Insulin receptor substrate 1 is a novel member of EGFR signaling in pancreatic cells.

Pancreatic ductal adenocarcinoma is an extremely incurable cancer type characterized by cells with highly proliferative capacity and resistance against the current therapeutic options. Our study reveals that IRS1 acts as a bridging molecule between EGFR and IGFR/InsR signalization providing a potential mechanism for the interplay between signaling pathways and bypassing EGFR-targeted or IGFR/InsR-targeted therapies. The analysis of IRS1 phosphorylation status in four pancreatic cell lines identified the impact of EGFR signaling on IRS1 activation in comparison with InsR/IGFR signaling.

Predictive value analysis of the interaction network of Tks4 scaffold protein in colon cancer.

Background: Colorectal carcinoma (CRC) has emerged as one of the most widespread cancers and was the third leading cause of cancer-related mortality in 2020. The role of the podosomal protein Tks4 in tumor formation and progression is well established, including its involvement in gastric carcinoma and hepatocellular carcinoma; however, exploration of Tks4 and its associated EMT-regulating interactome in the context of colon cancer remains largely unexplored.

Methods: We conducted a comprehensive bioinformatic analysis to investigate the mRNA and protein expression levels of Tks4 and its associated partner molecules (CD2AP, GRB2, WASL, SRC, CTTN, and CAPZA1) across different tumor types.

Unveiling epithelial plasticity regulation in lung cancer: Exploring the cross-talk among Tks4 scaffold protein partners.

The epithelial-to-mesenchymal transition (EMT) represents a hallmark event in the evolution of lung cancer. This work aims to study a recently described EMT-regulating protein, Tks4, and to explore its potential as a prognostic biomarker in non-small cell lung cancer. In this study, we used CRISPR/Cas9 method to knockout (KO) Tks4 to study its functional roles in invadopodia formation, migration, and regulation of EMT marker expressions and we identified Tks4-interacting proteins.

Survival outcomes of TAVR and self-expanding versus balloon-expandable valves in patients with advanced cardiac dysfunction.

Aims: There is a growing body of literature on long-term outcomes post-transcatheter aortic valve replacement (TAVR), but to our knowledge, few research have focused on patients with advanced cardiac dysfunction. This challenging category of patients was excluded from the Partner 3 clinical trial. There are no data to guide the choice of valve type in patients with severely depressed ejection fraction.

Studying the Association of TKS4 and CD2AP Scaffold Proteins and Their Implications in the Partial Epithelial-Mesenchymal Transition (EMT) Process.

Colon cancer is a leading cause of death worldwide. Identification of new molecular factors governing the invasiveness of colon cancer holds promise in developing screening and targeted therapeutic methods. The Tyrosine Kinase Substrate with four SH3 domains (TKS4) and the CD2-associated protein (CD2AP) have previously been linked to dynamic actin assembly related processes and cancer cell migration, although their co-instructive role during tumor formation remained unknown.

Outcomes of Provisional Stenting With Versus Without Side Branch Intervention in Patients With Bifurcation Lesion-Related ST-Segment Elevation Myocardial Infarction.

To date, the best approach to coronary bifurcation lesion remains unsettled, and the parameters to guide side branch ballooning or stenting are not yet defined. This study aimed to compare the survival outcomes after provisional stenting with versus without side branch intervention. A cohort was conducted on 132 patients who underwent coronary angiography at Toulouse University Hospital for ST-segment elevation myocardial infarction with large culprit nonleft main coronary bifurcation lesion.

Voluntary exercise does not increase gastrointestinal motility but increases spatial memory, intestinal eNOS, Akt levels, and abundance in the microbiome.

The interaction between the gut and brain is a great puzzle since it is mediated by very complex mechanisms. Therefore, the possible interactions of the brain-exercise-intestine-microbiome axis were investigated in a control (C, N = 6) and voluntarily exercised (VE, N = 8) middle-aged rats. The endurance capacity was assessed by VOmax on the treadmill, spatial memory by the Morris maze test, gastrointestinal motility by EMG, the microbiome by 16S RNA gene amplicon sequencing, caveolae by electron microscopy, and biochemical assays were used to measure protein levels and production of reactive oxygen species (ROS).

A Novel Cell-Based Model for a Rare Disease: The Tks4-KO Human Embryonic Stem Cell Line as a Frank-Ter Haar Syndrome Model System.

Tyrosine kinase substrate with four SH3 domains (Tks4) scaffold protein plays roles in cell migration and podosome formation and regulates systemic mechanisms such as adult bone homeostasis and adipogenesis. Mutations in the Tks4 gene () cause a rare developmental disorder called Frank-Ter Haar syndrome (FTHS), which leads to heart abnormalities, bone tissue defects, and reduced adiposity. We aimed to produce a human stem cell-based in vitro FTHS model system to study the effects of the loss of the Tks4 protein in different cell lineages and the accompanying effects on the cell signalome.

Peppermint extract inhibits protein aggregation.

The extracts of 7 herbs were screened and compared for their functional ability to inhibit the aggregation of trypsin as an appropriate model protein for in vitro fibrillation in aqueous ethanol at pH 7.0. Turbidity measurements, total phenolic content determination, aggregation kinetics, Congo red binding assay as well as transmission electron microscopy were used to analyse the inhibition of amyloid fibril formation.

Novel Roles of SH2 and SH3 Domains in Lipid Binding.

Signal transduction, the ability of cells to perceive information from the surroundings and alter behavior in response, is an essential property of life. Studies on tyrosine kinase action fundamentally changed our concept of cellular regulation. The induced assembly of subcellular hubs via the recognition of local protein or lipid modifications by modular protein interactions is now a central paradigm in signaling.

Recent Updates on the Significance of KRAS Mutations in Colorectal Cancer Biology.

The most commonly mutated isoform of RAS among all cancer subtypes is KRAS. In this review, we focus on the special role of KRAS mutations in colorectal cancer (CRC), aiming to collect recent data on KRAS-driven enhanced cell signalling, in vitro and in vivo research models, and CRC development-related processes such as metastasis and cancer stem cell formation. We attempt to cover the diverse nature of the effects of KRAS mutations on age-related CRC development.

Translation of Effects of Retinoids and Rexinoids: Extraction and Quality Assessment of RNA from Formalin-Fixed Tissues.

Retinoids and rexinoids directly and selectively activate their nuclear receptors, resulting in changes in the transcript levels of their target genes. Consequently, quantitating mRNA levels transcribed from cognate target genes is the most accurate measure of retinoid action. These changes can serve as relevant endpoints in biomarker trials, as well as in vivo preclinical studies.

Modelling the neuropathology of lysosomal storage disorders through disease-specific human induced pluripotent stem cells.

Mucopolysaccharidosis II (MPS II) is a lysosomal storage disorder (LSD), caused by iduronate 2-sulphatase (IDS) enzyme dysfunction. The neuropathology of the disease is not well understood, although the neural symptoms are currently incurable. MPS II-patient derived iPSC lines were established and differentiated to neuronal lineage.

Filamentous Aggregation of Sequestosome-1/p62 in Brain Neurons and Neuroepithelial Cells upon Tyr-Cre-Mediated Deletion of the Autophagy Gene Atg7.

Defects in autophagy and the resulting deposition of protein aggregates have been implicated in aging and neurodegenerative diseases. While gene targeting in the mouse has facilitated the characterization of these processes in different types of neurons, potential roles of autophagy and accumulation of protein substrates in neuroepithelial cells have remained elusive. Here we report that Atg7 Tyr-Cre mice, in which autophagy-related 7 (Atg7) is conditionally deleted under the control of the tyrosinase promoter, are a model for accumulations of the autophagy adapter and substrate sequestosome-1/p62 in both neuronal and neuroepithelial cells.

Lysosomal response in relation to α-synuclein pathology differs between Parkinson's disease and multiple system atrophy.

Intracellular deposition of pathologically altered α-synuclein mostly in neurons characterises Parkinson's disease (PD), while its accumulation predominantly in oligodendrocytes is a feature of multiple system atrophy (MSA). Recently a prion-like spreading of pathologic α-synuclein has been suggested to play a role in the pathogenesis of PD and MSA. This implicates a role of protein processing systems, including lysosomes, supported also by genetic studies in PD.

The Inhibitory Effect of Panax Ginseng Extract on Amyloid-like Fibril Formation of Trypsin in Aqueous Ethanol.

Background: In case of several chronic diseases, prevention is could be more effective than treatment. Functional foods that contain significant amounts of bioactive components gained considerable attention not only in traditional but in modern medicine as well. We have investigated how P.

Neurons derived from sporadic Alzheimer's disease iPSCs reveal elevated TAU hyperphosphorylation, increased amyloid levels, and GSK3B activation.

Background: Alzheimer's disease (AD) is the most common type of dementia, affecting one in eight adults over 65 years of age. The majority of AD cases are sporadic, with unknown etiology, and only 5% of all patients with AD present the familial monogenic form of the disease. In the present study, our aim was to establish an in vitro cell model based on patient-specific human neurons to study the pathomechanism of sporadic AD.

Comparison of 2D and 3D neural induction methods for the generation of neural progenitor cells from human induced pluripotent stem cells.

Neural progenitor cells (NPCs) from human induced pluripotent stem cells (hiPSCs) are frequently induced using 3D culture methodologies however, it is unknown whether spheroid-based (3D) neural induction is actually superior to monolayer (2D) neural induction. Our aim was to compare the efficiency of 2D induction with 3D induction method in their ability to generate NPCs, and subsequently neurons and astrocytes. Neural differentiation was analysed at the protein level qualitatively by immunocytochemistry and quantitatively by flow cytometry for NPC (SOX1, PAX6, NESTIN), neuronal (MAP2, TUBB3), cortical layer (TBR1, CUX1) and glial markers (SOX9, GFAP, AQP4).

Catheter-associated urinary tract infections and other infections in patients hospitalized for acute stroke: A prospective cohort study of two different silicone catheters.

Objective: Catheter-associated urinary tract infection (CAUTI) is the most common healthcare-associated infection. The primary aim of this study was to investigate whether the use of a silicone catheter coated with an ultrathin layer of a combination of the noble metals gold, palladium and silver (BIP™-silicone catheter) could reduce the incidence of CAUTI and antibiotic prescription compared with a standard silicone catheter in a cohort of acute neurological patients suffering primarily from stroke. At the same time, all infectious events requiring prescription of an antimicrobial agent were registered and are reported.

Jump into a New Fold-A Homology Based Model for the ABCG2/BCRP Multidrug Transporter.

ABCG2/BCRP is a membrane protein, involved in xenobiotic and endobiotic transport in key pharmacological barriers and drug metabolizing organs, in the protection of stem cells, and in multidrug resistance of cancer. Pharmacogenetic studies implicated the role of ABCG2 in response to widely used medicines and anticancer agents, as well as in gout. Its Q141K variant exhibits decreased functional expression thus increased drug accumulation and decreased urate secretion.

Intracellular processing of disease-associated α-synuclein in the human brain suggests prion-like cell-to-cell spread.

Dementia with Lewy bodies (DLB), Parkinson's disease (PD) and multiple system atrophy are characterized by the deposition of disease-associated α-synuclein. In the present study we 1) examined the molecular specificity of the novel anti-α-synuclein 5G4 antibody; 2) evaluated immunoreactivity patterns and their correlation in human brain tissue with micro- and astrogliosis in 57 cases with PD or DLB; and 3) performed a systematic immunoelectron microscopical mapping of subcellular localizations. 5G4 strongly binds to the high molecular weight fraction of β-sheet rich oligomers, while no binding to primarily disordered oligomers or monomers was observed.

Rapidly progressive dementia with thalamic degeneration and peculiar cortical prion protein immunoreactivity, but absence of proteinase K resistant PrP: a new disease entity?

Background: Human prion diseases are a group of rare fatal neurodegenerative conditions with well-developed clinical and neuropathological diagnostic criteria. Recent observations have expanded the spectrum of prion diseases beyond the classically recognized forms.

Results: In the present study we report six patients with a novel, apparently sporadic disease characterised by thalamic degeneration and rapidly progressive dementia (duration of illness 2-12 months; age at death: 55-81 years).

The highly conserved, N-terminal (RXXX)8 motif of mouse Shadoo mediates nuclear accumulation.

The prion protein (PrP)-known for its central role in transmissible spongiform encephalopathies-has been reported to possess two nuclear localization signals and localize in the nuclei of certain cells in various forms. Although these data are superficially contradictory, it is apparent that nuclear forms of the prion protein can be found in cells in either the healthy or the diseased state. Here we report that Shadoo (Sho)-a member of the prion protein superfamily-is also found in the nucleus of several neural and non-neural cell lines as visualized by using an YFP-Sho construct.

Guidelines for the use and interpretation of assays for monitoring autophagy.

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding.