A 2D cell segmentation protocol for monitoring multiple STAT signaling pathways by fluorescence microscopy.

Microscopic cell segmentation typically requires complex imaging, staining, and computational steps to achieve acceptable consistency. Here, we describe a protocol for the high-fidelity segmentation of the nucleus and cytoplasm in cell culture and apply it to monitor interferon-induced signal transducer and activator of transcription (STAT) signaling. We provide guidelines for sample preparation, image acquisition, and segmentation.

Presynaptic nanoscale components of retrograde synaptic signaling.

While our understanding of the nanoscale architecture of anterograde synaptic transmission is rapidly expanding, the qualitative and quantitative molecular principles underlying distinct mechanisms of retrograde synaptic communication remain elusive. We show that a particular form of tonic cannabinoid signaling is essential for setting target cell-dependent synaptic variability. It does not require the activity of the two major endocannabinoid-producing enzymes.

Assessment of a Large Language Model's Responses to Questions and Cases About Glaucoma and Retina Management.

Importance: Large language models (LLMs) are revolutionizing medical diagnosis and treatment, offering unprecedented accuracy and ease surpassing conventional search engines. Their integration into medical assistance programs will become pivotal for ophthalmologists as an adjunct for practicing evidence-based medicine. Therefore, the diagnostic and treatment accuracy of LLM-generated responses compared with fellowship-trained ophthalmologists can help assess their accuracy and validate their potential utility in ophthalmic subspecialties.

Design, Optimization, and Application of a 3D-Printed Polymer Sample Introduction System for the ICP-MS Analysis of Nanoparticles and Cells.

Commonly used sample introduction systems for inductively coupled plasma mass spectrometry (ICP-MS) are generally not well-suited for single particle ICP-MS (spICP-MS) applications due to their high sample requirements and low efficiency. In this study, the first completely 3D-printed, polymer SIS was developed to facilitate spICP-MS analysis. The system is based on a microconcentric pneumatic nebulizer and a single-pass spray chamber with an additional sheath gas flow to further facilitate the transport of larger droplets or particles.

Deep Learning for Localized Detection of Optic Disc Hemorrhages.

Purpose: To develop an automated deep learning system for detecting the presence and location of disc hemorrhages in optic disc photographs.

Design: Development and testing of a deep learning algorithm.

Methods: Optic disc photos (597 images with at least 1 disc hemorrhage and 1075 images without any disc hemorrhage from 1562 eyes) from 5 institutions were classified by expert graders based on the presence or absence of disc hemorrhage.

The Effect of Aerobic Exercise and Low-Impact Pilates Workout on the Adaptive Immune System.

Growing evidence indicates the pronounced effects of physical activity on immune functions, which may largely depend on the type of exercise, intensity, and duration. However, limited information is available regarding the effects of low-impact exercises, especially on the level of adaptive immune system. Our study aimed to investigate and compare the changes in a broad spectrum of lymphocyte subtypes after 14 weeks of aerobic-type total-body-shaping workouts (TBSW) and Pilates workouts (PW) among healthy individuals.

Effects of sub-chronic, in vivo administration of sigma-1 receptor ligands on platelet and aortic arachidonate cascade in streptozotocin-induced diabetic rats.

Background: Diabetes mellitus is a chronic metabolic disorder which induces endothelial dysfunction and platelet activation. Eicosanoids produced from arachidonic acid regulate cellular and vascular functions. Sigma-1 receptors (S1R) are expressed in platelets and endothelial cells and S1R expression is protective in diabetes.

Cellular Therapy Using Epitope-Imprinted Composite Nanoparticles to Remove α-Synuclein from an In Vitro Model.

Several degenerative disorders of the central nervous system, including Parkinson's disease (PD), are related to the pathological aggregation of proteins. Antibodies against toxic disease proteins, such as α-synuclein (SNCA), are therefore being developed as possible therapeutics. In this work, one peptide (YVGSKTKEGVVHGVA) from SNCA was used as the epitope to construct magnetic molecularly imprinted composite nanoparticles (MMIPs).

Effects of sub-chronic, in vivo administration of sigma non-opioid intracellular receptor 1 ligands on platelet and aortic arachidonate cascade in rats.

Platelets regulate cell-cell interactions and local circulation through eicosanoids from arachidonic acid. Sigma non-opioid intracellular receptor 1 (sigma-1 receptor) expressed in platelets and endothelial cells can regulate intracellular signalization. Our aim was to examine the influence of sub-chronic, in vivo-administered sigma-1 receptor ligands 2-morpholin-4-ylethyl 1-phenylcyclohexane-1-carboxylate (PRE-084); N-benzyl-2-[(1S)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolin-1-yl]ethan-1-amine; dihydrochloride, a new compound ((S)-L1); and N-[2-[4-methoxy-3-(2-phenylethoxy)phenyl]ethyl]-N-propylpropan-1-amine (NE-100) on the ex vivo arachidonic acid metabolism of the platelets and aorta of male rats.

Novel cyclic C-curcuminoids penetrating the blood-brain barrier: Design, synthesis and antiproliferative activity against astrocytoma and neuroblastoma cells.

Novel series of cyclic C-curcuminoids 17a-j and 19-22 were prepared as cytotoxic agents and evaluated against human neuroblastoma (SH-SY5Y) or human grade IV astrocytoma (CCF-STTG1) cell lines in low (∼0.1 nM - 10 nM) concentrations. Among the tested 21 derivatives, 16 displayed potent antiproliferative activity with IC values in the low nanomolar to picomolar range (IC = 7.

Blood-brain barrier dysfunction in L-ornithine induced acute pancreatitis in rats and the direct effect of L-ornithine on cultured brain endothelial cells.

Background: In severe acute pancreatitis (AP) the CNS is affected manifesting in neurological symptoms. Earlier research from our laboratory showed blood-brain barrier (BBB) permeability elevation in a taurocholate-induced AP model. Here we aimed to further explore BBB changes in AP using a different, non-invasive in vivo model induced by L-ornithine.

Nitric oxide stimulates type IV MSHA pilus retraction in via activation of the phosphodiesterase CdpA.

Bacteria use surface appendages called type IV pili to perform diverse activities including DNA uptake, twitching motility, and attachment to surfaces. The dynamic extension and retraction of pili are often required for these activities, but the stimuli that regulate these dynamics remain poorly characterized. To address this question, we study the bacterial pathogen , which uses mannose-sensitive hemagglutinin (MSHA) pili to attach to surfaces in aquatic environments as the first step in biofilm formation.

PharmacoSTORM nanoscale pharmacology reveals cariprazine binding on Islands of Calleja granule cells.

Immunolabeling and autoradiography have traditionally been applied as the methods-of-choice to visualize and collect molecular information about physiological and pathological processes. Here, we introduce PharmacoSTORM super-resolution imaging that combines the complementary advantages of these approaches and enables cell-type- and compartment-specific nanoscale molecular measurements. We exploited rational chemical design for fluorophore-tagged high-affinity receptor ligands and an enzyme inhibitor; and demonstrated broad PharmacoSTORM applicability for three protein classes and for cariprazine, a clinically approved antipsychotic and antidepressant drug.

S1R agonist modulates rat platelet eicosanoid synthesis and aggregation.

Sigma-1 receptor (S1R) is detected in different cell types and can regulate intracellular signaling pathways. S1R plays a role in the pathomechanism of diseases and the regulation of neurotransmitters. Fluvoxamine can bind to S1R and reduce the serotonin uptake of neurons and platelets.

Mac-1 Receptor Clustering Initiates Production of Pro-Inflammatory, Antibacterial Extracellular Vesicles From Neutrophils.

Depending on the prevailing environmental conditions, neutrophilic granulocytes release extracellular vesicles (EV) which have either anti-inflammatory effects on other neutrophils or pro-inflammatory and antibacterial effects. In the present study we investigated the molecular mechanisms underlying the biogenesis of functionally heterogenic EVs. We show that selective stimulation of Mac-1 integrin (complement receptor 3) by specific ligands initiates the generation of EVs which are able to impair bacterial growth and to induce the secretion of the pro-inflammatory cytokine IL-8 (aEV).

Identification of Reference Genes for Circadian Studies on Brain Microvessels and Choroid Plexus Samples Isolated from Rats.

Delivery of putative compounds of therapeutic value to the brain is limited by brain barriers: the blood-brain barrier located in the endothelium of the brain microvessels (BrMVs) and the blood-cerebrospinal fluid barrier located in the epithelium of the choroid plexus (ChP). Understanding their function and modulation by the circadian clock may enhance the efficacy of brain-targeting therapies. The aim of the present study was to evaluate the stability of 10 reference genes in the BrMV and ChP, isolated from male and female rats at six time points (ZT1, 5, 9, 13, 17, and 21).

Effects of Functional Training on Sarcopenia in Elderly Women in the Presence or Absence of ACE Inhibitors.

Sarcopenia, defined as loss of muscle mass and strength, develops gradually with aging or after chronic disease. Efforts are ongoing to identify the best interventions that can slow down or stop sarcopenia. Nutrition-based interventions and exercise therapy may be beneficial; however, pharmacotherapy also could play a role.

[Anomalies of coronary origin detected by cardiac CT].

Unlabelled: Összefoglaló. Bevezetés: Congenitalis coronariaanomáliának tekintik azokat a coronariamorfológiai rendellenességeket, melyek 1%-nál kisebb gyakorisággal fordulnak elő. Többségük nem jár tünettel, olykor azonban okozhatnak mellkasi fájdalmat, eszméletvesztést, és hirtelen halálhoz is vezethetnek.

Simvastatin, edaravone and dexamethasone protect against kainate-induced brain endothelial cell damage.

Background: Excitotoxicity is a central pathological pathway in many neurological diseases with blood-brain barrier (BBB) dysfunction. Kainate, an exogenous excitotoxin, induces epilepsy and BBB damage in animal models, but the direct effect of kainate on brain endothelial cells has not been studied in detail. Our aim was to examine the direct effects of kainate on cultured cells of the BBB and to test three anti-inflammatory and antioxidant drugs used in clinical practice, simvastatin, edaravone and dexamethasone, to protect against kainate-induced changes.

Assessment of a residual municipal solid waste landfill for prospective 'landfill mining'.

Landfill mining is a prospective tool for the recycling of valuable materials (waste-to-material) and secondary fuel (waste-to-energy) from old, therefore more or less stabilised municipal solid waste landfills. The main target of Horizon 2020 'SMARTGROUND' R&D was improving the availability and accessibility of data and information from both urban landfills and mining dumps through a set of activities to integrate all the data - from existing sources and new information retrieved with time progress - in a single EU database. Concerning urban landfills, a new sampling protocol was designed on the basis of the current Hungarian national municipal solid waste analysis standards, optimised for landfill mining.

The effects of Vitis vinifera L. phenolic compounds on a blood-brain barrier culture model: Expression of leptin receptors and protection against cytokine-induced damage.

Ethnopharmacological Relevance: The medicinal properties of grapes (Vitis vinifera L.) are well known since ancient times. Ethnobotanical grape preparations, like the Ayurvedic Darakchasava are used as cardiotonic and for the treatment of cardiovascular diseases.