Miracle-dz/UniFAR-FTUs huggingface dataset:
GATA4 Regulates Inflammation-Driven Pancreatic Ductal Adenocarcinoma Progression

Cancer-associated inflammation is a key molecular feature in the progression of pancreatic ductal adenocarcinoma (PDAC). GATA4 is a transcription factor that participates in the regulation and normal development of several endoderm- and mesoderm-derived tissues such as the pancreas. However, it remains unclear whether GATA4 is involved in the inflammation-driven development of pancreatic cancer. Here, we employed quantitative reverse transcription PCR, immunohistochemistry, and differential expression analysis to investigate the association between GATA4 and inflammation-driven PDAC. We found that overexpression of GATA4 in pancreatic tumor tissue was accompanied by increased levels of inflammatory macrophages. We used macrophage-conditioned medium to validate inflammation models following treatment with varying concentrations of lipopolysaccharide and determined whether GATA4-dependent inflammatory stimuli affected pancreatic cancer cell invasion and growth in vitro. Nude mouse models of dibutyltin dichloride-induced chronic pancreatitis with orthotopic tumor xenografts were used to evaluate the effect of the inflammatory microenvironment on GATA4 expression in vivo. Our findings indicate that overexpression of GATA4 dramatically aggravated inflammatory stimuli-induced pancreatic cancer cell invasion and growth via NF-κB and STAT3 signaling, whereas silencing of GATA4 attenuated invasion and growth. Overall, our findings suggest that inflammation-driven cancer progression is dependent on GATA4 expression and is mediated through the STAT3 and NF-κB signaling pathways.
The Embodied-Enactive-Interactive Brain: Bridging Neuroscience and Creative Arts Therapies

The recognition and incorporation of evidence-based neuroscientific concepts into creative arts therapeutic knowledge and practice seem valuable and advantageous for the purpose of integration and professional development. Moreover, exhilarating insights from the field of neuroscience coincide with the nature, conceptualization, goals, and methods of Creative Arts Therapies (CATs), enabling comprehensive understandings of the clinical landscape, from a translational perspective. This paper contextualizes and discusses dynamic brain functions that have been suggested to lie at the heart of intra- and inter-personal processes. Touching upon fundamental aspects of the self and self-other interaction, the state-of-the-art neuroscientific-informed views will shed light on mechanisms of the embodied, predictive and relational brain. The conceptual analysis introduces and interweaves the following contemporary perspectives of brain function: firstly, the grounding of mental activity in the lived, bodily experience will be delineated; secondly, the enactive account of internal models, or generative predictive representations, shaped by experience, will be defined and extensively deliberated; and thirdly, the interpersonal simulation and synchronization mechanisms that support empathy and mentalization will be thoroughly considered. Throughout the paper, the cross-talks between the brain and the body, within the brain through functionally connected neural networks and in the context of agent-environment dynamics, will be addressed. These communicative patterns will be elaborated on to unfold psychophysiological linkage, as well as psychopathological shifts, concluding with the neuroplastic change associated with the formulation of CATs. The manuscript suggests an integrative view of the brain-body-mind in contexts relevant to the therapeutic potential of the expressive creative arts and the main avenues by which neuroscience may ground, enlighten and enrich the clinical psychotherapeutic practice.
Seasonal Photophysiological Performance of Adult Western Baltic Fucus vesiculosus (Phaeophyceae) Under Ocean Warming and Acidification

Shallow coastal marine ecosystems are exposed to intensive warming events in the last decade, threatening keystone macroalgal species such as the bladder wrack (Fucus vesiculosus, Phaeophyceae) in the Baltic Sea. Herein, we experimentally tested in four consecutive benthic mesocosm experiments, if the single and combined impact of elevated seawater temperature (Δ + 5°C) and pCO2 (1100 ppm) under natural irradiance conditions seasonally affected the photophysiological performance (i.e., oxygen production, in vivo chlorophyll a fluorescence, energy dissipation pathways and chlorophyll concentration) of Baltic Sea Fucus. Photosynthesis was highest in spring/early summer when water temperature and solar irradiance increases naturally, and was lowest in winter (December to January/February). Temperature had a stronger effect than pCO2 on photosynthetic performance of Fucus in all seasons. In contrast to the expectation that warmer winter conditions might be beneficial, elevated temperature conditions and sub-optimal low winter light conditions decreased photophysiological performance of Fucus. In summer, western Baltic Sea Fucus already lives close to its upper thermal tolerance limit and future warming of the Baltic Sea during summer may probably become deleterious for this species. However, our results indicate that over most of the year a combination of future ocean warming and increased pCO2 will have slightly positive effects for Fucus photophysiological performance.
Research and Development of Microphysiological Systems in Japan Supported by the AMED-MPS Project

Microphysiological systems (MPS) have been actively developed as a new technology for in vitro toxicity testing platforms in recent years. MPS are culture techniques for the reconstruction of the specific functions of human organs or tissues in a limited space to create miniaturized human test systems. MPS have great promise as next-generation in vitro toxicity assessment systems. Here, I will review the current status of MPS and discuss the requirements that must be met in order for MPS to be implemented in the field of drug discovery, presenting the example of an in vitro cell assay system for drug-induced liver injury, which is the research subject in our laboratory. Projects aimed at the development of MPS were implemented early in Europe and the United States, and the AMED-MPS project was launched in Japan in 2017. The AMED-MPS project involves industry, government, and academia. Researchers in the field of drug discovery in the pharmaceutical industry also participate in the project. Based on the discussions made in the project, I will introduce the requirements that need to be met by liver-MPS as in vitro toxicity test platforms.
circDENND1B Participates in the Antiatherosclerotic Effect of IL-1β Monoclonal Antibody in Mouse by Promoting Cholesterol Efflux via miR-17-5p/Abca1 Axis

Inflammation is a crucial mediator of atherosclerosis, and several therapeutic methods that focus on inflammatory cytokines, including interleukin-1β (IL-1β), have proven effective in preventing atherogenesis. Circular RNAs (circRNAs) are a subclass of non-coding RNAs (ncRNAs) that can exert critical functions in the regulation of atherosclerosis. Here, using circRNA sequencing, we revealed that circRNA circDENND1B (mmu_circ_0000081) is a promising novel mediator of atherosclerosis in mouse. The expression of circDENND1B is negatively related to the progression of atherosclerosis and foam cell formation, and the upregulation of circDENND1B significantly alleviates foam cell formation induced by ox-LDL by promoting cholesterol efflux. Moreover, circDENND1B participates in the anti-atherosclerotic effect of IL-1β monoclonal antibody (IL-1β mAb), both in vivo and in vitro. With bioinformatic prediction and RNA pull-down assays, we determined that circDENND1B sponges mmu-miR-17-5p to promote Abca1 expression in cells treated with IL-1β mAb. Our study revealed that circDENND1B, a novel regulator of cholesterol efflux, is a potential therapeutic target in atherosclerosis and provides new insights into the interaction between inflammation and cholesterol transport.
Impact of Interactive Learning Environments on Learning and Cognitive Development of Children With Special Educational Needs: A Literature Review

Children with special educational needs (SEN) achieve lower educational levels than their peers without special needs, leading to a higher risk of social exclusion in the future. Inclusive education aims to promote learning and to benefit the cognitive development of these students, and numerous research studies have indicated that interactive environments benefit inclusion. However, it is necessary to know how these inclusive environments can positively impact the academic improvement and development of these students' cognitive skills. This article provides a review of the scientific literature from Web of Science, SCOPUS, ERIC, and PsychINFO to understand the impact of interactive environments on the academic learning and cognitive skill development of children with SEN. A total of 17 studies were selected. Those studies showed the effectiveness of interactive learning environments in promoting instrumental learning, increasing academic involvement, and improving the cognitive development of children with disabilities. Based on these results, it can be concluded that interaction-based interventions with an inclusive approach nurture the learning and cognitive development of students with SEN.
Comparative Genome-Wide Alternative Splicing Analysis of Longissimus Dorsi Muscles Between Japanese Black (Wagyu) and Chinese Red Steppes Cattle

Alternative splicing is a ubiquitous regulatory mechanism in gene expression that allows a single gene generating multiple messenger RNAs (mRNAs). Significant differences in fat deposition ability and meat quality traits have been reported between Japanese black cattle (Wagyu) and Chinese Red Steppes, which presented a unique model for analyzing the effects of transcriptional level on marbling fat in livestock. In previous studies, the differentially expressed genes (DGEs) in longissimus dorsi muscle (LDM) samples between Wagyu and other breeds of beef cattle have been reported. In this study, we further investigated the differences in alternative splicing in LDM between Wagyu and Chinese Red Steppes cattle. We identified several alternative splicing types including cassette exon, mutually exclusive exons, alternative 5′ splice site, alternative 3′ splice site, alternative start exon, and intron retention. In total, 115 differentially expressed alternatively spliced genes were obtained, of which 17 genes were enriched in the metabolic pathway. Among the 17 genes, 5 genes, including MCAT, CPT1B, HADHB, SIRT2, and DGAT1, appeared to be the novel spliced candidates that affect the lipid metabolism in cattle. Additionally, another 17 genes were enriched in the Gene Ontology (GO) terms related to muscle development, such as NR4A1, UQCC2, YBX3/CSDA, ITGA7, etc. Overall, altered splicing and expression levels of these novel candidates between Japanese black cattle and Chinese Red Steppes revealed by RNA-seq suggest their potential involvement in the muscle development and fat deposition of beef cattle.
Small-Scale Geochemical Heterogeneities and Seasonal Variation of Iron and Sulfide in Salt Marshes Revealed by Two-Dimensional Sensors

Loss of tidal wetlands is a world-wide phenomenon. Many factors may contribute to such loss, but among them are geochemical stressors such as exposure of the marsh plants to elevated levels on hydrogen sulfide in the pore water of the marsh peat. Here we report the results of a study of the geochemistry of iron and sulfide at different seasons in unrestored (JoCo) and partially restored (Big Egg) salt marshes in Jamaica Bay, a highly urbanized estuary in New York City where the loss of salt marsh area has accelerated in recent years. The spatial and temporal 2-dimensional distribution patterns of dissolved Fe2+ and H2S in salt marshes were in situ mapped with high resolution planar sensors for the first time. The vertical profiles of Fe2+ and hydrogen sulfide, as well as related solutes and redox potentials in marsh were also evaluated by sampling the pore water at discrete depths. Sediment cores were collected at various seasons and the solid phase Fe, S, N, C, and chromium reducible sulfide in marsh peat at discrete depths were further investigated in order to study Fe and S cycles, and their relationship to the organic matter cycling at different seasons. Our results revealed that the redox sensitive elements Fe2+ and S2– showed significantly heterogeneous and complex three dimensional distribution patterns in salt marsh, over mm to cm scales, directly associated with the plant roots due to the oxygen leakage from roots and redox diagenetic reactions. We hypothesize that the oxic layers with low/undetected H2S and Fe2+ formed around roots help marsh plants to survive in the high levels of H2S by reducing sulfide absorption. The overall concentrations of Fe2+ and H2S and distribution patterns also seasonally varied with temperature change. H2S level in JoCo sampling site could change from <0.02 mM in spring to >5 mM in fall season, reflecting significantly seasonal variation in the rates of bacterial oxidation of organic matter at this marsh site. Solid phase Fe and S showed that very high fractions of the diagenetically reactive iron at JoCo and Big Egg were associated with pyrite that can persist for long periods in anoxic sediments. This implies that there is insufficient diagenetically reactive iron to buffer the pore water hydrogen sulfide through formation of iron sulfides at JoCo and Big Egg.
SELDI TOF hmotnostní spektrometrie v onkologickém výzkumu - pilotní metodická data a potenciální klinické aplikace

Greplová K. , Pilný R. , Dubská L. , Brožková K. , Michalová E. , Vojtěšek B. , Žaloudík J., Vyzula R. , Nenutil R. , Valík D. : SELDI TOF mass spectrometry in cancer research – pilot methodological data and possible clinical applications We present our pilot results on application of SELDI TOF mass spectrometry in cancer research. We discuss applicability of this technology on various clinical material commonly studied in cancer patients such as serum, plasma, cell fractions, and native tissues.
From Prokaryotes to Eukaryotes: Insights Into the Molecular Structure of Glycogen Particles

Glycogen is a highly-branched polysaccharide that is widely distributed across the three life domains. It has versatile functions in physiological activities such as energy reserve, osmotic regulation, blood glucose homeostasis, and pH maintenance. Recent research also confirms that glycogen plays important roles in longevity and cognition. Intrinsically, glycogen function is determined by its structure that has been intensively studied for many years. The recent association of glycogen α-particle fragility with diabetic conditions further strengthens the importance of glycogen structure in its function. By using improved glycogen extraction procedures and a series of advanced analytical techniques, the fine molecular structure of glycogen particles in human beings and several model organisms such as Escherichia coli, Caenorhabditis elegans, Mus musculus, and Rat rattus have been characterized. However, there are still many unknowns about the assembly mechanisms of glycogen particles, the dynamic changes of glycogen structures, and the composition of glycogen associated proteins (glycogen proteome). In this review, we explored the recent progresses in glycogen studies with a focus on the structure of glycogen particles, which may not only provide insights into glycogen functions, but also facilitate the discovery of novel drug targets for the treatment of diabetes mellitus.
Anti-PD-1 Immunotherapy and Bee Venom for Relapsed and Refractory Liposarcoma: A Case Report

Cancer immunotherapies, including immune checkpoint inhibitors, elicit long-term clinical responses but many cancer patients do not respond. Intensive efforts are therefore underway to identify additional immune pathways that may be modulated to enhance the efficacy of existing immunotherapies. Bee venom strongly stimulates the immune system, and is used as a complementary therapy to treat cancer pain in patients with advanced tumors in China. Bee venom contains several allergenic protease inhibitors and peptides. It triggers hypersensitivity reactions; that is, it is an immune system agonist. The generation of a spontaneous T cell response against tumor-associated antigens requires innate immune activation; this drives type I interferon production. We report a patient with a relapsed and refractory liposarcoma who had undergone several operations, chemotherapies, and radiotherapies. The tumor was large. The patient had attained the maximum radiation exposure dose. The tumor was resistant to chemotherapy and was infiltrating the pericardium, lungs, and diaphragm. The patient was a poor candidate for resection. He thus received apitherapy (a combination of bee venom and acupuncture) to control pain; then apatinib (an anti-angiogenic drug) was given to inhibit tumor growth but was terminated early because the patient could not tolerate the side effects. Subsequently, a programmed death 1 inhibitor was combined with apitherapy. Bee venom served as an innate immune system agonist promoting immune cell priming and recruitment in the tumor microenvironment. The patient was finally able to undergo radical liposarcoma resection, and no evidence of recurrence was found at re-examination 16 months after surgery.
Safety and Efficacy of Vitamin K Antagonists vs. Novel Oral Anticoagulants in Patients With Left Ventricular Thrombus: A Meta-Analysis

Aims: A meta-analysis was conducted to evaluate the safety and efficacy of novel oral anticoagulants (NOACs) compared with vitamin K antagonists (VKAs) in patients with left ventricular thrombus (LVT). Methods and Results: We searched PubMed, Web of Science, and Cochrane Library for cohort studies comparing the use of VKAs vs. NOACs for the treatment of LVT from the earliest date available to September 30, 2020. The predetermined efficacy and safety outcomes included thromboembolic events, resolution of LVT, clinically significant bleedings, and all-cause death. Fixed-effects model was used to estimate the pooled effects. Publication bias analyses and sensitivity analyses were conducted to check the robustness of results. A total of 6 studies enrolling 837 patients (mean age 60.2 ± 1.6 years; 77.2% were male) were included. We found no significant differences in thromboembolic events [relative risk (RR) 1.69, 95% confidence interval (CI) 0.94–3.06, P 0.08, I2 12.7%], the rate of resolution of thrombus (RR 1.08, 95% CI 0.96–1.21, P 0.21, I2 4.8%), and clinically significant bleedings (RR 0.70, 95% CI 0.37–1.32, P 0.27, I2 0%) between the VKAs and NOACs group. Additionally, no significant difference in all-cause mortality was found between the two groups (RR 1.24, 95% CI 0.79–1.96, P 0.35, I2 0.0%). Sensitivity analyses, using the “1-study removed” method, detected no significant differences. Conclusion: NOACs and VKAs have similar efficacy and safety in treating LVT, prompting the inference that NOACs are the possible alternatives of VKAs in LVT therapy.
Identification of Hub Genes and MicroRNAs Associated With Idiopathic Pulmonary Arterial Hypertension by Integrated Bioinformatics Analyses

Objective The aim of this study is the identification of hub genes associated with idiopathic pulmonary arterial hypertension (IPAH). Materials and Methods GSE15197 gene expression data was downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified by screening IPAH patients and controls. The 5,000 genes with the greatest variances were analyzed using a weighted gene co-expression network analysis (WGCNA). Modules with the strongest correlation with IPAH were chosen, followed by a functional enrichment analysis. Protein–protein interaction (PPI) networks were constructed to identify hub gene candidates using calculated degrees. Real hub genes were found from the overlap of DEGs and candidate hub genes. microRNAs (miRNAs) targeting real hub genes were found by screening miRNet 2.0. The most important IPAH miRNAs were identified. Results There were 4,395 DEGs identified. WGCNA indicated that green and brown modules associated most strongly with IPAH. Functional enrichment analysis showed that green and brown module genes were mainly involved in protein digestion and absorption and proteoglycans in cancer, respectively. The top ten candidate hub genes in green and brown modules were identified, respectively. After overlapping with DEGs, 11 real hub genes were identified: EP300, MMP2, CDH2, CDK2, GNG10, ALB, SMC2, DHX15, CUL3, BTBD1, and LTN1. These genes were expressed with significant differences in IPAH versus controls, indicating a high diagnostic ability. The miRNA–gene network showed that hsa-mir-1-3p could associate with IPAH. Conclusion EP300, MMP2, CDH2, CDK2, GNG10, ALB, SMC2, DHX15, CUL3, BTBD1, and LTN1 may play essential roles in IPAH. Predicted miRNA hsa-mir-1-3p could regulate gene expression in IPAH. Such hub genes may contribute to the pathology and progression in IPAH, providing potential diagnostic and therapeutic opportunities for IPAH patients.
The α-Gliadins in Bread Wheat: Effect of Nitrogen Treatment on the Expression of the Major Celiac Disease Immunogenic Complex in Two RNAi Low-Gliadin Lines

Celiac Disease (CD) is an autoimmune disorder that affects approximately 1% of the worldwide population. The α-gliadins of wheat contain the 33-mer peptide, the most active peptide in CD both in adults and pediatric patients. In this study, we have characterized the variants and expression profile of an α-gliadins amplicon, harboring the 33-mer peptide, in two low-gliadin RNAi wheat lines, under two different Nitrogen (N) treatments. We estimated that the amplicon expands 45 different α-gliadin variants with high variability due to length, randomly distributed SNPs, and the presence of encoded CD epitopes. Expression of this amplicon is reduced in both RNAi lines in comparison to the wild type. High N treatment significantly increases transcripts of the amplicon in the wild type, but not in the transgenic lines. Classification of α-gliadin variants, considering the number of epitopes, revealed that amplicon variants containing the full complement of 33-mer peptide were affected by N treatment, increasing their expression when N was increased. Line D793 provided higher and more stable silencing through different N fertilization regimes, expressing fewer CD epitopes than D783. Results of this study are important for better understanding of RNAi α-gliadin silencing in response to N treatments, and for undertaking new strategies by RNAi or CRISPR/Cas toward obtaining new varieties suitable for people suffering gluten intolerances.