RESUMO
The dynamics of a soft particle suspended in a viscous fluid can be changed by the presence of an elastic boundary. Understanding the mechanisms and dynamics of soft-soft surface interactions can provide valuable insights into many important research fields, including biomedical engineering, soft robotics development, and materials science. This work investigates the anomalous transport properties of a soft nanoparticle near a visco-elastic interface, where the particle consists of a polymer assembly in the form of a micelle and the interface is represented by a lipid bilayer membrane. Mesoscopic simulations using a dissipative particle dynamics model are performed to examine the impact of micelle's proximity to the membrane on its Brownian motion. Two different sizes are considered, which correspond to ≈10-20nm in physical units. The wavelengths typically seen by the largest micelle fall within the range of wavenumbers where the Helfrich model captures fairly well the bilayer mechanical properties. Several independent simulations allowed us to compute the micelle trajectories during an observation time smaller than the diffusive time scale (whose order of magnitude is similar to the membrane relaxation time of the largest wavelengths), this time scale being hardly accessible by experiments. From the probability density function of the micelle normal position with respect to the membrane, it is observed that the position remains close to the starting position during ≈0.05τd (where τd corresponds to the diffusion time), which allowed us to compare the negative excess of mean-square displacement (MSD) to existing theories. In that time range, the MSD exhibits different behaviors along parallel and perpendicular directions. When the micelle is sufficiently close to the bilayer (its initial distance from the bilayer equals approximately twice its gyration radius), the micelle motion becomes quickly subdiffusive in the normal direction. Moreover, the temporal evolution of the micelle MSD excess in the perpendicular direction follows that of a nanoparticle near an elastic membrane. However, in the parallel direction, the MSD excess is rather similar to that of a nanoparticle near a liquid interface.
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OBJECTIVE: To assess the potential of near-infrared spectroscopy (NIRS) for in vivo arthroscopic monitoring of cartilage defects. METHOD: Sharp and blunt cartilage grooves were induced in the radiocarpal and intercarpal joints of Shetland ponies and monitored at baseline (0 weeks) and at three follow-up timepoints (11, 23, and 39 weeks) by measuring near-infrared spectra in vivo at and around the grooves. The animals were sacrificed after 39 weeks and the joints were harvested. Spectra were reacquired ex vivo to ensure reliability of in vivo measurements and for reference analyses. Additionally, cartilage thickness and instantaneous modulus were determined via computed tomography and mechanical testing, respectively. The relationship between the ex vivo spectra and cartilage reference properties was determined using convolutional neural network. RESULTS: In an independent test set, the trained networks yielded significant correlations for cartilage thickness (ρ = 0.473) and instantaneous modulus (ρ = 0.498). These networks were used to predict the reference properties at baseline and at follow-up time points. In the radiocarpal joint, cartilage thickness increased significantly with both groove types after baseline and remained swollen. Additionally, at 39 weeks, a significant difference was observed in cartilage thickness between controls and sharp grooves. For the instantaneous modulus, a significant decrease was observed with both groove types in the radiocarpal joint from baseline to 23 and 39 weeks. CONCLUSION: NIRS combined with machine learning enabled determination of cartilage properties in vivo, thereby providing longitudinal evaluation of post-intervention injury development. Additionally, radiocarpal joints were found more vulnerable to cartilage degeneration after damage than intercarpal joints.
Assuntos
Articulações do Carpo/diagnóstico por imagem , Doenças das Cartilagens/diagnóstico por imagem , Cartilagem Articular/diagnóstico por imagem , Aprendizado de Máquina , Redes Neurais de Computação , Espectroscopia de Luz Próxima ao Infravermelho , Articulação do Punho/diagnóstico por imagem , Animais , Artroscopia , Doenças das Cartilagens/patologia , Cartilagem Articular/lesões , Cartilagem Articular/patologia , Cavalos , Tamanho do ÓrgãoRESUMO
The aim of this study was to develop and evaluate a method for detecting Mycobacterium avium ssp. paratuberculosis (MAP) bacteria in bovine fecal, milk, and colostrum samples using immunomagnetic beads (IMB) and a rhodamine hydrazone immunosensor. Immunomagnetic beads were prepared by using purified antibodies from hyperimmunized sera that were coupled to Fe nanoparticles with diethylene triamine pentaacetic acid (DTPA) or ethyl (dimethyl aminopropyl) carbodiimide (EDC)-N-hydroxy succinimide (NHS) as linkers. Rhodamine hydrazone particles were synthesized and coupled to IgY anti-MAP antibodies using DTPA or EDC-NHS linkers. Separation efficiency of the IMB was tested on bovine fecal, milk, and colostrum samples experimentally contaminated with MAP. The studied methods were evaluated on their ability to detect MAP and separate bacteria in complex mediums. The ELISA results indicated 95% efficacy in antibody coupling to IMB, with the DTPA-IMB method being more efficient than the EDC-NHS-IMB method. By using the DTPA-IMB method, MAP bacteria were successfully recovered from fecal, milk, and colostrum samples. The DTPA-IMB method used in combination with the rhodamine hydrazone immunosensor had a limit of detection equal to 30 and 30,000 MAP cells/mL using chromogenic and fluorescent properties, respectively. Combining the DTPA-IMB separation method with the rhodamine hydrazone immunosensor provides a fast, sensitive, and cost-beneficial method for detecting MAP in bovine feces, milk, and colostrum.
Assuntos
Técnicas Biossensoriais , Doenças dos Bovinos , Mycobacterium avium subsp. paratuberculosis , Paratuberculose , Animais , Técnicas Biossensoriais/veterinária , Bovinos , Doenças dos Bovinos/diagnóstico , Colostro , Fezes , Feminino , Hidrazinas , Imunoensaio/veterinária , Leite , Gravidez , RodaminasRESUMO
AIMS: The current study aimed to investigate the ability of lactic acid bacteria (LABs) in removing four polycyclic aromatic hydrocarbons (PAHs) namely, benzo(a)pyrene (BaP), benz(a)anthracene (BaA), chrysene (Chr) and benzo(b)fluoranthene (BbF) from contaminated phosphate buffer saline (PBS). METHOD AND RESULTS: The effect of initial PAH concentrations (5, 10, 15, 20 µg ml-1 ), bacterial population (107 , 108 , 109 , 1010 CFU per ml) and pH (3, 5, 7) was studied to evaluate bacterial binding ability. All the tested bacteria could remove BaA, Chr, BbF and BaP from phosphate buffer solution and in almost all assays, removing of PAHs was as follows: BaP>Chr>BaA>BaF. Bifidobacterium lactis BB-12 had the lowest binding rate for all four PAHs, while the highest binding ability was related to Lactobacillus acidophilus LA-5. Moreover, cell viability was not required for the binding ability and even acid-treated, heat-treated and ultrasonic-treated bacterial cells showed more binding ability. The results showed that the bacteria-PAH complex was irreversible after washing with PBS. CONCLUSIONS: The removal of PAHs was significantly related to pH of media, strains of bacteria, type and concentration of PAHs SIGNIFICANCE AND IMPACT OF THE STUDY: This study has been focused on the reduction of polycyclic aromatic hydrocarbons using LABs and probiotics. Our results showed that not only live strains but also inactivated tested strains are able to remove PAHs from aqueous media, presenting new methods to diminish the amount of these contaminants in foods. Furthermore, the results of this study can be used in future research on evaluating the effects of oral administration of probiotic supplements and even dead probiotic strains on reducing PAHs in humans.
Assuntos
Lactobacillales , Hidrocarbonetos Policíclicos Aromáticos , Lactobacillales/química , Lactobacillales/metabolismo , Lactobacillales/fisiologia , Hidrocarbonetos Policíclicos Aromáticos/isolamento & purificação , Hidrocarbonetos Policíclicos Aromáticos/metabolismo , ProbióticosRESUMO
AIMS: To compare the efficacy of sitagliptin versus pioglitazone as add-on drugs in patients with poorly controlled diabetes with metformin and sulfonylureas. METHODS: This is a randomized, open-label, parallel assignment clinical trial. Patients who had inadequate glycemic control [7% (53 mmol/mol) ≤ A1C < 11% (97 mmol/mol)] despite a minimum 6-month period of active treatment with metformin 2000 mg/day plus gliclazide 240 mg/day were enrolled in the study. HbA1C, fasting blood glucose (FBG), fasting plasma lipid parameters [total cholesterol (TC0, low-density lipoprotein cholesterol (LDL-C), triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C)], systolic and diastolic blood pressure (SBP, DBP), weight, waist circumference, and body mass index were measured at baseline and after 17, 34, and 52 weeks of treatment. Generalized estimating equation analysis was done to compare treatment groups for continuous efficacy parameters. RESULTS: No significant difference in HbA1C reduction was observed between the treatment groups during the study course. (P = 0.149, adjusted P = 0.434; coefficient - 0.11 ± 0.08). The FBG (P = 0.032; coefficient 7.44 ± 3.48), HDL-C (P = 0.001; coefficient - 2.69 ± 0.83), TG (P = 0.027; coefficient 12.63 ± 5.71) and SBP (P < 0.001; coefficient 5.43 ± 1.26) changes from baseline, and weight gain were greater in the pioglitazone group. The mean changes in LDL-C and TC from baseline to week 52 were greater in the sitagliptin group (P = 0.034; coefficient - 7.40 ± 3.50, P = 0.013; coefficient - 7.16 ± 2.88, respectively). CONCLUSION: Sitagliptin and pioglitazone were equally effective in improvement of HbA1C. There were some differences in terms of lipid indices, weight gain, and SBP. The current study confirmed that both sitagliptin and pioglitazone are effective treatment options and the decision should be made for each individual based on the baseline characteristics.
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Biomarcadores/análise , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Pioglitazona/uso terapêutico , Fosfato de Sitagliptina/uso terapêutico , Compostos de Sulfonilureia/uso terapêutico , Glicemia/metabolismo , Quimioterapia Combinada , Feminino , Seguimentos , Hemoglobinas Glicadas/análise , Humanos , Hiperglicemia/prevenção & controle , Hipoglicemia/prevenção & controle , Masculino , Pessoa de Meia-Idade , PrognósticoRESUMO
1. Infectious bursal disease virus (IBDV) causes immunosuppression in chickens, increasing their susceptibility to other infectious diseases and resulting in vaccination failure. Here, we investigated the immune-depressing effect of IBDV on H9N2 avian influenza viral infection in the broiler chickens. 2. For this purpose, chickens were divided into four groups. In group A, chickens were inoculated with IBDV at 21 days of age and H9N2 avian influenza virus (AIV) 5 days later. Groups B and C only received AIV at 26 days of age and IBDV at 21 days, respectively. The control group (D) were inoculated with normal saline at the same times. Tissue samples from different organs were collected on the days 1, 3, 6, 9, and 12 after H9N2 infection. 3. Macroscopic observation showed IBD lesions in groups A and C, including swollen bursa with the presence of gelatinous exudates, haemorrhages in the thigh muscle, edema, and nephritis. 4. Reverse Transcription-PCR was used to study H9N2 AIV dissemination, and qRT-PCR to determine viral genome copy number in different organs. A considerable titre of AIV was found in the trachea, lungs, cecal tonsils, spleens, and feces of infected chickens. The genome copy number of the virus in the trachea and lungs of group A was significantly higher than that in group B on the first day after inoculation. But in the other days post inoculation, RT-PCR did not detect the AIV genome in group A. Although there might have been some immunosuppression in group A, IBDV could interfere with AIV replication in the chickens of this group. 5. In conclusion, we propose that pre-exposure to IBDV at 3 weeks of age reduces the replication and shedding of H9N2 in broiler chicken.
Assuntos
Infecções por Birnaviridae/veterinária , Galinhas , Vírus da Doença Infecciosa da Bursa/fisiologia , Vírus da Influenza A Subtipo H9N2/fisiologia , Influenza Aviária/virologia , Doenças das Aves Domésticas , Eliminação de Partículas Virais/fisiologia , Animais , Infecções por Birnaviridae/virologia , Coinfecção/veterinária , Coinfecção/virologia , Distribuição AleatóriaRESUMO
The role of tumour necrosis factor-alpha (TNF-α) is not fully understood in human leishmaniasis. We analysed the alterations in the levels of TNF-α, soluble TNF receptor type 1 (sTNFR I), IL-17 and IL-22 productions in active and healed leishmaniases. Blood samples were collected from volunteers with active cutaneous leishmaniasis (ACL), the same subjects after lesion healing (healed CL = HCL), volunteers with active visceral leishmaniasis (AVL), healed VL (HVL) and healthy controls. Levels of cytokines were titrated on Leishmania Ag-stimulated PBMC culture. The mean level of TNF-α production from stimulated cells was significantly higher in ACL than controls (P < 0·001) and significantly reduced after treatment in HCL volunteers (P < 0·05). The mean level of sTNFR I production was significantly higher in ACL than controls (P < 0·001) and significantly reduced after treatment in HCL volunteers (P < 0·05). The mean level of IL-22 production in AVL was significantly higher than controls (P < 0·05) and was significantly lower in HVL compared with AVL (P < 0·001) and controls (P < 0·05). The levels of TNF-α (P = 0·0025) and sTNFR I (P < 0·01) productions from PBMCs showed significant decreasing trend after treatment in each CL volunteer. Reduction in TNF-α is associated with clinical response to treatment and healing of CL lesions due to L. major.
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Leishmaniose Cutânea/sangue , Leishmaniose Visceral/sangue , Receptores Tipo I de Fatores de Necrose Tumoral/sangue , Fator de Necrose Tumoral alfa/sangue , Adulto , Antiprotozoários/uso terapêutico , Estudos de Casos e Controles , Feminino , Humanos , Interleucina-17/sangue , Interleucinas/sangue , Leishmaniose Cutânea/tratamento farmacológico , Leishmaniose Visceral/tratamento farmacológico , Masculino , Meglumina/uso terapêutico , Antimoniato de Meglumina , Pessoa de Meia-Idade , Compostos Organometálicos/uso terapêutico , Resultado do Tratamento , Adulto Jovem , Interleucina 22RESUMO
Prostate cancer is considered as the major cause of death among men around the world. There are a number of medicinal plants triggering apoptosis response in cancer cells, thus have a therapeutic potential. Therefore, further studies to characterize beneficial properties of these plants in order to introduce novel anti-cancer drugs are the interest of recent researches on the alternative medicine. On the other hand, due to traditional uses and availability of Urtica dioica extract, we decided to evaluate the efficacy of this medicinal herb on pc3 prostate cancer cell line. In the present study the cytotoxic effects of Urtica dioica extract were assessed by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay and trypan blue viability dye. Then, DNA fragmentation and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay were exploited to measure cell death and apoptosis stage. The expression levels of caspase 3, caspase 9 and Bcl-2 genes were quantified by Real-Time PCR. Finally, Cell cycle was analyzed by flow cytometry. MTT assay showed that dichloromethanolic extract of Urtica dioica significantly inhibited the cell growth. According to the DNA fragmentation and TUNEL assay results, the herbal extract was able to induce apoptosis in prostate cancer cells. Our findings also demonstrated that the plant extract substantially increases the caspase 3 and 9 mRNA expression, while decreases Bcl-2. Cell cycle arrest was occurred in G2 stage, due to the results of flow cytometry. These results indicate that dichloromethanolic extract of Urtica dioica can successfully induce apoptosis in PC3 cells. Therefore, it could be used as a novel therapeutic candidate for prostate tumor treatment.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Extratos Vegetais/farmacologia , Próstata/efeitos dos fármacos , Neoplasias da Próstata/tratamento farmacológico , Urtica dioica/química , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Caspase 3/genética , Caspase 9/genética , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Fragmentação do DNA/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Cloreto de Metileno/química , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Próstata/metabolismo , Próstata/patologia , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Proteínas Proto-Oncogênicas c-bcl-2/genéticaRESUMO
Breast cancer is the most common cancer among women in worldwide, especially in developing countries. Therefore, a large number of anticancer agents with herbal origins have been reported against this deadly disease. This study is the first to examine the cytotoxic and apoptotic effects of Urtica dioica in MDA-MB-468, human breast adenocarcinoma cells. The 3-(4,5-dimethylethiazol-2 yl)-2,5- diphenyltetrazolium (MTT) reduction and trypan-blue exclusion assay were performed in MDA-MB-468 cells as well as control cell line L929 to analyze the cytotoxic activity of the dichloromethane extract. In addition, Apoptosis induction of Urtica dioica on the MDA-MB-468 cells was assessed using TUNEL (terminal deoxy transferase (TdT)-mediated dUTP nick- end labeling) assay and DNA fragmentation analysis and real-time polymerase chain reaction (PCR). The results showed that the extract significantly inhibited cell growth and viability without inducing damage to normal control cells. Nuclei Staining in TUNEL and DNA fragments in DNA fragmentation assay and increase in the mRNA expression levels of caspase-3, caspase-9, decrease in the bcl2 and no significant change in the caspase-8 mRNA expression level, showed that the induction of apoptosis was the main mechanism of cell death that induce by Urtica dioica extract. Our results suggest that urtica dioica dichloromethane extract may contain potential bioactive compound(s) for the treatment of breast adenocarcinoma.
Assuntos
Apoptose/efeitos dos fármacos , Extratos Vegetais/farmacologia , Urtica dioica/química , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Caspase 3/genética , Caspase 3/metabolismo , Caspase 8/genética , Caspase 8/metabolismo , Caspase 9/genética , Caspase 9/metabolismo , Linhagem Celular Tumoral , Fragmentação do DNA/efeitos dos fármacos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Cloreto de Metileno/química , Extratos Vegetais/química , Folhas de Planta/química , Folhas de Planta/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Urtica dioica/metabolismoRESUMO
Due to the high prevalence and mortality rate of colorectal cancer (CRC), new treatment approaches like combination therapy seem to be necessary. The relationship between chronic inflammation and colorectal cancer development and progression has been shown to be important. Celecoxib, a selective COX-2 inhibitor, is the only non-steroidal anti-inflammatory drug (NSAID) that has been approved for cancer therapy and prevention. Because of cardiovascular side effects of COX-2 inhibitors, combination therapy may improve the therapeutic profile. 17-Demethoxy-17-allylamino geldanamycin (17-AAG), a heat shock protein 90 (HSP90) inhibitor, shows anti-inflammatory effects via down-regulation of the key mediators of inflammation such as Nuclear Factor κB (NF-kB), JAK/Signal Transducer and Activator of Transcription (JAK/STAT). Thus, we studied the effect(s) of combination of 17-AAG and celecoxib on HT-29 cells viability and apoptosis induction. Based on MTT results, we showed an increase in the inhibitory effect of celecoxib when combined with 17-AAG, especially at low a concentration of celecoxib. Flow cytometry analysis demonstrated that apoptosis induction is probably the mechanism of additive inhibitory effects of 17-AAG and celecoxib combination. To explore the possible mechanism of apoptosis induction by 17-AAG and celecoxib combination, levels of BAX and BCL-2 proteins were determined by western blotting. The BAX/BCL-2 ratio in the combination group was increased compared to 17-AAG or celecoxib alone, mainly via decreasing BCL-2 levels. In conclusion, 17-AAG, increased inhibitory effects of celecoxib on HT-29 cells, probably by induction of apoptosis.
Assuntos
Apoptose/efeitos dos fármacos , Benzoquinonas/farmacologia , Celecoxib/farmacologia , Proliferação de Células/efeitos dos fármacos , Proteínas de Choque Térmico HSP90/antagonistas & inibidores , Lactamas Macrocíclicas/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína X Associada a bcl-2/metabolismo , Western Blotting , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Inibidores de Ciclo-Oxigenase 2/farmacologia , Citometria de Fluxo , Proteínas de Choque Térmico HSP90/metabolismo , Células HT29 , Humanos , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteína X Associada a bcl-2/genéticaRESUMO
Some species of the Scrophularia genus have been extensively used as a natural remedy for treatment of various medical conditions. The objective of this study was to evaluate the growth inhibitory activity of Scrophularia frigida Boiss extracts as well as to study the effect of the potent extracts on the induction of apoptosis and cell cycle arrest on human breast cancer cells. S. frigida Boiss extracts exhibited obvious inhibitory effects on the growth of cancer cells and induced apoptosis. It is suggested that the extracts exert their anti-proliferative effect through multiple implications such as suppressing growth, arresting the cell cycle, increased DNA fragmentation, downregulation of the expression of human epidermal growth factor receptor 2 and myeloid cell Leukemia-1, and upregulation of pro-apoptotic messenger RNAs like caspase-3 and caspase-9. Taken together, the results obtained indicate that S. frigida Boiss extracts may contain effective compounds that can be used as a therapeutic anticancer agent.
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Apoptose/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Extratos Vegetais/farmacologia , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Scrophularia/química , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Neoplasias da Mama/fisiopatologia , Caspase 3/metabolismo , Caspase 9/metabolismo , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Fragmentação do DNA/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Feminino , Humanos , Proteína de Sequência 1 de Leucemia de Células Mieloides/metabolismo , Extratos Vegetais/química , Reação em Cadeia da Polimerase em Tempo Real , Scrophularia/metabolismoRESUMO
This study was designed to assess the beneficial effects of high-dose (cholecalciferol) vitamin D supplementation on metabolic profiles and pregnancy outcomes among pregnant women at risk for pre-eclampsia. This randomized double-blind placebo-controlled clinical trial was performed among 60 pregnant women at risk for pre-eclampsia according to abnormal uterine artery Doppler waveform. Subjects were randomly divided into 2 groups to receive 50 000 IU vitamin D supplements (n=30) or receive placebo (n=30) every 2 weeks from 20 to 32 weeks of gestation. Fasting blood samples were taken at baseline study and 12 weeks after the intervention to quantify relevant variables. Newborn's anthropometric measurements were determined. Pregnant women who received cholecalciferol supplements had significantly increased serum 25-hydroxyvitamin D concentrations (+17.92±2.28 vs. +0.27±3.19 ng/ml, p<0.001) compared with the placebo. The administration of cholecalciferol supplements, compared with the placebo, resulted in significant differences in serum insulin concentrations (+1.08±6.80 vs. +9.57±10.32 µIU/ml, p<0.001), homeostasis model of assessment-insulin resistance (HOMA-IR) (+0.19±1.47 vs. +2.10±2.67, p<0.001), homeostatic model assessment-beta cell function (HOMA-B) (+5.82±29.58 vs. +39.81±38.00, p<0.001) and quantitative insulin sensitivity check index (QUICKI) score (-0.009±0.03 vs. -0.04±0.03, p=0.004). Furthermore, cholecalciferol-supplemented pregnant women had increased HDL-cholesterol concentrations (+2.67 ± 8.83 vs. -3.23±7.76 mg/dl, p=0.008) compared with the placebo. Finally, cholecalciferol supplementation led to a significant rise in plasma total antioxidant capacity (TAC) concentrations (+79.00±136.69 vs. -66.91±176.02 mmol/l, p=0.001) compared with the placebo. Totally, the administration of cholecalciferol supplements among pregnant women at risk for pre-eclampsia for 12 weeks had favorable effects on insulin metabolism parameters, serum HDL-cholesterol, and plasma TAC concentrations.
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Colecalciferol/administração & dosagem , Adulto , Antioxidantes/análise , Proteína C-Reativa/análise , HDL-Colesterol/sangue , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Humanos , Insulina/sangue , Pré-Eclâmpsia/etiologia , Gravidez , Resultado da Gravidez , Fatores de RiscoRESUMO
MicroRNAs (miRNAs) are a large class of small noncoding RNAs approximately 22 nucleotides in length. They are the main regulators of gene expression, regulating specific oncogenes, tumor suppressors, cancer stem cells and metastasis. MicroRNAs have become valuable to cancer research in recent years. They appear as a significant biomarker in tumorigenesis. Briefly, the capacities of miRNA to identify between tumor and normal tissue, to distinguish between various subgroups of tumors and to foretell results or responses to therapy have attracted scientist's attention to these small RNAs. MicroRNAs' remarkable stability in both the tissue and bloodstream of cancer patients has elevated the possibility that miRNAs may prove to be a novel diagnostic biomarker. This review focuses on the utility of miRNAs as key biomarkers in cancer diagnosis, cancer prognosis and cancer therapy.
Assuntos
Biomarcadores Tumorais/genética , MicroRNAs/genética , Neoplasias , Carcinogênese/genética , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Humanos , Metástase Neoplásica/genética , Metástase Neoplásica/patologia , Neoplasias/diagnóstico , Neoplasias/genética , Neoplasias/mortalidade , Neoplasias/terapia , PrognósticoRESUMO
Trimethylamine N-oxide (TMAO), a common metabolite in animals and humans, can induce changes in the expression or conformation of heat shock proteins. It has also been introduced as a risk factor for atherosclerosis and a biomarker for kidney problems. On the other hand, increased levels of heat shock proteins 60 and 70 KDa are associated with increased atherosclerosis risk. This study was therefore designed to evaluate the possible effect(s) of TMAO on the expression of HSP60 and GRP78 at the mRNA and protein levels. Murine macrophage J774A.1 cells were treated with micromolar concentrations of TMAO and 4-phenylbutyric acid (4-PBA), a chemical chaperon, for different time intervals. Tunicamycin was also used as a control for induction of endoplasmic reticulum stress. Tunicamycin greatly increased both mRNA and protein levels of GRP78. Similarly but to a lesser extent compared to tunicamycin, TMAO also increased mRNA and protein levels of GRP78 in a dose and time-dependent manner. In contrast, 4-PBA failed to induce any changes. Similar to GRP78, HSP60 was also increased only at mRNA level in TMAO treated cells. 4-PBA also increased HSP60 mRNA levels, whereas, tunicamycin did not show any effect on either protein or mRNA levels of HSP60. Since both heat shock proteins are stress inducible and the elevation of GRP78 is a hallmark for endoplasmic reticulum stress induction, it can be concluded that TMAO may induce endoplasmic reticulum stress or may act through elevation of these heat shock proteins.
Assuntos
Chaperonina 60/biossíntese , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Proteínas de Choque Térmico HSP70/biossíntese , Proteínas de Choque Térmico/biossíntese , Macrófagos/metabolismo , Proteínas de Membrana/biossíntese , Metilaminas/farmacologia , Proteínas Mitocondriais/biossíntese , Animais , Butilaminas/farmacologia , Linhagem Celular , Chaperonina 60/genética , Chaperona BiP do Retículo Endoplasmático , Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico/genética , Macrófagos/efeitos dos fármacos , Proteínas de Membrana/genética , Camundongos , Proteínas Mitocondriais/genética , RNA Mensageiro/biossíntese , Tunicamicina/farmacologiaRESUMO
OBJECTIVES: The application of nanoparticles is widely spread in all aspects of modern life because of their unique features such as small size and high surface area. High surface area can be very reactive and produce reactive oxygen species (ROS). These nanoparticles can damage human and animal cells by increasing oxidative stress mechanism. Titanium dioxide nanoparticles (TiO2NPs) are among the top five nanoparticles used in consumer products, paints, and pharmaceutical preparations.TiO2 NPs have various capabilities such as robust oxidation, biocompatibility and photocatalytic properties. They are frequently used in a wide range of sciences, including pharmaceuticals, cosmetics, medicine and engineering. The ever increasing industrial and consumer applications of TiO2NPs raise concern over the possible risk association with their environmental exposure. METHODS: This study investigates the effects of TiO2NP on lung tissue by intraperitoneal injection to rats at different doses (15, 30, 60 and 70 mg/kg). RESULTS: Our results showed that intraperitoneal injection of TiO2NP creates capillary congestion and hemorrhage in alveolar wall, granulomas in lung parenchyma, and hemosiderin depositions in blood vessels adjacent to bronchioles without any inflammation. The pulmonary side effects could be due to the production of ROS post TiO2NP exposure (Tab. 1, Fig. 5, Ref. 27). Text in PDF www.elis.sk.
Assuntos
Capilares/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Nanopartículas Metálicas/efeitos adversos , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio , Titânio/farmacologia , Animais , Capilares/patologia , Exposição Ambiental , Granuloma/induzido quimicamente , Granuloma/patologia , Hemorragia/induzido quimicamente , Hemorragia/patologia , Injeções Intraperitoneais , Pulmão/patologia , Pneumopatias/induzido quimicamente , Ratos , Ratos Wistar , Titânio/efeitos adversosRESUMO
Developing electro-spun scaffolds with ideal mechanical properties for skin purposes can profit from using the Response Surface Methodology technique to define and optimize the outcome quality and required sterilization for use in vivo. This study investigated the effects of four main independent electrospinning variables for polycaprolactone nanofibers scaffold using multi-variable and multi-objective optimization. It was done to determine significant parameters on responses and find optimal conditions to reach the preferred properties. Young's modulus, elongation-at-break, and tensile strength were the responses. After obtaining appropriate models, the impact share of variables on the responses was determined using Sobol sensitivity analysis. The results showed that flow rate is the most significant parameter of elastic modulus and tensile strength responses, with 76.45 % and 41.27 % impact shares, respectively. The polymer concentration is the following significant parameter on elongation at break, tensile strength and, Young's modulus responses with 64.35 %, 39.485 and, 14.28 % impact share, respectively. Based on the optimized results, a skin scaffold with desired mechanical properties was achieved (under solution concentration of 10 % w/v, flow rate of 2 mL/h, nuzzle-collector distance of 15 cm, and applied voltage of 20 kV). Then it was sterilized with gamma radiation of various doses (25, 40, and 55 kGy) to use in vivo. The SEM analysis indicated no significant change in fibrous morphology due to gamma irradiation at any dosage. FTIR analysis demonstrated the breakup of ester bonds due to gamma irradiation. For samples irradiated by 25 kGy, the crystallinity percentage decreased and chains crosslinking without losing the mechanical stability was dominant. The studies demonstrated that 25 kGy of gamma irradiation could improve the mechanical properties of the optimized PCL skin scaffold, which is very promising for wound healing.
RESUMO
Low-pathogenic avian influenza virus (H9N2) is circulating in the poultry industry of many countries in the Middle East and Asia, causing serious economic damage. In this study the clinical signs, antibody response, viral shedding and efficacy of oil emulsion vaccines in Chukar partridges were investigated until 9 days post inoculation (d.p.i.). Seventy-five Chukar partridges (Alectoris chukar) were divided randomly in three groups of challenged (Group C), vaccinated and challenged (Group VC) and control (non-vaccinated and non-challenged [Group NC]), 25 birds/group. Groups C and VC were inoculated with 0.4 ml allantoic fluid containing 10(7) median embryo infective dose/bird of A/Chicken/Iran/772/1998(H9N2) avian influenza virus. Clinical signs, antibody response, viral shedding and vaccine efficacy were evaluated and compared among these groups over 9 days. Clinical signs such as coughing and sneezing with depression and decreased feed and water consumption were observed in Group C. In Group VC only a slight decrease in food and water consumption was observed. Both Groups C and VC showed maximum antibody titre at 9 d.p.i. At 1 d.p.i. the virus was detected from all tissues in challenged group, but the virus was not detected from the spleen and caecal tonsil of Group VC. Group C showed the longest period of viral shedding in the trachea and kidney.
Assuntos
Galliformes , Vírus da Influenza A Subtipo H9N2/patogenicidade , Influenza Aviária/imunologia , Influenza Aviária/prevenção & controle , Vacinas Virais/uso terapêutico , Animais , Anticorpos Antivirais/imunologia , Primers do DNA/genética , Ingestão de Líquidos/fisiologia , Ingestão de Alimentos/fisiologia , Genoma Viral/genética , Vírus da Influenza A Subtipo H9N2/genética , Influenza Aviária/fisiopatologia , Irã (Geográfico) , Reação em Cadeia da Polimerase Via Transcriptase Reversa/veterinária , Eliminação de Partículas Virais/imunologiaRESUMO
This paper presents a sheet of graphene as a simple band-pass filter in terahertz and infrared frequencies. The central frequency and quality factor of this band-pass filter can be tuned by changing the physical parameters, such as the substrate thickness, gate voltage, temperature, and conductivity of the graphene. The effects of these parameters on surface plasmon polariton waves and filter specifications are numerically depicted.