Nitazoxanide Exerts Immunomodulatory Effects on Peripheral Blood Mononuclear Cells from Type 2 Diabetes Patients.

BACKGROUND: Type 2 diabetes (T2D) is a low-grade inflammatory condition with abnormalities in the immune response mediated by T lymphocytes and macrophages. Drug repositioning for immunomodulatory molecules is an attractive proposal for treating T2D. Nitazoxanide (NTZ) is a broad-spectrum drug with promising immunomodulatory effects. Thus, we investigated the immunomodulatory effect of NTZ on peripheral blood mononuclear cells (PBMCs) from patients with T2D. METHODS: Fifty patients with T2D were selected, and the proliferative response of T lymphocytes and the M1/M2 ratio of macrophages post cell culture were evaluated by flow cytometry, as well as measuring the concentration of cytokines by ELISA and the relative expression of microRNAs (miRNAs) related to the immune response by real-time PCR. RESULTS: NTZ exerts an inhibitory effect on the cell proliferation of T lymphocytes stimulated with anti-CD3 and anti-CD28 antibodies without modifying cell viability, and significant decreases in the supernatant concentrations of interleukin (IL)-1ß, IL-2, IL-6, IL-10, and IL-12. Furthermore, NTZ negatively regulates the relative expression of miR-155-5p without changes in miR-146a-5p. The M1/M2 ratio of monocytes/macrophages decreased the M1 and increased the M2 subpopulation by NTZ. CONCLUSIONS: Our results suggest that NTZ exerts immunomodulatory effects on PBMCs from T2D patients, and shows potential alternative therapeutic benefits.

Changes in cardiovascular risk and clinical outcomes in a HIV/AIDS cohort study over a 1-year period at a specialized clinic in Mexico.

INTRODUCTION: The third report of the National Cholesterol Education Program guidelines recommends calculating the 10-year morbidity of atherosclerotic cardiovascular disease (ASCVD) using risk calculators when treating high blood cholesterol in adults. We analyzed the changes in cardiovascular risk (CVR) among Mexican patients with HIV. PATIENTS AND METHODS: This observational, prospective cohort study compared the CVR after 1 year of antiretroviral treatment among 460 HIV patients from a Mexican clinic. Changes using the ASCVD risk estimator and changes in clinical outcomes were analyzed. The results were categorized as low or high CVR using a cutoff of 7.5%. RESULTS: The CVR initially had a median of 2.3% (interquartile range [IQR]: 1%-4.8%), which changed to 2.4% (IQR: 1.5%-5.5%) after 1 year (P=0.001). After CVR stratification, we found that 84.3% of the patients had a low CVR, and 18% in this subgroup had metabolic syndrome (MS). Moreover, 15.7% had high CVR, and 47% in this subgroup had MS. The 4.3% of patients had an increase in CVR from the low to high subgroup, and 2.6% had a decrease in CVR from the high to low subgroup. Out of all patients, 22.3% had MS. CONCLUSION: More than 50% of the population had an increase in CVR after 1 year. Of these patients, 4.3% changed from the low to high CVR group. Although the guidelines proposed different time periods for performing CVR estimations, this study showed that such assessments offered valuable clinical data over a relatively short-term period.

Chrysin Induces Antidiabetic, Antidyslipidemic and Anti-Inflammatory Effects in Athymic Nude Diabetic Mice.

Extensive knowledge of diabetes and its complications is helpful to find new drugs for proper treatment to stop degenerative changes derived from this disease. In this context, chrysin (5,7-dihydroxyflavone) is a natural product that occurs in a variety of flowers and fruits with anti-inflammatory and antidiabetic effects, among others. Thus, a diabetic model in athymic nude mice was developed and used to establish the ability of chrysin to decrease the secretion of pro-inflammatory cytokines. Also, it was determined the acute (50 mg/kg) and sub-acute (50 mg/kg/day/10 days) antidiabetic and antihyperlipidemic activities after the period of time treatment. Results indicate that chrysin has significant acute antihyperglycemic and antidiabetic effects in nude diabetic mice (p < 0.05). Moreover, triglyceride blood levels were reduced and IL-1ß and TNF-α were diminished after 10 days' treatment compared with control group (p < 0.05). In conclusion, it was found that chrysin could produce similar effects as metformin, a drug used for the treatment of diabetes, since both test samples decreased glucose and triglycerides levels, they impaired the generation of pro-inflammatory cytokines involved in the development of diabetes and its consequences, such as atherosclerosis and other cardiovascular diseases.

Serum leptin is associated with metabolic syndrome in obese Mexican subjects.

BACKGROUND: The metabolic syndrome (MetS) is a cluster of metabolic abnormalities including insulin resistance, dyslipidemia, high blood pressure, and abdominal adiposity. Obese patients develop leptin resistance, and an increased waist circumference (WC) due to deposition of abdominal fat. The aim of this study was to evaluate the association between circulating leptin levels and MetS among sample adult Mexican workers. METHOD: A total of 204 workers aged 20-56 were evaluated. Anthropometric index, blood pressure, fasting plasma glucose, and lipid profile were measured by spectrophotometric methods. Fasting insulin and leptin were measured by inmunoenzimatic methods. Furthermore, homeostasis model assessment for insulin resistance (HOMA-IR) was calculated. RESULTS: The prevalence of MetS according to the ATP-III criteria was 33.8% and leptin concentrations were 2.5 times higher in women than men. Subjects with MetS had higher levels of leptin (26.7 ± 13.7) compared with those without MetS (20.1 ± 13.9; P <0.001). Leptin increased significantly while BMI increased as well (normal 14.0 ± 8.9, overweight 22.7 ± 11.7 and obese 31.4 ± 14.6) in addition to other variables such as WC, HDL-C, insulin levels, and HOMA index. Each component of MetS was stratified by sex and submitted by linear regression with a 95% of accuracy. The 50% and 53% of the BMI is explained by the concentration of leptin in men and women, respectively (P < 0.001). CONCLUSION: This study found that leptin was associated with the MetS, especially in obesity and insulin resistance, indicating a high risk for university workers to develop hypertension, DM2, and cardiovascular disease.

Decreased expression of T-cell costimulatory molecule CD28 on CD4 and CD8 T cells of mexican patients with pulmonary tuberculosis.

Patients with tuberculosis frequently develop anergy, a state of T-cell hyporesponsiveness in which defective T-cell costimulation could be a factor. To know if the expression of T-cell costimulatory molecules was altered in tuberculosis, we analyzed the peripheral blood T-cell phenotype of 23 Mexican patients with pulmonary tuberculosis. There was severe CD4 (P < .001) and CD8 (P < .01) lymphopenia and upregulation of costimulatory molecule CD30 on CD4 and CD8 T cells (P < .05); this increase was higher in relapsing tuberculosis. The main finding was severe downregulation of the major costimulatory molecule CD28 on both CD8 and CD4 T cells (P < .001). Depletion of the CD4/CD28 subset, a hitherto undescribed finding, is relevant because CD4 T cells constitute the main arm of the cell-mediated antimycobacterial immune response.

Impact of opportunistic Mycobacterium tuberculosis infection on the phenotype of peripheral blood T cells of AIDS patients.

While the detrimental consequences of opportunistic tuberculosis (TB) in the course and outcome of HIV-1 infection are well studied, little information about the impact of the mycobacterial infection on the phenotype of T lymphocytes is available. In this study we analyzed by cytofluorimetry the peripheral blood T cell phenotype of 13 patients with AIDS, 23 HIV-1 negative patients with active pulmonary TB, nine HIV-1/Mycobacterium tuberculosis coinfected individuals, and 21 age- and sex-matched healthy controls. CD4+ T cells were equally depleted in AIDS and coinfection (P<0.001). The findings suggest a rescuing effect of the added mycobacterial infection. CD3 T cell loss was not observed in coinfection, whereas it was severe in AIDS (P<0.001). Similar (albeit less striking) effects were observed with other markers (CD45RA, CD45RO, and CD27) that were diminished in CD4+ T cells of AIDS patients. Apparent detrimental effects of the added mycobacterial infection were the increased expression of the proapoptotic molecule CD95 on CD4+ T cells, and decreased expression of the major costimulatory molecule CD28 on CD8+ T cells. In this work we show that M. tuberculosis infection modifies the T cell phenotype of the HIV-1 infected individual.

The 19-kDa antigen of Mycobacterium tuberculosis is a major adhesin that binds the mannose receptor of THP-1 monocytic cells and promotes phagocytosis of mycobacteria.

Identification of mycobacterial adhesins is needed to understand better the pathogenesis of tuberculosis and to develop new strategies to fight this infection. In this work, THP-1 monocytic cells were incubated with Mycobacterium tuberculosis culture filtrate proteins labelled with biotin and a dominant 19-kDa adhesin was found. This adhesin was characterized as the glycosylated and acylated 19-kDa antigen (Rv 3763). These findings were confirmed in assays with culture filtrate proteins and cell-wall fractions from a recombinant Mycobacterium smegmatis strain that overexpresses the 19-kDa antigen. Further, fluorescent microspheres coated with recombinant culture filtrate proteins adhere to cells in higher numbers than microspheres coated with native M. smegmatis proteins. The binding of the 19-kDa antigen to cells was inhibited with mannose receptor competitor sugars, Ca(2+) chelators and with a monoclonal antibody to the human mannose receptor. Phagocytosis assays showed high-level binding of bacilli to THP-1 cells that was inhibited with alpha-methyl-mannoside, mannan, EDTA and mAbs to the mannose receptor and to the 19-kDa M. tuberculosis antigen. Immunoprecipitation, cell-surface ELISA and immunostaining confirmed the expression of the mannose receptor by THP-1 cells. In conclusion, here we show that the macrophage mannose receptor, considered a pathogen pattern recognition receptor, may interact with mannose residues of mycobacterial glycoproteins that could promote the phagocytosis of mycobacteria.