Angiotensin-converting enzymes 1 and 2 in the feces: presence and catalytic activity in the rat 2,4,6-trinitrobenzene sulfonic acid-induced model of colitis.

Background And Aim: Inflammatory bowel disease is challenging to diagnose. Fecal biomarkers offer noninvasive solutions. The renin-angiotensin-aldosterone system is implicated in intestinal inflammation.

β-Adrenoceptor Activation Favor Acquisition of Tumorigenic Properties in Non-Tumorigenic MCF-10A Breast Epithelial Cells.

Noradrenaline and adrenaline, and their cognate receptors, are currently accepted to participate in cancer progression. They may also participate in cancer initiation, although their role in this phase is much less explored. The aim of this work was to study the influence of adrenergic stimulation in several processes related to breast cancer carcinogenesis, using several adrenergic agonists in the MCF-10A non-tumorigenic breast cells.

Comparative Studies on the Photoreactivity, Efficacy, and Safety of Depigmenting Agents.

Depigmenting products are increasingly used to counteract skin hyperpigmentation and related psychosocial issues. This study aimed to compare different depigmenting agents-4-butylresorcinol; bakuchiol; tranexamic acid; ascorbyl glucoside; α-arbutin; and ascorbic acid-for photoreactivity; tyrosinase inhibition; and safety. Photoreactivity was assessed using the Reactive Oxygen Species assay.

Involvement of P2Y, P2Y, A and A Receptors in the Purinergic Inhibition of NMDA-Evoked Noradrenaline Release in the Rat Brain Cortex.

In the cerebral cortex, glutamate activates NMDA receptors (NMDARs), localized in noradrenergic neurons, inducing noradrenaline release that may have a permissive effect on glutamatergic transmission, and therefore, on the modulation of long-term plasticity. ATP is co-released with noradrenaline, and with its metabolites (ADP and adenosine) is involved in the purinergic modulation of electrically-evoked noradrenaline release. However, it is not known if noradrenaline release evoked by activation of NMDARs is also under purinergic modulation.

ACE and ACE2 catalytic activity in the fecal content along the gut.

Background: Angiotensin-converting enzyme (ACE) and ACE2 are two major enzymes of the renin-angiotensin-aldosterone system (RAAS), which control the formation/degradation of angiotensin (Ang) II and Ang1-7, regulating their opposite effects. We aimed at evaluating the catalytic activity of ACE and ACE2 in the intestinal content and corresponding intestinal tissue along the gut of Wistar Han rats.

Methods: Portions of the ileum, cecum, proximal colon, and distal colon, and the corresponding intestinal content were collected from Wistar Han rats.

Long-term 1,2-dimethylhydrazine triggers pathological remodeling of colon mucosa through repression of sestrin2, nuclear factor (erythroid-derived 2)-like 2, and sirtuin4 stimulating mitochondrial stress and metabolic reprogramming.

1,2-Dimethylhydrazine (DMH) is a plant toxicant that enters the food web through the diet. It is biotransformed into azoxymethane, a colon carcinogen, during the first hepatic passage. In mice, this study assessed the role of glutamate dehydrogenase (GDH), a key glutaminolysis enzyme in DMH-induced colorectal cancer (CRC).

Activation of β-Adrenoceptors Promotes Lipid Droplet Accumulation in MCF-7 Breast Cancer Cells via cAMP/PKA/EPAC Pathways.

Physiologically, β-adrenoceptors are major regulators of lipid metabolism, which may be reflected in alterations in lipid droplet dynamics. β-adrenoceptors have also been shown to participate in breast cancer carcinogenesis. Since lipid droplets may be seen as a hallmark of cancer, the present study aimed to investigate the role of β-adrenoceptors in the regulation of lipid droplet dynamics in MCF-7 breast cancer cells.

Contribution of adrenergic mechanisms for the stress-induced breast cancer carcinogenesis.

Breast cancer is the most common and deadliest type of cancer in women. Stress exposure has been associated with carcinogenesis and the stress released neurotransmitters, noradrenaline and adrenaline, and their cognate receptors, can participate in the carcinogenesis process, either by regulating tumor microenvironment or by promoting systemic changes. This work intends to provide an overview of the research done in this area and try to unravel the role of adrenergic ligands in the context of breast carcinogenesis.

β-Adrenoceptor Activation in Breast MCF-10A Cells Induces a Pattern of Catecholamine Production Similar to that of Tumorigenic MCF-7 Cells.

Adrenaline, which participates in the neuroendocrine response that occurs during stress and perimenopause, may be tumorigenic. This exploratory study aimed at investigating whether non-tumorigenic and tumorigenic human breast epithelial cell lines are able to synthesize adrenaline. The study was carried out in non-tumorigenic (MCF-10A) and tumorigenic (MCF-7) human breast cell lines.

Intracellular adenosine released from THP-1 differentiated human macrophages is involved in an autocrine control of Leishmania parasitic burden, mediated by adenosine A and A receptors.

Leishmania infected macrophages have conditions to produce adenosine. Despite its known immunosuppressive effects, no studies have yet established whether adenosine alter Leishmania parasitic burden upon macrophage infection. This work aimed at investigating whether endogenous adenosine exerts an autocrine modulation of macrophage response towards Leishmania infection, identifying its origin and potential pharmacological targets for visceral leishmaniasis (VL), using THP-1 differentiated macrophages.

Microglia P2Y Receptors Prevent Astrocyte Proliferation Mediated by P2Y Receptors.

Cerebral inflammation is a common feature of several neurodegenerative diseases that requires a fine interplay between astrocytes and microglia to acquire appropriate phenotypes for an efficient response to neuronal damage. During brain inflammation, ATP is massively released into the extracellular medium and converted into ADP. Both nucleotides acting on P2 receptors, modulate astrogliosis through mechanisms involving microglia-astrocytes communication.

Pharmacological modulation of HDAC1 and HDAC6 in vivo in a zebrafish model: Therapeutic implications for Parkinson's disease.

Histone deacetylases (HDACs) are key epigenetic enzymes and emerging drug targets in cancer and neurodegeneration. Pan-HDAC inhibitors provided neuroprotection in Parkinson's Disease (PD) models, however, the HDAC isoforms with highest neuroprotective potential remain unknown. Zebrafish larvae (powerful pharmacological testing tools bridging cellular and in vivo studies) have thus far been used in PD modelling with limited phenotypic characterization.

Microglia P2Y₆ receptors mediate nitric oxide release and astrocyte apoptosis.

Background: During cerebral inflammation uracil nucleotides leak to the extracellular medium and activate glial pyrimidine receptors contributing to the development of a reactive phenotype. Chronically activated microglia acquire an anti-inflammatory phenotype that favors neuronal differentiation, but the impact of these microglia on astrogliosis is unknown. We investigated the contribution of pyrimidine receptors to microglia-astrocyte signaling in a chronic model of inflammation and its impact on astrogliosis.

Purinergic modulation of norepinephrine release and uptake in rat brain cortex: contribution of glial cells.

The pathogenesis of psychiatric and neurodegenerative diseases is often associated with a deregulation of noradrenergic transmission. Considering the potential involvement of purinergic signaling in the modulation of noradrenergic transmission in the brain cortex, this study aimed to identify the P2Y receptor subtypes involved in the modulation of neuronal release and neuronal/glial uptake of norepinephrine. Electrical stimulation (100 pulses at 5 Hz) of rat cortical slices induced norepinephrine release that was inhibited by ATP and ADP (0.

P2Y receptors on astrocytes and microglia mediate opposite effects in astroglial proliferation.

Nucleotides released upon brain injury signal to astrocytes and microglia playing an important role in astrogliosis, but the participation of microglia in the purinergic modulation of astrogliosis is still unclear. Highly enriched astroglial cultures and co-cultures of astrocytes and microglia were used to investigate the influence of microglia in the modulation of astroglial proliferation mediated by nucleotides. In highly enriched astroglial cultures, adenosine-5'-triphosphate (ATP), adenosine 5'-O-(3-thio)-triphosphate (ATPγS), adenosine 5'-O-(3-thio)-diphosphate (ADPβS; 0.

Functional crosstalk of prejunctional receptors on the modulation of noradrenaline release in mesenteric vessels: A differential study of artery and vein.

The role of angiotensin II receptors, bradykinin receptors and β-adrenoceptors in the modulation of noradrenaline release and the influence of α(2)-autoinhibition in these effects was investigated in the mesenteric artery and vein. Rings of mesenteric vessels of male Wistar rats were labelled with [(3)H]-noradrenaline and the effects of modulators on tritium overflow evoked by 100 pulses at 2Hz (marked α(2)-autoinhibition) and by 20 pulses at 50Hz or 100 pulses at 2Hz plus yohimbine (1μM; reduced α(2)-autoinhibition) were evaluated. Angiotensin II and bradykinin enhanced noradrenaline release evoked by 100 pulses at 2Hz, in a concentration-dependent manner, in both vessels.

The P2Y(1) and P2Y(12) receptors mediate autoinhibition of transmitter release in sympathetic innervated tissues.

In the sympathetic nervous system, ATP is a co-transmitter and modulator of transmitter release, inhibiting noradrenaline release by acting on P2Y autoreceptors, but in peripheral tissues the subtypes involved have only scarcely been identified. We investigated the identity of the noradrenaline release-inhibiting P2Y subtypes in the epididymal portion of vas deferens and tail artery of the rat. The subtypes operating as autoreceptors, the signalling mechanism and cross-talk with alpha(2)-autoreceptors, was also investigated in the epididymal portion.

Interaction between adenosine A 2B-receptors and alpha2-adrenoceptors on the modulation of noradrenaline release in the rat vas deferens: possible involvement of a group 2 adenylyl cyclase isoform.

In the prostatic portion of rat vas deferens, activation of adenosine A 2B-receptors, beta2-adrenoceptors, adenylyl cyclase or protein kinase A caused a facilitation of noradrenaline release. Blockade of alpha2-adrenoceptors with yohimbine (1 microM) attenuated the facilitation mediated by adenosine A 2B-receptors and by direct activation of adenylyl cyclase with forskolin but not that mediated by beta2-adrenoceptors or by direct activation of protein kinase A with 8-bromoadenosine-3',5'-cyclicAMP. The adenosine A 2B- and the beta2-adrenoceptor-mediated facilitation was prevented by the adenylyl cyclase inhibitors, 2',5'-dideoxy-adenosine (3 microM) and 9-cyclopentyladenine (100 microM), at concentrations that also attenuated the release enhancing effect of forskolin, but were not changed by the phospholipase C inhibitor 1-[6-[((17beta)-3-methoxyestra-1,3,5[10]-trien-17-yl)amino]hexyl]-1H-pyrrole-2,5-dione (U-73122, 1 microM).

Coupling to protein kinases A and C of adenosine A2B receptors involved in the facilitation of noradrenaline release in the prostatic portion of rat vas deferens.

In the prostatic portion of rat vas deferens, the non-selective adenosine receptor agonist NECA (0.1-30 microM), but not the A(2A) agonist CGS 21680 (0.001-10 microM), caused a facilitation of electrically evoked noradrenaline release (up to 43 +/- 4%), when inhibitory adenosine A(1) receptors were blocked.