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1.
Arch Pharm (Weinheim) ; 357(6): e2300670, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38487979

RESUMO

Influenza A virus (IAV) is a highly contagious respiratory pathogen that significantly threatens global health by causing seasonal epidemics and occasional, unpredictable pandemics. To identify new compounds with therapeutic potential against IAV, we designed and synthesized a series of 4'-morpholinodiazenyl chalcones using the molecular hybridization method, performed a high-content screen against IAV, and found that (E)-1-{4-[(E)-morpholinodiazenyl]phenyl}-3-(3,4,5-trimethoxyphenyl)prop-2-en-1-one (MC-22) completely neutralized IAV infection. While MC-22 allowed IAV to successfully internalize into the cell and fuse at the acidic late endosomes, it prevented viral capsid uncoating and genome release. Since IAV majorly utilizes clathrin-mediated endocytosis (CME) for cellular entry, we examined whether MC-22 had any effect on CME, using nonviral cargoes that enter cells via clathrin-dependent or -independent pathways. Although MC-22 showed no effect on the uptake of choleratoxin B, a cargo that enters cells majorly via the clathrin-independent pathway, it significantly attenuated the clathrin-dependent internalization of both epidermal growth factor and transferrin. Cell biological analyses revealed a marked increase in the size of early endosomes upon MC-22 treatment, indicating an endosomal trafficking/maturation defect. This study reports the identification of MC-22 as a novel CME-targeting, highly potent IAV entry inhibitor, which is expected to neutralize a broad spectrum of viruses that enter the host cells via CME.


Assuntos
Antivirais , Clatrina , Vírus da Influenza A , Humanos , Vírus da Influenza A/efeitos dos fármacos , Clatrina/metabolismo , Antivirais/farmacologia , Antivirais/síntese química , Antivirais/química , Endocitose/efeitos dos fármacos , Animais , Chalconas/farmacologia , Chalconas/síntese química , Chalconas/química , Desenvelopamento do Vírus/efeitos dos fármacos , Cães , Células Madin Darby de Rim Canino , Internalização do Vírus/efeitos dos fármacos , Morfolinas/farmacologia , Morfolinas/síntese química , Morfolinas/química , Células A549 , Relação Estrutura-Atividade
2.
Am J Physiol Cell Physiol ; 324(5): C1061-C1077, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-36939202

RESUMO

The endothelial glycocalyx (EG) is a meshlike network present on the apical surface of the endothelium. Membrane-bound proteoglycans, the major backbone molecules of the EG, consist of glycosaminoglycans attached to core proteins. In addition to maintaining the integrity of the endothelial barrier, the EG regulates inflammation and perfusion and acts as a mechanosensor. The loss of the EG can cause endothelial dysfunction and drive the progression of vascular diseases including diabetic retinopathy. Therefore, the EG presents a novel therapeutic target for treatment of vascular complications. In this review article, we provide an overview of the structure and function of the EG in the retina. Our particular focus is on hyperglycemia-induced perturbations in the glycocalyx structure in the retina, potential underlying mechanisms, and clinical trials studying protective treatments against degradation of the EG.


Assuntos
Diabetes Mellitus , Retinopatia Diabética , Hiperglicemia , Doenças Vasculares , Humanos , Retinopatia Diabética/complicações , Retinopatia Diabética/metabolismo , Glicocálix/metabolismo , Endotélio Vascular/metabolismo , Hiperglicemia/metabolismo , Doenças Vasculares/metabolismo , Retina/metabolismo , Diabetes Mellitus/metabolismo
3.
Blood ; 137(11): 1538-1549, 2021 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-33512489

RESUMO

Neutrophils play a crucial role in the intertwined processes of thrombosis and inflammation. An altered neutrophil phenotype may contribute to inadequate resolution, which is known to be a major pathophysiological contributor of thromboinflammatory conditions such as sickle cell disease (SCD). The endogenous protein annexin A1 (AnxA1) facilitates inflammation resolution via formyl peptide receptors (FPRs). We sought to comprehensively elucidate the functional significance of targeting the neutrophil-dependent AnxA1/FPR2/ALX pathway in SCD. Administration of AnxA1 mimetic peptide AnxA1Ac2-26 ameliorated cerebral thrombotic responses in Sickle transgenic mice via regulation of the FPR2/ALX (a fundamental receptor involved in resolution) pathway. We found direct evidence that neutrophils with SCD phenotype play a key role in contributing to thromboinflammation. In addition, AnxA1Ac2-26 regulated activated SCD neutrophils through protein kinase B (Akt) and extracellular signal-regulated kinases (ERK1/2) to enable resolution. We present compelling conceptual evidence that targeting the AnxA1/FPR2/ALX pathway may provide new therapeutic possibilities against thromboinflammatory conditions such as SCD.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Anemia Falciforme/metabolismo , Anexina A1/metabolismo , Receptores de Formil Peptídeo/metabolismo , Receptores de Lipoxinas/metabolismo , Transdução de Sinais , Trombose/metabolismo , Adulto , Anemia Falciforme/complicações , Anemia Falciforme/patologia , Animais , Feminino , Humanos , Inflamação/etiologia , Inflamação/metabolismo , Inflamação/patologia , Masculino , Camundongos , Pessoa de Meia-Idade , Neutrófilos/metabolismo , Neutrófilos/patologia , Trombose/etiologia , Trombose/patologia , Adulto Jovem
4.
Environ Res ; 234: 116599, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37429400

RESUMO

The present research is targeted at E. cardamomum-derived TiO2-photocatalyst synthesis, reporting for the first time. The structural properties observed from the XRD pattern reveal that EC:TiO2 has an anatase phase and crystallite size is assessed by Debye-Scherrer's method (3.56 nm), WH-method (3.30 nm), and Modified-Debye-Scherrer's method (3.27 nm). An optical study by the UV-Vis spectrum shows strong absorption at 313 nm, and the corresponding band gap value is 3.28 eV. The topographical and morphological properties revealed by SEM and HRTEM images, elucidate the formation of multi-shaped particles of nano-size. Further, the phytochemicals on the EC:TiO2 NPs' surface are confirmed by the FTIR spectrum. The photocatalytic activity is well studied under UV light towards Congo Red dye, along with an effect of the dose of catalyst. EC:TiO2 (20 mg) has exhibited high photocatalytic efficiency up to 97% for 150 min of exposure due to the morphological, structural, and optical properties. CR degradation reaction exhibits pseudo-first-order kinetics, displaying a rate constant value of 0.01320 min-1. Reusability investigations reveal that after four photocatalysis cycles, EC:TiO2 has an effective efficiency of >85%. Additionally, EC:TiO2 NPs have been assessed for antibacterial activity and show potential against two bacterial species (S. aureus and P. aeruginosa). Therefore, these research outcomes from the eco-friendly and low-cost synthesis, are promising for the use of EC:TiO2 as a talented photocatalyst towards the removal of crystal violet dye as well as an antibacterial agent against bacterial pathogens.


Assuntos
Nanopartículas , Staphylococcus aureus , Nanopartículas/química , Raios Ultravioleta , Titânio/química , Antibacterianos/farmacologia , Antibacterianos/química , Bactérias
5.
Sensors (Basel) ; 23(19)2023 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-37836846

RESUMO

Due to the modern power system's rapid development, more scattered smart grid components are securely linked into the power system by encircling a wide electrical power network with the underpinning communication system. By enabling a wide range of applications, such as distributed energy management, system state forecasting, and cyberattack security, these components generate vast amounts of data that automate and improve the efficiency of the smart grid. Due to traditional computer technologies' inability to handle the massive amount of data that smart grid systems generate, AI-based alternatives have received a lot of interest. Long Short-Term Memory (LSTM) and recurrent Neural Networks (RNN) will be specifically developed in this study to address this issue by incorporating the adaptively time-developing energy system's attributes to enhance the model of the dynamic properties of contemporary Smart Grid (SG) that are impacted by Revised Encoding Scheme (RES) or system reconfiguration to differentiate LSTM changes & real-time threats. More specifically, we provide a federated instructional strategy for consumer sharing of power data to Power Grid (PG) that is supported by edge clouds, protects consumer privacy, and is communication-efficient. They then design two optimization problems for Energy Data Owners (EDO) and energy service operations, as well as a local information assessment method in Federated Learning (FL) by taking non-independent and identically distributed (IID) effects into consideration. The test results revealed that LSTM had a longer training duration, four hidden levels, and higher training loss than other models. The provided method works incredibly well in several situations to identify FDIA. The suggested approach may successfully induce EDOs to employ high-quality local models, increase the payout of the ESP, and decrease task latencies, according to extensive simulations, which are the last points. According to the verification results, every assault sample could be effectively recognized utilizing the current detection methods and the LSTM RNN-based structure created by Smart.

6.
Glycobiology ; 32(8): 720-734, 2022 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-35552402

RESUMO

INTRODUCTION: The endothelial glycocalyx regulates vascular permeability, inflammation, and coagulation, and acts as a mechanosensor. The loss of glycocalyx can cause endothelial injury and contribute to several microvascular complications and, therefore, may promote diabetic retinopathy. Studies have shown a partial loss of retinal glycocalyx in diabetes, but with few molecular details of the changes in glycosaminoglycan (GAG) composition. Therefore, the purpose of our study was to investigate the effect of hyperglycemia on GAGs of the retinal endothelial glycocalyx. METHODS: GAGs were isolated from rat retinal microvascular endothelial cells (RRMECs), media, and retinas, followed by liquid chromatography-mass spectrometry assays. Quantitative real-time polymerase chain reaction was used to study mRNA transcripts of the enzymes involved in GAG biosynthesis. RESULTS AND CONCLUSIONS: Hyperglycemia significantly increased the shedding of heparan sulfate (HS), chondroitin sulfate (CS), and hyaluronic acid (HA). There were no changes to the levels of HS in RRMEC monolayers grown in high-glucose media, but the levels of CS and HA decreased dramatically. Similarly, while HA decreased in the retinas of diabetic rats, the total GAG and CS levels increased. Hyperglycemia in RRMECs caused a significant increase in the mRNA levels of the enzymes involved in GAG biosynthesis (including EXTL-1,2,3, EXT-1,2, ChSY-1,3, and HAS-2,3), with these increases potentially being compensatory responses to overall glycocalyx loss. Both RRMECs and retinas of diabetic rats exhibited glucose-induced alterations in the disaccharide compositions and sulfation of HS and CS, with the changes in sulfation including N,6-O-sulfation on HS and 4-O-sulfation on CS.


Assuntos
Diabetes Mellitus Experimental , Hiperglicemia , Animais , Células Cultivadas , Sulfatos de Condroitina/química , Células Endoteliais , Glucose/farmacologia , Glicosaminoglicanos/química , Heparitina Sulfato/química , Ácido Hialurônico/química , RNA Mensageiro/genética , Ratos , Retina
7.
Exp Eye Res ; 213: 108846, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34801534

RESUMO

PURPOSE: Diabetic retinopathy is a vision-threatening complication of diabetes characterized by endothelial injury and vascular dysfunction. The loss of the endothelial glycocalyx, a dynamic layer lining all endothelial cells, contributes to several microvascular pathologies, including an increase in vascular permeability, leukocyte plugging, and capillary occlusion, and may drive the progression of retinopathy. Previously, a significant decrease in glycocalyx thickness has been observed in diabetic retinas. However, the effects of diabetes on specific components of the retinal glycocalyx have not yet been studied. Therefore, the aim of our study was to investigate changes in synthesis, expression, and shedding of retinal glycocalyx components induced by hyperglycemia, which could provide a novel therapeutic target for diabetic retinopathy. METHODS: Primary rat retinal microvascular endothelial cells (RRMECs) were grown under normal glucose (5 mM) or high-glucose (25 mM) conditions for 6 days. The mRNA and protein levels of the glycocalyx components were examined using qRT-PCR and Western blot analysis, respectively. Further, mass spectrometry was used to analyze protein intensities of core proteins. In addition, the streptozotocin-induced Type 1 diabetic rat model was used to study changes in the expression of the retinal glycocalyx in vivo. The shedding of the glycocalyx was studied in both culture medium and in plasma using Western blot analysis. RESULTS: A significant increase in the shedding of syndecan-1 and CD44 was observed both in vitro and in vivo under high-glucose conditions. The mRNA levels of syndecan-3 were significantly lower in the RRMECs grown under high glucose conditions, whereas those of syndecan-1, syndecan-2, syndecan-4, glypican-1, glypican-3, and CD44 were significantly higher. The protein expression of syndecan-3 and glypican-1 in RRMECs was reduced considerably following exposure to high glucose, whereas that of syndecan-1 and CD44 increased significantly. In addition, mass spectrometry data also suggests a significant increase in syndecan-4 and a significant decrease in glypican-3 protein levels with high glucose stimulation. In vivo, our data also suggest a significant decrease in the mRNA transcripts of syndecan-3 and an increase in mRNA levels of glypican-1 and CD44 in the retinas of diabetic rats. The diabetic rats exhibited a significant reduction in the retinal expression of syndecan-3 and CD44. However, the expression of syndecan-1 and glypican-1 increased significantly in the diabetic retina. CONCLUSIONS: One of the main findings of our study was the considerable diversity of glucose-induced changes in expression and shedding of various components of endothelial glycocalyx, for example, increased endothelial and retinal syndecan-1, but decreased endothelial and retinal syndecan-3. This indicates that the reported decrease in the retinal glycocalyx in diabetes in not a result of a non-specific shedding mechanism. Moreover, mRNA measurements indicated a similar diversity, with increases in endothelial and/or retinal levels of syndecan-1, glypican-1, and CD44, but a decrease for syndecan-3, with these increases in mRNA potentially a compensatory reaction to the overall loss of glycocalyx.


Assuntos
Retinopatia Diabética/metabolismo , Glicocálix/metabolismo , Hiperglicemia/metabolismo , Retina/metabolismo , Animais , Glicemia/metabolismo , Western Blotting , Células Cultivadas , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 1/metabolismo , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Ensaio de Imunoadsorção Enzimática , Glucose/farmacologia , Glipicanas/metabolismo , Receptores de Hialuronatos/metabolismo , Insulina/sangue , Masculino , Espectrometria de Massas , RNA Mensageiro/genética , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase em Tempo Real , Vasos Retinianos/citologia , Sindecanas/metabolismo
8.
Subst Use Misuse ; 56(12): 1837-1845, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34378487

RESUMO

BACKGROUND: People who use illicit drugs (PWUD) experience various adverse health outcomes leading to increased healthcare service utilization. PWUD are also a highly mobile population which poses challenges to healthcare delivery. The objective of this study was to identify migration patterns from the Downtown Eastside (DTES), an urban illicit drug scene in Vancouver and to estimate the impact of different migration patterns on two outcomes: a) emergency department (ED) visits and b) ED visits resulting in inpatient admission among PWUD. METHODS: Three prospective cohorts of PWUD in Vancouver were linked with regional ED data. We defined the optimal number of trajectory groups that best represented distinct patterns of migration from Vancouver's DTES using a latent class growth analysis. Then, generalized estimating equations were used to estimate the effect of migration patterns on the two ED outcomes. RESULTS: Four distinct migration trajectory patterns were identified among the 1210 included participants: PWUD who consistently lived in the DTES, those who migrated out of DTES early, those who migrated out of DTES late, and those who frequently revisited the DTES. Participants who frequently revisited the DTES had higher odds of an ED visit (adjusted odds ratio = 1.62; 95% confidence interval: 1.28-2.06). There was no significant association between migration patterns and inpatient admission. CONCLUSIONS: We found that PWUD who frequently revisited the DTES were more likely to have utilized the ED, suggesting that there may be a subgroup of PWUD who are at increased risk of experiencing negative health outcomes.Supplemental data for this article is available online at 10.1080/10826084.2021.1958849.


Assuntos
Usuários de Drogas , Drogas Ilícitas , Canadá , Serviço Hospitalar de Emergência , Humanos , Estudos Prospectivos
9.
FASEB J ; 32(5): 2381-2394, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29269399

RESUMO

Stroke continues to be a leading cause of death and disability worldwide, yet effective treatments are lacking. Previous studies have indicated that stem-cell transplantation could be an effective treatment. However, little is known about the direct impact of transplanted cells on injured brain tissue. We wanted to help fill this knowledge gap and investigated effects of hematopoietic stem/progenitor cells (HSPCs) on the cerebral microcirculation after ischemia-reperfusion injury (I/RI). Treatment of HSPCs in I/RI for up to 2 wk after cerebral I/RI led to decreased mortality rate, decreased infarct volume, improved functional outcome, reduced microglial activation, and reduced cerebral leukocyte adhesion. Confocal microscopy and fluorescence-activated cell sorting analyses showed transplanted HSPCs emigrate preferentially into ischemic cortex brain parenchyma. We isolated migrated HSPCs from the brain; using RNA sequencing to investigate the transcriptome, we found metallothionein (MT, particularly MT-I) transcripts were dramatically up-regulated. Finally, to confirm the significance of MT, we exogenously administered MT-I after cerebral I/RI and found that it produced neuroprotection in a manner similar to HSPC treatment. These findings provide novel evidence that the mechanism through which HSPCs promote repair after stroke maybe via direct action of HSPC-derived MT-I and could therefore be exploited as a useful therapeutic strategy for stroke.-Smith, H. K., Omura, S., Vital, S. A., Becker, F., Senchenkova, E. Y., Kaur, G., Tsunoda, I., Peirce, S. M., Gavins, F. N. E. Metallothionein I as a direct link between therapeutic hematopoietic stem/progenitor cells and cerebral protection in stroke.


Assuntos
Circulação Cerebrovascular , Transplante de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas/metabolismo , Metalotioneína/biossíntese , Microcirculação , Acidente Vascular Cerebral , Animais , Regulação da Expressão Gênica , Células-Tronco Hematopoéticas/patologia , Masculino , Camundongos , Acidente Vascular Cerebral/metabolismo , Acidente Vascular Cerebral/patologia , Acidente Vascular Cerebral/terapia
10.
Bioorg Chem ; 80: 24-35, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29864685

RESUMO

Designing of hybrid drugs with specific multitarget profile is a promising line of attack against inflammation. In light of this, a series of benzimidazole scaffold based hybrid molecules were designed by integrating benzimidazoles (containing pharmacophoric elements for COXs and LOXs inhibitors) with phthalimide subunit of thalidomide (pharmacophore element for TNF-α inhibitor) under one construct via molecular hybridization strategy. The designed molecules were synthesized and evaluated for their inhibitory activity against COXs (COX-1, COX-2), LOXs (5-LOX, 15-LOX) enzymes as well as TNF-α inhibitory effect. The results revealed that, compounds (3a-l) obtained showed inhibition in submicromolar range against COXs and LOXs targets whereas milder inhibitory activity was obtained against lipopolysaccharides (LPS)-induced TNF-α secretion by murine macrophage-like cells (RAW264.7). Within this class of compounds, 3j emerged as having alluring multiple inhibitory effects on set of COX-1/2 and 5-/15-LOX enzymes (COX-1 IC50 = 9.85 µM; COX-2 IC50 = 1.00 µM; SI = 9.85; 5-LOX IC50 = 0.32 µM; 15-LOX IC50 = 1.02 µM) in conjunction with a good anti-inflammatory and analgesic activities. Additionally, compound 3j showed gastrointestinal safety with reduced lipid peroxidation. Docking results of compound 3j with COX-2 and 5-LOX were also consistent with the in vivo anti-inflammatory results.


Assuntos
Analgésicos/síntese química , Benzimidazóis/química , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Animais , Araquidonato 5-Lipoxigenase/química , Araquidonato 5-Lipoxigenase/metabolismo , Benzimidazóis/farmacologia , Benzimidazóis/uso terapêutico , Sítios de Ligação , Domínio Catalítico , Ciclo-Oxigenase 1/química , Ciclo-Oxigenase 1/metabolismo , Ciclo-Oxigenase 2/química , Ciclo-Oxigenase 2/metabolismo , Inibidores de Ciclo-Oxigenase 2/síntese química , Inibidores de Ciclo-Oxigenase 2/farmacologia , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Inibidores de Ciclo-Oxigenase/síntese química , Inibidores de Ciclo-Oxigenase/farmacologia , Inibidores de Ciclo-Oxigenase/uso terapêutico , Desenho de Fármacos , Edema/induzido quimicamente , Edema/tratamento farmacológico , Edema/patologia , Peroxidação de Lipídeos/efeitos dos fármacos , Inibidores de Lipoxigenase/síntese química , Inibidores de Lipoxigenase/farmacologia , Inibidores de Lipoxigenase/uso terapêutico , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Simulação de Acoplamento Molecular , Células RAW 264.7
11.
Int J Mol Sci ; 19(4)2018 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-29659553

RESUMO

Cardiovascular disease (CVD) continues to be the leading cause of death in the world. Increased inflammation and an enhanced thrombotic milieu represent two major complications of CVD, which can culminate into an ischemic event. Treatment for these life-threatening complications remains reperfusion and restoration of blood flow. However, reperfusion strategies may result in ischemia-reperfusion injury (I/RI) secondary to various cardiovascular pathologies, including myocardial infarction and stroke, by furthering the inflammatory and thrombotic responses and delivering inflammatory mediators to the affected tissue. Annexin A1 (AnxA1) and its mimetic peptides are endogenous anti-inflammatory and pro-resolving mediators, known to have significant effects in resolving inflammation in a variety of disease models. Mounting evidence suggests that AnxA1, which interacts with the formyl peptide receptor (FPR) family, may have a significant role in mitigating I/RI associated complications. In this review article, we focus on how AnxA1 plays a protective role in the I/R based vascular pathologies.


Assuntos
Anexina A1/uso terapêutico , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Anexina A1/farmacologia , Humanos , Especificidade de Órgãos/efeitos dos fármacos
12.
Org Biomol Chem ; 13(16): 4673-9, 2015 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-25790762

RESUMO

A pyrimidine-based sensor () has been synthesized through the facile one pot reaction of pyrrole-2-carboxaldehyde, 2-aminobenzimidazole and 1, 3-dimethylbarbituric acid in methanol using a few drops of HCl as a catalyst. Further, compound was fabricated into its fluorescent organic nanoparticles (FONPs) and characterized using DLS and SEM. The photophysical evaluation of the FONPs was done against bacteria and fungi. It was observed that the fluorescence intensity of the FONPs was selectively enhanced in the presence of the Gram -ve bacterium Pseudomonas aeruginosa with a detection limit of 46 CFU. To the best of our knowledge, this study is the first report on the use of the FONPs of pyrimidine derivative for the detection of Pseudomonas aeruginosa in various samples.


Assuntos
Nanopartículas/química , Nanotecnologia/métodos , Pseudomonas aeruginosa/isolamento & purificação , Pirimidinas/química , Antibacterianos/química , Técnicas Biossensoriais , Fluorometria , Concentração de Íons de Hidrogênio , Luz , Limite de Detecção , Metanol/química , Microscopia Eletrônica de Varredura , Compostos Orgânicos/química , Fotoquímica , Espectrometria de Fluorescência , Espectrofotometria Ultravioleta , Células-Tronco , Água/química
13.
Plant Physiol ; 161(1): 252-65, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23124323

RESUMO

Cycles of whole-genome duplication (WGD) and diploidization are hallmarks of eukaryotic genome evolution and speciation. Polyploid wheat (Triticum aestivum) has had a massive increase in genome size largely due to recent WGDs. How these processes may impact the dynamics of gene evolution was studied by comparing the patterns of gene structure changes, alternative splicing (AS), and codon substitution rates among wheat and model grass genomes. In orthologous gene sets, significantly more acquired and lost exonic sequences were detected in wheat than in model grasses. In wheat, 35% of these gene structure rearrangements resulted in frame-shift mutations and premature termination codons. An increased codon mutation rate in the wheat lineage compared with Brachypodium distachyon was found for 17% of orthologs. The discovery of premature termination codons in 38% of expressed genes was consistent with ongoing pseudogenization of the wheat genome. The rates of AS within the individual wheat subgenomes (21%-25%) were similar to diploid plants. However, we uncovered a high level of AS pattern divergence between the duplicated homeologous copies of genes. Our results are consistent with the accelerated accumulation of AS isoforms, nonsynonymous mutations, and gene structure rearrangements in the wheat lineage, likely due to genetic redundancy created by WGDs. Whereas these processes mostly contribute to the degeneration of a duplicated genome and its diploidization, they have the potential to facilitate the origin of new functional variations, which, upon selection in the evolutionary lineage, may play an important role in the origin of novel traits.


Assuntos
Evolução Molecular , Genoma de Planta , Sintenia , Triticum/genética , Processamento Alternativo , Brachypodium/genética , Cromossomos de Plantas/genética , Códon sem Sentido/genética , DNA de Plantas/genética , Bases de Dados Genéticas , Éxons , Mutação da Fase de Leitura , Perfilação da Expressão Gênica , Ordem dos Genes , Íntrons , Taxa de Mutação , Fases de Leitura Aberta , Poliploidia , Pseudogenes , Seleção Genética
14.
J Pharm Bioallied Sci ; 16(Suppl 1): S993-S995, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38595632

RESUMO

Traumatic dental injuries (TDIs) have significant long-term consequences for the oral cavity's hard and soft tissues. Alveolar process fractures are particularly complicated. This case report describes the management and 12-month follow-up of a segmental maxillary alveolar process fracture involving laterally luxated primary incisors. A case of a 4-year-old boy was reported to the hospital 1 hour after an accidental fall at school, which resulted in a fracture of the maxillary alveolar process. Emergency treatment consisted of fracture reduction and repositioning of the primary incisors, followed by a semirigid splint between maxillary canines. The splints were removed at the end of week 4, and the affected primary incisors remained asymptomatic.

15.
PLoS One ; 19(1): e0292100, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38236900

RESUMO

Diabetes prediction is an ongoing study topic in which medical specialists are attempting to forecast the condition with greater precision. Diabetes typically stays lethargic, and on the off chance that patients are determined to have another illness, like harm to the kidney vessels, issues with the retina of the eye, or a heart issue, it can cause metabolic problems and various complexities in the body. Various worldwide learning procedures, including casting a ballot, supporting, and sacking, have been applied in this review. The Engineered Minority Oversampling Procedure (Destroyed), along with the K-overlay cross-approval approach, was utilized to achieve class evening out and approve the discoveries. Pima Indian Diabetes (PID) dataset is accumulated from the UCI Machine Learning (UCI ML) store for this review, and this dataset was picked. A highlighted engineering technique was used to calculate the influence of lifestyle factors. A two-phase classification model has been developed to predict insulin resistance using the Sequential Minimal Optimisation (SMO) and SMOTE approaches together. The SMOTE technique is used to preprocess data in the model's first phase, while SMO classes are used in the second phase. All other categorization techniques were outperformed by bagging decision trees in terms of Misclassification Error rate, Accuracy, Specificity, Precision, Recall, F1 measures, and ROC curve. The model was created using a combined SMOTE and SMO strategy, which achieved 99.07% correction with 0.1 ms of runtime. The suggested system's result is to enhance the classifier's performance in spotting illness early.


Assuntos
Algoritmos , Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/diagnóstico , Aprendizado de Máquina , Curva ROC , Previsões
16.
J Pharm Bioallied Sci ; 16(Suppl 1): S987-S989, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38595372

RESUMO

The most frequent cystic lesions that affect the jaw are radicular cysts. The current case report describes the surgical management of a radicular cyst in the periapical region of maxillary central and lateral incisors, and highlights the efficacy of natural platelet concentrate [platelet-rich fibrin (PRF)] along with Ostoden bone graft material used for postoperative healing. A 46-year-old male patient presented to the department with swelling in the palatal aspect of the maxillary anterior region. On radiographic examination, a radiolucent periapical lesion was evident in relation to the left maxillary central and lateral incisor. In the maxillary anterior region, root canal therapy was performed, followed by periapical surgery, and PRF with Ostoden bone graft was placed in the surgical site to initiate the healing at a faster rate. The patient was recalled at follow-ups after 7 days, 3, 6, and 9 months. No symptoms such as pain, inflammation, or discomfort were observed during the review period.

17.
Heliyon ; 10(8): e29429, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38628770

RESUMO

Polyelectrolyte complexes (PECs) formed by the interaction between oppositely charged polymers have emerged as promising carriers for accomplishing colon-specific release. In this study, we have explored the potential of polyelectrolyte complexes between a succinate derivative of Leucaena leucocephala galactomannan and cationic guar gum for colon delivery of synbiotic. The PECs were prepared using a polyelectrolyte complexation method and characterized. The PECs exhibited excellent stability, with high encapsulation efficiency for both probiotics (95.53 %) and prebiotics (83.33 %). In vitro studies demonstrated enhanced survivability and proliferation of the encapsulated probiotics in the presence of prebiotics (93.29 %). The SEM images revealed a smooth and firm structure with reduced number of pores when both prebiotic and probiotic were encapsulated together. The treatment with synbiotic PECs in acetic acid induced IBD rats significantly relieves colitis symptoms as was evident from colon/body ratio, DAI score and histopathology studies. An increase in the protein and reduced glutathione levels and reduction in superoxide dismutase activity was observed in colitic rats that received synbiotic treatment as compared to colitic rats. Overall, this study highlights the potential of Leucaena leucocephala succinate-cationic guar gum PECs as a promising system for colon-specific synbiotic delivery, with implications for improved gut health and the treatment of various gastrointestinal disorders.

18.
Chem Commun (Camb) ; 59(20): 2842-2853, 2023 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-36753294

RESUMO

Solvents are the major source of chemical waste from synthetic chemistry labs. Growing attention to more environmentally friendly sustainable processes demands novel technologies to substitute toxic or hazardous solvents. If not always, sometimes, water can be a suitable substitute for organic solvents, if used appropriately. However, the sole use of water as a solvent remains non-practical due to its incompatibility with organic reagents. Nonetheless, over the past few years, new additives have been disclosed to achieve chemistry in water that also include aqueous micelles as nanoreactors. Although one cannot claim micellar catalysis to be a greener technology for every single transformation, it remains the sustainable or greener alternative for many reactions. Literature precedents support that micellar technology has much more potential than just as a reaction medium, i.e., the role of the amphiphile as a ligand obviating phosphine ligands in catalysis, the shielding effect of micelles to protect water-sensitive reaction intermediates in catalysis, and the compartmentalization effect. While compiling the powerful impact of micellar catalysis, this article highlights two diverse recent technologies: (i) the design and employment of the surfactant PS-750-M in selective catalysis; (ii) the use of the semisynthetic HPMC polymer to enable ultrafast reactions in water.

19.
J Pharm Bioallied Sci ; 15(Suppl 1): S224-S229, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37654345

RESUMO

Introduction: The palatal rugae may alter their shape based on the various physical pressures that they had to endure. This study's objective is to assess the various alterations in the palatal rugae parameters among the complete denture wearers. Materials and Procedures: Forty subjects in all were chosen for the study. The control group interventional groups had an equal number of participants who were further equally distributed based on gender. For all of the participants, mucostatic maxillary alginate imprints were taken, and gypsum castings were created. They were called at the scheduled intervals of 2, 6, and 12 months following the treatment. The models used during those recalls and all of the palatal rugae were examined under a microscope for quantity, length, form, orientation, and unifications. The unpaired t-test was used to statistically examine palatal rugae alterations. Results: Following the wear of the dentures, the experimental group's primary, secondary, and fragmented rugae all gradually shrank in length. In terms of statistics, the alteration solely affected primary rugae and was significant (P < 0.001). After a year of wearing dentures, a minimal change in rugae's form was noticed in the denture groups, but it was statistically not substantial (P > 0.05). Conclusion: Due to the prolonged mechanical stress the dentures placed on the palatal rugae, complete denture users saw a significant reduction in the length of their primary rugae. Rugae number, orientation, and unification were among the other criteria that did not change during the course of the study. Analysis of the palatal rugae may not be useful in identifying people wearing full dentures. However, in forensic investigations, rugae may act as an adjunct to other methods like fingerprints and DNA analysis.

20.
ACS Appl Mater Interfaces ; 14(45): 50947-50955, 2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36341774

RESUMO

A novel strategy has been developed to spontaneously form ligand-free Pd(0) nanoparticles (NPs) from water- and air-sensitive Pd2dba3 in water. These NPs are thoroughly characterized by IR, NMR, and mass spectrometry, revealing that the metal-micelle binding plays a critical role in their stability and activity. High-resolution transmission electron microscopy supported the ultrasmall nature of NPs, whereas X-ray photoelectron spectroscopy analysis confirmed the zero-oxidation state of Pd. The shielding effect of micelles and enhanced stability of NPs enabled fast cross-couplings of water-sensitive triazine adducts of carboxylic acid to form nonsymmetrical biaryl ketones. These naturally formed NPs are more efficient than new synthetic NPs formed under a hydrogen atmosphere and traditional NPs formed using the air-sensitive Grignard reagent as a reductant. The activity of naturally formed NPs is compared with that of synthetic NPs over 34 substrates, revealing that naturally formed NPs are much more efficient than synthetic NPs.

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