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1. Introduction Irisin, a newly identified hormone containing 112 amino acids that is secreted mainly by skeletal muscle cells during exercise, is a cleavage product of fibronectin type III domain-containing [...], This study investigated the effects of irisin on vascular smooth muscle contractility in rat thoracic aorta, and the hypothesis that mitogen-activated protein kinase kinase (MEK1/2) signaling pathway, voltage-gated potassium ([K.sub.V]) channels, small-conductance calcium-activated potassium ([SK.sub.Ca]) channels, and large-conductance calcium-activated potassium ([BK.sub.Ca]) channels may have roles in these effects. Isometric contraction-relaxation responses of isolated thoracic aorta rings were measured with an organ bath model. The steady contraction was induced with [10.sup.-5] M phenylephrine (PHE), and then the concentration-dependent responses of irisin ([10.sup.-9] - [10.sup.-6] M) were examined in endothelium-intact and - denuded rat thoracic aortas. Also, the effects of irisin incubations on PHE-mediated contraction and acetylcholine (ACh)--mediated relaxation were studied. Irisin exerted the vasorelaxant effects in both endothelium-intact and -denuded aortic rings at concentrations of [10.sup.-8], [10.sup.-7], and [10.sup.-6] M compared with the control groups (p < 0.001). Besides, pre-incubation of aortic rings with irisin (10 nM, 100 nM, or 1 [micro]M for 30 min) augmented ACh-mediated ([10.sup.9] - [10.sup.5]) vasodilation in PHE-precontracted thoracic aorta segments but did not modulate PHE-mediated ([10.sup.9] - [10.sup.5]) contraction. In addition, MEK1/2 inhibitor U0126, [K.sub.V] channel blocker XE-991, [SK.sub.Ca] channel blocker apamin, and [BK.sub.Ca] channel blocker tetraethylammonium (TEA) incubations significantly inhibited the irisin-induced relaxation responses. In conclusion, the first physiological findings were obtained regarding the functional relaxing effects of irisin in rat thoracic aorta. The findings demonstrated that irisin induces relaxation responses in endothelium-intact and (or) endothelium-denuded aortic rings in a concentration-dependent manner. Furthermore, this study is the first to report that irisin-induced relaxation responses are related to the activity of the MEK1/2 pathway, [K.sub.V] channels, and calcium-activated [K.sup.+] ([SK.sub.Ca] and [BK.sub.Ca]) channels. Key words: irisin, rat thoracic aorta, vasodilation, mitogen-activated protein kinase kinase, potassium channels. Cette etude portait sur les effets de l&apos;irisine sur la contractilite du muscle lisse vasculaire dans l&apos;aorte thoracique de rat, avec pour hypothese que la voie de signalisation de la MEK1/2 (pour << mitogen-activated protein kinase kinase >>), les canaux potassiques dependants du voltage ([K.sub.V]), les canaux potassiques a faible conductance actives par le calcium ([SK.sub.Ca]) et les canaux potassiques a conductance elevee actives par le calcium ([BK.sub.Ca]) peuvent jouer un role dans ces effets. Nous avons mesure la contraction et la relaxation isometriques dans des anneaux isoles d&apos;aorte thoracique en bain d&apos;organe. Nous avons obtenu la contraction stable a l&apos;aide de phenylephrine (PHE) a [10.sup.-5] M, puis examine les reactions dependantes des concentrations d&apos;irisine ([10.sup.-9] - [10.sup.-6] M) dans des aortes thoraciques de rats denudees et dont l&apos;endothelium etait intact. Nous avons aussi etudie les effets de l&apos;incubation en presence d&apos;irisine sur la contraction mediee par la PHE et la relaxation mediee par l&apos;acetylcholine (ACh). Dans les anneaux dont l&apos;endothelium etait intact comme denudes, l&apos;irisine entrainait des effets vasorelaxants plus marques que chez les temoins a des concentrations de [10.sup.-8], de [10.sup.-7] et de [10.sup.-6] M (p < 0,001). Par ailleurs, l&apos;incubation prealable des anneaux aortiques en presence d&apos;irisine (10 nM, 100 nM ou 1 [micro]M pendant 30 minutes) entrainait une augmentation de la vasodilatation mediee par l&apos;ACh ([10.sup.9] - [10.sup.5]) dans les segments d&apos;aorte thoracique precontractes a l&apos;aide de PHE, mais sans modulation de la contraction mediee par la PHE ([10.sup.9] - [10.sup.5]). De plus, l&apos;incubation en presence de U0126 (un inhibiteur de la MEK1/2), de XE-991 (un bloqueur des canaux [K.sub.V]), d&apos;apamine (un bloqueur des canaux [SK.sub.Ca]) et de tetraethylammonium (ou TEA, un bloqueur des canaux [BK.sub.Ca]) entrainait une inhibition marquee de la relaxation entrainee par l&apos;irisine. En conclusion, nous avons obtenu les premiers resultats physiologiques quant a la relaxation fonctionnelle entrainee par l&apos;irisine dans l&apos;aorte thoracique chez le rat. Les resultats ont montre avec des anneaux aortiques denudes et/ou dont l&apos;endothelium etait intact que l&apos;irisine entraine des relaxations proportionnelles a la concentration. En outre, il s&apos;agit de la premiere etude qui rapporte que les relaxations entrainees par l&apos;irisine sont liees a l&apos;activite de la voie de signalisation de la MEK1/2, des canaux [K.sub.V] et des canaux [K.sub.+] actives par le calcium ([SK.sub.Ca] et [BK.sub.Ca]). [Traduit par la Redaction] Mots-cles : irisine, aorte thoracique de rat, vasodilatation, MEK1/2, canaux potassiques. more...

Agomelatine is a pharmaceutical compound that functions as an agonist for melatonin receptors, with a particular affinity for the MT1 and MT2 receptor subtypes. Its mode of action is integral to the regulation of diverse physiological processes, encompassing the orchestration of circadian rhythms, sleep-wake cycles, and mood modulation. In the present study, we delve into the intricate interplay between agomelatine and the modulation of estrus cycles, gestation periods, offspring numbers, and uterine contractions, shedding light on their collective impact on reproductive physiology. Both in vivo and in vitro experiments were performed. Wistar Albino rats, divided into four groups: two non-pregnant groups (D1 and D2) and two pregnant groups (G1 and G2). The D1 and G1 groups served as control groups, while the D2 and G2 groups received chronic agomelatine administration (10 mg/kg). Uterine contractions were assessed in vitro using myometrial strips. Luzindole, a melatonin receptor antagonist, was employed to investigate the pathway mediating agomelatine's effects on uterine contractions. In in vivo studies, chronic agomelatine administration extended the diestrus phase (p<0.05) in non-pregnant rats, prolonged the gestational period (p<0.01), and increased the fetal count (p<0.01) in pregnant rats. Additionally, agomelatine reduced plasma oxytocin and prostoglandin-E levels (p<0.01) during pregnancy. In vitro experiments showed that agomelatine dose-dependently inhibited spontaneous and oxytocin-induced myometrial contractions. Luzindole (2 µM) reverse the agomelatine-induced inhibition of myometrial contractions. These findings suggest that agomelatine holds the potential to modulate diverse reproductive parameters during the gestational period, influencing estrus cycling, gestational progression, offspring development, and the orchestration of uterine contractions. [ABSTRACT FROM AUTHOR] more...

Objective(s): The present research aimed to identify the functional effects and underlying mechanisms of metformin on the rat thoracic aorta. Materials and Methods: Thoracic aorta segments of Wistar Albino rats were put in the chambers of an isolated tissue bath system. The resting tone was adjusted to 1 g. Following the equilibration time, potassium chloride or phenylephrine was used to contract the vascular segments. The vessel segments were cumulatively treated with metformin (10-7-10-3 M) when a steady contraction was achieved. The described experimental approach was repeated after incubations with signaling pathway inhibitors and selective blockers of potassium channels to identify the effect mechanisms of metformin. Results: Metformin had a potent vasorelaxant effect in a concentration-dependent way (P<0.001). After the endothelium was removed, the vasorelaxant effect level of metformin was significantly reduced. The level of vasorelaxant effect of metformin was increased by the maintenance of perivascular adipose tissue. Following administrations of L-NAME, methylene blue, compound C, BIM-I, and potassium channel blockers, the level of vasodilatory action of metformin was significantly reduced (P<0.001). Conclusion: According to the results of this investigation, metformin significantly relaxes the thoracic aorta segments of rats. Metformin-mediated vasorelaxation involves the activation of numerous subtypes of potassium channels, including BKCa, IKCa, Kv, Kir, and K2p channels, as well as endothelium-dependent processes, including AMPK and eNOS/NO/sGS signaling pathways. Moreover, metformin-induced vasorelaxation is mediated through PVAT activation and the PKC signaling pathway. [ABSTRACT FROM AUTHOR] more...

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Colorectal cancer (CRC) is reported to be the third most common cancer worldwide and the fourth most common cause of cancer related deaths. CRC is considered to be a multifactorial disease whose risk varies due to the complex interaction between individual genetic basis and exposure to multiple endogenous factors. Glutathione S-transferases are pro-carcinogenic in CRC and are required for the conjugation between chemotherapeutics and broad spectrum xenobiotics. One hundred and eleven patients with CRC and 128 control subjects without any cancer history were enrolled in this study. Multiplex PCR was applied to determine polymorphisms for the GSTT1 and M1 genes, and PCR-RFLP was applied for the GSTP1 (Ile105Val) gene polymorphism. Values <0.05 were defined as statistically significant. We detected a significant high correlation between predisposition for CRC and presence of the Ile/Ile genotype of the GSTP1 (IIe105Val) gene polymorphism, but we did not find a significant relationship between predisposition for CRC and GSTT1 and M1 deletion polymorphisms. In addition, we did not determine a relationship between GSTT1, M1 and P1 gene polymorphisms and any clinicopathological features of CRC. GSTT1 null/GSTM1 positive and GSTT1 null/GSTM1 positive/GSTP1 Ile/ Ile genotypes were significantly higher in the patient group. Our results revealed that there is no relationship among CRC, its clinicopathologic features, and GSTT1 M1 gene polymorphisms. However, there was a significant correlation between CRC and the GSTP1 Ile/Ile genotype. Further studies with larger patient groups are required to delineate the relationships between GST gene polymorphisms and the clinicopathologic features of CRC in Turkey. more...