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1.
ACS Appl Bio Mater ; 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38581392

RESUMO

Carbon dots (CDs) have recently emerged in biomedical and agricultural domains, mainly for their probe applications in developing efficient sensors. However, the existing high-temperature approaches limit the industrial level scaling up to further translate them into different products by mass-scale fabrication of CDs. To address this, we have attempted to lower the synthesis temperature to 140 °C and synthesized different CDs using different organic acids and their combinations in a one-step approach (quantum yield 3.6% to 16.5%; average size 3 to 5 nm). Further, sensing applications of CDs have been explored in three different biological models, mainly Danio rerio (zebrafish) embryos, bacterial strains, and the Lactuca sativa (lettuce) plant. The 72 h exposure of D. rerio embryos to 0.5 and 1 mg/mL concentrations of CDs exhibited significant uptake without mortality, a 100% hatching rate, and nonsignificant alterations in heart rate. Bacterial bioimaging experiments revealed CD compatibility with Gram-positive (Bacillus subtilis) and Gram-negative (Serratia marcescens) strains without bactericidal effects. Furthermore, CDs demonstrated effective conduction and fluorescence within the vascular system of lettuce plants, indicating their potential as in vivo probes for plant tissues. The single-step low-temperature CD synthesis approach with efficient structural and optical properties enables the process as industrially viable to up-scale the technology readiness level. The bioimaging of CDs in different biological models indicates the possibility of developing a CD probe for diverse biosensing roles in diseases, metabolism, microbial contamination sensing, and more.

2.
Int J Biol Macromol ; 263(Pt 2): 130372, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38395275

RESUMO

The present study reports the synthesis of micellar conjugates, wherein curcumin (Cur), a bioactive compound with poor bioavailability, was covalently bonded to a bacterial exopolysaccharide (EPS). These conjugates were synthesized by utilizing succinic acid that linked Cur to the pyranosyl moiety of the EPS. The Cur-EPS conjugates appeared as spherical micelles in aqueous solution and were found to have an average hydrodynamic diameter of 254 ± 2.7 nm. The micellar conjugates showed superior stability than Cur as evident from their negative surface charge (-27 ± 1.8 mV) and low polydispersity index (PDI) (0.33 ± 0.04). The in vitro studies on release kinetics helped elucidate the pH-responsive characteristics of the Cur-EPS conjugate, as 87.50 ± 1.45 % of Cur was released at an acidic pH of 5.6, in contrast to 30.15 ± 2.61 % at systemic pH of 7.4 at 150 h. The conjugates were hemocompatible and exhibited cytotoxic effect against the osteosarcoma cell line (MG-63) after 48 h treatment. They also demonstrated superior antibacterial, antibiofilm, and antioxidant activities in comparison to free Cur. Therefore, the Cur-EPS conjugates have potential pharmaceutical applications as therapeutic biomaterial that can be applied as a drug delivery system.


Assuntos
Antineoplásicos , Neoplasias Ósseas , Curcumina , Humanos , Curcumina/química , Micelas , Antineoplásicos/química , Sistemas de Liberação de Medicamentos , Neoplasias Ósseas/tratamento farmacológico , Concentração de Íons de Hidrogênio , Portadores de Fármacos/química
3.
ACS Appl Mater Interfaces ; 16(8): 10601-10622, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38376231

RESUMO

Stainless steel (316L SS) has been widely used in orthopedic, cardiovascular stents, and other biomedical implant applications due to its strength, corrosion resistance, and biocompatibility. To address the weak interaction between steel implants and tissues, it is a widely adopted strategy to enhance implant performance through the application of bioactive coatings. In this study, Cu-doped brushite coatings were deposited successfully through pulse electrodeposition on steel substrates facilitated with a biosurfactant (BS) (i.e., surfactin). Further, the combined effect of various concentrations of Cu ions and BS on the structural, electrochemical, and biological properties was studied. The X-ray diffraction (XRD) confirms brushite composition with Cu substitution causing lattice contraction and a reduced crystallite size. The scanning electron microscopy (SEM) and energy-dispersive spectroscopy (EDS) studies reveal the morphological changes of the coatings with the incorporation of Cu, which is confirmed by X-ray photoelectron spectroscopy (XPS) and elemental mapping. The Fourier transform infrared (FTIR) and Raman spectroscopy confirm the brushite and Cu doping in the coatings, respectively. Increased surface roughness and mechanical properties of Cu-doped coatings were analyzed by using atomic force microscopic (AFM) and nanohardness tests, respectively. Electrochemical assessments demonstrate corrosion resistance enhancement in Cu-doped coatings, which is further improved with the addition of biosurfactants. In vitro biomineralization studies show the Cu-doped coating's potential for osseointegration, with added stability. The cytocompatibility of the coatings was analyzed using live/dead and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assays; cell adhesion, proliferation, and migration studies were evaluated using SEM. Antibacterial assays highlight significant improvement in the antibacterial properties of Cu-doped coatings with BS. Thus, the developed Cu-doped brushite coatings with BS demonstrate their potential in the realm of biomedical implant technologies, paving the way for further exploration.


Assuntos
Fosfatos de Cálcio , Aço Inoxidável , Fosfatos de Cálcio/química , Aço Inoxidável/química , Antibacterianos/química , Corrosão , Stents , Materiais Revestidos Biocompatíveis/farmacologia , Materiais Revestidos Biocompatíveis/química
4.
Biomed Mater ; 19(2)2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38194702

RESUMO

The quest for an ideal wound dressing material has been a strong motivation for researchers to explore novel biomaterials for this purpose. Such explorations have led to the extensive use of silk fibroin (SF) as a suitable polymer for several applications over the years. Unfortunately, another major silk protein-sericin has not received its due attention yet in spite of having favorable biological properties. In this study, we report an approach of blending SF and silk sericin (SS) without the usage of chemical crosslinkers is made possible by the usage of formic acid which evaporates to induceß-sheets formation to form cytocompatible films. Raman spectroscopy confirms the presence of SF/SS components in blend and formation ofß-sheet in films.In situ, gelation kinetics studies were conducted to understand the change in gelation properties with addition of sericin into SF. Methyl thiazolyl tetrazolium and live/dead assays were performed to study cellular attachment, viability and proliferation on SF/SS films. The antibacterial properties of SF/SS films were tested using Gram-negative and Gram-positive bacteria. The re-structured SF/SS films were stable, transparent, show good mechanical properties, antibacterial activity and cytocompatibility, therefore can serve as suitable biomaterial candidates for skin regeneration applications.


Assuntos
Fibroínas , Sericinas , Sericinas/química , Fibroínas/química , Engenharia Tecidual , Materiais Biocompatíveis/química , Antibacterianos
5.
Med Oncol ; 41(1): 36, 2023 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-38153604

RESUMO

The exact molecular mechanism underlying the heterogeneous drug response against breast carcinoma remains to be fully understood. It is urgently required to identify key genes that are intricately associated with varied clinical response of standard anti-cancer drugs, clinically used to treat breast cancer patients. In the present study, the utility of transcriptomic data of breast cancer patients in discerning the clinical drug response using machine learning-based approaches were evaluated. Here, a computational framework has been developed which can be used to identify key genes that can be linked with clinical drug response and progression of cancer, offering an immense opportunity to predict potential prognostic biomarkers and therapeutic targets. The framework concerned utilizes DeSeq2, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Cytoscape, and machine learning techniques to find these crucial genes. Total RNA extraction and qRT-PCR were performed to quantify relative expression of few hub genes selected from the networks. In our study, we have experimentally checked the expression of few key hub genes like APOA2, DLX5, APOC3, CAMK2B, and PAK6 that were predicted to play an immense role in breast cancer tumorigenesis and progression in response to anti-cancer drug Paclitaxel. However, further experimental validations will be required to get mechanistic insights of these genes in regulating the drug response and cancer progression which will likely to play pivotal role in cancer treatment and precision oncology.


Assuntos
Neoplasias da Mama , Medicina de Precisão , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Paclitaxel , Carcinogênese , Transformação Celular Neoplásica
6.
Tissue Eng Part C Methods ; 29(6): 242-256, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37171125

RESUMO

Wound healing (WH) is a complex and dynamic process that comprises of a series of molecular and cellular events that occur after tissue injury. The injuries of the maxillofacial and oral region caused by trauma or surgery result in undesirable WH such as delayed wound closure and formation of scar tissue. Skin tissue engineering (TE)/regeneration is an emerging approach toward faster, superior, and more effective resolution of clinically significant wounds effectively. A multitude of TE principles approaches are being put to action for the fabrication of hydrogels, electrospun sheets, 3D scaffolds, and thin films that can be used as wound dressings materials, sutures, or skin substitutes. Thin films are advantageous over other materials owing to their flexibility, ability to provide a barrier against external contamination, easy gaseous exchange, and easy monitoring of wounds. This review focuses on wound-dressing films and their significance and discusses various fabrication techniques. In addition, we explore various natural biopolymers that can be used for fabrication of skin TE materials. Impact Statement In this review article, critical evaluations of natural polymers used in skin regeneration were discussed. Further, the fabrication technology of the 2D and 3D material in wound healing were discussed.


Assuntos
Polímeros , Regeneração , Pele , Cicatrização , Odontologia
7.
Life Sci ; 321: 121620, 2023 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-37011534

RESUMO

AIMS: Natural Killer T (NKT) cells are reported to be both pro- and anti-atherosclerotic. With this meta-analysis, we evaluated the NKT population and their subsets in regulating the atherosclerotic disease in mice. MAIN METHODS: Eighteen pre-clinical (mice, n = 1276) and 6 clinical observational studies (humans, n = 116) met the eligibility criteria for inclusion. Random effects model was used and standard mean difference (SMD) was calculated for the cell counts and aortic lesion area. KEY FINDINGS: Lesion area decreased in the absence of whole NKT cell population (-1.33[95%CI, -2.14, -0.52]), and in the absence of only iNKT subset (-0.66[95%CI, -1.69, 0.37]). However, lesion area increased after over-expression/activation of iNKTs (1.40[95%CI, 0.28, 2.52]). Atherogenic diet (AD) or high fat diet (HFD) increased the number of NKT cells (2.51[95%CI, 1.42, 3.61]), whereas the iNKT cell numbers and iNKT cell-specific gene expression decreased in mice (-2.04[95%CI, -3.34, -0.75]) and atherosclerotic patients (-1.81[95 % CI, -2.89, -0.74]). SIGNIFICANCE: Here we show that, NKT and iNKT cells promote atherosclerosis. In general, NKT cell population increases with the progression of the plaque in mice and the numbers of iNKT cells reduce once the disease is established both in mice and humans.


Assuntos
Aterosclerose , Células T Matadoras Naturais , Humanos , Camundongos , Animais , Células T Matadoras Naturais/metabolismo , Células T Matadoras Naturais/patologia , Camundongos Knockout , Aterosclerose/metabolismo , Camundongos Endogâmicos C57BL
8.
HLA ; 102(1): 66-68, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36811603

RESUMO

HLA-A*02:01:01:241 differs from HLA-A*02:01:01:01 by a single nucleotide substitution at position 178 in intron 1.


Assuntos
Genômica , Antígenos HLA-A , Humanos , Alelos , Análise de Sequência de DNA , Antígenos HLA-A/genética , Sequenciamento de Nucleotídeos em Larga Escala
9.
Comput Methods Programs Biomed ; 229: 107251, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36473420

RESUMO

BACKGROUND: Anemia during pregnancy can complicate maternal and neonatal health and even lead to fatal consequences if not diagnosed early on. Around 99% of women who face maternal mortality are from middle or low-income countries. Early screening of anemia could facilitate improved health outcomes in pregnant women. Point of care techniques are preferred due to their ability to provide results rapidly and because they can be used by personnel with minimal or no training. Such techniques are especially useful in resource-constrained settings like rural parts of developing countries. OBJECTIVES: The aim of the study was to develop a tool using an Artificial Neural Network (ANN) to estimate hemoglobin values using color information recorded from blood sample images. Our method utilizes inexpensive consumables and a simple image acquisition setup that can be assembled easily. METHODS: This study explores a neural network model to estimate the hemoglobin content in an individual's blood sample. Blood samples were collected from 86 volunteers and the images of blood drops were obtained using an image acquisition setup designed by the team. The color intensity values calculated from the blood drop images were used as feature descriptors for the samples. The features obtained from our samples were consequently fed to the Artificial Neural Network. RESULTS: Our neural network that gives the best result has the architecture of 11 neurons in each of the 5 layers. The best model gave estimated hemoglobin levels by analyzing color of blood samples with an accuracy of ±1.8 g/dl Limits of agreement (LOA) and bias 0.03 g/dl (with mean error of 0.75 g/dl). The model was subsequently tested with a validation set prepared from an additional 65 samples. The estimated hemoglobin levels gave an accuracy of +2 g/dl to -1.9 g/dl Limits of agreement (LOA) and bias 0.06 g/dl (with mean error of 0.78 g/dl). CONCLUSION: Optimization of sensitivity and specificity has been able to achieve the sensitivity and specificity values as 95.5% and 52% respectively. These results are at par with the contemporary measurement techniques indicating that our method can be used as a workable screening technique itself.


Assuntos
Anemia , Recém-Nascido , Humanos , Feminino , Gravidez , Anemia/diagnóstico por imagem , Hemoglobinas/análise , Sensibilidade e Especificidade , Programas de Rastreamento
10.
Heliyon ; 8(8): e10435, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36090222

RESUMO

Background: Proinflammatory cytokine cascades play crucial roles in the onset and progression of myocardial ischemia and infarction. Clinically, elevated serum levels of pro-inflammatory cytokine interleukin-6 is a poor prognostic indicator for future cardiac events and cardiac morbidity. Despite several reports, there is no clear evidence of cardiac benefits of inhibiting IL-6 in pre-clinical and clinical settings. Objective: To analyze the available data systematically and perform a meta-analysis to show the evidence of effects of IL-6 inhibition on cardiac remodeling and mortality in ischemic animal models. Methods: We used PICO framework and the quality of the studies was assessed using SYRCLE's risk of bias tool. Studies with interventions i.e., genetic deletion or pharmacological inhibition of IL-6/IL-6R were included for the meta-analysis. Systematic review was synthesized by including pre-clinical as well as randomized clinical trials involving myocardial infarction patients treated with IL-6 inhibitors. The effect size of the pooled data was determined using standard mean difference and 95% confidence intervals. Results: A total of 12 pre-clinical studies were included in the review for analysis. Most of the studies showed an unclear risk of bias as the selection and reporting criteria were poorly described. We observed high heterogeneity in the included studies due to the varying duration of myocardial infarction and the dosage of IL-6 antibodies used in the studies. Overall inhibition of IL-6 significantly increased area at risk [p = 0.001, SMD = 0.49 (95% CI: -0.36, 1.35)] and significantly reduced ejection fraction [p = 0.001, SMD = -0.19 (95% CI: -1.39, 1.01)] and end-diastolic diameter [p = 0.02, SMD = -0.25 (95% CI: -0.87, 0.36)] of left ventricle post-MI, but no effects on infarct size [p < 0.01, SMD = 0.00; 95% CI: -1.34, 0.58). In randomized clinical trials, the overall effect on C-reactive protein remains significantly unchanged on CRP levels (SMD = -0.38; 95% CI: -1.94, 0.55) post-treatment with IL-6R inhibitor tocilizumab. The meta-regression demonstrates a significant positive correlation (p = 0.058) between the increase in ischemic area and duration of ischemia post-surgery in the absence of IL-6. This meta-analysis indicates mixed effect of IL-6 inhibition on cardiac remodeling post-MI, particularly in protecting the myocardium viability from damaging acute inflammation but not significant on cardiac function of ischemic animal models. Conclusion: Despite the well-established pro-inflammatory nature of IL-6 in myocardial ischemia, our meta-analysis reports a limited contribution of IL-6 in the cardiac remodeling of hearts in animal models of myocardial ischemia. Moreover, genetically deleted IL-6 murine models produced contrasting results. Additional pre-clinical studies exploring the pharmacological inhibition of IL-6R are required to determine the beneficial effects of IL-6 inhibitors in regulating cardiac remodeling. The findings from IL-6R inhibition have better clinical relevance compared to genetically inhibited IL-6.

11.
Mol Biol Rep ; 49(7): 7057-7068, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35717472

RESUMO

ß-thalassemia is a prevalent monogenic disorder characterized by reduced or absent synthesis of the ß-globin chain. Although great effort has been made to ameliorate the disease severity of ß-thalassemic patients, progress has been stymied due to limited understanding of the detailed molecular mechanism of disease pathogenesis. Recently, non-coding RNAs have been established as key players in regulating various physiological and pathological processes. Many ncRNAs are involved in hematopoiesis and erythroid development. Furthermore, various studies have also reported the complex interplay between different ncRNAs, such as miRNA, lncRNAs, etc. in regulating disease progression and pathogenesis. Both lncRNAs and miRNAs have been identified as independent regulators of globin gene expression and are intricately involved in disease pathogenesis; yet accumulating evidence suggests that the cross-talk between lncRNAs and miRNAs is intricately involved in the underlying globin gene expression, fine-tuning the effect of their independent regulation. In this review, we summarize the current progress of research on the roles of lncRNAs and miRNAs implicated in ß-thalassemia disease, including their interactions and regulatory networks. This can provide important insights into the detailed epigenetic regulation of globin gene switching and has the potential to develop novel therapeutic approaches against ß-thalassemia.


Assuntos
MicroRNAs , RNA Longo não Codificante , Talassemia beta , Biomarcadores , Epigênese Genética , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes/genética , Globinas/genética , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Prognóstico , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Talassemia beta/genética , Talassemia beta/terapia
12.
Mol Biol Rep ; 49(7): 6971-6973, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35467178

RESUMO

Non-coding RNAs (ncRNAs) like miRNAs, siRNA, lncRNAs, circRNAs, piRNAs, snoRNAs, snRNAs etc. form a collective group of RNAs that is instrumental to the various functions of the genome. With the advent of cutting-edge molecular biology tools and techniques, scientists have unearthed several mechanisms through which these ncRNAs act. Although our understanding may still be limited, yet scientists have been able to establish ncRNAs as major regulators of genetic inter-plays that dictate various pathophysiological conditions. This special issue of Molecular Biology Reports features a collection of research and review articles on ncRNAs and their involvement in different pathophysiological conditions that include different types of cancers. It is expected that this special issue will motivate researchers in the field to delve deeper into the world of ncRNAs and attempt to develop new diagnostic and therapeutic interventions for challenging clinical conditions.


Assuntos
MicroRNAs , RNA Longo não Codificante , MicroRNAs/genética , RNA Circular/genética , RNA Longo não Codificante/genética , RNA Interferente Pequeno , RNA Nucleolar Pequeno , RNA não Traduzido/genética
13.
Hum Vaccin Immunother ; 18(2): 2006026, 2022 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-34886756

RESUMO

Convalescent plasma therapy provides a useful therapeutic tool to treat infectious diseases, especially where no specific therapeutic strategies have been identified. The ongoing pandemic puts back the spotlight on this age-old method as a viable treatment option. In this review, we discuss the usage of this therapy in different diseases including COVID-19, and the possible mechanisms of action. The current review also discusses the progress of therapeutic applications of blood-derivatives, from the simple transfer of immunized animal sera, to the more target-specific intravenous administration of human immunoglobulins from a pool of convalescent individuals, in both infectious and non-infectious diseases of various etiologies.


Assuntos
COVID-19 , SARS-CoV-2 , Animais , Anticorpos Neutralizantes/uso terapêutico , Anticorpos Antivirais , COVID-19/terapia , Imunização Passiva , Pandemias/prevenção & controle , Soroterapia para COVID-19
14.
Mol Biol Rep ; 49(3): 2359-2373, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34822068

RESUMO

Beta-hemoglobinopathies exhibit a heterogeneous clinical picture with varying degrees of clinical severity. Pertaining to the limited treatment options available, where blood transfusion still remains the commonest mode of treatment, pharmacological induction of fetal hemoglobin (HbF) has been a lucrative therapeutic intervention. Till now more than 70 different HbF inducers have been identified. The practical usage of many pharmacological drugs has been limited due to safety concerns. Natural compounds, like Resveratrol, Ripamycin and Bergaptene, with limited cytotoxicity and high efficacy have started capturing the attention of researchers. In this review, we have summarized pharmacological drugs and bioactive compounds isolated from natural sources that have been shown to increase HbF significantly. It primarily discusses recently identified synthetic and natural compounds, their mechanism of action, and their suitable screening platforms, including high throughput drug screening technology and biosensors. It also delves into the topic of combinatorial therapy and drug repurposing for HbF induction. Overall, we aim to provide insights into where we stand in HbF induction strategies for treating ß-hemoglobinopathies.


Assuntos
Produtos Biológicos , Hemoglobinopatias , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Hemoglobina Fetal , Hemoglobinopatias/tratamento farmacológico , Humanos
15.
Front Nutr ; 8: 747956, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34621776

RESUMO

An entirely unknown species of coronavirus (COVID-19) outbreak occurred in December 2019. COVID-19 has already affected more than 180 million people causing ~3.91 million deaths globally till the end of June 2021. During this emergency, the food nutraceuticals can be a potential therapeutic candidate. Curcumin is the natural and safe bioactive compound of the turmeric (Curcuma longa L.) plant and is known to possess potent anti-microbial and immuno-modulatory properties. This review paper covers the various extraction and quantification techniques of curcumin and its usage to produce functional food. The potential of curcumin in boosting the immune system has also been explored. The review will help develop insight and new knowledge about curcumin's role as an immune-booster and therapeutic agent against COVID-19. The manuscript will also encourage and assist the scientists and researchers who have an association with drug development, pharmacology, functional foods, and nutraceuticals to develop curcumin-based formulations.

16.
Comput Biol Med ; 136: 104669, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34320442

RESUMO

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is a highly transmissible virus causing the ongoing global pandemic, COVID-19. Evidence suggests that viral and host microRNAs play pivotal roles in progression of such infections. The decisive impact of viral miRNAs and their putative targets in modulating the transcriptomic profile of its host, however remains unexplored. We hypothesized that the SARS-CoV-2 derived miRNAs can potentially play a contributory role in its pathogenicity and aid in its survival. A series of computational tools predicted 34 SARS-CoV-2 encoded miRNAs and their putative targets in the host. Immune and apoptotic pathways were identified as most enriched pathways. Further investigation using a dataset of SARS-CoV-2 infected cells (available from public repository- GSE150392) revealed that 46 genes related to immune and apoptosis-related functions were deregulated. Of these 46 genes, 42 genes were identified to be significantly up-regulated and 4 genes were down-regulated. In silico analysis revealed all of the these significantly down-regulated genes to be putative targets of 9 out of 34 of our predicted viral miRNAs. Overall, 123 out of 324 genes that are differentially regulated in SARS-CoV2 infected cells, and also identified as putative targets of viral miRNAs, were found to be significantly down-regulated. KEGG pathway analysis using these genes revealed p53 signaling as the most enriched pathway - a pathway that is known to influence immune responses. This study thus provides the theoretical foundation for the underlying molecular mechanisms involved in progression of viral pathogenesis.


Assuntos
COVID-19 , MicroRNAs , Biologia Computacional , Humanos , MicroRNAs/genética , RNA Viral , SARS-CoV-2
17.
Blood Cells Mol Dis ; 87: 102523, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33242839

RESUMO

Hemoglobin E (HbE)/ß-thalassemia is a form of ß-hemoglobinopathy that is well-known for its clinical heterogeneity. Individuals suffering from this condition are often found to exhibit increased fetal hemoglobin (HbF) levels - a factor that may contribute to their reduced blood transfusion requirements. This study hypothesized that the high HbF levels in HbE/ß-thalassemia individuals may be guided by microRNAs and explored their involvement in the disease pathophysiology. The miRNA expression profile of hematopoietic progenitor cells in HbE/ß-thalassemia patients was investigated and compared with that of healthy controls. Using miRNA PCR array experiments, eight miRNAs (hsa-miR-146a-5p, hsa-miR-146b-5p, hsa-miR-148b-3p, hsa-miR-155-5p, hsa-miR-192-5p, hsa-miR-335-5p, hsa-miR-7-5p, hsa-miR-98-5p) were identified to be significantly up-regulated whereas four miRNAs (hsa-let-7a-5p, hsa-miR-320a, hsa-let-7b-5p, hsa-miR-92a-3p) were significantly down-regulated. Target analysis found them to be associated with several biological processes and molecular functions including MAPK and HIF-1 signaling pathways - the pathways known to be associated with HbF upregulation. Results of dysregulated miRNAs further indicated that miR-17/92 cluster might be of critical importance in HbF regulation. The findings of our study thus identify key miRNAs that can be extrinsically manipulated to elevate HbF levels in ß-hemoglobinopathies.


Assuntos
Hemoglobina E/genética , MicroRNAs/genética , Talassemia beta/genética , Células Cultivadas , Regulação para Baixo , Hemoglobina Fetal/genética , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Transcriptoma , Regulação para Cima
18.
Biomed Mater ; 15(6): 064102, 2020 11 21.
Artigo em Inglês | MEDLINE | ID: mdl-33226007

RESUMO

Hydrophobic drug molecules pose a significant challenge in immobilization on super-hydrophobic metallic surfaces like conventional titanium implants. Pre-coating surface modifications may yield a better platform with improved wettability for such purposes. Such modifications, as depicted in this study, were hypothesized to provide the requisite roughness to assist deposition of polymers like silk fibroin (SF) as a drug-binding matrix in addition to significant improvement in early protein adsorption, which facilitates faster cellular adhesion and proliferation. A silk-based localized drug delivery module was developed on the titanium surface and tested for its surface roughness, wettability, biocompatibility and in vitro differentiation potential of cells cultured on the coated metallic surfaces with/without external supplementation of the active metabolite of Tibolone. Conditioning of the matrix-coated implants with osteogenic as well as osteoclastogenic media supplemented with Tibolone stimulated the expression of early osteogenic gene and calcium deposition in the extracellular matrix. Significant inhibition in resorptive activity was also observed in the presence of the drug. To assess the efficacy of localized delivery of Tibolone via topographically modified titanium implants for inducing early peri-implant bone formation, osteoporosis was artificially induced in rats subjected to bilateral ovariectomy and implants were placed thereafter. Bone-specific release of Tibolone through the biomimetic matrix in osteoporotic rats collectively indicated significant improvement in peri-implant bone growth after 2 and 4 weeks (p < 0.05 compared to dummy-coated implants). These findings demonstrate for the first time that Tibolone released from SF matrix-coated implants can accelerate the biological stability of bone fixtures.


Assuntos
Osso e Ossos/metabolismo , Norpregnenos/farmacologia , Osteoblastos/metabolismo , Osteogênese , Osteoporose/metabolismo , Fosfatase Alcalina/metabolismo , Animais , Regeneração Óssea , Reabsorção Óssea , Linhagem Celular Tumoral , Sobrevivência Celular , Curcumina/química , Sistemas de Liberação de Medicamentos , Feminino , Humanos , Técnicas In Vitro , Metais , Camundongos , Ovariectomia , Próteses e Implantes , Células RAW 264.7 , Ratos , Ratos Wistar , Propriedades de Superfície , Titânio/química
19.
Int J Biol Macromol ; 165(Pt A): 874-882, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-33011257

RESUMO

Combination of naturally occurring materials instead of chemically synthesized products has always been an attractive proposition in the field of tissue engineering. In this study, silk fibroin (SF) and xanthan gum(XG) were physically crosslinked to form biocompatible hydrogels. SF/XG hydrogels were prepared using ultrasonication, which induces ß-sheets from random coils in SF solution and allows entrapment of heated XG chains homogeneously in the SF network. It is a novel way of blending SF and XG polymers which avoids the usage of chemical crosslinkers. SF/XG blended solutions were used at different ratios for the hydrogel formation. Scanning electron microscopy (SEM) and micro-computed tomography (MCT) were used for morphological analysis of the interconnected network and porosity of the scaffolds, respectively. Rheological studies were performed to understand the changes in mechanical properties due to the incorporation of XG into SF hydrogels. Fourier transform infrared spectroscopy (FTIR) confirmed the presence of SF and XG moieties in the blend scaffolds. Additionally, thermal Analysis (TGA & DSC) established the homogenous mixture and presence of XG in the SF network without any phase separation. Furthermore, the MTT assay demonstrates the cytocompatibility of scaffolds using L929 fibroblast cells. Thus, fabricated SF/XG scaffolds could mimic natural cartilage ECM by exhibiting enhanced water swelling capacity and suitable porosity along with its cytocompatible studies, indicating its potential application in soft tissue engineering.


Assuntos
Materiais Biomiméticos , Fibroblastos/metabolismo , Fibroínas , Hidrogéis , Teste de Materiais , Polissacarídeos Bacterianos , Regeneração/efeitos dos fármacos , Animais , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Linhagem Celular , Fibroínas/química , Fibroínas/farmacologia , Hidrogéis/química , Hidrogéis/farmacologia , Camundongos , Polissacarídeos Bacterianos/química , Polissacarídeos Bacterianos/farmacologia
20.
Comput Methods Programs Biomed ; 195: 105669, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32763771

RESUMO

BACKGROUND AND OBJECTIVE: In this study, we have analysed pretreatment positron-emission tomography/ computed tomography (PET/CT) images of head and neck squamous cell carcinoma (HNSCC) patients. We have used a publicly available dataset for our analysis. The clinical features of the patient, PET quantitative parameters, and textural indices from pretreatment PET-CT images are selected for the study. The main objective of the study is to use classifiers to predict the outcome for HNSCC patients and compare the performance of the model with the conventional statistical model (CoxPH). METHODS: We have applied a 40% fixed SUV threshold method for tumour delineation. Clinical features of each patient are provided in the dataset, and other features are calculated using LIFEx software. For predicting the outcome, we have implemented three classifiers - Random Forest classifier, Gradient Boosted Decision tree (GBDT) and Decision tree classifier. We have trained each model using 93 data points and test the model performance using 39 data points. The best model - GBDT is chosen based on the performance metrics. RESULTS: It is observed that typically three features: MTV (Metabolic tumour Volume), primary tumour site and GLCM_correlation are significant for prediction of survival outcome. For testing cohort, GBDT achieves a balanced accuracy of 88%, where conventional statistical model reported a balanced accuracy of 81.5%. CONCLUSIONS: The proposed classifier achieves higher accuracy than the state of the art technique. Using this classifier we can estimate the HNSCC patient's outcome, and depending upon the outcome treatment policy can be selected.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Carcinoma de Células Escamosas/diagnóstico por imagem , Fluordesoxiglucose F18 , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico por imagem
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