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1.
Heliyon ; 10(7): e28492, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38571665

RESUMO

Introduction: miRNAs originating from colorectal cancer (CRC) tissue receive significant focus in the early diagnosis of CRC due to their stability in body fluids. However, if these miRNAs originated from alternative organs, their prognostic value will diminish. Thus, in this study, we aim to identify disease-specific miRNAs for colorectal cancer (CRC) by employing bioinformatics and experimental methodologies. Method: To identify CRC-specific miRNAs, we retrieved miRNA profiles of CRC and normal tissues from the Cancer Genome Atlas (TCGA) database. Subsequently, computational strategies were utilized to select potential candidate miRNAs. Following this, the expression levels of the potent miRNAs were assessed through RT-qPCR in both CRC tissue and serum samples from patients (N = 46), as well as healthy individuals (N = 46). Additionally, the associations between clinicopathological characteristics, survival outcomes, and diagnostic accuracy were evaluated. Results: A total of 8893 RNA-seq expression data were acquired from TCGA, comprising 8250 data from 19 distinct cancer types and 643 corresponding healthy samples. Based on the computational methodology, miR-549a, miR-552, and miR-592 were identified as the principal expressed miRNAs in colorectal cancer (CRC). Within these miRNAs, miR-552 displayed a substantial association with tumors at the N and T stages. miR-549a and miR-592 were observed to be linked exclusively to the invasion of tumor depth and tumor stage (TNM), respectively. The receiver operating characteristic (ROC) analysis conducted on the miRNA expression in serum samples revealed that all miRNAs exhibited an area under the ROC curve (AUC) of up to 0.86, thereby indicating their high diagnostic accuracy. Conclusion: Considering the strong associations of these three identified miRNAs with CRC, they can collectively serve as a panel for specific discrimination of CRC from other types of cancer within the body. Although this study focused solely on CRC, this approach can potentially be applied to other cancer types as well.

2.
Iran J Basic Med Sci ; 27(1): 97-106, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38164485

RESUMO

Objectives: Knowing the detrimental role of oxidative stress in wound healing and the anti-oxidant properties of Dexpanthenol (Dex), we aimed to produce Dex-loaded electrospun core/shell nanofibers for wound healing study. The novelty was measuring oxidative stress in wounds to know how oxidative stress was affected by Dex-loaded fibers. Materials and Methods: TPVA solution containing Dex 6% (w/v) (core) and PVA/chitosan solution (shell) were coaxially electrospun with variable injection rates of the shell solution. Fibers were then tested for physicochemical properties, drug release profile, and effects on wound healing. Levels of tissue lipid peroxidation and superoxide dismutase activity were measured. Results: Fibers produced at shell injection rate of 0.3 ml/hr (F3 fibers) showed core/shell structure with an average diameter of 252 nm, high hydrophilicity (swelling: 157% at equilibrium), and low weight loss (13.6%). Dex release from F3 fibers seemed to be ruled by the Fickian mechanism based on the Korsmeyer-Peppas model (R2 = 0.94, n = 0.37). Dex-loaded F3 fibers promoted fibroblast viability (128.4%) significantly on day 5 and also accelerated wound healing compared to the neat F3 fibers at macroscopic and microscopic levels on day 14 post-wounding. The important finding was a significant decrease in malondialdehyde (0.39 nmol/ mg protein) level and an increase in superoxide dismutase (5.29 unit/mg protein) activity in Dex-loaded F3 fiber-treated wound tissues. Conclusion: Dex-loaded core/shell fibers provided nano-scale scaffolds with sustained release profile that significantly lowered tissue oxidative stress. This finding pointed to the importance of lowering oxidative stress to achieve proper wound healing.

3.
Front Mol Biosci ; 9: 1030749, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36589227

RESUMO

Introduction: MicroRNAs have a significant role in the regulation of the transcriptome. Several miRNAs have been proposed as potential biomarkers in different malignancies. However, contradictory results have been reported on the capability of miRNA biomarkers in cancer detection. The human biological clock involves molecular mechanisms that regulate several genes over time. Therefore, the sampling time becomes one of the significant factors in gene expression studies. Method: In the present study, we have tried to find miRNAs with minimum fluctuation in expression levels at different time points that could be more accurate candidates as diagnostic biomarkers. The small RNA-seq raw data of ten healthy individuals across nine-time points were analyzed to identify miRNAs with stable expression. Results: We have found five oscillation patterns. The stable miRNAs were investigated in 779 small-RNA-seq datasets of eleven cancer types. All miRNAs with the highest differential expression were selected for further analysis. The selected miRNAs were explored for functional pathways. The predominantly enriched pathways were miRNA in cancer and the P53-signaling pathway. Finally, we have found seven miRNAs, including miR-142-3p, miR-199a-5p, miR-223-5p, let-7d-5p, miR-148b-3p, miR-340-5p, and miR-421. These miRNAs showed minimum fluctuation in healthy blood and were dysregulated in the blood of eleven cancer types. Conclusion: We have found a signature of seven stable miRNAs which dysregulate in several cancer types and may serve as potential pan-cancer biomarkers.

4.
J Biomol Struct Dyn ; 40(20): 10153-10161, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34154515

RESUMO

Understanding the atomic interaction mechanism between chitosan and insulin at different pH levels is essential in the design of chitosan-based drug-delivery systems. In the present study, insulin-loaded nanoparticles were prepared via ionic gelation of tripolyphosphate (TPP) and chitosan with 76 ± 5.5% encapsulation efficiency. Our results showed that the nanoparticles were spherical with a size of 254 nm. Furthermore, the in vitro release profile of insulin was evaluated for two different pH levels. The release of insulin from nanoparticles after 48 h at pH 4.0 was 92%, compared to 56% at pH 7.4. The kinetics of the release were best fitted by the Weibull equation, which described a burst release in the first five hours followed by a sustained insulin release for up to 48 h. Moreover, we designed a long single chain chitosan (128 kDa)/TPP nanoparticles in real size for the first time and studied the system behavior in acidic and neutral environments using molecular dynamic simulation for 40 nanoseconds (ns). Our results showed that chitosan chains opened more with higher root-mean-square deviation (RMSD) values at pH 4.0 than at pH 7.4. Also, RMSD plots for insulin and TPP molecules showed that insulin molecules diffused away from chitosan chains, and that TPP were randomly dispersed further away from the chitosan chain in an acidic medium than in a neutral one. The in silico studies were in agreement with our in vitro data. Thus self-assembled chitosan/TPP nanoparticles show promise as a means to release protein drugs in acidic environments.Communicated by Ramaswamy H. Sarma.


Assuntos
Quitosana , Nanopartículas , Quitosana/química , Insulina , Portadores de Fármacos/química , Simulação de Dinâmica Molecular , Tamanho da Partícula , Nanopartículas/química , Concentração de Íons de Hidrogênio
5.
Int J Mol Sci ; 21(15)2020 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-32756480

RESUMO

The pandemic of coronavirus disease 2019 (COVID-19), with rising numbers of patients worldwide, presents an urgent need for effective treatments. To date, there are no therapies or vaccines that are proven to be effective against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Several potential candidates or repurposed drugs are under investigation, including drugs that inhibit SARS-CoV-2 replication and block infection. The most promising therapy to date is remdesivir, which is US Food and Drug Administration (FDA) approved for emergency use in adults and children hospitalized with severe suspected or laboratory-confirmed COVID-19. Herein we summarize the general features of SARS-CoV-2's molecular and immune pathogenesis and discuss available pharmacological strategies, based on our present understanding of SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV) infections. Finally, we outline clinical trials currently in progress to investigate the efficacy of potential therapies for COVID-19.


Assuntos
Imunidade Adaptativa , Betacoronavirus/fisiologia , Infecções por Coronavirus/patologia , Pneumonia Viral/patologia , Anti-Inflamatórios/uso terapêutico , Antivirais/uso terapêutico , Betacoronavirus/isolamento & purificação , COVID-19 , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/terapia , Infecções por Coronavirus/virologia , Humanos , Imunoterapia , Coronavírus da Síndrome Respiratória do Oriente Médio/isolamento & purificação , Coronavírus da Síndrome Respiratória do Oriente Médio/fisiologia , Fases de Leitura Aberta/genética , Pandemias , Pneumonia Viral/imunologia , Pneumonia Viral/terapia , Pneumonia Viral/virologia , SARS-CoV-2
6.
Cancer Manag Res ; 12: 973-980, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32104079

RESUMO

BACKGROUND AND AIMS: MicroRNAs including miR146a have a regulatory role on the expression of genes and act with binding to 3'-UTR region of the genes. Cyclooxygenase-2 (COX-2) is involved in carcinogenesis as an inflammatory marker, and microRNA-146a (miR-146a) as a negative regulatory factor. We aimed to evaluate miR146a expression as a prognostic or diagnostic biomarker for esophageal squamous cell carcinoma (ESCC) and also an association between miR146a and COX2 expression. MATERIALS AND METHODS: We quantified the level of miR-146a and COX-2 expression in cancerous and adjacent normal tissue samples obtained from 34 patients with ESCC, using real-time-PCR. Statistical analyses were conducted using one-sample t-test. Receiver-operating characteristic (ROC) curve and Kaplan-Meier analysis were applied to assay miR146a as a diagnostic and prognostic marker, respectively, during 4 years of the study. Furthermore, the Cox regression model was performed to assay the hazard ratio (HR). The association between miR-146a and COX2 expression level in ESCC patients was evaluated by nonparametric Spearman's rho analysis. RESULTS: The results revealed a reduction of miR-146a expression in 50% of cancerous tissue when compared with adjacent normal regions (P-value=0.127). COX-2 expression in 80% of ESCC patients was higher than in the controls (P-value=0.001). Overall, in 60% of cases, direct association was seen between microRNA-146a and COX-2 expression level (correlation coefficient= 0.438, P-value=0.011). COX2 can be considered as a diagnostic biomarker (AUC=0.834, sensitivity=72%, specificity =83%, P-value<0.0001) but miR146a cannot be considered as a diagnostic biomarker (AUC=0.553, sensitivity=88%, specificity =28%, P-value=0.453). Survival analysis by Kaplan-Meier method showed miR146a and COX2 expression can be probably considered as prognostic biomarkers for ESCC because patients with high expression of miR146a had 7 months shorter life span and patients with low expression of COX2 had 8 months shorter life span. CONCLUSION: COX2 expression is a diagnostic biomarker. MiR-146a and COX2 expression can probably be considered as prognostic biomarkers for survival in ESCC.

7.
Circulation ; 141(16): 1318-1333, 2020 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-32008372

RESUMO

BACKGROUND: Impaired endothelium-dependent vasodilation is a hallmark of obesity-induced hypertension. The recognition that Ca2+ signaling in endothelial cells promotes vasodilation has led to the hypothesis that endothelial Ca2+ signaling is compromised during obesity, but the underlying abnormality is unknown. In this regard, transient receptor potential vanilloid 4 (TRPV4) ion channels are a major Ca2+ influx pathway in endothelial cells, and regulatory protein AKAP150 (A-kinase anchoring protein 150) enhances the activity of TRPV4 channels. METHODS: We used endothelium-specific knockout mice and high-fat diet-fed mice to assess the role of endothelial AKAP150-TRPV4 signaling in blood pressure regulation under normal and obese conditions. We further determined the role of peroxynitrite, an oxidant molecule generated from the reaction between nitric oxide and superoxide radicals, in impairing endothelial AKAP150-TRPV4 signaling in obesity and assessed the effectiveness of peroxynitrite inhibition in rescuing endothelial AKAP150-TRPV4 signaling in obesity. The clinical relevance of our findings was evaluated in arteries from nonobese and obese individuals. RESULTS: We show that Ca2+ influx through TRPV4 channels at myoendothelial projections to smooth muscle cells decreases resting blood pressure in nonobese mice, a response that is diminished in obese mice. Counterintuitively, release of the vasodilator molecule nitric oxide attenuated endothelial TRPV4 channel activity and vasodilation in obese animals. Increased activities of inducible nitric oxide synthase and NADPH oxidase 1 enzymes at myoendothelial projections in obese mice generated higher levels of nitric oxide and superoxide radicals, resulting in increased local peroxynitrite formation and subsequent oxidation of the regulatory protein AKAP150 at cysteine 36, to impair AKAP150-TRPV4 channel signaling at myoendothelial projections. Strategies that lowered peroxynitrite levels prevented cysteine 36 oxidation of AKAP150 and rescued endothelial AKAP150-TRPV4 signaling, vasodilation, and blood pressure in obesity. Peroxynitrite-dependent impairment of endothelial TRPV4 channel activity and vasodilation was also observed in the arteries from obese patients. CONCLUSIONS: These data suggest that a spatially restricted impairment of endothelial TRPV4 channels contributes to obesity-induced hypertension and imply that inhibiting peroxynitrite might represent a strategy for normalizing endothelial TRPV4 channel activity, vasodilation, and blood pressure in obesity.


Assuntos
Pressão Sanguínea , Dieta Hiperlipídica/efeitos adversos , Endotélio Vascular , Hipertensão , Obesidade , Ácido Peroxinitroso/metabolismo , Canais de Cátion TRPV/metabolismo , Proteínas de Ancoragem à Quinase A/genética , Proteínas de Ancoragem à Quinase A/metabolismo , Animais , Sinalização do Cálcio , Endotélio Vascular/metabolismo , Endotélio Vascular/fisiopatologia , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , Humanos , Hipertensão/genética , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Knockout , Obesidade/genética , Obesidade/metabolismo , Obesidade/fisiopatologia , Ácido Peroxinitroso/genética , Canais de Cátion TRPV/genética , Vasodilatação
8.
Brain Sci ; 11(1)2020 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-33396186

RESUMO

Neuroanatomy laboratory training is crucial for the education of neurosurgery residents and medical students. Since the brain is a complex and three-dimensional structure, it is challenging to understand the anatomical relationship of the cortex, internal structures, arteries, and veins without appropriate adjuncts. Several injection agents-including the inks/dyes, latex, polyester, acrylic resins, phenol, polyethylene glycol, and phenoxyethanol-have been explored. Colored silicon injection protocols for the head and neck vessels' perfusion have greatly aided the study of neuroanatomy and surgical planning. This report presents a colored silicone injection method in detail, and also highlights the technical shortcomings of the standard techniques and workarounds for common challenges during 35 human cadaveric head injections. The human cadaveric head preparation and the coloring of the head vessels are divided into decapitation, tissue fixation with 10% formalin, the placement of the Silastic tubing into the parent vessels, the cleaning of the vessels from clots, and the injection of the colored silicone into the vessels. We describe the technical details of the preparation, injection, and preservation of cadaveric heads, and outline common challenges during colored silicone injection, which include the dislocation of the Silastic tubing during the injection, the injection of the wrong or inappropriate colored silicone into the vessel, intracranial vessel perforation, the incomplete silicone casting of the vessel, and silicone leakage from small vessels in the neck. Solutions to these common challenges are provided. Ethyl alcohol fixed, colored human heads provided the long-term preservation of tissue, and improve the sample consistency and preservation for the teaching of neuroanatomy and surgical technique.

9.
Med J Islam Repub Iran ; 34: 128, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33437724

RESUMO

Background: In a resource-demanding COVID-19 pandemic, guidelines can free up health care resources needed for providing better care to those with COVID-19 and other patients. This study was performed to design a guideline to manage patients with colorectal cancers during the COVID-19pandemic. Methods: To design this guideline, major topics and headings of colon and rectal cancers (CRC) were selected and included. Based on the extent of COVID-19 infection in the community and availability of hospital resources, the guideline has been designed for 2 major COVID-19 phases. Several multidisciplinary discussion sessions were held to review the comments of experts, finalize the data, and write the guideline. Results: This guideline has been prepared in 2 main COVID-19 phases of the community/hospital. Phase A refers to the condition where a large number of COVID-19 patients are admitted to the hospital, but limited surgical ICU beds and facilities are still accessible. In phase B, many people are affected by COVID-19, and all hospital resources are allocated for COVID 19 patients. In phase A, 4 major groups are discussed, including malignant and suspicious colorectal polyps, colon cancers, rectal cancers, and recurrent cancers. The approach to emergent cases, including obstruction, bleeding, and perforation, will be presented in phase B. Conclusion: This guideline is a comprehensive instruction on the approach to colorectal cancers during the COVID-19 pandemic that covers the major topics of colon and rectal cancers in detail.

10.
Int J Pharm ; 572: 118710, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31629731

RESUMO

The smart self-regulated drug delivery systems for insulin administration are desirable to achieve glycemic control, and decrease the long-term micro- and macro vascular complications. In this study, we developed an injectable nano-complex formulation for closed-loop insulin delivery after subcutaneous administration and release of insulin in response to increased blood glucose levels. The nano-complex was prepared by mixing oppositely charged chitosan and PLGA nanoparticles. PLGA nanoparticles were prepared using double-emulsion solvent diffusion method, and were loaded with glucose oxidase (GOx) and catalase (CAT) enzymes. These negatively charged particles decrease micro-environmental pH, by gluconic acid production in the glucose molecules presence. Positively charged chitosan nanoparticles were prepared using ionic gelation method, and were loaded with insulin. These nanoparticles (NPs) released insulin by dissociation in acidic pH caused by the GOx activity. Following in vitro studies, in vivo evaluation of nano-complex formulations in streptozocin induced diabetic rats showed significant glycemic regulation up to 98 h after subcutaneous administration.


Assuntos
Quitosana/administração & dosagem , Diabetes Mellitus Experimental/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Glucose Oxidase/administração & dosagem , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Nanopartículas/administração & dosagem , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/administração & dosagem , Animais , Glicemia/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Quitosana/química , Diabetes Mellitus Experimental/sangue , Composição de Medicamentos , Liberação Controlada de Fármacos , Glucose Oxidase/química , Hipoglicemiantes/química , Insulina/química , Masculino , Camundongos , Nanopartículas/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Ratos Wistar
11.
J Neurosci Rural Pract ; 10(2): 334-338, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31001030

RESUMO

Nonthrombotic intracranial venous occlusive disease (NIVOD) has been implicated in the pathophysiology of idiopathic intracranial hypertension (IIH) and various non-IIH headache syndromes. Endovascular stenting of stenotic, dominant transverse sinuses (TSs) may reduce trans-stenosis pressure gradients, decrease intracranial pressure, and alleviate symptoms in a subset of NIVOD patients. We present a case in which concurrent stenting of the occipito-marginal sinus obliterated the residual trans-stenosis pressure gradient across an initially stented dominant TS. We hypothesize that this observation may be explained using an electric-hydraulic analogy, and that this patient's dominant TS and occipito-marginal sinus may be modeled as a parallel hemodynamic circuit. Neurointerventionalists should be aware of parallel hemodynamic drainage patterns and consider manometry and possibly additional stenting of stenotic, parallel venous outflow pathways if TS stenting alone fails to obliterate the trans-stenosis pressure gradient.

12.
Mater Sci Eng C Mater Biol Appl ; 99: 129-139, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30889664

RESUMO

The aim of this study is to evaluate a core-shell nanofiber as a useful matrix for tuning Rosuvastatin (RSV) release and osteogenic differentiation in vitro. Polyvinyl alcohol (PVA) and silk fibroin were used as the shell and the core, respectively. To obtain a linear and beadless core-shell structure and an optimal release profile, the shell/core flow rate ratio was varied (0, 0.4, 0.6, 0.8, and 1). Formation of continuous nanofibers with an obvious core/sheath structure was proved using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Differential scanning calorimetry indicated the presence of two distinct phase structures in the nanofibers. Also, RSV molecules were dispersed in an amorphous state in the nanofibers. The in vitro release profile of the core-shell structure exhibited a biphasic release profile and the amount of released RSV was controlled by adjusting the shell flow rate. Human adipose-derived stem cells cultured on the RSV loaded nanofibers were found to improve cell proliferation and assist osteogenic differentiation as revealed by Alizarin red staining and real-time RT-PCR.


Assuntos
Tecido Adiposo/citologia , Fibroínas/química , Nanofibras/química , Osteogênese/efeitos dos fármacos , Álcool de Polivinil/química , Rosuvastatina Cálcica/farmacologia , Células-Tronco/citologia , Engenharia Tecidual/métodos , Adulto , Animais , Bombyx , Varredura Diferencial de Calorimetria , Adesão Celular/efeitos dos fármacos , Adesão Celular/genética , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/genética , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Liberação Controlada de Fármacos , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Cinética , Pessoa de Meia-Idade , Nanofibras/ultraestrutura , Osteogênese/genética , Células-Tronco/efeitos dos fármacos , Células-Tronco/metabolismo , Molhabilidade
13.
Spine (Phila Pa 1976) ; 44(11): E640-E649, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30475332

RESUMO

STUDY DESIGN: Case-control whole-genome sequencing analysis of a highly select, young cohort with symptomatic lumbar disk herniation (LDH) compared with the standard variation in a large reference population. OBJECTIVE: To assess genetic influences predisposing pediatric and young adult patients to symptomatic LDH. SUMMARY OF BACKGROUND DATA: LDH has traditionally been attributed to natural weakening or mechanical insult, but recent literature supports a potential genetic influence. METHODS: Young patients with symptomatic, clinically confirmed LDH who underwent surgical treatment were included. Patients were younger than the average age of presentation, limiting the influence of environmental risks. DNA collected from these patients was compared with a reference genome (1000 Genomes Project). A genome-wide association study using whole-genome sequencing was used to characterize genetic mutations potentially associated with LDH. RESULTS: Among the 61 candidate genes flagged, 20 had missense mutations in 2 or more LDH cases. Missense mutations in collagen-encoding genes were observed in 12 of 15 patients (80%). A potential association with clinical presentation was indicated by odds ratios of key single-nucleotide polymorphism (SNP) variants in genes that encode collagen. Relative to the reference population, the LDH cohort demonstrated two statistically significant SNP variants in the gene encoding for aggrecan, a protein that facilitates load-bearing properties in the cartilaginous end plate. Aggrecan genes SNPs rs3817428 and rs11638262 were significantly associated with decreased odds of symptomatic LDH: odds ratio 0.05 (0.02-0.11) and 0.04 (0-0.26), respectively (P < 1 × 10 for both). CONCLUSION: These results suggest that collagen-encoding variants may be a genetic risk factor for LDH. They also shed new light on the role of variants that impact aggrecan, which sustains the cartilaginous end plate. Genetic predisposition to LDH may therefore be related to a multimodal combination of mutations that affect the nucleus pulposus, annulus fibrosus, and the cartilaginous end plates. LEVEL OF EVIDENCE: 4.


Assuntos
Predisposição Genética para Doença/genética , Deslocamento do Disco Intervertebral/diagnóstico por imagem , Deslocamento do Disco Intervertebral/genética , Vértebras Lombares/diagnóstico por imagem , Polimorfismo de Nucleotídeo Único/genética , Adolescente , Adulto , Agrecanas/genética , Estudos de Casos e Controles , Feminino , Estudo de Associação Genômica Ampla/métodos , Humanos , Degeneração do Disco Intervertebral , Masculino , Adulto Jovem
14.
Biomed Mater ; 14(2): 025002, 2018 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-30523938

RESUMO

To begin developing a silk fibroin (SF) nanofibrous scaffolds that could promote osteogenesis, whilst enabling to deliver an active amount of Rosuvastatin (RSV) to the cells in long-time period, the present study aims to immobilize RSV onto the SF nanofibers through the argon radio frequency. Thus, the effect of plasma exposure times (0, 1, 3, and 5 min) was investigated on the morphology, loading efficiency, release profile, and osteogenesis activity. The successful loading of RSV on the SF nanofibers was proved by Fourier transformed infrared spectroscopy, Differential scanning calorimetry, and energy dispersive spectroscopy. In vitro drug release studies demonstrated that the RSV release was prolonged over a period of 21 d for plasma treated mats, while the non-plasma treated samples released the whole drug after 72 h. Moreover, the dose of RSV was controlled by the plasma exposure times, in which the highest amount of the released RSV was achieved after 3 min exposing to plasma. As suggested by MTT assay, the released amounts of RSV had no toxicity on the seeded human adipose tissue-derived stem cells and enhanced their proliferation. Moreover, using real-time reverse transcriptase-polymerase chain reaction and alizarin red staining proved that RSV-immobilized SF mats stimulate both early and late osteogenic gene differentiation in comparison with pure SF nanofibers. However, the highest differentiation was observed on the SF nanofibers treated with argon plasma for 3 min. The results support the potential of plasma treatment on sustained release of the RSV from SF nanofibers for osteogenesis enhancement.


Assuntos
Anticolesterolemiantes/farmacologia , Fibroínas/química , Osteogênese/efeitos dos fármacos , Rosuvastatina Cálcica/farmacologia , Alicerces Teciduais/química , Tecido Adiposo/citologia , Animais , Argônio , Bombyx , Adesão Celular , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Durapatita/química , Eletroquímica , Humanos , Nanofibras/química , Gases em Plasma/química , Engenharia Tecidual/métodos
15.
Eur J Med Chem ; 132: 42-62, 2017 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-28340413

RESUMO

Histone deacetylases (HDACs) are attractive therapeutic targets for the treatment of cancer and other diseases. It has four classes (I-IV), among them especially class I isozyme are involved in promoting tumor cells proliferation, angiogenesis, differentiation, invasion and metastasis and also viable targets for cancer therapeutics. A novel series of coumarin-based benzamides was designed and synthesized as HDAC inhibitors. The cytotoxic activity of the synthesized compounds (8a-u) was evaluated against six human cancer cell lines including HCT116, A2780, MCF7, PC3, HL60 and A549 and a single normal cell line (Huvec). We evaluated their inhibitory activities against pan HDAC and HDAC1 isoform. Four compounds (8f, 8q, 8r and 8u) showed significant cytotoxicity with IC50 in the range of 0.53-57.59 µM on cancer cells and potent pan-HDAC inhibitory activity (consists of HDAC isoenzymes) (IC50 = 0.80-14.81 µM) and HDAC1 inhibitory activity (IC50 = 0.47-0.87 µM and also, had no effect on Huvec (human normal cell line) viability (IC50 > 100 µM). Among them, 8u displayed a higher potency for HDAC1 inhibition with IC50 value of 0.47 ± 0.02 µM near equal to the reference drug Entinostat (IC50 = 0.41 ± 0.06 µM). Molecular docking studies and Molecular dynamics simulation of compound 8a displayed possible mode of interaction between this compound and HDAC1enzyme.


Assuntos
Antineoplásicos/síntese química , Benzamidas/síntese química , Cumarínicos/síntese química , Inibidores de Histona Desacetilases/síntese química , Antineoplásicos/farmacologia , Benzamidas/farmacologia , Linhagem Celular Tumoral , Cumarínicos/farmacologia , Desenho de Fármacos , Histona Desacetilase 1/antagonistas & inibidores , Inibidores de Histona Desacetilases/farmacologia , Humanos , Concentração Inibidora 50 , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Relação Estrutura-Atividade
17.
J Biomol Struct Dyn ; 34(11): 2505-17, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26609886

RESUMO

Pesticide detection is a main concern of food safety experts. Therefore, it is urgent to design an accurate, rapid, and cheap test. Biosensors that detect pesticide residues could replace current methods, such as HPLC or GC-MC. This research designs a biosensor based on aptamer (Oligonucleotide ss-DNA) in the receptor role, silver nanoparticles (AgNPs) as optical sensors and salt (NaCl) as the aggregative inducer of AgNPs to detect the presence of Acetamiprid. After optimization, .6 µM aptamer and 100 mM salt were employed. The selectivity and sensitivity of the complex were examined by different pesticides and different Acetamiprid concentrations. To simulate in vitro experimental conditions, bioinformatics software was used as in silico analysis. The results showed the detection of Acetamiprid at the .02 ppm (89.8 nM) level in addition to selectivity. Docking outputs introduced two loops as active sites in aptamer and confirmed aptamer-Acetamiprid bonding. Circular dichroism spectroscopy (CD) confirmed upon Acetamiprid binding, aptamer was folded due to stem-loop formation. Stability of the Apt-Acetamiprid complex in a simulated aqueous media was examined by molecular dynamic studies.


Assuntos
Aptâmeros de Nucleotídeos/química , Técnicas Biossensoriais , Nanopartículas Metálicas/química , Piridinas/química , Dicroísmo Circular , Ligação de Hidrogênio , Modelos Moleculares , Conformação Molecular , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Nanotecnologia , Neonicotinoides , Prata , Relação Estrutura-Atividade
18.
World Neurosurg ; 87: 235-41, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26615787

RESUMO

BACKGROUND: The advent of improved surgical instruments and neuronavigation and descriptions of safe-entry zones have allowed neurosurgeons to resect brainstem lesions with an acceptable morbidity. The authors describe the technique of petrosal fissure dissection to the lateral transpeduncular safe-entry zone at the middle cerebellar peduncle (MCP) for resection of deep-seated central pontine pathologies. This approach allows the surgeon to obtain less cerebellar retraction and a more direct, more shallow, and shorter approach compared with the approach without opening this fissure. METHODS: An illustrative case is used to highlight the technique of dissecting the petrosal fissure to obtain a direct surgical corridor to the MCP. Anatomic dissections are used to define better the relative relationships of this fissure to the MCP and adjacent structures. RESULTS: Dissection of the petrosal fissure provides a direct trajectory to the lateral transpeduncular entry zone at the MCP and can enhance exposure of this structure, while minimizing morbidity to the corticospinal tract and cerebellum during approaches to central pontine pathologies. CONCLUSIONS: For resection of lesions within the pons via the retrosigmoid craniotomy, dissection of the petrosal fissure allows for a more direct and shorter route to the central pontine and lateral pontine lesion compared with an approach without expansion of this potential space.


Assuntos
Cerebelo/cirurgia , Procedimentos Neurocirúrgicos/métodos , Osso Petroso/cirurgia , Ponte/cirurgia , Adulto , Tronco Encefálico/cirurgia , Doenças dos Nervos Cranianos/cirurgia , Craniotomia/métodos , Feminino , Humanos , Malformações Arteriovenosas Intracranianas/cirurgia , Microcirurgia , Neuronavegação , Complicações Pós-Operatórias/epidemiologia , Tratos Piramidais/cirurgia
19.
Clin Spine Surg ; 29(7): 285-90, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-23274399

RESUMO

STUDY DESIGN: The authors retrospectively reviewed a consecutive series of 231 patients with anterior lumbar interbody fusion (ALIF). OBJECTIVE: To determine the correlations among common medical conditions, demographics, and the natural history of lumbar surgery with outcomes of ALIF. SUMMARY OF BACKGROUND DATA: Multiple spinal disorders are treated with ALIF with excellent success rates. Nonetheless, adverse outcomes and complications related to patients' overall demographics, comorbidities, or cigarette smoking have been reported. METHODS: The age, sex, body mass index (BMI), comorbidities, history of smoking or previous lumbar surgery, operative parameters, and complications of 231 patients who underwent ALIF were analyzed. Regression analyses of all variables with complications and surgical outcomes based on total Prolo scores were performed. Two models predicting Prolo outcome score were generated. The first model used BMI and sex interaction, whereas the second model used sex, level of surgery, presence of diabetes mellitus, and BMI as variables. RESULTS: At follow-up, the rate of successful fusion was 99%. The overall complication rate was 13.8%, 1.8% of which occurred intraoperatively and 12% during follow-up. The incidence of complications failed to correlate with demographics, comorbidities, smoking, or previous lumbar surgery (P>0.5). ALIF at T12-L4 was the only factor significantly associated with poor patient outcomes (P=0.024). Both models successfully predicted outcome (P=0.05), although the second model did so only for males. CONCLUSIONS: Surgical level of ALIF correlated with poor patient outcomes as measured by Prolo functional scale. BMI emerged as a significant predictor of Prolo total score. Both multivariate models also successfully predicted outcomes. Surgical or follow-up complications were not associated with patients' preoperative status.


Assuntos
Índice de Massa Corporal , Vértebras Lombares/cirurgia , Fusão Vertebral/métodos , Resultado do Tratamento , Adolescente , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Estudos Retrospectivos , Doenças da Coluna Vertebral/cirurgia , Adulto Jovem
20.
Med J Islam Repub Iran ; 28: 19, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25250264

RESUMO

BACKGROUND: Approach to the small intestine has been difficult even with newer methods. Double-balloon enteroscopy (DBE) has been created for diagnostic and therapeutic interventions in diseases of the small intestine. Small intestinal diseases have different etiologies in each country. The DBE has been introduced in recent years in Iran. Our aim was to study the indications and results of DBE in some academic centers in Iran. METHODS: Fifty-five patients with symptoms and signs related to small intestine without definitive diagnosis but with previous workup were enrolled in the study. The DBE was performed in three different medical universities in Iran. RESULTS: The mean age of the patients that underwent the DBE was 47.2 ± 17.3 years. Abdominal pain (54.5%) and occult gastrointestinal bleeding (23.6%) were the most common presentations. Small bowel lesions were detected in 26 patients (47.3%); the most common lesions were ulcer (46.2%) and polyps (19.2%). Crohn's disease (12.7%) was the commonest diagnosis found in DBE procedure. Patients presenting with abdominal pain orl ower hemoglobin level were more likely to be diagnosed (both p≤ 0.05). Small intestinal diseases were ultimately diagnosed in 47.3% of the patients. Twenty percent of the patients had another disease outside the small bowel. CONCLUSIONS: DBE is an effective and relatively safe diagnostic and therapeutic option for small bowel evaluations. Accurate selection of patients and more experience technicians and physicians will improve the efficacy of this procedure in Iran.

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