Green Solid Lipid Nanoparticles by Fatty Acid Coacervation: An Innovative Nasal Delivery Tool for Drugs Targeting Cerebrovascular and Neurological Diseases.

Cerebrovascular and neurological diseases are characterized by neuroinflammation, which alters the neurovascular unit, whose interaction with the choroid plexus is critical for maintaining brain homeostasis and producing cerebrospinal fluid. Dysfunctions in such process can lead to conditions such as idiopathic normal pressure hydrocephalus, a common disease in older adults. Potential pharmacological treatments, based upon intranasal administration, are worthy of investigation because they might improve symptoms and avoid surgery by overcoming the blood-brain barrier and avoiding hepatic metabolism.

Evidence-Based Anti-Diabetic Properties of Plant from the Occitan Valleys of the Piedmont Alps.

Data on urban and rural diabetes prevalence ratios show a significantly lower presence of diabetes in rural areas. Several bioactive compounds of plant origin are known to exert anti-diabetic properties. Interestingly, most of them naturally occur in different plants present in mountainous areas and are linked to traditions of herbal use.

G protein-coupled receptor 21 in macrophages: An in vitro study.

GPR21 is an orphan and constitutively active receptor belonging to the superfamily of G-Protein Coupled Receptors (GPCRs). GPR21 couples to the G family of G proteins and is expressed in macrophages. Studies of GPR21 knock-out mice indicated that GPR21 may be involved in promoting macrophage migration.

CNS-Sparing Histamine H Receptor Antagonist as a Candidate to Prevent the Diabetes-Associated Gastrointestinal Symptoms.

Among the histamine receptors, growing evidence points to the histamine H receptor as a pharmacological candidate to counteract the autonomic neuropathy associated with diabetes. The study aimed to evaluate the effect of PF00868087 (also known as ZPL-868), a CNS-sparing histamine H receptor antagonist, on the autonomic neuropathy of the intestinal tract associated with diabetes. Diabetes was induced in male BALB/c mice by a single high dose of streptozotocin (150 mg/kg).

The Interplay between Histamine H Receptor and the Kidney Function: The Lesson from H Receptor Knockout Mice.

Previous studies implicated the histamine H receptor in renal pathophysiology. The aim here is to elucidate the role of this receptor on renal function using H receptor knockout mice (HR). Healthy and diabetic HR mice compared to their C57BL/6J wild-type counterpart for renal function and the expression of crucial tubular proteins.

GPR21 Inhibition Increases Glucose-Uptake in HepG2 Cells.

GPR21 is a constitutively active, orphan, G-protein-coupled receptor, with in vivo studies suggesting its involvement in the modulation of insulin sensitivity. However, its precise contribution is not fully understood. As the liver is both a major target of insulin signalling and critically involved in glucose metabolism, the aim of this study was to examine the role of GPR21 in the regulation of glucose uptake and production in human hepatocytes.

Superoxide Dismutase Administration: A Review of Proposed Human Uses.

Superoxide dismutases (SODs) are metalloenzymes that play a major role in antioxidant defense against oxidative stress in the body. SOD supplementation may therefore trigger the endogenous antioxidant machinery for the neutralization of free-radical excess and be used in a variety of pathological settings. This paper aimed to provide an extensive review of the possible uses of SODs in a range of pathological settings, as well as describe the current pitfalls and the delivery strategies that are in development to solve bioavailability issues.

Effect of Beta 3 Adrenoreceptor Modulation on Patency of the Ductus Arteriosus.

β3-adrenoreceptor (β3-AR), a G-protein coupled receptor, has peculiar regulatory properties in response to oxygen and widespread localization. β3-AR is expressed in the most frequent neoplasms, also occurring in pregnant women, and its blockade reduces tumor growth, indicating β3-AR-blockers as a promising alternative to antineoplastic drugs during pregnancy. However, β3-AR involvement in prenatal morphogenesis and the consequences of its blockade for the fetus remain unknown.

Strategies to expand the therapeutic potential of superoxide dismutase by exploiting delivery approaches.

The overproduction of free radicals can cause oxidative-stress damage to a range of biomolecules, and thus potentially contribute to several pathologies, from neurodegenerative disorders to cardiovascular diseases and metabolic disorders. Endogenous antioxidant enzymes, such as superoxide dismutase (SOD), play an important role in diminishing oxidative stress. SOD supplementation could therefore be an effective preventive strategy to reduce the risk of free-radical overproduction.

Nanosponges as protein delivery systems: Insulin, a case study.

Cyclodextrin-based nanosponges have been found to bepromising drug delivery systems. This paper investigates an application that still needs to be studied in depth, that is, the oral delivery of peptides and proteins, choosing insulin as a case study. The nanospongewas synthesized by crosslinkingβ-cyclodextrins withpyromellitic dianhydride, adopting a top-down approach for its subsequent formulation.

Sedentariness and Urinary Metabolite Profile in Type 2 Diabetic Patients, a Cross-Sectional Study.

Recent findings indicate a significant association between sedentary (SED)-time and type 2 diabetes mellitus(T2DM). The aim of this study was to investigate whether different levels of SED-time could impact on biochemical and physiological processes occurring in sedentary and physically inactive T2DM patients. In particular, patients from the "Italian Diabetes and Exercise Study (IDES)_2 trial belonging to the first and fourth quartile of SED-time were compared.

Post-translational inhibition of YAP oncogene expression by 4-hydroxynonenal in bladder cancer cells.

The transcriptional regulator YAP plays an important role in cancer progression and is negatively controlled by the Hippo pathway. YAP is frequently overexpressed in human cancers, including bladder cancer. Interestingly, YAP expression and activity can be inhibited by pro-oxidant conditions; moreover, YAP itself can also affect the cellular redox status through multiple mechanisms.

Effect of Bilastine on Diabetic Nephropathy in DBA2/J Mice.

Diabetic nephropathy is an unmet therapeutic need, and the search for new therapeutic strategies is warranted. Previous data point to histamine H receptor as a possible target for glomerular dysfunction associated with long term hyperglycaemia. Therefore, this study investigated the effects of the H receptor antagonist bilastine on renal morphology and function in a murine model of streptozotocin-induced diabetes.

Histamine in the kidneys: what is its role in renal pathophysiology?

Starting with a role for histamine role in renal haemodynamics, evidence has accumulated, over time, suggesting a wider range of actions on renal function and this has renewed interest in the pathophysiological role of histamine in the kidney. Here we provide an up-to-date review of this topic. As the kidney expresses enzymes that synthesize and metabolise histamine, along with its receptors, all the components for histaminergic transmission are present in this tissue.

Analyzing Cysteine Site Neighbors in Proteins to Reveal Dimethyl Fumarate Targets.

This work proposes a novel approach by which to consistently classify cysteine sites in proteins in terms of their reactivity toward dimethyl fumarate (DMF) and fumarate. Dimethyl fumarate-based drug products have been approved for use as oral treatments for psoriasis and relapsing-remitting multiple sclerosis. The adduction of DMF and its (re)active metabolites to certain cysteine residues in proteins is thought to underlie their effects.

Histamine and diabetic nephropathy: an up-to-date overview.

The classification of diabetic nephropathy (DN) as a vascular complication of diabetes makes the possible involvement of histamine, an endogenous amine that is well known for its vasoactive properties, an interesting topic for study. The aim of the present review is to provide an extensive overview of the possible involvement of histamine in the onset and progression of DN. The evidence collected on the role of histamine in kidney function together with its well-known pleiotropic action suggest that this amine may act simultaneously on glomerular hyperfiltration, tubular inflammation, fibrosis development and tubular hypertrophy.

Histamine H receptor antagonism prevents the progression of diabetic nephropathy in male DBA2/J mice.

Due to the incidence of diabetes and the related morbidity of diabetic nephropathy, identification of new therapeutic strategies represents a priority. In the last few decades new and growing evidence on the possible role of histamine in diabetes has been provided. In particular, the histamine receptor HR is emerging as a new promising pharmacological target for diabetic nephropathy.

Solid lipid nanoparticles delivering anti-inflammatory drugs to treat inflammatory bowel disease: Effects in an model.

Aim: To improve anti-inflammatory activity while reducing drug doses, we developed a nanoformulation carrying dexamethasone and butyrate.

Methods: Dexamethasone cholesteryl butyrate-solid lipid nanoparticles (DxCb-SLN) were obtained with the warm microemulsion method. The anti-inflammatory activity of this novel nanoformulation has been investigated (cell adhesion to human vascular endothelial cells and pro-inflammatory cytokine release by lipopolysaccharide-induced polymorphonuclear cells) and (disease activity index and cytokine plasma concentrations in a dextran sulfate sodium-induced mouse colitis) models.

Histamine type 1-receptor activation by low dose of histamine undermines human glomerular slit diaphragm integrity.

Histamine has been reported to decrease the ultrafiltration coefficient, which inversely correlates with glomerular permselectivity, however the mechanism(s) underling this effect have never been investigated. This study aimed to assess whether histamine could exert a direct detrimental effect on podocyte permeability and the possible involvement of two key proteins for the glomerular slit diaphragm (SD) integrity, zonula occludens-1 (ZO-1) and P-cadherin. The effect of histamine (100 pM-1000nM) on coloured podocytes junctional integrity was evaluated functionally by a transwell assay of monolayer permeability and morphologically by electron microscopy.

Role of histamine H4 receptor ligands in bleomycin-induced pulmonary fibrosis.

Fibrosis of lung tissue is a disease where a chronic inflammatory process determines a pathological remodelling of lung parenchyma. The animal model obtained by intra-tracheal administration of bleomycin in C57BL/6 mice is one of the most validated murine model. Bleomycin stimulates oxidative stress and the production of pro-inflammatory mediators.

Histamine in diabetes: Is it time to reconsider?

The first studies of histamine and diabetes date back to the 1950s. Since that time the involvement of histamine in diabetes was related to its well known vasoactive properties and permeability leakage effects. In particular, the first evidence for a correlation between histamine and diabetes arose in 1989 when an increase in plasma and leucocyte histamine content was observed.

H3 receptor renal expression in normal and diabetic rats.

Introduction: To extend our previous observation of H4R upregulation in the kidney of diabetic rats, we evaluated in the same specimens the presence of the H3R.

Materials And Methods: Kidney specimens from 24 8-week-old male Wistar rats (12 non-diabetic and 12 diabetic animals) were processed for both immunohistochemical and immunofluorescence analyses.

Results And Conclusion: H3R is expressed in the apical membrane by collecting duct cells in the kidney of rats and it is significantly increased in diabetic animals.

Histamine receptor expression in human renal tubules: a comparative pharmacological evaluation.

Objective And Design: The aim of this study is to evaluate the expression of the histamine receptors, particularly focusing on the H4R in human renal tubules.

Material: The ex vivo evaluation was carried on specimens from human renal cortex. Primary and immortalized tubular epithelial cells (TECs) and the HK-2 cell line were used as in vitro models.