Oxidative stress damage circumscribed to the central temporal retinal pigment epithelium in early experimental non-exudative age-related macular degeneration.

Non-exudative age-related macular degeneration (NE-AMD) represents the leading cause of blindness in the elderly. The macular retinal pigment epithelium (RPE) lies in a high oxidative environment because its high metabolic demand, mitochondria concentration, reactive oxygen species levels, and macular blood flow. It has been suggested that oxidative stress-induced damage to the RPE plays a key role in NE-AMD pathogenesis.

Plantar lymphatic network.

Anatomical descriptions of the lymphatic system of the foot remain imprecise. In the present report, we aim to elucidate the anatomical lymphatic plantar network in order to improve current clinical practice on the foot. Lower limbs from a total of 25 human cadavers, 4 amputated limbs, and 8 term fetuses were studied.

Histamine receptors and cancer pharmacology: an update.

In the present review, we will discuss the recent advances in the understanding of the role of histamine and histamine receptors in cancer biology. The controversial role of the histaminergic system in different neoplasias including gastric, colorectal, oesophageal, oral, pancreatic, liver, lung, skin, blood and breast cancers will be reviewed. The expression of histamine receptor subtypes, with special emphasis on the histamine H receptor, in different cell lines and human tumours, the signal transduction pathways and the associated biological responses as well as the in vivo treatment of experimental tumours with pharmacological ligands will be described.

Transient Receptor Potential Canonical 3 and Nuclear Factor of Activated T Cells C3 Signaling Pathway Critically Regulates Myocardial Fibrosis.

Aims: Cardiac fibroblasts (CFs) are emerging as major contributors to myocardial fibrosis (MF), a final common pathway of many etiologies of heart disease. Here, we studied the functional relevance of transient receptor potential canonical 3 (TRPC3) channels and nuclear factor of activated T cells c3 (NFATc3) signaling in rodent and human ventricular CFs, and whether their modulation would limit MF.

Results: A positive feedback loop between TRPC3 and NFATc3 drove a rat ventricular CF fibrotic phenotype.

Brain Structural and Amyloid Correlates of Recovery From Semantic Interference in Cognitively Normal Individuals With or Without Family History of Late-Onset Alzheimer's Disease.

Failure to recover from proactive semantic interference (frPSI) has been shown to be more sensitive than traditional cognitive measures in different populations with preclinical Alzheimer's disease. The authors sought to characterize the structural and amyloid in vivo correlates of frPSI in cognitively normal offspring of patients with late-onset Alzheimer's disease (O-LOAD), compared with individuals without a family history of neurodegenerative disorders (CS). The authors evaluated the LASSI-L, a test tapping frPSI and other types of semantic interference and delayed recall on the RAVLT, along with 3-T MRI volumetry and positron emission tomography Pittsburgh compound B, in 27 O-LOAD and 18 CS with equivalent age, sex, years of education, ethnicity, premorbid intelligence, and mood symptoms.

M1 Macrophage Polarization Is Dependent on TRPC1-Mediated Calcium Entry.

Macrophage plasticity is essential for innate immunity, but in-depth signaling mechanism(s) regulating their functional phenotypes are ill-defined. Here we report that interferon (IFN) γ priming of naive macrophages induces store-mediated Ca entry and inhibition of Ca entry impairs polarization to M1 inflammatory phenotype. In vitro and in vivo functional analyses revealed ORAI1 to be a primary contributor to basal Ca influx in macrophages, whereas IFNγ-induced Ca influx was mediated by TRPC1.

Transient receptor potential channel 6 knockdown prevents apoptosis of renal tubular epithelial cells upon oxidative stress via autophagy activation.

Reactive oxygen species (ROS) are generated under various pathological conditions such as renal ischemia/reperfusion (I/R) injury and provoke damage to multiple cellular organelles and processes. Overproduction of ROS causes oxidative stress and contributes to damages of renal proximal tubular cells (PTC), which are the main cause of the pathogenesis of renal I/R injury. Autophagy is a dynamic process that removes long-lived proteins and damaged organelles via lysosome-mediated degradation, which has an antioxidant effect that relieves oxidative stress.

Hours of service regulations for professional drivers in continental Latin America.

Objectives: To describe the hours of service provisions in continental Latin America.

Design: Information on regulations of service hours was extracted from either the national transportation authorities or ministries of transportation (or the equivalent institution) from each country.

Setting: Seventeen sovereign countries in continental Latin America (Argentina, Bolivia, Brazil, Chile, Colombia, Costa Rica, Ecuador, El Salvador, Guatemala, Honduras, Mexico, Nicaragua, Panama, Paraguay, Peru, Uruguay, Venezuela).

Heterotrimeric G-protein subunit Gα contributes to agonist-sensitive apoptosis and degranulation in murine platelets.

Gα , a heterotrimeric G-protein subunit, regulates various cell functions including ion channel activity, cell differentiation, proliferation and apoptosis. Platelet-expressed Gα is decisive for the extent of tissue injury following ischemia/reperfusion. However, it is not known whether Gα plays a role in the regulation of platelet apoptosis, which is characterized by caspase activation, cell shrinkage and cell membrane scrambling with phosphatidylserine (PS) translocation to the platelet surface.

Radiosensitivity enhancement of human thyroid carcinoma cells by the inhibitors of histone deacetylase sodium butyrate and valproic acid.

Radiotherapy is one of the leading treatments for clinical cancer therapy. External beam radiotherapy has been proposed as an adjuvant treatment for patients bearing differentiated thyroid cancer refractory to conventional therapy. Our purpose was to study the combined effect of HDAC inhibitors (HDACi) and ionizing irradiation in thyroid cancer cell lines (Nthy-ori 3-1, WRO, TPC-1 and 8505c).

Melanopsin Phototransduction Is Repurposed by ipRGC Subtypes to Shape the Function of Distinct Visual Circuits.

Melanopsin is expressed in distinct types of intrinsically photosensitive retinal ganglion cells (ipRGCs), which drive behaviors from circadian photoentrainment to contrast detection. A major unanswered question is how the same photopigment, melanopsin, influences such vastly different functions. Here we show that melanopsin's role in contrast detection begins in the retina, via direct effects on M4 ipRGC (ON alpha RGC) signaling.

Immunomodulatory role of histamine H4 receptor in breast cancer.

Background: Although the role of histamine H4 receptor (H4R) in immune cells is being extensively investigated, its immunomodulatory function in cancer is completely unknown. This study aimed to investigate the role of H4R in antitumour immunity in a model of triple-negative breast cancer.

Methods: We evaluated growth parameters, histological characteristics and the composition of tumour, splenic and tumour draining lymph node (TDLN) immune subsets, in a syngeneic model, developed orthotopically with 4T1 cells in H4R knockout (H4R-KO) and wild-type mice.

Gαi Proteins are Indispensable for Hearing.

Background/aims: From invertebrates to mammals, Gαi proteins act together with their common binding partner Gpsm2 to govern cell polarization and planar organization in virtually any polarized cell. Recently, we demonstrated that Gαi3-deficiency in pre-hearing murine cochleae pointed to a role of Gαi3 for asymmetric migration of the kinocilium as well as the orientation and shape of the stereociliary ("hair") bundle, a requirement for the progression of mature hearing. We found that the lack of Gαi3 impairs stereociliary elongation and hair bundle shape in high-frequency cochlear regions, linked to elevated hearing thresholds for high-frequency sound.

Extracellular pH and lung infections in cystic fibrosis.

Cystic fibrosis (CF) is an autosomal recessive disease caused by CFTR mutations. It is characterized by high NaCl concentration in sweat and the production of a thick and sticky mucus, occluding secretory ducts, intestine and airways, accompanied by chronic inflammation and infections of the lungs. This causes a progressive and lethal decline in lung function.

A NOX4/TRPC6 Pathway in Podocyte Calcium Regulation and Renal Damage in Diabetic Kidney Disease.

Loss of glomerular podocytes is an indicator of diabetic kidney disease (DKD). The damage to these cells has been attributed in part to elevated intrarenal oxidative stress. The primary source of the renal reactive oxygen species, particularly HO, is NADPH oxidase 4 (NOX4).

Balance of Go1α and Go2α expression regulates motor function via the striatal dopaminergic system.

The heterotrimeric G-protein Go with its splice variants, Go1α and Go2α, seems to be involved in the regulation of motor function but isoform-specific effects are still unclear. We found that Go1α-/- knockouts performed worse on the rota-rod than Go2α-/- and wild-type (WT) mice. In Go1+2α-/- mice motor function was partially recovered.

Regional Heterogeneity of D2-Receptor Signaling in the Dorsal Striatum and Nucleus Accumbens.

Dopamine input to the dorsal and ventral striatum originates from separate populations of midbrain neurons. Despite differences in afferent inputs and behavioral output, little is known about how dopamine release is encoded by dopamine receptors on medium spiny neurons (MSNs) across striatal subregions. Here we examined the activation of D2 receptors following the synaptic release of dopamine in the dorsal striatum (DStr) and nucleus accumbens (NAc) shell.

Chemical Characterization of an Encapsulated Red Wine Powder and Its Effects on Neuronal Cells.

Red wine polyphenols are known for their implications for human health protection, although they suffer from high instability. For this reason, a red wine powder was prepared by freeze-drying encapsulation in maltodextrin/arabic gum matrix, and its composition was determined by means of high-performance liquid chromatography coupled quadrupole time-of-flight mass spectrometry (HPLC-MS-QTOF). More than thirty polyphenols, including anthocyanins, flavanols, flavonols, phenolic acids and stilbenoids, were identified.

Nicotine Modulates Mitochondrial Dynamics in Hippocampal Neurons.

Mitochondria are widely recognized as fundamental organelles for cellular physiology and constitute the main energy source for different cellular processes. The location, morphology, and interactions of mitochondria with other organelles, such as the endoplasmic reticulum (ER), have emerged as critical events capable of determining cellular fate. Mitochondria-related functions have proven particularly relevant in neurons; mitochondria are necessary for proper neuronal morphogenesis and the highly energy-demanding synaptic transmission process.

N-acetyl cysteine reverts the proinflammatory state induced by cigarette smoke extract in lung Calu-3 cells.

Chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF) are lethal pulmonary diseases. Cigarette consumption is the main cause for development of COPD, while CF is produced by mutations in the CFTR gene. Although these diseases have a different etiology, both share a CFTR activity impairment and proinflammatory state even under sterile conditions.

Chronic stress promotes colitis by disturbing the gut microbiota and triggering immune system response.

Chronic stress is known to promote inflammatory bowel disease (IBD), but the underlying mechanism remains largely unresolved. Here, we found chronic stress to sensitize mice to dextran sulfate sodium (DSS)-induced colitis; to increase the infiltration of B cells, neutrophils, and proinflammatory ly6C macrophages in colonic lamina propria; and to present with decreased thymus and mesenteric lymph node (MLN) coefficients. Circulating total white blood cells were significantly increased after stress, and the proportion of MLN-associated immune cells were largely changed.

Depression promotes prostate cancer invasion and metastasis via a sympathetic-cAMP-FAK signaling pathway.

Depression drives cancer progression and induces poor clinical outcome. However, the mechanisms underlying depression and cancer outcomes are unclear. In this work, we investigated 98 prostate cancer patients and found that patients with high score of psychological depression were correlated with tumor invasion and metastasis.

Antidepression action of BDNF requires and is mimicked by Gαi1/3 expression in the hippocampus.

Stress-related alterations in brain-derived neurotrophic factor (BDNF) expression, a neurotrophin that plays a key role in synaptic plasticity, are believed to contribute to the pathophysiology of depression. Here, we show that in a chronic mild stress (CMS) model of depression the Gαi1 and Gαi3 subunits of heterotrimeric G proteins are down-regulated in the hippocampus, a key limbic structure associated with major depressive disorder. We provide evidence that Gαi1 and Gαi3 (Gαi1/3) are required for the activation of TrkB downstream signaling pathways.

Inhibition of TRPC1-Dependent Store-Operated Calcium Entry Improves Synaptic Stability and Motor Performance in a Mouse Model of Huntington's Disease.

Background: Huntington disease (HD) is a dominantly inherited neurodegenerative disorder caused by a CAG repeat expansion in the huntingtin gene. We previously discovered that mutant Huntingtin sensitizes type 1 inositol 1,4,5-trisphosphate receptor (InsP3R1) to InsP3. This causes calcium leakage from the endoplasmic reticulum (ER) and a compensatory increase in neuronal store-operated calcium (nSOC) entry.

TRPC proteins contribute to development of diabetic retinopathy and regulate glyoxalase 1 activity and methylglyoxal accumulation.

Objective: Diabetic retinopathy (DR) is induced by an accumulation of reactive metabolites such as ROS, RNS, and RCS species, which were reported to modulate the activity of cation channels of the TRPC family. In this study, we use Trpc1/4/5/6 compound knockout mice to analyze the contribution of these TRPC proteins to diabetic retinopathy.

Methods: We used Nanostring- and qPCR-based analysis to determine mRNA levels of TRPC channels in control and diabetic retinae and retinal cell types.