Miracle-dz/UniFAR-FTUs huggingface dataset:
Dynamic Physiological Culture of Ex Vivo Human Tissue: A Systematic Review

Simple Summary Within cancer research, a strong emphasis is placed on the development of models that accurately reproduce the conditions in which tumours develop and grow. A limitation of several models is that they fail to replicate the tumour’s blood supply. Our aim was to evaluate the concurrent literature regarding dynamic physiological culture techniques that have been used to successfully culture human tissue. We conducted a systematic review of the literature and identified 22 articles that described the use of different dynamic culture techniques in order to create a system that was physiologically representative. The most common method described was the use of perfusion culture. This article serves as a detailed reference of novel technologies that can be implemented within cancer research in order to improve the physiological conditions of current culture techniques. Realistic cancer models will translate into a greater understanding of the disease which will directly impact on patient outcomes. Abstract Conventional static culture fails to replicate the physiological conditions that exist in vivo. Recent advances in biomedical engineering have resulted in the creation of novel dynamic culturing systems that permit the recapitulation of normal physiological processes ex vivo. Whilst the physiological benefit for its use in the culture of two-dimensional cellular monolayer has been validated, its role in the context of primary human tissue culture has yet to be determined. This systematic review identified 22 articles that combined dynamic physiological culture techniques with primary human tissue culture. The most frequent method described (55%) utilised dynamic perfusion culture. A diverse range of primary human tissue was successfully cultured. The median duration of successful ex vivo culture of primary human tissue for all articles was eight days; however, a wide range was noted (5 h–60 days). Six articles (27%) reported successful culture of primary human tissue for greater than 20 days. This review illustrates the physiological benefit of combining dynamic culture with primary human tissue culture in both long-term culture success rates and preservation of native functionality of the tissue ex vivo. Further research efforts should focus on developing precise biochemical sensors that would allow for real-time monitoring and automated self-regulation of the culture system in order to maintain homeostasis. Combining these techniques allows the creation of an accurate system that can be used to gain a greater understanding of human physiology.
Combined Effect of Deoxynivalenol (DON) and Porcine Circovirus Type 2 (Pcv2) on Inflammatory Cytokine mRNA Expression

A host’s immune system can be invaded by mycotoxin deoxynivalenol (DON) poisoning and porcine circovirus type 2 (PCV2) infections, which affect the host’s natural immune function. Pro-inflammatory cytokines, IL-1β and IL-6, are important regulators in the process of natural immune response, which participate in inflammatory response and enhance immune-mediated tissue damage. Preliminary studies have shown that DON promotes PCV2 infection by activating the MAPK signaling pathway. Here, we explored whether the mRNA expression of IL-1β and IL-6, induced by the combination of DON and PCV2, would depend on the MAPK signaling pathway. Specific pharmacological antagonists U0126, SP600125 and SB203580, were used to inhibit the activities of ERK, JNK and p38 in the MAPK signaling pathway, respectively. Then, the mRNA expression of IL-1β and IL-6 in PK-15 cells was detected to explore the effect of the MAPK signaling pathway on IL-1β and IL-6 mRNA induced by DON and PCV2. The results showed that PK-15 cells treated with DON or PCV2 induced the mRNA expression of IL-1β and IL-6 in a time- and dose-dependent manner. The combination of DON and PCV2 has an additive effect on inducing the mRNA expression of IL-1β and IL-6. Additionally, both DON and PCV2 could induce the mRNA expression of IL-1β and IL-6 via the ERK and the p38 MAPK signal pathways, while PCV2 could induce it via the JNK signal pathway. Taken together, our results suggest that MAPKs play a contributory role in IL-1β and IL-6 mRNA expression when induced by both DON and PCV2.
T-Type Ca2+ Enhancer SAK3 Activates CaMKII and Proteasome Activities in Lewy Body Dementia Mice Model

Lewy bodies are pathological characteristics of Lewy body dementia (LBD) and are composed of α-synuclein (α-Syn), which is mostly degraded via the ubiquitin–proteasome system. More importantly, 26S proteasomal activity decreases in the brain of LBD patients. We recently introduced a T-type calcium channel enhancer SAK3 (ethyl-8-methyl-2,4-dioxo-2-(piperidin-1-yl)- 2H-spiro[cyclopentane-1,3-imidazo [1,2-a]pyridin]-2-ene-3-carboxylate) for Alzheimer’s disease therapeutics. SAK3 enhanced the proteasome activity via CaMKII activation in amyloid precursor protein knock-in mice, promoting the degradation of amyloid-β plaques to improve cognition. At this point, we addressed whether SAK3 promotes the degradation of misfolded α-Syn and the aggregates in α-Syn preformed fibril (PFF)-injected mice. The mice were injected with α-Syn PFF in the dorsal striatum, and SAK3 (0.5 or 1.0 mg/kg) was administered orally for three months, either immediately or during the last month after injection. SAK3 significantly inhibited the accumulation of fibrilized phosphorylated-α-Syn in the substantia nigra. Accordingly, SAK3 significantly recovered mesencephalic dopamine neurons from cell death. Decreased α-Syn accumulation was closely associated with increased proteasome activity. Elevated CaMKII/Rpt-6 signaling possibly mediates the enhanced proteasome activity after SAK3 administration in the cortex and hippocampus. CaMKII/Rpt-6 activation also accounted for improved memory and cognition in α-Syn PFF-injected mice. These findings indicate that CaMKII/Rpt-6-dependent proteasomal activation by SAK3 recovers from α-Syn pathology in LBD.
Constitutive PSGL-1 Correlates with CD30 and TCR Pathways and Represents a Potential Target for Immunotherapy in Anaplastic Large T-Cell Lymphoma

Simple Summary P-selectin glycoprotein ligand-1 (PSGL-1), coded by the SELPLG gene, is the major ligand of selectins and plays a pivotal role in tethering, rolling and extravasation of immune cells. PSGL-1 involvement in core molecular programs, such as SYK, PLCγ2, PI3Kγ or MAPK pathways, suggests additional functions beyond the modulation of cell trafficking. Recently, several studies identified a novel mechanism responsible for PSGL-1-mediated immune suppression in the tumor microenvironment and proved a novel concept of PSGL-1 as a critical checkpoint molecule for tumor immunotherapy. The immunotherapeutic approach has gained an ever-growing interest in the treatment of several hematological malignancies, and in particular, novel targets for immunotherapy are still highly sought-after in T-cell lymphomas. Based on our results obtained through gene expression profiling and immunohistochemical analysis, PSGL-1, already suggested as a potential target in multiple myeloma humoral immunotherapy, could be considered noteworthy among the candidates. Abstract Due to the high expression of P-selectin glycoprotein ligand-1 (PSGL-1) in lymphoproliferative disorders and in multiple myeloma, it has been considered as a potential target for humoral immunotherapy, as well as an immune checkpoint inhibitor in T-cells. By investigating the expression of SELPLG in 678 T- and B-cell samples by gene expression profiling (GEP), further supported by tissue microarray and immunohistochemical analysis, we identified anaplastic large T-cell lymphoma (ALCL) as constitutively expressing SELPLG at high levels. Moreover, GEP analysis in CD30+ ALCLs highlighted a positive correlation of SELPLG with TNFRSF8 (CD30-coding gene) and T-cell receptor (TCR)-signaling genes (LCK, LAT, SYK and JUN), suggesting that the common dysregulation of TCR expression in ALCLs may be bypassed by the involvement of PSGL-1 in T-cell activation and survival. Finally, we evaluated the effects elicited by in vitro treatment with two anti-PSGL-1 antibodies (KPL-1 and TB5) on the activation of the complement system and induction of apoptosis in human ALCL cell lines. In conclusion, our data demonstrated that PSGL-1 is specifically enriched in ALCLs, altering cell motility and viability due to its involvement in CD30 and TCR signaling, and it might be considered as a promising candidate for novel immunotherapeutic approaches in ALCLs.
Karyological Diversification in the Genus Lyciasalamandra (Urodela: Salamandridae)

Simple Summary The Lycian salamanders of the genus Lyciasalamandra are characterized by a debated taxonomy and phylogenetic relationships. They have been the subject of various molecular and phylogenetic analyses, but their chromosomal diversity is completely unknown. We here present a comparative cytogenetic analysis on five out of the seven described species and seven subspecies of Lyciasalamandra, providing the first karyological assessment on the genus and comparing them to closely related representatives of the genus Salamandra. We analyzed the occurrence and distribution of different conserved (chromosome number and morphology) and highly variable karyological features. We found an impressive diversity in the configuration of nucleolus organizing regions (NORs), which alternatively occur either as heteromorphic or homomorphic loci on distinct regions of different chromosome pairs. We highlight that the observed peculiar taxon-specific pattern of chromosome markers supports the taxonomic validity of the different studied evolutionary lineages and is consistent with a scenario of synchronous evolution in the Lycian salamanders. Abstract We performed the first cytogenetic analysis on five out of the seven species of the genus Lyciasalamandra, including seven subspecies, and representatives of its sister genus Salamandra. All the studied species have a similar karyotype of 2n = 24, mostly composed of biarmed elements. C-bands were observed on all chromosomes, at centromeric, telomeric and interstitial position. We found a peculiar taxon-specific NOR configuration, including either heteromorphic and homomorphic NORs on distinct regions of different chromosomes. Lyciasalamandra a. antalyana and L. helverseni showed two homomorphic NORs (pairs 8 and 2, respectively), while heteromorphic NORs were found in L. billae (pairs 6, 12), L. flavimembris (pairs 2, 12), L. l. luschani (pairs 2, 12), L. l. basoglui (pairs 6, 12), L. l. finikensis (pairs 2, 6) and S. lanzai (pairs 8, 10). Homomorphic NORs with an additional supernumerary site were shown by S. s. salamandra (pairs 2, 8) and S. s. gigliolii (pairs 2, 10). This unexpected highly variable NOR configuration is probably derived from multiple independent NOR translocations and paracentric inversions and correlated to lineage divergence in Lyciasalamandra. These results support the taxonomic validity of the studied taxa and are consistent with a hypothesized scenario of synchronous evolution in the genus.
Enhanced Optical and Antibacterial Activity of Hydrothermally Synthesized Cobalt-Doped Zinc Oxide Cylindrical Microcrystals

Cobalt (Co) doped zinc oxide (ZnO) microcrystals (MCs) are prepared by using the hydrothermal method from the precursor’s mixture of zinc chloride (ZnCl2), cobalt-II chloride hexahydrate (CoCl2·6H2O), and potassium hydroxide (KOH). The smooth round cylindrical morphologies of the synthesized microcrystals of Co-doped ZnO show an increase in absorption with the cobalt doping. The antibacterial activity of the as-obtained Co-doped ZnO-MCs was tested against the bacterial strains of gram-negative (Escherichia coli, Klebsiella pneumonia) and gram-positive bacteria (Staphylococcus aureus, Streptococcus pyogenes) via the agar well diffusion method. The zones of inhibition (ZOI) for Co-doped ZnO-MCs against E. coli and K. pneumoniae were found to be 17 and 19 mm, and 15 and 16 mm against S. Aureus and S. pyogenes, respectively. The prepared Co-doped ZnO-MCs were thus established as a probable antibacterial agent against gram-negative bacterial strains.
Mediterranean Diet Adherence and Eating Disorders in Spanish Nurses with Shift Patterns: A Cross-Sectional Study

Background and Objectives: Shift work has a significant influence on the mental health of workers. Nursing is characterised by a rotational work system. This study aimed to determine whether there was a link between adherence to the Mediterranean diet (MD) and the risk of suffering an eating disorder (ED) in nurses according to their work shift. Materials and Methods: A total of 240 women (nurses and nursing assistants) were evaluated and completed the PREDIMED-PLUS questionnaire on adherence to the MD and the EAT-26 (Eating Attitude Test, 26 items). Results: The results indicate that there are no differences in adherence to the MD depending on the work shift, being that adherence to the diet is already low. Statistically significant differences appear depending on the work shift in the following dimensions: restrictive behaviours and bulimia subscales (presenting higher scores in the 7-h rotating shift versus the fixed morning shift or 12-h rotating shift) and for total EAT-26 score. Conclusion: Whilst they do not condition adherence to a MD, the nursing shifts that are the most changing in terms of time patterns may condition restrictive behaviours and compensatory risk behaviours related to an ED.
Recent Progress in the Synthesis of MoS2 Thin Films for Sensing, Photovoltaic and Plasmonic Applications: A Review

In the surge of recent successes of 2D materials following the rise of graphene, molybdenum disulfide (2D-MoS2) has been attracting growing attention from both fundamental and applications viewpoints, owing to the combination of its unique nanoscale properties. For instance, the bandgap of 2D-MoS2, which changes from direct (in the bulk form) to indirect for ultrathin films (few layers), offers new prospects for various applications in optoelectronics. In this review, we present the latest scientific advances in the field of synthesis and characterization of 2D-MoS2 films while highlighting some of their applications in energy harvesting, gas sensing, and plasmonic devices. A survey of the physical and chemical processing routes of 2D-MoS2 is presented first, followed by a detailed description and listing of the most relevant characterization techniques used to study the MoS2 nanomaterial as well as theoretical simulations of its interesting optical properties. Finally, the challenges related to the synthesis of high quality and fairly controllable MoS2 thin films are discussed along with their integration into novel functional devices.
Mesenchymal Stem Cells as a Gene Delivery Tool: Promise, Problems, and Prospects

The cell-based approach in gene therapy arises as a promising strategy to provide safe, targeted, and efficient gene delivery. Owing to their unique features, as homing and tumor-tropism, mesenchymal stem cells (MSCs) have recently been introduced as an encouraging vehicle in gene therapy. Nevertheless, non-viral transfer of nucleic acids into MSCs remains limited due to various factors related to the main stakeholders of the process (e.g., nucleic acids, carriers, or cells). In this review, we have summarized the main types of nucleic acids used to transfect MSCs, the pros and cons, and applications of each. Then, we have emphasized on the most efficient lipid-based carriers for nucleic acids to MSCs, their main features, and some of their applications. While a myriad of studies have demonstrated the therapeutic potential for engineered MSCs therapy in various illnesses, optimization for clinical use is an ongoing challenge. On the way of improvement, genetically modified MSCs have been combined with various novel techniques and tools (e.g., exosomes, spheroids, 3D-Bioprinting, etc.,) aiming for more efficient and safe applications in biomedicine.
Potential Role and Impact of Peripheral Blood Mononuclear Cells in Radiographic Axial Spondyloarthritis-Associated Endothelial Dysfunction

Endothelial dysfunction (ED) is well known as a process that can lead to atherosclerosis and is frequently presented in radiographic axial spondyloarthritis (r-axSpA) patients. Here, we investigated cellular and molecular mechanisms underlying r-axSpA-related ED, and analyzed the potential effect of peripheral blood mononuclear cells (PBMCs) in promoting endothelial injury in r-axSpA. A total of 30 r-axSpA patients and 32 healthy donors (HDs) were evaluated. The endothelial function, inflammatory and atherogenic profile, and oxidative stress were quantified. In vitro studies were designed to evaluate the effect of PBMCs from r-axSpA patients on aberrant endothelial activation. Compared to HDs, our study found that, associated with ED and the plasma proatherogenic profile present in r-axSpA, PBMCs from these patients displayed a pro-oxidative, proinflammatory, and proatherogenic phenotype, with most molecular changes noticed in lymphocytes. Correlation studies revealed the relationship between this phenotype and the microvascular function. Additional in vitro studies confirmed that PBMCs from r-axSpA patients promoted endothelial injury. Altogether, this study suggests the relevance of r-axSpA itself as a strong and independent cardiovascular risk factor, contributing to a dysfunctional endothelium and atherogenic status by aberrant activation of PBMCs. Lymphocytes could be the main contributors in the development of ED and subsequent atherosclerosis in this pathology.
Characterization and Analysis of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRs) in Pandemic and Non-Pandemic Vibrio parahaemolyticus Isolates from Seafood Sources

Vibrio parahaemolyticus is one of the significant seafood-borne pathogens causing gastroenteritis in humans. Clustered regularly interspaced short palindromic repeats (CRISPR) are commonly detected in the genomes of V. parahaemolyticus and the polymorphism of CRISPR patterns has been applied as a genetic marker for tracking its evolution. In this work, a total of 15 pandemic and 36 non-pandemic V. parahaemolyticus isolates obtained from seafood between 2000 and 2012 were characterized based on hemolytic activity, antimicrobial susceptibility, and CRISPR elements. The results showed that 15/17 of the V. parahaemolyticus seafood isolates carrying the thermostable direct hemolysin gene (tdh+) were Kanagawa phenomenon (KP) positive. The Multiple Antibiotic Resistance (MAR) index ranged between 0.1 and 0.4, and 45% of the isolates have an MAR index ≥ 0.2. A total of 19 isolates were positive for CRISPR detection, including all tdh+ trh− isolates, two of tdh− trh+, and each of tdh+ trh+ and tdh− trh−. Four spacer types (Sp1 to Sp4) were identified, and CRISPR-positive isolates had at least one type of spacer homolog to the region of Vibrio alginolyticus megaplasmid. It is of interest that a specific CRISPR profile and spacer sequence type was observed with correlations to the hemolysin genotype (tdh/trh). Thus, these provide essential data on the exposure of foreign genetic elements and indicate shared ancestry within different genotypes of V. parahaemolyticus isolates.
Genome-Wide SNP Analysis for Milk Performance Traits in Indigenous Sheep: A Case Study in the Egyptian Barki Sheep

Simple Summary The Barki sheep is one of the three main breeds in Egypt, which is spread mainly throughout the northwestern coastal zone, which has harsh conditions. Considering the harsh, semi-arid habitat of this breed, milk performance traits such as milk yield and milk composition have a very important role in the feeding of newborn lambs and affect their growth during the early stage of life. In this study, rare milk performance data and genomic information of Barki sheep were used to uncover diversified genomic regions that could explain the variability of milk yield and milk quality traits in the studied population of Barki ewes. Genome-wide analysis identified genomic regions harboring interesting candidate genes such as SLC5A8, NUB1, TBC1D1, KLF3 and ABHD5 for milk yield and PPARA and FBLN1 genes for milk quality traits. The findings offer valuable information for obtaining a better understanding of the genetics of milk performance traits and contribute to the genetic improvement of these traits in Barki sheep. Abstract Sheep milk yield and milk composition traits play an important role in supplying newborn lambs with essential components such as amino acids, energy, vitamins and immune antibodies and are also of interest in terms of the nutritional value of the milk for human consumption. The aim of this study was to identify genomic regions and candidate genes for milk yield and milk composition traits through genome-wide SNP analyses between high and low performing ewes of the Egyptian Barki sheep breed, which is well adapted to the harsh conditions of North-East Africa. Therefore, out of a herd of 111 ewes of the Egyptian Barki sheep breed (IBD = 0.08), ewes representing extremes in milk yield and milk quality traits (n = 25 for each group of animals) were genotyped using the Illumina OvineSNP50 V2 BeadChip. The fixation index (FST) for each SNP was calculated between the diversified groups. FST values were Z-transformed and used to identify putative SNPs for further analysis (Z(FST) > 10). Genome-wide SNP analysis revealed genomic regions covering promising candidate genes related to milk performance traits such as SLC5A8, NUB1, TBC1D1, KLF3 and ABHD5 for milk yield and PPARA and FBLN1 genes for milk quality trait. The results of this study may contribute to the genetic improvement of milk performance traits in Barki sheep breed and to the general understanding of the genetic contribution to variability in milk yield and quality traits.
Molecular Biomarkers in Idiopathic Pulmonary Fibrosis: State of the Art and Future Directions

Idiopathic pulmonary fibrosis (IPF), the most lethal form of interstitial pneumonia of unknown cause, is associated with a specific radiological and histopathological pattern (the so-called “usual interstitial pneumonia” pattern) and has a median survival estimated to be between 3 and 5 years after diagnosis. However, evidence shows that IPF has different clinical phenotypes, which are characterized by a variable disease course over time. At present, the natural history of IPF is unpredictable for individual patients, although some genetic factors and circulating biomarkers have been associated with different prognoses. Since in its early stages, IPF may be asymptomatic, leading to a delayed diagnosis. Two drugs, pirfenidone and nintedanib, have been shown to modify the disease course by slowing down the decline in lung function. It is also known that 5–10% of the IPF patients may be affected by episodes of acute and often fatal decline. The acute worsening of disease is sometimes attributed to identifiable conditions, such as pneumonia or heart failure; but many of these events occur without an identifiable cause. These idiopathic acute worsenings are termed acute exacerbations of IPF. To date, clinical biomarkers, diagnostic, prognostic, and theranostic, are not well characterized. However, they could become useful tools helping facilitate diagnoses, monitoring disease progression and treatment efficacy. The aim of this review is to cover molecular mechanisms underlying IPF and research into new clinical biomarkers, to be utilized in diagnosis and prognosis, even in patients treated with antifibrotic drugs.