergic Landscape of Type 2 Diabetes Mellitus.

Adenosine triphosphate (ATP) is the key energy intermediate of cellular metabolic processes and a ubiquitous extracellular messenger. As an extracellular messenger, ATP acts at plasma membrane P2 receptors (P2Rs). The levels of extracellular ATP (eATP) are set by both passive and active release mechanisms and degradation processes.

Acetylcholine Upregulates Virulence Factors, Enhancing Parasite Pathogenicity in Experimental Liver Amebiasis.

is an invasive enteric protozoan, whose infections are associated to high morbidity and mortality rates. However, only less than 10% of infected patients develop invasive amebiasis. The ability of to adapt to the intestinal microenvironment could be determinant in triggering pathogenic behavior.

Chemoresistance in Breast Cancer Patients Associated With Changes in P2X7 and A2A Purinergic Receptors in CD8 T Lymphocytes.

Breast cancer (BRCA) is the most frequent cancer type that afflicts women. Unfortunately, despite all the current therapeutic strategies, many patients develop chemoresistance hampering the efficacy of treatment. Hence, an early indicator of therapy efficacy might aid in the search for better treatment and patient survival.

T Regulatory Cell Frequency During Maintenance Phase Chemotherapy for Pediatric Acute Lymphoblastic Leukemia.

Background: Drugs used in cancer treatment specifically kill T regulatory cells.

Objective: To determine different phenotypes of T regulatory cells during the maintenance phase chemotherapy for pediatric acute lymphoblastic leukemia (ALL).

Materials: We evaluated the percentages of regulatory T cells by flow cytometry.

Myeloid-Derived Suppressor Cells Show Different Frequencies in Diabetics and Subjects with Arterial Hypertension.

Type 2 diabetes mellitus (DM2) is strongly associated with other comorbidities such as obesity, atherosclerosis, and hypertension. Obesity is associated with sustained low-grade inflammatory response due to the production of proinflammatory cytokines. This inflammatory process promotes the differentiation of some myeloid cells, including myeloid-derived suppressor cells (MDSCs).

Expression and activity of AIM2-inflammasome in rheumatoid arthritis patients.

Introduction: AIM2 inflammasome activation leads to the release of IL-β, which plays an important role in rheumatoid arthritis pathogenesis. In this work, we evaluated AIM2 expression and activity in RA patients and healthy controls.

Methods: AIM2 and RANKL expression were evaluated by flow cytometry.

Variability in the virulence of specific Mycobacterium tuberculosis clinical isolates alters the capacity of human dendritic cells to signal for T cells.

Background: Once in the pulmonary alveoli, Mycobacterium tuberculosis (Mtb) enters into contact with alveolar macrophages and dendritic cells (DCs). DCs represent the link between the innate and adaptive immune system owing to their capacity to be both a sentinel and an orchestrator of the antigen-specific immune responses against Mtb. The effect that the virulence of Mtb has on the interaction between the bacilli and human DCs has not been fully explored.

Circulating miR-146a, miR-34a and miR-375 in type 2 diabetes patients, pre-diabetic and normal-glycaemic individuals in relation to β-cell function, insulin resistance and metabolic parameters.

The pathogenesis of type 2 diabetes (T2D) is associated with a progressive loss of pancreatic β-cell mass. It is known that miR-146a, miR-34a, and miR-375 are involved in β-cell functionality. In this work, we evaluated the levels of these miRNAs in normal-glycaemic individuals, pre-diabetic, and T2D patients in relation to β-cell functionality, insulin resistance, and metabolic parameters.

P2X4 receptor as a modulator in the function of P2X receptor in CD4+ T cells from peripheral blood and adipose tissue.

Obesity is characterized by immune cell infiltration and inflammation. Purinergic receptors such as P2X1, 4 and 7 are expressed on immune cells and their activation contributes with an inflammatory response. However, the simultaneous expression of P2X1, 4 and 7 during overweight or obesity have not been described.

Increased Levels of AIM2 and Circulating Mitochondrial DNA in Type 2 Diabetes.

Background: Chronic inflammation has critical role in Type 2 diabetes (T2D), in which IL-1β contributes in insulin resistance and beta cell dysfunction. The activation of NLRP3 and AIM2 by endogens ligands, such as mtDNA can lead to the release of active form of IL-1β.

Objective: To evaluate AIM2 expression and activation as well as circulating mtDNA levels in T2D patients.

Type-2 diabetes alters the basal phenotype of human macrophages and diminishes their capacity to respond, internalise, and control Mycobacterium tuberculosis.

Background: Type 2 diabetes (T2D) is a risk factor for the development of tuberculosis (TB), although the associated mechanisms are not known.

Objectives: To study the association between T2D and the basal phenotype of macrophages, and their immune response to Mycobacterium tuberculosis (Mtb) infection.

Methods: We evaluated the influence of T2D on the response of monocyte-derived macrophages (MDM) to Mtb in patients with T2D (n = 10) compared to healthy subjects (n = 9), before and after infection with Mtb clinical isolates bearing different degrees of virulence.

The presence of the 1068 G>A variant of P2X7 receptors is associated to an increase in IL-1Ra levels, insulin secretion and pancreatic β-cell function but not with glycemic control in type 2 diabetes patients.

It has been reported that an increased function of the P2X purinergic receptor is associated with an increase in both insulin sensitivity and secretion. Accordingly, we explored the possible effect of the 1068 G>A polymorphism of the gene P2RX7 on glucose homeostasis and the levels of the anti-inflammatory cytokine IL-1Ra in T2D patients. The presence of the 1068 G>A polymorphism in T2D patients (n = 100) and healthy subjects (n = 100) was determined by DNA sequencing, and serum levels of IL-1Ra were measured by ELISA.

LL-37, HNP-1, and HBD2/3 modulate the secretion of cytokines TNF-α, IL-6, IFN-γ, IL-10 and MMP1 in human primary cell cultures.

The aim of this study was to evaluate the effects of the LL-37, HNP-1 and HBD2/3 peptides on cytokine and MMP production in human polymorphonuclear cells, mononuclear cells and chondrocytes. The levels of cytokines in supernatants from mononuclear and polymorphonuclear cell cultures were measured with a cytometric bead array by flow cytometry. Likewise, the levels of metalloproteinase/MMP-1, 3, and 13 were measured in supernatants from chondrocyte cultures using an ELISA.

Diminished levels of regulatory T cell subsets (CD8+Foxp3, CD4+Foxp3 and CD4+CD39+Foxp3) but increased Foxp3 expression in adipose tissue from overweight subjects.

Objectives: The aim of this study was to identify regulatory T cell (Treg) subsets residing in adipose tissue, demonstrate their immunosuppressive functions, and assess the possible role of Sirt1 in their function in overweight subjects.

Methods: Fat samples were obtained by lipoaspiration from healthy overweight (n = 15) and normoweight (n = 11) subjects. We obtained the stromal vascular fraction and then isolated the mononuclear cells by Ficoll-Hypaque sedimentation.

LL-37 immunomodulatory activity during Mycobacterium tuberculosis infection in macrophages.

Tuberculosis is one of the most important infectious diseases worldwide. The susceptibility to this disease depends to a great extent on the innate immune response against mycobacteria. Host defense peptides (HDP) are one of the first barriers to counteract infection.

Evaluation of the expression and function of the P2X7 receptor and ART1 in human regulatory T-cell subsets.

Regulatory T cells that express CD39 (CD39+ Treg) exhibit specific immunomodulatory properties. Ectonucleotidase CD39 hydrolyses ATP and ADP. ATP is a ligand of the P2X7 receptor and induces the shedding of CD62L and apoptosis.

Specific therapy to regulate inflammation in rheumatoid arthritis: molecular aspects.

Rheumatoid arthritis (RA) is a chronic inflammatory disease in which persistent inflammation of synovial tissue results in a progressive functional decline of the joint and premature mortality. TNF inhibitors were the first biological disease-modifying antirheumatic drugs (DMARDs) used to treat RA. Since then, new biological drugs have emerged, such as inhibitors of IL-1, IL-6 and others, with different mechanisms of action that include the depletion of B cells and the inhibition of T-cell costimulation.

The His155Tyr (489C>T) single nucleotide polymorphism of P2RX7 gene confers an enhanced function of P2X7 receptor in immune cells from patients with rheumatoid arthritis.

We assessed the possible association between several single nucleotide polymorphisms (SNP) of P2RX7 gene with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). We determined the function of P2X7 receptor and the frequency of the 489C>T, 1096C>G, and 1513A>C SNP of P2RX7 gene in 111 and 122 patients with SLE and RA, and 98 healthy subjects. We found no significant association between the SNPs studied and SLE or RA.

Abnormal expression and function of Dectin-1 receptor in type 2 diabetes mellitus patients with poor glycemic control (HbA1c>8%).

Dectin-1 is a key innate receptor involved in various cellular responses and may have a direct role in chronic inflammatory conditions such as type 2 diabetes mellitus. The aim of this work was to evaluate the expression and function of Dectin-1 in peripheral blood mononuclear cells from T2D patients. Dectin-1 expression was analyzed by flow cytometry and RT-PCR in monocytes and lymphocyte subpopulations from T2D patients (n=34) and healthy subjects (n=29).