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1.
Molecules ; 27(19)2022 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-36234850

RESUMO

The article systematizes information about the sources of ß-glucan, its technological functions and practical aspects of its use in dairy and milk-based products. According to the analysis of scientific information, the main characteristics of ß-glucan classifications were considered: the source of origin, chemical structure, and methods of obtention. It has been established that the most popular in the food technology of dairy products are ß-glucans from oat and barley cereal, which exhibit pronounced technological functions in the composition of dairy products (gel formation, high moisture-binding capacity, increased yield of finished products, formation of texture, and original sensory indicators). The expediency of using ß-glucan from yeast and mushrooms as a source of biologically active substances that ensure the functional orientation of the finished product has been revealed. For the first time, information on the use of ß-glucan of various origins in the most common groups of dairy and milk-based products has been systematized. The analytical review has scientific and practical significance for scientists and specialists in the field of food production, in particular dairy products of increased nutritional value.


Assuntos
Leite , beta-Glucanas , Animais , Grão Comestível , Tecnologia de Alimentos , Valor Nutritivo , beta-Glucanas/química
2.
Molecules ; 27(19)2022 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-36235221

RESUMO

Verbena officinalis L. is a traditionally important medicinal herb that has a rich source of bioactive phytoconstituents with biological benefits. The objective of this study was to assess the metabolic profile and in vitro biological potential of V. officinalis. The bioactive phytoconstituents were evaluated by preliminary phytochemical studies, estimation of polyphenolic contents, and gas chromatography-mass spectrometry (GC-MS) analysis of all fractions (crude methanolic, n-hexane, ethyl acetate, and n-butanol) of V. officinalis. The biological investigation was performed by different assays including antioxidant assays (DPPH, ABTS, CUPRAC, and FRAP), enzyme inhibition assays (urease and α-glucosidase), and hemolytic activity. The ethyl acetate extract had the maximum concentration of total phenolic and total flavonoid contents (394.30 ± 1.09 mg GAE·g-1 DE and 137.35 ± 0.94 mg QE·g-1 DE, respectively). Significant antioxidant potential was observed in all fractions by all four antioxidant methods. Maximum urease inhibitory activity in terms of IC50 value was shown by ethyl acetate fraction (10 ± 1.60 µg mL-1) in comparison to standard hydroxy urea (9.8 ± 1.20 µg·mL-1). The n-hexane extract showed good α-glucosidase inhibitory efficacy (420 ± 20 µg·mL-1) as compared to other extract/fractions. Minimum hemolytic activity was found in crude methanolic fraction (6.5 ± 0.94%) in comparison to positive standard Triton X-100 (93.5 ± 0.48%). The GC-MS analysis of all extract/fractions of V. officinalis including crude methanolic, n-hexane, ethyl acetate, and n-butanol fractions, resulted in the identification of 24, 56, 25, and 9 bioactive compounds, respectively, with 80% quality index. Furthermore, the bioactive compounds identified by GC-MS were analyzed using in silico molecular docking studies to determine the binding affinity between ligands and enzymes (urease and α-glucosidase). In conclusion, V. officinalis possesses multiple therapeutical potentials, and further research is needed to explore its use in the treatment of chronic diseases.


Assuntos
Antioxidantes , Verbena , 1-Butanol , Acetatos , Antioxidantes/química , Flavonoides/química , Cromatografia Gasosa-Espectrometria de Massas , Hexanos , Ligantes , Metanol/química , Simulação de Acoplamento Molecular , Octoxinol/análise , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Ureia/análise , Urease , alfa-Glucosidases
3.
Microb Cell Fact ; 19(1): 213, 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33228670

RESUMO

BACKGROUND: Colorectal cancer (CRC) is a major clinical challenge, and the gut microbiome plays important roles in the occurrence and metastasis of CRC. Lactobacillus and their metabolites are thought to be able to suppress the growth of CRC cells. However, the antimetastatic mechanism of Lactobacillus or their metabolites toward CRC cells is not clear. Therefore, the aim of this study was to assess the inhibitory mechanism of cell-free supernatants (CFSs) of L. rhamnosus GG, L. casei M3, and L. plantarum YYC-3 on metastasis of CRC cells. RESULTS: YYC-3 CFS showed the highest inhibitory effect on CRC cell growth, invasion and migration, and inhibited MMP2, MMP9, and VEGFA gene and protein expression, and protein secretion. Furthermore, it suppressed the activities of MMPs by gelatin zymography. Moreover, the effective compounds in these CFSs were analyzed by Q Exactive Focus liquid chromatography-mass spectrometry. CONCLUSIONS: Our results showed that metabolite secretions of YYC-3 may inhibited cell metastasis by downregulating the VEGF/MMPs signaling pathway. These data suggest that treatment of CRC cells with metabolites from L. plantarum YYC-3 may reduce colon cancer metastasis.


Assuntos
Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/microbiologia , Lactobacillus/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Células CACO-2 , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Células HT29 , Humanos , Lacticaseibacillus casei/metabolismo , Lactobacillus plantarum/metabolismo , Lacticaseibacillus rhamnosus/metabolismo , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 9 da Matriz/genética , Metástase Neoplásica/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/genética
4.
Sensors (Basel) ; 20(8)2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32326488

RESUMO

Oscillation monitoring commonly requires complex setups integrating various types of sensors associated with intensive computations to achieve an adequate rate of observations and accuracy. This research presents a simple, cost-effective approach that allows two-dimensional oscillation monitoring by terrestrial photogrammetry using non-metric cameras. Tedious camera calibration procedures are eliminated by using a grid target that allows geometric correction to be performed to the frame's region of interest at which oscillations are monitored. Region-based convolutional neural networks (Faster R-CNN) techniques are adopted to minimize the light exposure limitations, commonly constraining applications of terrestrial photogrammetry. The proposed monitoring procedure is tested at outdoor conditions to check its reliability and accuracy and examining the effect of using Faster R-CNN on monitoring results. The proposed artificial intelligence (AI) aided oscillation monitoring allowed sub-millimeter accuracy monitoring with observation rates up to 60 frames per second and gained the benefit of high optical zoom offered by market available bridge cameras to monitor oscillation of targets 100 m apart with high accuracy.

5.
Graefes Arch Clin Exp Ophthalmol ; 256(12): 2473-2481, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30128605

RESUMO

PURPOSE: To determine the short-term safety of human recombinant decorin protein in preventing proliferative vitreoretinopathy (PVR) in perforating injuries. METHODS: This is a prospective, single-center, open-label, interventional case series. Single intravitreal injection of decorin 200 µg (n = 4) or 400 µg (n = 8) was given 48 h after injury. At the tenth day, pars plana vitrectomy was done whenever indicated. Flash electroretinogram (ERG) was done before and 3 months post-injection. We assessed ocular inflammation, ERG changes, and retinal layer integrity by optical coherence tomography (OCT). Systemic and vitreous pharmacokinetics were also evaluated. RESULTS: Twelve patients (12 eyes) with perforating globe injuries (zone III) were included and followed for a median of 6 months. Intravitreal decorin injection was well tolerated with no ocular or systemic safety adverse events. Decorin retinal safety was demonstrated anatomically by intact retinal layer by OCT, and functionally by flash ERG which did not show any significant worsening during the study and the final mean logMAR best-corrected visual acuity (BCVA) which was 1.15 (20/280) and 0.7 (20/100) for groups A and B, respectively, and ≥ 20/200 in 75% of all eyes. Decorin serum and vitreous levels were elevated following trauma, with higher and extended levels following intravitreal injection. CONCLUSIONS: No short-term safety concerns were detected after a single intravitreal injection of decorin in patients with perforating injuries. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT02865031.


Assuntos
Decorina/administração & dosagem , Ferimentos Oculares Penetrantes/complicações , Retina/patologia , Vitreorretinopatia Proliferativa/prevenção & controle , Corpo Vítreo/patologia , Adolescente , Adulto , Relação Dose-Resposta a Droga , Eletrorretinografia , Ferimentos Oculares Penetrantes/diagnóstico , Ferimentos Oculares Penetrantes/cirurgia , Feminino , Seguimentos , Humanos , Injeções Intravítreas , Masculino , Projetos Piloto , Estudos Prospectivos , Tomografia de Coerência Óptica , Resultado do Tratamento , Acuidade Visual , Vitrectomia , Vitreorretinopatia Proliferativa/complicações , Vitreorretinopatia Proliferativa/diagnóstico , Adulto Jovem
7.
BMC Ophthalmol ; 16: 74, 2016 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-27255356

RESUMO

BACKGROUND: Extracellular matrix remodelling regulated by matrix-metalloproteinase (MMP) inducer (CD147) is a crucial process during tumor cell invasion and regulation of blood supply. In this study, we evaluated the correlation of CD147 and MMP-2 expression with major prognostic factors for uveal melanoma and the development of metastasis. METHODS: The expression of CD147 and MMP-2 was analyzed in 49 samples of uveal melanomas. Triple immunofluorescence stainings using markers against glial cells (GFAP), endothelial cells (CD34) and macrophages (CD68) were performed to further analyse the exact localisation of CD147 and MMP-2 positivity. In 28 cases clinical metastatic disease were found. The remaining 21 cases showed no signs of metastatic disease for an average follow-up of 10 years. Correlation analysis (Pearson correlation) was performed to analyse the association of CD147 and MMP-2 expression with known prognostic factors, vasculogenic mimicry (VM), the mature vasculature (von Willebrand Factor) and tumor induced angiogenesis (by means of Endoglin expression). RESULTS: CD147 and MMP-2 were expressed in 47 (96.0 %) of the uveal melanomas. CD147 up-regulation was significantly correlated with a higher MMP-2 expression. The overall expression analysis revealed no significant difference in the metastatic (p = 0.777) and non-metastatic subgroup (p = 0.585). No correlation of CD147 expression and any system of blood supply was evident. In the non-metastatic sub-group a significant correlation of clustered CD147 positive cells with largest basal diameter (p = 0.039), height (p = 0.047) and TNM-stage (p = 0.013) was evident. CONCLUSIONS: These data may indicate that CD147 regulates MMP-2 expression in uveal melanoma cells.


Assuntos
Basigina/metabolismo , Biomarcadores Tumorais/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Melanoma/metabolismo , Neoplasias Uveais/metabolismo , Idoso , Feminino , Humanos , Imuno-Histoquímica , Masculino , Melanoma/patologia , Neoplasias Uveais/patologia
8.
Clin Exp Ophthalmol ; 44(5): 400-9, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26590370

RESUMO

BACKGROUND: To evaluate the regulation of blood supply in primary uveal melanomas through caveolin-1 (Cav-1)/phosphoinositol-3 kinase (PI3K). METHODS: The expression of Cav-1 and PI3K was analysed in 51 paraffin sections of metastatic (n = 30) and non-metastastic uveal melanomas (n = 21). Two trained observers quantified Cav-1 and PI3K immunofluorescensce expression by determining intensity of staining and percentage of positive cells. The expression was correlated with known prognostic factors. Besides angiogenesis by means of endoglin expression, the normal vasculature (von Willebrand Factor expression) was evaluated semi-quantitatively. Vasculogenic mimicry (VM) was analysed by CD31/PAS staining. RESULTS: All examined specimens expressed Cav-1 with a mean of 90.34% Cav-1 positive cells (range, 3.23-100%). Metastatic disease was associated with a higher Cav-1 expression. The correlation of Cav-1 with well-established prognostic factors showed a significant association between Cav-1 expression and largest tumour diameter (P = 0.022), tumour node metastasis classification (P = 0.008) and invasion of optic nerve head (P = 0.048). PI3K was expressed by all uveal melanomas with a mean of 87.28% cells showing PI3K expression. A higher level of PI3K was significantly associated with larger height (P = 0.042) and progressed tumour node metastasis stage (P = 0.016). The percentage of PI3K and Cav-1 positive cells were significantly associated (P = 0.034). For PI3K and Cav-1 expression a non-significant association with VM was shown (P = 0.064 and P = 0.072, respectively). No correlation of PI3K or Cav-1 with angiogenesis or mature vasculature was seen (P > 0.05). CONCLUSIONS: Cav-1 expression may be especially up-regulated in larger uveal melanomas. As it was correlated with PI3K expression and VM in this series of uveal melanoma, Cav-1 might induce the formation of VM via the PI3K-signalling cascade.


Assuntos
Biomarcadores Tumorais/metabolismo , Caveolina 1/metabolismo , Elafina/metabolismo , Melanoma/enzimologia , Neovascularização Patológica/metabolismo , Neoplasias Uveais/enzimologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Vasos Sanguíneos/metabolismo , Endoglina/metabolismo , Feminino , Técnica Indireta de Fluorescência para Anticorpo , Humanos , Metástase Linfática , Masculino , Melanoma/irrigação sanguínea , Microscopia de Fluorescência , Pessoa de Meia-Idade , Fator de Crescimento Transformador beta1/metabolismo , Fator de Crescimento Transformador beta3/metabolismo , Regulação para Cima , Neoplasias Uveais/irrigação sanguínea , Fator de von Willebrand/metabolismo
9.
Int J Exp Pathol ; 96(2): 103-10, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25670226

RESUMO

The aim of this study was to evaluate the use of different fixatives on the reliability of histopathological changes in a rabbit model of proliferative vitreoretinopathy (PVR). Twenty eyes from 10 rabbits were divided into four groups. The right eyes were used in two experimental groups (each n = 5), and the left, in two control groups (each n = 5). Using a newly developed scleral incision marker, an oblique scleral incision was standardized in the experimental groups, followed by intravitreal injection of 0.4 ml autologous blood and the left for wound repair for four weeks. Eyes were enucleated at four weeks. The groups differed in the type of used fixative solution (formaldehyde 4% vs. 1% buffered formaldehyde and 1.25% glutaraldehyde). The eyes were evaluated for the development of fibrosis, retinal detachment (RD), and processed for histopathology. Fibrous ingrowth of a variable degree was present in the experimental groups originating from the trauma site. Experimental eyes fixed with formaldehyde 4% had RD extension that was greater than that fixed in formaldehyde/glutaraldehyde mixture; however, the difference did not reach statistical significance (P = 0.15). This difference was not fully explained by the fibrosis which developed. In addition, in control groups, formaldehyde 4% induced a fixative-dependent retinal separation that was absent in eyes fixed with formaldehyde/glutaraldehyde mixture (P = 0.03). In conclusion, a mixture of buffered formaldehyde 1% and glutaraldehyde 1.25% combined with standardized scleral incision resulted in consistent pathological changes. A reliable PVR model is a condition sine qua non to evaluate antifibrotic treatment strategies.


Assuntos
Modelos Animais de Doenças , Olho/efeitos dos fármacos , Olho/patologia , Fixadores/farmacologia , Vitreorretinopatia Proliferativa/patologia , Animais , Feminino , Fibrose/induzido quimicamente , Fibrose/epidemiologia , Fixadores/efeitos adversos , Formaldeído/efeitos adversos , Formaldeído/farmacologia , Glutaral/efeitos adversos , Glutaral/farmacologia , Técnicas de Preparação Histocitológica/métodos , Incidência , Coelhos , Reprodutibilidade dos Testes , Descolamento Retiniano/induzido quimicamente , Descolamento Retiniano/epidemiologia , Vitreorretinopatia Proliferativa/etiologia , Ferimentos e Lesões/complicações
10.
Graefes Arch Clin Exp Ophthalmol ; 253(5): 699-704, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25056526

RESUMO

PURPOSE: This study evaluates the potential of serum pro-inflammatory cytokines as AMD biomarkers. METHODS: Serum samples from 30 age-related macular degeneration (AMD) patients and 15 age-matched controls were examined for 16 inflammatory cytokines using multiplex ELISA. Patients were divided into three subgroups (improvement/no change/deterioration during anti-VEGF treatment) by OCT and funduscopy, and correlated to the cytokine levels. RESULTS: Serum concentrations of IL-1α, IL-1ß, IL-4, IL-5, IL-10, IL-13, and IL-17 were significantly higher in AMD patients than in controls. None of the co-variables expressed a significant effect on the tested cytokines. Only IL-1a and IL-17 showed a statistically significant difference between groups (improved, unchanged, deteriorated) as determined by one-way ANOVA. Patients with increased macular thickness during treatment showed significantly lower levels of IL-17 compared to improved cases and to unchanged cases (p = 0.004, 0.03 respectively, Dunnett's T3 post hoc multiple test). TNF-α was significantly higher in improved cases compared to deteriorated cases (p =0.03, Dunnett's T3 post hoc multiple test). IL-17 was a significant predictor for macular oedema using linear regression (ß = -0.888, p <0.05). CONCLUSION: Elevation of IL-1α, IL-1ß, IL-4, IL-5, IL-10, IL-13, and IL-17 in the serum of AMD patients supports the hypothesis of AMD as an inflammatory disease. Patients with high IL-17 and TNF-α serum levels were more likely to have a favourable course under VEGF therapy. These cytokines may be used as easy-to-obtain biomarkers.


Assuntos
Biomarcadores/sangue , Citocinas/sangue , Degeneração Macular/sangue , Edema Macular/sangue , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/uso terapêutico , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoensaio , Injeções Intravítreas , Degeneração Macular/diagnóstico , Edema Macular/diagnóstico , Masculino , Projetos Piloto , Retina/patologia , Tomografia de Coerência Óptica , Acuidade Visual/fisiologia
11.
Opt Express ; 22 Suppl 3: A895-907, 2014 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-24922395

RESUMO

With the high population growth rate, especially in developing countries, and the scarcity of land resources, buildings are becoming so close to each other, depriving the lower floors and the alleys from sunlight and consequently causing health problems. Therefore, there is an urgent need for cost-effective efficient light redirecting panels that guide sun rays into those dim places. In this paper, we address this problem. A novel sine wave based panel is presented to redirect/diverge light downward and enhance the illumination level in those dark places. Simulation results show that the proposed panel improves the illuminance values by more than 200% and 400% in autumn and winter respectively, operates over wide solar altitude ranges, and redirects light efficiently. Experimental and simulation results are in good agreement.

12.
Exp Eye Res ; 123: 72-86, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24742493

RESUMO

This study evaluates the use of the TGF-ß receptor 1 inhibitor LY-364947 (LY) to prevent proliferative vitreoretinopathy (PVR). For the in vitro experiments Human Tenon's Fibroblasts (HTFs) and retinal pigment epithelial (RPE) cells were treated with different concentrations of LY to determine HTF proliferation and RPE transdifferentiation. For in vivo testing 30 rabbits underwent a PVR trauma model. The animals received different concentrations of intravitreally injected LY, with or without vitrectomy. LY treatment reduced HTF proliferation and RPE transdifferentiation in vitro. In vivo intravitreal injection of LY prevented PVR development significantly. This positive effect was also present when LY injection was combined with vitrectomy. Intravitreal injection of LY prevented tractional retinal detachment in 14 out of 15 animals. In conclusion, treatment with the TGF-ß receptor 1 inhibitor LY reduces HTF proliferation and RPE transdifferentiation in vitro and prevents proliferative vitreoretinopathy and subsequent tractional retinal detachment in vivo.


Assuntos
Modelos Animais de Doenças , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Pirazóis/farmacologia , Pirróis/farmacologia , Receptores de Fatores de Crescimento Transformadores beta/antagonistas & inibidores , Vitreorretinopatia Proliferativa/prevenção & controle , Animais , Proliferação de Células/efeitos dos fármacos , Transdiferenciação Celular/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Humanos , Injeções Intravítreas , Coelhos , Receptor do Fator de Crescimento Transformador beta Tipo I , Epitélio Pigmentado da Retina/citologia , Cápsula de Tenon/citologia , Sais de Tetrazólio/metabolismo , Tiazóis/metabolismo , Vitreorretinopatia Proliferativa/metabolismo , Vitreorretinopatia Proliferativa/patologia
13.
Ophthalmic Res ; 51(3): 167-71, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24642512

RESUMO

BACKGROUND: Dye solutions such as indocyanine green (ICG) are used for the staining of intraocular structures. The aim of the presented study was to investigate the effects of ICG on bovine retinal function using different concentrations of ICG. METHODS: Bovine retina preparations were perfused with a standard solution and the electroretinogram was recorded. The nutrient solution was substituted by an ICG solution at varying concentrations for 45 min. Afterwards the preparations were reperfused with standard solution for at least 85 min. RESULTS: Significant reductions in b-wave amplitude were found for concentrations of 0.0025% (p = 0.0099) and 0.025% (p = 0.0378). For the concentration of 0.025%, the b-wave amplitude remained significantly decreased (p = 0.0082) after the observation period, but a full recovery of the b-wave was observed for the concentration of 0.0025% (p = 0.1917). CONCLUSION: Intraocular application of sufficient ICG concentrations for internal limiting membrane staining seems not possible without interfering with retinal function.


Assuntos
Corantes/farmacologia , Verde de Indocianina/farmacologia , Retina/efeitos dos fármacos , Animais , Bovinos , Relação Dose-Resposta a Droga , Eletrorretinografia/efeitos dos fármacos , Modelos Animais
14.
ScientificWorldJournal ; 2014: 878704, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25045751

RESUMO

Ambient fine particulate matter (PM2.5) samples were collected from January to December 2007 to investigate the sources and chemical speciation in Palestine, Jordan, and Israel. The 24-h PM2.5 samples were collected on 6-day intervals at eleven urban and rural sites simultaneously. Major chemical components including metals, ions, and organic and elemental carbon were analyzed. The mass concentrations of PM2.5 across the 11 sites varied from 20.6 to 40.3 µg/m(3), with an average of 28.7 µg/m(3). Seasonal variation of PM2.5 concentrations was substantial, with higher average concentrations (37.3 µg/m(3)) in the summer (April-June) months compared to winter (October-December) months (26.0 µg/m(3)) due mainly to high contributions of sulfate and crustal components. PM2.5 concentrations in the spring were greatly impacted by regional dust storms. Carbonaceous mass was the most abundant component, contributing 40% to the total PM2.5 mass averaged across the eleven sites. Crustal components averaged 19.1% of the PM2.5 mass and sulfate, ammonium, and nitrate accounted for 16.2%, 6.4%, and 3.7%, respectively, of the total PM2.5 mass. The results of this study demonstrate the need to better protect the health and welfare of the residents on both sides of the Jordan River in the Middle East.


Assuntos
Aerossóis/análise , Poluentes Atmosféricos/análise , Monitoramento Ambiental/métodos , Material Particulado/análise , Oriente Médio
15.
Cancer Res Commun ; 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39258975

RESUMO

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths in the United States, with a median survival period of approximately 10 months. There is an urgent need for the development of effective targeted therapies for the treatment of HCC. Proline-, glutamic acid- and leucine-rich protein 1 (PELP1) signaling is implicated in the progression of many cancers, although its specific contribution to the progression of HCC is not yet well understood. Analysis of TCGA HCC gene expression data sets and immunohistochemistry analysis of HCC tissue microarray revealed that HCC tumors had elevated expression of PELP1 compared to normal tissues, and high expression of PELP1 is associated with unfavorable survival outcomes. Suppression of PELP1 expression using shRNA significantly reduced the cell viability, clonogenicity, and invasion of HCC cells. Importantly, SMIP34, a first-in-class small molecule inhibitor targeting PELP1, effectively decreased the cell viability, clonogenic survival and invasiveness of HCC cells. Gene expression analysis using RNA-seq revealed that PELP1-knockdown (KD) cells exhibited a decrease in c-Myc, E2F, and other oncogenic pathways related to HCC. Mechanistic studies showed that SMIP34 treatment impaired the Rix complex, a critical component of ribosomal biogenesis, in HCC cells. Further, the knockdown or pharmacological inhibition of PELP1 significantly decelerated the HCC tumor growth in xenograft models. In summary, our study findings indicate that PELP1 could serve as a promising target for therapeutic intervention in HCC.

16.
Cell Physiol Biochem ; 32(1): 218-34, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23899884

RESUMO

AIMS: To investigate the outcomes of Rho-kinase inhibition in the electrophysiological ex vivo model of the isolated perfused vertebrate retina under hypoxia. METHODS: Bovine retinas were perfused with an oxygen saturated nutrient solution with or without the Rho-kinase inhibitor H-1152P. The retinas were stimulated repeatedly until stable amplitudes were reached and the electroretinogram was recorded at five minute intervals. Hypoxia was induced for 15, 30, and 45 minutes, after which the oxygen saturation was restored. The extent of the cell damage and glial reactivity was determined by Ethidium homodimer-1 staining, immunohistochemistry, and Western blot. RESULTS: Hypoxia caused a time-dependent reduction of the b-wave amplitudes, which could not be prevented by the H-1152P. Although the Rho-kinase inhibitor maintained higher b-wave amplitudes, these effects did not reach statistical significance. Hypoxia also resulted in an increase in cell damage and the activation of the glial cells in the untreated retinas whereas the administration of H-1152P significantly reduced the extent of these events. CONCLUSION: H-1152P exerted a neuroprotective effect against necrosis on the isolated bovine retina under hypoxia together with a reduction in glial cell reactivity. However, the inhibitor could not prevent the hypoxia induced retinal dysfunction possibly due to the interference with synaptic modulation.


Assuntos
1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/análogos & derivados , Hipóxia Celular , Fármacos Neuroprotetores/farmacologia , Retina/efeitos dos fármacos , Quinases Associadas a rho/antagonistas & inibidores , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/farmacologia , Animais , Catepsina B/metabolismo , Bovinos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Gliose , Microglia/citologia , Microglia/metabolismo , Retina/citologia , Retina/metabolismo , Quinases Associadas a rho/metabolismo
17.
Graefes Arch Clin Exp Ophthalmol ; 251(10): 2403-13, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23893090

RESUMO

BACKGROUND: To evaluate the capability of adjuvant intraocular ranibizumab (Lucentis) injections in the treatment of rubeosis and intraocular pressure in patients with rubeosis and neovascular glaucoma. METHODS: Ten eyes with rubeosis (R) and ten eyes with neovascular glaucoma (NVG) received Lucentis injections (ranibizumab 0.5 mg/0.05 ml) in this prospective, monocenter, 12-months, interventional case series. The primary efficacy outcome measure was the change of degree of iris rubeosis as documented by iris fluorescein angiography measured after 12 months. Secondary outcomes were intraocular pressure (IOP), best-corrected visual acuity (BCVA, logMAR), numbers of additional interventions or antiglaucoma medications administered after injection, the gonioscopic status of the anterior chamber angle, and central retinal thickness. RESULTS: In the R group, 3.6 injections and in the NVG group 2.3 injections of Lucentis were administered. Additional treatments were photocoagulation (n = 19), cyclodestructive procedures (n = 9), cryopexy (n = 3), and vitrectomy (n = 1). The mean stage of rubeosis was 3.4 ± 0.7 in the R group and 3.6 ± 0.8 in the NVG group at baseline. At month 12, the rubeosis was almost resolved in the R group (0.1 ± 0.3, p < 0.001), and decreased significantly in the NVG group (0.7 ± 1.1, p < 0.001). In the NVG subgroup, mean IOP was 41.4 ± 13.4 mmHg at baseline, which decreased rapidly (18.2 ± 12.3, day-14, p = 0.005) and stabilized during the follow-up (15.6 ± 2.0 mmHg, p < 0.05). BCVA improved significantly in both groups (p < 0.05, at month 12). CONCLUSIONS: Injection of 0.5 mg ranibizumab appears to be beneficial as an adjuvant treatment in neovascular glaucoma and rubeosis due to its anti-angiogenic properties and its ability to prevent establishment or progression of anterior chamber angle obstruction. Conventional therapeutic procedures addressing the retinal ischemia are still required in a stage-wise treatment approach.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Glaucoma Neovascular/tratamento farmacológico , Pressão Intraocular/efeitos dos fármacos , Iris/irrigação sanguínea , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Hipertensivos/uso terapêutico , Feminino , Angiofluoresceinografia , Fluorofotometria , Glaucoma Neovascular/diagnóstico , Gonioscopia , Humanos , Injeções Intraoculares , Injeções Intravítreas , Masculino , Pessoa de Meia-Idade , Neovascularização Patológica/diagnóstico , Neovascularização Patológica/tratamento farmacológico , Estudos Prospectivos , Ranibizumab , Tonometria Ocular , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Acuidade Visual/fisiologia
18.
Ophthalmologica ; 230(2): 81-6, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23887050

RESUMO

PURPOSE OF THE STUDY: To investigate the outcome of brilliant blue G (BBG)-assisted internal limiting membrane peeling in macular hole surgery after a follow-up of 6 months. PROCEDURES: In this retrospective study 20 eyes have been treated with BBG-assisted macular hole surgery. After a follow-up of 6 months, the functional and anatomical outcomes have been analyzed. RESULTS: The mean preoperative best-corrected visual acuity (BCVA) was 0.7 logMAR units (mean ± SD 0.66 ± 0.27). After 3 months, the mean BCVA increased not significantly to 0.4 (0.54 ± 0.30), but a significant improvement to 0.2 logMAR units (0.28 ± 0.23) could be detected after 6 months compared to baseline (p < 0.01). Primary macular hole closure after a single surgery was found in 17 of 20 eyes. CONCLUSION AND MESSAGE: BBG exhibits sufficient staining qualities and safety profile leading to a significant functional improvement after successful macular hole surgery.


Assuntos
Membrana Basal/cirurgia , Corantes , Perfurações Retinianas/cirurgia , Corantes de Rosanilina , Adulto , Idoso , Membrana Basal/patologia , Feminino , Angiofluoresceinografia , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Perfurações Retinianas/fisiopatologia , Estudos Retrospectivos , Coloração e Rotulagem/métodos , Tomografia de Coerência Óptica , Resultado do Tratamento , Acuidade Visual/fisiologia
19.
Invest Ophthalmol Vis Sci ; 64(15): 39, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38153753

RESUMO

Purpose: Proliferative vitreoretinopathy (PVR) is the most common cause of failure of surgically repaired rhegmatogenous retinal detachment (RRD). Chemically induced and cell injection PVR models do not fully simulate the clinical characteristics of PVR in the post-RRD context. There is an unmet need for translational models in which to study mechanisms and treatments specific to RRD-PVR. Methods: RRD was induced in adult Dutch Belted rabbits. Posterior segments were fixed or processed for RNA sequencing at 6 hours and 2, 7, 14, and 35 days after induction. Histochemical staining and immunolabeling for glial fibrillary acidic protein, alpha smooth muscle actin, vascular endothelial growth factor receptor 2, CD68, and RPE 65 kDa protein were performed, and labeling intensity was scored. Single cell RNA sequencing was performed. Results: Acute histopathological changes included intravitreal and intraretinal hemorrhage, leukocytic vitritis, chorioretinitis, and retinal rarefaction. Chronic lesions showed retinal atrophy, gliosis, fibrotic subretinal membranes, and epiretinal fibrovascular proliferation. Fibrillar collagen was present in the fibrocellular and fibrovascular membranes in chronic lesions. Moderate to strong labeling of glia and vasculature was detected in chronic lesions. At day 14, most cells profiled by single cell sequencing were identified as Mϋller glia and microglia, consistent with immunolabeling. Expression of several fibrillar collagen genes was upregulated in chronic lesions. Conclusions: Histological and transcriptional features of this rabbit model simulate important features of human RRD-PVR, including the transition to chronic intraretinal and periretinal fibrosis. This animal model of RRD with features of PVR will enable further research on targeted treatment interventions.


Assuntos
Descolamento Retiniano , Vitreorretinopatia Proliferativa , Adulto , Animais , Humanos , Coelhos , Vitreorretinopatia Proliferativa/etiologia , Descolamento Retiniano/etiologia , Fator A de Crescimento do Endotélio Vascular , Modelos Animais , Fibrose , Colágenos Fibrilares
20.
Sci Rep ; 12(1): 21616, 2022 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-36517560

RESUMO

The process of optimizing building designs requires developing several architectural and structural layout alternatives. Traditionally, limited number of design iterations can be conducted manually, which is time consuming and results in non-optimum designs in terms of limited functionality or high costs. The goal of this research is to develop an advanced Building Information Modeling (BIM) model for automating and optimizing design of building layouts and structural elements to reach minimum construction cost while abiding by the functionality constraints of the architectural design. The developed model integrates concepts from structural design, BIM modeling, and computer programming into one advanced optimization framework. The model was tested and validated in 11 case studies and is found to reduce the structural materials cost by up to 15% per floor without compromising the defined space requirements.

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