RESUMEN
Hepatocellular carcinoma (HCC) is a challenging cancer with high mortality rates, limited predictability, and a lack of effective prognostic indicators. The relationship between small nucleolar RNAs (snoRNAs) and HCC is poorly understood. Based on the literature data, snoRNA studies were primarily focused on viral-related causes of HCC, such as Hepatitis B or C viruses (HBV or HCV). According to these studies, we selected four snoRNAs (snoRA12, snoRA47, snoRA80E, and snoRD126) for exploration in the context of non-viral-related causes, including non-alcoholic steatohepatitis (NASH), non-alcoholic fatty liver diseases (NAFLD), and alcohol steatohepatitis. The primary goal of this study was to gain a deeper understanding of how snoRNA expression affects patient outcomes and whether it can serve as a prognostic tool for non-viral HCC. We conducted a study on tissue samples from 35 HCC patients who had undergone resection at Pilsen University Hospital. SnoRA12, snoRA47, snoRA80E, and snoRD126 were studied by quantitative real-time PCR (qRT-PCR) in tumor and non-tumor adjacent tissue (NTAT) samples. Kaplan-Meier analysis was performed to assess the association of snoRNAs expression levels with patient outcomes: time to recurrence (TTR), disease-free survival (DFS) and overall survival (OS). In tumor tissues, snoRA12, snoRA47 and snoRA80E were upregulated, while snoRD-126 was downregulated compared to NTAT. Low expression of snoRA47 and snoRD126 in patients was associated with longer TTR and DFS. The individual expression of snoRA12 and snoRA80E did not show associations with TTR and DFS. However, a combination of medium expression of snoRD126 and snoRA80E was associated with longer TTR and DFS, while high and low expressions of the combined snoRA126 and snoRA80E showed no significant association with TTR, DFS, and OS. Conversely, a combination of high expression of snoRA12 and snoRD126 was associated with shorter TTR. In conclusion, the results indicate that snoRA47 and snoRD126 exhibit good prognostic power specifically for non-viral related HCC. Both snoRA47 and snoRD126 showed favorable prognostication in single and combined analysis when assessing patient outcomes. Also, in combination analysis, snoRA80E and snoRA12 showed favorable prognosis, but not alone.
RESUMEN
Recent complications on the use of polypropylene meshes for hernia repair has led to the development of meshes or films, which were based on resorbable polymers such as polycaprolactone (PCL), polylactic acid (PLA) and poly(lactic-co-glycolic acid) (PLGA). These materials are able to create suitable bioactive environment for the growth and development of cells. In this research, we mainly focused on the relations among structure, mechanical performance and biocompatiblity of PCL/PLA and PCL/PLGA and blends prepared by solution casting. The films were characterized regarding the chemical structure, morphology, physicochemical properties, cytotoxicity, biocompatibility and cell growth. All the films showed high tensile strength ranging from 9.5 to 11.8 MPa. SAXS showed that the lamellar stack structure typical for PCL was present even in the blend films while the morphological parameters of the stacks varied slightly with the content of PLGA or PLA in the blends. WAXS indicated preferential orientation of crystallites (and thus, also the lamellar stacks) in the blend films. In vitro studies revealed that PCL/PLGA films displayed better cell adhesion, spreading and proliferation than PCL/PLA and PCL films. Further the effect of blending on the degradation was investigated, to understand the significant variable within the process that could provide further control of cell adhesion. The results showed that the investigated blend films are promising materials for biomedical applications.
Asunto(s)
Implantes Absorbibles , Glicoles , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Dispersión del Ángulo Pequeño , Difracción de Rayos X , PoliésteresRESUMEN
Hydrogel based matrices and titanium dioxide (TiO2) nanoparticles (NPs) are well established materials in bone tissue engineering. Nevertheless, there is still a challenge to design appropriate composites with enhanced mechanical properties and improved cell growth. Progressing in this direction, we synthesized nanocomposite hydrogels by impregnating TiO2 NPs in a chitosan and cellulose-based hydrogel matrix containing polyvinyl alcohol (PVA), to enhance the mechanical stability and swelling capacity. Although, TiO2 has been incorporated into single and double component matrix systems, it has rarely been combined with a tri-component hydrogel matrix system. The doping of NPs was confirmed by Fourier transform infrared spectroscopy, Raman spectroscopy, scanning electron microscopy and small- and wide-angle X-ray scattering. Our results showed that incorporation of TiO2 NPs improved the tensile properties of the hydrogels significantly. Furthermore, we performed biological evaluation of scaffolds, swelling degree, bioactivity assessment, and hemolytic tests to prove that all types of hydrogels were safe for use in the human body. The culturing of human osteoblast-like cells MG-63 on hydrogels showed better adhesion of cells in the presence of TiO2 and showed increasing proliferation with increasing amount of TiO2. Our results showed that the sample with the highest TiO2 concentration, CS/MC/PVA/TiO2 (1 %) had the best biological properties.
Asunto(s)
Quitosano , Nanopartículas , Humanos , Quitosano/farmacología , Quitosano/química , Celulosa/farmacología , Hidrogeles/farmacología , Hidrogeles/química , Nanopartículas/química , Alcohol Polivinílico/químicaRESUMEN
Colorectal cancer (CRC) is the third most common cancer worldwide, and metastatic CRC is a fatal disease. The CRC-affected tissues show several molecular markers that could be used as a fresh strategy to create newer methods of treating the condition. The liver and the peritoneum are where metastasis occurs most frequently. Once the tumor has metastasized to the liver, peritoneal carcinomatosis is frequently regarded as the disease's final stage. However, nearly 50% of CRC patients with peritoneal carcinomatosis do not have liver metastases. New diagnostic and therapeutic approaches must be developed due to the disease's poor response to present treatment choices in advanced stages and the necessity of an accurate diagnosis in the early stages. Many unique and amazing nanomaterials with promise for both diagnosis and treatment may be found in nanotechnology. Numerous nanomaterials and nanoformulations, including carbon nanotubes, dendrimers, liposomes, silica nanoparticles, gold nanoparticles, metal-organic frameworks, core-shell polymeric nano-formulations, and nano-emulsion systems, among others, can be used for targeted anticancer drug delivery and diagnostic purposes in CRC. Theranostic approaches combined with nanomedicine have been proposed as a revolutionary approach to improve CRC detection and treatment. This review highlights recent studies, potential, and challenges for the development of nanoplatforms for the detection and treatment of CRC.
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Neoplasias Colorrectales , Nanopartículas del Metal , Nanopartículas , Nanotubos de Carbono , Neoplasias Peritoneales , Humanos , Nanomedicina/métodos , Medicina de Precisión , Oro , Nanopartículas/uso terapéutico , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/tratamiento farmacológico , Nanomedicina Teranóstica , Sistemas de Liberación de Medicamentos/métodosRESUMEN
The extracts of 7 herbs were screened and compared for their functional ability to inhibit the aggregation of trypsin as an appropriate model protein for in vitro fibrillation in aqueous ethanol at pH 7.0. Turbidity measurements, total phenolic content determination, aggregation kinetics, Congo red binding assay as well as transmission electron microscopy were used to analyse the inhibition of amyloid fibril formation. This correlated with the total phenolic content of the herb extracts. The peppermint extract proved to be the most potent anti-amyloidogenic agent. Results showed that the peppermint extract exerted dose-dependent inhibitory effect on trypsin fibril formation.
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Aceites de Plantas/farmacología , Agregado de Proteínas/efectos de los fármacos , Agregación Patológica de Proteínas/tratamiento farmacológico , Mentha piperita/metabolismo , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Aceites de Plantas/metabolismoRESUMEN
During the study of inhibition of amyloid fibril formation, α-chymotrypsin protein was developed in 55% ethanol at pH 7.0. We investigated the inhibitory effect of different spices on amyloid fibril formation using turbidity measurements and Congo red binding assays. We found that all spices except the black pepper and caraway seed prevented fibril formation. The highest inhibition was measured with the clove, which reduced the amount of aggregates by 90%. We studied the inhibitory effect of the cloves at different concentrations on aggregation, it was found that the inhibitory activity of clove is dependent on concentration. We have measured the total phenolic content of the spice extracts too. Based on all these findings we have come to the following conclusion: Our results indicate that spices can contain other compounds too - not only phenolic compounds - which influence the formation of amyloid fibrils, and the effectiveness of various phenolic compounds are different.
Asunto(s)
Amiloide/efectos de los fármacos , Fenoles/farmacología , Extractos Vegetales/farmacología , Agregado de Proteínas/efectos de los fármacos , Agregación Patológica de Proteínas , Especias , Syzygium , Amiloide/química , Quimotripsina/química , Etanol/química , Concentración de Iones de Hidrógeno , Nefelometría y Turbidimetría , Fenoles/aislamiento & purificación , Extractos Vegetales/aislamiento & purificación , Syzygium/químicaRESUMEN
We tested the amyloid fibril formation inhibitory effect of seven teas diluted in 55% ethanol at pH 7.0 at a protein concentration of 0.15 mg/ml α-chymotrypsin. In the experiments we investigated the formation and inhibition of amyloid fibrils by turbidity measurements, aggregation kinetics experiments and Congo red binding assay. The results suggest that the different teas effectively inhibit the formation of amyloidlike fibrils. The two most potent inhibitors were peppermint and melilot, extracts which almost completely inhibited the formation of aggregates in 5-fold dilution. The inhibitory effect on the aggregation formation of melilot and peppermint extracts was concentration dependant. The extent of inhibition was found to be proportional with the total concentration of phenolic compounds.