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1.
Math Biosci Eng ; 20(4): 6591-6611, 2023 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-37161119

RESUMO

In this research paper, we presented a four-dimensional mathematical system modeling the anaerobic mineralization of phenol in a two-step microbial food-web. The inflowing concentrations of the hydrogen and the phenol are considered in our model. We considered the case of general class of nonlinear growth kinetics, instead of Monod kinetics. Due to some conservative relations, the proposed model was reduced to a two-dimensional system. The stability of the steady states was carried out. Based on the species growth rates and the three main operating parameters of the model, represented by the dilution rate and input concentrations of the phenol and the hydrogen, we showed that the system can have up to four steady states. We gave the necessary and sufficient conditions ensuring the existence and the stability for each feasible equilibrium state. We showed that in specific cases, the positive steady state exists and is stable. We gave numerical simulations validating the obtained results.


Assuntos
Calcinose , Fenol , Humanos , Anaerobiose , Fenóis , Hidrogênio
2.
Math Biosci Eng ; 19(3): 2853-2875, 2022 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-35240810

RESUMO

A generalized "SVEIR" epidemic model with general nonlinear incidence rate has been proposed as a candidate model for measles virus dynamics. The basic reproduction number $ \mathcal{R} $, an important epidemiologic index, was calculated using the next generation matrix method. The existence and uniqueness of the steady states, namely, disease-free equilibrium ($ \mathcal{E}_0 $) and endemic equilibrium ($ \mathcal{E}_1 $) was studied. Therefore, the local and global stability analysis are carried out. It is proved that $ \mathcal{E}_0 $ is locally asymptotically stable once $ \mathcal{R} $ is less than. However, if $ \mathcal{R} > 1 $ then $ \mathcal{E}_0 $ is unstable. We proved also that $ \mathcal{E}_1 $ is locally asymptotically stable once $ \mathcal{R} > 1 $. The global stability of both equilibrium $ \mathcal{E}_0 $ and $ \mathcal{E}_1 $ is discussed where we proved that $ \mathcal{E}_0 $ is globally asymptotically stable once $ \mathcal{R}\leq 1 $, and $ \mathcal{E}_1 $ is globally asymptotically stable once $ \mathcal{R} > 1 $. The sensitivity analysis of the basic reproduction number $ \mathcal{R} $ with respect to the model parameters is carried out. In a second step, a vaccination strategy related to this model will be considered to optimise the infected and exposed individuals. We formulated a nonlinear optimal control problem and the existence, uniqueness and the characterisation of the optimal solution was discussed. An algorithm inspired from the Gauss-Seidel method was used to resolve the optimal control problem. Some numerical tests was given confirming the obtained theoretical results.


Assuntos
Epidemias , Sarampo , Algoritmos , Número Básico de Reprodução , Humanos , Sarampo/epidemiologia
3.
Curr Pharm Biotechnol ; 23(7): 988-997, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34264183

RESUMO

BACKGROUND: Abelmoschus esculentus (AE) (okra), is an edible plant used in many food applications. OBJECTIVE: This study explored whether sulfated AE (SAE) has promising cancer chemopreventive activities that may recommend it as a functional food supplement instead of (or in addition to) AE for the population at risk of cancer and in the health food industry. METHODS: Cytochrome P450-1A (CYP1A) was estimated by fluorescence enzymatic reaction, using ß-naphthoflavone-treated cells (CYP1A inducer). Peroxyl and hydroxyl radical scavenging was assayed by oxygen radical absorbance capacity assay. Flow cytometry was used to analyze apoptosis/necrosis in MCF-7 cells, cell cycle phases in MCF-7 cells, and macrophage binding to fluorescein isothiocyanate-lipopolysaccharide (FITC-LPS). Nitric oxide was determined by Griess assay in LPS-stimulated macrophages, and cytotoxicity was determined by MTT assay. Diethylnitrosamine (DEN) was used to induce hepatic tumor initiation in rats. Placental glutathione-S-transferase (GSTP; an initiation marker) was stained in a fluorescence immunohistochemical analysis of liver sections, and histopathological changes were examined. RESULTS: SAE exhibited strong antitumor initiation and antitumor promotion activities. It suppressed CYP1A, scavenged peroxyl and hydroxyl radicals, induced macrophage proliferation, suppressed macrophage binding to FITC-LPS, inhibited nitric oxide generation, showed specific cytotoxicity to human breast MCF-7 adenocarcinoma cells, and disturbed the cell cycle phases (S and G2/M phases) in association with an increased percentage of apoptotic/necrotic MCF-7 cells. Over a short time period, DEN stimulated liver cancer initiation, but SAE treatment reduced the DEN-induced histopathological alterations and inhibited CYP1A and GSTP. CONCLUSION: SAE extract has the potential for use as an alternative to AE in health foods to provide cancer chemoprevention in populations at risk for cancer.


Assuntos
Abelmoschus , Neoplasias , Abelmoschus/química , Animais , Apoptose , Feminino , Fluoresceína-5-Isotiocianato/química , Humanos , Lipopolissacarídeos/química , Óxido Nítrico/química , Placenta , Extratos Vegetais/farmacologia , Gravidez , Ratos , Sulfatos/química , Sulfatos/isolamento & purificação , Sulfatos/farmacologia
4.
Int J Biol Macromol ; 180: 753-759, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33727189

RESUMO

Polymeric wood hemicelluloses are depicted to join cellulose, starch and chitosan as key polysaccharides for sustainable materials engineering. However, the approaches to incorporate hemicelluloses in emerging bio-based products are challenged by lack of specific benefit, other than the biomass-origin, although their utilization would contribute to sustainable material use since they currently are a side stream that is not valorized. Here we demonstrate wood-xylans as swelling modifiers for neutral and charged nanocellulose films that have already entered the sustainable packaging applications, however, suffer from humidity sensitivity. The oxidative modification is used to modulate the water-solubility of xylan and hence enable adsorption in an aqueous environment. A high molecular weight grade, hence less water-soluble, adsorbed preferentially on the neutral surface while the adsorbed amount on a negatively charged surface was independent of the molecular weight, and hence, solubility. The adsorption of the oxidized xylans on a neutral cellulose surface resulted in an increase in the amount of water in the film while on the negatively charged cellulose the total amount of water decreased. The finding of synergy of two hygroscopic materials to decrease swelling in hydrophilic bio-polymer films demonstrates the oxidized macromolecule xylan as structurally functional component in emerging cellulose products.


Assuntos
Celulose/química , Nanoestruturas/química , Madeira/química , Xilanos/química , Adsorção , Sequência de Carboidratos , Elasticidade , Interações Hidrofóbicas e Hidrofílicas , Microscopia de Força Atômica , Dados de Sequência Molecular , Oxirredução , Solubilidade , Propriedades de Superfície , Viscosidade , Água/química
5.
Nutr Cancer ; 73(5): 856-868, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32482099

RESUMO

Enterolobium cyclocarpum (EC) is an edible plant and a gum source for food industries. Its sulfated polysaccharide extract (SEC) was examined for cancer chemopreventive properties to estimate its anti-tumor activity. The modulation of carcinogen metabolism and the antioxidant activity revealed that SEC is a potent tumor anti-initiator since it inhibited cytochrome P450-1A (CYP1A) and induced carcinogen detoxification enzyme glutathione-S-transferase. SEC is also a weak scavenger for hydroxyl and peroxyl radicals. SEC was found to modulate macrophage functions into an anti-inflammatory pattern, where it enhanced macrophage proliferation and phagocytosis of fluorescein isothiocyanate-lipopolysaccharide (FITC-LPS). In addition, SEC strongly inhibited the nitric oxide (NO) generation in LPS-stimulated macrophages and induced the binding affinity of FITC-LPS to macrophages. SEC exhibited specific cytotoxicity against human hepatocellular Hep G2 carcinoma cells. SEC disturbed the cell cycle phase, as indicated by the concomitant arrest in S- and G2/M-phases that was associated with necrosis induction. A short-term initiation model for liver cancer was prepared using diethylnitrosamine (DEN) in rats. SEC inhibited the DEN-histopathological findings and reduced both CYP1A and the tumor initiation marker placental glutathione S-transferase (GSTP). Taken together, SEC could be used as an alternative gum in health food industries to provide cancer prevention in high-risk populations.


Assuntos
Fabaceae , Neoplasias , Animais , Antioxidantes , Dietilnitrosamina , Feminino , Humanos , Placenta , Extratos Vegetais/farmacologia , Gravidez , Ratos , Sulfatos
6.
Nanomaterials (Basel) ; 10(4)2020 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-32252493

RESUMO

In the past two decades, research on electrospinning has boomed due to its advantages of simple process, small fiber diameter, and special physical and chemical properties. The electrospun fibers are collected in a non-woven state in most cases (electrospun non-woven fabrics, ESNWs), which renders the electrospinning method an optimum approach for non-woven fabric manufacturing on the nano-scale. The present study establishes a convenient preparation procedure for converting water-soluble dialdehyde cellulose (DAC) into DAC-based electrospun non-woven fabrics (ESNWs) reinforced with poly(vinyl alcohol) (PVA). The aldehyde content, which was quantified by colorimetry using Schiff's reagent, was 11.1 mmol per gram of DAC, which corresponds to a conversion yield of ca. 90%. DAC is fully water-soluble at room temperature between 10 and 30 wt%, and aqueous solutions turn into hydrogels within 24 h. To overcome gelation, NaHSO3, which forms bisulfite adducts with aldehyde functions, was added to the DAC and its concentration was optimized at 1 wt%. The electrospun (ES) dope containing 5 wt% DAC, 5 wt% PVA, and 1 wt% NaHSO3 in an aqueous solution was successfully transformed into ESNW, with an average fiber diameter of 345 ± 43 nm. Post-spinning treatment with excess hexamethylene diisocyanate was performed to insolubilize the ESNW materials. The occurrence of this chemical conversion was confirmed by energy-dispersive X-ray elemental analysis and vibrational spectra. The cross-linked DAC/PVA ESNW retained its thin fiber network upon soaking in distilled water, increasing the average fiber diameter to 424 ± 95 nm. This suggests that DAC/PVA-ESNWs will be applicable for incorporation or immobilization of biologically active substances.

7.
J Raman Spectrosc ; 51(3): 422-431, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32214622

RESUMO

Vibrational spectroscopy is a very suitable tool for investigating the plant cell wall in situ with almost no sample preparation. The structural information of all different constituents is contained in a single spectrum. Interpretation therefore heavily relies on reference spectra and understanding of the vibrational behavior of the components under study. For the first time, we show infrared (IR) and Raman spectra of dibenzodioxocin (DBDO), an important lignin substructure. A detailed vibrational assignment of the molecule, based on quantum chemical computations, is given in the Supporting Information; the main results are found in the paper. Furthermore, we show IR and Raman spectra of synthetic guaiacyl lignin (dehydrogenation polymer-G-DHP). Raman spectra of DBDO and G-DHP both differ with respect to the excitation wavelength and therefore reveal different features of the substructure/polymer. This study confirms the idea previously put forward that Raman at 532 nm selectively probes end groups of lignin, whereas Raman at 785 nm and IR seem to represent the majority of lignin substructures.

8.
Int J Nanomedicine ; 14: 5569-5579, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31413563

RESUMO

Background: Gold nanoparticles (AuNPs) have been considered as an ideal candidate in various biomedical applications due to their ease of tailoring into different size, shape, and decorations with different functionalities. The current study was conducted to investigate the epigenetic alteration in the lung in response to AuNPs administration regarding microRNA-155 (miR-155) gene which can be involved in AuNP-induced lung pathogenesis. Methods: Thirty-two Wister rats were divided into two equal groups, control group and AuNPs treated group which received a single intravenous (IV) injection of plain spherical AuNPs (0.015 mg/kg body wt) with an average diameter size of 25±3 nm. Lung samples were collected from both the control and injected groups at one day, one week, one month and two months post-injection. The alteration of relative expression of miR-155 gene and two of its putative target genes; tumor protein 53 inducible nuclear protein 1 (TP53INP1) and protein S (PROS1) was investigated by real time PCR and protein S (PS) expression was analyzed by Western blotting technique. Results: The obtained results revealed that AuNPs administration significantly increases the expression level of miR-155 and reduce relative mRNA expression of TP53INP1 and PROS1 genes at one day post-injection. In contrast, a significant down-regulation of miR-155 level of expression concurrent with up-regulation of expression level of TP53INP1 and PROS1 genes were shown at one week, one month and two months post-injection. PS levels were mirrored to their PROS1 mRNA levels except for two month post-injection time point. Conclusions: These findings indicate epigenetic modulation in the lung in response to AuNPs administration regarding the miR-155 gene which can be involved in AuNP-induced lung pathogenesis.


Assuntos
Regulação da Expressão Gênica , Ouro/administração & dosagem , Proteínas de Choque Térmico/metabolismo , Pulmão/metabolismo , Nanopartículas Metálicas/administração & dosagem , MicroRNAs/genética , Proteínas Nucleares/metabolismo , Proteína S/genética , Animais , Proteínas Reguladoras de Apoptose , Proteínas Sanguíneas , Endocitose , Proteínas de Choque Térmico/genética , Pulmão/ultraestrutura , Masculino , Nanopartículas Metálicas/ultraestrutura , MicroRNAs/metabolismo , Proteínas Nucleares/genética , Proteína S/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Wistar
9.
Sci Rep ; 8(1): 11779, 2018 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-30068992

RESUMO

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

10.
Sci Rep ; 8(1): 9202, 2018 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-29907856

RESUMO

DDB1- and CUL4-associated factor 17 (Dcaf17) is a member of DCAF family genes that encode substrate receptor proteins for Cullin-RING E3 ubiquitin ligases, which play critical roles in many cellular processes. To unravel the function of DCAF17, we performed expression profiling of Dcaf17 in different tissues of wild type mouse by qRT-PCR and generated Dcaf17 knockout mice by gene targeting. Expression profiling of Dcaf17 showed highest expression in testis. Analyses of Dcaf17 transcripts during post-natal development of testis at different ages displayed gradual increase in Dcaf17 mRNA levels with the age. Although Dcaf17 disruption did not have any effect on female fertility, Dcaf17 deletion led to male infertility due to abnormal sperm development. The Dcaf17 -/- mice produced low number of sperm with abnormal shape and significantly low motility. Histological examination of the Dcaf17 -/- testis revealed impaired spermatogenesis with presence of vacuoles and sloughed cells in the seminiferous tubules. Disruption of Dcaf17 caused asymmetric acrosome capping, impaired nuclear compaction and abnormal round spermatid to elongated spermatid transition. For the first time, these data indicate that DCAF17 is essential for spermiogenesis.


Assuntos
Envelhecimento , Deleção de Genes , Infertilidade Masculina , Túbulos Seminíferos , Espermátides , Espermatogênese , Complexos Ubiquitina-Proteína Ligase/deficiência , Envelhecimento/genética , Envelhecimento/metabolismo , Envelhecimento/patologia , Animais , Infertilidade Masculina/enzimologia , Infertilidade Masculina/genética , Infertilidade Masculina/patologia , Masculino , Camundongos , Camundongos Knockout , Túbulos Seminíferos/enzimologia , Túbulos Seminíferos/patologia , Motilidade dos Espermatozoides/genética , Espermátides/enzimologia , Espermátides/patologia
11.
Int J Mol Sci ; 19(2)2018 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-29385708

RESUMO

Increased expression of heat shock proteins (HSPs) following heat stress or other stress conditions is a common physiological response in almost all living organisms. Modification of cytosolic proteins including HSPs by O-GlcNAc has been shown to enhance their capabilities for counteracting lethal levels of cellular stress. Since HSPs are key players in stress resistance and protein homeostasis, we aimed to analyze their forms at the cellular and molecular level using camel and human HSPs as models for efficient and moderate thermotolerant mammals, respectively. In this study, we cloned the cDNA encoding two inducible HSP members, HSPA6 and CRYAB from both camel (Camelus dromedarius) and human in a Myc-tagged mammalian expression vector. Expression of these chaperones in COS-1 cells revealed protein bands of approximately 25-kDa for both camel and human CRYAB and 70-kDa for camel HSPA6 and its human homologue. While localization and trafficking of the camel and human HSPs revealed similar cytosolic localization, we could demonstrate altered glycan structure between camel and human HSPA6. Interestingly, the glycoform of camel HSPA6 was rapidly formed and stabilized under normal and stress culture conditions whereas human HSPA6 reacted differently under similar thermal and hypoxic stress conditions. Our data suggest that efficient glycosylation of camel HSPA6 is among the mechanisms that provide camelids with a superior capability for alleviating stressful environmental circumstances.


Assuntos
Proteínas de Choque Térmico HSP70 , Modelos Moleculares , Cadeia B de alfa-Cristalina , Animais , Células COS , Camelus , Hipóxia Celular , Chlorocebus aethiops , Proteínas de Choque Térmico HSP70/química , Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico HSP70/metabolismo , Humanos , Isoformas de Proteínas , Cadeia B de alfa-Cristalina/química , Cadeia B de alfa-Cristalina/genética , Cadeia B de alfa-Cristalina/metabolismo
12.
Biomacromolecules ; 19(3): 973-979, 2018 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-29414240

RESUMO

Nanocellulose-based self-standing films are becoming a substrate for flexible electronics, diagnostics, and sensors. Strength and surface chemistry are vital variables for these film-based endeavors, the former is one of the assets of nanocellulose. To contribute to the latter, nanocellulose films are tuned with a side-specific functionalization, having an aldehyde and a carboxyl side. The functionalities were obtained combining premodification of the film components by periodate oxidation with ozone post-treatment. Periodate oxidation of cellulose nanocrystals results in film components that interact through intra- and intermolecular hemiacetals and lead to films with an elastic modulus of 11 GPa. The ozone treatment of one film side induces conversion of the aldehyde into carboxyl functionalities. The ozone treatment on individual crystals was largely destructive. Remarkably, such degradation is not observed for the self-standing film, and the film strength at break is preserved. Preserving a physically intact film despite ozone treatment is a credit to using the dry film structure held together by interparticle covalent linkages. Additionally, gas-phase post-treatment avoids disintegration that could result from immersion into solvents. The crystalline cellulose "Janus" film is suggested as an interfacial component in biomaterial engineering, separation technology, or in layered composite materials for tunable affinity between the layers.


Assuntos
Celulose/química , Membranas Artificiais , Nanopartículas/química , Ozônio/química , Aldeídos/química , Oxirredução
13.
Biotechnol Rep (Amst) ; 17: 55-62, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29321979

RESUMO

Soyasapogenol B (SB) is known to have many biological activities such as hepatoprotective, anti-inflammatory, anti-mutagenic, antiviral and anticancer activities. Enzymatic conversion of soyasaponins to SB was carried out using saponin hydrolase (SH) extracted from Aspergillus flavus. The partially purified enzyme was immobilized on different carriers by physical adsorption, covalent binding or entrapment. Among the investigated carriers, Eupergit C and sugarcane bagasse (SCB) activated by DIC and NHS were the most suitable two carriers for immobilization (the immobilized forms recovered 46.5 and 37.1% of the loaded enzyme activity, respectively). Under optimized immobilization conditions, immobilized SH on Eupergit C and on activated SBC recovered 87.7 and 83.3% of its original activity, respectively. Compared to free SH, immobilized SH on Eupergit C and on activated SCB showed higher optimum pH, activation energy, half-lives and lower deactivation constant rate. Also, their SB productivities were improved by 2.3- and 2.2-folds compared to free SH (87.7 and 83.3 vs. 37.5%, respectively). Hence, being SCB more sustainable and an inexpensive material, it can be considered a good alternative to Eupergit C as a support for SH immobilization. SH immobilization on industrially applicable and inexpensive carrier is necessary to improve SB yield and reduce its production cost. The chemical structure of SCB and the resulting cellulose derivatives were studied by ATR-IR spectroscopy. The thermal analysis technique was used to study the chemical treatment of SCB and coupling with the enzyme. This technique confirmed the removal of lignin and hemicellulose by chemical treatment of SCB.

14.
Biotechnol J ; 12(9)2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28731613

RESUMO

Polyesters of 2,5-furandicarboxylic acid (FDCA) have gained attention as they can be regarded as the bio-based alternatives to the petroleum-based polyesters of terephthalic acid. However, only little is known about the biodegradation and enzymatic hydrolysis of FDCA-based polyesters. This work aims to investigate the influence of different polyols on enzymatic hydrolysis of FDCA-based polyesters. A series of polyesters containing various polyols are synthesized and analyzed regarding susceptibility to enzymatic hydrolysis by cutinase 1 from Thermobifida cellulosilytica (Thc_Cut1). FDCA-based polyesters' number average molecular weight (Mn ) ranged from 9360-35 800 g mol-1 according to gel permeation chromatography (GPC) analysis. Differential scanning calorimetry (DSC) analyses show decreasing glass transition temperature (Tg ) with increasing diol chain length. Crystallinity of all polyesters is below 1% except for polyesters containing 1,6-hexanediol, 1,8-octanediol, and 1,12-dodecanediol for which calculated crystallinities are 27, 37, and 30%, respectively. Thc_Cut1 hydrolyzes all tested polyesters with preference for polyesters containing 1,5-pentanediol and 1,9-nonanediol (57.7 ± 7.5 and 52.8 ± 4.0% released FDCA). Enzyme activity increases when the linear diol 1,3-propanediol is replaced by the branched analog 1,2-propanediol or ethoxy units are introduced into the polyester chain. The results will contribute to expand the knowledge of microbial biodegradation of FDCA-based polyesters.


Assuntos
Hidrolases de Éster Carboxílico/metabolismo , Ácidos Dicarboxílicos/metabolismo , Furanos/metabolismo , Poliésteres/metabolismo , Polímeros/química , Actinobacteria/enzimologia , Ácidos Dicarboxílicos/análise , Ácidos Dicarboxílicos/química , Furanos/análise , Furanos/química , Hidrólise , Imageamento por Ressonância Magnética , Poliésteres/análise , Poliésteres/química , Polímeros/metabolismo
15.
Biomacromolecules ; 17(9): 2972-80, 2016 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-27529432

RESUMO

The cleavage of the C2-C3 bond in the building units of 1 → 4-linked polysaccharides by periodate formally results in two aldehyde units, which are present in several masked forms. The structural elucidation of such polysaccharide dialdehydes remains a big challenge. Since polysaccharide derivatives are increasingly applied in materials technology, unveiling the exact structure is of utmost importance. To address this issue for xylan, dialdehyde xylan (DAX, oxidation degree of 91.5%) has been synthesized as water-soluble polymer. The ATR-FTIR spectrum of DAX showed free aldehyde to be absent and exhibited a characteristic absorption at 858 cm(-1) related to hemiacetal groups. By a combination of 1D and 2D NMR techniques, it was confirmed that oxidized xylan is present as poly(2,6-dihydroxy-3-methoxy-5-methyl-3,5-diyl-1,4-dioxane). Based on GPC analysis, the DAX polymer shows a slightly lower molar mass (6.6 kDa) compared to the starting material (7.7 kDa) right after oxidation, and degraded further after one month of storage in 0.1 M NaCl solution (4.3 kDa). The oxidized xylan demonstrated lower thermal stability upon TGA analysis and a greater amount of residual char (20.6%) compared to the unmodified xylan (13.7%).


Assuntos
Aldeídos/química , Ácido Periódico/química , Polímeros/química , Polissacarídeos/síntese química , Água/química , Xilanos/química , Peso Molecular , Oxirredução
16.
Endocr Pract ; 22(10): 1199-1203, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27409819

RESUMO

OBJECTIVE: Thyroid nodules with fine-needle aspiration (FNA) cytology categorized as atypia of undetermined significance (AUS) often undergo additional diagnostic analysis with the Afirma Gene Expression Classifier (GEC), which classifies these as either high probability of being benign (GEC-B) or suspicious for malignancy (GEC-S). Our goal was to assess the clinical validity and utility of GEC in the evaluation of AUS cytology and evaluate the performance of ultrasonography (USG) for predicting malignancy in this subset. METHODS: We conducted a study with a retrospective cohort of patients from January 2012 to January 2014 who had FNA of thyroid nodules >1 cm in size with AUS cytology. RESULTS: Cleveland Clinic Florida has an overall prevalence of AUS of 5%. A total of 119 cases with nodules >1 cm in size were reported as AUS. Forty-eight (40.3%) had a GEC performed after the first FNA (AUS-1), and 27 of these were GEC-S. Of those 27, 21 went for surgery and 14 (66.6%) had thyroid cancer on histopathology. The remaining 71 with AUS-1 were sent for a second FNA: 19 nodules were benign and did not undergo further evaluation, while the remaining 52 were reported as AUS for the second consecutive time (AUS-2). AUS-2 samples were sent for GEC. Of these 52 AUS-2, 38 (73.1%) were reported as GEC-S. Thirty-five went for surgery and 32 (91.4%) had confirmed malignancy on histopathology. Positive predictive value (PPV) was 91.4% for AUS-2 and 66.6% for AUS-1. Moreover, AUS-2 nodules that were hypoechoic and solid on USG showed a PPV of 92% for malignancy. CONCLUSION: In our practice, the diagnostic accuracy to predict malignancy with GEC for AUS-1 nodules was poor (PPV, 66.6%). The PPV of GEC testing was markedly higher at 91.4% performed after two consecutive AUS cytologies. AUS-2 nodules that were solid and hypoechoic on USG also had a high probability to be malignant (PPV, 92%). We recommend repeat FNA on AUS-1 nodules rather than proceeding directly to GEC testing. Also, we suggest that among AUS-2 nodules, surgery can be recommended when USG shows solid and hypoechoic features with GEC testing reserved for the remainder. ABBREVIATIONS: AUS = atypia of undetermined significance FNA = fine-needle aspiration GEC = gene expression classifier GEC-B = GEC-benign GEC-S = GEC-suspicious for malignancy NPV = negative predictive value PPV = positive predictive value USG = ultrasonography.


Assuntos
Técnicas de Diagnóstico Molecular/métodos , Neoplasias da Glândula Tireoide/diagnóstico , Nódulo da Glândula Tireoide/diagnóstico , Transcriptoma , Ultrassonografia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia por Agulha Fina , Diagnóstico Diferencial , Feminino , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Neoplasias da Glândula Tireoide/classificação , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/classificação , Nódulo da Glândula Tireoide/genética , Nódulo da Glândula Tireoide/patologia , Adulto Jovem
17.
South Med J ; 109(5): 277-81, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27135722

RESUMO

OBJECTIVES: The African American population has a higher prevalence of advanced colon adenomas when compared with non-Hispanic whites and Hispanics, but the risk in other black populations has not been evaluated. Although the Afro-Caribbean population is a significant demographic segment in some regions of the United States, the data are limited on the prevalence of colon adenomas in this group and there is no comparison with a non-Hispanic white population. The objective of our study was to compare the prevalence of adenomas in Afro-Caribbean versus non-Hispanic white populations. METHODS: A total of 880 Afro-Caribbean patients and 1828 non-Hispanic white patients undergoing their first screening colonoscopy between January 2008 and August 2014 was included in the study. RESULTS: A total of 2708 patients met entry criteria for the study. The adenoma detection rate among Afro-Caribbeans was 29% and 31% among non-Hispanic whites. There was no statistically significant difference in the prevalence of adenomas in the two groups (P = 0.28), and the rate of advanced adenomas also was similar in both groups (8.6% in Afro-Caribbeans, 9.2% in non-Hispanic whites; P = 0.60). A multivariate analysis also found no difference in the occurrence of adenomas (P = 0.60) or advanced adenomas (P = 0.99) between Afro-Caribbeans and non-Hispanic whites. CONCLUSIONS: We found a similar adenoma detection rate and advanced adenoma prevalence among Afro-Caribbeans and non-Hispanic whites undergoing their first screening colonoscopy. As such, the Afro-Caribbean population may not have the same risk of colorectal neoplasia as what has been described for African Americans. Based on these results, it is appropriate to initiate colorectal cancer screening for Afro-Caribbeans at age 50 as recommended for non-Hispanic whites.


Assuntos
Adenoma/diagnóstico , Negro ou Afro-Americano/estatística & dados numéricos , Colonoscopia , Neoplasias Colorretais/diagnóstico , População Branca/estatística & dados numéricos , Fatores Etários , Região do Caribe/etnologia , Detecção Precoce de Câncer , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Fumar/epidemiologia , Estados Unidos/epidemiologia
18.
Sci Pharm ; 84(1): 1-18, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27110495

RESUMO

The design, synthesis, and in vitro antiproliferative activity of a novel series of sulfide (4a-i) and sulfoxide (5a-h) derivatives of benzimidazole, in which different aromatic and heteroaromatic acetamides are linked to benzimidazole via sulfide (4a-i) and sulfoxide (5a-h) linker, are reported and the structure-activity relationship is discussed. The new derivatives were prepared by coupling 2-(mercaptomethyl)benzimidazole with 2-bromo-N-(substituted) acetamides in dry acetone in the presence of anhydrous potassium carbonate. With very few exceptions, all of the synthesized compounds showed varying antiprolific activities against HepG2, MCF-7, and A549 cell lines. Compound 5a was very similar in potency to doxorubicin as an anticancer drug, with IC50 values 4.1 ± 0.5, 4.1 ± 0.5, and 5.0 ± 0.6 µg/mL versus 4.2 ± 0.5, 4.9 ± 0.6, and 6.1 ± 0.6 µg/mL against HepG2, MCF-7, and A549 cell lines, respectively. In contrast, none of the compounds showed activity against human prostate PC3 cancer cells. Additionally, the sulfoxide derivatives were more potent than the corresponding sulfides.

19.
Carbohydr Polym ; 95(1): 578-87, 2013 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-23618309

RESUMO

Honey isolate Bacillus subtilis M was cultivated in shake flasks and in 16-l bioreactor cultures to investigate cell growth, bio-metabolites production kinetics and bioprocess scalability. The respective maximal levan and levansucrase productions of 59.5 g/l and 74.1 U/ml were achieved in bioreactor cultures under pH controlled condition (pH=7.0) after only 24 h. Crude levan (levE) was isolated, characterized and fractionated into F1, F2, and F3 with different molecular weight (21.8, 13.118, 9.53 kDa). (1)H NMR and (13)C NMR spectroscopy proved that LevE and their fractions were mainly ß-(2, 6)-linked levan-type polysaccharide. The cancer chemo-preventive activity indicated that the levE and its fraction 3 were promising inhibitors of cytochrome P-450 1A activity, inducers of glutathione-S-transferase activity in Murine hepatomaHepa1c1c7cells and possessed highest radical scavenging affinity to both ROO and OH. They inhibited the induced-DNA fragmentation. None of the tested samples triggered apoptosis or necrosis in splenocytes, except F2.


Assuntos
Antineoplásicos/metabolismo , Bacillus subtilis/metabolismo , Frutanos/metabolismo , Hexosiltransferases/metabolismo , Neoplasias/enzimologia , Animais , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Antioxidantes/isolamento & purificação , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Reatores Biológicos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Citocromo P-450 CYP1A1/antagonistas & inibidores , Fragmentação do DNA , Inibidores Enzimáticos/isolamento & purificação , Inibidores Enzimáticos/metabolismo , Inibidores Enzimáticos/farmacologia , Frutanos/isolamento & purificação , Frutanos/farmacologia , Glutationa Transferase/metabolismo , Espectroscopia de Ressonância Magnética , Camundongos , Testes para Micronúcleos , Baço/citologia
20.
Carbohydr Polym ; 93(2): 740-6, 2013 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-23499118

RESUMO

A sequential optimization strategy, based on statistical experimental designs, was employed to enhance the production of invertase by Lactobacillus brevis Mm-6 isolated from breast milk. First, a 2-level Plackett-Burman design was applied to screen the bioprocess parameters that significantly influence the invertase production. The second optimization step was performed using fractional factorial design in order to optimize the amounts of variables have the highest positive significant effect on the invertase production. A maximal enzyme activity of 1399U/ml was more than five folds the activity obtained using the basal medium. Invertase was immobilized onto grafted alginate beads to improve the enzyme's stability. Immobilization process increased the operational temperature from 30 to 60°C compared to the free enzyme. The reusability test proved the durability of the grafted alginate beads for 15 cycles with retention of 100% of the immobilized enzyme activity to be more convenient for industrial uses.


Assuntos
Alginatos/metabolismo , Proteínas de Bactérias/isolamento & purificação , Ensaios Enzimáticos/métodos , Levilactobacillus brevis/enzimologia , beta-Frutofuranosidase/isolamento & purificação , Proteínas de Bactérias/metabolismo , Meios de Cultura/metabolismo , Ativação Enzimática , Estabilidade Enzimática , Enzimas Imobilizadas/metabolismo , Feminino , Ácido Glucurônico/metabolismo , Ácidos Hexurônicos/metabolismo , Humanos , Levilactobacillus brevis/isolamento & purificação , Leite Humano/microbiologia , Sacarose/metabolismo , Temperatura , beta-Frutofuranosidase/metabolismo
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