Formulation and Evaluation of Different Nanogels of Tapinarof for Treatment of Psoriasis.

Psoriasis is an immune-mediated skin condition. There are many therapeutic options for its treatment; however, none of them is completely effective. Tapinarof is a promising new active substance; it was recently approved by the FDA for the treatment of psoriasis.

GraphCPP: The new state-of-the-art method for cell-penetrating peptide prediction via graph neural networks.

Background And Purpose: Cell-penetrating peptides (CPPs) are short amino acid sequences that can penetrate cell membranes and deliver molecules into cells. Several models have been developed for their discovery, yet these models often face challenges in accurately predicting membrane penetration due to the complex nature of peptide-cell interactions. Hence, there is a need for innovative approaches that can enhance predictive performance.

Sustainable and Safe -alkylation of -heterocycles by Propylene Carbonate under Neat Reaction Conditions.

A new, eco-friendly process utilising the green solvent propylene carbonate (PC) has been developed to perform -alkylation of -, - and/or -containing heterocyclic compounds. PC in these reactions served as both the reagent and solvent. Importantly, no genotoxic alkyl halides were required.

Advantages of Induced Circular Dichroism Spectroscopy for Qualitative and Quantitative Analysis of Solution-Phase Cyclodextrin Host-Guest Complexes.

The presence of a chiral or chirally perturbed chromophore in the molecule under investigation is a fundamental requirement for the appearance of a circular dichroism (CD) spectrum. For native and for most of the substituted cyclodextrins, this condition is not applicable, because although chiral, cyclodextrins lack a chromophore group and therefore have no characteristic CD spectra over 220 nm. The reason this method can be used is that if the guest molecule has a chromophore group and this is in the right proximity to the cyclodextrin, it becomes chirally perturbed.

Molecular Dynamics Simulations of Drug-Conjugated Cell-Penetrating Peptides.

Cell-penetrating peptides (CPPs) are small peptides capable of translocating through biological membranes carrying various attached cargo into cells and even into the nucleus. They may also participate in transcellular transport. Our in silico study intends to model several peptides and their conjugates.

Urocortin stimulates the ERK1/2 signaling pathway and the proliferation of HeLa cells via CRF receptor 1.

Corticotropin-releasing factor (CRF) stimulates adrenocorticotropic hormone (ACTH) secretion from the pituitary gland and is an essential regulator of the hypothalamic-pituitary-adrenocortical axis. Isoforms of CRF receptor are known to mediate the effects of urocortin stress ligands on the regulation of stress responses, anxiety, and feeding behavior; however, urocortin stress ligands also influence cell proliferation. In view of the tumor-promoting capacity of prolonged stress, here we investigated (a) the effect of urocortin on cell proliferative signaling via extracellular signal-regulated kinase 1/2, (b) the expression and cellular distribution of the specific CRF receptor isoforms, and (c) the intracellular localization of phosphorylated ERK1/2 in HeLa cells.

Traumatic Brain Injury Induces Microglial and Caspase3 Activation in the Retina.

Traumatic brain injury (TBI) is among the main causes of sudden death after head trauma. These injuries can result in severe degeneration and neuronal cell death in the CNS, including the retina, which is a crucial part of the brain responsible for perceiving and transmitting visual information. The long-term effects of mild-repetitive TBI (rmTBI) are far less studied thus far, even though damage induced by repetitive injuries occurring in the brain is more common, especially amongst athletes.

The In Vitro Activity of Fluconazole, Amphotericin B and Echinocandins Against Cyberlindnera fabianii Planktonic Cells and Biofilms.

Until recently, little was known about the susceptibility pattern of Cyberlindnera fabianii (Cy. fabianii) planktonic cells and biofilms regarding the most frequently administered systemic antifungals, despite the high mortality rate and its potential role in catheter-related infections. In the current study, the activity of fluconazole, amphotericin B and echinocandins (anidulafungin, caspofungin and micafungin) was determined against planktonic and sessile cells of Cy.

Small Molecules as Toll-like Receptor 4 Modulators Drug and Computational Repurposing.

The innate immunity toll-like receptor 4 (TLR4) system is a receptor of paramount importance as a therapeutic target. Virtual screening following a "computer-aided drug repurposing" approach was applied to the discovery of novel TLR4 modulators with a non-lipopolysaccharide-like structure. We screened almost 29,000 approved drugs and drug-like molecules from commercial, public, and academia chemical libraries and, after biological assays, identified several compounds with TLR4 antagonist activity.

The Role of Side Chains in the Fine-Tuning of the Metal-Binding Ability of Multihistidine Peptides.

The systematic studies of copper(II), nickel(II) and zinc(II) ion complexes of protected multihistidine peptides containing amino acids with different side chains (Ac-SarHAH-NH, Ac-HADH-NH, Ac-HDAH-NH, Ac-HXHYH-NH X, Y = A, F, D or K, Ac-HXHAHXH-NH, X = F or D) have provided information about the metal ion and protein interaction and have made it possible to draw conclusions regarding general trends in the coordination of metal complexes of multihistidine peptides. The stability of the metal complexes significantly depends on the position of the histidines and amino acids, which are present in the neighbourhood of the histidine amino acids as well. The most significant effect was observed on peptides containing aspartic acid or phenylalanine.

Prolonged treatment with the proteasome inhibitor MG-132 induces apoptosis in PC12 rat pheochromocytoma cells.

Rat pheochromocytoma (PC12) cells were treated with the proteasome inhibitor MG-132 and morphological changes were recorded. Initially, neuronal differentiation was induced but after 24 h signs of morphological deterioration became apparent. We performed nuclear staining, flow cytometry and WST-1 assay then analyzed signal transduction pathways involving Akt, p38 MAPK (Mitogen-Activated Protein Kinase), JNK (c-Jun N-terminal Kinase), c-Jun and caspase-3.

Urocortin stimulates ERK1/2 phosphorylation and proliferation but reduces ATP production of MCF7 breast cancer cells.

Urocortins are members of the stress-related corticotropin-releasing factor family. Small amounts of them are present in the circulation and they are produced locally in various tissues of higher vertebrates. Aside from regulating circulation, or food uptake they also influence, via auto- and paracrine mechanisms, cell proliferation.

Cerebral Microbleeds May Be Less Detectable by Susceptibility Weighted Imaging MRI From 24 to 72 Hours After Traumatic Brain Injury.

A former rodent study showed that cerebral traumatic microbleeds (TMBs) may temporarily become invisible shortly after injury when detected by susceptibility weighted imaging (SWI). The present study aims to validate this phenomenon in human SWI. In this retrospective study, 46 traumatic brain injury (TBI) patients in various forms of severity were included and willingly complied with our strict selection criteria.

LED-Induced Microglial Activation and Rise in Caspase3 Suggest a Reorganization in the Retina.

Vision is our primary sense as the human eye is the gateway for more than 65% of information reaching the human brain. Today's increased exposure to different wavelengths and intensities of light from light emitting diode (LED) sources could induce retinal degeneration and accompanying neuronal cell death. Damage induced by chronic phototoxic reactions occurring in the retina accumulates over years and it has been suggested as being responsible for the etiology of many debilitating ocular conditions.

Thermodynamics and structural characterization of the nickel(II) and zinc(II) complexes of various peptide fragments of tau protein.

Nickel(II) and zinc(II) complexes of various peptide fragments of tau protein have been investigated by potentiometric, UV-Vis, CD and ESI-MS techniques. The peptides include the native fragment tau(9-16) (Ac-EVMEDHAG-NH), and the Gln/Lys and Tyr/Ala mutated peptides (Ac-KGGYTMHK-NH and Ac-KGGATMHK-NH) of tau(26-33). Similar to copper(II) the complexes of a chimeric peptide containing both His14 and His32 residues in one molecule (Ac-EDHAGTMHQD-NH) were also studied.

Laparoscopic-Assisted Percutaneous Endoscopic Gastrostomy Reduces Major Complications in High-Risk Pediatric Patients.

Purpose: Percutaneous endoscopic gastrostomy (PEG) is a safe method to feed patients with feeding difficulty. This study aimed to compare the outcomes of conventional PEG and laparoscopic-assisted PEG (L-PEG) placement in high-risk pediatric patients.

Methods: In our tertiary pediatric department, 90 PEG insertions were performed between 2014 and 2019.

Effect of Pioglitazone on endoplasmic reticulum stress regarding in situ perfusion rat model.

Background: Ischemia-reperfusion injury (IRI) can cause insufficient microcirculation of the transplanted organ and results in a diminished and inferior graft survival rate.

Objective: This study aimed to investigate the effect of different doses of an anti-diabetic drug, Pioglitazone (Pio), on endoplasmic reticulum stress and histopathological changes, using an in situ perfusion rat model.

Methods: Sixty male Wistar rats were used and were divided into six groups, consisting of the control group, vehicle-treated group and four Pio-treated groups (10, 20, 30 and 40 mg/kg Pio was administered).

Microbleeds show a characteristic distribution in cerebral fat embolism.

This systematic review aims to test the hypothesis that microbleeds detected by MRI are common and show a characteristic pattern in cerebral fat embolism (CFE). Eighty-four papers involving 140 CFE patients were eligible for this review based on a systematic literature search up to 31 January 2020. An additional case was added from hospital records.

Increased sTREM-1 levels identify cirrhotic patients with bacterial infection and predict their 90-day mortality.

Background And Aims: Patients with cirrhosis are susceptible to bacterial infections (BIs) that are major causes of specific complications and mortality. However, the diagnosis of BIs can often be difficult in advanced disease stage since their symptoms may overlap with the ones of acute decompensation (AD). Soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) is released from monocytes/macrophages and neutrophils during activation and has been reported to correlate with activity of various inflammatory processes.

Abnormal ferritin levels predict development of poor outcomes in cirrhotic outpatients: a cohort study.

Background: Both iron overload and iron deficient anemia can associate with cirrhosis. At the same time, inflammation might be continuously present in cirrhotic patients due to bacterial translocation and patients' susceptibility to infections. Ferritin is a sensitive and widely available marker of iron homeostasis, in addition it acts as an acute phase protein.

Copper (II) binding properties of an octapeptide fragment from the R3 region of tau protein: A combined potentiometric, spectroscopic and mass spectrometric study.

The copper(II) complexes of a peptide fragment of the R3 domain of tau protein (tau(326-333) Ac-GNIHHKPG-NH) and its mutants (Ac-GNGHHKPG-NH, Ac-GNIHHKAG-NH, Ac-GNGAHKPG-NH and Ac-GNGHAKPG-NH) have been studied by potentiometric and spectroscopic (UV-Vis, CD) methods. ESR spectroscopy and mass spectrometry were also used to prove the coordination mode of the mononuclear complexes and the formation of dinuclear species, respectively. It has been demonstrated that the (326-333) fragment of tau protein is a versatile and effective ligand for copper(II) coordination.

PREDICT identifies precipitating events associated with the clinical course of acutely decompensated cirrhosis.

Background & Aims: Acute decompensation (AD) of cirrhosis may present without acute-on-chronic liver failure (ACLF) (AD-No ACLF), or with ACLF (AD-ACLF), defined by organ failure(s). Herein, we aimed to analyze and characterize the precipitants leading to both of these AD phenotypes.

Methods: The multicenter, prospective, observational PREDICT study (NCT03056612) included 1,273 non-electively hospitalized patients with AD (No ACLF = 1,071; ACLF = 202).

ConjuPepDB: a database of peptide-drug conjugates.

Peptide-drug conjugates are organic molecules composed of (i) a small drug molecule, (ii) a peptide and (iii) a linker. The drug molecule is mandatory for the biological action, however, its efficacy can be enhanced by targeted delivery, which often also reduces unwanted side effects. For site-specificity the peptide part is mainly responsible.

Follow-up Study of Microflora Changes in Crevicular Gingival Fluid in Obese Subjects After Bariatric Surgery.

The objective of our study was to investigate the effect of weight loss on the crevicular microflora following bariatric surgery. Crevicular fluid samples were taken from 57 subjects: 22 were in the normal control group; 18 in the obese control group; and 17 patients had had bariatric surgery, who underwent a repeat sampling 6 to 12 months after the operation. Crevicular fluid samples were analyzed by MALDI-TOF MS analysis.