Synthesis of new 4-butyl-arylpiperazine-3-(1H-indol-3-yl)pyrrolidine-2,5-dione derivatives and evaluation for their 5-HT1A_{1A} and D2_{2} receptor affinity and serotonin transporter inhibition

A series of novel 4-butyl-arylpiperazine-3-(1H-indol-3-yl)pyrrolidine-2,5-dione derivatives were synthesized and evaluated for their 5-HT$_{1A}$/D2 receptor affinity and serotonin reuptake inhibition. The compounds exhibited high affinity for the 5-HT$_{1A}$ receptor, (especially 4d K$_{i}$ = 0.4 nM) which depended on the substitution pattern at the phenylpiperazine moiety. From this series screen, compound 4c emerged with promising mixed receptor profiles for the 5-HT$_{1A}$/D2 receptors and the serotonin transporter (K$_{i}$ = 1.3 nM, 182 nM and 64 nM, respectively).long-chain arylpiperazinesdepression5-HT$_{1A}$ receptor ligandsschizophreniamulti-target ligand

Związek pentraksyny 3 z retinopatią w odniesieniu do miażdżycy tętnic szyjnych oraz skurczowej i rozkurczowej funkcji serca u chorych na cukrzycę typu 2 — badanie pilotażowe

Wstęp. Retinopatia cukrzycowa jest główną przyczyną utraty wzroku na całym świecie, a jej występowanie szacuje się na 35,4%. W kilku badaniach udowodniono, że przewlekły stan zapalny o niewielkim nasileniu może brać udział w patogenezie retinopatii cukrzycowej. Niektóre z nich wskazują, że retinopatia cukrzycowa może być związana z powikłaniami makroangiopatycznymi, co stanowi podłoże koncepcji „common soil” cukrzycowych powikłań mikro- i makronaczyniowych. Celem badania była ocena związku stężenia pentraksyny 3 (PTX3), biomarkera procesów zapalnych, z występowaniem retinopatii cukrzycowej w powiązaniu z obecnością miażdżycy w tętnicach szyjnych oraz skurczową i rozkurczową funkcją serca. Materiał i metody. Do badania zakwalifikowano 43 pacjentów chorujących na cukrzycę typu 2 i podzielono na dwie grupy w zależności od obecności bądź braku retinopatii cukrzycowej. Dokonano pomiarów antropometrycznych, oznaczeń wybranych parametrów biochemicznych oraz przeprowadzono badanie ultrasonograficzne tętnic szyjnych oraz serca. Wyniki. Nie wykazano bezpośredniego związku stężenia PTX3 z obecnością retinopatii cukrzycowej, jednak ujawniono istotny związek pomiędzy stężeniem PTX3 a odsetkiem HbA1c, wiekiem i IMT (intima media thickness) tętnic szyjnych w grupie pacjentów z retinopatią cukrzycową. Wnioski. Bardzo istotne wydaje się prowadzenie dalszych, większych badań nad biomarkerami zapalnymi, takimi jak na przykład PTX3, oraz powikłaniami mikro- i makronaczyniowymi cukrzycy w celu zidentyfikowania pacjentów szczególnego ryzyka i wczesnego zastosowania skutecznego leczenia

A ligand-receptor interactome atlas of the zebrafish

Summary: Studies in zebrafish can unravel the functions of cellular communication and thus identify novel bench-to-bedside drugs targeting cellular communication signaling molecules. Due to the incomplete annotation of zebrafish proteome, the knowledge of zebrafish receptors, ligands, and tools to explore their interactome is limited. To address this gap, we de novo predicted the cellular localization of zebrafish reference proteome using deep learning algorithm. We combined the predicted and existing annotations on cellular localization of zebrafish proteins and created repositories of zebrafish ligands, membrane receptome, and interactome as well as associated diseases and targeting drugs. Unlike other tools, our interactome atlas is based on both the physical interaction data of zebrafish proteome and existing human ligand-receptor pair databases. The resources are available as R and Python scripts. DanioTalk provides a novel resource for researchers interested in targeting cellular communication in zebrafish, as we demonstrate in applications studying synapse and axo-glial interactome. DanioTalk methodology can be applied to build and explore the ligand-receptor atlas of other non-mammalian model organisms

Pentraxin 3 and retinopathy among type 2 diabetic patients in relation to carotid atherosclerosis and systolic and diastolic cardiac function — a pilot study

Introduction. Diabetic retinopathy (DR) is the leading cause of vision loss worldwide. Global prevalence of any diabetic retinopathy is assessed to be 35.4%. Several studies proved that chronic low-grade inflammation may be involved in the pathogenesis of DR. Some studies indicate that macroangiopathic diabetic complications may be associated with microangiopathic ones that is why a “common soil” mechanism of diabetic micro- and macroangiogpathy has been proposed. The aim of this study was to evaluate the association of pentraxin 3 (PTX3), an inflammation’s biomarker, with diabetic retinopathy in relation to atherosclerosis in carotid arteries and systolic and diastolic cardiac function. Material and methods. 43 eligible patients with type 2 diabetes were enrolled into the study and dived into two groups on the basis of presence or lack of retinopathy. Anthropometric, biochemical and carotid as well as cardiac ultrasound parameters were analyzed. Results. There was no direct association between PTX3 concentration and the presence of diabetic retinopathy, but there was a significant correlation between PTX3 and HbA1c value, age and IMT (intima media thickness) in carotid arteries among patients with diabetic retinopathy. Conclusions. There is a great need for further, larger, studies on inflammatory biomarkers such as PTX3 and micro and macrovascular complications of diabetes mellitus in order to detect predisposed patients early enough to implement early therapeutic intervention of this complication

Pentraxin 3 and atherosclerosis among type 2 diabetic patients

Type 2 diabetes is contemporarily a major social and epidemiological problem and among others is a strong risk factor for cardiovascular diseases. Pentraxin 3, a potential early biomarker of atherosclerosis, is an acute-phase reactant produced by the peripheral tissues where the inflammation takes place. In this study we examined a group of patients with type 2 diabetes with and without cardiovascular complications compared to persons with normal glucose tolerance (patients with cardiovascular complications and healthy volunteers). Plasma pentraxin 3 concentration as well as some basic biochemical blood analysis were performed. Moreover, transcranial and carotid Doppler ultrasound examination as well as transthoracic echocardiography were performed. It turned out that there was an association of plasma pentraxin 3 concentration and carotid atherosclerosis found in the control group of patients with cardiovascular complications but with normal glucose tolerance. In the group of patients with type 2 diabetes and cardiovascular complications we have found an association of plasma pentraxin 3 concentration with diastolic left ventricular dysfunction. Additionally, in the group of patients with type 2 diabetes without cardiovascular disease plasma pentraxin 3 concentration was associated with elevated urinary albumin creatinine ratio. Further studies, on a larger group of patients, are required to confirm these observations