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Efficient repair of DNA double-strand breaks in the Ig heavy chain gene locus is crucial for B-cell antibody class switch recombination (CSR). The regulatory dynamics of the repair pathway direct CSR preferentially through nonhomologous end joining (NHEJ) over alternative end joining (AEJ). Here, we demonstrate that the histone acetyl reader BRD2 suppresses AEJ and aberrant recombination as well as random genomic sequence capture at the CSR junctions. BRD2 deficiency impairs switch (S) region synapse, optimal DNA damage response (DDR), and increases DNA break end resection. Unlike BRD4, a similar bromodomain protein involved in NHEJ and CSR, BRD2 loss does not elevate RPA phosphorylation and R-loop formation in the S region. As BRD2 stabilizes the cohesion loader protein NIPBL in the S regions, the loss of BRD2 or NIPBL shows comparable deregulation of S-S synapsis, DDR, and DNA repair pathway choice during CSR. This finding extends beyond CSR, as NIPBL and BRD4 have been linked to Cornelia de Lange syndrome, a developmental disorder exhibiting defective NHEJ and Ig isotype switching. The interplay between these proteins sheds light on the intricate mechanisms governing DNA repair and immune system functionality.
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Proteínas que Contêm Bromodomínio , Reparo do DNA por Junção de Extremidades , Switching de Imunoglobulina , Fatores de Transcrição , Animais , Humanos , Camundongos , Linfócitos B/imunologia , Linfócitos B/metabolismo , Proteínas que Contêm Bromodomínio/metabolismo , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Quebras de DNA de Cadeia Dupla , Reparo do DNA por Junção de Extremidades/genética , Reparo do DNA , Switching de Imunoglobulina/genética , Proteínas Nucleares/metabolismo , Proteínas Nucleares/genética , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética , Recombinação Genética , Fatores de Transcrição/metabolismoRESUMO
OBJECTIVE: This work aimed to compare between the laryngoscopy positions; sniffing, simple head extension and head hyperextension positions to assess whether the laryngeal view, intubation time and intubation difficulty could improve with one of these positions than the others. DESIGN: Prospective randomized three arms clinical trial. SETTING: Operation room, the phoniatrics unit [removed for blind peer review]. PARTICIPANTS: The study included 75 cases with 25 cases in each group. Group "A" with head in the sniffing position, Group "B" with the head in simple extension position, Group "C" with head in hyperextension position. RESULTS: The three groups were compared regarding intubation time and laryngoscopic view time. Intubation time showed statistically significant difference between the three groups. Mean of sniffing group (No. = 25) was 13.19 s (± 3.35). Mean of simple extension group (No. = 25) was 11.29 s (± 3.14). Mean of Hyperextension group (No. = 25) was 14.39 s (± 4.14). Laryngoscopic view time showed statistically highly significant difference between the three groups. Mean of sniffing group (No. = 25) was 17.19 s (± 7.27). Mean of simple group (No. = 25) was 12.18 s (± 4.46). Mean of hyperextension group (No. = 25) was 17.08 s (± 6.51). CONCLUSION: Comparing the sniffing, the simple extension and the hyperextension positions, the simple extension position showed the best time regarding intubation time and laryngoscopic view time.
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Laringoscopia , Laringe , Adulto , Humanos , Intubação Intratraqueal , Postura , Estudos ProspectivosRESUMO
PURPOSE: Gastrointestinal perforation is a significant injury that originates mainly from gastrointestinal ulcers. It is associated with a high rate of morbidity and mortality. The height of the column of the air under the diaphragm can be used to estimate the amount of peritoneal soiling due to viscus perforation. This study aimed to determine the correlation between this estimate and the incidence of morbidity and mortality. METHODS: To achieve this aim, a prospective cohort study was conducted on 83 patients at Kasr al ainy hospital who, between March 2021 and March 2022, presented to the emergency department with free air under the diaphragm at chest X-ray and required surgical intervention for a perforated viscus. For each case, the amount of peritoneal soiling and the amount of air under the diaphragm as determined by a chest X-ray were recorded. RESULTS: The mean air under the diaphragm in a plain erect chest X-ray was 1.78 ± 1.92 cm, and the mean amount of peritoneal soiling was 1201.83 ± 948.99 CC. There are positive correlations between the amount of air under the diaphragm as shown on an X-ray and the size of the perforation (p = 0.034), the amount of peritoneal soiling (p = 0.003), and the mortality (p = 0.013). CONCLUSION: There was a statistically significant correlation between air under the diaphragm according to X-ray and the amount of peritoneal soiling in patients with a perforated viscus. This measure can be used as a sensitive tool to predict morbidity and mortality as more free air in the chest X-ray is associated with significant mortality. These results may enhance the decision making using sensitive and available tool of diagnosis.
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Diafragma , Pneumoperitônio , Humanos , Prognóstico , Estudos Prospectivos , TóraxRESUMO
Advances in diagnostic imaging have provided unprecedented opportunities to detect diseases at early stages and with high reliability. Diagnostic imaging is also crucial to monitoring the progress or remission of disease and thus is often the central basis of therapeutic decision-making. Currently, several diagnostic imaging modalities (computed tomography, magnetic resonance imaging, and positron emission tomography, among others) are routinely used in clinics and present their own advantages and limitations. In vivo near-infrared (NIR) fluorescence imaging has recently emerged as an attractive imaging modality combining low cost, high sensitivity, and relative safety. As a preclinical tool, it can be used to investigate disease mechanisms and for testing novel diagnostics and therapeutics prior to their clinical use. However, the limited depth of tissue penetration is a major challenge to efficient clinical use. Therefore, the current clinical use of fluorescence imaging is limited to a few applications such as image-guided surgery on tumors and retinal angiography, using FDA-approved dyes. Progress in fluorophore development and NIR imaging technologies holds promise to extend their clinical application to oncology, cardiovascular diseases, plastic surgery, and brain imaging, among others. Nanotechnology is expected to revolutionize diagnostic in vivo fluorescence imaging through targeted delivery of NIR fluorescent probes using antibody conjugation. In this review, we discuss the latest advances in in vivo fluorescence imaging technologies, NIR fluorescent probes, and current and future clinical applications.
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Corantes Fluorescentes , Cirurgia Assistida por Computador , Imageamento por Ressonância Magnética , Imagem Óptica/métodos , Reprodutibilidade dos TestesRESUMO
Background and aim: Circulating hematopoietic stem cells (HSCs), circulating endothelial progenitor cells (EPCs) and cancer stem cells (CSCs) contribute to tumor development and progression and can predict patient outcome. The aim of this study was to investigate the frequency of circulating HSCs, EPCs and CSCs in the peripheral blood of patients with hepatocellular carcinoma (HCC) and to explore their potential prognostic significance for HCC patients.Methods: The study included 30 HCC patients and 20 healthy controls. The HSCs and EPCs were enumerated with CD45, CD34, CD133, CD144 markers, while CSCs were enumerated with CD45, CD44, CD133 markers using flow cytometry.Results: The mean percentages of circulating HSCs were significantly lower in HCC patients than the controls (p = .001), whereas the mean percentages of EPCs within the HSCs subpopulation were significantly higher in the HCC patients than the controls (p = .002). The absolute count of CSCs within 100,000 peripheral blood mononuclear cells was 23.5 ± 3.4 in the HCC patients. Also, the mean percentages of circulating HSCs, EPCs and the number of CSCs were significantly increased in patients with multiple hepatic focal lesions than in patients with a single hepatic focal lesion. Both circulating HSCs and EPCs showed significant positive correlation with the level of AFP and with the numbers of CSCs. In the meantime, the numbers of CSCs revealed significant direct correlation with ALT, AST and AFP levels. The one-year overall survival (OS) of the patients was 77.5%. High levels of CSCs, HSCs and EPCs at diagnosis were all associated with worse outcome for the HCC patients.Conclusions: Significant changes in the levels of the circulating HSCs, EPCs and CSCs occur in HCC. These changes help the diagnosis and the prediction of HCC outcome, as higher levels of these cells are associated with worse OS.
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Carcinoma Hepatocelular/patologia , Células Progenitoras Endoteliais/patologia , Células-Tronco Hematopoéticas/patologia , Neoplasias Hepáticas/patologia , Células-Tronco Neoplásicas/patologia , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/diagnóstico , Estudos de Casos e Controles , Citometria de Fluxo , Humanos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/diagnóstico , PrognósticoRESUMO
INTRODUCTION: The following provides clinical reporting of seven neonates with iatrogenic pharyngeal trauma due to forceful untrained use of nasogastric feeding tube. A range of symptoms were observed beginning with excessive frothy secretions culminating in more severe pneumothorax in some. These cases are presented in the context of an exhaustive literature review producing only 50 similar cases worldwide. Special attention is paid toward accurate diagnosis, prognosis, and guidance on most effective modes of treatment. PATIENTS AND METHODS: Using Medtronic flexible nasopharyngolaryngeal endoscope, examination of the presented neonates was done in the neonatal care unit. Some neonates underwent videofluroscopic study. CONCLUSION: Ryle tube insertion in neonates could result in range of complications that could be easily avoided and managed.
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Intubação Gastrointestinal , Doenças Faríngeas , Esôfago , Humanos , Recém-Nascido , Intubação Gastrointestinal/efeitos adversos , FaringeRESUMO
Chlorfenapyr is a novel class of insecticide-miticide used for crop protection. It poses substantial risks to the reproductive ability of birds as well as environmental stability. This study was focused on the remediation of chlorfenapyr-polluted soil and water through the combined application of green nanotechnology, solubility improving agents and phytoremediation. An analysis using electron microscopy showed that the green synthesis resulted in circular ficus iron nanoparticles (F-Fe0) with diameters of 2.46 nm-11.49 nm, while the ipomoea-silver (Ip-Ag0) and brassica-silver nanoparticles (Br-Ag0) were circular, cubical, hexagonal, triangular and rod -like in shape with sizes ranging from 6.27 to 21.23 nm in IP-Ag0 and from 6.05 to 15.02 nm in Br-Ag0. After 24 h of treatment with F-Fe0, Ip-Ag0 and Br-Ag0 supported on activated charcoal (Ach), the chlorfenapyr in the aqueous solution was reduced to 86%, 79.70%, and 79.70%, respectively, compared to the 6.16% in aqueous solution. Moreover, after 24 h of treatment with Plantago major plus F-Fe0Ach, P. major plus Ip-Ag0Ach, and P. major plus Br-Ag0Ach, the chlorfenapyr in the aqueous solution was reduced to 93.7%, 91.30%, and 92.92%, respectively, as compared to the 69.27% in P. major. After four days of exposure, the percentage of chlorfenapyr degradation in the soil (i.e. control) only reached 12.40%,while the degradation rates were enhanced by 71.22%, 57.32% and 73.10%, respectively, in the presence of P. major plus nanoparticles (F-Fe0, Ip-Ag0 and Br-Ag0). The integration of green nanotechnology, solubility-improving agents, and phytoremediation by Plantago major has played a major role in the remediation of soil and water contaminated with chlorfenapyr.
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Nanopartículas Metálicas , Água , Biodegradação Ambiental , Piretrinas , Prata , Solo , SolubilidadeRESUMO
A 28-year-old man was admitted dead to the emergency department of the regional hospital. All resuscitation attempts were unsuccessful in this case. Attending officers stated that he was suspected of possessing drugs at the time of arrest and had taken them quickly to cover up. Upon arrival at the hospital, signs of violence were noted all over his body. During the autopsy, two large blue plastic packages were found in the antrum of the stomach. The first was 6.3 × 2.2 cm and had two tight knots, while the second was 7.6 x 1.7 cm and had a single knot. Both packages were irregularly shaped and contained tablet debris that was clearly leaking, as a large amount of gastric juice was present in both packages. A confirmatory forensic toxicology analysis revealed toxic concentrations of methamphetamine in the blood of the dissected case. The patient died of acute methamphetamine intoxication associated with a severe stress condition resulting from violent resistance during arrest.
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Transporte Intracorporal de Contrabando , Corpos Estranhos , Metanfetamina , Masculino , Humanos , Adulto , Corpos Estranhos/complicações , Metanfetamina/análise , Estômago/química , AutopsiaRESUMO
Brain cancers, especially glioblastoma multiforme, are associated with poor prognosis due to the limited efficacy of current therapies. Nanomedicine has emerged as a versatile technology to treat various diseases, including cancers, and has played an indispensable role in combatting the COVID-19 pandemic as evidenced by the role that lipid nanocarrier-based vaccines have played. The tunability of nanocarrier physicochemical properties -including size, shape, surface chemistry, and drug release kinetics- has resulted in the development of a wide range of nanocarriers for brain cancer treatment. These nanocarriers can improve the pharmacokinetics of drugs, increase blood-brain barrier transfer efficiency, and specifically target brain cancer cells. These unique features would potentially allow for more efficient treatment of brain cancer with fewer side effects and better therapeutic outcomes. This review provides an overview of brain cancers, current therapeutic options, and challenges to efficient brain cancer treatment. The latest advances in nanomedicine strategies are investigated with an emphasis on targeted and stimulus-responsive nanocarriers and their potential for clinical translation.
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Neoplasias Encefálicas , Portadores de Fármacos , Nanopartículas , Humanos , Neoplasias Encefálicas/tratamento farmacológico , Portadores de Fármacos/química , Nanopartículas/química , Nanopartículas/uso terapêutico , Nanomedicina/métodos , Barreira Hematoencefálica/metabolismo , COVID-19 , Animais , Sistemas de Liberação de Medicamentos/métodos , SARS-CoV-2 , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologiaRESUMO
The aquatic plant water hyacinth was dried then cross-linked with sodium alginate to produce ionic cross-linked microspheres. The mechanism of controlling cadmium (Cd) and lead (Pb) in wastewater was tested by DFT at B3LYP level using LANL2DZ basis set. Modeling results indicated that the hydrated metals could interact with sodium alginate (SA)/water hyacinth (WH) microspheres through hydrogen bonding. Adsorption energies showed comparable results while total dipole moment and HOMO/LUMO band gap energy showed slight selectivity towards the remediation of Pb. FTIR spectra of cross-linked microspheres indicated that WH is forming a composite with SA to change its structure into a microsphere to remove Cd and Pb from water. Raman mapping revealed that the active sites along the surface of the microspheres enable for possible adsorption of metals through its surface. This finding is supported by molecular electrostatic potential and optical confocal microscopy. Atomic absorption spectroscopy results confirmed that the microspheres are more selective for Pb than Cd. It could be concluded that WH cross-linked with SA showed the potential to remove heavy metals through its unique active surface as confirmed by both molecular modeling and experimental findings.
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Alginatos , Cádmio , Chumbo , Microesferas , Águas Residuárias , Poluentes Químicos da Água , Purificação da Água , Alginatos/química , Cádmio/química , Chumbo/química , Chumbo/isolamento & purificação , Poluentes Químicos da Água/química , Águas Residuárias/química , Adsorção , Purificação da Água/métodos , Eichhornia/química , Análise Custo-BenefícioRESUMO
Maximum power point tracking (MPPT) is a technique involved in photovoltaic (PV) systems for optimizing the output power of solar panels. Traditional solutions like perturb and observe (P&O) and Incremental Conductance (IC) are commonly utilized to follow the MPP under various environmental circumstances. However, these algorithms suffer from slow tracking speed and low dynamics under fast-changing environment conditions. To cope with these demerits, a data-driven artificial neural network (ANN) algorithm for MPPT is proposed in this paper. By leveraging the learning capabilities of the ANN, the PV operating point can be adapted to dynamic changes in solar irradiation and temperature. Consequently, it offers promising solutions for MPPT in fast-changing environments as well as overcoming the limitations of traditional MPPT techniques. In this paper, simulations verification and experimental validation of a proposed data-driven ANN-MPPT technique are presented. Additionally, the proposed technique is analyzed and compared to traditional MPPT methods. The numerical and experimental findings indicate that, of the examined MPPT methods, the proposed ANN-MPPT approach achieves the highest MPPT efficiency at 98.16% and the shortest tracking time of 1.3 s.
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Over the past decades, evidence has consistently shown that treatment of central nervous system (CNS)-related disorders, including Alzheimer's disease, Parkinson's disease, stroke, multiple sclerosis, and brain cancer, is limited due to the presence of the blood-brain barrier (BBB). To assist with the development of new therapeutics, it is crucial to engineer a drug delivery system that can cross the BBB efficiently and reach target cells within the brain. In this study, we present a potentially efficient strategy for targeted brain delivery through utilization of folic acid (FA)-conjugated brush polymers, that specifically target the reduced folate carrier (RFC, SLC19A1) expressed on brain endothelial cells. Here, azide (N3)-decorated brush polymers were prepared in a straightforward manner coupling a heterotelechelic α-NH2, ω-N3-poly(2-ethyl-2-oxazoline) (NH2-PEtOx-N3) to N-acylated poly(amino ester) (NPAE)-based brushes. Strain-promoted azide-alkyne cycloaddition (SPAAC) 'click chemistry' with DBCO-folic acid (FA) yielded FA-brush polymers. Interestingly, while azide functionalization of the brush polymers dramatically reduced their association to brain microvascular endothelial cells (hCMEC/D3), the introduction of FA to azide led to a substantial accumulation of the brush polymers in hCMEC/D3 cells. The ability of the polymeric brush polymers to traverse the BBB was quantitatively assessed using different in vitro BBB models including static Transwell and microfluidic platforms. FA-brush polymers showed efficient transport across hCMEC/D3 cells in a manner dependent on FA composition, whereas nonfunctionalized brush polymers exhibited limited trafficking under the same conditions. Further, cellular uptake inhibition studies suggested that the interaction and transport pathway of FA-brush polymers across BBB relies on the RFC-mediated pathways. The potential application of the developed FA-brush polymers in brain cancer delivery was also investigated in a microfluidic model of BBB-glioblastoma. Brush polymers with more FA units successfully presented an enhanced accumulation into U-87 MG glioma cells following its BBB crossing, compared to controls. These results demonstrate that FA-modified brush polymers hold a great potential for more efficient delivery of future brain therapeutics.
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Barreira Hematoencefálica , Neoplasias Encefálicas , Ácido Fólico , Polímeros , Ácido Fólico/química , Ácido Fólico/metabolismo , Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/efeitos dos fármacos , Humanos , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Polímeros/química , Sistemas de Liberação de Medicamentos/métodos , Linhagem Celular Tumoral , Células Endoteliais/metabolismo , Células Endoteliais/efeitos dos fármacos , Portadores de Fármacos/químicaRESUMO
Glioblastoma multiforme (GBM) is an aggressive brain cancer with high malignancy and resistance to conventional treatments, resulting in a bleak prognosis. Nanoparticles offer a way to cross the blood-brain barrier (BBB) and deliver precise therapies to tumor sites with reduced side effects. In this study, we developed angiopep-2 (Ang2)-functionalized lipid cubosomes loaded with cisplatin (CDDP) and temozolomide (TMZ) for crossing the BBB and providing targeted glioblastoma therapy. Developed lipid cubosomes showed a particle size of around 300 nm and possessed an internal ordered inverse primitive cubic phase, a high conjugation efficiency of Ang2 to the particle surface, and an encapsulation efficiency of more than 70% of CDDP and TMZ. In vitro models, including BBB hCMEC/D3 cell tight monolayer, 3D BBB cell spheroid, and microfluidic BBB/GBM-on-a-chip models with cocultured BBB and glioblastoma cells, were employed to study the efficiency of the developed cubosomes to cross the BBB and showed that Ang2-functionalized cubosomes can penetrate the BBB more effectively. Furthermore, Ang2-functionalized cubosomes showed significantly higher uptake by U87 glioblastoma cells, with a 3-fold increase observed in the BBB/GBM-on-a-chip model as compared to that of the bare cubosomes. Additionally, the in vivo biodistribution showed that Ang2 modification could significantly enhance the brain accumulation of cubosomes in comparison to that of non-functionalized particles. Moreover, CDDP-loaded Ang2-functionalized cubosomes presented an enhanced toxic effect on U87 spheroids. These findings suggest that the developed Ang2-cubosomes are prospective for improved BBB crossing and enhanced delivery of therapeutics to glioblastoma and are worth pursuing further as a potential application of nanomedicine for GBM treatment.
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Neoplasias Encefálicas , Glioblastoma , Nanopartículas , Peptídeos , Humanos , Glioblastoma/tratamento farmacológico , Glioblastoma/patologia , Barreira Hematoencefálica/patologia , Distribuição Tecidual , Estudos Prospectivos , Linhagem Celular Tumoral , Temozolomida , Neoplasias Encefálicas/patologia , Nanopartículas/uso terapêutico , Lipídeos/uso terapêuticoRESUMO
INTRODUCTION: Globally, injuries account for 9% of all deaths, with road accidents contributing to approximately a quarter of these fatalities. A major concern is the inadequacy of pre-hospital care (emergency medical services provided before arrival at a hospital) and delays in transportation to medical facilities, identified as leading causes of preventable injury-related deaths. This study explores the experiences of emergency health professionals (EHPs) in peri-hospital services (emergency medical services provided immediately upon arrival and within the hospital setting). METHODS: A qualitative exploratory design, underpinned by Van Manen's (1990) descriptive phenomenological principles, was used. Thirty EHPs from five central and southern Jordanian emergency departments were purposefully sampled, including physicians, nurses, and paramedics from both emergency departments and pre-hospital services. RESULTS: Two primary themes emerged: (1) In Search of Clarity: The Unsettled Journey of Pre-hospital Emergency Care Providers; (2) Frustrations on the Frontline: Role Ambiguity and Emotional Exhaustion in Trauma Care, with EHPs reporting fluid and unclear roles, physical and verbal abuse, and limited authority in critical interventions. CONCLUSION: The study highlights several service lapses in peri-hospital care that negatively impact healthcare professionals, posing risks to patient safety. These findings urge decision-makers to devise actionable strategies to rectify these deficiencies, enhancing care quality and thereby decreasing injury-induced mortality and morbidity.
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Serviços Médicos de Emergência , Pessoal de Saúde , Humanos , Jordânia , Serviço Hospitalar de Emergência , Pesquisa Qualitativa , Atitude do Pessoal de SaúdeRESUMO
A 3-unit cellulose model molecule was built and optimized using DFT B3LYP/6-31G(d,p). The electronic properties of the optimized structure of cellulose were investigated in terms of total dipole moment (TDM), HOMO-LUMO band gap (ΔE), and molecular electrostatic potential (MESP). Cellulose demonstrated a TDM of 9.106 Debye and ΔE of 7.647 eV. The hydrogen atom of the hydroxyl group of the CH2OH group of each cellulose unit was replaced by an alkali metal atom (X) such that the 3-unit cellulose once had 1X atom, then 2X, then 3X atoms, where X = Li, Na or K, both without and with 2, 4 and 6 water molecules (W), respectively, to study also the effect of hydration. Without hydration, the values of TDM decreased for all of the proposed interaction, but increased with hydration, while ΔE decreased in all interactions, confirming that interaction cellulose-alkali metal interaction, especially with hydration, resulted in more reactive structures. Mapping of HOMO-LUMO and MESP indicated significant change in the electron density distribution around cellulose under the effect of interaction with the alkali metals, both with and without hydration. The plots of projected density of states also clearly demonstrated the contribution of each alkali metal as well as water in the molecular orbitals, reflecting their effect on the electronic properties of cellulose and cellulose-alkali metals composites. The theoretical calculations were experimentally verified using FTIR and FT-Raman spectroscopy.
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B cells generate functionally different classes of antibodies through class-switch recombination (CSR), which requires classical non-homologous end joining (C-NHEJ) to join the DNA breaks at the donor and acceptor switch (S) regions. We show that the RNA-binding protein HNRNPU promotes C-NHEJ-mediated S-S joining through the 53BP1-shieldin DNA-repair complex. Notably, HNRNPU binds to the S region RNA/DNA G-quadruplexes, contributing to regulating R-loop and single-stranded DNA (ssDNA) accumulation. HNRNPU is an intrinsically disordered protein that interacts with both C-NHEJ and R-loop complexes in an RNA-dependent manner. Strikingly, recruitment of HNRNPU and the C-NHEJ factors is highly sensitive to liquid-liquid phase separation inhibitors, suggestive of DNA-repair condensate formation. We propose that HNRNPU facilitates CSR by forming and stabilizing the C-NHEJ ribonucleoprotein complex and preventing excessive R-loop accumulation, which otherwise would cause persistent DNA breaks and aberrant DNA repair, leading to genomic instability.
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Proteínas de Ligação a DNA , Estruturas R-Loop , DNA , Quebras de DNA de Cadeia Dupla , Reparo do DNA por Junção de Extremidades , DNA de Cadeia Simples , Proteínas de Ligação a DNA/metabolismo , Switching de Imunoglobulina , Isotipos de Imunoglobulinas/genética , RNA , Ribonucleoproteínas Nucleares Heterogêneas Grupo U/metabolismoRESUMO
BACKGROUND: One of the main causes of cancer-related deaths is breast cancer. Fascin-1(FSCN1) is an actin-binding protein that is present in the mesenchymal, neuronal, and endothelial cells of mammals. Patients with breast cancer have been found to have FSCN1 overexpression. CD44 is crucial for the development, invasion, and tumour spread. Therefore, we aimed to investigate the role of FSCN1&CD44 gene polymorphisms in breast cancer (BC) risk and prognosis. MATERIALS & METHODS: A total of 96 BC patients and 50 controls were included in the case-control study for risk prediction. We examined the association between The SNPs on FSCN1(rs3801004) and CD44(rs353639) and BC susceptibility and clinicopathological features using a real-time PCR in a cohort of the Egyptian population. Results: A significant association of both SNPs on FSCN1(rs3801004)C allele and CD44(rs353639)A allele and BC susceptibility(adjusted OR=4.38,95%CI:2.6-7.4,p<0.001, and adjusted OR=4.44,95%CI:2.65-7.44,p <0.001,respectively). Moreover, CC genotype in FSCN1(rs3801004) were likely to progress to developing G2&G3 and N2&N3 and stage II & stage IV, according to the TNM staging and GG+GC genotypes increased within individuals who had a positive family history of BC. Individuals who carry at least one A allele for CD44rs353639 were likely to progress developing N2 according to the TNM in BC patients. CONCLUSIONS: These findings suggest that both SNPs on FSCN1 (rs3801004) and CD44 (rs353639) affected BC susceptibility. FSCN1 (rs3801004) genetic variants may have a significant effect on BC prognosis. However, CD44 (rs353639) affected lymph node invasions in BC patients.
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Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Prognóstico , Estudos de Casos e Controles , Predisposição Genética para Doença , Egito , Células Endoteliais , Genótipo , Polimorfismo de Nucleotídeo Único , Proteínas dos Microfilamentos/genética , Receptores de Hialuronatos/genética , Proteínas de Transporte/genéticaRESUMO
Bioactive glass (BG) was prepared by sol-gel method following the composition 60-([Formula: see text]) SiO2.34CaO.6P2O5, where x = 10 (FeO, CuO, ZnO or GeO). Samples were then studied with FTIR. Biological activities of the studied samples were processed with antibacterial test. Model molecules for different glass compositions were built and calculated with density functional theory at B3LYP/6-31 g(d) level. Some important parameters such as total dipole moment (TDM), HOMO/LUMO band gap energy (ΔE), and molecular electrostatic potential beside infrared spectra were calculated. Modeling data indicated that P4O10 vibrational characteristics are enhanced by the addition of SiO2.CaO due to electron rush resonating along whole crystal. FTIR results confirmed that the addition of ZnO to P4O10.SiO2.CaO significantly impacted the vibrational characteristics, unlike the other alternatives CuO, FeO and GeO that caused a smaller change in spectral indexing. The obtained values of TDM and ΔE indicated that P4O10.SiO2.CaO doped with ZnO is the most reactive composition. All the prepared BG composites showed antibacterial activity against three different pathogenic bacterial strains, with ZnO-doped BG demonstrating the highest antibacterial activity, confirming the molecular modeling calculations.
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Dióxido de Silício , Óxido de Zinco , Óxido de Zinco/farmacologia , Antibacterianos/farmacologia , ÓxidosRESUMO
Polytetrafluoroethylene (PTFE) is one of the most significant fluoropolymers, and one of the most recent initiatives is to increase its performance by using metal oxides (MOs). Consequently, the surface modifications of PTFE with two metal oxides (MOs), SiO2 and ZnO, individually and as a mixture of the two MOs, were modeled using density functional theory (DFT). The B3LYPL/LANL2DZ model was used in the studies conducted to follow up the changes in electronic properties. The total dipole moment (TDM) and HOMO/LUMO band gap energy (∆E) of PTFE, which were 0.000 Debye and 8.517 eV respectively, were enhanced to 13.008 Debye and 0.690 eV in the case of PTFE/4ZnO/4SiO2. Moreover, with increasing nano filler (PTFE/8ZnO/8SiO2), TDM changed to 10.605 Debye and ∆E decreased to 0.273 eV leading to further improvement in the electronic properties. The molecular electrostatic potential (MESP) and quantitative structure activity relationship (QSAR) studies revealed that surface modification of PTFE with ZnO and SiO2 increased its electrical and thermal stability. The improved PTFE/ZnO/SiO2 composite can, therefore, be used as a self-cleaning layer for astronaut suits based on the findings of relatively high mobility, minimal reactivity to the surrounding environment, and thermal stability.