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1.
Artigo em Inglês | MEDLINE | ID: mdl-38340307

RESUMO

Alzheimer's disease is one of the most common causes of dementia and is a neurodegenerative disease that occurs with memory loss, loss of language, thinking and problem-solving skills. In this study, it was aimed to reveal the relationship between Alzheimer's disease and the variable number tandem repeat (VNTR) polymorphism in the aggrecan (ACAN) gene. Thus, it is thought that it will contribute to enlightenment about disease by contributing to the pathophysiology of Alzheimer's disease. A total of 203 people, including 102 patients diagnosed with Alzheimer's and 101 healthy individuals, were included in the study. Deoxyribonucleic acid (DNA) extraction was performed from the blood samples taken. The variable number tandem repeat (VNTR) polymorphism of the ACAN gene was determined using the Polymerase Chain Reaction (PCR) method. In our study, the 30 R, 31 R and 33 R alleles were the most repetitive alleles in patients and controls. 30 R, 31 R and shorter alleles were more common in patients than in the control group and were found to be statistically significant (p = 0.042). According to our results, 30 R and 31 R alleles of the VNTR polymorphism in the ACAN gene may be associated with Alzheimer's disease. In addition, having less than 30 repeat alleles increases the risk of the disease by 2,202 times. Our study is the first to investigate the relationship between ACAN gene VNTR polymorphism and Alzheimer's disease. Further studies are needed to definitively relate it.

2.
Artigo em Inglês | MEDLINE | ID: mdl-34770196

RESUMO

Microbial C1 gas conversion technologies have developed into a potentially promising technology for converting waste gases (CO2, CO) into chemicals, fuels, and other materials. However, the mass transfer constraint of these poorly soluble substrates to microorganisms is an important challenge to maximize the efficiencies of the processes. These technologies have attracted significant scientific interest in recent years, and many reactor designs have been explored. Syngas fermentation and hydrogenotrophic methanation use molecular hydrogen as an electron donor. Furthermore, the sequestration of CO2 and the generation of valuable chemicals through the application of a biocathode in bioelectrochemical cells have been evaluated for their great potential to contribute to sustainability. Through a process termed microbial chain elongation, the product portfolio from C1 gas conversion may be expanded further by carefully driving microorganisms to perform acetogenesis, solventogenesis, and reverse ß-oxidation. The purpose of this review is to provide an overview of the various kinds of bioreactors that are employed in these microbial C1 conversion processes.


Assuntos
Reatores Biológicos , Gases , Fermentação , Hidrogênio , Oxirredução
3.
Sci Adv ; 7(27)2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34215585

RESUMO

Targeting of the most aggressive tumor cell subpopulations is key for effective management of most solid malignancies. However, the metastable nature of tumor heterogeneity, which allows cells to transition between strong and weak tumorigenic phenotypes, and the lack of reliable markers of tumor-promoting properties hamper identification of the most relevant cells. To overcome these obstacles, we designed a functional microRNA (miR)-based live-cell reporter assay to identify highly tumorigenic cells in xenotransplants of primary Ewing sarcoma (EwS) 3D cultures. Leveraging the inverse relationship between cell pluripotency and miR-145 expression, we successfully separated highly tumorigenic, metastasis-prone (miR-145low) cells from poorly tumorigenic, nonmetastatic (miR-145high) counterparts. Gene expression and functional studies of the two cell populations identified the EPHB2 receptor as a prognostic biomarker in patients with EwS and a major promoter of metastasis. Our study provides a simple and powerful means to identify and isolate tumor cells that display aggressive behavior.

4.
Life Sci Alliance ; 4(2)2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33361335

RESUMO

Synovial sarcoma (SyS) is an aggressive mesenchymal malignancy invariably associated with the chromosomal translocation t(X:18; p11:q11), which results in the in-frame fusion of the BAF complex gene SS18 to one of three SSX genes. Fusion of SS18 to SSX generates an aberrant transcriptional regulator, which, in permissive cells, drives tumor development by initiating major chromatin remodeling events that disrupt the balance between BAF-mediated gene activation and polycomb-dependent repression. Here, we developed SyS organoids and performed genome-wide epigenomic profiling of these models and mesenchymal precursors to define SyS-specific chromatin remodeling mechanisms and dependencies. We show that SS18-SSX induces broad BAF domains at its binding sites, which oppose polycomb repressor complex (PRC) 2 activity, while facilitating recruitment of a non-canonical (nc)PRC1 variant. Along with the uncoupling of polycomb complexes, we observed H3K27me3 eviction, H2AK119ub deposition and the establishment of de novo active regulatory elements that drive SyS identity. These alterations are completely reversible upon SS18-SSX depletion and are associated with vulnerability to USP7 loss, a core member of ncPRC1.1. Using the power of primary tumor organoids, our work helps define the mechanisms of epigenetic dysregulation on which SyS cells are dependent.


Assuntos
Montagem e Desmontagem da Cromatina , Cromatina/genética , Epigênese Genética , Regulação Neoplásica da Expressão Gênica , Sarcoma Sinovial/genética , Sítios de Ligação , Cromatina/metabolismo , Proteínas de Ligação a DNA/química , Proteínas de Ligação a DNA/metabolismo , Perfilação da Expressão Gênica , Histonas/metabolismo , Humanos , Complexos Multiproteicos/metabolismo , Organoides , Ligação Proteica , Transporte Proteico , Sarcoma Sinovial/metabolismo , Transcriptoma
5.
Chemosphere ; 261: 127734, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32771714

RESUMO

CO is one of the toxic components of syngas, which is the major source of air pollution. Syngas fermentation technology has the ability to convert toxic gases into valuable biofuels, such as ethanol. Fermentative ethanol production is an important method that can be used to promote environmental protection. CO can be converted into ethanol, via the Wood-Ljungdahl pathway, using Clostridium ljungdahlii. The components of the growing medium--especially the trace-element solution and yeast extract--are the main reasons for the high costs associated with this process, however, and this especially impacts scaled-up operations. In this study, cheaper substitutes for these components were used in order to determine their effect on ethanol production. The study comprised three main parts--the optimization of CO concentration, and the substitution of corn syrup and whey powder in the process. The optimum volume of CO for ethanol production was found to be 10 mL. Corn syrup can be used instead of trace-element solution, but the use of yeast extract with the corn syrup was determined to be essential. Up to 1.4 g/L ethanol production was observed with the addition of 15 mL corn syrup. Whey powder had the advantage of being usable without yeast extract, with up to 2.5 g/L ethanol being produced from a 30-g/L concentration. The main finding was that either corn syrup or whey powder can be used as substitutes for expensive basal-medium components.


Assuntos
Biocombustíveis/análise , Monóxido de Carbono/química , Etanol/análise , Xarope de Milho Rico em Frutose/química , Soro do Leite/química , Monóxido de Carbono/metabolismo , Clostridium/metabolismo , Meios de Cultura/metabolismo , Etanol/metabolismo , Fermentação , Xarope de Milho Rico em Frutose/metabolismo , Pós , Soro do Leite/metabolismo
7.
Cell Rep ; 30(13): 4567-4583.e5, 2020 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-32234488

RESUMO

Ewing sarcoma (EwS) is associated with poor prognosis despite current multimodal therapy. Targeting of EWS-FLI1, the fusion protein responsible for its pathogenesis, and its principal downstream targets has not yet produced satisfactory therapeutic options, fueling the search for alternative approaches. Here, we show that the oncofetal RNA-binding protein LIN28B regulates the stability of EWS-FLI1 mRNA in ~10% of EwSs. LIN28B depletion in these tumors leads to a decrease in the expression of EWS-FLI1 and its direct transcriptional network, abrogating EwS cell self-renewal and tumorigenicity. Moreover, pharmacological inhibition of LIN28B mimics the effect of LIN28B depletion, suggesting that LIN28B sustains the emergence of a subset of EwS in which it also serves as an effective therapeutic target.


Assuntos
Proteínas de Fusão Oncogênica/metabolismo , Proteína Proto-Oncogênica c-fli-1/metabolismo , Proteína EWS de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/metabolismo , Sarcoma de Ewing/patologia , Animais , Carcinogênese/genética , Carcinogênese/patologia , Linhagem Celular Tumoral , Proliferação de Células , Autorrenovação Celular , Células Clonais , Regulação Neoplásica da Expressão Gênica , Humanos , Cinética , Camundongos , Estabilidade Proteica , Estabilidade de RNA , Proteínas de Ligação a RNA/genética , Sarcoma de Ewing/genética , Esferoides Celulares/patologia
8.
Bioresour Technol ; 292: 121959, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31421594

RESUMO

The aim of this study was to comparatively evaluate the effect of hydrothermal carbonization (HTC) conditions on the yield and the fuel properties of hydrochar obtained from food waste (FW) and its digestate (FD). The mass yield of hydrochars from FW and FD were found between 47.0 and 69.8%, 43.0 and 58.2%, respectively, under tested conditions. Based on both mass and energy yields, optimum temperature and duration were selected as 200 °C and 60 min for FW and 200 °C and 30 min for FD. FW and FD hydrochars produced optimum conditions had similar properties to lignite. The selected hydrochars were also subjected to steam gasification and combustion experiments. The combustion reactivity of hydrochars was found to be higher than that of lignite. Steam gasification produced 57-59 mol H2/kg hydrochar. The overall results emphasize the potential of H2 production by integrated systems of dark fermentation, HTC and steam gasification, besides production of solid fuel.


Assuntos
Carbono , Carvão Mineral , Alimentos , Vapor , Temperatura
9.
Biomed Pharmacother ; 68(6): 729-36, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25194441

RESUMO

Conventional cancer chemotherapies cannot differentiate between healthy and cancer cells, and lead to severe side effects and systemic toxicity. Another major problem is the drug resistance development before or during the treatment. In the last decades, different kinds of controlled drug delivery systems have been developed to overcome these shortcomings. The studies aim targeted drug delivery to tumor site. Magnetic nanoparticles (MNP) are potentially important in cancer treatment since they can be targeted to tumor site by an externally applied magnetic field. In this study, MNPs were synthesized, covered with biocompatible polyethylene glycol (PEG) and conjugated with folic acid. Then, anti-cancer drug idarubicin was loaded onto the nanoparticles. Shape, size, crystal and chemical structures, and magnetic properties of synthesized nanoparticles were characterized. The characterization of synthesized nanoparticles was performed by dynamic light scattering (DLS), Fourier transform-infrared spectroscopy (FT-IR), transmission electron microscopy (TEM), scanning electron microscopy (SEM) analyses. Internalization and accumulation of MNPs in MCF-7 cells were illustrated by light and confocal microscopy. Empty MNPs did not have any toxicity in the concentration ranges of 0-500µg/mL on MCF-7 cells, while drug-loaded nanoparticles led to significant toxicity in a concentration-dependent manner. Besides, idarubicin-loaded MNPs exhibited higher toxicity compared to free idarubicin. The results are promising for improvement in cancer chemotherapy.


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias da Mama/metabolismo , Sistemas de Liberação de Medicamentos/métodos , Ácido Fólico/administração & dosagem , Idarubicina/administração & dosagem , Nanopartículas de Magnetita/administração & dosagem , Antineoplásicos/metabolismo , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/fisiologia , Feminino , Ácido Fólico/metabolismo , Humanos , Idarubicina/metabolismo , Células MCF-7
10.
Bioresour Technol ; 112: 131-6, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22420990

RESUMO

Beet molasses and black strap are two major waste streams of the sugar industry. They both contain high amounts of sucrose, making them suitable substrates for biological hydrogen production. Photofermentation, usually used to convert organic acids to hydrogen, has the potential capacity to effectively use a variety of feed stocks, including sugars. A comparative study on photofermentative biohydrogen production from beet molasses, black strap, and sucrose was conducted. With yields of 10.5 mol H(2)/mol sucrose for beet molasses (1g/l sugar); 8 mol H(2)/mol sucrose for black strap (1g/l sugar) and 14 mol H(2)/mol sucrose for pure sucrose, a one stage photofermentation system appears promising as an alternative to two-stage systems given the potential savings in energy input and operational costs.


Assuntos
Carboidratos/química , Fermentação/fisiologia , Hidrogênio/metabolismo , Resíduos Industriais , Fotobiologia/métodos , Beta vulgaris/química , Beta vulgaris/efeitos dos fármacos , Fermentação/efeitos dos fármacos , Concentração de Íons de Hidrogênio/efeitos dos fármacos , Cinética , Melaço/análise , Sacarose/farmacologia , Fatores de Tempo
11.
Bioresour Technol ; 102(18): 8557-68, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21530244

RESUMO

In many respects, hydrogen is an ideal biofuel. However, practical, sustainable means of its production are presently lacking. Here we review recent efforts to apply the capacity of photosynthetic bacteria to capture solar energy and use it to drive the nearly complete conversion of substrates to hydrogen and carbon dioxide. This process, called photofermentation, has the potential capacity to use a variety of feedstocks, including the effluents of dark fermentations, leading to the development of various configurations of two-stage systems, or various industrial and agricultural waste streams rich in sugars or organic acids. The metabolic and enzymatic properties of this system are presented and the possible waste streams that might be successfully used are discussed. Recently, various immobilized systems have been developed and their advantages and disadvantages are examined.


Assuntos
Biotecnologia/métodos , Fermentação/efeitos da radiação , Hidrogênio/metabolismo , Luz , Resíduos/análise , Redes e Vias Metabólicas
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