In vitro and ex vivo activity of the fluoroquinolone DC-159a against mycobacteria.

Antimicrobial resistance is a global health problem. In 2021, it was estimated almost half a million of multidrug-resistant tuberculosis (MDR-TB) cases. Besides, non-tuberculous mycobacteria (NTM) are highly resistant to several drugs and the emergence of fluoroquinolone (FQ) resistant M.

Transforming growth factor-β, Interleukin-23 and interleukin-1β modulate TH22 response during active multidrug-resistant tuberculosis.

We previously reported that patients with multidrug-resistant tuberculosis (MDR-TB) showed low systemic and Mtb-induced Th22 responses associated to high sputum bacillary load and severe lung lesions suggesting that Th22 response could influence the ability of these patients to control bacillary growth and tissue damage. In MDR-TB patients, the percentage of IL-22 cells inversely correlates with the proportion of senescent PD-1 T cells. Herein, we aimed to evaluate the pathways involved on the regulation of systemic and Mtb-induced Th22 response in MDR-TB and fully drug-susceptible TB patients (S-TB) and healthy donors.

Proteomic Analysis Identifies Molecular Players and Biological Processes Specific to SARS-CoV-2 Exposure in Endothelial Cells.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been responsible for the severe pandemic of acute respiratory disease, coronavirus disease 2019 (COVID-19), experienced in the 21st century. The clinical manifestations range from mild symptoms to abnormal blood coagulation and severe respiratory failure. In severe cases, COVID-19 manifests as a thromboinflammatory disease.

Functional polymorphisms of DNA repair genes in Latin America reinforces the heterogeneity of Myelodysplastic Syndrome.

Nucleotide excision repair pathway (NER) is an essential mechanism for single-strand breaks (SSB) repair while xeroderma pigmentosum family (XPA to XPG) is the most important system to NER. Myelodysplastic syndrome (MDS) is a heterogeneous hematological cancer characterized by cytopenias and risk of acute myeloid leukemia (AML) transformation. MDS pathogenesis has been associated with problems of DNA repair system.

Genetic diversity of sp. paratuberculosis by mycobacterial interspersed repetitive Unit-Variable number tandem repeat and multi-locus short-sequence repeat one-sentence summary: Genetic diversity of sp. paratuberculosis isolates.

Background: Paratuberculosis is an enteric disease caused by Mycobacterium avium sp. paratuberculosis (MAP) that affects mainly ruminant producing losses to the livestock industry. Many molecular epidemiological methods have been used to discriminate MAP isolates.

Th22 response induced by Mycobacterium tuberculosis strains is closely related to severity of pulmonary lesions and bacillary load in patients with multi-drug-resistant tuberculosis.

The role of interleukin-22 (IL-22) in the pathogenesis or tissue repair in human tuberculosis (TB) remains to be established. Here, we aimed to explore the ex-vivo and in-vitro T helper 22 (Th22) response in TB patients and healthy donors (HD) induced by different local multi-drug-resistant (MDR) Mvcobacterium tuberculosis (Mtb) strains. For this purpose, peripheral blood mononuclear cells from drug-susceptible (S-TB) MDR-TB patients and HD were stimulated with local MDR strains and the laboratory strain H37Rv.

Platelet Toll-Like Receptors Mediate Thromboinflammatory Responses in Patients With Essential Thrombocythemia.

Essential thrombocythemia (ET) is comprised among chronic myeloproliferative neoplasms (MPN) and is caused by driver mutations in 2, , and , which lead to megakaryocyte proliferation and prominent thrombocytosis. Thrombosis remains the main cause of morbidity in ET and is driven by the interplay between blood cells, the endothelium, the clotting cascade, and host-derived inflammatory mediators. Platelet activation plays a key role in the thrombotic predisposition, although the underlying mechanisms remain poorly defined.

Crystal violet decolorization assay for rapid detection of multidrug-resistant isolates: A multicenter study.

Background: Effective control of tuberculosis is achieved by early diagnosis and drug susceptibility testing for initiation of appropriate treatment. The performance of crystal violet decolorization assay (CVDA) for susceptibility testing of Mycobacterium tuberculosis to isoniazid (INH) and rifampicin (RIF) was compared in a multicenter study.

Methods: Seventy-two M.

Platelet TLR4 at the crossroads of thrombosis and the innate immune response.

Platelet TLR-4 activation by pathogen- or damage-associated molecular pattern molecules triggers pro-thrombotic, proinflammatory, and pro-coagulant effector responses. Moreover, platelet TLR4 has a prominent role as a sensor of high lipopolysaccharide circulating levels during sepsis and in the clearance of pathogens mediated by neutrophils. This review presents evidence pointing to TLR4 as a bridge connecting thrombosis and innate immunity.

Impact of the Reticular Stress and Unfolded Protein Response on the inflammatory response in endometrial stromal cells.

During decidualization, endometrial stromal cells undergo reticular stress (RS) and unfolded protein response (UPR), allowing the endoplasmic reticulum-expansion and immunomodulators production. Physiological RS generates the activation of sensing proteins, inflammasome activation and mature-IL-1β secretion, associated with pro-implantatory effects. We focus on the impact of RS and UPR on decidualized cells and whether they induce a physiological sterile inflammatory response through IL-1β production.

Selective hemangioma cell dysfunction and apoptosis triggered by in vitro treatment with imiquimod.

Infantile hemangiomas are the most common benign tumors of infancy, characterized by unregulated angiogenesis and endothelial cells with high mitotic rate. Although spontaneous regression occurs, sometimes treatment is required and alternatives to corticosteroids should be considered to reduce side effects. Imiquimod is an imidazoquinoline, approved for some skin pathologies other than hemangioma.

VIP induces the decidualization program and conditions the immunoregulation of the implantation process.

The decidualization process involves phenotype and functional changes on endometrial cells and the modulation of mediators with immunoregulatory properties as the vasoactive intestinal peptide (VIP). We investigate VIP contribution to the decidualization program and to immunoregulation throughout the human embryo implantation process. The decidualization of Human endometrial stromal cell line (HESC) with Medroxyprogesterone-dibutyryl-cAMP increased VIP/VPAC-receptors system.

Neutrophil extracellular trap formation and circulating nucleosomes in patients with chronic myeloproliferative neoplasms.

The mechanisms underlying increased thrombotic risk in chronic myeloproliferative neoplasms (MPN) are incompletely understood. We assessed whether neutrophil extracellular traps (NETs), which promote thrombosis, contribute to the procoagulant state in essential thrombocythemia, polycythemia vera and myelofibrosis (MF) patients. Although MPN neutrophils showed increased basal reactive oxygen species (ROS), enhanced NETosis by unstimulated neutrophils was an infrequent finding, whereas PMA-triggered NETosis was impaired, particularly in MF, due to decreased PMA-triggered ROS production.

Novel Use of All-Trans-Retinoic Acid in A Model of Lipopolysaccharide-Immunosuppression to Decrease the Generation of Myeloid-Derived Suppressor Cells by Reducing the Proliferation of CD34+ Precursor Cells.

All-trans-retinoic acid (ATRA) is a derivative of vitamin A with antiproliferative properties. Endotoxin shock and subsequent immunosuppression (IS) by lipopolysaccharide (LPS) stimulates myelopoiesis with expansion of myeloid-derived suppressor cells (MDSC). Since we have previously shown that ATRA reverses the IS state by decreasing functional MDSC, our aim was to investigate if ATRA was able to modulate MDSC generation by regulating myelopoiesis in murine hematopoietic organs.

VIP treatment prevents embryo resorption by modulating efferocytosis and activation profile of maternal macrophages in the CBAxDBA resorption prone model.

Successful embryo implantation occurs followed by a local pro-inflammatory response subsequently shifted toward a tolerogenic one. VIP (vasoactive intestinal peptide) has embryotrofic, anti-inflammatory and tolerogenic effects. In this sense, we investigated whether the in vivo treatment with VIP contributes to an immunosuppressant local microenvironment associated with an improved pregnancy outcome in the CBA/J × DBA/2 resorption prone model.

Galectins in the regulation of platelet biology.

Platelets are anucleated blood cells derived from megakaryocytes, and although they are essential for proper hemostasis, their function extends to physiologic processes such as tissue repair, wound remodeling, and antimicrobial host defense, or pathologic conditions such as thrombosis, atherosclerosis, chronic inflammatory diseases, and cancer. Recently, we demonstrated that two structurally divergent members of the galectin family, galectin-1 and galectin-8, are potent platelet agonists. The emergence of galectins as soluble mediators capable of triggering platelet activation opens a new field of research that will provide further insights into the mechanisms linking inflammatory responses to thrombus formation and could expand our view of the role of platelets much beyond hemostasis to their pathophysiologic role during inflammation and cancer.

Galectins: new agonists of platelet activation.

Platelet activation at sites of vascular injury leads to the formation of a hemostatic plug and is crucial for hemostasis. However, uncontrolled platelet activation may lead to the formation of occlusive thrombi. Several soluble or matricellular proteins can activate platelets.

Chemokine receptor CCR1 disruption limits renal damage in a murine model of hemolytic uremic syndrome.

Shiga toxin (Stx)-producing Escherichia coli is the main etiological agent that causes hemolytic uremic syndrome (HUS), a microangiopathic disease characterized by hemolytic anemia, thrombocytopenia, and acute renal failure. Although direct cytotoxic effects on endothelial cells by Stx are the primary pathogenic event, there is evidence that indicates the inflammatory response mediated by polymorphonuclear neutrophils and monocytes as the key event during HUS development. Because the chemokine receptor CCR1 participates in the pathogenesis of several renal diseases by orchestrating myeloid cell kidney infiltration, we specifically addressed the contribution of CCR1 in a murine model of HUS.