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1.
Mol Cell ; 66(3): 358-372.e7, 2017 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-28475871

RESUMO

A decline in proteasome function is causally connected to neuronal aging and aging-associated neuropathologies. By using hippocampal neurons in culture and in vivo, we show that aging triggers a reduction and a cytoplasm-to-nucleus redistribution of the E3 ubiquitin ligase mahogunin (MGRN1). Proteasome impairment induces MGRN1 monoubiquitination, the key post-translational modification for its nuclear entry. One potential mechanism for MGRN1 monoubiquitination is via progressive deubiquitination at the proteasome of polyubiquitinated MGRN1. Once in the nucleus, MGRN1 potentiates the transcriptional cellular response to proteotoxic stress. Inhibition of MGRN1 impairs ATF3-mediated neuronal responsiveness to proteosomal stress and increases neuronal stress, while increasing MGRN1 ameliorates signs of neuronal aging, including cognitive performance in old animals. Our results imply that, among others, the strength of neuronal survival in a proteasomal deterioration background, like during aging, depends on the fine-tuning of ubiquitination-deubiquitination.


Assuntos
Envelhecimento/metabolismo , Núcleo Celular/enzimologia , Citoplasma/enzimologia , Hipocampo/enzimologia , Neurônios/enzimologia , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina/metabolismo , Ubiquitinação , Fator 3 Ativador da Transcrição/genética , Fator 3 Ativador da Transcrição/metabolismo , Transporte Ativo do Núcleo Celular , Envelhecimento/genética , Envelhecimento/patologia , Animais , Comportamento Animal , Núcleo Celular/ultraestrutura , Sobrevivência Celular , Cromatina/enzimologia , Cognição , Células HEK293 , Hipocampo/ultraestrutura , Humanos , Aprendizagem em Labirinto , Camundongos Endogâmicos C57BL , Neurônios/ultraestrutura , Complexo de Endopeptidases do Proteassoma/metabolismo , Interferência de RNA , Ratos Wistar , Transdução de Sinais , Estresse Fisiológico , Transcrição Gênica , Transfecção , Ubiquitina-Proteína Ligases/genética
2.
EMBO Rep ; 22(11): e51696, 2021 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-34569685

RESUMO

Neuroinflammation is a common feature of many neurodegenerative diseases. It fosters a dysfunctional neuron-microglia-astrocyte crosstalk that, in turn, maintains microglial cells in a perniciously reactive state that often enhances neuronal damage. The molecular components that mediate this critical communication are not fully explored. Here, we show that secreted frizzled-related protein 1 (SFRP1), a multifunctional regulator of cell-to-cell communication, is part of the cellular crosstalk underlying neuroinflammation. In mouse models of acute and chronic neuroinflammation, SFRP1, largely astrocyte-derived, promotes and sustains microglial activation, and thus a chronic inflammatory state. SFRP1 promotes the upregulation of components of the hypoxia-induced factor-dependent inflammatory pathway and, to a lower extent, of those downstream of the nuclear factor-kappa B. We thus propose that SFRP1 acts as an astrocyte-to-microglia amplifier of neuroinflammation, representing a potential valuable therapeutic target for counteracting the harmful effect of chronic inflammation in several neurodegenerative diseases.


Assuntos
Astrócitos , Microglia , Animais , Inflamação/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos , Microglia/metabolismo , Doenças Neuroinflamatórias
3.
Am J Dermatopathol ; 44(12): 936-939, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-35925554

RESUMO

ABSTRACT: We report a case of mycosis fungoides (MF) in an 18-year-old man whose neoplastic T cells expressed CD4, CD8, and CD56, with no evidence of TCR-delta or Epstein-Barr virus (EBER) expression. Clinically, neither hypopigmentation nor hyperpigmentation nor poikilodermatous skin lesions were present, and the lesions subsided with oral corticoids and retinoids and environmental solar ultraviolet exposure. Our case represents the oldest patient reported so far with nonpoikilodermatous, CD8/CD56 MF and adds to the phenotypic diversity of MF in the pediatric population. This distinct phenotype does not seem to be linked to a more aggressive course than the classic CD-4 positive one.


Assuntos
Infecções por Vírus Epstein-Barr , Micose Fungoide , Neoplasias Cutâneas , Criança , Humanos , Herpesvirus Humano 4 , Micose Fungoide/patologia , Neoplasias Cutâneas/patologia , Linfócitos T CD8-Positivos/patologia
4.
Sensors (Basel) ; 22(23)2022 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-36502141

RESUMO

Solar-induced chlorophyll fluorescence (SIF) is used as a proxy of photosynthetic efficiency. However, interpreting top-of-canopy (TOC) SIF in relation to photosynthesis remains challenging due to the distortion introduced by the canopy's structural effects (i.e., fluorescence re-absorption, sunlit-shaded leaves, etc.) and sun-canopy-sensor geometry (i.e., direct radiation infilling). Therefore, ground-based, high-spatial-resolution data sets are needed to characterize the described effects and to be able to downscale TOC SIF to the leafs where the photosynthetic processes are taking place. We herein introduce HyScreen, a ground-based push-broom hyperspectral imaging system designed to measure red (F687) and far-red (F760) SIF and vegetation indices from TOC with single-leaf spatial resolution. This paper presents measurement protocols, the data processing chain and a case study of SIF retrieval. Raw data from two imaging sensors were processed to top-of-canopy radiance by dark-current correction, radiometric calibration, and empirical line correction. In the next step, the improved Fraunhofer line descrimination (iFLD) and spectral-fitting method (SFM) were used for SIF retrieval, and vegetation indices were calculated. With the developed protocol and data processing chain, we estimated a signal-to-noise ratio (SNR) between 50 and 200 from reference panels with reflectance from 5% to 95% and noise equivalent radiance (NER) of 0.04 (5%) to 0.18 (95%) mW m-2 sr-1 nm-1. The results from the case study showed that non-vegetation targets had SIF values close to 0 mW m-2 sr-1 nm-1, whereas vegetation targets had a mean F687 of 1.13 and F760 of 1.96 mW m-2 sr-1 nm-1 from the SFM method. HyScreen showed good performance for SIF retrievals at both F687 and F760; nevertheless, we recommend further adaptations to correct for the effects of noise, varying illumination and sensor optics. In conclusion, due to its high spatial resolution, Hyscreen is a promising tool for investigating the relationship between leafs and TOC SIF as well as their relationship with plants' photosynthetic capacity.


Assuntos
Clorofila , Fotossíntese , Estações do Ano , Luz Solar , Folhas de Planta
5.
Medicina (Kaunas) ; 58(5)2022 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-35629983

RESUMO

Background and Objectives. The aim of this study is to compare clinical and epidemiological characteristics and outcomes in patients with versus without nosocomial COVID-19 after exposure to SARS-CoV-2 and to analyze the risk factors for severe outcomes of COVID-19 in a long-term hospital in Spain. Materials and methods. This retrospective, single-center observational study included all inpatients in a long-term hospital during a COVID-19 outbreak from 21 January to 15 March 2021. Results. Of 108 admitted patients, 65 (60.2%) were diagnosed with nosocomial COVID-19 disease (n = 34 women (52.3%), median age 77 years). In the univariable analysis, risk factors associated with nosocomial COVID-19 were dementia (OR 4.98 95% CI 1.58-15.75), dyspnea (OR 5.34 95% CI 1.69-16.82), asthenia (OR 5.10, 95% CI 1.40-18.60) and NECesidades PALiativas (NECPAL) (OR 1.28 95% CI 1.10-1.48). In the multivariable analysis, risk factors independently associated with nosocomial COVID-19 infection were dyspnea (aOR 7.39; 95% CI 1.27-43.11) and NECPAL (aOR 1.25; 95% CI 1.03-1.52). Of the 65 patients diagnosed with nosocomial COVID-19, 29 (44.6%) died, compared to 7/43 (16.2%) non-infected patients (OR 4.14, 95% CI 1.61-10.67). Factors associated with mortality in nosocomial COVID-19 were confusion (aOR 3.83; 95% CI 1.03-14.27) and dyspnea (aOR 7.47; 95% CI 1.87-29.82). The NECPAL tool played an important predictive role in both nosocomial COVID-19 infection and mortality (aOR 1.19, 95% CI: 1.00-1.41). Conclusions. In a long-term hospital, nosocomial COVID-19 main clinical characteristics associated with infection were dyspnea and NECPAL. Mortality was higher in the group with nosocomial COVID-19; risk factors were confusion and dyspnea. The NECPAL tool may help to predict progression and death in COVID-19.


Assuntos
COVID-19 , Infecção Hospitalar , Idoso , Infecção Hospitalar/epidemiologia , Dispneia/etiologia , Feminino , Hospitais , Humanos , Estudos Retrospectivos , SARS-CoV-2 , Espanha/epidemiologia
6.
Acta Derm Venereol ; 101(8): adv00525, 2021 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-34396424

RESUMO

The aim of this study was to compare tumour burden in patients who underwent surgery for melanoma and cutaneous squamous cell carcinoma during nationwide lockdown in Spain due to COVID-19 (for the period 14 March to 13 June 2020) and during the same dates in 2019 before the COVID-19 pandemic. In addition, associations between median tumour burden (Breslow thickness for melanoma and maximum clinical diameter for cutaneous squamous cell carcinoma) and demographic, clinical, and medical factors were analysed, building a multivariate linear regression model. During the 3 months of lockdown, there was a significant decrease in skin tumours operated on (41% decrease for melanoma (n = 352 vs n = 207) and 44% decrease for cutaneous squamous cell carcinoma (n = 770 vs n = 429)) compared with the previous year. The proportion of large skin tumours operated on increased. Fear of SARS-CoV-2 infection, with respect to family member/close contact, and detection of the lesion by the patient or doctor, were related to thicker melanomas; and fear of being diagnosed with cancer, and detection of the lesion by the patient or relatives, were related to larger size cutaneous squamous cell carcinoma. In conclusion, lockdown due to COVID-19 has resulted in a reduction in treatment of skin cancer.


Assuntos
COVID-19 , Carcinoma de Células Escamosas , Melanoma , Neoplasias Cutâneas , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/cirurgia , Controle de Doenças Transmissíveis , Humanos , Melanoma/epidemiologia , Melanoma/cirurgia , Pandemias , SARS-CoV-2 , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/cirurgia , Carga Tumoral
7.
Remote Sens Environ ; 264: 112609, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34602655

RESUMO

Remote sensing-based measurements of solar-induced chlorophyll fluorescence (SIF) are useful for assessing plant functioning at different spatial and temporal scales. SIF is the most direct measure of photosynthesis and is therefore considered important to advance capacity for the monitoring of gross primary production (GPP) while it has also been suggested that its yield facilitates the early detection of vegetation stress. However, due to the influence of different confounding effects, the apparent SIF signal measured at canopy level differs from the fluorescence emitted at leaf level, which makes its physiological interpretation challenging. One of these effects is the scattering of SIF emitted from leaves on its way through the canopy. The escape fraction ( f esc ) describes the scattering of SIF within the canopy and corresponds to the ratio of apparent SIF at canopy level to SIF at leaf level. In the present study, the fluorescence correction vegetation index (FCVI) was used to determine f esc of far-red SIF for three structurally different crops (sugar beet, winter wheat, and fruit trees) from a diurnal data set recorded by the airborne imaging spectrometer HyPlant. This unique data set, for the first time, allowed a joint analysis of spatial and temporal dynamics of structural effects and thus the downscaling of far-red SIF from canopy ( SIF 760 canopy ) to leaf level ( SIF 760 leaf ). For a homogeneous crop such as winter wheat, it seems to be sufficient to determine f esc once a day to reliably scale SIF760 from canopy to leaf level. In contrast, for more complex canopies such as fruit trees, calculating f esc for each observation time throughout the day is strongly recommended. The compensation for structural effects, in combination with normalizing SIF760 to remove the effect of incoming radiation, further allowed the estimation of SIF emission efficiency ( ε SIF ) at leaf level, a parameter directly related to the diurnal variations of plant photosynthetic efficiency.

8.
Cytokine ; 105: 73-79, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29471285

RESUMO

BACKGROUND: Omega-3 fatty acids have the potential to decrease inflammation and modify gene transcription. Whether docosahexanoic acid (DHA) supplementation can modify systemic inflammatory and subcutaneous adipose tissue (SAT) gene expression in HIV-infected patients is unknown. METHODS: A randomized, double-blind, placebo-controlled trial that enrolled 84 antiretroviral-treated patients who had fasting TG levels from 2.26 to 5.65 mmol/l and received DHA or placebo for 48 weeks was performed (ClinicalTrials.gov, NCT02005900). Systemic inflammatory and SAT gene expression was assessed at baseline and at week 48 in 39 patients. RESULTS: Patients receiving DHA had a 43.9% median decline in fasting TG levels at week 4 (IQR: -31% to -56%), compared with -2.9% (-18.6% to 16.5%) in the placebo group (P < 0.0001). High sensitivity C reactive protein (hsCRP) and arachidonic acid levels significantly decreased in the DHA group. Adipogenesis-related and mitochondrial-related gene expression did not experience significant changes. Mitochondrial DNA (mtDNA) significantly decreased in the placebo group. SAT inflammation-related gene expression (Tumor necrosis factor alpha [TNF-α], and monocyte chemoattractant protein-1 [MCP-1]) significantly decreased in the DHA group. CONCLUSIONS: DHA supplementation down-regulated inflammatory gene expression in SAT. DHA impact on markers of systemic inflammation was restricted to hsCRP and arachidonic acid.


Assuntos
Terapia Antirretroviral de Alta Atividade , Suplementos Nutricionais , Ácidos Docosa-Hexaenoicos/uso terapêutico , Regulação da Expressão Gênica , Infecções por HIV/tratamento farmacológico , Infecções por HIV/genética , Inflamação/genética , Gordura Subcutânea/metabolismo , Adipócitos/metabolismo , Adulto , Ácido Araquidônico/metabolismo , Biomarcadores/metabolismo , Glicemia/metabolismo , Diferenciação Celular/genética , DNA Mitocondrial/genética , Ácidos Docosa-Hexaenoicos/farmacologia , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Infecções por HIV/sangue , Homeostase , Humanos , Inflamação/sangue , Mediadores da Inflamação/metabolismo , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Placebos , Gordura Subcutânea/efeitos dos fármacos
9.
J Sci Food Agric ; 98(1): 225-230, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28580634

RESUMO

BACKGROUND: Olive oil extraction generates a large amount of residue consisting mainly of the pomace and leaves when using a two-phase centrifugation system. The aim of this study was to assess the content of phenolic and triterpene compounds in the by-products produced in Spanish olive oil mills. RESULTS: Olive pomace had concentrations of phenolic and triterpene substances lower than 2 and 3 g kg-1 , respectively. The leaves contained a high concentration of these substances, although those collected from ground-picked olives had lost most of their phenolic compounds. Moreover, the sediment from the bottom of the olive oil storage tanks did not have a significant amount of these substances. By contrast, a new by-product called olive pomace skin has been revealed as a very rich source of triterpenic acids, the content of which can reach up to 120 g kg-1 in this waste product, maslinic acid comprising around 70% of total triterpenics. CONCLUSION: Among the by-products generated during extraction of olive oil, olive pomace skin has been discovered to be a very rich source of triterpenic acids, which can reach up to 120 g kg-1 of the waste. These results will contribute to the valorization of olive oil by-products. © 2017 Society of Chemical Industry.


Assuntos
Olea/química , Fenóis/análise , Extratos Vegetais/análise , Triterpenos/análise , Resíduos/análise , Manipulação de Alimentos , Frutas/química , Azeite de Oliva/química
11.
Addict Biol ; 22(2): 411-422, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26632340

RESUMO

The drive to eat is regulated by two compensatory brain pathways termed as homeostatic and hedonic. Hypothalamic orexinergic (ORX) neurons regulate metabolism, feeding and reward, thus controlling physiological and hedonic appetite. Circadian regulation of feeding, metabolism and rhythmic activity of ORX cells are driven by the brain suprachiasmatic clock. How the circadian clock impacts on ORX signalling and feeding-reward rhythms is, however, unknown. Here we used mice lacking the nuclear receptor REV-ERBα, a transcription repressor and a key component of the molecular clockwork, to study food-reward behaviour. Rev-Erbα mutant mice showed highly motivated behaviours to obtain palatable food, an increase in the intake and preference for tasty diets, and in the expression of the ORX protein in the hypothalamus. Palatable food intake was inhibited in animals treated with the ORX1R antagonist. Analyzing the Orx promoter, we found Retinoic acid-related Orphan receptor Response Element binding sites for Rev-Erbα. Furthermore, Rev-Erbα dampened the activation of Orx in vitro and in vivo. Our data provide evidence for a possible repressive role of Rev-Erbα in the regulation of ORX signalling, highlighting an implication of the circadian clockwork in modulating food-reward behaviours with an important impact for the central regulation of overeating.


Assuntos
Ingestão de Alimentos/genética , Comportamento Alimentar/fisiologia , Hipotálamo/metabolismo , Neurônios/metabolismo , Membro 1 do Grupo D da Subfamília 1 de Receptores Nucleares/genética , Orexinas/metabolismo , Animais , Ritmo Circadiano , Ingestão de Alimentos/efeitos dos fármacos , Comportamento Alimentar/efeitos dos fármacos , Masculino , Camundongos , Camundongos Knockout , Antagonistas dos Receptores de Orexina/farmacologia , Receptores de Orexina/metabolismo , Regiões Promotoras Genéticas , Transdução de Sinais
12.
J Antimicrob Chemother ; 70(4): 1139-45, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25525195

RESUMO

OBJECTIVES: Maximizing ART efficiency is of growing interest. This study assessed the efficacy, safety, pharmacokinetics and economics of a darunavir dose-reduction strategy. METHODS: This was a multicentre, randomized, open-label clinical trial in HIV-infected patients with plasma HIV-1 RNA <50 copies/mL while receiving triple ART including 800 mg of darunavir once daily. Participants were randomized to continue 800 mg of darunavir (DRV800) or to 600 mg of darunavir (DRV600), both once daily. Treatment failure was defined as two consecutive HIV-1 RNA determinations >50 copies/mL or discontinuation of study treatment by week 48. The study was registered at https://www.clinicaltrialsregister.eu (trial number 2011-006272-39). RESULTS: Fifty participants were allocated to each arm. The mean (SD) CD4+ T cell count at baseline was 562 (303) cells/mm(3) and HIV-1 RNA had been <50 copies/mL for a median (IQR) of 106.9 (43.4-227.9) weeks before enrolment. At week 48 no treatment failure had occurred in 45/50 (90%) DRV600 patients and in 47/50 (94%) DRV800 patients (difference -4%; 95% CI lower limit, -12.9%). When only patients with virological data were considered, that endpoint was met by 45/48 (94%) in the DRV600 arm and 47/49 (96%) in the DRV800 arm (difference -2.2%; 95% CI lower limit, -9.6%). Darunavir exposure was similar in the two arms. The average reduction in annual cost per successfully treated DRV600-arm patient was US$7273. CONCLUSIONS: The efficacy of a darunavir daily dose of 600 mg seemed to be similar to the efficacy of the standard 800 mg dose in virologically suppressed HIV-infected patients on triple ART. This strategy can potentially translate to substantial savings in the cost of care of HIV-infected patients.


Assuntos
Antirretrovirais/administração & dosagem , Infecções por HIV/tratamento farmacológico , HIV-1/isolamento & purificação , Quimioterapia de Manutenção/métodos , Sulfonamidas/administração & dosagem , Carga Viral , Adulto , Antirretrovirais/efeitos adversos , Antirretrovirais/economia , Antirretrovirais/farmacocinética , Darunavir , Feminino , Humanos , Quimioterapia de Manutenção/efeitos adversos , Quimioterapia de Manutenção/economia , Masculino , Pessoa de Meia-Idade , Plasma/virologia , Sulfonamidas/efeitos adversos , Sulfonamidas/economia , Sulfonamidas/farmacocinética , Resultado do Tratamento
13.
J Cutan Pathol ; 42(11): 884-8, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26269328

RESUMO

Glandular structures are well documented to appear in peripheral nerve sheath tumors. These epithelial elements are usually present in malignant peripheral nerve sheath tumors although a few cases of glandular benign peripheral nerve sheath tumors have also been described, most of them being schwannomas. A neurofibroma with glands is considered to be a rare type of divergent differentiation, but a neurofibroma containing gland-like or pseudoglandular structures have not, to our knowledge, been described. We report a 33-year-old patient with a well-demarcated dermal neoplasm, composed of neoplastic Schwann cells, perineurial-like cells and fibroblasts in a matrix with collagen fibers and myxoid areas. A part of the tumor consisted of microcystic gland-like spaces lined by flat cells. These cells were either S100 positive or negative, with no epithelial membrane antigen, cytokeratin or CD31 immunostaining. Recognition of the presence of pseudoglandular elements in neurofibromas is important to distinguish them from other tumoral lesions, some of them with malignant potential.


Assuntos
Neoplasias Epiteliais e Glandulares/patologia , Neurofibroma Plexiforme/patologia , Adulto , Diagnóstico Diferencial , Feminino , Humanos , Neoplasias Epiteliais e Glandulares/diagnóstico , Neoplasias Epiteliais e Glandulares/ultraestrutura , Neurilemoma/diagnóstico , Neurilemoma/patologia , Neurilemoma/ultraestrutura , Neurofibroma Plexiforme/diagnóstico , Neurofibroma Plexiforme/ultraestrutura
14.
Ann Surg Oncol ; 21(4): 1138-46, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24390708

RESUMO

PURPOSE: To identify quality indicators and establish acceptable quality limits (AQLs) in pancreatic oncologic surgery using a formal statistical methodology. METHODS: Indicators have been identified through systematic literature reviews and guidelines for pancreatic surgery. AQLs were determined for each indicator with confidence intervals of 99.8 and 95 % above and below the weighted average by sample size from the different series examined. RESULTS: Several indicators have been identified with the following results as AQLs: resectability rate >59 %; morbidity, mortality, and pancreatic fistula rate in pancreaticoduodenectomy <55, <5, and <16 %, respectively; morbidity, mortality, and fistula rate in distal pancreatectomy <53, <4, and <31 %, respectively; number of lymph nodes retrieved >15; R1 resection <46 %; survival at 1, 3, and 5 years >54, >19, and >8 %, respectively. CONCLUSIONS: A series of different indicators for quality surgical care outcome in pancreatic cancer, as well as their limits, have been determined according to a standard methodology.


Assuntos
Avaliação de Resultados em Cuidados de Saúde/normas , Pancreatectomia , Neoplasias Pancreáticas/cirurgia , Garantia da Qualidade dos Cuidados de Saúde/normas , Humanos , Prognóstico
15.
Physiol Plant ; 150(1): 95-106, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23742320

RESUMO

In a previous work, it was shown that bicarbonate (one of the most important factors causing Fe chlorosis in Strategy I plants) can limit the expression of several genes involved in Fe acquisition. Hypoxia is considered another important factor causing Fe chlorosis, mainly on calcareous soils. However, to date it is not known whether hypoxia aggravates Fe chlorosis by affecting bicarbonate concentration or by specific negative effects on Fe acquisition. Results found in this work show that hypoxia, generated by eliminating the aeration of the nutrient solution, can limit the expression of several Fe acquisition genes in Fe-deficient Arabidopsis, cucumber and pea plants, like the genes for ferric reductases AtFRO2, PsFRO1 and CsFRO1; iron transporters AtIRT1, PsRIT1 and CsIRT1; H(+) -ATPase CsHA1; and transcription factors AtFIT, AtbHLH38, and AtbHLH39. Interestingly, the limitation of the expression of Fe-acquisition genes by hypoxia did not occur in the Arabidopsis ethylene constitutive mutant ctr1, which suggests that the negative effect of hypoxia is related to ethylene, an hormone involved in the upregulation of Fe acquisition genes. As for hypoxia, results obtained by applying bicarbonate to the nutrient solution suggests that ethylene is also involved in its negative effect, since ACC (1-aminocyclopropane-1-carboxylic acid; ethylene precursor) partially reversed the negative effect of bicarbonate on the expression of Fe acquisition genes. Taken together, the results obtained show that hypoxia and bicarbonate could induce Fe chlorosis by limiting the expression of Fe acquisition genes, probably because each factor negatively affects different steps of ethylene synthesis and/or signaling.


Assuntos
Bicarbonatos/metabolismo , Etilenos/biossíntese , Regulação da Expressão Gênica de Plantas , Ferro/metabolismo , Oxigênio/fisiologia , Arabidopsis , Cucumis sativus/genética , Pisum sativum/genética , Transdução de Sinais/genética
16.
Cir Esp ; 92(8): 532-8, 2014 Oct.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-24878428

RESUMO

INTRODUCTION: Involvement of surgical resection margins is a fundamental prognostic factor in pancreatic oncological surgery. However, there is a lack of standardized histopathology definition. The aims of this study are to investigate the real rate of R1 resections when surgical specimens are evaluated according to a standardized protocol and to study its survival implications. PATIENTS Y METHODS: One hundred consecutive surgically resected patients with pancreatic ductal adenocarcinoma were included in the study. They were further divided in 2 groups: pre-protocol, evaluated before the introduction of the standardized protocol and post-protocol, analyzed with the standardized protocol. RESULTS: R0 resection rate in the pre-protocol group was 78%, falling to 47% after the introduction of the standardized protocol (p=0,003). The posterior retroperitoneal margin was the most frequently involved margin. In cases with tumors located at the pancreatic head and analyzed according to the standardized protocol R1 involvement negatively affected survival. Median survival in the R0 group was 22 months versus 16 in those with the margin involved (HR: 2.044; IC 95% 1,00-4,16; P=.043). CONCLUSIONS: Standardized evaluation of the retroperitoneal margins in pancreatic cancer increases the rate of R1 patients. In cases with pancreatic cancer located at the pancreatic head involvement of posterior retroperitoneal margin significantly decreases survival.


Assuntos
Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos
17.
Dalton Trans ; 53(22): 9433-9440, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38758133

RESUMO

A series of cyclometallated gold(III) complexes 21-27 of general formula [Au(dppta)(azdtc)Cl] (dppta = N,N-diisopropyl-P,P-diphenylphosphinothioic amide-κ2C,S; azdtc = azol(in)ium-2-dithiocarboxylate-κ1S) were prepared and characterized by spectroscopic and diffractometric techniques. Treatment of [Au(dppta)(azdtc)Cl] complexes with methanol led to their quantitative transformation into a novel family of (C^S, S^S)-cyclometallated gold(III) complexes of general formula [Au(dppta)(azmtd)] (azmdt = azol(in)ium-2-(methoxy)methanedithiol-κ2S,S) 28-34. All the [Au(dppta)(azdtc)Cl] complexes 21-27 catalyzed the alkylation of indoles, whereas [Au(dppta)(azmtd)] complexes 28-34 were inactive. Among the synthesized derivatives, complex 22 displayed the highest catalytic activity, leading to a series of functionalized indoles in excellent yields.

18.
Transl Cancer Res ; 13(5): 2564-2570, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38881927

RESUMO

Background: Spontaneous remission (SR) is defined as the complete or partial disappearance of a diagnosed malignant disease in the absence of known active medical treatment. The role of the immune system is thought to be important, but has not yet been elucidated. On this matter, there are studies that suggest that the abscopal effect (AE), which is defined as the remission of untreated lesions beyond the irradiated area, may be explained by the activation of a systemic immune response against the tumor. Sclerosing epithelioid fibrosarcoma (SEF) is a rare variant of soft tissue sarcoma that is characterized by a slow evolution, with local recurrences and late metastases. The treatment is based on surgery, leaving a minimal role to chemotherapy (ChT) and radiotherapy (RT) for metastatic unresectable disease, and no cases of SR have been reported in the literature so far. Case Description: We present the case of a patient with a lung metastatic recurrence of SEF, diagnosed and treated with surgery 8 years before. After progression to pazopanib and other ChT drugs, because of the chest pain associated with a pleural mass invading the second costal arch, the patient received antalgic local RT treatment. Months later, and without any further treatment, a partial remission of all the tumoral lesions was presented, and she is alive 25 years after the first diagnosis. Conclusions: As far as reported in the literature, this is the first case of SR in SEF. Among the possible causes of this SR, we think that the most plausible is that palliative treatment with RT of the pleural mass induced an AE, leading to a reduction of all tumoral lesions, even those outside the irradiated region.

19.
Microbiol Spectr ; 12(1): e0285523, 2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38095475

RESUMO

IMPORTANCE: Numerous international organizations, including the World Health Organization, have been drawing attention to the global increase in sexually transmitted infections. Twenty years ago, lymphogranuloma venereum (LGV) was mainly considered a tropical disease; in recent decades, however, LGV has been increasingly present in high-income countries. This increase has been linked to men who have sex with men who participate in highly interconnected sexual networks, leading to a rapid spread of LGV. This study focuses on the spread of LGV, presenting the largest time series of LGV prevalence in Spain, which includes more than a thousand diagnosed cases in one large city. The number of LGV cases diagnosed was analyzed over time, and a selection of strains was subjected to molecular genotyping. The results indicate that the LGV epidemic is gradually evolving toward an increasingly complex diversification due to the selection of successful genovariants that have emerged by mutation and recombination events, suggesting that we are moving toward an unpredictable scenario.


Assuntos
Epidemias , Linfogranuloma Venéreo , Minorias Sexuais e de Gênero , Masculino , Humanos , Linfogranuloma Venéreo/epidemiologia , Linfogranuloma Venéreo/diagnóstico , Chlamydia trachomatis/genética , Homossexualidade Masculina
20.
Microorganisms ; 12(9)2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39338549

RESUMO

HEV antibody detection constitutes the main screening test for HEV infection. The aim of this study is to compare the sensitivity and specificity of four techniques: LIAISON® MUREX DiaSorin anti-HEV IgG and anti-HEV IgM assays, Hepatitis E VIRCLIA® IgM and IgG monotests, WANTAI HEV-IgM and IgG ELISA and VIDAS® anti-HEV IgM and IgG tests in five panels of samples configurated according to the immunoblot (RecomLine, Mikrogen, Neuss, Germany). Anti-HEV IgM sensitivity in the acute phase was 100% in all techniques, while sensitivity, including the immediate convalescence phase, was 96.74% for LIAISON®, 83.14% for VIRCLIA®, 84.78% for WANTAI and 88.04% for VIDAS®. Anti-HEV IgM specificity was 100% for both LIAISON® and VIRCLIA®. Anti-HEV IgM WANTAI agreed with VIRCLIA® with a good Kappa coefficient (κ = 0.71). Anti-HEV IgG post-infection sensitivity was 100% for LIAISON®, VIDAS® and VIRCLIA® and 99% for WANTAI. Anti-HEV IgG specificity reached 97.17% for LIAISON and 88.68% for VIRCLIA®. Our results demonstrated a better capacity of LIAISON® MUREX anti-HEV IgM than that of competitors for detecting acute infections as well as accurate anti-HEV IgG results and in how to resolve them.

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