Potential molecular patterns for tuberculosis susceptibility in diabetic patients with poor glycaemic control: a pilot study.

Type 2 diabetes (DM2) is an increasingly prevalent disease that challenges tuberculosis (TB) control strategies worldwide. It is significant that DM2 patients with poor glycemic control (PDM2) are prone to developing tuberculosis. Furthermore, elucidating the molecular mechanisms that govern this susceptibility is imperative to address this problem. Therefore, a pilot transcriptomic study was performed. Human blood samples from healthy controls (CTRL, HbA1c < 6.5%), tuberculosis (TB), comorbidity TB-DM2, DM2 (HbA1c 6.5-8.9%), and PDM2 (HbA1c > 10%) groups (n = 4 each) were analyzed by differential expression using microarrays. We use a network strategy to identify potential molecular patterns linking the differentially expressed genes (DEGs) specific for TB-DM2 and PDM2 (p-value < 0.05, fold change > 2). We define OSM, PRKCD, and SOCS3 as key regulatory genes (KRGs) that modulate the immune system and related pathways. RT-qPCR assays confirmed upregulation of OSM, PRKCD, and SOCS3 genes (p < 0.05) in TB-DM2 patients (n = 18) compared to CTRL, DM2, PDM2, or TB groups (n = 17, 19, 15, and 9, respectively). Furthermore, OSM, PRKCD, and SOCS3 were associated with PDM2 susceptibility pathways toward TB-DM2 and formed a putative protein-protein interaction confirmed in STRING. Our results reveal potential molecular patterns where OSM, PRKCD, and SOCS3 are KRGs underlying the compromised immune response and susceptibility of patients with PDM2 to develop tuberculosis. Therefore, this work paved the way for fundamental research of new molecular targets in TB-DM2. Addressing their cellular implications, and the impact on the diagnosis, treatment, and clinical management of TB-DM2 could help improve the strategy to end tuberculosis for this vulnerable population.

Overexpression of TLR7 and TLR9 Occurs Before Onset Symptoms In First-Degree Relatives of Rheumatoid Arthritis Patients.

BACKGROUND: Autoantibodies have a central role in the physiopathology of Rheumatoid Arthritis (RA). However, the responsible factors that trigger and perpetuate the autoantibodies production are unknown. Toll-like receptors (TLRs) have been considered as promotors of autoantibodies production to break down the immunotolerance in RA. AIM OF THE STUDY: Evaluate the expression levels of TLR7 and TLR9 as well as their correlation with autoantibodies in first-degree relatives (FDR) of RA patients (seropositive and seronegative to ACPA), respect to early RA (eRA) and chronic RA (cRA) patients. METHODS: We selected 32 RA patients (16 as eRA and 16 as cRA) and 32 FDR of RA patients (16 seropositive and 16 seronegative to ACPA). Expression levels of TLR7 and TLR9 in whole blood samples from each group were measured by real-time PCR using total RNA extracted from each subject. Also, correlation analysis between TLRs expression and autoantibodies was performed. RESULTS: The expression of TLR7 and TLR9 was diminished in RA patients (p <0.01) but elevated in ACPA- FDR (p <0.0001) and ACPA+ FDR (p <0.05) with a positive correlation between them (r = 0.749, p <0.000). Moreover, the expression levels of TLR7 correlate positively with ACPA levels in both seropositive ACPA+ FDR subjects (r = 0.582, p = 0.018) and eRA patients (r = 0.593, p = 0.020). CONCLUSIONS: Our results showed overexpression of TLR7 and TLR9 may occur in preclinical RA subjects. TLR7 overexpression correlated with ACPA levels' production, suggesting TLR7 may play a role in ACPA development.

Momordica Charantia: A Review of Its Effects on Metabolic Diseases and Mechanisms of Action.

The global rise in the prevalence of metabolic diseases such as diabetes, obesity, and dyslipidemia is a serious public health issue. The search for safe and effective complementary and alternative therapies to treat metabolic disorders is a key field of research. Momordica charantia (MC) is a tropical and subtropical vine of the Cucurbitaceae family used as a medicinal plant since ancient times. Although MC has been widely studied for its hypoglycemic potential, hypolipidemic and antiobesity effects have also been reported in preclinical studies and clinical trials. This study aims to review the metabolic effects of MC reported in clinical trials as well as its mechanisms of action.

The Neuroprotective Effect of Erythropoietin in Rat Hippocampus in an Endotoxic Shock Model.

BACKGROUND: Sepsis is characterized by an early systemic inflammation in response to infection. In the brain, inflammation is associated with expression of pro-inflammatory cytokines (e.g. tumor necrosis factor-α, interleukin-1ß and interleukin-6, among others) that may induce an overproduction of reactive oxygen and nitrogen species. The constitutive expression of cytokines in the brain is low, but may be induced by various stimuli, including lipopolysaccharide, which causes neuronal damage. Erythropoietin, among other effects, acts as a multifunctional neurotrophic factor implicated in neurogenesis, angiogenesis, vascular permeability, and immune regulation in the central nervous system. In an experimental model of endotoxic shock, we studied the neuroprotective capacity of erythropoietin in the rat hippocampus and compared with melatonin, a neurohormone with an important antioxidant and immunomodulatory effect. METHODS: In 21-day-old male Wistar rats divided into eight groups, we administered by intraperitoneal injection lipopolysaccharide, erythropoietin, melatonin, or combinations thereof. The hippocampus was dissected and morphological (histological analysis) and biochemical (cytokine levels) studies were conducted. RESULTS: The number of dead neuronal cells in histological sections in groups treated with lipopolysaccharide was higher compared to the erythropoietin group. There was a greater decrease (70%) in interleukin-1ß concentrations in rats with endotoxic shock that received erythropoietin compared to the lipopolysaccharide group. CONCLUSIONS: The neuronal cell loss caused by endotoxic shock and interleukin-1ß levels were reduced by the administration of the hematopoietic cytokine erythropoietin in this experimental model.