RESUMO
In recent years, the world has seen an alarming increase in obesity and is closely associated with insulin resistance, which is a state of low-grade inflammation, the latter characterized by elevated levels of proinflammatory cytokines in blood and tissues. A shift in energy balance alters systemic metabolic regulation and the important role that chronic inflammation, endoplasmic reticulum (ER) dysfunction, and activation of the unfolded protein response (UPR) plays in this process.Why obesity is so closely associated with insulin resistance and inflammation is not understood well. This suggests that there are probably many causes for obesity-related insulin resistance and inflammation. One of the faulty mechanisms is protein homeostasis, protein quality control system included protein folding, chaperone activity, and ER-associated degradation leading to endoplasmic reticulum (ER) stress.The ER is a vast membranous network responsible for the trafficking of a wide range of proteins and plays a central role in integrating multiple metabolic signals critical in cellular homeostasis. Conditions that may trigger unfolded protein response activation include increased protein synthesis, the presence of mutant or misfolded proteins, inhibition of protein glycosylation, imbalance of ER calcium levels, glucose and energy deprivation, hypoxia, pathogens, or pathogen-associated components and toxins. Thus, characterizing the mechanisms contributing to obesity and identifying potential targets for its prevention and treatment will have a great impact on the control of associated conditions, particularly T2D.
Assuntos
Estresse do Retículo Endoplasmático , Obesidade , Resposta a Proteínas não Dobradas , Humanos , Obesidade/metabolismo , Animais , Retículo Endoplasmático/metabolismo , Resistência à Insulina , Inflamação/metabolismoRESUMO
In this investigation, two new thermophilic bacteria were isolated. The new isolates were characterized by 16S rRNA, biochemical, morphological, and physiological analyzes and the isolates were identified as Geobacillus stearothermophilus strain Gecek20 and thermophilic Anoxybacillus flavithermus strain Gecek19. Various biological activities of extracellular Ag-NPs synthesized from thermophilic G. stearothermophilus strain Gecek20 and thermophilic A. flavithermus strain Gecek19 were evaluated. The produced NPs were analyzed by SEM, SEM-EDX, and XRD analyses. The antioxidant abilities of new synthesized Ag-NPs from thermophilic G. stearothermophilus strain Gecek20 (T1-Ag-NPs) and new synthesized Ag-NPs from thermophilic A. flavithermus strain Gecek19 (T2-Ag-NPs) were studied by DPPH inhibition and metal chelating ability. The highest DPPH and metal chelating abilities of T1-Ag-NPs and T2-Ag-NPs at 200 mg/L concentration were 93.17 and 90.85%, and 75.80 and 83.64%, respectively. The extracellular green synthesized T1-Ag-NPs and T2-AgN-Ps showed DNA nuclease activity at all tested concentrations. Moreover, both new synthesized Ag-NPs had antimicrobial activity against the strains studied, especially on Gram positive bacteria. T1-Ag-NPs and T2-AgNPs also showed powerful Escherichia coli growth inhibition. The highest biofilm inhibition percentages of T1-Ag-NPs and T2-Ag-NPs against Pseudomonas aeruginosa and Staphylococcus aureus were 100.0%, respectively, at 500 mg/L.
Assuntos
Anoxybacillus , Geobacillus stearothermophilus , Nanopartículas Metálicas , RNA Ribossômico 16S , Prata/farmacologia , Escherichia coliRESUMO
There are limited data about humoral response to vaccine in Behçet's syndrome (BS). We compared SARS-CoV-2 antibody response after two doses of inactivated (Sinovac/CoronaVac) or mRNA (Pfizer/BioNTech) vaccines in patients with BS and healthy controls (HCs). We studied 166 (92M/74F) patients with BS (mean age: 42.9 ± 9.6 years) and 165 (75M/90F) healthy controls (mean age: 42.4 ± 10.4 years), in a single-center cross-sectional design between April 2021 and October 2021. A total of 80 patients with BS and 89 HCs received two doses of CoronaVac, while 86 patients with BS and 76 HCs were vaccinated with BioNTech. All study subjects had a negative history for COVID-19. Serum samples were collected at least 21 days after the second dose of the vaccine. Anti-spike IgG antibody titers were measured quantitatively using a commercially available immunoassay method. We found that the great majority in both patient and HC groups had detectable antibodies after either CoronaVac (96.3% vs 100%) or BioNTech (98.8% vs 100%). Among those vaccinated with CoronaVac, BS patients had significantly lower median (IQR) titers compared to HCs [36.5 (12.5-128.5) vs 102 (59-180), p < 0.001]. On the other hand, antibody titers did not differ among patients with BS and HCs who were vaccinated with BioNTech [1648.5 (527.0-3693.8) vs 1516.0 (836.3-2599.5), p = 0.512). Among different treatment regimen subgroups in both vaccine groups, those who were using anti-TNF-based treatment had the lowest antibody titers. However, the difference was statistically significant only among those vaccinated with CoronaVac. Among patients vaccinated with BioNTech, there was no statistically significant difference between different treatment regimen groups. Compared to inactivated COVID-19 vaccine, mRNA-based vaccine elicited higher antibody titers among BS patients. Only in the CoronaVac group, patients especially those using anti-TNF agents were found to have low titers compared to healthy subjects. BS patients vaccinated with BioNTech were found to have similar seroconversion rates and antibody levels compared to healthy controls. Further studies should assess whether the low antibody titers are associated with diminished protection against COVID-19 in both vaccine groups.
Assuntos
Síndrome de Behçet , COVID-19 , Vacinas Virais , Adulto , Anticorpos Antivirais , Formação de Anticorpos , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Estudos Transversais , Humanos , Pessoa de Meia-Idade , RNA Mensageiro , SARS-CoV-2 , Inibidores do Fator de Necrose Tumoral , Vacinas de Produtos Inativados , Vacinas Virais/efeitos adversosRESUMO
Acrylamide is a compound that occurs with high temperature during food processing and causes oxidative damage. Recently, the importance of antioxidative components is increasing to prevent oxidative damage. Lactoferrin is an antioxidant protein mainly found in milk. Therefore, the aim of this study is to determine the dose-dependent protective effects of lactoferrin on oxidative damage caused by acrylamide. In this study, HepG2 cell lines were treated with lactoferrin doses (0, 25, 50, 100µM) and half maximal inhibitory concentration of acrylamide. After 24 hours malondialdehyde, superoxide dismutase, catalase and glutathione reductase levels were measured. Acrylamide significantly increased malondialdehyde levels in HepG2 cells compared to the control group; however, catalase, superoxide dismutase and glutathione reductace significantly reduced. On the other hand, added lactoferrin doses (50-100µM) significantly reduced lipid peroxidation levels. Besides, it was found that glutathione reductase, catalase and superoxide dismutase levels significantly increased. As a result, the protective effect of lactoferrin against the oxidative damage caused by acrylamide in HepG2 cells was determined. This effect is thought to be due to the antioxidant capacity of lactoferrin. In this context, it is recommended that more studies are carried out on the mechanism of action of lactoferrin on oxidative stress caused by acrylamide.
Assuntos
Acrilamida , Estresse Oxidativo , Acrilamida/toxicidade , Glutationa RedutaseRESUMO
O-linked N-acetyl-glucosamine (O-GlcNAc) is a post-translational protein modification that regulates cell signaling and involves in several pathological conditions. O-GlcNAc transferase (OGT) catalyzes the attachment, while O-GlcNAcase (OGA) splits the GlcNAc molecules from the serine or threonine residues of the nuclear and cellular proteins. The hexosamine biosynthesis pathway (HBP) is a small branch of glycolysis that provides a substrate for the OGT and serves as a nutrient sensor. In this study, we investigated the impact of external O-GlcNAc modification stimulus on the insulin signal transduction, unfolded protein response, and HBP in 3T3-L1 cells. First, we treated cells with glucosamine and PUGNAc to stimulate the O-GlcNAcylation of total proteins. Also, we treated cells with tunicamycin as a positive internal control, which is a widely-used endoplasmic reticulum stressor. We used two in vitro models to understand the impact of the cellular state of insulin sensibility on this hypothesis. So, we employed insulin-sensitive preadipocytes and insulin-resistant adipocytes to answer these questions. Secondly, the OGT-silencing achieved in the insulin-resistant preadipocyte model by using the short-hairpin RNA (shRNA) interference method. Thereafter, the cells treated with the above-mentioned compounds to understand the role of the diminished O-GlcNAc protein modification on the insulin signal transduction, unfolded protein response, and HBP. We found that elevated O-GlcNAcylation of the total proteins displayed a definite correlation in insulin resistance and endoplasmic reticulum stress. Furthermore, we identified that the degree of this correlation depends on the cellular state of insulin sensitivity. Moreover, reduced O-GlcNAcylation of the total proteins by the shRNA-mediated silencing of the OGT gene, which is the only gene to modify proteins with the O-GlcNAc molecule, reversed the insulin resistance and endoplasmic reticulum stress phenotype, even with the externally stimulated O-GlcNAc modification conditions. In conclusion, our results suggest that OGT regulates insulin receptor signaling and unfolded protein response by modulating O-GlcNAc levels of total proteins, in response to insulin resistance. Therefore, it can be a potential therapeutic target to prevent insulin resistance and endoplasmic reticulum stress.
Assuntos
Acetilglucosamina/metabolismo , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Resistência à Insulina , N-Acetilglucosaminiltransferases/metabolismo , Processamento de Proteína Pós-Traducional , Resposta a Proteínas não Dobradas/efeitos dos fármacos , Células 3T3-L1 , Acetilglucosamina/análogos & derivados , Acetilglucosamina/farmacologia , Adipócitos/efeitos dos fármacos , Animais , Resistência a Medicamentos , Glucosamina/farmacologia , Glicólise , Hexosaminas/biossíntese , Camundongos , N-Acetilglucosaminiltransferases/antagonistas & inibidores , Oximas/farmacologia , Fenilcarbamatos/farmacologia , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Interferência de RNA , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/farmacologia , Transdução de Sinais/efeitos dos fármacos , Tunicamicina/farmacologia , beta-N-Acetil-Hexosaminidases/metabolismoRESUMO
In this study, we reported the design and the fabrication of Ag and TiO2 modified polycaprolactone (PCL) electrospun nanofiber (NF) mats. The as-prepared NF mats were fabricated by one-step electrospinning and it was exploited for three different purposes (i) reusable SERS substrate for quantitative analysis to trace organic pollutants, (ii) photocatalyst for degradation of organic pollutants and (iii) antibacterial agent for killing of bacteria. Three different nanofiber mats, PCL, PCL-TiO2, PCL/TiO2-Ag NFs. were fabricated and further investigated. The morphologies and structures of the as-prepared nanofiber mats were carried out using X-ray diffraction spectroscopy (XRD), field emission scanning electron microscopy (FE-SEM), energy-dispersive X-ray spectroscopy (EDX) and fourier transform infrared spectroscopy (FT-IR) techniques. PCL/TiO2-Ag NFs served as a highly effective SERS platform with a detection limit of 10â¯nM for the detection of methylene blue dye (MB). A remarkable feature of the presented platform is the ability to reuse the PCL/TiO2-Ag NFs for SERS analysis of MB; availing from its capability for self-cleaning under UV light. By employing PCL/TiO2-Ag NFs nanocatalyst, complete photocatalytic degradation of the probe analytes MB and ibuprofen (Ibu) under UV irradiation was accomplished not more than 180â¯min. Moreover, PCL/TiO2-Ag NF mats showed a highly promising bactericidal feature against gram-negative Escherichia coli and gram-positive Staphylococcus aureus bacteria, which immensely emerged due to the presence of Ag NPs. This new trending nanofiber is assumed to lead a bunch of changes in the field of photocatalytic, SERS and antibacterial studies.
Assuntos
Nanofibras/química , Poliésteres/química , Prata/química , Titânio/química , Antibacterianos/química , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Poluentes Ambientais/química , Azul de Metileno/química , Nanofibras/toxicidade , Fotólise , Análise Espectral Raman/instrumentaçãoRESUMO
Microextraction procedures for the separation of Pb(II) from water and food samples extracts were developed. A deep eutectic solvent composed of α-benzoin oxime and iron(III) chloride dissolved in phenol was applied as a phase separator support. In addition, this deep eutectic mixture worked as an efficient extractor of Pb(II). The developed microextraction process showed a high ability to tolerate the common coexisting ions in the real samples. The optimum conditions for quantitative recoveries of Pb(II) from aqueous extracts were at pH 2.0, conducted by adding 150 µL from the deep eutectic solvent. The quantitative recoveries were obtained with various initial sample volumes up to 30 mL. Limits of detection and limits of quantification of 0.008 and 0.025 µg L-1 were achieved with a relative standard deviation (RSD%) of 2.9, which indicates the accuracy and sensitivity of the developed procedure. Recoveries from the reference materials, including TMDA 64.2, TMDA 53.3, and NCSDC-73349, were 100%, 97%, and 102%, respectively. Real samples, such as tap, lake, and river water, as well as food samples, including salted peanuts, chickpeas, roasted yellow corn, pistachios, and almonds, were successfully applied for Pb(II) analysis by atomic absorption spectroscopy (AAS) after applying the developed deep eutectic solvent-based microextraction procedures.
Assuntos
Compostos Férricos/isolamento & purificação , Chumbo/isolamento & purificação , Poluentes Químicos da Água/isolamento & purificação , Água/química , Animais , Compostos Férricos/química , Contaminação de Alimentos , Humanos , Chumbo/toxicidade , Limite de Detecção , Microextração em Fase Líquida , Leite/química , Espectrofotometria Atômica , Poluentes Químicos da Água/químicaRESUMO
A flower-like Fe3O4/GO/CdSe nanodot magnetic hybrid material was produced and applied to magnetic solid-phase extraction of ibuprofen from pharmaceuticals, water, and urine samples. The material was characterized by X-ray diffraction, Raman spectroscopy and field emission scanning electron microscopy and SEM-EDX. The pH value, volume of sample solution, amount of sorbent, type and volume of elution solvent and extraction time were optimized. Following elution with acetone, ibuprofen was quantified by HPLC-DAD detection. The recoveries of ibuprofen from spiked real samples ranged between 87 and 109%, and the intra-day and inter-day relative standard deviations from 1.25 to 3.02%. The limit of detection, limit of quantification and preconcentration factor are 0.36 ng·mL-1,1.20 ng·mL-1 and 150, respectively. Graphical abstract Schematic representation of the combination of flower-like Fe3O4/GO/CdSe nanodot-based magnetic solid phase extraction (MSPE) and high-performance liquid chromatography (HPLC) procedure for the extraction and analysis of ibuprofen in pharmaceuticals, water, and urine samples.
RESUMO
A MWCNT@MoSe2 nanorod hybrid material was synthesized by a hydrothermal method and used as an adsorbent for trace levels of Pb(II) and Cu(II). The material was characterized by Raman spectroscopy, XRD, SEM, SEM-EDX, SEM-mapping and BET methods. The hybrid material is demonstrated to be a viable sorbent for ultrasound-assisted solid phase extraction of Pb(II) and Cu(II) at pH 5.5. Following desorption with 3 M HNO3, the two elements were quantified by FAAS. Key parameters affecting the extraction efficiency, including eluent conditions, amount of adsorbent, sample volume were optimized. No significant interference by other ions is observed. The accuracy of the method was evaluated by the analysis of the certified reference materials TMDA-53.3 (lake water) and SPS-WW2 (waste water level 2). The recoveries were in good agreement with certified values. The method was successfully applied to the extraction/preconcentration of Pb(II) and Cu(II) in different real samples. Graphical abstract A hybrid material of type MWCNT@MoSe2 was synthesized, characterized, and used as adsorbent for Pb(II) and Cu(II). Key parameters affecting the extraction efficiency, including eluent conditions, amount of adsorbent, sample volume were optimized. The method was applied to the extraction of analytes in water samples.
RESUMO
A sensitive, rapid, reliable, and easily applicable method based on magnetic solid phase extraction (MSPE) combined with HPLC-PDA was developed for monitoring propoxur (PRO) and fenitrothion (FEN) pesticides in environmental water samples. The effect of major experimental variables on the extraction efficiency of both the pesticides was investigated and optimized systematically. For this purpose, a new magnetic material containing decanoic acid on the surface of particles was synthesized and characterized by XRD, FT-IR, SEM, EDX, and TGA analysis in detail. The simultaneous determination of pesticide molecules was carried out by using a Luna Omega C18 column, isocratic elution of acetonitrile (ACN): Water (70:30 v/v) with a flow rate of 1.2 mL min-1. After MSPE, the linear range for pesticide molecules (r2 > 0.9982) was obtained in the range of 5-800 and 10-800 ng mL-1, respectively. The limit of detections (LOD) are 1.43 and 4.71 ng mL-1 for PRO and FEN, respectively while RSDs % are below 3.5%. The applicability of the proposed method in four different environmental samples were also investigated using a standard addition-recovery procedure. Average recoveries at two spiking levels were over the range of 91.3-102.5% with RSD < 5.0% (n = 3). The obtained results show that decanoic acid grafted magnetic particles in MSPE combined with HPLC-PDA is a fast and simple method for the determination of PRO and FEN in environmental water samples.
Assuntos
Ácidos Decanoicos/química , Fenitrotion/química , Nanopartículas de Magnetita/química , Resíduos de Praguicidas/química , Propoxur/química , Cromatografia Líquida de Alta Pressão , Ácidos Decanoicos/análise , Ácidos Decanoicos/isolamento & purificação , Monitoramento Ambiental , Fenitrotion/análise , Fenitrotion/isolamento & purificação , Limite de Detecção , Estrutura Molecular , Resíduos de Praguicidas/análise , Resíduos de Praguicidas/isolamento & purificação , Propoxur/análise , Propoxur/isolamento & purificação , Reprodutibilidade dos Testes , Extração em Fase SólidaRESUMO
Genetic variations might play a role in susceptibility to temporomandibular joint internal derangement (TMJ-ID) and osteoarthritis of the joint (TMJOA). Vitamin D receptor (VDR) polymorphisms have been shown to be associated with disc degeneration-linked pathologies, particularly osteoarthritis (OA). The aim of this study was to evaluate whether VDR polymorphisms present susceptibility to TMJ-ID/TMJOA. The study included 49 unrelated TMJ-ID patients with OA (31.7 ± 7.9) that were grouped and evaluated as having anterior disk displacement with reduction (ADDwR, n = 24) (31.58 ± 8.25) and without reduction (ADDwoR, n = 25) (31.8 ± 7.53) and 70 healthy controls (28.22 ± 5.9). DNA was extracted from blood samples using the standard proteinase K/phenol-chloroform method. Apa1 and Taq1 polymorphisms were investigated using a polymerase chain reaction-based restriction fragment length polymorphism assay. When TMJ-ID patients, ADDwR cases and ADDwoR cases versus healthy controls were compared, Apa1 Aa genotype compared to AA genotype had odds ratios of 1.65, 1.79 and 1.64 respectively (p > 0.05). In TMJ-ID women versus healthy women Aa genotype had 2.06 fold (p = 0.15) odds compared to AA genotype. Taq1 results showed that in TMJ-ID patients and ADDwoR cases the Tt genotype had odds ratios of 0.63 and 0.44 fold (p > 0.05) respectively. In TMJ-ID women the Tt and tt genotypes had odds ratios of 0.53 and 0.73 (p > 0.05). Combined VDR genotypes revealed that AATT had a 3.3 fold (p = 1.21) odds ratio while AATt had a 2.0 fold odds ratio (p = 0.29) (OR 0.59, 95% CI 0.23-1.49, p = 0.26) compared to AaTt. Although our results do not confirm susceptibility of VDR polymorphisms to TMJ-ID/TMJOA ,this relation needs to be further evaluated in a large cohort study.
Assuntos
Osteoartrite/genética , Receptores de Calcitriol/genética , Transtornos da Articulação Temporomandibular/genética , Adulto , Alelos , Estudos de Coortes , Feminino , Frequência do Gene/genética , Predisposição Genética para Doença/genética , Genótipo , Humanos , Masculino , Razão de Chances , Polimorfismo Genético , Receptores de Calcitriol/fisiologia , Articulação Temporomandibular/fisiologia , Turquia , Vitamina D/metabolismoRESUMO
In recent years, the world has seen an alarming increase in obesity and closely associated with insulin resistance which is a state of low-grade inflammation, the latter characterized by elevated levels of proinflammatory cytokines in blood and tissues. A shift in energy balance alters systemic metabolic regulation and the important role that chronic inflammation, endoplasmic reticulum (ER) dysfunction, and activation of the unfolded protein response (UPR) play in this process.Why obesity is so closely associated with insulin resistance and inflammation is not understood well. This suggests that there are probably other causes for obesity-related insulin resistance and inflammation. One of these appears to be endoplasmic reticulum (ER) stress.The ER is a vast membranous network responsible for the trafficking of a wide range of proteins and plays a central role in integrating multiple metabolic signals critical in cellular homeostasis. Conditions that may trigger unfolded protein response activation include increased protein synthesis, the presence of mutant or misfolded proteins, inhibition of protein glycosylation, imbalance of ER calcium levels, glucose and energy deprivation, hypoxia, pathogens or pathogen-associated components and toxins. Thus, characterizing the mechanisms contributing to obesity and identifying potential targets for its prevention and treatment will have a great impact on the control of associated conditions, particularly T2D.
Assuntos
Estresse do Retículo Endoplasmático/fisiologia , Retículo Endoplasmático/fisiologia , Obesidade/fisiopatologia , Animais , Humanos , Inflamação/fisiopatologia , Resistência à Insulina/fisiologiaRESUMO
Nanosized single crystal orthorhombic Bi2WO6 was synthesized by a hydrothermal method and used as a sorbent for vortex assisted solid phase extraction of lead(II). The crystal and molecular structure of the sorbent was examined using XRD, Raman, SEM and SEM-EDX analysis. Various parameters affecting extraction efficiency were optimized by using multivariate design. The effect of diverse ions on the extraction also was studied. Lead was quantified by flame atomic absorption spectrometry (FAAS). The recoveries of lead(II) from spiked samples (at a typical spiking level of 200-400 ng·mL-1) are >95%. Other figures of merit includes (a) a detection limit of 6 ng·mL-1, (b) a preconcentration factor of 50, (c) a relative standard deviation of 1.6%, and (d) and adsorption capacity of 6.6 mg·g-1. The procedure was successfully applied to accurate determination of lead in (spiked) pomegranate and water samples. Graphical abstract Nanosized single crystal orthorhombic Bi2WO6 was synthesized and characterized by a hydrothermal method and used as a sorbent for vortex assisted solid phase extraction of lead(II). The procedure was successfully applied to accurate determination of lead in (spiked) pomegranate and water samples.
RESUMO
PURPOSE: BK virus (BKV) nephropathy has increasingly become an important cause of morbidity in renal transplant recipients. We evaluated the frequency and associated factors for BKV infection in a center performing mainly living donor transplantations over a long time period. METHODS: One hundred consecutive renal transplant patients were included. Quarterly visits were planned to examine urine for decoy cells and to measure the BKV DNA in the blood and urine. Renal biopsy was performed in case of deteriorated allograft function. Serological examinations for BKV immunoglobulin G (IgG) were performed in donors. RESULTS: Throughout the entire follow-up period, the rates of viruria, viremia, and the positivity of decoy cells were 12%, 6%, and 13%, respectively. The negative and positive predictive values of decoy cells were 93.1% and 69.2%, respectively, for viruria, and 99.2% and 45.5%, respectively, for viremia. Biopsy-proven BKV nephropathy was observed in 1 patient. The BKV IgG was positive in all living donors. Viruria and viremia were associated with deceased donor transplantation, acute rejection, and pulse steroid therapy. In addition, viremia was associated with antithymocyte globulin therapy and a short duration of the posttransplant period. CONCLUSIONS: The frequency of BKV infection was lower in our transplant unit compared to previous reports. Reduced doses of immunosuppression seem to be the main factor that may explain the reduced frequency. However, an active screening strategy is still of importance for this patient group.
Assuntos
Vírus BK , Nefropatias/epidemiologia , Transplante de Rim , Infecções por Polyomavirus/epidemiologia , Infecções Tumorais por Vírus/epidemiologia , Adulto , Anticorpos Antivirais/imunologia , Biópsia , DNA Viral/sangue , DNA Viral/urina , Feminino , Rejeição de Enxerto/prevenção & controle , Humanos , Imunoglobulina G/imunologia , Imunossupressores/administração & dosagem , Rim/patologia , Nefropatias/patologia , Nefropatias/virologia , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Infecções por Polyomavirus/imunologia , Infecções por Polyomavirus/metabolismo , Infecções por Polyomavirus/patologia , Transplantes/patologia , Infecções Tumorais por Vírus/imunologia , Infecções Tumorais por Vírus/metabolismo , Infecções Tumorais por Vírus/patologia , Viremia/epidemiologia , Viremia/metabolismoRESUMO
Patients with sarcoidosis usually have a benign course and a favourable prognosis. Although spontaneous remission is common, a progressive disease with a severe prognosis occurs in a small but significant number of patients. The aim of this study was to evaluate the potential significance of HLA antigens as a clinical marker on the outcome of sarcoidosis patients. We conducted a retrospective cohort study for HLA class I and II allels in 74 sarcoidosis patients and 72 healthy transplant donors. Bronchoscopy and bronchial biopsies were performed in each patient. Two or more positive bronchial biopsy samples revealing granulomatous inflammation was defined as diffuse while one positive biopsy sample was considered as limited endobronchial disease. Three or more extrapulmonary organ involvement was denoted as severe extrapulmonary disease. The patients were followed-up at least for eight years. Incidence of progressive disease was significantly high in patients with positive HLA-DRB1*07, DRB1*14 (p<0.05) and DRB1*15 (p <0.001) allels. HLA-DRB1*14 and DRB1*15 were associated with severe extrapulmonary organ involvement (p<0.001). HLA-DRB1 *14 (p<0.05) and DRB1*15 (p<0.001) were significantly more frequent in patients with diffuse endobronchial involvement. Incidence of familial disease was 14.8% with a 6.7% identical HLA typing. Presence of HLA class I and II allels may influence the severity and prognosis of sarcoidosis significantly. Apart from defining genetic susceptibility, HLA class I and class II allels appear to be relevant and crucial markers for the to predict the clinical outcome of sarcoidosis. Distinct heterogenity of sarcoidosis may arise from the particular presence of different allels in invidual patients.
Assuntos
Predisposição Genética para Doença/genética , Antígenos HLA/genética , Cadeias HLA-DRB1/genética , Sarcoidose Pulmonar/genética , Adulto , Alelos , Broncoscopia/métodos , Progressão da Doença , Feminino , Antígenos HLA/imunologia , Cadeias HLA-DRB1/imunologia , Humanos , Incidência , Masculino , Avaliação de Resultados em Cuidados de Saúde , Prognóstico , Estudos Retrospectivos , Sarcoidose Pulmonar/diagnóstico por imagem , Sarcoidose Pulmonar/mortalidade , Sarcoidose Pulmonar/fisiopatologia , População Branca/etnologiaRESUMO
Mammalian target of rapamycin, mTOR, is a major sensor of nutrient and energy availability in the cell and regulates a variety of cellular processes, including growth, proliferation, and metabolism. Loss of the tuberous sclerosis complex genes (TSC1 or TSC2) leads to constitutive activation of mTOR and downstream signaling elements, resulting in the development of tumors, neurological disorders, and at the cellular level, severe insulin/IGF-1 resistance. Here, we show that loss of TSC1 or TSC2 in cell lines and mouse or human tumors causes endoplasmic reticulum (ER) stress and activates the unfolded protein response (UPR). The resulting ER stress plays a significant role in the mTOR-mediated negative-feedback inhibition of insulin action and increases the vulnerability to apoptosis. These results demonstrate ER stress as a critical component of the pathologies associated with dysregulated mTOR activity and offer the possibility to exploit this mechanism for new therapeutic opportunities.
Assuntos
Apoptose/fisiologia , Insulina/metabolismo , Transdução de Sinais/fisiologia , Proteínas Supressoras de Tumor/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Antineoplásicos/metabolismo , Linhagem Celular , Pré-Escolar , Retículo Endoplasmático/metabolismo , Genes Supressores de Tumor , Humanos , Proteínas Substratos do Receptor de Insulina , Resistência à Insulina/fisiologia , Alvo Mecanístico do Complexo 1 de Rapamicina , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Complexos Multiproteicos , Neoplasias/metabolismo , Neoplasias/patologia , Neurônios/citologia , Neurônios/metabolismo , Estresse Oxidativo , Fenilbutiratos/metabolismo , Proteínas , Sirolimo/metabolismo , Serina-Treonina Quinases TOR , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteína 1 do Complexo Esclerose Tuberosa , Proteína 2 do Complexo Esclerose Tuberosa , Proteínas Supressoras de Tumor/genética , eIF-2 Quinase/genética , eIF-2 Quinase/metabolismoRESUMO
1-(2-Pyridylazo)-2-naphthol impregnated activated carbon cloth (PAN-imp-ACC) was prepared as a solid phase sorbent and, for the first time, was used for the simultaneous separation and preconcentration of trace amounts of lead, cadmium and nickel in water, soil and sewage sludge samples prior to determination by flame atomic absorption spectrometry (FAAS). The parameters governing the efficiency of the method were optimized, including the pH, the eluent type and volume, the sample and eluent flow rates, diverse ions effects and the sample volume. A preconcentration factor of 100 was achieved for all the metal ions, with detection limits of 0.1-2.8 µg L(-1) and relative standard deviations below 6.3%. The adsorption capacity of the PAN-imp-ACC for Pb(II), Cd(II) and Ni(II) ions was found to be 45.0 mg g(-1), 45.0 mg g(-1) and 43.2 mg g(-1), respectively. The method was validated by the analysis of the certified reference materials TMDA-64.2 fortified Lake Ontario water and BCR-146R Sewage Sludge Amended Soil (Industrial Origin). The procedure was applied to determine the analytes content in real samples.
Assuntos
Carbono/química , Monitoramento Ambiental/métodos , Metais/análise , Naftóis/química , Extração em Fase Sólida , Poluentes Químicos da Água/análise , Adsorção , Cádmio/análise , Íons/análise , Chumbo/análise , Níquel/análise , Ontário , Poluentes do Solo/análise , Espectrofotometria AtômicaRESUMO
A solid-phase extraction method for separation and preconcentration of Ir(IV) ion by using activated carbon cloth (ACC) has been presented. Ir(IV) as their 1-(2-pyridylazo) 2-naphtol (PAN) chelate was adsorbed on ACC at pH 2.0 and was eluted from ACC with acidic dimethylformamide (DMF). The Ir(IV) concentration was determined at 536 nm as Ir(IV)-PAN complex by using UV-vis spectrophotometer. The analytical parameters including pH, sample and eluent flow rates, amount of PAN, eluent type, concentration, and sample volume were optimized. The effects of foreign ions on the recoveries of iridium were also investigated. The preconcentration factor was calculated as 60. The limit of detection (LOD) and the limit of quantification (LOQ) of the method were found as 0.039 and 0.129 µg L(-1), respectively. The method was applied to soil and water samples for iridium determination.
Assuntos
Carvão Vegetal/química , Monitoramento Ambiental/métodos , Poluentes Ambientais/análise , Irídio/análise , Adsorção , Poluentes Ambientais/química , Irídio/química , Limite de Detecção , Naftóis , Solo/química , Extração em Fase Sólida/métodos , Espectrofotometria/métodos , Água/químicaRESUMO
A rapid, simple, selective, economical, and sensitive dispersive liquid-liquid microextraction methodology has been established for the preconcentration of copper (Cu) at trace levels. The Cu(II) was complexed with 1-(2-pyridylazo)-2-naphthol; ethanol and carbon tetrachloride were used as disperser and extraction solvents, respectively. To obtain quantitative recovery of Cu(II), the effects of parameters influencing its extraction efficiency and subsequent determinations, i.e., pH, amount of complexing reagent, extraction time, and type and volume of disperser and extraction solvents, were examined. LOD and LOQ were 0.06 and 0.20 microg/L, respectively. The enrichment factor of the proposed method was 60, and the RSD <5%. TMDA 51.3 and TMDA 70 fortified water certified reference materials were analyzed for validation of the procedure. The developed microextraction procedure has been used for the preconcentration of Cu(II) in water samples with acceptable results.
Assuntos
Cobre/química , Microextração em Fase Líquida/métodos , Naftóis/química , Espectrofotometria Atômica/métodos , Compostos Azo , Centrifugação , Concentração de Íons de Hidrogênio , Naftalenos , Fatores de TempoRESUMO
Helicobacter pylori is a Gram-negative bacterium that has been linked to peptic ulcer disease, gastric lymphoma, and gastric carcinoma. Apart from its well-demonstrated role in gastroduodenal diseases, some authors have suggested a potential role of Helicobacter pylori infection in several extra-intestinal pathologies including haematological, cardiovascular, neurological, metabolic, autoimmune, and dermatological diseases. Some studies suggest an association between Helicobacter pylori infection and skin diseases such as chronic idiopathic urticaria and rosacea. There have also been few case reports documenting association between Helicobacter pylori and psoriasis vulgaris, Behçet's disease, alopecia areata, Henoch-Schönlein purpura, and Sweet's syndrome. However, more systematic studies are required to clarify the proposed association between Helicobacter pylori and skin diseases; most of the studies do not show relevant relationships of these diseases with Helicobacter pylori infections. This review discusses skin diseases that are believed to be associated with Helicobacter pylori.