Miracle-dz/UniFAR-FTUs huggingface dataset:
The Alterations in Mitochondrial Dynamics Following Cerebral Ischemia/Reperfusion Injury

Cerebral ischemia results in a poor oxygen supply and cerebral infarction. Reperfusion to the ischemic area is the best therapeutic approach. Although reperfusion after ischemia has beneficial effects, it also causes ischemia/reperfusion (I/R) injury. Increases in oxidative stress, mitochondrial dysfunction, and cell death in the brain, resulting in brain infarction, have also been observed following cerebral I/R injury. Mitochondria are dynamic organelles, including mitochondrial fusion and fission. Both processes are essential for mitochondrial homeostasis and cell survival. Several studies demonstrated that an imbalance in mitochondrial dynamics after cerebral ischemia, with or without reperfusion injury, plays an important role in the regulation of cell survival and infarct area size. Mitochondrial dysmorphology/dysfunction and inflammatory processes also occur after cerebral ischemia. Knowledge surrounding the mechanisms involved in the imbalance in mitochondrial dynamics following cerebral ischemia with or without reperfusion injury would help in the prevention or treatment of the adverse effects of cerebral injury. Therefore, this review aims to summarize and discuss the roles of mitochondrial dynamics, mitochondrial function, and inflammatory processes in cerebral ischemia with or without reperfusion injury from in vitro and in vivo studies. Any contradictory findings are incorporated and discussed.
Contribution of CYP2D6 Functional Activity to Oxycodone Efficacy in Pain Management: Genetic Polymorphisms, Phenoconversion, and Tissue-Selective Metabolism

Oxycodone is a widely used opioid for the management of chronic pain. Analgesic effects observed following the administration of oxycodone are mediated mostly by agonistic effects on the μ-opioid receptor. Wide inter-subject variability observed in oxycodone efficacy could be explained by polymorphisms in the gene coding for the μ-opioid receptor (OPRM1). In humans, oxycodone is converted into several metabolites, particularly into oxymorphone, an active metabolite with potent μ-opioid receptor agonist activity. The CYP2D6 enzyme is principally responsible for the conversion of oxycodone to oxymorphone. The CYP2D6 gene is highly polymorphic with encoded protein activities, ranging from non-functioning to high-functioning enzymes. Several pharmacogenetic studies have shown the importance of CYP2D6-mediated conversion of oxycodone to oxymorphone for analgesic efficacy. Pharmacogenetic testing could optimize oxycodone therapy and help achieve adequate pain control, avoiding harmful side effects. However, the most recent Clinical Pharmacogenetics Implementation Consortium guidelines fell short of recommending pharmacogenomic testing for oxycodone treatment. In this review, we (1) analyze pharmacogenomic and drug-interaction studies to delineate the association between CYP2D6 activity and oxycodone efficacy, (2) review evidence from CYP3A4 drug-interaction studies to untangle the nature of oxycodone metabolism and its efficacy, (3) report on the current knowledge linking the efficacy of oxycodone to OPRM1 variants, and (4) discuss the potential role of CYP2D6 brain expression on the local formation of oxymorphone. In conclusion, we opine that pharmacogenetic testing, especially for CYP2D6 with considerations of phenoconversion due to concomitant drug administration, should be appraised to improve oxycodone efficacy.
Segmental Assessment of Trunk Control in Moderate-to-Late Preterm Infants Related to Sitting Development

(1) Background: The assessment of postural segment control in premature infants seems to be critical during the onset of upright gross motor development, especially sitting. Identifying correlations between postural segment control and the development of sitting milestones could help with promoting optimal gross motor movement. However, data on this topic in home-raised premature infants via longitudinal design are still limited. The purpose of this study was to examine relationships between postural segment control and sitting development through series assessments from the corrected age of 4 months until the early onset of independent sitting attainment. (2) Methods: 33 moderate-to-late premature infants were recruited. Their trunk segment control was assessed using the Segmental Assessment of Trunk Control (SATCo), and sitting development was examined by the Alberta Infant Motor Scale (AIMS). Relationships between SATCo and sitting scores were analysed using Spearman’s rank correlation (rs). (3) Results: significant fair-to-good correlations between segmental trunk control and sitting scales were found from 4 months (rs = 0.370–0.420, p < 0.05) to the age of independent sitting attainment (rs = 0.561–0.602, p < 0.01). (4) Conclusion: relationships between the trunk segment control and sitting ability of moderate-to-late preterm infants were increased in accordance with age.
Identification and Characterization of Novel circRNAs Involved in Muscle Growth of Blunt Snout Bream (Megalobrama amblycephala)

Circular RNAs (circRNAs), a novel class of endogenous RNAs, have been recognized to play important roles in the growth of animals. However, the regulatory mechanism of circRNAs on fish muscle growth is still unclear. In this study, we performed whole transcriptome analysis of skeletal muscles from two populations with different growth rates (fast-growing and slow-growing) of blunt snout bream (Megalobrama amblycephala), an important fish species for aquaculture. The selected circRNAs were validated by qPCR and Sanger sequencing. Pairs of circRNA–miRNA–mRNA networks were constructed with the predicted differentially expressed (DE) pairs, which revealed regulatory roles in muscle myogenesis and hypertrophy. As a result, a total of 445 circRNAs were identified, including 42 DE circRNAs between fast-growing (FG) and slow-growing (SG) groups. Many of these DE circRNAs were related with aminoglycan biosynthetic and metabolic processes, cytokinetic processes, and the adherens junction pathway. The functional prediction results showed that novel_circ_0001608 and novel_circ_0002886, competing to bind with dre-miR-153b-5p and dre-miR-124-6-5p, might act as competing endogenous RNAs (ceRNAs) to control MamblycephalaGene14755 (pik3r1) and MamblycephalaGene10444 (apip) level, respectively, thus playing an important regulatory role in muscle growth. Overall, these results will not only help us to further understand the novel RNA transcripts in M. amblycephala, but also provide new clues to investigate the potential mechanism of circRNAs regulating fish growth and muscle development.
In Silico Analysis to Explore Lineage-Independent and -Dependent Transcriptional Programs Associated with the Process of Endothelial and Neural Differentiation of Human Induced Pluripotent Stem Cells

Despite a major interest in understanding how the endothelial cell phenotype is established, the underlying molecular basis of this process is not yet fully understood. We have previously reported the generation of induced pluripotent stem cells (iPS) from human umbilical vein endothelial cells and differentiation of the resulting HiPS back to endothelial cells (Ec-Diff), as well as neural (Nn-Diff) cell lineage that contained both neurons and astrocytes. Furthermore, the identities of these cell lineages were established by gene array analysis. Here, we explored the same arrays to gain insight into the gene alteration processes that accompany the establishment of endothelial vs. non-endothelial neural cell phenotypes. We compared the expression of genes that code for transcription factors and epigenetic regulators when HiPS is differentiated into these endothelial and non-endothelial lineages. Our in silico analyses have identified cohorts of genes that are similarly up- or downregulated in both lineages, as well as those that exhibit lineage-specific alterations. Based on these results, we propose that genes that are similarly altered in both lineages participate in priming the stem cell for differentiation in a lineage-independent manner, whereas those that are differentially altered in endothelial compared to neural cells participate in a lineage-specific differentiation process. Specific GATA family members and their cofactors and epigenetic regulators (DNMT3B, PRDM14, HELLS) with a major role in regulating DNA methylation were among participants in priming HiPS for lineage-independent differentiation. In addition, we identified distinct cohorts of transcription factors and epigenetic regulators whose alterations correlated specifically with the establishment of endothelial vs. non-endothelial neural lineages.
Social Resources for Transplanted Children and Families in European Union Hospitals of ERN TransplantChild

Social well-being is an intrinsic part of the current concept of health. In the context of chronic disease, there are many challenges we face in order to provide social well-being to patients and their families, even more if we talk about rare diseases. TransplantChild, a European Reference Network (ERN) in paediatric transplantation, works to improve the quality of life of transplanted children. It is not possible to improve the quality of life if the human and material resources are not available. With this study, we want to identify the economic aids, facilities, services, and financed products that are offered to families in different European centres. We also want to find out who provides these resources and the accessibility to them. We designed an ad hoc survey using the EU Survey software tool. The survey was sent to representatives of the 26 ERN members. In this article we present the results obtained in relation to two of the aspects analysed: long-term financial assistance and drugs, pharmaceuticals and medical devices. Some resources are equally available in all participating centres but there are significant differences in others, such as education aids or parapharmacy product financing. A local analysis of these differences is necessary to find feasible solutions for equal opportunities for all transplanted children in Europe. The experience of centres that already provide certain solutions successfully may facilitate the implementation of these solutions in other hospitals.
Lepidium sativum Secondary Metabolites (Essential Oils): In Vitro and In Silico Studies on Human Hepatocellular Carcinoma Cell Lines

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and the greatest cause of cancer-related death in the world. Garden cress (Lepidium sativum) seeds have been proven to possess extraordinary antioxidant, anti-inflammatory, hypothermic, and analgesic properties. In this study, in vitro cytotoxic efficiency evaluation of L. sativum fractions was performed against two hepatocellular carcinoma cell lines (HuH-7 and HEPG-2), and the expression of some apoptotic genes was explored. In addition, the chemical composition of a potent extract of L. sativum was analyzed using gas chromatography coupled with mass spectrometry. Then, molecular docking analysis was implemented to identify the potential targets of the L. sativum components’ most potent extract. Overall, the n-hexane extract was the most potent against the two HCC cell lines. Moreover, these cytotoxicity levels were supported by the significant downregulation of EGFR and BCL2 gene expression levels and the upregulation of SMAD3, BAX, and P53 expression levels in both HuH-7 and HEPG2 cell lines. Regarding L. sativum’s chemical composition, GC–MS analysis of the n-hexane extract led to the identification of thirty compounds, including, mainly, hydrocarbons and terpenoids, as well as other volatile compounds. Furthermore, the binding affinities and interactions of the n-hexane fraction’s major metabolites were predicted against EGFR and BCL2 molecular targets using the molecular docking technique. These findings reveal the potential use of L. Sativum in the management of HCC.
Less Polar Compounds and Targeted Antioxidant Potential (In Vitro and In Vivo) of Codium adhaerens C. Agardh 1822

Codium adhaerens from the Adriatic Sea (Croatia) was comprehensively investigated regarding less polar compounds for the first time. Although there are several phytochemical studies on C. adhaerens from other regions, this is the first report on volatile organic compounds (VOCs) from fresh (FrCa) and air-dried (DrCa) samples. The novelty is also related to its targeted antioxidant potential in vitro and in vivo. The main aims were to: (a) identify and compare VOCs of FrCa and DrCa obtained by headspace solid-phase microextraction (HS-SPME) and hydrodistillation (HD); (b) determine fatty acid (FA) composition of freeze-dried sample (FdCa); (c) determine the composition of less polar fractions of FdCa by high-performance liquid chromatography–high-resolution mass spectrometry with electrospray ionisation (UHPLC-ESI-HRMS); and (d) comprehensively evaluate the antioxidant activity of the fractions by four in vitro assays and in vivo zebrafish model (including embryotoxicity). Significant changes of VOCs were found after air drying. ω6 FAs were present in higher content than ω3 FAs indicating C. adhaerens as a good source of dietary polyunsaturated FAs. The results obtained in vivo correlate well with in vitro methods and both fractions exerted similar antioxidative responses which is in agreement with the high abundance of present biomolecules with known antioxidant properties (e.g., fucoxanthin, pheophytin a, and pheophorbide a). These results suggest that C. adhaerens might be a potent source of natural antioxidants that could be further used in the research of oxidative stress-related diseases.
The Interaction between microRNAs and the Wnt/β-Catenin Signaling Pathway in Osteoarthritis

Osteoarthritis (OA) is a chronic disease affecting the whole joint, which still lacks a disease-modifying treatment. This suggests an incomplete understanding of underlying molecular mechanisms. The Wnt/β-catenin pathway is involved in different pathophysiological processes of OA. Interestingly, both excessive stimulation and suppression of this pathway can contribute to the pathogenesis of OA. microRNAs have been shown to regulate different cellular processes in different diseases, including the metabolic activity of chondrocytes and osteocytes. To bridge these findings, here we attempt to give a conclusive overview of microRNA regulation of the Wnt/β-catenin pathway in bone and cartilage, which may provide insights to advance the development of miRNA-based therapeutics for OA treatment.
Topical Lidocaine plus Diclofenac as a Local Anesthetic Agent in Central Venous Catheterization; a Randomized Controlled Clinical Trial

Introduction: Various methods of analgesia can be used to reduce or prevent procedural pain in emergency department (ED). This study aimed to evaluate the effectiveness of topical lidocaine-diclofenac combination compared to lidocaine-prilocaine combination (Xyla-P) in reduction of the pain during central venous catheter (CVC) insertion. Methods: In this randomized clinical trial, 100 adult patients requiring CVC insertion in the ED were enrolled. These patients were randomly divided into two groups. The site of CVC insertion was covered with 2 g of topical Xyla-P cream in the first group, and 2 g of topical lidocaine-diclofenac cream in the second group. The primary outcome was the pain during CVC implantation. The secondary outcomes were physician satisfaction and the incidence of side effects. Results: On the visual analog scale (VAS), the pain score during CVC insertion was significantly lower in the second group (p = 0.027). However, there was no difference in pain scores during lidocaine injection between the two groups (p = 0.386). Also, there was no significant difference in the rate of side effects between the two groups (p = 1.0). The physician’s satisfaction with the first group was significantly lower than the second group (p = 0.042). Conclusion: Although the CVC insertion pain was significantly lower in patients who received the topical combination of Lidocaine plus Diclofenac, there was no clinically important difference between the two groups and both topical anesthetics were effective and safe in reducing pain intensity. Also, lidocaine-diclofenac combination cream was more cost-effective than Xyla-P cream.
Influence of Titanium Dioxide Nanoparticles on Human Health and the Environment

Nanotechnology has enabled tremendous breakthroughs in the development of materials and, nowadays, is well established in various economic fields. Among the various nanomaterials, TiO2 nanoparticles (NPs) occupy a special position, as they are distinguished by their high availability, high photocatalytic activity, and favorable price, which make them useful in the production of paints, plastics, paper, cosmetics, food, furniture, etc. In textiles, TiO2 NPs are widely used in chemical finishing processes to impart various protective functional properties to the fibers for the production of high-tech textile products with high added value. Such applications contribute to the overall consumption of TiO2 NPs, which gives rise to reasonable considerations about the impact of TiO2 NPs on human health and the environment, and debates regarding whether the extent of the benefits gained from the use of TiO2 NPs justifies the potential risks. In this study, different TiO2 NPs exposure modes are discussed, and their toxicity mechanisms—evaluated in various in vitro and in vivo studies—are briefly described, considering the molecular interactions with human health and the environment. In addition, in the conclusion of this study, the toxicity and biocompatibility of TiO2 NPs are discussed, along with relevant risk management strategies.
Evaluating the Inclusion of Cold-Pressed Rapeseed Cake in the Concentrate for Dairy Cows upon Ruminal Biohydrogenation Process, Ruminal Microbial Community and Milk Production and Acceptability

Simple Summary Soybean meal and palm oil are important protein and energy sources in European livestock production, respectively. In the next decades, the demand for these feedstuffs is supposed to increase as the world population and its demand for meat and dairy products increases. Alternatives to replace those feedstuffs are necessary. It is necessary to promote low-input, local, and circular production systems: in this sense, adopting feeding systems that use cheaper and local alternative feedstuffs represents a good strategy. One of them is the product obtained after a simple pressing process for the production of biofuels. Cold pressing usually produces oil that can be used as biofuel and a cake rich in fat and with high oil quality but with lower protein content than the conventionally solvent-extracted cakes. Therefore, the availability of cold-pressed cakes can represent an example of integration between the industry and livestock production. The objective of this study was to assess the suitability of formulating cold-pressed rapeseed cake (CPRC) in a dairy cows’ concentrate as a substitute for conventional feedstuffs. Feeding CPRC has the advantage of slightly improving the milk fatty acid profile and consumer acceptance. In conclusion, CPRC can replace conventional feedstuffs without detrimental effects on milk production and composition. Abstract The aim of this trial was to assess the effect of feeding a concentrate including cold-pressed rapeseed cake (CPRC) on productive performance, milk quality and its sensory properties, ruminal biohydrogenation, and bacterial communities. Eighteen cows were paired, and two experimental diets (control vs. CPRC) were distributed within the pair. Concentrates were iso-energetic and iso-proteic and contained similar amounts of fat. The average days in milk, milk yield, and body weight of the animals were (mean ± SD) 172 ± 112 d, 585 ± 26 kg, and 25.4 ± 6.2 kg/d, respectively. The experiment lasted for 10 wk. Feeding CPRC resulted in lower ruminal saturated (p < 0.001) and higher monounsaturated (p = 0.002) fatty acids. Feeding CPRC increased Ruminococcus, Prevotella, and Entodinium but decreased Blautia; p-75-a5; undefined genera within orders Clostridiaceae and RF39 and within families Christensenellaceae, Lachnospiracease, and Ruminococcaceae; and fungi from the phylum neocallimastigomycota. The milk fatty acid profile was characterized by a lower n6:n3 ratio (p = 0.028). Feeding CPRC did not affect the milk yield, milk quality, or fat corrected milk (p > 0.05). Feeding CPRC improved the overall milk acceptability (p = 0.047). In conclusion, CPRC affected some microbial taxa, modified the biohydrogenation process, and improved the milk fatty acid profile and consumer acceptance without detrimental effects on milk production and composition.
Bioactive Glass Applications: A Literature Review of Human Clinical Trials

The use of bioactive glasses in dentistry, reconstructive surgery, and in the treatment of infections can be considered broadly beneficial based on the emerging literature about the potential bioactivity and biocompatibility of these materials, particularly with reference to Bioglass® 45S5, BonAlive® and 19-93B3 bioactive glasses. Several investigations have been performed (i) to obtain bioactive glasses in different forms, such as bulk materials, powders, composites, and porous scaffolds and (ii) to investigate their possible applications in the biomedical field. Although in vivo studies in animals provide us with an initial insight into the biological performance of these systems and represent an unavoidable phase to be performed before clinical trials, only clinical studies can demonstrate the behavior of these materials in the complex physiological human environment. This paper aims to carefully review the main published investigations dealing with clinical trials in order to better understand the performance of bioactive glasses, evaluate challenges, and provide an essential source of information for the tailoring of their design in future applications. Finally, the paper highlights the need for further research and for specific studies intended to assess the effect of some specific dissolution products from bioactive glasses, focusing on their osteogenic and angiogenic potential.
New Incretin Combination Treatments under Investigation in Obesity and Metabolism: A Systematic Review

The worldwide upward trend in obesity in adults and the increased incidence of overweight children suggests that the future risk of obesity-related illnesses will be increased. The existing anti-obesity drugs act either in the central nervous system (CNS) or in the peripheral tissues, controlling the appetite and metabolism. However, weight regain is a common homeostatic response; current anti-obesity medications show limited effectiveness in achieving long-term weight loss maintenance; in addition to being linked to various side effects. Combined anti-obesity medications (per os or injectable) target more than one of the molecular pathways involved in weight regulation, as well as structures in the CNS. In this systematic review, we conducted a search of PubMed and The ClinicalTrials.gov up to February 2021. We summarized the Food and Drug Administration (FDA)-approved medications, and we focused on the combined pharmacological treatments, related to the incretin hormones, currently in a clinical trial phase. We also assessed the mechanism of action and therapeutic utility of these novel hybrid peptides and potential interactions with other regulatory hormones that may have beneficial effects on obesity. As we improve our understanding of the pathophysiology of obesity, we hope to identify more novel treatment strategies.