Water and Electrolyte Content in Hypertension in the Skin (WHYSKI) in Primary Aldosteronism.

Background: Primary aldosteronism (PA), the most common curable salt-dependent form of arterial hypertension, features renal K loss and enhanced Na reabsorption. We investigated whether the electrolyte, water, and TonEBP (tonicity-responsive enhancer binding protein)/ (nuclear factor of activated T cells 5) content is altered in the skin of patients with PA and corrected by surgical cure.

Methods: We obtained skin biopsies from 80 subjects: 49 consecutive patients with PA, optimally treated with a mineralocorticoid receptor antagonist; 6 essential hypertensives; and 25 normotensive controls.

Improving laryngeal cancer detection using chaotic metaheuristics integration with squeeze-and-excitation resnet model.

Laryngeal cancer (LC) represents a substantial world health problem, with diminished survival rates attributed to late-stage diagnoses. Correct treatment for LC is complex, particularly in the final stages. This kind of cancer is a complex malignancy inside the head and neck region of patients.

Water and Electrolyte Content in Salt-Dependent HYpertension in the SKIn (WHYSKI): Effect of Surgical Cure of Primary Aldosteronism.

Unlabelled:  INTRODUCTION: This study will test the hypothesis that primary aldosteronism (PA) involves alterations in Na, K, and water content in the skin that are corrected by adrenalectomy.

Aim And Methods: In skin biopsies, we will measure the content of Na, K, water, by physical-chemical methods and the osmotic-stress-responsive transcription factor Tonicity-responsive Enhancer Binding Protein (TonEBP, NFAT5) mRNA copy number by droplet digital PCR, in sex-balanced cohorts of 18 -75-year-old consecutive consenting patients with unilateral and bilateral PA, primary (essential) hypertension, and normotension. Before surgery, the patients with unilateral PA will receive the mineralocorticoid receptor antagonist (MRA) canrenone at doses that correct hypokalemia and high blood pressure values.

[Sick fat (adiposopathy) as the main contributor to metabolic syndrome].

Obesity, primarily the accumulation of visceral fat (prone to lipolysis and inflammation) is considered the most important pathogenetic link in insulin resistance, metabolic syndrome and type 2 diabetes mellitus. of the review was to present and summarize current information on the negative impact of adipose tissue dysfunction and the role of this phenomenon in the pathogenesis of the metabolic syndrome and type 2 diabetes mellitus. .

From the Identification to the Dissection of the Physiological Role of the Mitochondrial Calcium Uniporter: An Ongoing Story.

The notion of mitochondria being involved in the decoding and shaping of intracellular Ca signals has been circulating since the end of the 19th century. Despite that, the molecular identity of the channel that mediates Ca ion transport into mitochondria remained elusive for several years. Only in the last decade, the genes and pathways responsible for the mitochondrial uptake of Ca began to be cloned and characterized.

PKA compartmentalization links cAMP signaling and autophagy.

Autophagy is a highly regulated degradative process crucial for maintaining cell homeostasis. This important catabolic mechanism can be nonspecific, but usually occurs with fine spatial selectivity (compartmentalization), engaging only specific subcellular sites. While the molecular machines driving autophagy are well understood, the involvement of localized signaling events in this process is not well defined.

Compartmentalized Signaling in Aging and Neurodegeneration.

The cyclic AMP (cAMP) signalling cascade is necessary for cell homeostasis and plays important roles in many processes. This is particularly relevant during ageing and age-related diseases, where drastic changes, generally decreases, in cAMP levels have been associated with the progressive decline in overall cell function and, eventually, the loss of cellular integrity. The functional relevance of reduced cAMP is clearly supported by the finding that increases in cAMP levels can reverse some of the effects of ageing.

Intracellular protein kinase CK2 inhibition by ferulic acid-based trimodal nanodevice.

Protein kinase CK2, a pleiotropic and constitutively active kinase, is strictly involved in different diseases, especially in cancer. Many efforts have been carried out to develop specific CK2 inhibitors and recently, it has been evidenced that ferulic acid (FA) represents a promising, albeit cell impermeable, CK2 inhibitor. In the present study, the potential of a nanotechnological approach to cope with intracellular CK2 regulation was explored.

Co-Loaded Curcumin and Methotrexate Nanocapsules Enhance Cytotoxicity against Non-Small-Cell Lung Cancer Cells.

: As part of the efforts to find natural alternatives for cancer treatment and to overcome the barriers of cellular resistance to chemotherapeutic agents, polymeric nanocapsules containing curcumin and/or methotrexate were prepared by an interfacial deposition of preformed polymer method. : Physicochemical properties, drug release experiments and in vitro cytotoxicity of these nanocapsules were performed against the Calu-3 lung cancer cell line. : The colloidal suspensions of nanocapsules showed suitable size (287 to 325 nm), negative charge (-33 to -41 mV) and high encapsulation efficiency (82.

Development of W/O/W emulsion with gallic acid in the internal aqueous phase.

The aim of this work is to develop a W/O/W multiple emulsion with gallic acid in the internal aqueous phase (W). A quantification method for gallic acid using HPLC-UV was developed and validated. In the first step, a simple W/O emulsion was prepared with distilled water, polyglycerol polyricinoleate, sodium chloride, gallic acid and pH 5.

Phosphorylation of p23-1 cochaperone by protein kinase CK2 affects root development in Arabidopsis.

Root growth is a fundamental process in plants and assures nutrient and water uptake required for efficient photosynthesis and metabolism. Postembryonic development of roots is controlled by the functionality of the meristem. Several hormones and signaling molecules regulate the size of the meristem, and among them, auxins play a major role.

Protein kinase CK2 subunits exert specific and coordinated functions in skeletal muscle differentiation and fusogenic activity.

Casein kinase 2 (CK2) is a tetrameric protein kinase composed of 2 catalytic (α and α') and 2 regulatory β subunits. Our study provides the first molecular and cellular characterization of the different CK2 subunits, highlighting their individual roles in skeletal muscle specification and differentiation. Analysis of C2C12 cell knockout for each CK2 subunit reveals that: ) CK2β is mandatory for the expression of the muscle master regulator myogenic differentiation 1 in proliferating myoblasts, thus controlling both myogenic commitment and subsequent muscle-specific gene expression and myotube formation; ) CK2α is involved in the activation of the muscle-specific gene program; and ) CK2α' activity regulates myoblast fusion by mediating plasma membrane translocation of fusogenic proteins essential for membrane coalescence, like myomixer.

Aldosterone Stimulates Its Biosynthesis Via a Novel GPER-Mediated Mechanism.

Context: The G protein-coupled estrogen receptor (GPER) mediates an aldosterone secretagogue effect of 17β-estradiol in human HAC15 adrenocortical cells after estrogen receptor β blockade. Because GPER mediates mineralocorticoid receptor-independent aldosterone effects in other cell types, we hypothesized that aldosterone could modulate its own synthesis via GPER activation.

Methods: HAC15 cells were exposed to aldosterone in the presence or absence of canrenone, a mineralocorticoid receptor antagonist, and/or of the selective GPER antagonist G36.

Сapsule endoscopy for diagnosis of celiac disease.

In this review we analyzed the guidelines for diagnosis and management of celiac disease, as well as the recent studies published on this issue. Capsule endoscopy could be used in patients unwilling or unable to undergo conventional endoscopy, in patients who have discordant results between serological and histopathological investigation, in patients with nonresponsive or refractory celiac disease.

Biotechnological applications of nanostructured hybrids of polyamine carbon quantum dots and iron oxide nanoparticles.

The combination of different nanomaterials has been investigated during the past few decades and represents an exciting challenge for the unexpected emerging properties of the resulting nano-hybrids. Spermidine (Spd), a biogenic polyamine, has emerged as a useful functional monomer for the development of carbon quantum dots (CQDs). Herein, an electrostatically stabilized ternary hybrid, constituted of iron oxide-DNA (the core) and spermidine carbon quantum dots (CQD, the shell), was self-assembled and fully characterized.

Methods to Measure Intracellular Ca Concentration Using Ca-Sensitive Dyes.

Ca ion is universally considered the most versatile second messenger responsible for decoding and regulating the majority of the signaling pathways within the cell. The study of intracellular Ca concentration ([Ca]) dynamics is consequently of primary importance for the interpretation of cellular biology. This chapter will present a relatively simple, largely diffused, and nevertheless robust method to measure variations of [Ca] by the use of the Ca-sensitive chemical dye Fura-2.

Recent advances in the molecular mechanism of mitochondrial calcium uptake.

In the last few decades, a large body of experimental evidence has highlighted the complex role for mitochondria in eukaryotic cells: they are not only the site of aerobic metabolism (thus providing most of the ATP supply for endergonic processes) but also a crucial checkpoint of cell death processes (both necrosis and apoptosis) and autophagy. For this purpose, mitochondria must receive and decode the wide variety of physiological and pathological stimuli impacting on the cell. The "old" notion that mitochondria possess a sophisticated machinery for accumulating and releasing Ca , the most common and versatile second messenger of eukaryotic cells, is thus no surprise.

Long-lasting anti-platelet activity of cilostazol from poly(ε-caprolactone)-poly(ethylene glycol) blend nanocapsules.

Cilostazol (CLZ) acts as a vasodilator and antiplatelet agent and is the main drug for the treatment of intermittent claudication (IC) related to peripheral arterial disease (PAD). The usual oral dose is 100 mg twice a day, which represents a disadvantage in treatment compliance. CLZ presents several side effects, such as headache, runny nose, and dizziness.

Evaluation of larvicidal activity and ecotoxicity of linalool, methyl cinnamate and methyl cinnamate/linalool in combination against Aedes aegypti.

The frequent use of synthetic pesticides to control Aedes aegypti population can lead to environmental and/or human contamination and the emergence of resistant insects. Linalool and methyl cinnamate are presented as an alternative to the synthetic pesticides, since they can exhibit larvicidal, repellent and/or insecticidal activity and are considered safe for use. The aim of this study was to evaluate the larvicidal activity of methyl cinnamate, linalool and methyl cinnamate/linalool in combination (MC-L) (1:4 ratio, respectively) against Aedes aegypti.

Loss-of-function mutations in the SIGMAR1 gene cause distal hereditary motor neuropathy by impairing ER-mitochondria tethering and Ca2+ signalling.

Distal hereditary motor neuropathies (dHMNs) are clinically and genetically heterogeneous neurological conditions characterized by degeneration of the lower motor neurons. So far, 18 dHMN genes have been identified, however, about 80% of dHMN cases remain without a molecular diagnosis. By a combination of autozygosity mapping, identity-by-descent segment detection and whole-exome sequencing approaches, we identified two novel homozygous mutations in the SIGMAR1 gene (p.

Spray-dried Eudragit® L100 microparticles containing ferulic acid: Formulation, in vitro cytoprotection and in vivo anti-platelet effect.

This paper aimed to obtain new spray-dried microparticles containing ferulic acid (FA) prepared by using a methacrylic polymer (Eudragit® L100). Microparticles were intended for oral use in order to provide a controlled release, and improved in vitro and in vivo biological effects. FA-loaded Eudragit® L100 microparticles were obtained by spray-drying.

Spray-dried solid dispersions containing ferulic acid: comparative analysis of three carriers, in vitro dissolution, antioxidant potential and in vivo anti-platelet effect.

This article aimed to improve the relative solubility and dissolution rate of ferulic acid (FA) by the use of spray-dried solid dispersions (SDs) in order to ensure its in vitro antioxidant potential and to enhance its in vivo anti-platelet effect. These SDs were prepared by spray-drying at 10 and 20% of drug concentration using polyvinylpyrrolidone K30 (PVP-K30), polyethylene glycol 6000 (PEG 6000) and poloxamer-188 (PLX-188) as carriers. SDs and physical mixtures (PM) were characterized by SEM, XRPD, FTIR spectroscopy and TGA analysis.

The presence of Microlobius foetidus cause changes in the antioxidant defense of Urochloa decumbens?

Urochloa decumbens (Stapf) R. D. Webster (Poaceae) is an exotic species with has spread rapidly through the Cerrado area of Pantanal, Mato Grosso do Sul, Brazil.

Design, validation and efficacy of bisubstrate inhibitors specifically affecting ecto-CK2 kinase activity.

By derivatizing the purely competitive CK2 inhibitor N1-(4,5,6,7-tetrabromo-1H-benzimidazol-2-yl)-propane-1,3-diamine (K137) at its 3-amino position with a peptidic fragment composed of three or four glutamic or aspartic acid residues, a new family of bisubstrate inhibitors has been generated whose ability to simultaneously interact with both the ATP and the phosphoacceptor substrate-binding sites has been probed by running mixed competition kinetics and by mutational mapping of the kinase residues implicated in substrate recognition. The most effective bisubstrate inhibitor, K137-E4, interacts with three functional regions of the kinase: the hydrophobic pocket close to the ATP-binding site, the basic residues of the p+1 loop that recognizes the acidic determinant at position n+1 and the basic residues of α-helixC that recognize the acidic determinant at position n+3. Compared with the parent inhibitor (K137), K137-E4 is severalfold more potent (IC50 25 compared with 130 nM) and more selective, failing to inhibit any other kinase as drastically as CK2 out of 140 enzymes, whereas 35 kinases are inhibited more potently than CK2 by K137.