Cardiorenal Fat: A Cardiovascular Risk Factor With Implications in Chronic Kidney Disease.

There is a growing interest in the potential role of adipose tissues in cardiac and renal pathophysiology, and determining the mechanisms by which fat compartments around the heart and kidneys influence cardiovascular disease is of clinical importance in both general and high-risk populations. Epicardial fat and perirenal fat have been associated with adverse outcomes in chronic kidney disease (CKD) patients. Epicardial fat is a rich source of free fatty acids and is capable of secreting inflammatory and pro-atherogenic cytokines that promote atherosclerosis through a local paracrine effect.

An updated overview of e-cigarette impact on human health.

The electronic cigarette (e-cigarette), for many considered as a safe alternative to conventional cigarettes, has revolutionised the tobacco industry in the last decades. In e-cigarettes, tobacco combustion is replaced by e-liquid heating, leading some manufacturers to propose that e-cigarettes have less harmful respiratory effects than tobacco consumption. Other innovative features such as the adjustment of nicotine content and the choice of pleasant flavours have won over many users.

Natural products and analogs as preventive agents for metabolic syndrome via peroxisome proliferator-activated receptors: An overview.

Natural products and synthetic analogs have drawn much attention as potential therapeutical drugs to treat metabolic syndrome. We reviewed the underlying mechanisms of 32 natural products and analogs with potential pharmacological effects in vitro, and especially in rodent models and/or patients, that usually act on the PPAR pathway, along with other molecular targets. Recent outstanding total syntheses or semisyntheses of these lead compounds are stated.

Oral Unsaturated Fat Load Impairs Postprandial Systemic Inflammation in Primary Hypercholesterolemia Patients.

Primary hypercholesterolemia (PH) is a lipid disorder characterized by elevated levels of cholesterol and low-density lipoprotein (LDL). Low-grade systemic inflammation is associated with PH, which might explain the higher incidence of cardiovascular diseases in this setting. To evaluate the effect of an oral unsaturated fat load (OUFL) on different immune parameters and functional consequences in patients with PH in postprandial state.

Peripheral blood levels of CXCL10 are a useful marker for diabetic polyneuropathy in subjects with type 2 diabetes.

Background: Diabetic peripheral neuropathy (DPN) is a chronic complication of diabetes mellitus associated with high morbidity and mortality. Major risk factors for DPN include metabolic changes, duration of diabetes, nerve ischaemia and derangements in regeneration and nerve repair programmes. Chemokines have been previously implicated in the pathogenesis of various neuropathies and neuropathic pain processes.

Expression of Phosphorylated BRD4 Is Markedly Associated with the Activation Status of the PP2A Pathway and Shows a Strong Prognostic Value in Triple Negative Breast Cancer Patients.

The bromodomain-containing protein 4 (BRD4), a member of the bromodomain and extra-terminal domain (BET) protein family, has emerged in the last years as a promising molecular target in many tumors including breast cancer. The triple negative breast cancer (TNBC) represents the molecular subtype with the worst prognosis and a current therapeutic challenge, and TNBC cells have been reported to show a preferential sensitivity to BET inhibitors. Interestingly, BRD4 phosphorylation (pBRD4) was found as an alteration that confers resistance to BET inhibition and PP2A proposed as the phosphatase responsible to regulate pBRD4 levels.

Transcriptome profiles discriminate between Gram-positive and Gram-negative sepsis in preterm neonates.

Background: Genome-wide expression profiles have been previously employed as clinical research diagnostic tools for newborn sepsis. We aimed to determine if transcriptomic profiles could discriminate between Gram-positive and Gram-negative bacterial sepsis in preterm infants.

Methods: Prospective, observational, double-cohort study was conducted in very low birth weight infants with clinical signs and culture-positive sepsis.

Overexpression of genes involved in lymphocyte activation and regulation are associated with reduced CRM-derived cardiac remodelling after STEMI.

Aims: Lymphopenia after ST-segment elevation myocardial infarction (STEMI) correlates with deleterious cardiac consequences and worse prognosis. An in-depth examination of genes implicated in lymphocyte proliferation, activation and regulation and their association with short- and long-term cardiac structure and function is therefore of great interest.

Methods: Peripheral blood mononuclear cells were isolated from 10 control subjects and 64 patients with a first STEMI treated with primary percutaneous coronary intervention and submitted to cardiac magnetic resonance after 1 week and 6 months.

Implementing Precision Medicine in Human Frailty through Epigenetic Biomarkers.

The main epigenetic features in aging are: reduced bulk levels of core histones, altered pattern of histone post-translational modifications, changes in the pattern of DNA methylation, replacement of canonical histones with histone variants, and altered expression of non-coding RNA. The identification of epigenetic mechanisms may contribute to the early detection of age-associated subclinical changes or deficits at the molecular and/or cellular level, to predict the development of frailty, or even more interestingly, to improve health trajectories in older adults. Frailty reflects a state of increased vulnerability to stressors as a result of decreased physiologic reserves, and even dysregulation of multiple physiologic systems leading to adverse health outcomes for individuals of the same chronological age.

The nuclear retinoid-related orphan receptor RORα controls adipose tissue inflammation in patients with morbid obesity and diabetes.

Background/aims: Inflammation governs adipose tissue (AT) dysfunction in obesity. Retinoic acid receptor-related orphan receptor alpha (RORα) is associated with inflammation and insulin resistance in animal studies, but its role in human obesity remains elusive. We investigated the expression and function of RORα on AT inflammation in patients with morbid obesity with/without diabetes.

Bazedoxifene increases the proliferation of human arterial endothelial cells but does not affect the expression of cyclins A, B, and D1 and of p27.

Objective: Endothelial dysfunction and denudation are considered a first step in atherosclerosis. Endothelial proliferation is key for cellular repair. The effect of bazedoxifene on the vascular endothelium has not been explored.

Overexpression of glucose 6 phosphate dehydrogenase preserves mouse pancreatic beta cells function until late in life.

NAD(P)H donates electrons for reductive biosynthesis and antioxidant defense across all forms of life. Glucose-6-phosphate dehydrogenase (G6PD) is a critical enzyme to provide NADPH. G6PD deficiency is present in more than 400 million people worldwide.

L-selectin regulates human neutrophil transendothelial migration.

The migration of circulating neutrophils towards damaged or infected tissue is absolutely critical to the inflammatory response. L-selectin is a cell adhesion molecule abundantly expressed on circulating neutrophils. For over two decades, neutrophil L-selectin has been assigned the exclusive role of supporting tethering and rolling - the initial stages of the multi-step adhesion cascade.

Similar Clinical Course and Significance of Circulating Innate and Adaptive Immune Cell Counts in STEMI and COVID-19.

This study aimed to assess the time course of circulating neutrophil and lymphocyte counts and their ratio (NLR) in ST-segment elevation myocardial infarction (STEMI) and coronavirus disease (COVID)-19 and explore their associations with clinical events and structural damage. Circulating neutrophil, lymphocyte and NLR were sequentially measured in 659 patients admitted for STEMI and in 103 COVID-19 patients. The dynamics detected in STEMI (within a few hours) were replicated in COVID-19 (within a few days).

TET2-Loss-of-Function-Driven Clonal Hematopoiesis Exacerbates Experimental Insulin Resistance in Aging and Obesity.

Human aging is frequently accompanied by the acquisition of somatic mutations in the hematopoietic system that induce clonal hematopoiesis, leading to the development of a mutant clone of hematopoietic progenitors and leukocytes. This somatic-mutation-driven clonal hematopoiesis has been associated with an increased incidence of cardiovascular disease and type 2 diabetes, but whether this epidemiological association reflects a direct, causal contribution of mutant hematopoietic and immune cells to age-related metabolic abnormalities remains unexplored. Here, we show that inactivating mutations in the epigenetic regulator TET2, which lead to clonal hematopoiesis, aggravate age- and obesity-related insulin resistance in mice.

Comparative transcriptome analysis identifies CARM1 and DNMT3A as genes associated with osteoporosis.

To identify new candidate genes in osteoporosis, mainly involved in epigenetic mechanisms, we compared whole gene-expression in osteoblasts (OBs) obtained from women undergoing hip replacement surgery due to fragility fracture and severe osteoarthritis. Then, we analyzed the association of several SNPs with BMD in 1028 women. Microarray analysis yielded 2542 differentially expressed transcripts belonging to 1798 annotated genes, of which 45.

Autocrine CCL5 Effect Mediates Trastuzumab Resistance by ERK Pathway Activation in HER2-Positive Breast Cancer.

HER2-positive breast cancer is currently managed with chemotherapy in combination with specific anti-HER2 therapies, including trastuzumab. However, a high percentage of patients with HER2-positive tumors do not respond to trastuzumab (primary resistance) or either recur (acquired resistance), mostly due to molecular alterations in the tumor that are either unknown or undetermined in clinical practice. Those alterations may cause the tumor to be refractory to treatment with trastuzumab, promoting tumor proliferation and metastasis.

Predictors of live birth in women with a history of biochemical pregnancies after assisted reproduction treatment.

Objectives: To ascertain whether women with a history of biochemical pregnancies (BPs) in in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) treatment cycles have decreased chances of live birth (LB); and (2) to build a predictive model for LB in this particular population of infertile women.

Methods: In order to achieve the first objective, data from 1536 women that had a LB using autologous fresh or frozen embryos, or dropped out of further IVF/ICSI treatments after completing one to three unsuccessful treatment cycles were retrospectively analyzed. A subpopulation of 90 women that experienced one or more BPs in our assisted reproduction unit were selected to build a predictive logistic regression model for LB.

Acetogenins from Annonaceae family. Their potential biological applications.

The aim of this contribution has been to continue with the knowledge about newly isolated acetogenins from Annonaceae family for the last fifteen years. This review will report classification, extraction, isolation, elucidation of the structure, biological activities and mechanism of action of such interesting natural products. In fact, out of the 532 compounds reviewed, 115 previously non-described annonaceous acetogenins have been added to the list of isolated compounds from 2005 to May 2019.

Relaxant and antiadrenergic effects of ranolazine in human saphenous vein.

Objectives: Ranolazine improves vascular function in animal models. We evaluate the effects of ranolazine on vascular function and adrenergic response in human saphenous vein.

Methods: Rings from 53 patients undergoing coronary artery bypass grafting were mounted in organ baths.

Angiotensin II and leukocyte trafficking: New insights for an old vascular mediator. Role of redox-signaling pathways.

Inflammation and activation of the immune system are key molecular and cellular events in the pathogenesis of cardiovascular diseases, including atherosclerosis, hypertension-induced target-organ damage, and abdominal aortic aneurysm. Angiotensin II (Ang-II) is the main effector peptide hormone of the renin-angiotensin system. Beyond its role as a potent vasoconstrictor and regulator of blood pressure and fluid homeostasis, Ang-II is intimately involved in the development of vascular lesions in cardiovascular diseases through the activation of different immune cells.

1-(2'-Bromobenzyl)-6,7-dihydroxy--methyl-tetrahydroisoquinoline and 1,2-Demethyl-nuciferine as Agonists in Human D Dopamine Receptors.

Certain D-like dopamine receptor (DR) agonists are useful therapeutically as antiparkinsonian drugs, whereas D-like DR antagonists or partial agonists are proven effective as antipsychotics. Two isoquinoline derivatives, 1-(2'-bromobenzyl)-6,7-dihydroxy--methyl-tetrahydroisoquinoline (Br-BTHIQ, ) and 1,2-demethyl-nuciferine (aporphine, ), were herein synthesized, and their dopaminergic affinity in cloned human DR, DR, and DR subtypes and their behavior as agonists/antagonists were evaluated. They showed affinity values () for hD, hD, and hD DR within the nanomolar range.