Modulation of myeloid-derived suppressor cell functions by oral inflammatory diseases and important oral pathogens.

The oral cavity presents a diverse microbiota in a dynamic balance with the host. Disruption of the microbial community can promote dysregulation of local immune response which could generate oral diseases. Additionally, alterations in host immune system can result in inflammatory disorders. Different microorganisms have been associated with establishment and progression of the oral diseases. Oral cavity pathogens/diseases can modulate components of the inflammatory response. Myeloid-derived suppressor cells (MDSCs) own immunoregulatory functions and have been involved in different inflammatory conditions such as infectious processes, autoimmune diseases, and cancer. The aim of this review is to provide a comprehensive overview of generation, phenotypes, and biological functions of the MDSCs in oral inflammatory diseases. Also, it is addressed the biological aspects of MDSCs in presence of major oral pathogens. MDSCs have been mainly analyzed in periodontal disease and Sjögren's syndrome and could be involved in the outcome of these diseases. Studies including the participation of MDSCs in other important oral diseases are very scarce. Major oral bacterial and fungal pathogens can modulate expansion, subpopulations, recruitment, metabolism, immunosuppressive activity and osteoclastogenic potential of MDSCs. Moreover, MDSC plasticity is exhibited in presence of oral inflammatory diseases/oral pathogens and appears to be relevant in the disease progression and potentially useful in the searching of possible treatments. Further analyses of MDSCs in oral cavity context could allow to understand the contribution of these cells in the fine-tuned balance between host immune system and microorganism of the oral biofilm, as well as their involvement in the development of oral diseases when this balance is altered.

AT1 receptor downregulation: A mechanism for improving glucose homeostasis.

There is a pathophysiological correlation between arterial hypertension and diabetes mellitus, established since the pre-diabetic state in the entity known as insulin resistance. It is known that high concentrations of angiotensin-II enable chronic activation of the AT1 receptor, promoting sustained vasoconstriction and the consequent development of high blood pressure. Furthermore, the chronic activation of the AT1 receptor has been associated with the development of insulin resistance. From a molecular outlook, the AT1 receptor signaling pathway can activate the JNK kinase. Once activated, this kinase can block the insulin signaling pathway, favoring the resistance to this hormone. In accordance with the previously mentioned mechanisms, the negative regulation of the AT1 receptor could have beneficial effects in treating metabolic syndrome and type 2 diabetes mellitus. This review explains the clinical correlation of the metabolic response that diabetic patients present when receiving negatively regulatory drugs of the AT1 receptor.

The Increased Expression of Regulator of G-Protein Signaling 2 (RGS2) Inhibits Insulin-Induced Akt Phosphorylation and Is Associated with Uncontrolled Glycemia in Patients with Type 2 Diabetes.

Experimental evidence in mice models has demonstrated that a high regulator of G-protein signaling 2 (RSG2) protein levels precede an insulin resistance state. In the same context, a diet rich in saturated fatty acids induces an increase in RGS2 protein expression, which has been associated with decreased basal metabolism in mice; however, the above has not yet been analyzed in humans. For this reason, in the present study, we examined the association between RGS2 expression and insulin resistance state. The incubation with palmitic acid (PA), which inhibits insulin-mediated Akt Ser473 phosphorylation, resulted in the increased RGS2 expression in human umbilical vein endothelial-CS (HUVEC-CS) cells. The RGS2 overexpression without PA was enough to inhibit insulin-mediated Akt Ser473 phosphorylation in HUVEC-CS cells. Remarkably, the platelet RGS2 expression levels were higher in type 2 diabetes mellitus (T2DM) patients than in healthy donors. Moreover, an unbiased principal component analysis (PCA) revealed that RGS2 expression level positively correlated with glycated hemoglobin (HbA1c) and negatively with age and high-density lipoprotein cholesterol (HDL) in T2DM patients. Furthermore, PCA showed that healthy subjects segregated from T2DM patients by having lower levels of HbA1c and RGS2. These results demonstrate that RGS2 overexpression leads to decreased insulin signaling in a human endothelial cell line and is associated with poorly controlled diabetes.

Inverse correlation between levels of glycated haemoglobin and expression levels of SERCA protein in Mexican patients with type 2 diabetes mellitus.

We examined the association between sarco/endoplasmic reticulum calcium ATPase (SERCA) expression and glycated hemoglobin (HbA1c) levels since alterations in this protein expression are associated with the genesis of insulin resistance. HbA1c levels and SERCA protein expression from platelets of Mexican patients diagnosed with type 2 diabetes mellitus (T2DM) were analyzed showing lower values of SERCA expression against the normal values we find in healthy people. Interestingly, as diabetes condition got worse; SERCA protein expression decreased gradually until it was undetectable. The results showed an inverse correlation between HbA1c and SERCA protein expression in T2DM patients. .

Comparison of the Purelyse® - IS6110 nested PCR with the Xpert® MTB/RIF test in clinical samples with suspected tuberculosis.

Tuberculosis (TB) has a high incidence, prevalence and mortality in the world. Due to its high level of transmission and long-term pharmacological treatment, it is important to have sensitive and specific diagnostic tests. Recently, the PureLyse® system, which is a novel DNA extraction method, was proposed to be an important tool for molecular diagnosis of TB. Here, we compare the PureLyse® system followed by an IS6110 nested PCR (PureLyse® - IS6110 nested PCR) with the Xpert® MTB/RIF test for Mycobacterium tuberculosis complex (MTBC) identification in 40 clinical samples. Among the 40 samples, 26 samples were positive and 14 negative for the Xpert® MTB/RIF test as well as for the PureLyse® - IS6110 nested PCR. According to the Xpert® MTB/RIF test, positive samples presented different bacillary concentrations from "High" to "Very low" and rifampin resistance was observed in 5 samples. The concordance of both molecular methods makes the PureLyse® - IS6110 nested PCR suitable for MTBC detection in patients for low-income resources.