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1.
Heliyon ; 10(5): e26426, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38463762

RESUMO

In this report, naturally available materials have been utilized in the development of acoustic absorbers. This work presents the study of the effect of oil palm trunks dust (OPTD) loading to the mechanical and acoustical properties of elastomeric thermoplastic polyurethane (TPU). Four composite sheets of 3-mm thickness were prepared by varying the OPTD loadings with 10-40% wt into the polyurethane. Density, modulus elasticity, sound absorption coefficient and sound transmission loss of the samples were measured according to corresponding standards. The OPTD is found to reduce the density of the elastomeric polyurethane and at the same time, it increases the Young's modulus up to 215 MPa. The composite material can be applied as sound absorber panel installed in front of a rigid wall with an air gap. Increasing the air gap, thus lowering the air stiffness, shifts the absorption peak to a lower frequency. With OPTD loadings, the formation of micro-pores in the inner structure helps to improve the peak of sound absorption of the panel at the resonant frequency which can reach above 0.9. As the OPTD loading has effect on density, the effect on the sound transmission loss at the mass-controlled region is also apparent.

2.
Heliyon ; 10(4): e25508, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38384568

RESUMO

Fused deposition modeling (FDM) is currently used in several fields, such as architecture, manufacturing, and medical applications. FDM was initially developed to produce and create prototypes, but the expense appears excessive for producing final products. Nevertheless, in this day and age, engineers have developed a low-cost 3D printer. One of the major issues with low-cost 3D printers is the low dimensional accuracy and high tolerances of the printed products. Herein, different printing parameters, i.e., layer thickness, printing speed, and raster angle, need to be investigated to enhance the surface roughness of the parts produced using FDM. Thus, the present study focuses on investigating the performance of the surface finish produced by FDM by manipulating different parameters such as layer thickness, printing speed, and raster angle. Taguchi's method, based on the L9 array for experimental design, was employed to elucidate the response variables. The sample model was developed following ISO standards, utilizing polylactic acid (PLA)-aluminum as the filament material. The analysis of variance results indicated that the layer thickness and raster angle significantly affect the surface roughness of the printed parts, with statistical P-values of 0.016 and 0.039, respectively. This enables an easy selection of the optimal printing parameters to achieve the desired surface roughness. The dimensional accuracy of the fabricated part was also evaluated. Thirteen dimensions of the part features were analyzed, and the results showed that the FDM machine exhibited good accuracy for most of the shapes, with a deviation below 5%.

3.
EMBO J ; 43(3): 339-361, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38238476

RESUMO

Hematopoietic stem cell (HSC) divisional fate and function are determined by cellular metabolism, yet the contribution of specific cellular organelles and metabolic pathways to blood maintenance and stress-induced responses in the bone marrow remains poorly understood. The outer mitochondrial membrane-localized E3 ubiquitin ligase MITOL/MARCHF5 (encoded by the Mitol gene) is known to regulate mitochondrial and endoplasmic reticulum (ER) interaction and to promote cell survival. Here, we investigated the functional involvement of MITOL in HSC maintenance by generating MX1-cre inducible Mitol knockout mice. MITOL deletion in the bone marrow resulted in HSC exhaustion and impairment of bone marrow reconstitution capability in vivo. Interestingly, MITOL loss did not induce major mitochondrial dysfunction in hematopoietic stem and progenitor cells. In contrast, MITOL deletion induced prolonged ER stress in HSCs, which triggered cellular apoptosis regulated by IRE1α. In line, dampening of ER stress signaling by IRE1α inihibitor KIRA6 partially rescued apoptosis of long-term-reconstituting HSC. In summary, our observations indicate that MITOL is a principal regulator of hematopoietic homeostasis and protects blood stem cells from cell death through its function in ER stress signaling.


Assuntos
Endorribonucleases , Proteínas Serina-Treonina Quinases , Camundongos , Animais , Proteínas Serina-Treonina Quinases/genética , Apoptose , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Células-Tronco Hematopoéticas/metabolismo
4.
BMC Musculoskelet Disord ; 23(1): 400, 2022 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-35484524

RESUMO

BACKGROUND: Chronic pain has a major impact on a patient's quality of life, affecting physical and psychological functioning. It has debilitating consequences on social and economic aspects too. This study aimed to explore the status of health-related quality of life (HRQoL) of Malaysian patients suffering from chronic non-malignant pain. METHODS: Four hospitals offering pain clinic services were involved in this multicentre cross-sectional study conducted between June and September 2020. Adult patients who had been diagnosed with non-malignant chronic pain lasting for at least three months and able to communicate in English or Malay language were recruited in this study. Participants were informed about the study and were made aware that their participation was entirely voluntary. A battery of questionnaires consists of the EuroQol-5 dimensions-5 levels questionnaire (EQ-5D-5L) and the EuroQol visual analogue scale (EQ VAS), the Pain Self-Efficacy questionnaire (PSEQ) and the Pain Catastrophizing Scale (PCS) were self-administered by the patients. Besides, a structured questionnaire was used to collect their socio-demographic information, pain condition, sleep quality and working status. Participants' usage of pain medications was quantified using the Quantitative Analgesic Questionnaire (QAQ). RESULTS: A total of 255 patients participated in this study. A median EQ-5D index value of 0.669 (IQR: 0.475, 0.799) and a median EQ VAS score of 60.0 (IQR: 50.0, 80.0) were recorded. Malay ethnicity (Adj. B: 0.77; 95% CI: 0.029, 0.126; p = 0.002) and a higher level of self-efficacy (Adj. B: 0.008; 95% CI: 0.006, 0.011; p < 0.001) were predictors of a better HRQoL, while suffering from pain in the back and lower limb region (Adj. B: -0.089; 95% CI: - 0.142, - 0.036; p = 0.001), the use of a larger amount of pain medications (Adj. B: -0.013; 95% CI: - 0.019, - 0.006; p < 0.001), and a higher degree of pain magnification (Adj. B: -0.015; 95% CI: - 0.023, - 0.008; p < 0.001) were associated with a poorer HRQoL. CONCLUSIONS: These findings suggested that Malay ethnicity and a higher level of self-efficacy were predictors of a better HRQoL in patients with chronic pain, whereas pain-related factors such as higher usage of medication, specific pain site and pain magnification style were predictors of poorer HRQoL.


Assuntos
Dor Crônica , Qualidade de Vida , Adulto , Dor Crônica/diagnóstico , Estudos Transversais , Humanos , Qualidade de Vida/psicologia , Inquéritos e Questionários , Escala Visual Analógica
5.
ACS Appl Mater Interfaces ; 14(11): 13836-13847, 2022 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-35286068

RESUMO

Both 3-hydroxy-2-butanone and triethylamine are highly toxic and harmful to human health, and their chronic inhalation can cause respiratory diseases, eye lesions, dermatitis, headache, dizziness, drowsiness, and even fatality. Developing sensors for detecting such toxic gases with low power consumption, high response with superselectivity, and stability is crucial for healthcare and environmental monitoring. This study presents a typical gas sensor fabricated based on AuPdO modified Cu-doped K2W4O13 nanowires, which can selectively detect 3-hydroxy-2-butanone and triethylamine at 120 and 200 °C, respectively. The sensor displays excellent sensing performance at reduced operating temperature, high selectivity, fast response/recovery, and stability, which can be attributed to a synergistic effect of Cu dopants and AuPdO nanoparticles on the K2W4O13 host. The enhanced sensing response and selectivity could be attributed to the oxygen vacancies/defects, bandgap excitation, the electronic sensitization, the reversible redox reaction of PdO and Cu, the cocatalytic activity of AuPdO, and Schottky barrier contacts at the interface of tungsten oxide and Au. The significant variations in the activation capacities of Cu-doped K2W4O13, Pd/PdO, and Au nanoparticles toward 3H-2B and TEA, and the diffusion depth of the two gases in the coated sensing layer may cause dual selectivity. The designed gas sensor materials can serve as a sensitive target for detecting toxic biomarkers and hold broad application prospects in food and environmental safety inspection.

6.
EMBO J ; 41(8): e109463, 2022 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-35229328

RESUMO

In order to support bone marrow regeneration after myeloablation, hematopoietic stem cells (HSCs) actively divide to provide both stem and progenitor cells. However, the mechanisms regulating HSC function and cell fate choice during hematopoietic recovery remain unclear. We herein provide novel insights into HSC regulation during regeneration by focusing on mitochondrial metabolism and ATP citrate lyase (ACLY). After 5-fluorouracil-induced myeloablation, HSCs highly expressing endothelial protein C receptor (EPCRhigh ) were enriched within the stem cell fraction at the expense of more proliferative EPCRLow HSCs. These EPCRHigh HSCs were initially more primitive than EPCRLow HSCs and enabled stem cell expansion by enhancing histone acetylation, due to increased activity of ACLY in the early phase of hematopoietic regeneration. In the late phase of recovery, HSCs enhanced differentiation potential by increasing the accessibility of cis-regulatory elements in progenitor cell-related genes, such as CD48. In conditions of reduced mitochondrial metabolism and ACLY activity, these HSCs maintained stem cell phenotypes, while ACLY-dependent histone acetylation promoted differentiation into CD48+ progenitor cells. Collectively, these results indicate that the dynamic control of ACLY-dependent metabolism and epigenetic alterations is essential for HSC regulation during hematopoietic regeneration.


Assuntos
ATP Citrato (pro-S)-Liase , Medula Óssea , ATP Citrato (pro-S)-Liase/genética , ATP Citrato (pro-S)-Liase/metabolismo , Receptor de Proteína C Endotelial/metabolismo , Células-Tronco Hematopoéticas/fisiologia , Histonas/metabolismo
7.
Cells Tissues Organs ; 211(2): 212-221, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-33640894

RESUMO

Although ribosomes are generally known to be a translational machinery, some ribosomal proteins also have accessory functions involving early development and differentiation. Previously, we reported that ribosome incorporation into human dermal fibroblasts generated embryoid body-like cell clusters, altered cellular fate, and differentiated into cells of all 3 germ layers. However, the molecular phenomena induced by ribosome incorporation in the cell remained unknown. Here, we demonstrate that ribosome incorporation into human breast cancer cell MCF7 leads to ribosome-induced cell clusters (RICs) formation accompanying with epithelial-mesenchymal transition (EMT)-like gene expression. Following ribosome incorporation, MCF7 cells cease proliferation, which is caused by inhibition of cell cycle transition from G0 to G1 phase. Further, MCF7 RICs show induced expression of EMT markers, TGF-ß1 and Snail along with autophagy markers and tumor suppressor gene p53. These findings indicate that the incorporation of ribosome into cancer cells induces an EMT-like phenomenon and changes the cancer cell characteristics.


Assuntos
Neoplasias da Mama , Transição Epitelial-Mesenquimal , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Pontos de Checagem do Ciclo Celular , Diferenciação Celular , Linhagem Celular Tumoral , Movimento Celular , Transição Epitelial-Mesenquimal/genética , Feminino , Humanos , Ribossomos/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Fator de Crescimento Transformador beta1/farmacologia
8.
Cell Mol Biol (Noisy-le-grand) ; 67(2): 33-43, 2021 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-34817376

RESUMO

Notch signaling is an evolutionary conserved pathway that plays a central role in development and differentiation of eukaryotic cells. It has been well documented that Notch signaling is inevitable for neuronal cell growth and homeostasis. It regulates process of differentiation from early embryonic stages to fully developed brain. To achieve this streamlined development of neuronal cells, a number of cellular processes are being orchestrated by the Notch signaling. Abrogated Notch signaling is related to several brain tumors, including glioblastomas. On the other hand, microRNAs are small molecules that play decisive role in mediating and modulating Notch signaling. This review discusses the crucial role of Notch signaling in development of nervous system and how this versatile pathway interplay with microRNAs in glioblastoma. This review sheds light on interplay between abrogated Notch signaling and miRNAs in the regulation of neuronal differentiation with special focus on miRNAs mediated regulation of tumorigenesis in glioblastoma. Furthermore, it discusses different aspects of neurogenesis modulated by the Notch signaling that could be exploited for the identification of new diagnostic tools and therapies for the treatment of glioblastoma.


Assuntos
Neoplasias Encefálicas/genética , Glioblastoma/genética , MicroRNAs/genética , Neurogênese/genética , Receptores Notch/metabolismo , Transdução de Sinais , Animais , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Carcinogênese/genética , Carcinogênese/metabolismo , Carcinogênese/patologia , Diferenciação Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Glioblastoma/metabolismo , Glioblastoma/patologia , Humanos
9.
BMJ Open Ophthalmol ; 6(1): e000790, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34557590

RESUMO

OBJECTIVE: To estimate prevalence and causes of blindness and vision impairment and assess cataract surgical coverage and quality of cataract surgery in Kabul. METHODS AND ANALYSIS: A total of 3751 adults aged 50 years and above were recruited from 77 randomly selected clusters. Each participant underwent presenting and pinhole visual acuity assessment and lens examination. Those with pinhole visual acuity <6/12 in either eye had a dilated fundus examination to determine the cause of reduced vision. Those with apparent lens opacity were interviewed on barriers to cataract surgery. RESULTS: The age-adjusted and sex-adjusted prevalence of blindness was 2.4% (95% CI: 1.8% to 3.0%). Prevalence of severe, moderate and mild vision impairment was 2.2% (95% CI: 1.7% to 2.7%), 6.9% (95% CI: 6.0% to 7.9%) and 8.7% (95% CI: 7.5% to 9.8%), respectively. Cataract was the main cause of blindness (36.8%), severe (54.4%) and moderate (46.1%) vision impairment. Uncorrected refractive error was the leading cause of mild vision impairment (20.3%). Age-related macular degeneration was the second leading cause of blindness (23.0%). In people with a presenting visual acuity of <3/60, cataract surgical coverage was 89.7%, and effective cataract surgical coverage was 67.8%. The major barriers to uptake of the available cataract surgical services were the need for surgery was not felt (23.7%) and cost (22.0%). CONCLUSION: Kabul province has a high prevalence of blindness, largely due to cataract and age-related macular generation. The quality of cataract surgery is also lagging in terms of good visual outcomes. This calls for immediate efforts to improving the reach and quality of existing eye services and readiness to respond to the increasing burden of posterior eye disease.

10.
Biochem Biophys Rep ; 26: 100946, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33644423

RESUMO

Previously we reported that, lactic acid bacteria (LAB) can induce human dermal fibroblast (HDF) cells to form multipotent cell clusters which are able to transdifferentiate into three germ layer derived cell lineages. Later on, we confirmed that ribosome is responsible for the LAB-induced transdifferentiation and ribosomes from diverse organisms can mimic the LAB effect on HDF cells. In our present study we have shown that, upon incorporation of ribosomes, non-small cell lung cancer cell line A549 and gastric tubular adenocarcinoma cell line H-111-TC are transformed into spheroid like morphology those can be transdifferentiated into adipocytes and osteoblast. Our qPCR analysis has revealed that, during the formation of ribosome induced cancer cell spheroids, the expression of the cancer cell associated markers and cell cycle/proliferation markers were altered at different time point. Through our investigation, here we report a novel and a non-invasive approach for cancer cell reprogramming by incorporating ribosomes.

11.
Trends Cell Biol ; 30(11): 835-836, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32921525

RESUMO

The transplantation of healthy hematopoietic stem cells (HSCs) contained in the bone marrow is a frontline treatment option for hematopoietic diseases. Detailed analysis of post-transplant HSC kinetics is crucial as the initial engraftment of HSCs influences prognosis. Dong et al. have explored the dynamic change in HSC cell fate upon bone marrow transplantation through the utilization of single-cell transcriptomic analysis.


Assuntos
Transplante de Medula Óssea , Transplante de Células-Tronco Hematopoéticas , Diferenciação Celular , Células-Tronco Hematopoéticas , Humanos , Transcriptoma
12.
Cell Death Dis ; 11(2): 146, 2020 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-32094322

RESUMO

Renal fibrosis arises by the generation of matrix-producing fibroblasts and myofibroblasts through the epithelial-mesenchymal transition (EMT), a process in which epithelial cells undergo a transition into a fibroblast phenotype. A key feature of the EMT is the reorganization of the cytoskeletons, which may involve the Ca2+-binding protein S100A16, a newly reported member of the S100 protein family. However, very few studies have examined the role of S100A16 in renal tubulointerstitial fibrosis. In this study, S100A16 expression was examined by immunohistochemical staining of kidney biopsy specimens from patients with various nephropathies and kidney tissues from a unilateral ureteral obstruction (UUO) mouse model. Renal histological changes were investigated in S100A16Tg, S100A16+/-, and WT mouse kidneys after UUO. The expression of epithelia marker E-cadherin, mesenchymal markers N-cadherin, and vimentin, extracellular matrix protein, and S100A16, as well as the organization of F-actin, were investigated in S100A16 overexpression or knockdown HK-2 cells. Mass spectrometry was employed to screen for S100A16 binding proteins in HK-2 cells. The results indicated that S100A16 is high expressed and associated with renal tubulointerstitial fibrosis in patient kidney biopsies and in those from UUO mice. S100A16 promotes renal interstitial fibrosis in UUO mice. S100A16 expression responded to increasing Ca2+ and interacted with myosin-9 during kidney injury or TGF-ß stimulation to promote cytoskeleton reorganization and EMT progression in renal tubulointerstitial fibrosis. Therefore, S100A16 is a critical regulator of renal tubulointerstitial fibroblast activation and is therefore a potential therapeutic target for the treatment of renal fibrosis.


Assuntos
Citoesqueleto/metabolismo , Fibrose/metabolismo , Cadeias Pesadas de Miosina/metabolismo , Proteínas S100/metabolismo , Animais , Proteínas de Ligação ao Cálcio/metabolismo , Proteínas do Citoesqueleto/metabolismo , Células Epiteliais/metabolismo , Transição Epitelial-Mesenquimal/fisiologia , Fibrose/patologia , Humanos , Rim/patologia , Nefropatias/patologia , Camundongos Endogâmicos C57BL , Miosinas/metabolismo
13.
FASEB J ; 34(3): 4591-4601, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32017279

RESUMO

Injury of renal tubular epithelial cells is a key feature of the pathogenicity associated with tubulointerstitial fibrosis and other kidney diseases. HUWE1, an E3 ubiquitin ligase, acts by participating in ubiquitination and degradation of its target proteins. However, the detailed mechanisms by which HUWE1 might regulate fibrosis in renal tubular epithelial cells have not been established. Here, the possible regulation of renal tubulointerstitial fibrosis by HUWE1 was investigated by examining the expression of HUWE1 and EGFR in unilateral ureteral obstruction (UUO) mice. Markedly consistent reciprocal changes in HUWE1 and EGFR expression were observed at the protein and mRNA levels in the kidney after UUO injury. Expression of HUWE1 inhibited TGF-ß-induced injury to HK-2 cells, while HUWE1 overexpression decreased the expression of EGFR. Further analysis indicated that HUWE1 physically interacted with EGFR and promoted its ubiquitination and degradation. HUWE1 expression also showed clinical relevance in renal disease, as it notably decreased in multiple types of clinical nephropathy, while EGFR expression significantly increased when compared to the normal kidney. Therefore, this study demonstrated that HUWE1, which serves as an E3 ubiquitin ligase specific for EGFR, promotes EGFR ubiquitination and degradation, thereby regulating EGFR expression and providing protection against kidney injury.


Assuntos
Fibrose/metabolismo , Fibrose/patologia , Nefropatias/metabolismo , Nefropatias/patologia , Rim/metabolismo , Rim/patologia , Proteínas Supressoras de Tumor/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Animais , Western Blotting , Linhagem Celular , Receptores ErbB/genética , Receptores ErbB/metabolismo , Imunofluorescência , Humanos , Imuno-Histoquímica , Nefropatias/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Transdução de Sinais/genética , Transdução de Sinais/fisiologia , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismo , Proteínas Supressoras de Tumor/genética , Ubiquitina-Proteína Ligases/genética , Ubiquitinação/genética , Ubiquitinação/fisiologia , Obstrução Ureteral/genética , Obstrução Ureteral/metabolismo
14.
World J Plast Surg ; 8(2): 181-184, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31309054

RESUMO

BACKGROUND: About 60-70% of ganglion cysts are found in dorsal part of the wrist. This study compared aspiration followed by intra-lesional steroid (triamcinolone acetate) injection and surgical excision in the management of dorsal wrist ganglion. METHODS: From Aug 2016 to Aug 2018 in Department of General Surgery, Government Medical College Srinagar, India, 86 Patients with dorsal wrist ganglions were enrolled. The patients were divided to two groups undergoing two different treatment modalities including 68 patients of aspiration with intralesional triamcinolone acetonide injected into the cyst (group A) and 18 patients with surgical excision (group B). Follow up time was 1, 3, 6 and 12 months. RESULTS: Successful treatment was noticed in 59 patients of group A (86.8%), and in 15 patients of group B (83.3%). CONCLUSION: Aspiration followed by intra-lesional steroid injection was better managed in comparison to surgical excision.

15.
Exp Mol Med ; 51(5): 1-12, 2019 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-31113930

RESUMO

The main functions of the epithelial sodium channel (ENaC) in the kidney distal nephron are mediation of sodium and water balance and stabilization of blood pressure. Estrogen has important effects on sodium and water balance and on premenopausal blood pressure, but its role in the regulation of ENaC function is not fully understood. Female Sprague-Dawley rats were treated with 17ß-estradiol for 6 weeks following bilateral ovariectomy. Plasma estrogen, aldosterone, creatinine, and electrolytes were analyzed, and α-ENaC and derlin-1 protein expression in the kidney was determined by immunohistochemistry and western blotting. The expression levels of α-ENaC, derlin-1, AMPK, and related molecules were also examined by western blotting and real-time PCR in cultured mouse renal collecting duct (mpkCCDc14) epithelial cells following estrogen treatment. Immunofluorescence and coimmunoprecipitation were performed to detect α-ENaC binding with derlin-1 and α-ENaC ubiquitination. The results demonstrated that the loss of estrogen elevated systolic blood pressure in ovariectomized (OVX) rats. OVX rat kidneys showed increased α-ENaC expression but decreased derlin-1 expression. In contrast, estrogen treatment decreased α-ENaC expression but increased derlin-1 expression in mpkCCDc14 cells. Moreover, estrogen induced α-ENaC ubiquitination by promoting the interaction of α-ENaC with derlin-1 and evoked phosphorylation of AMPK in mpkCCDc14 cells. Our study indicates that estrogen reduces ENaC expression and blood pressure in OVX rats through derlin-1 upregulation and AMPK activation.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Canais Epiteliais de Sódio/metabolismo , Estrogênios/metabolismo , Proteínas de Membrana/metabolismo , Animais , Pressão Sanguínea , Linhagem Celular , Ativação Enzimática , Canais Epiteliais de Sódio/análise , Feminino , Rim/fisiologia , Rim/ultraestrutura , Proteínas de Membrana/análise , Proteínas de Membrana/genética , Camundongos , Ratos , Ratos Sprague-Dawley
16.
Anal Biochem ; 566: 50-57, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30439368

RESUMO

A novel label-free electrochemiluminescent (ECL) immunosensor based upon luminol functionalized platinum nanoparticles loaded on graphene sheets (Lu-Pt@GS) as sensing platform was fabricated for highly sensitive and selective determination of prostate specific antigen (PSA). In this work, for the first time luminol was employed as both ECL luminescence reagent and reductants to in-situ reduce H2PtCl6 forming Pt NPs on surface of GS. A great deal of luminol could be attached onto the surface of Pt NPs within the reduction process, which can generate strong ECL emission. Pt NPs not only could enhance ECL signals of luminol but supply active sites for the immobilization of PSA antibodies with micro friendly environment. For preventing the consecutive reaction among luminol and H2O2, single-step cycle pulse was adopted, resulting in stable and strong ECL signals. Under optimized experimental conditions, the proposed ECL immunosensor acquired a wide linear range of 1 pg/mL to 10 ng/mL with a relatively low detection limit of 0.3 pg/mL for PSA. Furthermore, due to high sensitivity, simplicity and cost-effectiveness, the designed immunosensor provides a new method for detecting other important biomarkers in clinical analysis.


Assuntos
Técnicas Biossensoriais/métodos , Técnicas Eletroquímicas/métodos , Imunoensaio/métodos , Calicreínas/análise , Medições Luminescentes/métodos , Luminol/química , Nanopartículas Metálicas/química , Antígeno Prostático Específico/análise , Anticorpos Imobilizados/química , Ensaios Enzimáticos/métodos , Grafite/química , Humanos , Limite de Detecção , Substâncias Luminescentes/química , Masculino , Platina/química
17.
Dev Growth Differ ; 60(5): 241-247, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29845598

RESUMO

Ribosomes are intracellular organelles ubiquitous in all organisms, which translate information from mRNAs to synthesize proteins. They are complex macromolecules composed of dozens of proteins and ribosomal RNAs. Other than translation, some ribosomal proteins also have side-jobs called "Moonlighting" function. The majority of these moonlighting functions influence cancer progression, early development and differentiation. Recently, we discovered that ribosome is involved in the regulation of cellular transdifferentiation of human dermal fibroblasts (HDFs). In vitro incorporation of ribosomes into HDFs arrests cell proliferation and induces the formation of cell clusters, that differentiate into three germ layer derived cells upon induction by differentiation mediums. The discovery of ribosome induced transdifferentiation, that is not based on genetic modification, find new possibilities for the treatment of cancer and congenital diseases, as well as to understand early development and cellular lineage differentiation.


Assuntos
Transdiferenciação Celular/fisiologia , Ribossomos/metabolismo , Animais , Proliferação de Células/genética , Proliferação de Células/fisiologia , Transdiferenciação Celular/genética , Camadas Germinativas/citologia , Camadas Germinativas/metabolismo , Humanos
18.
Iran J Pharm Res ; 16(3): 953-965, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29201086

RESUMO

Quinoxalines display diverse and interesting pharmacological activities as antibacterial, antiviral, antiparasitic and anticancer agents. Particularly, their 1`4-di-N-oxide derivatives have proved to be cytotoxic agents that are active under hypoxic conditions as that of solid tumours. A new series of quinoxaline 1`4-di-N-oxide substitutes at 7-position with esters group were synthetized and characterized by infrared (IR), proton nuclear magnetic resonance (1H-NMR), spectroscopy, and elemental analysis. Seventeen derivatives (M1-M3, E1-E8, P1-P3 and DR1-DR3) were selected and evaluated for antitumor activities using the NCI-60 human tumor cell lines screen. Results showed that E7, P3 and E6 were the most active compounds against the cell lines tested. Substitutions at 7-position with esters group not necessarily affect the biological activity, but the nature of the esters group could exert an influence on the selectivity. Additionally, substitutions at 2-position influenced the cytotoxic activity of the compounds.

19.
Laryngoscope ; 126(11): 2445-2450, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27296477

RESUMO

OBJECTIVES/HYPOTHESIS: Surgery and postoperative radiation therapy are commonly used in the treatment of advanced sinonasal cancer. However, post-treatment radiation changes to the brain often mimic radiologic findings suggestive of tumor recurrence, leading to potential unnecessary intracranial biopsies. The objective of this study was to determine clinical factors that predict signs of tumor recurrence versus radiation necrosis in post-therapy sinonasal malignancies with intracranial extension. STUDY DESIGN: Retrospective study. METHODS: Twenty-six patients with sinonasal malignancy with intracranial extension underwent surgery and radiation ± chemotherapy between 2010 and 2014 at the University of Arizona. We analyzed sinonasal cancer type, stage, total radiation dosimetry, time until imaging changes, surgical pathology, associated imaging, and patient demographics. RESULTS: Thirteen of 26 patients had postoperative imaging changes seen on surveillance magnetic resonance imaging (MRI). Five were deemed to have tumor recurrence due to new metastasis seen on positron emission tomography/computed tomography scan. Four patients were observed with serial imaging that confirmed pseudoprogression. In four patients, there was sufficient concern due to persistent MRI changes, which prompted surgical biopsy, and only one of them was positive for tumor recurrence. Factors that favored tumor recurrence included faster onset of imaging changes on MRI (55 vs. 186 days, P < .05). CONCLUSIONS: Intracranial tumor recurrence can be difficult to distinguish between radiation necrosis in sinonasal cancers treated with surgery and postoperative radiation ± chemotherapy. Patients with sub-total resection and rapid onset of MRI changes in postsurveillance scans are more likely to have tumor recurrence versus radiation necrosis. Future imaging techniques or tests that investigate tumor biomarkers are necessary to prevent unnecessary biopsies. LEVEL OF EVIDENCE: 4 Laryngoscope, 126:2445-2450, 2016.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Encéfalo/patologia , Encéfalo/efeitos da radiação , Recidiva Local de Neoplasia/diagnóstico por imagem , Neoplasias Induzidas por Radiação/diagnóstico por imagem , Neoplasias dos Seios Paranasais/diagnóstico por imagem , Complicações Pós-Operatórias/diagnóstico por imagem , Lesões por Radiação/patologia , Idoso , Encéfalo/diagnóstico por imagem , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/cirurgia , Terapia Combinada , Diagnóstico Diferencial , Progressão da Doença , Feminino , Humanos , Incidência , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Necrose/diagnóstico por imagem , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/etiologia , Neoplasias Induzidas por Radiação/epidemiologia , Neoplasias Induzidas por Radiação/etiologia , Neoplasias dos Seios Paranasais/radioterapia , Neoplasias dos Seios Paranasais/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Lesões por Radiação/diagnóstico por imagem , Estudos Retrospectivos , Fatores de Tempo
20.
Neurosurgery ; 78(1): 84-90, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26348011

RESUMO

BACKGROUND: Unplanned readmission after surgical procedures is an important quality metric. Yet, readmission rates and causes have not been evaluated for patients after transsphenoidal surgery for pituitary tumors. OBJECTIVE: To analyze unplanned 30-day readmissions at a pituitary center and to encourage the development of effective clinical pathways to prevent readmission. METHODS: A retrospective review of adult patients who underwent transsphenoidal surgery for pituitary lesions at Barrow Neurological Institute (January 2011-March 2014) was performed to identify causes of unplanned readmission within 30 days of surgery. Patient demographics, tumor details, surgical complications, and endocrine function were documented. RESULTS: Of 303 patients who had transsphenoidal surgery, 27 (8.9%) were readmitted within 30 days. Most of the 27 (15 [55.6%]) had delayed hyponatremia. Other causes were diabetes insipidus (4 [14.8%]), adrenal insufficiency (2 [7.4%]), and cerebrospinal fluid leak, epistaxis, cardiac arrhythmia, pneumonia, urinary tract infection, and hypoglycemia (1 each [3.7%]). Outpatient sodium screening was performed as needed. In cases of hyponatremia, the mean postoperative day of readmission was day 8 (range, 6-12 days) and the mean serum sodium was 119 mmol/L (range, 111-129 mmol/L). Numerous patient and surgical factors were examined, and no specific predictors of readmission were identified. We developed an outpatient care pathway for managing hyponatremia with the goal of improving readmission rates. CONCLUSION: This study establishes a quality benchmark for readmission rates after transsphenoidal surgery for pituitary lesions and identifies delayed hyponatremia as the primary cause. Implementation of an outpatient care pathway for managing hyponatremia may improve readmission rates.


Assuntos
Adenoma/cirurgia , Hiponatremia/diagnóstico , Readmissão do Paciente/tendências , Neoplasias Hipofisárias/cirurgia , Complicações Pós-Operatórias/diagnóstico , Seio Esfenoidal/cirurgia , Adenoma/diagnóstico , Adenoma/epidemiologia , Adulto , Idoso , Vazamento de Líquido Cefalorraquidiano/diagnóstico , Vazamento de Líquido Cefalorraquidiano/epidemiologia , Feminino , Humanos , Hiponatremia/epidemiologia , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo
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