Miracle-dz/UniFAR-FTUs huggingface dataset:
Novel Prognostic Immunohistochemical Markers in Uveal Melanoma-Literature Review

Simple Summary The following study provides an overview of the English-language literature on the search for new prognostic factors for uveal melanoma. Uveal melanoma is the most common primary intraocular tumor in adults, and although it is a relatively rare disease, it poses a significant health problem. About half of the patients develop distant metastases, and unfortunately there are currently no effective treatments for the disease at such an advanced stage. The search for new prognostic factors is important to understand the biology of the disease and to be able to monitor patients more effectively. At the same time, it creates an opportunity to find new therapeutic targets. We focused our attention on immunohistochemical research because it is a widely used method, relatively cheap, technically simple, and gives reproducible results. The analysis of this study will enable other researchers to verify their research plans and may also be a source of inspiration for creating new ones. Abstract Uveal melanoma is the most common primary intraocular neoplasm in adults. As there are currently no effective methods of treating the disease in the metastatic stage, there is a need to search for new prognostic factors that would enable a reliable assessment of the patient’s condition and constitute a possible therapeutic target. In this review, we have prepared the results of English-language studies on new prognostic factors determined with immunohistochemical methods. We found 64 articles in which the expression of various proteins was associated in a statistically significant manner with the histopathological and clinical prognostic factors identified by AJCC. The results of our work clearly show that the biology of uveal melanoma is extraordinarily complex. Numerous studies have shed new light on the complexity of the processes involved in the development of this cancer. Moreover, a careful analysis of the expression of individual proteins may allow the identification of homogeneous groups of patients requiring different treatment regimens.
Urinary Tartaric Acid, a Biomarker of Wine Intake, Correlates with Lower Total and LDL Cholesterol

Postmenopausal women are at higher risk of developing cardiovascular diseases due to changes in lipid profile and body fat, among others. The aim of this study was to evaluate the association of urinary tartaric acid, a biomarker of wine consumption, with anthropometric (weight, waist circumference, body mass index (BMI), and waist-to-height ratio), blood pressure, and biochemical variables (blood glucose and lipid profile) that may be affected during the menopausal transition. This sub-study of the PREDIMED (Prevención con Dieta Mediterránea) trial included a sample of 230 women aged 60–80 years with high cardiovascular risk at baseline. Urine samples were diluted and filtered, and tartaric acid was analyzed by liquid chromatography coupled to electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). Correlations between tartaric acid and the study variables were adjusted for age, education level, smoking status, physical activity, BMI, cholesterol-lowering, antihypertensive, and insulin treatment, total energy intake, and consumption of fruits, vegetables, and raisins. A strong association was observed between wine consumption and urinary tartaric acid (0.01 μg/mg (95% confidence interval (CI): 0.01, 0.01), p-value < 0.001). Total and low-density lipoprotein (LDL) cholesterol were inversely correlated with urinary tartaric acid (−3.13 μg/mg (−5.54, −0.71), p-value = 0.016 and −3.03 μg/mg (−5.62, −0.42), p-value = 0.027, respectively), whereas other biochemical and anthropometric variables were unrelated. The results suggest that wine consumption may have a positive effect on cardiovascular health in postmenopausal women, underpinning its nutraceutical properties.
Th17-Related Cytokines as Potential Discriminatory Markers between Neuromyelitis Optica (Devic’s Disease) and Multiple Sclerosis—A Review

Multiple sclerosis (MS) and Devic’s disease (NMO; neuromyelitis optica) are autoimmune, inflammatory diseases of the central nervous system (CNS), the etiology of which remains unclear. It is a serious limitation in the treatment of these diseases. The resemblance of the clinical pictures of these two conditions generates a partial possibility of introducing similar treatment, but on the other hand, a high risk of misdiagnosis. Therefore, a better understanding and comparative characterization of the immunopathogenic mechanisms of each of these diseases are essential to improve their discriminatory diagnosis and more effective treatment. In this review, special attention is given to Th17 cells and Th17-related cytokines in the context of their potential usefulness as discriminatory markers for MS and NMO. The discussed results emphasize the role of Th17 immune response in both MS and NMO pathogenesis, which, however, cannot be considered without taking into account the broader perspective of immune response mechanisms.
Why Are Turkish University Students Addicted to the Internet? A Moderated Mediation Model

Internet addiction has become a significant problem that primarily affects young people. It has an essential effect on the individual’s self-perception and assessment of their competencies. This study aimed to reveal whether there is a significant relationship between the level of internet addiction of university students and their age and self-esteem. For this purpose, internet addiction and self-esteem scales were used in addition to questions such as age, gender, the purpose of internet use, and internet daily usage time. We used a quantitative research method to obtain cross-sectional data from 400 Turkish young people using online surveys. Correlation, regression, mediation, and moderation analyses were performed using SPSS and the PROCESS macro plugin for data analysis. Internet addiction was significantly associated with self-esteem, gender, age, and daily internet usage. In addition, we discovered that self-esteem and daily usage time played a mediation role in the effect of the age variable on internet addiction. Moreover, the moderation roles of social networks, gender, and location in the impact of self-esteem on internet addiction were determined. With this study, we understood that as age increases, self-esteem triggers the decrease of internet addiction. In this sense, policies should be developed to increase self-esteem among young people to ensure the conscious use of the internet.
Magnetization Reversal and Dynamics in Epitaxial Fe/Pt Spintronic Bilayers Stimulated by Interfacial Fe3O4 Nanoparticles

We have explored the impact of elevated growth and annealing temperatures on the local interfacial structure of thin Fe(12 nm)/Pt(10 nm) spintronic bilayers, epitaxially grown on MgO (100), and their correlation to magnetization reversal and dynamics. Electron-beam evaporation growth and subsequent annealing at 450 °C causes significant roughening of the MgO/Fe interface with irregular steps and multilevel (100) MgO surface terraces. Consequently, threading dislocations emerging at the step edges propagated in the Fe layer and terminated at the Fe/Pt interface, which appears pitted with pits 1.5–3 nm deep on the Fe side. Most of the pits are filled with the overlying Pt, whereby others by ferrimagnetic Fe3O4, forming nanoparticles that occupy nearly 9% of the Fe/Pt interfacial area. Fe3O4 nanoparticles occur at the termination sites of threading dislocations at the Fe/Pt interface, and their population density is equivalent to the density of threading dislocations in the Fe layer. The morphology of the Fe/Fe3O4/Pt system has a strong impact on the magnetization reversal, enhancing the coercive field and inducing an exchange bias below 200 K. Furthermore, low-temperature spin pumping and inverse spin Hall effect voltage measurements reveal that below their blocking temperature the nanoparticles can influence the spin current transmission and the spin rectification effects.
Negative Influence by the Force: Mechanically Induced Hyperpolarization via K2P Background Potassium Channels

The two-pore domain K2P subunits form background (leak) potassium channels, which are characterized by constitutive, although not necessarily constant activity, at all membrane potential values. Among the fifteen pore-forming K2P subunits encoded by the KCNK genes, the three members of the TREK subfamily, TREK-1, TREK-2, and TRAAK are mechanosensitive ion channels. Mechanically induced opening of these channels generally results in outward K+ current under physiological conditions, with consequent hyperpolarization and inhibition of membrane potential-dependent cellular functions. In the past decade, great advances have been made in the investigation of the molecular determinants of mechanosensation, and members of the TREK subfamily have emerged among the best-understood examples of mammalian ion channels directly influenced by the tension of the phospholipid bilayer. In parallel, the crucial contribution of mechano-gated TREK channels to the regulation of membrane potential in several cell types has been reported. In this review, we summarize the general principles underlying the mechanical activation of K2P channels, and focus on the physiological roles of mechanically induced hyperpolarization.
Identification and Characterization of Cannabidiol as an OX1R Antagonist by Computational and In Vitro Functional Validation

The potential, multifaceted therapeutic profile of cannabidiol (CBD), a major constituent derived from the Cannabis sativa plant, covers a wide range of neurological and psychiatric disorders, ranging from anxiety to pediatric epilepsy and drug addiction. However, the molecular targets responsible for these effects have been only partially identified. In this view, the involvement of the orexin system, the key regulator in arousal and the sleep/wake cycle, and in motivation and reward processes, including drug addiction, prompted us to explore, using computational and experimental approaches, the possibility that CBD could act as a ligand of orexin receptors, orexin 1 receptor of type 1 (OX1R) and type 2 (OX2R). Ligand-binding assays showed that CBD is a selective ligand of OX1R in the low micromolar range (Ki 1.58 ± 0.2 μM) while in vitro functional assays, carried out by intracellular calcium imaging and mobilization assays, showed that CBD acts as an antagonist at this receptor. Finally, the putative binding mode of CBD has been inferred by molecular docking and molecular dynamics simulations and its selectivity toward the OX1R subtype rationalized at the molecular level. This study provides the first evidence that CBD acts as an OX1R antagonist, supporting its potential use in addictive disorders and/or body weight regulation.
Malpigmentation of Common Sole (Solea solea) during Metamorphosis Is Associated with Differential Synaptic-Related Gene Expression

Simple Summary Common sole (Solea solea) is an important species for the aquaculture industry. Defects in pigmentation of the species are very common in farmed conditions. Differences in gene expression between normally pigmented juveniles and those that present both sides full pigmented, ocular and blind, were investigated. Differentially expressed transcripts were functionally annotated, and gene ontology was carried out. The results indicated that ambicolorated juveniles showed a significant upregulation of genes involved in the signal transmission at the synaptic level and regulation of ion channels, affecting the plasticity and the development of the synapses, as well as the transmission of signals or ions through channels. Abstract In farmed flatfish, such as common sole, color disturbances are common. Dyschromia is a general term that includes the color defects on the blind and ocular sides of the fish. The purpose was to examine the difference in gene expression between normal pigmented and juveniles who present ambicoloration. The analysis was carried out with next-generation sequencing techniques and de novo assembly of the transcriptome. Transcripts that showed significant differences (FDR < 0.05) in the expression between the two groups, were related to those of zebrafish (Danio rerio), functionally identified, and classified into categories of the gene ontology. The results revealed that ambicolorated juveniles exhibit a divergent function, mainly of the central nervous system at the synaptic level, as well as the ionic channels. The close association of chromophore cells with the growth of nerve cells and the nervous system was recorded. The pathway, glutamate binding–activation of AMPA and NMDA receptors–long-term stimulation of postsynaptic potential–LTP (long term potentiation)–plasticity of synapses, appears to be affected. In addition, the development of synapses also seems to be affected by the interaction of the LGI (leucine-rich glioma inactivated) protein family with the ADAM (a disintegrin and metalloprotease) ones.
Environmentally Relevant Mixture of Pesticides Affect Mobility and DNA Integrity of Early Life Stages of Rainbow Trout (Oncorhynchus mykiss)

The aim of this study was to analyze the impact of three concentrations of a pesticide mixture on the first development stages of rainbow trout (Oncorhynchus mykiss). The mixture was made up of three commonly used pesticides in viticulture: glyphosate (GLY), chlorpyrifos (CPF) and copper sulfate (Cu). Eyed stage embryos were exposed for 3 weeks to three concentrations of the pesticide mixture. Lethal and sub-lethal effects were assessed through a number of phenotypic and molecular endpoints including survival, hatching delay, hatching success, biometry, swimming activity, DNA damage (Comet assay), lipid peroxidation (TBARS), protein carbonyl content and gene expression. Ten target genes involved in antioxidant defenses, DNA repair, mitochondrial metabolism and apoptosis were analyzed using real-time RT-qPCR. No significant increase of mortality, half-hatch, growth defects, TBARS and protein carbonyl contents were observed whatever the pesticide mixture concentration. In contrast, DNA damage and swimming activity were significantly more elevated at the highest pesticide mixture concentration. Gene transcription was up-regulated for genes involved in detoxification (gst and mt1), DNA repair (ogg1), mitochondrial metabolism (cox1 and 12S), and cholinergic system (ache). This study highlighted the induction of adaptive molecular and behavioral responses of rainbow trout larvae when exposed to environmentally realistic concentrations of a mixture of pesticides.
Characterization of the Psychrotrophic Lactic Acid Bacterium Leuconostoc gelidum subsp. aenigmaticum LS4 Isolated from Kimchi Based on Comparative Analyses of Its Genomic and Phenotypic Properties

With the aim of developing a new food starter culture, twenty-three psychrotrophic lactic acid bacteria (LAB) were isolated from 16 kimchi samples. One strain, Leuconostoc gelidum subsp. aenigmaticum LS4, which had typical psychrotrophic characteristics, was selected, and its phenotypic and genomic properties as a starter culture were investigated. The complete genome of L. aenigmaticum LS4 consisted of one circular chromosome (1,988,425 bp) and two plasmids (19,308 bp and 11,283 bp), with a guanine–cytosine content of 36.8%. L. aenigmaticum LS4 could grow at 5 °C but not at 37 °C, and maximum cell growth was obtained at 15~25 °C. L. aenigmaticum LS4 did not show any harmful characteristics such as hemolysis, undesirable enzyme activities, biogenic amine production, or antibiotic resistance. L. aenigmaticum LS4 was investigated for its suitability for technological processes (pH, temperature and NaCl treatment). L. aenigmaticum LS4 exhibited strong antimicrobial activity caused by the production of organic acids and bacteriocin, and it produced an exopolysaccharide composed of glucose with a molecular weight of 3.7 × 106 Da. Furthermore, L. aenigmaticum LS4 improved the organoleptic qualities of kimchi juice. Our results indicate that L. aenigmaticum LS4 could be used as a functional starter culture for food (vegetable or fruit) fermentation at low temperatures.
Impact of a Single Nucleotide Change or Non-Nucleoside Modifications in G-Rich Region on the Quadruplex–Duplex Hybrid Formation

In this paper, a method to discriminate between two target RNA sequences that differ by one nucleotide only is presented. The method relies on the formation of alternative structures, i.e., quadruplex–duplex hybrid (QDH) and duplex with dangling ends (Dss), after hybridization of DNA or RNA G-rich oligonucleotides with target sequences containing 5′–GGGCUGG–3′ or 5′–GGGCGGG–3′ fragments. Using biophysical methods, we studied the effect of oligonucleotide types (DNA, RNA), non-nucleotide modifications (aliphatic linkers or abasic), and covalently attached G4 ligand on the ability of G-rich oligonucleotides to assemble a G-quadruplex motif. We demonstrated that all examined non-nucleotide modifications could mimic the external loops in the G-quadruplex domain of QDH structures without affecting their stability. Additionally, some modifications, in particular the presence of two abasic residues in the G-rich oligonucleotide, can induce the formation of non-canonical QDH instead of the Dss structure upon hybridization to a target sequence containing the GGGCUGG motif. Our results offer new insight into the sequential requirements for the formation of G-quadruplexes and provide important data on the effects of non-nucleotide modifications on G-quadruplex formation.
Kinins and Their Receptors as Potential Therapeutic Targets in Retinal Pathologies

The kallikrein-kinin system (KKS) contributes to retinal inflammation and neovascularization, notably in diabetic retinopathy (DR) and neovascular age-related macular degeneration (AMD). Bradykinin type 1 (B1R) and type 2 (B2R) receptors are G-protein-coupled receptors that sense and mediate the effects of kinins. While B2R is constitutively expressed and regulates a plethora of physiological processes, B1R is almost undetectable under physiological conditions and contributes to pathological inflammation. Several KKS components (kininogens, tissue and plasma kallikreins, and kinin receptors) are overexpressed in human and animal models of retinal diseases, and their inhibition, particularly B1R, reduces inflammation and pathological neovascularization. In this review, we provide an overview of the KKS with emphasis on kinin receptors in the healthy retina and their detrimental roles in DR and AMD. We highlight the crosstalk between the KKS and the renin–angiotensin system (RAS), which is known to be detrimental in ocular pathologies. Targeting the KKS, particularly the B1R, is a promising therapy in retinal diseases, and B1R may represent an effector of the detrimental effects of RAS (Ang II-AT1R).
Metabolite Profile and In Vitro Beneficial Effects of Black Garlic (Allium sativum L.) Polar Extract

Over the centuries, humans have traditionally used garlic (Allium sativum L.) as a food ingredient (spice) and remedy for many diseases. To confirm this, many extensive studies recognized the therapeutic effects of garlic bulbs. More recently, black garlic (BG), made by heat-ageing white garlic bulbs, has increased its popularity in cuisine and traditional medicine around the world, but there is still limited information on its composition and potential beneficial effects. In this study, the metabolite profile of methanol extract of BG (BGE) was determined by high-performance liquid chromatography coupled to tandem mass spectrometry in high-resolution mode. Results allowed to establish that BGE major components were sulfur derivatives, saccharides, peptides, organic acids, a phenylpropanoid derivative, saponins, and compounds typical of glycerophospholipid metabolism. Characterization of the BGE action in cancer cells revealed that antioxidant, metabolic, and hepatoprotective effects occur upon treatment as well as induction of maturation of acute myeloid leukemia cells. These results are interesting from the impact point of view of BG consumption as a functional food for potential prevention of metabolic and tumor diseases.
Risk Factors Associated with 30-Day Mortality in Older Patients with Influenza

Background: Influenza is a common viral condition, but factors related to short-term mortality have not been fully studied in older adults. Our objective was to determine whether there is an association between geriatric factors and 30-day mortality. Methods: This was a retrospective cohort design. All patients aged 75 years and over, with a diagnosis of influenza confirmed by a positive RT-PCR, were included. The primary endpoint was death within the 30 days after diagnosis. Results: 114 patients were included; 14 (12.3%) patients died within 30 days. In multivariate analysis these patients were older (OR: 1.37 95% CI (1.05, 1.79), p = 0.021), and had a lower ADL score (OR: 0.36 95% CI (0, 17; 0.75), p = 0.006), and a higher SOFA score (OR: 2.30 95% CI (1.07, 4.94), p = 0.03). Oseltamivir treatment, initiated within the first 48 h, was independently associated with survival (OR: 0.04 95% CI (0.002, 0.78), p = 0.034). Conclusions: Identification of mortality risk factors makes it possible to consider specific secondary prevention measures such as the rapid introduction of antiviral treatment. Combined with primary prevention, these measures could help to limit the mortality associated with influenza in older patients.
The Role of Mitochondria-Derived Peptides in Cardiovascular Diseases and Their Potential as Therapeutic Targets

Mitochondria-derived peptides (MDPs) are small peptides hidden in the mitochondrial DNA, maintaining mitochondrial function and protecting cells under different stresses. Currently, three types of MDPs have been identified: Humanin, MOTS-c and SHLP1-6. MDPs have demonstrated anti-apoptotic and anti-inflammatory activities, reactive oxygen species and oxidative stress-protecting properties both in vitro and in vivo. Recent research suggests that MDPs have a significant cardioprotective role, affecting CVDs (cardiovascular diseases) development and progression. CVDs are the leading cause of death globally; this term combines disorders of the blood vessels and heart. In this review, we focus on the recent progress in understanding the relationships between MDPs and the main cardiovascular risk factors (atherosclerosis, insulin resistance, hyperlipidaemia and ageing). We also will discuss the therapeutic application of MDPs, modified and synthetic MDPs, and their potential as novel biomarkers and therapeutic targets.
A Potentially Misleading Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) typically presents in patients with a chronic liver disease and rarely develops in healthy liver, especially within an accessory liver lobe. We present a case of a healthy 64-years-old woman who showed a serum alpha-fetoprotein (AFP) value of 226.3 µg/mL during a screening blood test. Past medical history was negative for chronic liver disease or cirrhosis. Intraoperative finding was an ovaloid mass connected with the second hepatic segment by a thin pedicle of hepatic tissue. Lesion was safely resected by laparoscopic approach. Histopathology analysis showed a trabecular hepatocellular carcinoma. After a 6-month follow up, there was no evidence of recurrent disease. This case report showed how serum AFP remains a highly sensitive marker, although the presentation of HCC was unusual. To our knowledge, this is the second case reported in the literature.