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OBJECTIVE: The objective of this study was to investigate the ultrasonographic characteristics and outcomes of fetuses with atypical and non-visualized fetal gallbladder in our tertiary care hospital. METHODS: A retrospective analysis was conducted on cases in which the fetal gallbladder was not visualized or exhibited atypical characteristics at our institution over a four-year period. The patients were divided into two groups: absent gallbladder and atypical gallbladder. The groups with isolated and additional anomalies were analyzed according to their ante- and postnatal characteristics. RESULTS: The study comprised 78 patients (37 absent, 41 atypical gallbladder). In the isolated fetal absence of gallbladder group, the gallbladder was visualized in three of 13 patients during antenatal ultrasonographic follow-up and in half of the remaining 10 patients during postnatal follow-up. In the postnatal period, five newborns with absent isolated gallbladder are being followed up with suspicion of biliary atresia and isolated gallbladder agenesis. In the absence of a gallbladder with an additional anomaly group, 58% of fetuses died during the intrauterine and neonatal period. Fetuses in the isolated atypical gallbladder group are being followed as healthy after birth. Pregnancies with atypical gallbladder appearance and additional anomalies resulted in 33% neonatal death, 12% intrauterine demise, and 25% termination of pregnancy. CONCLUSION: In instances where the fetal gallbladder is not consistently discernible, it is imperative to exercise caution with regard to the possibility of biliary atresia. In the event that the fetal gallbladder exhibits unusual characteristics, a meticulous examination for the presence of additional anomalies is recommended.
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Actinic keratosis (AK) is characterized by a reddish or occasionally skin-toned rough patch on sun-damaged skin, and it is regarded as a precursor to squamous cell carcinoma (SCC). Photodynamic therapy (PDT), utilizing 5-aminolevulinic acid (ALA) along with red light, is a recognized treatment option for AK that is limited by the penetration depth of light and the distribution of the photosensitizer into the skin. Cold atmospheric plasma (CAP) is a partially ionized gas with permeability-enhancing and anti-cancer properties. This study analyzed, in vitro, whether a combined treatment of CAP and ALA-PDT may improve the efficacy of the treatment. In addition, the effect of the application sequence of ALA and CAP was investigated using in vitro assays and the molecular characterization of human oral SCC cell lines (SCC-9, SCC-15, SCC-111), human cutaneous SCC cell lines (SCL-1, SCL-2, A431), and normal human epidermal keratinocytes (HEKn). The anti-tumor effect was determined by migration, invasion, and apoptosis assays and supported the improved efficacy of ALA-PDT in combination with CAP. However, the application sequence ALA-CAP-red light seems to be more efficacious than CAP-ALA-red light, which is probably due to increased intracellular ROS levels when ALA is applied first, followed by CAP and red light treatment. Furthermore, the expression of apoptosis- and senescence-related molecules (caspase-3, -6, -9, p16INK4a, p21CIP1) was increased, and different genes of the junctional network (ZO-1, CX31, CLDN1, CTNNB1) were induced after the combined treatment of CAP plus ALA-PDT. HEKn, however, were much less affected than SCC cells. Overall, the results show that CAP may improve the anti-tumor effects of conventional ALA-PDT on SCC cells. Whether this combined application is successful in treating AK in vivo has to be carefully examined in follow-up studies.
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Ácido Aminolevulínico , Apoptose , Carcinoma de Células Escamosas , Fotoquimioterapia , Gases em Plasma , Humanos , Fotoquimioterapia/métodos , Gases em Plasma/farmacologia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Ácido Aminolevulínico/farmacologia , Apoptose/efeitos dos fármacos , Fármacos Fotossensibilizantes/farmacologia , Movimento Celular/efeitos dos fármacos , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismoRESUMO
Despite the progress in the development of innovative EEG acquisition systems, their use in dynamic applications is still limited by motion artifacts compromising the interpretation of the collected signals. Therefore, extensive research on the genesis of motion artifacts in EEG recordings is still needed to optimize existing technologies, shedding light on possible solutions to overcome the current limitations. We identified three potential sources of motion artifacts occurring at three different levels of a traditional biopotential acquisition chain: the skin-electrode interface, the connecting cables between the detection and the acquisition systems, and the electrode-amplifier system. The identified sources of motion artifacts were modelled starting from experimental observations carried out on EEG signals. Consequently, we designed customized EEG electrode systems aiming at experimentally disentangling the possible causes of motion artifacts. Both analytical and experimental observations indicated two main residual sites responsible for motion artifacts: the connecting cables between the electrodes and the amplifier and the sudden changes in electrode-skin impedance due to electrode movements. We concluded that further advancements in EEG technology should focus on the transduction stage of the biopotentials amplification chain, such as the electrode technology and its interfacing with the acquisition system.
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Artefatos , Eletrodos , Eletroencefalografia , Eletroencefalografia/métodos , Eletroencefalografia/instrumentação , Humanos , Processamento de Sinais Assistido por Computador , Movimento (Física) , Amplificadores Eletrônicos , Impedância Elétrica , Desenho de EquipamentoRESUMO
Insulin participates in glucose homeostasis in the body and regulates glucose, protein, and lipid metabolism. Chronic hyperglycemia triggers oxidative stress and the generation of reactive oxygen species (ROS), leading to oxidized insulin variants. Oxidative protein modifications can cause functional changes or altered immunogenicity as known from the context of autoimmune disorders. However, studies on the biological function of native and oxidized insulin on glucose homeostasis and cellular function are lacking. Native insulin showed heterogenous effects on metabolic activity, proliferation, glucose carrier transporter (GLUT) 4, and insulin receptor (INSR) expression, as well as glucose uptake in cell lines of five different human tissues. Diverse ROS compositions produced by different gas plasma approaches enabled the investigations of variously modified insulin (oxIns) with individual oxidative post-translational modification (oxPTM) patterns as identified using high-resolution mass spectrometric analysis. Specific oxIns variants promoted cellular metabolism and proliferation in several cell lines investigated, and nitrogen plasma emission lines could be linked to insulin nitration and elevated glucose uptake. In addition, insulin oxidation modified blood glucose levels in the chicken embryos (in ovo), underlining the importance of assessing protein oxidation and function in health and disease.
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Proteins belonging to the CAP superfamily are present in all kingdoms of life and have been implicated in various processes, including sperm maturation and cancer progression. They are mostly secreted glycoproteins and share a unique conserved CAP domain. The precise mode of action of these proteins, however, has remained elusive. Saccharomyces cerevisiae expresses three members of this protein family, which bind sterols in vitro and promote sterol secretion from cells. This sterol-binding and export function of yeast Pry proteins is conserved in the mammalian CRISP proteins and other CAP superfamily members. CRISP3 is an abundant protein of the human seminal plasma and interacts with alpha-1-B glycoprotein (A1BG), a human plasma glycoprotein that is upregulated in different types of cancers. Here we examined whether the interaction between CRISP proteins and A1BG affects the sterol-binding function of CAP family members. Co-expression of A1BG with CAP proteins abolished their sterol export function in yeast and their interaction inhibits sterol-binding in vitro. We map the interaction between A1BG and CRISP2 to the third of five repeated immunoglobulin-like (Ig) domains within A1BG. Interestingly, the interaction between A1BG and CRISP2 requires magnesium, suggesting that coordination of Mg2+ by the highly conserved tetrad residues within the CAP domain is essential for a stable interaction between the two proteins. The observation that A1BG modulates the sterol-binding function of CRISP2, has potential implications for the role of A1BG and related Ig domain containing proteins in cancer progression and the toxicity of reptile venoms containing CRISP proteins.
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Cyclic alternating patterns (CAP) occur in electroencephalogram (EEG) signals during non-rapid eye movement sleep. The analysis of CAP can offer insights into various sleep disorders. The first step is the identification of phases A and B for the CAP cycles. In this work, we develop an easy-to-implement accurate system to differentiate between CAP A and CAP B. Small segments of the EEG signal are processed using Gaussian filters to obtain sub-band components. Features are extracted using some statistical characteristics of these signal components. Minimum redundancy maximum relevance test is employed to identify the more significant features. Three different machine learning classifiers are considered and their performance is compared. The results are analyzed for both the balanced and unbalanced datasets. The k-nearest neighbour (kNN) classifier achieves 79.14 % accuracy and F-1 score of 79.24 % for the balanced dataset. The proposed method outperforms the existing methods for CAP classification. It is easy-to-implement and can be considered as a candidate for real-time deployment.
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Protein translation is globally downregulated under stress conditions. Many proteins that are synthesized under stress conditions use a cap-independent translation initiation pathway. A subset of cellular mRNAs that encode for these proteins contain stable secondary structures within their 5' untranslated region (5'UTR), and initiate cap-independent translation using elements called Cap-Independent Translation Enhancers (CITEs) or Internal Ribosome Entry Sites (IRESs) within their 5'UTRs. The interaction among initiation factors such as eIF4E, eIF4A and eIF4GI, especially in regulating the eIF4F complex during non-canonical translation initiation of different 5'UTR mRNAs, is poorly understood. Here, equilibrium-binding assays, circular dichroism studies and in vitro translation assays were employed to elucidate the recruitment of these initiation factors to the highly structured 5'UTRs of fibroblast-growth factor 9 (FGF-9) and hypoxia inducible factor 1 subunit alpha (HIF-1α) encoding mRNAs. We showed that eIF4A and eIF4E enhanced eIF4GI's binding affinity to the uncapped 5'UTR of HIF-1α mRNA, inducing conformational changes in the protein/RNA complex. In contrast, these factors have no effect on the binding of eIF4GI to the 5'UTR of FGF-9 mRNA. Recently, Izidoro, M. S. et al. reported that the interaction of 42nt unstructured RNA to human eIF4F complex is dominated by eIF4E and ATP-bound state of eIF4A. Here we show that structured 5'UTR mRNA binding mitigates this requirement. Based on these observations, we describe two possible cap-independent translation mechanisms for FGF-9 and HIF-1α encoding mRNAs employed by cells to mitigate cellular stress conditions.
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Lipids, possessing unsaturated fatty acid chains and polar regions with nucleophilic heteroatoms, represent suitable oxidation targets for autologous and heterologous reactive species. Lipid peroxidation products (LPPs) are highly heterogeneous, including hydroperoxides, alkenals, chlorination, or glycation. Accordingly, delineation of lipid targets, species type, resulting products, and oxidation level remains challenging. To this end, liposomal biomimetic models incorporating a phosphatidylcholine, -ethanolamine, and a sphingomyelin were used to deconvolute effects on a single lipid scale to predict potential modification product outcomes. To introduce oxidative modifications, gas plasma technology, a powerful pro-oxidant tool to promote LPP formation by forming highly abundant reactive species in the gas and liquid phases, was employed to liposomes. The plasma parameters (gas type/combination) were modified to modulate the resulting species-profile and LPP formation by enriching specific reactive species types over others. HR-LC-MS (Münzel and et al., 2017) [2] was employed for LPP identification. Moreover, the heavy oxygen isotope 18O was used to trace O2-incorporation into LPPs, providing first information on the plasma-mediated lipid peroxidation mechanism. We found that combination of lipid class and gas composition predetermined the type of attack: admixture of O2 to the plasma and the presence of nitrogen atoms with free electrons in the molecule lead to chlorination of the amide bond and headgroup. Here, atomic oxygen driven formation of hypochlorite is the major reactive species. In contrast, POPC yields mainly to LPPs with oxidation of the oleic acid tail, especially truncations, epoxidation, and hydroperoxide formation. Here, singlet oxygen is assumingly the major driver. 18O labelling revealed that gas phase derived reactive species are dominantly incorporated into the LPPs, supporting previous findings on gas-liquid interface chemistry. In summary, we here provided the first insights into gas plasma-mediated lipid peroxidation, which, employed in more complex cell and tissue models, may support identifying mechanisms of actions in plasma medicine.
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Prosthesis loosening due to lack of osteointegration between an implant and surrounding bone tissue is one of the most common causes of implant failure. Further, bacterial contamination and biofilm formation onto implants represent a serious complication after surgery. The enhancement of osteointegration can be achieved by using bioconductive materials that promote biological responses in the body, stimulating bone growth and thus bonding to tissue. Through the incorporation of antibacterial substances in bioconductive, biodegradable calcium phosphate (CaP) coatings, faster osteointegration and bactericidal properties can be achieved. In this study, Cu-doped CaP supraparticles are spray-dried and suspension-sprayed CaP ceramic coatings with antibacterial properties are prepared using high-velocity suspension flame spraying (HVSFS). The objective was to increase the coatings' porosity and investigate which Cu-doped supraparticles have the strongest antibacterial properties when introduced into the coating layers. Biocompatibility was tested on human Osteosarcoma cells MG63. A porosity of at least 13% was achieved and the supraparticles could be implemented, enhancing it up to 16%. The results showed that the addition of Cu-doped supraparticles did not significantly reduce the number of viable cells compared to the Cu-free sample, demonstrating good biocompatibility. The antimicrobial activity was assessed against the bacterial strains Escherichia coli and Staphylococcus aureus, with Safe Airborne Antibacterial testing showing a significant reduction in both Gram-positive and Gram-negative strains on the Cu-doped coatings.
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Background: Complications in community-acquired pneumonia (CAP), including cardiovascular events (CVE), can occur during an acute episode and in the long term. We aimed to analyse the role of endothelial damage biomarkers (C-terminal endothelin-1 precursor fragment [CT-proET-1] and mid-regional pro-adrenomedullin [MR-proADM]), in contrast to classic inflammation markers (C Reactive Protein [CRP] and procalcitonin [PCT]) in patients admitted for CAP and their relationship with ICU admission, CVE and mortality in the short and long term; Methods: Biomarkers were analysed in 515 patients with CAP at day 1, 285 at day 5 and 280 at day 30. Traditional inflammatory biomarkers and endothelial damage biomarkers were measured. ICU admission, CVE and mortality (in-hospital and 1-year follow-up) were assessed using receiver operating characteristic (ROC) curve analysis and univariate logistic regression. Results: A statistically significant association was observed between initial, raised CT-proET-1 and MR-proADM levels, the need for ICU admission and the development of in-hospital CVE or in-hospital mortality. Both endothelial markers maintained a strong association at day 30 with 1-year follow-up CVE. At day 1, CRP and PCT were only associated with ICU admission. On day 30, there was no association between inflammatory markers and long-term CVE or death. The odds ratio (OR) and area under the curve (AUC) of endothelial biomarkers were superior to those of classic biomarkers for all outcomes considered. Conclusions: Endothelial biomarkers are better indicators than classic ones in predicting worse outcomes in both the short and long term, especially CVE. MR-proADM is the best biomarker for predicting complications in CAP.
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In this study, we analyze metal-insulator-metal (MIM) capacitors with different thicknesses of SixNy film (650 Å, 500 Å, and 400 Å) and varying levels of film quality to improve their capacitance density. SixNy thicknesses of 650 Å, 500 Å, and 400 Å are used with four different conditions, designated as MIM (N content 1.49), NEWMIM (N content 28.1), DAMANIT (N content 1.43), and NIT (N content 0.30). We divide the C-V characteristics into two categories: voltage coefficient of capacitance (VCC) and temperature coefficient of capacitance (TCC). There was an overall increase in the VCC as the thickness of the SixNy film decreased, with some variation depending on the condition. However, the TCC did not vary significantly with thickness, only with condition. At the same thickness, the NIT condition yielded the highest capacitance density, while the MIM condition showed the lowest capacitance density. This difference was due to the actual thickness of the film and the variation in its k-value depending on the condition. The most influential factor for capacitance uniformity was the thickness uniformity of the SixNy film.
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PURPOSE: The study purpose was to investigate the laboratory-based performance of three commercially available shell add-on products under varsity-level impact conditions. METHODS: Pendulum impact tests were conducted at multiple locations (front, front boss, rear, side) and speeds (3.1, 4.9, 6.4 m/s) using two helmet models. Tests were performed with a single add-on configuration for baseline comparisons and a double add-on configuration to simulate collisions with both players wearing shell add-ons. A linear mixed-effect model was used to evaluate peak linear acceleration (PLA), peak rotational acceleration (PRA), and concussion risk, which was calculated from a bivariate injury risk function, based on shell add-on and test configuration. RESULTS: All shell add-ons decreased peak head kinematics and injury risk compared to controls, with the Guardian NXT producing the largest reductions (PLA: 7.9%, PRA: 14.1%, Risk: 34.1%) compared to the SAFR Helmet Cover (PLA: 4.5%, PRA: 9.3%, Risk: 24.7%) and Guardian XT (PLA: 3.2%, PRA: 5.0%, Risk: 15.5%). The same trend was observed in the double add-on test configuration. However, the Guardian NXT (PLA: 17.1%; PRA: 11.5%; Risk: 62.8%) and SAFR Helmet Cover (PLA: 12.2%; PRA: 9.1%; Risk: 52.2%) produced larger reductions in peak head kinematics and injury risk than the Guardian XT (PLA: 5.7%, PRA: 2.2%, Risk: 21.8%). CONCLUSION: In laboratory-based assessments that simulated varsity-level impact conditions, the Guardian NXT was associated with larger reductions in PLA, PRA, and injury risk compared to the SAFR Helmet Cover and Guardian XT. Although shell add-ons can enhance head protection, helmet model selection should be prioritized.
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Futebol Americano , Dispositivos de Proteção da Cabeça , Humanos , Futebol Americano/lesões , Fenômenos Biomecânicos , Aceleração , Concussão Encefálica/prevenção & controle , Concussão Encefálica/fisiopatologia , Desenho de Equipamento , Equipamentos EsportivosRESUMO
The transplantation of CD34+ hematopoietic stem-progenitor cells (HSPCs) derived from cord blood serves as the standard treatment for selected hematological, oncological, metabolic, and immunodeficiency disorders, of which the dose is pivotal to the clinical outcome. Based on numerous maternal and neonatal parameters, we evaluated the predictive power of mathematical pipelines to the proportion of CD34+ cells in the final cryopreserved cord blood product adopting both parametric and non-parametric algorithms. Twenty-four predictor variables associated with the cord blood processing of 802 processed cord blood units randomly sampled in 2020-2022 were retrieved and analyzed. Prediction models were developed by adopting the parametric (multivariate linear regression) and non-parametric (random forest and back propagation neural network) statistical models to investigate the data patterns for determining the single outcome (i.e., the proportion of CD34+ cells). The multivariate linear regression model produced the lowest root-mean-square deviation (0.0982). However, the model created by the back propagation neural network produced the highest median absolute deviation (0.0689) and predictive power (56.99%) in comparison to the random forest and multivariate linear regression. The predictive model depending on a combination of continuous and discrete maternal with neonatal parameters associated with cord blood processing can predict the CD34+ dose in the final product for clinical utilization. The back propagation neural network algorithm produces a model with the highest predictive power which can be widely applied to assisting cell banks for optimal cord blood unit selection to ensure the highest chance of transplantation success.
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Algoritmos , Antígenos CD34 , Sangue Fetal , Células-Tronco Hematopoéticas , Aprendizado de Máquina , Humanos , Sangue Fetal/citologia , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/metabolismo , Antígenos CD34/metabolismo , Feminino , Redes Neurais de Computação , Transplante de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Recém-Nascido , Criopreservação/métodosRESUMO
BACKGROUND: Cold atmospheric plasma (CAP) has been shown to improve the recovery of transected peripheral nerves. We determined the protective role of CAP-activated saline (CAP-AS) treatment in the acute and subacute stages of spinal cord injury (SCI) in mice. METHODS: C57BL/6 SCI mice were treated with CAP-AS for 14 days. Injury recovery was assessed weekly for four weeks by conducting motor function tests, including the Basso Mouse Scale (BMS) and footprint test. Transcriptome analysis was conducted on day 14 to elucidate potential mechanisms, which were further validated through immunofluorescence examinations of the injured spinal cord tissues on day 28 and the levels of proinflammatory cytokines produced by macrophages in vitro. RESULTS: Compared to the SCI group, the CAP-AS-treated groups presented significantly better hindlimb motor function after four weeks. The downregulated (SCI vs. SCI + CAP-AS, with CAP-AS activated for 20 min) differentially expressed genes (DEGs) were enriched in the extracellular region, extracellular matrix (ECM), and ECM-receptor interaction. In contrast, the upregulated DEGs were enriched in immune response-associated pathways. Histological changes in the CAP-AS-treated groups were observed to further validate the predicted mechanisms 28 days post-injury. The alleviation of secondary injury was confirmed by an increase in GFAP-positive and NFH-positive areas, and enhanced outgrowth of 5-HT-positive fibers. Inhibited ECM remodeling was confirmed by a decrease in the areas positive for PDGFRß, fibronectin, and laminin. A decrease in the infiltration of macrophages and activation of microglia was determined by a decrease in CD68-positive and F4/80-positive areas. The inhibitory effect of CAP-AS on inflammation was further supported by a decrease in the levels of the proinflammatory cytokines IL-1ß, IL-6, and TNF-α in CAP-AS-treated M1 macrophages. CONCLUSION: CAP-AS can alleviate secondary injury in SCI model mice by inhibiting ECM remodeling in injured tissues and reducing the infiltration or activation of proinflammatory macrophages/microglia.
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Chemical modifications of cellular RNAs play key roles in gene expression and host defense. The cap-adjacent N6,2'-O-dimethyladenosine (m6Am) is a prevalent modification of vertebrate and viral mRNAs and is catalyzed by the newly discovered N6 methyltransferase PCIF1. However, its role in gene expression remains unclear due to conflicting reports on its effects on mRNA stability and translation. In this study, we investigated the impact of siRNA-mediated transient suppression of PCIF1 on global mRNA expression in HeLa cells. We identified a subset of differentially expressed genes (DEGs) that exhibited minimal overlap with previously reported DEGs. Subsequent validation revealed that PCIF1 positively and negatively regulates RAB23 and CNOT6 expression, respectively, at both the mRNA and protein levels. Mechanistic analyses demonstrated that PCIF1 regulates the stability of these target mRNAs rather than their transcription, and rescue experiments confirmed the requirement of PCIF1's methyltransferase activity for these regulations. Furthermore, MeRIP-qPCR analysis showed that PCIF1 suppression significantly reduced the m6A levels of RAB23 and CNOT6 mRNAs. These findings suggest that PCIF1 regulates the stability of specific mRNAs in opposite ways through m6A modification, providing new insights into the role of m6Am in the regulation of gene expression.
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Metiltransferases , Estabilidade de RNA , RNA Mensageiro , Proteínas rab de Ligação ao GTP , Humanos , Estabilidade de RNA/genética , Metiltransferases/metabolismo , Metiltransferases/genética , Células HeLa , Proteínas rab de Ligação ao GTP/metabolismo , Proteínas rab de Ligação ao GTP/genética , RNA Mensageiro/metabolismo , RNA Mensageiro/genética , Adenosina/metabolismo , Adenosina/análogos & derivados , Fatores de Transcrição/metabolismo , Capuzes de RNA/metabolismo , Proteínas Nucleares , Proteínas Adaptadoras de Transdução de SinalRESUMO
Influenza poses a significant threat to global health, with the ability to cause severe epidemics and pandemics. The polymerase basic protein 2 (PB2) of the influenza virus plays a crucial role in the viral replication process, making the CAP-binding domain of PB2 an attractive target for antiviral drug development. This study aimed to identify and evaluate potential inhibitors of the influenza polymerase PB2 CAP-binding domain using computational drug discovery methods. We employed a comprehensive computational approach involving virtual screening, molecular docking, and 500 ns molecular dynamics (MD) simulations. Compounds were selected from the Diverse lib database and assessed for their binding affinity and stability in interaction with the PB2 CAP-binding domain. The study utilized the generalized amber force field (GAFF) for MD simulations to further evaluate the dynamic behaviour and stability of the interactions. Among the screened compounds, compounds 1, 3, and 4 showed promising binding affinities. Compound 4 demonstrated the highest binding stability and the most favourable free energy profile, indicating strong and consistent interaction with the target domain. Compound 3 displayed moderate stability with dynamic conformational changes, while Compound 1 maintained robust interactions throughout the simulations. Comparative analyses of these compounds against a control compound highlighted their potential efficacy. Compound 4 emerged as the most promising inhibitor, with substantial stability and strong binding affinity to the PB2 CAP-binding domain. These findings suggest that compound 4, along with compounds 1 and 3, holds the potential for further development into effective antiviral agents against influenza. Future studies should focus on experimental validation of these compounds and exploration of resistance mechanisms to enhance their therapeutic utility.
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Antivirais , Descoberta de Drogas , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , RNA Polimerase Dependente de RNA , Proteínas Virais , Antivirais/farmacologia , Antivirais/química , Proteínas Virais/metabolismo , Proteínas Virais/química , Proteínas Virais/antagonistas & inibidores , RNA Polimerase Dependente de RNA/química , RNA Polimerase Dependente de RNA/metabolismo , RNA Polimerase Dependente de RNA/antagonistas & inibidores , Ligação Proteica , Humanos , Sítios de Ligação , Influenza Humana/tratamento farmacológico , Influenza Humana/virologia , TermodinâmicaRESUMO
The emergence of high-resistance strains to known antifungal drugs has highlighted the urgency of developing novel therapies for chronic dermatophytosis as a global health problem. An experimental dermatophytosis model in guinea pigs was developed to investigate the in vivo wound healing effects of cold atmospheric plasma (CAP) on T. rubrum skin invasion. Guinea pigs were experimentally infected with T. rubrum and wound healing was evaluated at 1, 4, 8 and 12 days post infection in the CAP-treated, terbinafine-treated and non-treated controls. Our results showed that CAP strongly inhibited the fungal virulence in vitro in culture media and in vivo on the skin lesions of experimentally infected guinea pigs even more efficient than that of terbinafine, resulting in complete wound healing at 8 days post infection. These results indicate that CAP would be considered as a promising tool comparable to conventional chemical therapies, for the treatment of drug-resistant chronic dermatophytosis caused by T. rubrum.
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Root cap cuticles (RCCs), comprising mainly very-long-chain fatty acids (VLCFAs), promote salt tolerance by preventing ion influx. Glycosylphosphatidylinositol-anchored lipid transfer protein (LTPG)1 and LTPG2 participate in VLCFA deposition in the extracellular region, aiding RCC formation in the lateral roots. In this study, we investigated whether LTPG1 and LTPG2 have similar functions in the primary roots of young Arabidopsis thaliana. Phenotypic analyses, fluorescence microscopy, and quantitative real-time reverse transcription polymerase chain reaction confirmed that NaCl exposure induced LTPG1 and LTPG2 expression and promoted RCC formation in young primary roots. The loss of RCC in the ltpg1 and ltpg2 mutants resulted in increased NaCl sensitivity of root elongation. NaCl also upregulated the expression of several NaCl-responsive genes in ltpg1 and ltpg2. We conclude that RCC formation via LTPG function is pivotal in enhancing salt tolerance in young primary roots.
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Proteínas de Arabidopsis , Arabidopsis , Proteínas de Transporte , Regulação da Expressão Gênica de Plantas , Tolerância ao Sal , Cloreto de Sódio , Arabidopsis/genética , Arabidopsis/metabolismo , Arabidopsis/crescimento & desenvolvimento , Tolerância ao Sal/genética , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Cloreto de Sódio/farmacologia , Proteínas de Transporte/metabolismo , Proteínas de Transporte/genética , Plântula/crescimento & desenvolvimento , Plântula/metabolismo , Plântula/genética , Plântula/efeitos dos fármacos , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/metabolismo , Raízes de Plantas/genética , Raízes de Plantas/efeitos dos fármacos , Glicosilfosfatidilinositóis/metabolismo , Coifa/metabolismo , Coifa/genética , Coifa/crescimento & desenvolvimento , MutaçãoRESUMO
Significance: Consistent and accurate probe placement is a crucial step towards enhancing the reproducibility of longitudinal and group-based functional neuroimaging studies. While the selection of headgear is central to these efforts, there does not currently exist a standardized design that can accommodate diverse probe configurations and experimental procedures. Aim: We aim to provide the community with an open-source software pipeline for conveniently creating low-cost, 3-D printable neuroimaging head caps with anatomically significant landmarks integrated into the structure of the cap. Approach: We utilize our advanced 3-D head mesh generation toolbox and 10-20 head landmark calculations to quickly convert a subject's anatomical scan or an atlas into a 3-D printable head cap model. The 3-D modeling environment of the open-source Blender platform permits advanced mesh processing features to customize the cap. The design process is streamlined into a Blender add-on named "NeuroCaptain". Results: Using the intuitive user interface, we create various head cap models using brain atlases, and share those with the community. The resulting mesh-based head cap designs are readily 3-D printable using off-the-shelf printers and filaments while accurately preserving the head topology and landmarks. Conclusions: The methods developed in this work result in a widely accessible tool for community members to design, customize and fabricate caps that incorporate anatomically derived landmarks. This not only permits personalized head cap designs to achieve improved accuracy, but also offers an open platform for the community to propose standardizable head caps to facilitate multi-centered data collection and sharing.