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AIMS: The current work aims to fully characterize a new antimicrobial agent against Acinetobacter baumannii, which continues to represent a growing threat to healthcare settings worldwide. With minimal treatment options due to the extensive spread of resistance to almost all the available antimicrobials, the hunt for new antimicrobial agents is a high priority. METHODS AND RESULTS: An Egyptian soil-derived bacterium strain NHM-077B proved to be a promising source for a new antimicrobial agent. Bio-guided fractionation of the culture supernatants of NHM-077B followed by chemical structure elucidation identified the active antimicrobial agent as 1-hydroxy phenazine. Chemical synthesis yielded more derivatives, including dihydrophenazine (DHP), which proved to be the most potent against A. baumannii, yet it exhibited a marginally safe cytotoxicity profile against human skin fibroblasts. Proteomics analysis of the cells treated with DHP revealed multiple proteins with altered expression that could be correlated to the observed phenotypes and potential mechanism of the antimicrobial action of DHP. DHP is a multipronged agent that affects membrane integrity, increases susceptibility to oxidative stress, interferes with amino acids/protein synthesis, and modulates virulence-related proteins. Interestingly, DHP in subinhibitory concentrations re-sensitizes the highly virulent carbapenem-resistant A. baumannii strain AB5075 to carbapenems providing great hope in regaining some of the benefits of this important class of antibiotics. CONCLUSIONS: This work underscores the potential of DHP as a promising new agent with multifunctional roles as both a classical and nonconventional antimicrobial agent that is urgently needed.
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Acinetobacter baumannii , Antibacterianos , Carbapenémicos , Farmacorresistencia Bacteriana Múltiple , Pruebas de Sensibilidad Microbiana , Estrés Oxidativo , Fenazinas , Acinetobacter baumannii/efectos de los fármacos , Fenazinas/farmacología , Fenazinas/química , Estrés Oxidativo/efectos de los fármacos , Carbapenémicos/farmacología , Antibacterianos/farmacología , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Humanos , Infecciones por Acinetobacter/tratamiento farmacológico , Infecciones por Acinetobacter/microbiología , Microbiología del SueloRESUMEN
Introduction: Autism spectrum disorders (ASDs) are a group of neurodevelopmental disorders with poor social interaction, communication issues, aberrant motor movements, and limited repetitive interests and behaviour. Spirulina platensis (SP) contains several multi-nutrients and has a wide range of neuroprotective properties.Aim: The target of the current experiment is to detect the protective effects of S. platensis on valproic-induced autism in adult female albino rats' siblings for the first time.Materials and Methods: Twelve Pregnant rats were separated into four main groups; Group I (control); Group II (S. platensis); Group III (autistic group); and Group IV (autistic SP-treated group). Fifteen offspring pups from each group were sacrificed, brain was divided for biochemical analysis as superoxide dismutase and malondialdehyde were evaluated spectrophotometrically while interleukin-6, interleukin-12, Bcl-2-associated X protein, B-cell lymphoma-2, Beclin-1, brain-derived neurotrophic factor were assessed by ELISA, other division of brain were used for gene expression of PI3k, Akt and mTOR pathway, last division of brain were stained using (H&E) and Giemsa stains. Tumour necrosis factor alpha (TNF-α) and Synaptophysin (SYN) markers were used for immunohistochemical staining.Results: Autistic Group (III) showed an increment in levels of MDA, IL-6, IL12 and BAX while showing a decrement in SOD, Bcl-2 and Beclin-1 as well as increased PI3k, Akt and mTOR gene expression. Autistic Group (III) also exhibited hypocellularity and disorganization of hippocampal and prefrontal cortex cells. The autistic SP-treated group (IV) showed improvement in these biochemical markers and pathological changes. Our findings suggest that Spirulina platensis will be significant in managing autism.
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The nanoparticle (NP) protein corona represents an interface between biological components and NPs, dictating their cellular interaction and biological fate. To assess the success of cellular targeting, NPs modified with targeting ligands are incubated with target cells in serum-free culture medium or in the presence of fetal bovine serum (FBS). In the former, the role of the corona is overlooked, and in the latter, the effects of a corona that does not represent the one forming in humans nor the respective disease state are considered. Via proteomic analysis, we demonstrate how the difference in the composition of FBS, sera from healthy human volunteers, and breast cancer patients (BrCr Pt) results in the formation of completely different protein coronas around the same NP. Successful in vitro targeting of breast cancer cells was only observed when NPs were incubated with target cells in the presence of BrCr Pt sera only. In such cases, the success of targeting was not attributed to the targeting ligand itself, but to the adsorption of specific serum proteins that facilitate NP uptake by cancer cells in the presence of BrCr Pt sera. This work therefore demonstrates how the serum source affects the reliability of in vitro experiments assessing NP-cell interactions and the consequent success or failure of active targeting and may in fact indicate an additional reason for the limited clinical success of drug targeting by NPs in cancer.
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Neoplasias de la Mama , Quitosano , Nanopartículas , Corona de Proteínas , Neoplasias de la Mama/tratamiento farmacológico , Femenino , Ácido Fólico , Humanos , Nanopartículas/metabolismo , Corona de Proteínas/metabolismo , Proteómica , Reproducibilidad de los Resultados , Albúmina Sérica BovinaRESUMEN
Metabolomics is a potential approach to paving new avenues for clinical diagnosis, molecular medicine, and therapeutic drug monitoring and development. The conventional metabolomics analysis pipeline depends on the data-independent acquisition (DIA) technique. Although powerful, it still suffers from stochastic, non-reproducible ion selection across samples. Despite the presence of different metabolomics workbenches, metabolite identification remains a tedious and time-consuming task. Consequently, sequential windowed acquisition of all theoretical MS (SWATH) acquisition has attracted much attention to overcome this limitation. This article aims to develop a novel SWATH platform for data analysis with a generation of an accurate mass spectral library for metabolite identification using SWATH acquisition. The workflow was validated using inclusion/exclusion compound lists. The false-positive identification was 3.4% from the non-endogenous drugs with 96.6% specificity. The workflow has proven to overcome background noise despite the complexity of the SWATH sample. From the Human Metabolome Database (HMDB), 1282 compounds were tested in various biological samples to demonstrate the feasibility of the workflow. The current study identified 377 compounds in positive and 303 in negative modes with 392 unique non-redundant metabolites. Finally, a free software tool, SASA, was developed to analyze SWATH-acquired samples using the proposed pipeline.
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Metaboloma , Metabolómica , Bases de Datos Factuales , Humanos , Metabolómica/métodos , Programas Informáticos , Flujo de TrabajoRESUMEN
Industrial water has a dual problem because of its strong acidic characteristics and the presence of heavy metals. Removing heavy metals from water in these severe conditions has special requirements. For this problem, an economic method was used for removing iron (Fe), copper (Cu), chromium (Cr), nickel (Ni) and manganese (Mn) with extremely acidic characteristics from water. This method depends on the preparation of nanohybrids through host-guest interactions based on nanolayered structures, organic species (stearic acid), polyvinyl alcohol (PVA) and carbon nanotubes (CNTs). The formation of nanohybrids was confirmed using different techniques through the expansion of the interlayered spacing of the nanolayered structure from 0.76 nm to 1.60 nm, 1.40 nm and 1.06 nm. This nano-spacing is suitable for trapping and confining the different kinds of heavy metal. The experimental results indicated that the prepared nanohybrid was more effective than GreensandPlus, which is used on the market for purifying water. The high activity of the nanohybrid is obvious in the removal of both copper and nickel because the GreensandPlus was completely inactive for these heavy metals under severe conditions. Finally, these experimental results introduce new promising materials for purifying industrial water that can work under severe conditions.
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Energy and water related problems have attracted strong attention from scientists across the world because of deficient energy and water pollution. Following this line, new strategy depended on preparing nanolayers of Al/Zn and magnetic nanoparticles of cobalt iron oxides nanocomposite in addition to long chains of hydrocarbons of stearic acid to be used as roofs, fillers and pillars; respectively, to design optical-active nanohybrids in sunlight for removing the colored pollutants from water in few minutes. By using long chains of hydrocarbons of stearic acid, X-ray diffraction (XRD) results and TEM images showed expansion of the interlayered spacing from 0.76 nm to 2.02 nm and insertion of magnetic nanoparticles among the nanolayers of Al/Zn. The optical properties and activities showed that the nanohybrid structure based on zinc oxide led to clear reduction of the band gap energy from 3.3 eV to 2.75 eV to be effective in sunlight. Photocatalytic degradation of the dye of acid green 1 confirmed the high activity of the prepared zinc oxide nanohybrids because of a complete removal of the dye after ten minutes in sunlight. Finally, this strategy was effective for producing photo-active nanohybrids for using renewable and non-polluting energy for purifying water.
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Nanocompuestos , Óxido de Zinc , Catálisis , Magnetismo , Nanocompuestos/química , Luz Solar , AguaRESUMEN
PURPOSE: Protein misfolding and aggregation result in proteotoxic stress and underlie the pathogenesis of many diseases. To overcome proteotoxicity, cells compartmentalize misfolded and aggregated proteins in different inclusion bodies. The aggresome is a paranuclear inclusion body that functions as a storage compartment for misfolded proteins. Choroid plexus tumors (CPTs) are rare neoplasms comprised of three pathological subgroups. The underlying mechanisms of their pathogenesis remain unclear. This study aims to elucidate the prognostic role and the biological effects of aggresomes in pediatric CPTs. METHODS: We examined the presence of aggresomes in 42 patient-derived tumor tissues by immunohistochemistry and we identified their impact on patients' outcomes. We then investigated the proteogenomics signature associated with aggresomes using whole-genome DNA methylation and proteomic analysis to define their role in the pathogenesis of pediatric CPTs. RESULTS: Aggresomes were detected in 64.2% of samples and were distributed among different pathological and molecular subgroups. The presence of aggresomes with different percentages was correlated with patients' outcomes. The ≥ 25% cutoff had the most significant impact on overall and event-free survival (p-value < 0.001) compared to the pathological and the molecular stratifications. CONCLUSIONS: These results support the role of aggresome as a novel prognostic molecular marker for pediatric CPTs that was comparable to the molecular classification in segregating samples into two distinct subgroups, and to the pathological stratification in the prediction of patients' outcomes. Moreover, the proteogenomic signature of CPTs displayed altered protein homeostasis, manifested by enrichment in processes related to protein quality control.
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Neoplasias del Plexo Coroideo/patología , Cuerpos de Inclusión/patología , Niño , Femenino , Humanos , Masculino , Pronóstico , Proteómica , Proteostasis/fisiología , Estudios RetrospectivosRESUMEN
During the last decade, metaproteomics has provided a better understanding and functional characterization of the microbiome. A large body of evidence now reveals interspecies, species of bacteria-host interactions, via the secreted modulatory microbial protein "metaproteome". Although high-throughput state-of-art mass spectrometry has recently empowered metaproteomics, its profile remains unclear, and, most importantly, the exact consequences and underlying mechanism of these protein molecules on the host are insufficiently understood. Here we address the current progress in the study of the human metaproteome, suggesting possible modulation, a metaproteome dysbiotic signature, challenges, and future perspectives.
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Interacciones Huésped-Patógeno , Microbiota , Proteómica/métodos , Proteínas Bacterianas/metabolismo , Disbiosis , Humanos , Proteómica/tendenciasRESUMEN
BACKGROUND: Type 2 diabetes is an endocrine disorder characterized by compromised insulin sensitivity that eventually leads to overt disease. Adipose stem cells (ASCs) showed promising potency in improving type 2 diabetes and its complications through their immunomodulatory and differentiation capabilities. However, the hyperglycaemia of the diabetic microenvironment may exert a detrimental effect on the functionality of ASCs. Herein, we investigate ASC homeostasis and regenerative potential in the diabetic milieu. METHODS: We conducted data collection and functional enrichment analysis to investigate the differential gene expression profile of MSCs in the diabetic microenvironment. Next, ASCs were cultured in a medium containing diabetic serum (DS) or normal non-diabetic serum (NS) for six days and one-month periods. Proteomic analysis was carried out, and ASCs were then evaluated for apoptosis, changes in the expression of surface markers and DNA repair genes, intracellular oxidative stress, and differentiation capacity. The crosstalk between the ASCs and the diabetic microenvironment was determined by the expression of pro and anti-inflammatory cytokines and cytokine receptors. RESULTS: The enrichment of MSCs differentially expressed genes in diabetes points to an alteration in oxidative stress regulating pathways in MSCs. Next, proteomic analysis of ASCs in DS revealed differentially expressed proteins that are related to enhanced cellular apoptosis, DNA damage and oxidative stress, altered immunomodulatory and differentiation potential. Our experiments confirmed these data and showed that ASCs cultured in DS suffered apoptosis, intracellular oxidative stress, and defective DNA repair. Under diabetic conditions, ASCs also showed compromised osteogenic, adipogenic, and angiogenic differentiation capacities. Both pro- and anti-inflammatory cytokine expression were significantly altered by culture of ASCs in DS denoting defective immunomodulatory potential. Interestingly, ASCs showed induction of antioxidative stress genes and proteins such as SIRT1, TERF1, Clusterin and PKM2. CONCLUSION: We propose that this deterioration in the regenerative function of ASCs is partially mediated by the induced oxidative stress and the diabetic inflammatory milieu. The induction of antioxidative stress factors in ASCs may indicate an adaptation mechanism to the increased oxidative stress in the diabetic microenvironment.
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BACKGROUND: Pericytes (PCs) are multipotent contractile cells that wrap around the endothelial cells (ECs) to maintain the blood vessel's functionality and integrity. The hyperglycemia associated with Type 2 diabetes mellitus (T2DM) was shown to impair the function of PCs and increase the risk of diabetes complications. In this study, we aimed to investigate the deleterious effect of the diabetic microenvironment on the regenerative capacities of human PCs. METHODS: PCs isolated from human adipose tissue were cultured in the presence or absence of serum collected from diabetic patients. The functionality of PCs was analyzed after 6, 14, and 30 days. RESULTS: Microscopic examination of PCs cultured in DS (DS-PCs) showed increased aggregate formation and altered surface topography with hyperbolic invaginations. Compared to PCs cultured in normal serum (NS-PCs), DS-PCs showed more fragmented mitochondria and thicker nuclear membrane. DS caused impaired angiogenic differentiation of PCs as confirmed by tube formation, decreased VEGF-A and IGF-1 gene expression, upregulated TSP1, PF4, actin-related protein 2/3 complex, and downregulated COL21A1 protein expression. These cells suffered more pronounced apoptosis and showed higher expression of Clic4, apoptosis facilitator BCl-2-like protein, serine/threonine protein phosphatase, and caspase-7 proteins. DS-PCs showed dysregulated DNA repair genes CDKN1A, SIRT1, XRCC5 TERF2, and upregulation of the pro-inflammatory genes ICAM1, IL-6, and TNF-α. Further, DS-treated cells also showed disruption in the expression of the focal adhesion and binding proteins TSP1, TGF-ß, fibronectin, and PCDH7. Interestingly, DS-PCs showed resistance mechanisms upon exposure to diabetic microenvironment by maintaining the intracellular reactive oxygen species (ROS) level and upregulation of extracellular matrix (ECM) organizing proteins as vinculin, IQGAP1, and tubulin beta chain. CONCLUSION: These data showed that the diabetic microenvironment exert a deleterious effect on the regenerative capacities of human adipose tissue-derived PCs, and may thus have possible implications on the vascular complications of T2DM. Nevertheless, PCs have shown remarkable protective mechanisms when initially exposed to DS and thus they could provide a promising cellular therapy for T2DM.
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Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/terapia , Diabetes Mellitus Tipo 2/metabolismo , Pericitos , Células Endoteliales/metabolismo , Tejido Adiposo/metabolismo , Apoptosis , Células CultivadasRESUMEN
BACKGROUND: Attempts to subtype, type 2 diabetes (T2D) have mostly focused on newly diagnosed European patients. In this study, our aim was to subtype T2D in a non-white Emirati ethnic population with long-standing disease, using unsupervised soft clustering, based on etiological determinants. METHODS: The Auto Cluster model in the IBM SPSS Modeler was used to cluster data from 348 Emirati patients with long-standing T2D. Five predictor variables (fasting blood glucose (FBG), fasting serum insulin (FSI), body mass index (BMI), hemoglobin A1c (HbA1c) and age at diagnosis) were used to determine the appropriate number of clusters and their clinical characteristics. Multinomial logistic regression was used to validate clustering results. RESULTS: Five clusters were identified; the first four matched Ahlqvist et al subgroups: severe insulin-resistant diabetes (SIRD), severe insulin-deficient diabetes (SIDD), mild age-related diabetes (MARD), mild obesity-related diabetes (MOD), and a fifth new subtype of mild early onset diabetes (MEOD). The Modeler algorithm allows for soft assignments, in which a data point can be assigned to multiple clusters with different probabilities. There were 151 patients (43%) with membership in cluster peaks with no overlap. The remaining 197 patients (57%) showed extensive overlap between clusters at the base of distributions. CONCLUSIONS: Despite the complex picture of long-standing T2D with comorbidities and complications, our study demonstrates the feasibility of identifying subtypes and their underlying causes. While clustering provides valuable insights into the architecture of T2D subtypes, its application to individual patient management would remain limited due to overlapping characteristics. Therefore, integrating simplified, personalized metabolic profiles with clustering holds greater promise for guiding clinical decisions than subtyping alone.
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Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/sangre , Masculino , Femenino , Persona de Mediana Edad , Glucemia/análisis , Hemoglobina Glucada/análisis , Índice de Masa Corporal , Análisis por Conglomerados , Adulto , Anciano , Insulina/sangre , Resistencia a la Insulina , Emiratos Árabes Unidos/epidemiologíaRESUMEN
Water pollution has emerged as a major challenge for the scientific community because of the rapid expansion of the population and the industrial sector in the world. The current study focuses on introducing a new track for designing new optical nanocomposites for purifying water in addition to providing a new additive for building new nanohybrids. These targets were achieved through building a ternary system of Co/Ti/Zn nanocomposites and nanolayered structures. The Co/Ti/Zn nanolayered structures were prepared and intercalated by different kinds of organic acids: monocarboxylic and dicarboxylic acids. Long chains of organic acids were used to construct series of organic-inorganic nanohybrids. X-ray diffraction, thermal analyses, Fourier Transform Infrared spectroscopy, and scanning electron microscopy confirmed the formation of nanolayered structures and nanohybrids. The optical properties of the nanolayered structure showed that the Co/Ti/Zn LDH became photo-active compared with the usual Al/Zn LDH because of the reduction in the band gap energy from 5.3 eV to 3.3 eV. After thermal treatment, a highly photo-active nanocomposite was produced through observing more reduction for the band gap energy to become 2.8 eV. In addition, the dye of Acid Green 1 completely decomposed and converted to water and carbon dioxide during 17 min of UV radiation by the dual Co/Ti-doped zinc oxide nanocomposite. In addition, the kinetic study confirmed that the high optical activity of the dual Co/Ti-doped zinc oxide nanocomposite accelerated the degradation of the green dyes. Finally, from these results it could be concluded that designing effective nanocomposite for purification of water was accomplished through converting 2D nanolayered structures to a 3D porous structure of Ni/Ti/Zn nanocomposites. In addition, a new additive was achieved for heterostructured hybrids through building new Co/Ti/Zn/organic nanohybrids.
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The tRNA adaptation index (tAI) is a translation efficiency metric that considers weighted values (S ij values) for codon-tRNA wobble interaction efficiencies. The initial implementation of the tAI had significant flaws. For instance, generated S ij weights were optimized based on gene expression in Saccharomyces cerevisiae, which is expected to vary among different species. Consequently, a species-specific approach (stAI) was developed to overcome those limitations. However, the stAI method employed a hill climbing algorithm to optimize the S ij weights, which is not ideal for obtaining the best set of S ij weights because it could struggle to find the global maximum given a complex search space, even after using different starting positions. In addition, it did not perform well in computing the tAI of fungal genomes in comparison with the original implementation. We developed a novel approach named genetic tAI (gtAI) implemented as a Python package (https://github.com/AliYoussef96/gtAI), which employs a genetic algorithm to obtain the best set of S ij weights and follows a new codon usage-based workflow that better computes the tAI of genomes from the three domains of life. The gtAI has significantly improved the correlation with the codon adaptation index (CAI) and the prediction of protein abundance (empirical data) compared to the stAI.
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AIMS: Ewing's Sarcoma is an extremely aggressive tumor in children. The disease is associated with highly metastatic rate, especially at the time of diagnosis, contributing to a lower survival rate and poor prognosis. The study aimed to identify predictive biomarkers for metastatic Ewing's sarcoma through in-depth analysis of the plasma proteome profile of pediatric Ewing's sarcoma patients. MAIN METHODS: Plasma samples from Ewing's sarcoma patients and control individuals were profiled using both shotgun and dimethyl-labeled proteomics analysis. Subsequently, Ewing's sarcoma patients were further stratified according to their metastatic state and chemotherapy response. Western blot was used for validation. Univariate and multivariate analyses were performed to determine proteome metastasis predictors. Receiver operating characteristic (ROC) analysis was done to assess the diagnostic significance of the potential plasma Ewing's sarcoma biomarkers. KEY FINDINGS: Our results revealed a set of proteins significantly associated with the metastatic Ewing's sarcoma disease profile. These proteins include ceruloplasmin and several immunoglobulins. Additionally, our study disclosed significant differentially expressed proteins in pediatric Ewing's sarcoma, including CD5 antigen-like, clusterin, and dermcidin. Stable isotope dimethyl labeling and western blot further confirmed our results, strengthening the impact of such proteins in disease development. Furthermore, an unbiased ROC curve evaluated and confirmed the predictive power of these biomarker candidates. SIGNIFICANCE: This study presented potential empirical predictive circulating biomarkers for determining the disease status of pediatric Ewing's sarcoma, which is vital for early prediction.
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Neoplasias Óseas , Sarcoma de Ewing , Humanos , Niño , Sarcoma de Ewing/diagnóstico , Neoplasias Óseas/metabolismo , Pronóstico , ProteomaRESUMEN
IMPORTANCE: Decreasing the camptothecin productivity by fungi with storage and subculturing is the challenge that halts their further implementation to be an industrial platform for camptothecin (CPT) production. The highest differentially abundant proteins were Pleckstrin homology (PH) domain-containing proteins and Peptidyl-prolyl cis/trans isomerase that fluctuated with the subculturing of A. terreus with a remarkable relation to CPT biosynthesis and restored with addition of F. elastica microbiome.
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Dominios Homólogos a Pleckstrina , Proteómica , Isomerasa de Peptidilprolil , CamptotecinaRESUMEN
Three years after the pandemic, we still have an imprecise comprehension of the pathogen landscape and we are left with an urgent need for early detection methods and effective therapy for severe COVID-19 patients. The implications of infection go beyond pulmonary damage since the virus hijacks the host's cellular machinery and consumes its resources. Here, we profiled the plasma proteome and metabolome of a cohort of 57 control and severe COVID-19 cases using high-resolution mass spectrometry. We analyzed their proteome and metabolome profiles with multiple depths and methodologies as conventional single omics analysis and other multi-omics integrative methods to obtain the most comprehensive method that portrays an in-depth molecular landscape of the disease. Our findings revealed that integrating the knowledge-based and statistical-based techniques (knowledge-statistical network) outperformed other methods not only on the pathway detection level but even on the number of features detected within pathways. The versatile usage of this approach could provide us with a better understanding of the molecular mechanisms behind any biological system and provide multi-dimensional therapeutic solutions by simultaneously targeting more than one pathogenic factor.
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COVID-19 , Humanos , Multiómica , Proteoma , Conocimiento , Bases del ConocimientoRESUMEN
BACKGROUND: Globally, patients with diabetes suffer from increased disease severity and mortality due to coronavirus disease 2019 (COVID-19). Old age, high body mass index (BMI), comorbidities, and complications of diabetes are recognized as major risk factors for infection severity and mortality. AIM: To investigate the risk and predictors of higher severity and mortality among in-hospital patients with COVID-19 and type 2 diabetes (T2D) during the first wave of the pandemic in Dubai (March-September 2020). METHODS: In this cross-sectional nested case-control study, a total of 1083 patients with COVID-19 were recruited. This study included 890 men and 193 women. Of these, 427 had T2D and 656 were non-diabetic. The clinical, radiographic, and laboratory data of the patients with and without T2D were compared. Independent predictors of mortality in COVID-19 non-survivors were identified in patients with and without T2D. RESULTS: T2D patients with COVID-19 were older and had higher BMI than those without T2D. They had higher rates of comorbidities such as hypertension, ischemic heart disease, heart failure, and more life-threatening complications. All laboratory parameters of disease severity were significantly higher than in those without T2D. Therefore, these patients had a longer hospital stay and a significantly higher mortality rate. They died from COVID-19 at a rate three times higher than patients without. Most laboratory and radiographic severity indices in non-survivors were high in patients with and without T2D. In the univariate analysis of the predictors of mortality among all COVID-19 non-survivors, significant associations were identified with old age, increased white blood cell count, lym-phopenia, and elevated serum troponin levels. In multivariate analysis, only lymphopenia was identified as an independent predictor of mortality among T2D non-survivors. CONCLUSION: Patients with COVID-19 and T2D were older with higher BMI, more comorbidities, higher disease severity indices, more severe proinflammatory state with cardiac involvement, and died from COVID-19 at three times the rate of patients without T2D. The identified mortality predictors will help healthcare workers prioritize the management of patients with COVID-19.
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It is well known that layered double hydroxides (LDHs) are two-dimensional (2D) layered compounds. However, we modified these 2D layered compounds to become one-dimensional (1D) nanostructures destined for high-performance supercapacitors applications. In this direction, silicon was inserted inside the nanolayers of Co-LDHs producing nanofibers of Si/Co LDHs through the intercalation of cyanate anions as pillars for building nanolayered structures. Additionally, nanoparticles were observed by controlling the preparation conditions and the silicon percentage. Scanning electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy and thermal analyses have been used to characterize the nanolayered structures of Si/Co LDHs. The electrochemical characterization was performed by cyclic voltammetry and galvanic charge-discharge technique in 2M KOH electrolyte solution using three-electrode cell system. The calculated specific capacitance results indicated that the change of morphology from nanoparticles or plates to nanofibers had a positive effect for improving the performance of specific capacitance of Si/Co LDHs. The specific capacitance enhanced to be 621.5 F g-1 in the case of the nanofiber of Si/Co LDHs. Similarly, the excellent cyclic stability (84.5%) was observed for the nanofiber. These results were explained through the attribute of the nanofibrous morphology and synergistic effects between the electric double layer capacitive character of the silicon and the pseudo capacitance nature of the cobalt. The high capacitance of ternary Si/Co/cyanate LDHs nanocomposites was suggested to be used as active electrode materials for high-performance supercapacitors applications.
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Water pollution and deficient energy are the main challenges for the scientific society across the world. In this trend, new approaches include designing zinc oxide nanohybrids to be very active in sunlight. In this line, organic and magnetic species intercalate among the nanolayers of Al/Zn to build inorganic-magnetic-organic nanohybrid structures. A series of nanolayered and nanohybrid structures have been prepared through intercalating very fine particles of cobalt iron oxide nanocomposites and long chains of organic fatty acids such as n-capric acid and stearic acid inside the nanolayered structures of Al/Zn. By thermal treatment, zinc oxide nanohybrids have been prepared and used for purifying water from colored pollutants using solar energy. The optical measurements have shown that the nanohybrid structure of zinc oxide leads to a clear reduction of band gap energy from 3.30 eV to 2.60 eV to be effective in sunlight. In this line, a complete removal of the colored pollutants (naphthol green B) was achieved after ten minutes in the presence of zinc oxide nanohybrid and sunlight. Finally, this new approach for designing photoactive nanohybrids leads to positive results for facing the energy- and water-related problems through using renewable and non-polluting energy for purifying water.
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Mesenchymal stromal cells (MSCs) have shown promise in liver cancer treatment. However, when MSCs are recruited to hepatic site of injury, they acquire cancerous promoting phenotype. AIMS: To assess the influence of Hepatocellular carcinoma (HCC) microenvironment on human adipose MSCs (hA-MSCs) and predict hA-MSCs intracellular miRNAs role. MATERIALS AND METHODS: After indirect co-culturing with Huh-7 cells, hA-MSCs were characterized via cell cycle profile, proliferation and migration potentials by MTT and scratch assays respectively. Functional enrichment analysis of deregulated proteins and miRNA targets was also analyzed. KEY FINDINGS: Co-cultured hA-MSCs could acquire a cancer-associated phenotype as shown by upregulation of CAF, cancer markers, and downregulation of differentiation markers. Migration of these cancer-associated cells was increased concomitantly with upregulation of adhesion molecules, but not epithelial to mesenchymal transition markers. Co-cultured cells showed increased proliferation confirmed by downregulation in cell percentage in G0/G1, G2/M and upregulation in S phases of cell cycle. Upregulation of miR-17-5p and 615-5p in co-cultured hA-MSCs was also observed. Functional enrichment analysis of dysregulated proteins in co-cultured hA-MSCs, including our selected miRNAs targets, showed their involvement in development of cancer-associated characteristics. SIGNIFICANCE: This study suggests an interaction between tumor cells and surrounding stromal components to generate cancer associated phenotype of some CAF-like characteristics, known to favor cancer progression. This sheds the light on the use of hA-MSCs in HCC therapy. hA-MSCs modulation may be partially achieved via dysregulation of intracellular miR17-5P and 615-5p expression, suggesting an important role for miRNAs in HCC pathogenesis, and as a possible therapeutic candidate.