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High fructose diet has been defined as a risk factor and directly contributes to the development of cardiovascular disease and/or type 2 diabetes. In this paper, we evaluate the cardiovascular efficacy of antidiabetic phytotherapy in conditions of fructose-induced cardiometabolic damage model in rodents. Our findings indicate that high fructose diet has negative effects on the cardiovascular autonomic control. The blood glucose, pulse rate, arterial pressure and breathing rate changes induced by high fructose intake in rats was prevented by pronounced antidiabetic and antioxidant action of medical plants of Artsakh and Institute of Hydroponics Problems of NAS RA (Stevia rebaudiana, Lycium barbarum, Leonurus cardiac, Melissa officinalis, Smilax officinalis, Mentha piperita, Hypericum perforatum, Sambucus nigra, Ganoderma lucidum). The ethnobotanical phytotherapy reduced cardiovascular risk factors associated with of dietary carbohydrates, especially fructose containing beverages. [ABSTRACT FROM AUTHOR]

Stevia rebaudianaBertoni has been imported to the RA and Artsakh, and passed through the phase of production test. Complex researches have been carried out concerning to biological, biochemical and physiological influence of Stevia rebaudianaBertoni and food safety. As a result, it was provided, at least, 2,0-2,5 t/ha harvest in dry leaves soil culture and 4,5-5,0 t/ha harvest of preferable quality with the use of hydroponic phytotechnology. Stevia rebaudianaBertoni was proposed by NAS Institute of HydroponicsProblems of RA and was registered in RA National institute of standards, as a new technical cultured plant in Armenia [15]. [ABSTRACT FROM AUTHOR]

Abstract In less than half a century, allergy, originally perceived as a rare disease, has become a major public health threat, today affecting the lives of more than 60 million people in Europe, and probably close to one billion worldwide, thereby heavily impacting the budgets of public health systems. More disturbingly, its prevalence and impact are on the rise, a development that has been associated with environmental and lifestyle changes accompanying the continuous process of urbanization and globalization. Therefore, there is an urgent need to prioritize and concert research efforts in the field of allergy, in order to achieve sustainable results on prevention, diagnosis and treatment of this most prevalent chronic disease of the 21st century. The European Academy of Allergy and Clinical Immunology (EAACI) is the leading professional organization in the field of allergy, promoting excellence in clinical care, education, training and basic and translational research, all with the ultimate goal of improving the health of allergic patients. The European Federation of Allergy and Airways Diseases Patients’ Associations (EFA) is a non-profit network of allergy, asthma and Chronic Obstructive Pulmonary Disorder (COPD) patients’ organizations. In support of their missions, the present EAACI Position Paper, in collaboration with EFA, highlights the most important research needs in the field of allergy to serve as key recommendations for future research funding at the national and European levels. Although allergies may involve almost every organ of the body and an array of diverse external factors act as triggers, there are several common themes that need to be prioritized in research efforts. As in many other chronic diseases, effective prevention, curative treatment and accurate, rapid diagnosis represent major unmet needs. Detailed phenotyping/endotyping stands out as widely required in order to arrange or re-categorize clinical syndromes into more coherent, uniform and treatment-responsive groups. Research efforts to unveil the basic pathophysiologic pathways and mechanisms, thus leading to the comprehension and resolution of the pathophysiologic complexity of allergies will allow for the design of novel patient-oriented diagnostic and treatment protocols. Several allergic diseases require well-controlled epidemiological description and surveillance, using disease registries, pharmacoeconomic evaluation, as well as large biobanks. Additionally, there is a need for extensive studies to bring promising new biotechnological innovations, such as biological agents, vaccines of modified allergen molecules and engineered components for allergy diagnosis, closer to clinical practice. Finally, particular attention should be paid to the difficult-to-manage, precarious and costly severe disease forms and/or exacerbations. Nonetheless, currently arising treatments, mainly in the fields of immunotherapy and biologicals, hold great promise for targeted and causal management of allergic conditions. Active involvement of all stakeholders, including Patient Organizations and policy makers are necessary to achieve the aims emphasized herein.

Abstract Background Familial Mediterranean fever is a genetic autoinflammatory disease most commonly affecting the ethnic groups originating from around the Mediterranean Sea. Apoptosis plays an important role in down-regulation of the inflammatory response by reducing the lifespan of activated immunocompetent cells. Thus, increased apoptosis may be associated with pathogenesis of familial Mediterranean fever. Methods In the present study we determined the serum levels of apoptotic marker, Annexin A5, in familial Mediterranean fever patients, within an attack and attack-free, in comparison to healthy subjects and assessed the influence of colchicine treatment on this parameter. In addition, in all study subjects serum levels of C-reactive protein and interleukine-1β, and the total leukocyte count were also determined. Results Our results demonstrated that pathogenesis of familial Mediterranean fever is characterized by the increased levels of circulating Annexin A5, which is higher in patients within the attack and which associate with the increased levels of C-reactive protein and interleukine-1β and total leukocyte count. Conclusions The results obtained indicate elevated rates of apoptosis of subpopulations of leukocytes involved in autoinflammation and recurrent episodes of fever in familial Mediterranean fever. It was also revealed that regular colchicine treatment sufficiently decreases the rate of apoptosis in familial Mediterranean fever patients by affecting the intensity of autoinflammatory reactions.

Abstract Background In the present study we assessed the functional state of the major mediator of the immune response, the complement system, in post-traumatic stress disorder (PTSD). Methods Thirty one PTSD patients within 13 years from traumatic event and the same number of sex- and age-matched healthy volunteers were involved in this study. In the blood serum of the study subjects hemolytic activities of the classical and alternative complement pathways, as well as the activities of the individual complement components have been measured. Correlation analysis between all measured parameters was also performed. Results According to the results obtained PTSD is characterized by hyperactivation of the complement classical pathway, hypoactivation of the complement alternative pathway and overactivation of the terminal pathway. Conclusions The results obtained provide further evidence on the involvement of the inflammatory component in pathogenesis of PTSD.

Introduction: Exosome-enriched small extracellular vesicles (sEVs) are nanosized organelles known to participate in long distance communication between cells, including in the skin. Atopic dermatitis (AD) is a chronic inflammatory skin disease for which filaggrin ( FLG ) gene mutations are the strongest genetic risk factor. Filaggrin insufficiency affects multiple cellular function, but it is unclear if sEV-mediated cellular communication originating from the affected keratinocytes is also altered, and if this influences peptide and lipid antigen presentation to T cells in the skin., Methods: Available mRNA and protein expression datasets from filaggrin-insufficient keratinocytes (shFLG), organotypic models and AD skin were used for gene ontology analysis with FunRich tool. sEVs secreted by shFLG and control shC cells were isolated from conditioned media by differential centrifugation. Mass spectrometry was carried out for lipidomic and proteomic profiling of the cells and sEVs. T cell responses to protein, peptide, CD1a lipid antigens, as well as phospholipase A2-digested or intact sEVs were measured by ELISpot and ELISA., Results: Data analysis revealed extensive remodeling of the sEV compartment in filaggrin insufficient keratinocytes, 3D models and the AD skin. Lipidomic profiles of shFLGsEV showed a reduction in the long chain (LCFAs) and polyunsaturated fatty acids (PUFAs; permissive CD1a ligands) and increased content of the bulky headgroup sphingolipids (non-permissive ligands). This resulted in a reduction of CD1a-mediated interferon-γ T cell responses to the lipids liberated from shFLG-generated sEVs in comparison to those induced by sEVs from control cells, and an increase in interleukin 13 secretion. The altered sEV lipidome reflected a generalized alteration in the cellular lipidome in filaggrin-insufficient cells and the skin of AD patients, resulting from a downregulation of key enzymes implicated in fatty acid elongation and desaturation, i.e., enzymes of the ACSL, ELOVL and FADS family., Discussion: We determined that sEVs constitute a source of antigens suitable for CD1a-mediated presentation to T cells. Lipids enclosed within the sEVs secreted on the background of filaggrin insufficiency contribute to allergic inflammation by reducing type 1 responses and inducing a type 2 bias from CD1a-restricted T cells, thus likely perpetuating allergic inflammation in the skin., Competing Interests: Author GO has served on advisory boards or holds consultancies or research grants with Eli Lilly, Novartis, Janssen, BMS and UCB Pharma, Regeneron/Sanofi, Roche, Anaptysbio. GO has patent filed in the CD1a field. SJB holds or has recently held research grants from the Wellcome Trust, British Skin Foundation, EU/IMI H2020 ‘BIOMAP’, European Lead Factory, Charles Wolfson Charitable Trust, Rosetrees Trust, Stoneygate Trust, Pfizer, and consultancies with Abbvie, Sosei Heptares and Janssen. SG has a patent on B-cell targeting of EVs and is scientific advisor of Anjarium Biosciences. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kobiela, Hewelt-Belka, Frąckowiak, Kordulewska, Hovhannisyan, Bogucka, Etherington, Piróg, Dapic, Gabrielsson, Brown, Ogg and Gutowska-Owsiak.)

International cooperation beyond borders, institutions, and intergenerationally is an important aspect of science and research-based learning. Timing of learning also matters. Early exposure to group research-based learning can potentially have lasting positive impacts on youth and their careers in life sciences. Here, we report our work on the International Group Project (IGP), which builds on the International Biology Olympiad (IBO) organized in Yerevan, Armenia, in 2022. The IBO is an annual international competition for high school students held since 1990 around the world. We envisioned the IGP as a novel opportunity for life sciences research-based education among youth. We formed diverse IGP research teams 2 months before the IBO, and comprised high school students from 32 countries, communicating in a digital environment via videoconferencing. Each team formulated a research question in an IGP theme from five domains of life sciences: "Biomedicine," "Molecular and cell biology," "Bioinformatics and Artificial Intelligence," "Bionics and Biomimicry," "Across Species." Subsequently, team members collectively solved their research question by applying life sciences methodologies under supervision from a facilitator scientist. Each team created a poster based on their research and presented in-person to the public at a satellite activity at the IBO. A special subcommittee of the IBO International Jury graded posters and allocated prizes based on scientific ingenuity and presentation quality. This experience from the IGP lends evidence to the feasibility of research-based learning in life sciences for high school youth beyond borders. Moving research-based learning upstream and internationally is well poised to advance 21st century life sciences from both interdisciplinary and intergenerational standpoints. The historic impact of the COVID-19 pandemic suggests that youth engagement in research-based learning and innovation in life sciences is timely.

Long noncoding RNAs (lncRNAs) are linked to cancer via pathogenic changes in their expression levels. Yet, it remains unclear whether lncRNAs can also impact tumour cell fitness via function-altering somatic "driver" mutations. To search for such driver-lncRNAs, we here perform a genome-wide analysis of fitness-altering single nucleotide variants (SNVs) across a cohort of 2583 primary and 3527 metastatic tumours. The resulting 54 mutated and positively-selected lncRNAs are significantly enriched for previously-reported cancer genes and a range of clinical and genomic features. A number of these lncRNAs promote tumour cell proliferation when overexpressed in in vitro models. Our results also highlight a dense SNV hotspot in the widely-studied NEAT1 oncogene. To directly evaluate the functional significance of NEAT1 SNVs, we use in cellulo mutagenesis to introduce tumour-like mutations in the gene and observe a significant and reproducible increase in cell fitness, both in vitro and in a mouse model. Mechanistic studies reveal that SNVs remodel the NEAT1 ribonucleoprotein and boost subnuclear paraspeckles. In summary, this work demonstrates the utility of driver analysis for mapping cancer-promoting lncRNAs, and provides experimental evidence that somatic mutations can act through lncRNAs to enhance pathological cancer cell fitness., (© 2023. The Author(s).)

Filaggrin (FLG) protein is indispensable for multiple aspects of the epidermal barrier function but its accumulation in a monomeric filaggrin form may initiate premature keratinocytes death; it is unclear how filaggrin levels are controlled before the formation of storing keratohyalin granules. Here we show that keratinocyte-secreted small extracellular vesicles (sEVs) may contain filaggrin-related cargo providing a route of eliminating excess filaggrin from keratinocytes; blocking of sEV release has cytotoxic effects on those cells. Filaggrin-containing sEVs are found in plasma in both healthy individuals and atopic dermatitis patients. Staphylococcus aureus (S. aureus) enhances packaging and secretion of filaggrin-relevant products within the sEVs for enhanced export via a TLR2-mediated mechanism which is also linked to the ubiquitination process. This filaggrin removal system, preventing premature keratinocyte death and epidermal barrier dysfunction, is exploited by S. aureus which promotes filaggrin elimination from the skin that could help safeguard bacterial growth., (© 2023 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles.)

CAR T cell-based therapies have revolutionized the treatment of hematological malignancies such as leukemia and lymphoma within the last years. In contrast to the success in hematological cancers, the treatment of solid tumors with CAR T cells is still a major challenge in the field and attempts to overcome these hurdles have not been successful yet. Radiation therapy is used for management of various malignancies for decades and its therapeutic role ranges from local therapy to a priming agent in cancer immunotherapy. Combinations of radiation with immune checkpoint inhibitors have already proven successful in clinical trials. Therefore, a combination of radiation therapy may have the potential to overcome the current limitations of CAR T cell therapy in solid tumor entities. So far, only limited research was conducted in the area of CAR T cells and radiation. In this review we will discuss the potential and risks of such a combination in the treatment of cancer patients., (© 2023. The Author(s).)

Chimeric virus-like particles (cVLPs) show great potential in improving public health as they are safe and effective vaccine candidates. The capsid protein of caliciviruses has been described previously as a self-assembling, highly immunogenic delivery platform. The ability to significantly induce cellular and humoral immunity can be used to boost the immune response to low immunogenic foreign antigens displayed on the surface of VLPs. Capsid proteins of caliciviruses despite sequence differences share similar architecture with structural loops that can be genetically modified to present foreign epitopes on the surface of cVLPs. Here, based on the VP1 protein of norovirus (NoV), we investigated the impact of the localization of the epitope in different structural loops of the P domain on the immunogenicity of the presented epitope. In this study, three distinct loops of NoV VP1 protein were genetically modified to present a multivalent influenza virus epitope consisting of a tandem repeat of M2/NP epitopes. cVLPs presenting influenza virus-conserved epitopes in different localizations were produced in the insect cells and used to immunize BALB/c mice. Specific reaction to influenza epitopes was compared in sera from vaccinated mice to determine whether the localization of the foreign epitope has an impact on the immunogenicity., Competing Interests: Authors MP, BG and MC were employed by the company NanoExpo sp. z o.o. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Panasiuk, Chraniuk, Zimmer, Hovhannisyan, Krapchev, Peszyńska-Sularz, Narajczyk, Węsławski, Konopacka and Gromadzka.)

The presence of the ultramicroelement Se in food is irreplaceable. Se is a component of more than 30 biologically active compounds found in humans and animals. Se levels less than 1 mg/kg have been found to be beneficial to plants. Radish is one of the most commonly cultivated vegetables worldwide and is rich in bioactive substances, vitamins, enzymes, and minerals. Radish increases resistance and protects the human body from a number of diseases, particularly diabetes, cardiovascular, and gastrointestinal diseases. The physiological multifunctional (anti-diabetic, antioxidant, and anti-inflammatory) activity of the Se-enriched plant material was also studied. This is of practical significance because the data obtained can be the basis for the development of biotechnology for the enrichment of vegetable plants with Se.

Background: Cytotoxicity testing is a primary method to establish the safety of biomaterials, e.g., biocomposites. Biomaterials involve a wide range of medical materials, which are usually solid materials and are used in bone regeneration, cardiology, or dermatology. Current advancements in science and technology provide several standard cytotoxicity testing methods that are sufficiently sensitive to detect various levels of cellular toxicity, i.e., from low to high. The aim was to compare the direct and indirect methodology described in the ISO guidelines UNE-EN ISO 10993-5:2009 Part 5., Methods: Cell proliferation was measured using WST-1 assay, and cytotoxicity was measured using LDH test kit., Results: The results indicate that the molecular surface of biomaterials have impact on the cytotoxicity and proliferation profile. Based on these results, we confirm that the indirect method does not provide a clear picture of the cell condition after the exposure to the surface, and moreover, cannot provide complete results about the effects of the material., Conclusions: Comparison of both methods shows that it is pivotal to investigate biomaterials at the very early stages using both indirect and direct methods to access the influence of the released toxins and surface of the material on the cell condition.