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1.
Inorg Chem ; 63(17): 7806-7819, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38622498

RESUMO

The structure and Li conductivity has been investigated in the Li1+xTi2-xInx(PO4)3 (0 ≤ x ≤ 2) series prepared by the ceramic route at 900 °C. The XRD patterns of 0 ≤ x ≤ 0.2 samples show the presence of rhombohedral (S.G. R3̅c); those of 0.2 ≤ x ≤ 1 samples display both rhombohedral and orthorhombic (S.G. Pbca), and 1 ≤ x ≤ 2 samples exhibit only monoclinic (S.G. P21/n) phases. At intermediate compositions, the secondary LiTiPO5 phase was detected. The Rietveld analysis of XRD patterns was used to deduce unit-cell parameters, chemical composition, and percentage of phases. The amount of In3+, deduced from structural refinements of three phases, was confirmed by 31P MAS NMR spectroscopy. The Li mobility was investigated by 7Li MAS NMR and impedance spectroscopies. The Li conductivity increased with the Li content in rhombohedral but decreased in orthorhombic, increasing again in monoclinic samples. The maximum conductivity was obtained in the rhombohedral x = 0.2 sample (σb = 1.9 × 10-3 S·cm-1), with an activation energy Eb = 0.27 eV. In this composition, the overall Li conductivity was σov = 1.7 × 10-4 S·cm-1 and Eov = 0.32 eV, making this composition a potential solid electrolyte for all-solid-state batteries. Another maximum conductivity was detected in the monoclinic x ∼ 1.25 sample (σov = 1.4 × 10-5 S·cm-1), with an activation energy Eov = 0.39 eV. Structural models deduced with the Rietveld technique were used to analyze the conduction channels and justify the transport properties of different Li1+xTi2-x Inx(PO4)3 phases.

2.
Eur J Immunol ; 52(3): 447-461, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34935145

RESUMO

Effective function of CD8+ T cells and enhanced innate activation of DCs in response to HIV-1 is linked to protective antiviral immunity in controllers. Manipulation of DC targeting the master regulator TANK-binding Kinase 1 (TBK1) might be useful to acquire controller-like properties. Here, we evaluated the impact of the combination of 2´3´-c´diAM(PS)2 and Poly I:C as potential adjuvants capable of potentiating DC´s abilities to induce polyfunctional HIV-1 specific CD8+ T-cell responses in vitro and in vivo using a humanized BLT mouse model. Adjuvant combination enhanced TBK-1 phosphorylation and IL-12 and IFN-ß expression on DC and increased their ability to activate polyfunctional HIV-1-specific CD8+ T cells in vitro. Moreover, higher proportions of hBLT mice vaccinated with ADJ-DC exhibited less severe CD4+ T-cell depletion following HIV-1 infection compared to control groups. This was associated with infiltration of CD8+ T cells in the white pulp from the spleen, reduced spread of infected p24+ cells to LN, and with preserved abilities of CD8+ T cells from the spleen and blood of vaccinated animals to induce specific polyfunctional responses upon antigen stimulation. Therefore, priming of DC with PolyI:C and STING agonists might be useful for future HIV-1 vaccine studies.


Assuntos
Vacinas contra a AIDS , HIV-1 , Vacinas contra a AIDS/metabolismo , Adjuvantes Imunológicos/farmacologia , Animais , Linfócitos T CD4-Positivos , Linfócitos T CD8-Positivos , Células Dendríticas , Proteína do Núcleo p24 do HIV/metabolismo , Tecido Linfoide , Camundongos , Poli I-C/farmacologia
3.
Inorg Chem ; 62(42): 17062-17073, 2023 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-37828755

RESUMO

The parallel 29Si magic angle spinning nuclear magnetic resonance (MAS NMR) and Fourier-transform infrared study of synthetic micas made it possible to compare structural features of the tetrasilicic magnesium mica K(Mg2.5□0.5) Si4O10(OH)2 (TMM) and their K(Mg3)(Si3.5Mg0.5)O10(OH)2 (TMMA) and K(Mg3)(Si3.5Be0.5)O10(OH)2 (TMMB) derivatives. In the TMM mica, SiO4 tetrahedra are elongated in the plane ab and shortened along the c* direction with respect to those of the phlogopite (Phl) K(Mg3)(Si3Al)O10(OH)2. The substitution of Si4+ by R2+ (Mg2+ or Be2+) produces, besides the 29Si MAS NMR signal of Si (3Si) at -91.2 ppm, new components at -84.4 or -87.5 ppm that correspond to Si (2Si1Mg) or Si(2Si1Be) environments. Tetrahedral cation distributions in TMM/TMMA, TMM/TMMB solid solutions are investigated with respect to the TMM/Phl series by means of NMR and Monte Carlo simulations, concluding that divalent Mg2+ and Be2+ are further dispersed than trivalent Al3+ cations in tetrahedral sheets of micas. In three analyzed series, cation distributions display features between those of the homogeneous dispersion of charges of phlogopites and the maximum dispersion of charges of TMM derivatives. In three series, the location of charge deficits that compensate K+ cations changes from octahedral in TMM to tetrahedral sheets in phlogopite and TMMA and TMMB derivatives.

4.
J Nerv Ment Dis ; 211(2): 141-149, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36095251

RESUMO

ABSTRACT: People exposed to potentially traumatic events (PTEs) may develop distinct symptom patterns, which may require different therapeutic approaches. We aimed to identify classes of people exposed to PTEs based on the presence of posttraumatic stress disorder (PTSD) clusters, anxiety, and depression and to explore which cognitive factors (rumination, worry, and negative cognitions) are associated with class membership. Latent class analyses were conducted to identify subgroups of 258 PTE-exposed Spanish adults. A three-class solution emerged: a resilient class with low odds of all symptoms ( n = 188); a partial PTSD class, characterized by partial PTSD clusters, moderate anxiety, and low depression ( n = 36); and a high symptom class, characterized by high PTSD, moderate anxiety, and low depression ( n = 34). These classes related meaningfully to rumination, worry, and negative cognitions. Distinct symptom patterns of PTSD clusters, anxiety, and depression can be distinguished in people exposed to PTEs and relate to cognitive risk factors of psychopathology.


Assuntos
Transtornos de Estresse Pós-Traumáticos , Adulto , Humanos , Transtornos de Estresse Pós-Traumáticos/psicologia , Depressão/etiologia , Depressão/psicologia , Transtornos de Ansiedade/complicações , Ansiedade/etiologia , Cognição
5.
Am J Drug Alcohol Abuse ; 49(6): 705-722, 2023 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-38011685

RESUMO

Background: Previous studies have reviewed the evidence on the increase in alcohol consumption after a terrorist attack. However, an increase does not necessarily imply the presence of an alcohol use disorder.Objectives: To conduct a systematic and meta-analytic review of the literature on the prevalence of increased alcohol consumption and alcohol use disorders in adult exposed to terrorism.Methods: A search of PsycINFO, MEDLINE and PTSDpubs identified 29 studies published up to March 2023 in which 38 adult samples totaling 282,753 persons exposed to terrorism were assessed. Using inverse variance heterogeneity models, pooled prevalence rates of increased alcohol use and alcohol use disorders were calculated.Results: 6% (95% CI [2.9, 9.5]) of the adults exposed to a terrorist attack increased their alcohol consumption. The prevalence of increased alcohol use varied depending on the degree of exposure (p = .006, R2 = .18) and the procedure for measuring increases (p = .043, R2 = .37). The prevalence of alcohol use disorders in adults exposed to a terrorist attack was 5.5% (95% CI [3.7, 7.5]), a rate that was not higher than that obtained in the general population and varied depending on the type of alcohol disorder (p = .015, R2 = .30).Conclusions: A relevant number of adults exposed to terrorist attacks will subsequently increase their alcohol consumption, but this increase is not associated with an increase in the prevalence of alcohol use disorders. Effects of terrorism on people's health are potentially widespread, but concerns of excessive alcohol use after terrorist attacks may be unwarranted.


Assuntos
Alcoolismo , Transtornos de Estresse Pós-Traumáticos , Terrorismo , Adulto , Humanos , Consumo de Bebidas Alcoólicas/epidemiologia , Prevalência , Transtornos de Estresse Pós-Traumáticos/epidemiologia
6.
Int J Mol Sci ; 24(6)2023 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-36982905

RESUMO

A collection of repurposing drugs (Prestwick Chemical Library) containing 1200 compounds was screened to investigate the drugs' antimicrobial effects against planktonic cultures of the respiratory pathogen Streptococcus pneumoniae. After four discrimination rounds, a set of seven compounds was finally selected, namely (i) clofilium tosylate; (ii) vanoxerine; (iii) mitoxantrone dihydrochloride; (iv) amiodarone hydrochloride; (v) tamoxifen citrate; (vi) terfenadine; and (vii) clomiphene citrate (Z, E). These molecules arrested pneumococcal growth in a liquid medium and induced a decrease in bacterial viability between 90.0% and 99.9% at 25 µM concentration, with minimal inhibitory concentrations (MICs) also in the micromolar range. Moreover, all compounds but mitoxantrone caused a remarkable increase in the permeability of the bacterial membrane and share a common, minimal chemical structure consisting of an aliphatic amine linked to a phenyl moiety via a short carbon/oxygen linker. These results open new possibilities to tackle pneumococcal disease through drug repositioning and provide clues for the design of novel membrane-targeted antimicrobials with a related chemical structure.


Assuntos
Anti-Infecciosos , Infecções Pneumocócicas , Humanos , Streptococcus pneumoniae , Antibacterianos/farmacologia , Reposicionamento de Medicamentos , Mitoxantrona/farmacologia , Infecções Pneumocócicas/tratamento farmacológico , Anti-Infecciosos/farmacologia , Testes de Sensibilidade Microbiana , Membrana Celular
7.
Scand J Psychol ; 63(6): 680-688, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35674334

RESUMO

There are two parallel lines of research on the relationship between personality and depression, one based on the Big Five personality model and one on Beck's cognitive theory of depression. However, no study has jointly examined the dimensions and facets of the Big Five and the dysfunctional attitudes of Beck's theory. This was the objective of the present study. The Revised NEO Personality Inventory (NEO PI-R), the Dysfunctional Attitude Scale (DAS-A), and the Beck Depression Inventory (BDI-IA) were applied to 221 adults from the Spanish general population (53.7% females; mean age: 38.3 years). Various multiple linear regression analyses revealed that only the facet of depression was significantly related to depressive symptomatology. The different associations of the broad and specific personality traits and the need to control as many third variables as possible to prevent the finding of spurious relationships are discussed.


Assuntos
Atitude , Depressão , Adulto , Feminino , Humanos , Masculino , Depressão/psicologia , Inventário de Personalidade , Escalas de Graduação Psiquiátrica , Transtornos da Personalidade
8.
Gastroenterol Hepatol ; 45(4): 249-255, 2022 Apr.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-34562521

RESUMO

OBJECTIVES: Porphyria cutanea tarda (PCT) is common and usually associated with HCV chronic infection and HFE polymorphisms. Since DAA IFN-free regimens availability, SVR for HCV is nearly a constant and we wonder whether HCV SVR determine PCT evolution. METHODS: Retrospective observational study including patients with HCV associated PCT from the Gastroenterology and Infectious Diseases Departments at our Hospital, treated with DAA (Apr/2015-Apr/2017). Clinical variables of PCT were collected at PCT diagnosis, after PCT treatment, before DAA use and after SVR achievement. UROD activity and C282Y/H63D polymorphisms were registered. SPSS 22.0. RESULTS: 13 HCV-PCT patients included: median age 52.5 years; 4 females; 8 HCV/HIV co-infected (all on undetectable viral load). Classical PCT factors: 12 smoked, 9 alcohol abuse, 6 former IDU. 10 type I PCT and 1 type II PCT. HFE polymorphism: 2 cases with C282Y/H63D; H63D polymorphism in 8. PCT manifestations resolved with PCT treatment in 4 patients, almost completely in 7 patients, 1 patient referred stabilization and one worsened. After DAA treatment all the residual lesions resolved, what always led to specific treatment interruption. CONCLUSIONS: Our series of cases of HCV-associated PCT shows that SVR after DAA treatment leads to PCT resolution. Porphyrin levels are not needed after ending PCT specific treatment interruption when there are no residual skin lesions in HCV-associated PCT.


Assuntos
Hepatite C Crônica , Hepatite C , Porfiria Cutânea Tardia , Antivirais/uso terapêutico , Feminino , Hepatite C/complicações , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Humanos , Pessoa de Meia-Idade , Mutação , Porfiria Cutânea Tardia/complicações , Porfiria Cutânea Tardia/etiologia , Resposta Viral Sustentada
9.
Omega (Westport) ; : 302228221104303, 2022 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-35617603

RESUMO

The Inventory of Complicated Grief (ICG) is the most widely used instrument to measure complicated grief (CG), but its psychometric properties have hardly been examined in relatives of those who died by violent means. The objective of this study was to obtain evidence of validity of the ICG in a relatives of those who died due to terrorist attacks in Spain. The factorial structure, internal consistency, and relationship with depression, anxiety, and post-traumatic stress were analyzed in a Spanish sample of 211 relatives of people who died in terrorist attacks. The ICG presented a one-factor structure that supports the validity of its total score. This score showed excellent internal consistency indices (alpha = .927; omega = .932) and adequate correlation indices with depression, anxiety, and post-traumatic stress (r = .71, .63 and .76, respectively). The ICG provides reliable and valid measures of CG in adults who have lost a family member due to violent death.

10.
Biomacromolecules ; 22(12): 5363-5373, 2021 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-34846847

RESUMO

Dynamic binding events are key to arrive at functionality in nature, and these events are often governed by electrostatic or hydrophobic interactions. Synthetic supramolecular polymers are promising candidates to obtain biomaterials that mimic this dynamicity. Here, we created four new functional monomers based on the benzene-1,3,5-tricarboxamide (BTA) motif. Choline or atropine groups were introduced to obtain functional monomers capable of competing with the cell wall of Streptococcus pneumoniae for binding of essential choline-binding proteins (CBPs). Atropine-functionalized monomers BTA-Atr and BTA-Atr3 were too hydrophobic to form homogeneous assemblies, while choline-functionalized monomers BTA-Chol and BTA-Chol3 were unable to form fibers due to charge repulsion. However, copolymerization of BTA-Chol3 with non-functionalized BTA-(OH)3 yielded dynamic fibers, similar to BTA-(OH)3. These copolymers showed an increased affinity toward CBPs compared to free choline due to multivalent effects. BTA-based supramolecular copolymers are therefore a versatile platform to design bioactive and dynamic supramolecular polymers with novel biotechnological properties.


Assuntos
Anti-Infecciosos , Streptococcus pneumoniae , Materiais Biocompatíveis/metabolismo , Colina/farmacologia , Polímeros/química , Streptococcus pneumoniae/metabolismo
11.
BMC Infect Dis ; 21(1): 129, 2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-33516173

RESUMO

BACKGROUND: HIV infection has become a chronic disease and well-being of people living with HIV (PLHIV) is now of particular concern. The objectives of this paper were to describe self-rated health among PLHIV, on ART and on ART virally suppressed and to analyse its determinants. METHODS: Data were obtained from a second-generation surveillance system based on a cross-sectional one-day survey in public hospitals. Epidemiological and clinical data were collected among HIV-infected inpatients and outpatients receiving HIV-related care the day of the survey in 86 hospitals in 2019. Self-rated health was measured using a question included in the National Health Survey: "In the last 12 months, how would you rate your health status?" an ordinal variable with five categories (very good, good, moderate, bad and very bad). For the analysis, these responses were dichotomized into two categories: 1 = very good/good and 0 = moderate, bad or very bad health status. Factors associated with very good/good self-rated health were estimated using logistic regression. RESULTS: Of 800 PLHIV, 67.5% perceived their health as very good/good, 68.4% among PLHIV on ART and 71.7% of those virally suppressed. Having university education (adjusted odds ratio (aOR):2.1), being unemployed (aOR:0.3) or retired (aOR:0.2), ever being diagnosed of AIDS (aOR:0.6), comorbidities (aOR:0.3), less than 2 year since HIV diagnosis (aOR:0.3) and not receiving ART (aOR:0.3) were associated with good self-rated health. Moreover, among PLHIV on ART, viral load less than 200 copies (aOR:3.2) were related to better perceived health. Bad adherence was inversely associated with good self-rated health among PLHIV on ART (aOR:0.5) and of those virally suppressed (aOR:0.4). CONCLUSIONS: Nearly seven in 10 PLHIV in Spain considered their health status as very good/good, being higher among virally suppressed PLHIV. Both demographic and clinical determinants affect quality of life.


Assuntos
Autoavaliação Diagnóstica , Infecções por HIV/epidemiologia , Nível de Saúde , Adulto , Antirretrovirais/uso terapêutico , Estudos Transversais , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Espanha/epidemiologia , Inquéritos e Questionários , Carga Viral , Adulto Jovem
12.
Int J Mol Sci ; 22(3)2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33540681

RESUMO

D-amino acid oxidase (DAAO) is an enzyme that catalyzes the oxidation of D-amino acids generating H2O2. The enzymatic chimera formed by DAAO bound to the choline-binding domain of N-acetylmuramoyl-L-alanine amidase (CLytA) induces cytotoxicity in several pancreatic and colorectal carcinoma and glioblastoma cell models. In the current work, we determined whether the effect of CLytA-DAAO immobilized in magnetic nanoparticles, gold nanoparticles, and alginate capsules offered some advantages as compared to the free CLytA-DAAO. Results indicate that the immobilization of CLytA-DAAO in magnetic nanoparticles increases the stability of the enzyme, extending its time of action. Besides, we compared the effect induced by CLytA-DAAO with the direct addition of hydrogen peroxide, demonstrating that the progressive generation of reactive oxygen species by CLytA-DAAO is more effective in inducing cytotoxicity than the direct addition of H2O2. Furthermore, a pilot study has been initiated in biopsies obtained from pancreatic and colorectal carcinoma and glioblastoma patients to evaluate the expression of the main genes involved in resistance to CLytA-DAAO cytotoxicity. Based on our findings, we propose that CLytA-DAAO immobilized in magnetic nanoparticles could be effective in a high percentage of patients and, therefore, be used as an anti-cancer therapy for pancreatic and colorectal carcinoma and glioblastoma.


Assuntos
D-Aminoácido Oxidase/metabolismo , Nanopartículas de Magnetita/química , Neoplasias/terapia , Espécies Reativas de Oxigênio/metabolismo , Proteínas Recombinantes de Fusão/química , Linhagem Celular Tumoral , Neoplasias Colorretais/terapia , D-Aminoácido Oxidase/uso terapêutico , Glioblastoma/terapia , Humanos , Peróxido de Hidrogênio/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias Pancreáticas/terapia , Espécies Reativas de Oxigênio/toxicidade , Neoplasias Pancreáticas
13.
J Clin Rheumatol ; 27(8): e307-e311, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32091451

RESUMO

BACKGROUND AND OBJECTIVE: Ankylosing spondylitis (AS) is an inflammatory disease, and choroidal thickness (CT) has been proposed and evaluated as a potential marker of systemic inflammation associated with AS and other inflammatory diseases. This study compared CT measurements taken from patients with severe AS disease activity without eye inflammation with those taken from healthy subjects. METHODS: This cross-sectional, multicenter study compared CT in 44 patients with high AS disease activity, and no history of eye inflammation with CT in 44 matched healthy subjects aged between 18 and 65 years. In the AS group, the correlation between CT and C-reactive protein, human leukocyte antigen (HLA) B27 positivity, disease duration, and disease activity was calculated. RESULTS: Mean CT values of patients with AS were significantly higher in the right eye, the left eye, and the thickest choroid eye. The right eye mean CT was 338.3 ± 82.8 µm among patients with AS and 290.5 ± 71.2 µm among healthy subjects (p = 0.005). The left eye mean CT was 339.5 ± 84.7 µm for patients with AS and 298.4 ± 68.9 µm for healthy subjects (P = 0.015). The thickest choroid eye CT was 358.4 ± 82.1 µm among patients with AS and 314.1 ± 65.2 µm among healthy subjects (P = 0.006). We did not find a significant correlation between CT and disease activity, C-reactive protein, human leukocyte antigen B27 positivity, or disease duration. CONCLUSIONS: Patients with active AS but without a history of eye inflammation had a thicker choroid than healthy subjects. This finding suggests that CT is a marker of systemic inflammation in patients with inflammatory disease, regardless of known eye symptoms.


Assuntos
Espondilite Anquilosante , Adolescente , Adulto , Idoso , Corioide/diagnóstico por imagem , Estudos Transversais , Humanos , Inflamação/diagnóstico , Pessoa de Meia-Idade , Espondilite Anquilosante/complicações , Espondilite Anquilosante/diagnóstico , Tomografia de Coerência Óptica , Adulto Jovem
14.
Chembiochem ; 21(4): 432-441, 2020 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-31456307

RESUMO

A common interpretation of Anfinsen's hypothesis states that one amino acid sequence should fold into a single, native, ordered state, or a highly similar set thereof, coinciding with the global minimum in the folding-energy landscape, which, in turn, is responsible for the function of the protein. However, this classical view is challenged by many proteins and peptide sequences, which can adopt exchangeable, significantly dissimilar conformations that even fulfill different biological roles. The similarities and differences of concepts related to these proteins, mainly chameleon sequences, metamorphic proteins, and switch peptides, which are all denoted herein "turncoat" polypeptides, are reviewed. As well as adding a twist to the conventional view of protein folding, the lack of structural definition adds clear versatility to the activity of proteins and can be used as a tool for protein design and further application in biotechnology and biomedicine.


Assuntos
Peptídeos/química , Conformação Proteica , Dobramento de Proteína , Proteínas/química , Sequência de Aminoácidos , Modelos Moleculares , Termodinâmica
15.
Appl Environ Microbiol ; 86(12)2020 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-32303541

RESUMO

Phasin PhaF from Pseudomonas putida consists of a modular protein whose N-terminal domain (BioF) has been demonstrated to be responsible for binding to the polyhydroxyalkanoate (PHA) granule. BioF has been exploited for biotechnological purposes as an affinity tag in the functionalization of PHA beads with fusion proteins both in vivo and in vitro The structural model of this domain suggests an amphipathic α-helical conformation with the hydrophobic residues facing the PHA granule. In this work, we analyzed the mean hydrophobicity and the hydrophobic moment of the native BioF tag to rationally design shorter versions that maintain affinity for the granule. Hybrid proteins containing the green fluorescent protein (GFP) fused to the BioF derivatives were studied for in vivo localization on PHA, stability on the surface of the PHA granule against pH, temperature, and ionic strength, and their possible influence on PHA synthesis. Based on the results obtained, a minimized BioF tag for PHA functionalization has been proposed (MinP) that retains similar binding properties but possesses an attractive biotechnological potential derived from its reduced size. The MinP tag was further validated by analyzing the functionality and stability of the fusion proteins MinP-ß-galactosidase and MinP-CueO from Escherichia coliIMPORTANCE Polyhydroxyalkanoates (PHAs) are biocompatible, nontoxic, and biodegradable biopolymers with exceptional applications in the industrial and medical fields. The complex structure of the PHA granule can be exploited as a toolbox to display molecules of interest on their surface. Phasins, the most abundant group of proteins on the granule, have been employed as anchoring tags to obtain functionalized PHA beads for high-affinity bioseparation, enzyme immobilization, diagnostics, or cell targeting. Here, a shorter module based on the previously designed BioF tag has been demonstrated to maintain the affinity for the PHA granule, with higher stability and similar functionalization efficiency. The use of a 67% shorter peptide, which maintains the binding properties of the entire protein, constitutes an advantage for the immobilization of recombinant proteins on the PHA surface both in vitro and in vivo.


Assuntos
Proteínas de Bactérias/metabolismo , Proteínas de Ligação a DNA/metabolismo , Poli-Hidroxialcanoatos/metabolismo , Pseudomonas putida/metabolismo , Biotecnologia , Enzimas Imobilizadas/metabolismo , Interações Hidrofóbicas e Hidrofílicas , Proteínas Recombinantes/metabolismo
16.
Int J Mol Sci ; 21(22)2020 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-33198289

RESUMO

The combination of the choline binding domain of the amidase N-acetylmuramoyl-L-alanine (CLytA)-D-amino acid oxidase (DAAO) (CLytA-DAAO) and D-Alanine induces cell death in several pancreatic and colorectal carcinoma and glioblastoma cell lines. In glioblastoma cell lines, CLytA-DAAO-induced cell death was inhibited by a pan-caspase inhibitor, suggesting a classical apoptotic cell death. Meanwhile, the cell death induced in pancreatic and colon carcinoma cell lines is some type of programmed necrosis. In this article, we studied the mechanisms that trigger CLytA-DAAO-induced cell death in pancreatic and colorectal carcinoma and glioblastoma cell lines and we acquire a further insight into the necrotic cell death induced in pancreatic and colorectal carcinoma cell lines. We have analyzed the intracellular calcium mobilization, mitochondrial membrane potential, PARP-1 participation and AIF translocation. Although the mitochondrial membrane depolarization plays a crucial role, our results suggest that CLytA-DAAO-induced cell death is context dependent. We have previously detected pancreatic and colorectal carcinoma cell lines (Hs766T and HT-29, respectively) that were resistant to CLytA-DAAO-induced cell death. In this study, we have examined the putative mechanism underlying the resistance in these cell lines, evaluating both detoxification mechanisms and the inflammatory and survival responses. Overall, our results provide a better understanding on the cell death mechanism induced by CLytA-DAAO, a promising therapy against cancer.


Assuntos
Fator de Indução de Apoptose/metabolismo , Neoplasias Colorretais/metabolismo , D-Aminoácido Oxidase/metabolismo , N-Acetil-Muramil-L-Alanina Amidase/metabolismo , Neoplasias Pancreáticas/metabolismo , Poli(ADP-Ribose) Polimerase-1/metabolismo , Antineoplásicos/farmacologia , Apoptose , Biópsia , Cálcio/metabolismo , Morte Celular , Linhagem Celular Tumoral , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Células HT29 , Humanos , Inflamação , Potencial da Membrana Mitocondrial , Subunidade p50 de NF-kappa B/metabolismo , Necrose , Estresse Oxidativo , RNA Interferente Pequeno/metabolismo , Espécies Reativas de Oxigênio/metabolismo
17.
Gastroenterol Hepatol ; 43(5): 273-283, 2020 May.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-32247533

RESUMO

Extraintestinal manifestations, in general, and in particular arthropathies, are a common problem in patients with inflammatory bowel disease. In fact, the relationship between those 2entities is close and there are increasingly more data which suggest that the bowel plays a significant role in the aetiopathogenesis of spondyloarthritis. The association of inflammatory bowel disease with any kind of spondyloarthritis represents a challenging clinical scenario. It is therefore necessary that both gastroenterologists and rheumatologists work together and establish a fluent communication that enables the patient to receive the most appropriate treatment for each specific situation. The aim of this review is to make some recommendations about the treatment of patients with inflammatory bowel disease and associated spondyloarthritis, in each different clinical scenario.


Assuntos
Colite Ulcerativa/terapia , Doença de Crohn/terapia , Espondiloartropatias/terapia , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Antirreumáticos/uso terapêutico , Colite Ulcerativa/complicações , Doença de Crohn/complicações , Progressão da Doença , Quimioterapia Combinada , Gastroenterologia , Predisposição Genética para Doença , Antígeno HLA-B27/análise , Humanos , Imunossupressores/uso terapêutico , Comunicação Interdisciplinar , Reumatologia , Espondiloartropatias/complicações , Espondiloartropatias/diagnóstico , Uveíte Anterior/complicações
18.
J Clin Rheumatol ; 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-33779125

RESUMO

OBJECTIVE: Choroidal thickness (CT) has been evaluated as a marker of systemic inflammation in ankylosing spondylitis (AS). This study evaluates the CT of AS patients before and after 6 months of biological treatment. METHODS: This longitudinal multicenter study evaluated CT in 44 AS patients. The correlations between CT and C-reactive protein (CRP) with disease activity indices were calculated. The concordance between CT and CRP was determined. We assessed factors associated with response to treatment. Clinically important improvement was defined as a decrease in Ankylosing Spondylitis Disease Activity Score of 1.1 points or greater. RESULTS: Forty-four eyes in patients aged 18 to 65 years were included. Mean CT values were significantly higher at baseline than after 6 months of treatment (baseline: 355.28 ± 80.46 µm; 6 months: 341.26 ± 81.06 µm; p < 0.001). There was a 95% concordance between CT and CRP at baseline and 6 months. Clinically important improvement was associated with lower baseline CT and age as independent factors (odds ratios, 0.97 [95% confidence interval, 0.91-0.93; p = 0.009] and 0.81 [95% confidence interval, 0.7-0.95; p = 0.005]), with baseline CT of less than 374 µm (sensitivity 78%, specificity 78%, area under the curve 0.70, likelihood ratio 3.6). CONCLUSIONS: Choroidal thickness decreased significantly after 6 months of biological treatment in all treatment groups. Choroidal thickness and CRP had a 95% concordance. A high CT was associated with a risk of biological treatment failure. Choroidal thickness can be considered a useful biomarker of inflammation and a factor associated with response to treatment in AS.

19.
Clin Exp Rheumatol ; 37(2): 215-221, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30299251

RESUMO

OBJECTIVES: The aim of this study was to assess the clinical and genetic characteristics associated with the presence of peripheral arthritis (PA) at disease onset in patients with ankylosing spondylitis (AS). METHODS: 456 Spanish AS patients, diagnosed according to the modified New York Criteria, who had at least ten years of follow-up since initial disease onset were selected from the National Spondyloarthropathies Registry (REGISPONSER). 18.9% of AS patients initially presented PA. Clinical variables and 384 single nucleotide polymorphisms (SNPs) distributed in 190 genes were analysed. SNP genotyping was performed using the Illumina GoldenGate genotyping platform. Association tests for allele frequencies and for categorical clinical variables were performed by the χ2 test and with the unpaired t-test for continuous variables. p-values of <0.05 were considered statistically significant. RESULTS: AS patients with PA showed an earlier age of disease onset (p=0.021), longer disease duration (p=0.020) and longer duration of AS symptoms from onset (p=0.034) than AS patients without PA. We found significant associations with the presence of PA at disease onset in 14 SNPs located in 10 genes: HLA-DQB2 (rs2857210 and rs9276615), HLA-DOB (rs2857151, rs2621332 and rs1383261), JAK2 (rs7857730), IL-23R (rs11209008 and rs10489630), CYP1B1 (rs1056836), NELL1 (rs8176786), KL (rs564481), and MEFV (rs224204), IL-2RB (rs743777) and IL-1A (rs1800587). CONCLUSIONS: Both clinical and genetic factors are associated with the presence of PA at disease onset in Spanish AS patients. The results suggest that this subset of AS patients with PA at disease onset might have differentiation factors involved in disease pathogenesis.


Assuntos
Polimorfismo de Nucleotídeo Único , Espondilite Anquilosante , Frequência do Gene , Predisposição Genética para Doença , Antígeno HLA-B27 , Humanos , Pirina , Sistema de Registros , Espondilite Anquilosante/genética
20.
J Clin Rheumatol ; 25(1): 4-8, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29215382

RESUMO

OBJECTIVE: The aim of this study was to compare the functional results of 2 different procedure types, medical or surgical used in treating native joint septic arthritis. METHODS: In this cohort study, we reviewed the clinical registries of patients admitted to a single third-level hospital with the diagnosis of septic arthritis during the period of January 1, 2008, to January 31, 2016. RESULTS: A total of 63 cases of septic arthritis were identified in which the initial approach for 49 patients was medical (arthrocentesis), whereas the initial approach for 14 patients was surgical (arthroscopy or arthrotomy). Of the 49 patients who received initial medical treatment (IMT), 15 patients (30%) later required surgical treatment because of poor progress. The median age of the patients was 60 (SD, 18) years. The group who received IMT were older than those who received initial surgical treatment (median, 64 years [interquartile range {IQR}, 54-76 years], vs. 48 years [IQR, 30-60 years]). There was a larger percentage of male patients in the surgical group (78% vs. 42% [p = 0.018]). Thirty percent of the medical group had been receiving corticosteroid treatment (p = 0.018). Results of complete recovery of joint functionality showed no significant differences after 1 year (68% with MT vs. 67% with ST, p = 0.91). Both groups had similar symptom duration until diagnosis, duration of antibiotic therapy (median, 30 days [IQR, 28-49 days], vs. 29.5 days [IQR, 27-49] days), and mortality rate (3 in the medical group). CONCLUSIONS: The results of the study show that initial surgical treatment in patients with native joint septic arthritis is not superior to IMT. However, half of the patients with shoulder and hip infections treated with IMT eventually required surgical intervention, suggesting that perhaps this should be the preferred initial approach in these cases.


Assuntos
Antibacterianos/uso terapêutico , Artrite Infecciosa/tratamento farmacológico , Artrite Infecciosa/cirurgia , Artrocentese , Artroscopia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recuperação de Função Fisiológica , Estudos Retrospectivos , Espanha , Resultado do Tratamento
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