Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 29
Filtrar
1.
Arch Craniofac Surg ; 24(4): 174-178, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37654237

RESUMO

BACKGROUND: This study aimed to identify the location of the optic foramen in relation to the anterior sphenoid sinus wall, which is essential information for surgeons in planning and performing endoscopic transnasal surgery. METHODS: Computed tomography scans of 200 orbits from 100 adult patients with no abnormalities were examined. The results included the location of the optic foramen in relation to the anterior sphenoid sinus wall and the distance between them, as well as the distance from the optic foramen and the anterior sphenoid sinus wall to the carotid prominence in the posterior sphenoid sinus. RESULTS: The optic foramen was anterior to the anterior sphenoid sinus wall in 48.5% of orbits, and posterior in the remaining 51.5%. The mean distance from the optic foramen to the anterior sphenoid sinus wall was 3.82 ± 1.25 mm. The mean distances from the optic foramen and the anterior sphenoid sinus wall to the carotid prominence were 7.67 ± 1.73 and 7.95 ± 2.53 mm, respectively. CONCLUSION: The optic foramen was anterior to the anterior wall of the sphenoid sinus in approximately half of the orbits examined in this study, and posterior in the remaining half. The mean distance from the optic foramen to the anterior sphenoid sinus wall of the sphenoid sinus was 3.82 ± 1.25 mm.

2.
Phys Chem Chem Phys ; 25(35): 23829-23835, 2023 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-37641558

RESUMO

We theoretically study the role of adsorbed gas molecules on the electronic and optical properties of monolayer ß12-borophene with {a,b,c,d,e} atoms in its unit cell. We focus our attention on molecules NH3, NO, NO2, and CO, which provide additional states permitted by the host electrons. Utilizing the six-band tight-binding model based on an inversion symmetry (between {a,e} and {b,d} atoms) and the Kubo formalism, we survey the anisotropic electronic dispersion and the optical multi-interband spectrum produced by molecule-boron coupling. We consider the highest possibilities for the position of molecules on the boron atoms. For molecules on {a,e} atoms, the inherent metallic phase of ß12-borophene becomes electron-doped semiconducting, while for molecules on {b,d} and c atoms, the metallic phase remains unchanged. For molecules on {a,e} and {b,d} atoms, we observe a redshift (blueshift) optical spectrum for longitudinal/transverse (Hall) component, while for molecules on c atoms, we find a redshift (blueshift) optical spectrum for longitudinal (transverse/Hall) component. We expect that this study provides useful information for engineering field-effect transistor-based gas sensors.

3.
Comput Methods Programs Biomed ; 232: 107451, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36893580

RESUMO

BACKGROUND AND OBJECTIVES: Advanced artificial intelligence and machine learning have great potential to redefine how skin lesions are detected, mapped, tracked and documented. Here, we propose a 3D whole-body imaging system known as 3DSkin-mapper to enable automated detection, evaluation and mapping of skin lesions. METHODS: A modular camera rig arranged in a cylindrical configuration was designed to automatically capture images of the entire skin surface of a subject synchronously from multiple angles. Based on the images, we developed algorithms for 3D model reconstruction, data processing and skin lesion detection and tracking based on deep convolutional neural networks. We also introduced a customised, user-friendly, and adaptable interface that enables individuals to interactively visualise, manipulate, and annotate the images. The interface includes built-in features such as mapping 2D skin lesions onto the corresponding 3D model. RESULTS: The proposed system is developed for skin lesion screening, the focus of this paper is to introduce the system instead of clinical study. Using synthetic and real images we demonstrate the effectiveness of the proposed system by providing multiple views of a target skin lesion, enabling further 3D geometry analysis and longitudinal tracking. Skin lesions are identified as outliers which deserve more attention from a skin cancer physician. Our detector leverages expert annotated labels to learn representations of skin lesions, while capturing the effects of anatomical variability. It takes only a few seconds to capture the entire skin surface, and about half an hour to process and analyse the images. CONCLUSIONS: Our experiments show that the proposed system allows fast and easy whole body 3D imaging. It can be used by dermatological clinics to conduct skin screening, detect and track skin lesions over time, identify suspicious lesions, and document pigmented lesions. The system can potentially save clinicians time and effort significantly. The 3D imaging and analysis has the potential to change the paradigm of whole body photography with many applications in skin diseases, including inflammatory and pigmentary disorders. With reduced time requirements for recording and documenting high-quality skin information, doctors could spend more time providing better-quality treatment based on more detailed and accurate information.


Assuntos
Neoplasias Cutâneas , Imagem Corporal Total , Humanos , Inteligência Artificial , Redes Neurais de Computação , Neoplasias Cutâneas/diagnóstico por imagem , Algoritmos
4.
Case Rep Gastroenterol ; 17(1): 82-88, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36760465

RESUMO

Lately, emerging data suggest an association between the development of inflammatory bowel disease and anti-interleukin-17 therapy. Megacolon is a life-threatening complication of acute severe ulcerative colitis (ASUC), but its treatment has not yet been established in current practice guidelines. We report a rare case of known psoriasis treated by secukinumab in a patient who presented with ASUC and colonic dilatation. Neither steroids nor standard infliximab regimen was effective. Finally, rescue therapy with accelerated infliximab strategy resulted in excellent recovery. In certain cases of steroid-refractory ASUC complicated by megacolon, accelerated infliximab regimen can be an alternative to surgery.

5.
Indian J Radiol Imaging ; 32(3): 287-293, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36177272

RESUMO

Background Acoustic radiation force impulse point shear wave elastography (ARFI-pSWE), measuring shear-wave velocity (SWV), has been utilized to examine the liver stiffness caused by different etiologies. However, information on its reliability in staging liver fibrosis in chronic hepatitis B (CHB) patients is scarce. Purpose The aim of the study is to examine the diagnostic performance of ARFI-pSWE and determine the optimal SWV cut-off values to predict significant fibrosis ( F ≥2) and cirrhosis (F4) in CHB patients. Material and Methods All 114 adult CHB patients visiting the University Medical Center, Ho Chi Minh City, Vietnam between February 2019 and March 2021 underwent liver stiffness measurement using ARFI-pSWE and FibroScan. SWV results were tested against FibroScan for sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). The area under the receiver operating characteristic (AUROC) curve was used to identify the optimal SWV cut-off values. Results There was a strong agreement between ARFI-pSWE and FibroScan ( r = 0.92, p <0.001). The optimal SWV cut-off value for detecting significant fibrosis was 1.37 m/s with an AUROC of 0.975, sensitivity of 83.3%, specificity of 100%, PPV of 100%, and NPV of 81%. The optimal cut-off value for predicting cirrhosis was 1.70 m/s with an AUROC of 0.986, sensitivity of 97%, specificity of 93%, PPV of 95%, and NPV of 96%. Conclusion ARFI-pSWE could be an effective technique for evaluating liver fibrosis in CHB patients. SWV cut-off values of 1.37 and 1.70 m/s could be used to diagnose significant fibrosis and cirrhosis, respectively.

6.
J Craniofac Surg ; 33(8): 2513-2521, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35901453

RESUMO

BACKGROUND: Cleft rhinoplasty is a challenging form of nasal correction of both esthetic and functional deformities. The septal cartilage in many Asian patients are not sufficient and weak. Does a combination of the septal cartilage and the bony septum have both esthetic and functional benefits to secondary unilateral cleft rhinoplasty? PATIENTS AND METHODS: Thirty patients with a unilateral cleft lip palate underwent open rhinoplasty from October 2018 to January 2021. After preserving a 10 mm L-strut, the posterior cartilaginous and bony septum were harvested as an integrative unit. The osteocartilaginous graft was used as a caudal septal extension graft and an extended spreader graft. Correcting the asymmetry of the tip and tip projection followed. The intraoperative harvested composite graft was analyzed. Acoustic rhinometry and the 3-dimensional anthropometric measurements of the external nose were assessed before and after surgery. RESULTS: The osteocartilaginous unit was much larger than the cartilaginous part of this unit. The mean nasal tip height and the nasolabial angle increased significantly after surgery. The measurement of cross-sectional areas and volumes by acoustic rhinometry revealed that septorhinoplasty provided a significant increase in the function of both nasal cavities. CONCLUSIONS: This septal bony cartilaginous graft is effective for cleft lip nasal deformity when correcting the deviated septum, creating a supporting frame to correct the nasal tip asymmetry, improving function.


Assuntos
Fenda Labial , Fissura Palatina , Rinoplastia , Humanos , Rinoplastia/métodos , Fenda Labial/cirurgia , Septo Nasal/cirurgia , Estética Dentária , Nariz/cirurgia , Nariz/anormalidades , Fissura Palatina/cirurgia , Cartilagem/transplante , Transplante Ósseo , Resultado do Tratamento
7.
Molecules ; 27(8)2022 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-35458771

RESUMO

α-Glucosidase plays a role in hydrolyzing complex carbohydrates into glucose, which is easily absorbed, causing postprandial hyperglycemia. Inhibition of α-glucosidase is therefore an ideal approach to preventing this condition. A novel polyprenylated benzoylphloroglucinol, which we named schomburgkianone I (1), was isolated from the fruit of Garcinia schomburgkiana, along with an already-reported compound, guttiferone K (2). The structures of the two compounds were determined using NMR and HRESIMS analysis, and comparisons were made with previous studies. Compounds 1 and 2 exhibited potent α-glucosidase inhibition (IC50s of 21.2 and 34.8 µM, respectively), outperforming the acarbose positive control. Compound 1 produced wide zones of inhibition against Staphylococcus aureus and Enterococcus faecium (of 21 and 20 mm, respectively), compared with the 19 and 20 mm zones of compound 2, at a concentration of 50 µg/mL. The MIC value of compound 1 against S. aureus was 13.32 µM. An in silico molecular docking model suggested that both compounds are potent inhibitors of enzyme α-glucosidase and are therefore leading candidates as therapies for diabetes mellitus.


Assuntos
Anti-Infecciosos , Garcinia , Frutas , Garcinia/química , Inibidores de Glicosídeo Hidrolases/química , Simulação de Acoplamento Molecular , Staphylococcus aureus , alfa-Glucosidases
8.
Sensors (Basel) ; 20(19)2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33036332

RESUMO

Tin sulfide (SnS) is known for its effective gas-detecting ability at low temperatures. However, the development of a portable and flexible SnS sensor is hindered by its high resistance, low response, and long recovery time. Like other chalcogenides, the electronic and gas-sensing properties of SnS strongly depend on its surface defects. Therefore, understanding the effects of its surface defects on its electronic and gas-sensing properties is a key factor in developing low-temperature SnS gas sensors. Herein, using thin SnS films annealed at different temperatures, we demonstrate that SnS exhibits n-type semiconducting behavior upon the appearance of S vacancies. Furthermore, the presence of S vacancies imparts the n-type SnS sensor with better sensing performance under UV illumination at room temperature (25 °C) than that of a p-type SnS sensor. These results are thoroughly investigated using various experimental analysis techniques and theoretical calculations using density functional theory. In addition, n-type SnS deposited on a polyimide substrate can be used to fabricate high-stability flexible sensors, which can be further developed for real applications.

9.
Data Brief ; 30: 105497, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32300629

RESUMO

We report in this article the cytotoxicity of Streptomyces sp. SS1-1 against the human lung cancer A549 cell line, its draft genome sequence and a total of 20 predicted secondary metabolite biosynthetic gene clusters. Streptomyces sp. SS1-1 was an endophytic bacterial strain isolated from the plant Catharanthus roseus in Ho Chi Minh City, Vietnam. When cultured in the PY medium, this strain shows a cytotoxic effect on the A549 cell line. The draft genome of Streptomyces sp. SS1-1 has four contigs of total 7,815,656 bp and the GC content of this genome is 72.2%. AntiSMASH analysis reveals 20 putative biosynthetic gene clusters for the largest contig. The genome sequencing of Streptomyces sp. SS1-1 is essential for the molecular identification of gene cluster(s) responsible for secondary metabolite(s) with cytotoxic activity.

10.
ACS Chem Biol ; 14(6): 1235-1242, 2019 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-31082193

RESUMO

PF-06651600 was developed as an irreversible inhibitor of JAK3 with selectivity over the other three JAK isoforms. A high level of selectivity toward JAK3 is achieved by the covalent interaction of PF-06651600 with a unique cysteine residue (Cys-909) in the catalytic domain of JAK3, which is replaced by a serine residue in the other JAK isoforms. Importantly, 10 other kinases in the kinome have a cysteine at the equivalent position of Cys-909 in JAK3. Five of those kinases belong to the TEC kinase family including BTK, BMX, ITK, RLK, and TEC and are also inhibited by PF-06651600. Preclinical data demonstrate that inhibition of the cytolytic function of CD8+ T cells and NK cells by PF-06651600 is driven by the inhibition of TEC kinases. On the basis of the underlying pathophysiology of inflammatory diseases such as rheumatoid arthritis, inflammatory bowel disease, alopecia areata, and vitiligo, the dual activity of PF-06651600 toward JAK3 and the TEC kinase family may provide a beneficial inhibitory profile for therapeutic intervention.


Assuntos
Janus Quinase 3/antagonistas & inibidores , Inibidores de Proteínas Quinases/farmacologia , Proteínas Tirosina Quinases/antagonistas & inibidores , Pirimidinas/farmacologia , Pirróis/farmacologia , Animais , Antígenos CD/imunologia , Antígenos de Diferenciação de Linfócitos T/imunologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Humanos , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/imunologia , Lectinas Tipo C/antagonistas & inibidores , Lectinas Tipo C/imunologia , Camundongos
11.
Braz Oral Res ; 32: e126, 2018 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-30569973

RESUMO

Novel biomarkers for screening, diagnosis and monitoring the treatment of nasopharyngeal carcinoma (NPC), one of the most common cancers in Vietnam, are urgently required. Increasing evidence suggests that microRNA-141 (miR-141) is associated with NPC, owing to its ability to affect the expression of genes that modulate tumorigenesis. Unfortunately, research on miR-141 expression in Vietnamese patients is limited. Therefore, the objective of the current study was to evaluate miR-141 expression and assess whether miR-141 might be a potential biomarker for diagnosis of NPC in Vietnamese patients. Total RNA isolated from 40 NPC biopsy samples and 37 non-cancerous samples was analyzed by quantitative reverse-transcription PCR. The miR-141 expression levels were compared between NPC biopsy and non-cancerous samples. The frequency of miR-141 detection was 37.50% and 10.80% in the NPC and non-cancerous samples, respectively (p = 0.0143). The miR-141 expression was 5.27 times higher in tumor samples than non-cancerous samples. Additionally, the RR (Relative risk) and OR (Odds ratio) were 1.83 (95%CI = 1.2576-2.6675, p = 0.0016) and 4.95 (95%CI = 1.4625-16.7541, p = 0.01), respectively. In conclusion, miR-141 was up-regulated in the biopsy samples and thus may be a potential biomarker for NPC in the Vietnamese population.


Assuntos
MicroRNAs/análise , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/genética , Adolescente , Adulto , Idoso , Povo Asiático , Biomarcadores Tumorais/análise , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/patologia , Reação em Cadeia da Polimerase em Tempo Real , Valores de Referência , Regulação para Cima , Vietnã , Adulto Jovem
12.
Drug Metab Dispos ; 46(5): 692-696, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29439128

RESUMO

Targeted protein quantification using liquid chromatography-tandem mass spectrometry with stable isotope-labeled standards is recognized as the gold standard of practice for protein quantification. Such assays, however, can only cover a limited number of proteins, and developing targeted methods for larger numbers of proteins requires substantial investment. Alternatively, large-scale global proteomic experiments along with computational methods such as the "total protein approach" (TPA) have the potential to provide extensive protein quantification. In this study, we compared the TPA-based quantitation of seven major hepatic uptake transporters in four human liver tissue samples using global proteomic data obtained from two multiplexed tandem mass tag experiments (performed in two independent laboratories) to the quantitative data from targeted proteomic assays. The TPA-based quantitation of these hepatic transporters [sodium-taurocholate cotransporting polypeptide (NTCP/SLC10A1), organic anion transporter 2 (OAT2/SLC22A7), OAT7/SLC22A9, organic anion-transporting polypeptide 1B1 (OATP1B1/SLCO1B1), OATP1B3/SLCO1B3, OATP2B1/SLCO2B1, and organic cation transporter (OCT1/SLC22A1)] showed good-to-excellent correlations (Pearson r = 0.74-1.00) to the targeted data. In addition, the values were similar to those measured by targeted proteomics with 71% and 86% of the data sets falling within 3-fold of the targeted data. A comparison of the TPA-based quantifications of enzyme abundances to available literature data showed that the majority of the enzyme quantifications fell within the reference data intervals. In conclusion, these results demonstrate the capability of multiplexed global proteomic experiments to detect differences in protein expression between samples and provide reasonable estimations of protein expression levels.


Assuntos
Transporte Biológico/fisiologia , Fígado/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Preparações Farmacêuticas/metabolismo , Cromatografia Líquida/métodos , Hepatócitos/metabolismo , Humanos , Proteômica/métodos , Espectrometria de Massas em Tandem/métodos
13.
J Tissue Eng Regen Med ; 12(1): 186-190, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-27943665

RESUMO

Chronic venous leg ulcers are profoundly debilitating and result in billions in health care expenditure. Thus, there is a quest for engineered and innovative approaches. Herein we present a 63-year-old patient with a 30 year history of venous stasis and left lower extremity ulcers, which have been refractory to standard of care, anticoagulation and venous stripping. The medial ulcer was treated with transplantation of autologous adipose mesenchymal stem cell (AMSC)-enriched, high-density lipoaspirate (HDL) on OASIS wound matrix and compression therapy. The lateral ulcer was treated as a control with standard debridement and compression therapy. Four weeks later, both ulcers received daily topical timolol. Three months later, the test ulcer was completely epithelized and remains healed for over 15 months. However, the control showed minimal signs of improvement. In companion studies in our laboratory, human AMSC were cultured in Minimum Essential Medium Eagle Alpha Modifications (MEMα) with fetal bovine serum (FBS). Timolol was administered to AMSC prior to treatment with epinephrine and 104 bacteria/ml heat-killed Staphylococcus aureus. The MEMα with FBS devoid of AMSC served as a background control. After 24 h, cell culture supernatants and protein lysates were collected to determine cytokine production. There was a statistical significant decrease in pro-inflammatory interleukin-6 and -8 induced by the bacteria (to model the wound environment) in AMSC in the presence of timolol compared with control (p < 0.5). This is the first case of a successful combination of autologous AMSC-enriched, HDL with topical timolol for the healing of chronic venous leg ulcers. Copyright © 2016 John Wiley & Sons, Ltd.


Assuntos
Tecido Adiposo/citologia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Timolol/farmacologia , Cicatrização/efeitos dos fármacos , Adulto , Idoso , Doença Crônica , Terapia Combinada , Citocinas/metabolismo , Humanos , Mediadores da Inflamação/metabolismo , Masculino , Pessoa de Meia-Idade , Timolol/uso terapêutico , Transplante Autólogo , Úlcera Varicosa/patologia , Úlcera Varicosa/terapia
14.
Lancet Haematol ; 5(1): e44-e52, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29248669

RESUMO

BACKGROUND: Haemopoietic stem-cell transplantation (HSCT) eradicates host haemopoiesis before venous infusion of haemopoietic stem cells (HSCs). The pathway to cellular recovery has been difficult to study in human beings because of risks associated with interventions during aplasia. We investigated whether 18F-fluorothymidine (18F-FLT) imaging was safe during allogenic HSCT and allowed visualisation of early cellular proliferation and detection of patterns of cellular engraftment after HSCT. METHODS: Eligible patients were aged 18-55 years, had high-risk haematological malignancies. All patients underwent myeloablation followed by HSCT. The imaging primary endpoint was detection of early subclinical engraftment after HSCT with 18F-FLT PET or CT. Imaging was done 1 day before and 5 or 9, and 28 days, and 1 year after HSCT. This study is registered with ClinicalTrials.gov, number NCT01338987. FINDINGS: Between April 1, 2014, and Dec 31, 2015, 23 patients were enrolled and assessable for toxic effects after completing accrual. 18F-FLT was not associated with any adverse events or delayed engraftment. 18F-FLT imaging objectively identified subclinical bone-marrow recovery within 5 days of HSC infusion, which was up to 20 days before engraftment became clinically evident. Quantitatively, 18F-FLT intensity differed significantly between myeloablative infusion before HSCT and subclinical HSC recovery (p=0·00031). 18F-FLT biodistribution over time revealed a previously unknown path of cellular recovery of haemopoiesis in vivo that mirrored fetal ontogeny. INTERPRETATION: 18F-FLT allowed quantification and tracking of subclinical bone-marrow repopulation in human beings and revealed new insights into the biology of HSC recovery after HSCT. FUNDING: National Institutes of Health, Ben's Run/Ben's Gift, Albert and Elizabeth Tucker Foundation, Mex Frates Leukemia Fund, Jones Family fund, and Oklahoma Center for Adult Stem Cell Research.


Assuntos
Neoplasias Hematológicas/diagnóstico por imagem , Neoplasias Hematológicas/cirurgia , Transplante de Células-Tronco Hematopoéticas , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X , Adulto , Didesoxinucleosídeos/farmacocinética , Feminino , Humanos , Masculino , Projetos Piloto , Estudos Prospectivos , Distribuição Tecidual
15.
Health Care Women Int ; 39(4): 442-449, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29125392

RESUMO

Cervical cancer remains the second most common cancer amongst female aged 15 to 44 years old in Vietnam. We estimated medical costs for the treatment of cervical cancer patients. We employed the standard costing approach and health care provider perspective. We first computed the unit cost of 22 medical services related to cervical cancer treatments and then, based on standard cervical cancer treatment protocols, we estimated the cost of nine treatment scenarios for cervical cancer patients. We found that the medical costs for treatment of cervical cancers at central hospitals in Vietnam increased as the cancer progresses into later stages.


Assuntos
Custos de Cuidados de Saúde/estatística & dados numéricos , Infecções por Papillomavirus/economia , Infecções por Papillomavirus/terapia , Neoplasias do Colo do Útero/economia , Neoplasias do Colo do Útero/terapia , Adolescente , Adulto , Antineoplásicos/economia , Feminino , Gastos em Saúde , Preços Hospitalares/estatística & dados numéricos , Humanos , Vietnã , Adulto Jovem
16.
Braz. oral res. (Online) ; 32: e126, 2018. graf
Artigo em Inglês | LILACS | ID: biblio-974437

RESUMO

Abstract: Novel biomarkers for screening, diagnosis and monitoring the treatment of nasopharyngeal carcinoma (NPC), one of the most common cancers in Vietnam, are urgently required. Increasing evidence suggests that microRNA-141 (miR-141) is associated with NPC, owing to its ability to affect the expression of genes that modulate tumorigenesis. Unfortunately, research on miR-141 expression in Vietnamese patients is limited. Therefore, the objective of the current study was to evaluate miR-141 expression and assess whether miR-141 might be a potential biomarker for diagnosis of NPC in Vietnamese patients. Total RNA isolated from 40 NPC biopsy samples and 37 non-cancerous samples was analyzed by quantitative reverse-transcription PCR. The miR-141 expression levels were compared between NPC biopsy and non-cancerous samples. The frequency of miR-141 detection was 37.50% and 10.80% in the NPC and non-cancerous samples, respectively (p = 0.0143). The miR-141 expression was 5.27 times higher in tumor samples than non-cancerous samples. Additionally, the RR (Relative risk) and OR (Odds ratio) were 1.83 (95%CI = 1.2576-2.6675, p = 0.0016) and 4.95 (95%CI = 1.4625-16.7541, p = 0.01), respectively. In conclusion, miR-141 was up-regulated in the biopsy samples and thus may be a potential biomarker for NPC in the Vietnamese population.


Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Neoplasias Nasofaríngeas/genética , MicroRNAs/análise , Carcinoma Nasofaríngeo/genética , Valores de Referência , Vietnã , Biomarcadores Tumorais/análise , Estudos de Casos e Controles , Regulação para Cima , Neoplasias Nasofaríngeas/patologia , Povo Asiático , Reação em Cadeia da Polimerase em Tempo Real , Carcinoma Nasofaríngeo/patologia , Pessoa de Meia-Idade
17.
Cell Chem Biol ; 24(1): 3-8, 2017 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-28065657

RESUMO

γ-Secretase, a four-subunit transmembrane aspartic proteinase, is a highly valued drug target in Alzheimer's disease and cancer. Despite significant progress in structural studies, the respective molecular mechanisms and binding modes of γ-secretase inhibitors (GSIs) and modulators (GSMs) remain uncertain. Here, we developed biotinylated cleavable-linker photoprobes based on the BMS-708163 GSI to study its interaction with γ-secretase. Comparison of four cleavable linkers indicated that the hydrazine-labile N-1-(4,4-dimethyl-2,6-dioxocyclohexylidene)ethyl (Dde) linker was cleaved most efficiently to release photolabeled and affinity-captured presenilin-1 (PS1), the catalytic subunit of γ-secretase. Peptide mapping showed that the BMS-708163-based probe photoinserted at L282 of PS1. This insertion site was consistent with the results of molecular dynamics simulations of the γ-secretase complex with inhibitor. Taken together, this work reveals the binding site of a GSI and offers insights into the mechanism of action of this class of inhibitors.


Assuntos
Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores , Inibidores Enzimáticos/farmacologia , Sondas Moleculares/farmacologia , Oxidiazóis/farmacologia , Sulfonamidas/farmacologia , Secretases da Proteína Precursora do Amiloide/metabolismo , Sítios de Ligação/efeitos dos fármacos , Inibidores Enzimáticos/química , Humanos , Simulação de Dinâmica Molecular , Sondas Moleculares/síntese química , Sondas Moleculares/química , Estrutura Molecular , Oxidiazóis/química , Sulfonamidas/síntese química , Sulfonamidas/química
18.
Methods Mol Biol ; 1513: 11-22, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-27807827

RESUMO

A powerful interplay exists between the recognition of gene families, sensitive techniques in proteomics, and the interrogation of protein function using chemical probes. The most prominent methods, such as affinity capture, activity-based protein profiling and photoaffinity labeling, are extensively reviewed in the literature. Here we briefly review additional methods developed in the past 15 years. These include "stability proteomics" methods such as proteomically analyzed cellular thermal shift assays and the use of chemical oxidation as a probe of structure, the use of multiple bead-linked kinase inhibitors to analyze inhibitor specificities, and advances in the use of proteolysis-targeting chimeras for selective protein elimination.


Assuntos
Antineoplásicos/farmacologia , Descoberta de Drogas/métodos , Proteínas de Neoplasias/genética , Inibidores de Proteínas Quinases/farmacologia , Proteínas Quinases/genética , Proteômica/métodos , Bioensaio , Expressão Gênica , Humanos , Células K562 , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/metabolismo , Oxirredução , Desnaturação Proteica/efeitos dos fármacos , Proteínas Quinases/metabolismo , Estabilidade Proteica/efeitos dos fármacos , Termodinâmica
19.
J Mol Model ; 22(7): 165, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27342250

RESUMO

CD44 is a cell-surface glycoprotein and receptor for hyaluronan, one of the major components of the tumor extracellular matrix. There is evidence that the interaction between CD44 and hyaluronan promotes breast cancer metastasis. Recently, the molecule F-19848A was shown to inhibit hyaluronan binding to receptor CD44 in a cell-based assay. In this study, we investigated the mechanism and energetics of F-19848A binding to CD44 using molecular simulation. Using the molecular mechanics/Poisson Boltzmann surface area (MM-PBSA) method, we obtained the binding free energy and inhibition constant of the complex. The van der Waals (vdW) interaction and the extended portion of F-19848A play key roles in the binding affinity. We screened natural products from a traditional Chinese medicine database to search for CD44 inhibitors. From combining pharmaceutical requirements with docking and molecular dynamics simulations, we found ten compounds that are potentially better or equal to the F-19848A ligand at binding to CD44 receptor. Therefore, we have identified new candidates of CD44 inhibitors, based on molecular simulation, which may be effective small molecules for the therapy of breast cancer.


Assuntos
Antineoplásicos/química , Receptores de Hialuronatos/química , Ácido Hialurônico/química , Simulação de Dinâmica Molecular , Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Sítios de Ligação , Ligação Competitiva/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Humanos , Receptores de Hialuronatos/antagonistas & inibidores , Receptores de Hialuronatos/metabolismo , Ácido Hialurônico/metabolismo , Ligação de Hidrogênio , Ligantes , Estrutura Molecular , Ligação Proteica/efeitos dos fármacos , Domínios Proteicos , Termodinâmica
20.
Biomed Res Int ; 2016: 8490482, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27239476

RESUMO

Azurin from Pseudomonas aeruginosa is known anticancer bacteriocin, which can specifically penetrate human cancer cells and induce apoptosis. We hypothesized that pathogenic and commensal bacteria with long term residence in human body can produce azurin-like bacteriocins as a weapon against the invasion of cancers. In our previous work, putative bacteriocins have been screened from complete genomes of 66 dominant bacteria species in human gut microbiota and subsequently characterized by subjecting them as functional annotation algorithms with azurin as control. We have qualitatively predicted 14 putative bacteriocins that possessed functional properties very similar to those of azurin. In this work, we perform a number of quantitative and structure-based analyses including hydrophobic percentage calculation, structural modeling, and molecular docking study of bacteriocins of interest against protein p53, a cancer target. Finally, we have identified 8 putative bacteriocins that bind p53 in a same manner as p28-azurin and azurin, in which 3 peptides (p1seq16, p2seq20, and p3seq24) shared with our previous study and 5 novel ones (p1seq09, p2seq05, p2seq08, p3seq02, and p3seq17) discovered in the first time. These bacteriocins are suggested for further in vitro tests in different neoplastic line cells.


Assuntos
Antineoplásicos/farmacologia , Azurina/farmacologia , Bacteriocinas/isolamento & purificação , Bacteriocinas/farmacologia , Microbioma Gastrointestinal/fisiologia , Trato Gastrointestinal/microbiologia , Proteína Supressora de Tumor p53/metabolismo , Antineoplásicos/isolamento & purificação , Estudos de Avaliação como Assunto , Humanos , Interações Hidrofóbicas e Hidrofílicas , Simulação de Acoplamento Molecular
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA