Evaluation of an Antisense Oligonucleotide Targeting CAG Repeats: A Patient-Customized Therapy Study for Huntington's Disease.

Huntington's disease is a genetic disorder characterized by progressive neuronal cell damage in some areas of the brain; symptoms are commonly associated with chorea, rigidity and dystonia. The symptoms in Huntington's Disease are caused by a pathological increase in the number of Cytokine-Adenine-Guanine (CAG) repeats on the first exon of the Huntingtin gene, which causes a protein to have an excessive number of glutamine residues; this alteration leads to a change in the protein's conformation and function. Therefore, the purpose of this work was to design, synthesize and evaluate an antisense oligonucleotide (ASO; 95 nucleotides) HTT 90-5 directed to the Huntingtin CAG repeats in primary leukocyte culture cells from a patient with Huntington's Disease; approximately 500,000 leukocytes per well extracted from venous blood were used, to which 100 pMol of ASO were administered, and the expression of Huntingtin was subsequently evaluated at 72 h by RT-PCR.

Comparison of Ten Surrogate Insulin Resistance and Obesity Markers to Identify Metabolic Syndrome in Mexican Adults.

Metabolic syndrome () is a group of clinical traits directly linked to type 2 diabetes mellitus and cardiovascular diseases, whose prevalence has been rising nationally and internationally. We aimed to evaluate ten known and novel surrogate markers of insulin resistance and obesity to identify in Mexican adults. The present cross-sectional study analyzed 10575 participants from ENSANUT-2018.

Modulator Effect of AT1 Receptor Knockdown on THP-1 Macrophage Proinflammatory Activity.

Unlabelled: Currently, it is known that angiotensin II (AngII) induces inflammation, and an ATR blockade has anti-inflammatory effects. The use of an AT receptor antagonist promotes the inhibition of the secretion of multiple proinflammatory cytokines in macrophages, as well as a decrease in the concentration of reactive oxygen species. The aim of this study was to determine the effect of AT receptor gene silencing on the modulation of cytokines (e.

Cardiovascular effect of preeclampsia upon offspring development: Are (Pro) renin-renin receptor ((P)RR) and gender related?

Objectives: Preeclampsia (PE) is a complication of pregnancy that might increase progeny risk of cardiovascular and metabolic problems, mainly in males. Renin angiotensin aldosterone system is known to be involved. (Pro) renin/renin receptor ((P)RR) has been shown to participate in cardiovascular pathology.

siRNA Targeting ECE-1 Partially Reverses Pulmonary Arterial Hypertensionassociated Damage in a Monocrotaline Model.

Aims: The aim of this study was to develop a possible treatment for pulmonary arterial hypertension.

Background: Pulmonary arterial hypertension (PAH) is a rare disease characterised by a pulmonary arterial pressure greater than 20 mmHg. One of the factors that contribute to PAH is an increase in the production of endothelin-1, a polypeptide that increases vascular resistance in the pulmonary arteries, leading to increased pulmonary arterial pressure and right ventricular hypertrophy.

Effect of Supplementation with Omega-3 Polyunsaturated Fatty Acids on Metabolic Modulators in Skeletal Muscle of Rats with an Obesogenic High-Fat Diet.

Previous studies provided evidence of the benefits of omega-3 polyunsaturated fatty acids (ω-3 PUFA) on the cardiovascular system and inflammation. However, its possible effect on skeletal muscle is unknown. This study aimed to evaluate whether ω-3 PUFA reverses the dysregulation of metabolic modulators in the skeletal muscle of rats on a high-fat obesogenic diet.

The Roles of MicroRNAs in Asthma and Emerging Insights into the Effects of Vitamin D Supplementation.

Asthma is one of the most common chronic non-communicable diseases worldwide, characterized by variable airflow limitation secondary to airway narrowing, airway wall thickening, and increased mucus resulting from chronic inflammation and airway remodeling. Current epidemiological studies reported that hypovitaminosis D is frequent in patients with asthma and is associated with worsening the disease and that supplementation with vitamin D improves asthma symptoms. However, despite several advances in the field, the molecular mechanisms of asthma have yet to be comprehensively understood.

The Additive Antinociceptive Effect of Resveratrol and Ketorolac in the Formalin Test in Mice.

Pain represents one of the leading causes of suffering and disability worldwide. Currently available drugs cannot treat all types of pain and may have adverse effects. Hence, the use of pharmacological combinations is an alternative treatment strategy.

Glycine: The Smallest Anti-Inflammatory Micronutrient.

Glycine is a non-essential amino acid with many functions and effects. Glycine can bind to specific receptors and transporters that are expressed in many types of cells throughout an organism to exert its effects. There have been many studies focused on the anti-inflammatory effects of glycine, including its abilities to decrease pro-inflammatory cytokines and the concentration of free fatty acids, to improve the insulin response, and to mediate other changes.

Whole Blood Expression Levels of Long Noncoding RNAs: HOTAIRM1, GAS5, MZF1-AS1, and OIP5-AS1 as Biomarkers in Adolescents with Obesity-Related Asthma.

Asthma is a heterogeneous entity encompassing distinct endotypes and varying phenotypes, characterized by common clinical manifestations, such as shortness of breath, wheezing, and variable airflow obstruction. Two major asthma endotypes based on molecular patterns are described: type 2 endotype (allergic-asthma) and T2 low endotype (obesity-related asthma). Long noncoding RNAs (lncRNAs) are transcripts of more than 200 nucleotides in length, currently involved in many diverse biological functions, such as chromatin remodeling, gene transcription, protein transport, and microRNA processing.

Promoter methylation status of , and in peripheral blood leukocytes in adolescents with obesity-related asthma.

A higher Th17-immune response characterises obesity and obesity-related asthma phenotype. Nevertheless, obesity-related asthma has a more significant Th17-immune response than obesity alone. Retinoid-related orphan receptor C (RORC) is the essential transcription factor for Th17 polarisation.

Glycine Effect on the Expression Profile of Orphan Receptors GPR21, GPR26, GPR39, GPR82 and GPR6 in a Model of Inflammation in 3T3-L1 Cells.

Background: Chronic or low-grade inflammation is a process where various immune cells are recruited from the periphery into adipose tissue. This event gives rise to localised inflammation, in addition to having a close interaction with cardiometabolic pathologies where the mediation of orphan receptors is observed. The aim of this study was to analyse the participation of the orphan receptors GPR21, GPR39, GPR82 and GPR6 in a chronic inflammatory process in 3T3-L1 cells.

siRNA knockdown of angiopoietin 2 significantly reduces neovascularization in diabetic rats.

Diabetes is a disease that leads to proliferative diabetic retinopathy (PDR), which is associated with an increase of new vessels formation due to an overexpression of angiogenic factors, such as angiopoietin 2 (ANGPT2). The aim of this work was to design a siRNA targeting ANGPT2 to decrease the retinal neovascularization associated with PDR. Adult male Wistar rats weighing 325-375 g were used.

Expression profiles of GPR21, GPR39, GPR135, and GPR153 orphan receptors in different cancers.

Orphan receptors have unknown endogenous ligands, are expressed in different tissues, and participate in various diseases such as diabetes, hypertension and cancer. We studied the expression profiles of GPR21, GPR39, GPR135 and GPR153 orphan receptors in several tumour tissues. Cervical, breast, skin, prostate, and astrocytoma tissues were analysed for orphan receptor gene expression using Real time PCR analysis.

Retinol-binding protein 4 and plasminogen activator inhibitor-1 as potential prognostic biomarkers of non-allergic asthma caused by obesity in adolescents.

Background: Non-allergic asthma caused by obesity is a complication of the low-grade chronic inflammation inherent in obesity. Consequently, the serum concentrations of adipokines such as retinol-binding protein 4 (RBP4) and plasminogen activator inhibitor-1 (PAI-1) increase. No gold standard molecule for the prediction of non-allergic asthma among obese patients has been identified.

Associations of TNFA, IL17A, and RORC mRNA expression levels in peripheral blood leukocytes with obesity-related asthma in adolescents.

Obesity is associated with a unique non-T2 asthma phenotype, characterised by a Th17 immune response. Retinoid-related orphan receptor C (RORC) is the master transcription factor for Th17 polarisation. We investigated the association of TNFA, IL17A, and RORC mRNA expression levels with the non-T2 phenotype.

α-Amyrin induces GLUT4 translocation mediated by AMPK and PPARδ/γ in C2C12 myoblasts.

α-Amyrin, a natural pentacyclic triterpene, has an antihyperglycemic effect in mice and dual PPARδ/γ action in 3T3-L1 adipocytes, and potential in the control of type 2 diabetes (T2D). About 80% of glucose uptake occurs in skeletal muscle cells, playing a significant role in insulin resistance (IR) and T2D. Peroxisome-proliferator activated receptors (PPARs), in particular PPARδ and PPARγ, are involved in the regulation of lipids and carbohydrates and, along with adenosine-monophosphate (AMP) - activated protein kinase (AMPK) and protein kinase B (Akt), are implicated in translocation of glucose transporter 4 (GLUT4); however, it is still unknown whether α-amyrin can affect these pathways in skeletal muscle cells.

Antisclerothic effect of tibolone by reducing proinflammatory cytokines expression, ROS production and LDL-ox uptake in THP-1 macrophages.

Background: Cardiovascular disease is more frequent in menopausal women, which has been related to factor such as weight gain, altered fat distribution, and increased inflammation markers including adipokines (MCP-1, TNF-α, IL-6) and cytokines (IL-1, IL-6, TNF-α) produced by macrophages. In addition to their phagocytic activity, macrophages secrete cytokines and chemokines that induces cell recruitment, which is a process related to vascular damage that favors the formation of atheromatous plaques. Tibolone (Tb) therapy is used to reduce the symptoms of menopause as well as osteoporosis and it has been shown to decreases the risk of fractures.

Modifications in GPR21 and GPR82 genes expression as a consequence of metabolic syndrome etiology.

Metabolic syndrome (MS) has been related with alterations in expression levels of orphan G protein coupled receptors (GPCRs) such as GPR21 and GPR82, which could be involved in some of the elements that characterizes the metabolic syndrome. The aim of this work was to evaluate changes in GPR21 and GPR82 receptors expression in two models of metabolic syndrome: one genetic (Zucker rats), and the other based on a diet (70% fructose for 9 weeks). GPR21 and GPR82 gene expressions were evaluated in brain, heart, aorta, liver and kidney by RT-qPCR.

The regulatory effect of bromocriptine on cardiac hypertrophy by prolactin and D2 receptor modulation.

Background: Bromocriptine, a dopamine agonist, used for the treatment of hyperprolactinemia, type 2 diabetes, ovarian hyper-stimulation syndrome, has also effects on the cardiac remodeling process, but the mechanism of action is unknown. The aim of this work was to determinate the effect during hypertrophic process through molecular mechanisms that include prolactin receptor (Prlr) and receptor of dopamine 2 (D2 r) expression.

Methods: We used a model of cardiac hypertrophy induced by an aortocaval fistula (ACF) surgery in rats.

Decreased methylation profiles in the TNFA gene promoters in type 1 macrophages and in the IL17A and RORC gene promoters in Th17 lymphocytes have a causal association with non-atopic asthma caused by obesity: A hypothesis.

Obesity is a serious public health problem worldwide and has been associated in epidemiological studies with a unique type of non-atopic asthma, although the causal association of asthma and obesity has certain criteria, such as the strength of association, consistency, specificity, temporality, biological gradient, coherence, analogy and experimentation; nevertheless, the biological plausibility of this association remains uncertain. Various mechanisms have been postulated, such as immunological, hormonal, mechanical, environmental, genetic and epigenetic mechanisms. Our hypothesis favours immunological mechanisms because some cytokines, such as tumour necrosis factor alpha (TNF-α) and interleukin (IL)-17A, are responsible for orchestrating low-grade systemic inflammation associated with obesity; however, these cytokines are regulated by epigenetic mechanisms, such as gene promoter methylation.

Silencing of GPR82 with Interference RNA Improved Metabolic Profiles in Rats with High Fructose Intake.

Metabolic syndrome (MS) is a clinical condition, constituted by alterations that lead to the onset of type II diabetes and cardiovascular disease. It has been reported that orphan G-protein-coupled receptor 82 (GPR82) participates in metabolic processes. The aim of this study was to evaluate the function of GPR82 in MS using a small interfering RNA (siRNA) against this receptor.

High Fructose Intake and Adipogenesis.

In modern societies, high fructose intake from sugar-sweetened beverages has contributed to obesity development. In the diet, sucrose and high fructose corn syrup are the main sources of fructose and can be metabolized in the intestine and transported into the systemic circulation. The liver can metabolize around 70% of fructose intake, while the remaining is metabolized by other tissues.