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1.
FASEB J ; 38(3): e23454, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38315457

RESUMO

Mitochondria shape intracellular Ca2+ signaling through the concerted activity of Ca2+ uptake via mitochondrial calcium uniporters and efflux by Na+ /Ca2+ exchangers (NCLX). Here, we describe a novel relationship among NCLX, intracellular Ca2+ , and autophagic activity. Conditions that stimulate autophagy in vivo and in vitro, such as caloric restriction and nutrient deprivation, upregulate NCLX expression in hepatic tissue and cells. Conversely, knockdown of NCLX impairs basal and starvation-induced autophagy. Similarly, acute inhibition of NCLX activity by CGP 37157 affects bulk and endoplasmic reticulum autophagy (ER-phagy) without significant impacts on mitophagy. Mechanistically, CGP 37157 inhibited the formation of FIP200 puncta and downstream autophagosome biogenesis. Inhibition of NCLX caused decreased cytosolic Ca2+ levels, and intracellular Ca2+ chelation similarly suppressed autophagy. Furthermore, chelation did not exhibit an additive effect on NCLX inhibition of autophagy, demonstrating that mitochondrial Ca2+ efflux regulates autophagy through the modulation of Ca2+ signaling. Collectively, our results show that the mitochondrial Ca2+ extrusion pathway through NCLX is an important regulatory node linking nutrient restriction and autophagy regulation.


Assuntos
Sinalização do Cálcio , Cálcio , Clonazepam/análogos & derivados , Tiazepinas , Sinalização do Cálcio/fisiologia , Cálcio/metabolismo , Trocador de Sódio e Cálcio , Mitocôndrias/metabolismo , Autofagia , Sódio/metabolismo
2.
Proc Natl Acad Sci U S A ; 119(26): e2122582119, 2022 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-35733265

RESUMO

Plants use photoperiodism to activate flowering in response to a particular daylength. In rice, flowering is accelerated in short-day conditions, and even a brief exposure to light during the dark period (night-break) is sufficient to delay flowering. Although many of the genes involved in controlling flowering in rice have been uncovered, how the long- and short-day flowering pathways are integrated, and the mechanism of photoperiod perception is not understood. While many of the signaling components controlling photoperiod-activated flowering are conserved between Arabidopsis and rice, flowering in these two systems is activated by opposite photoperiods. Here we establish that photoperiodism in rice is controlled by the evening complex (EC). We show that mutants in the EC genes LUX ARRYTHMO (LUX) and EARLY FLOWERING3 (ELF3) paralogs abolish rice flowering. We also show that the EC directly binds and suppresses the expression of flowering repressors, including PRR37 and Ghd7. We further demonstrate that light acts via phyB to cause a rapid and sustained posttranslational modification of ELF3-1. Our results suggest a mechanism by which the EC is able to control both long- and short-day flowering pathways.


Assuntos
Flores , Oryza , Fotoperíodo , Arabidopsis/genética , Arabidopsis/crescimento & desenvolvimento , Flores/genética , Flores/crescimento & desenvolvimento , Flores/efeitos da radiação , Regulação da Expressão Gênica de Plantas , Luz , Oryza/genética , Oryza/crescimento & desenvolvimento , Oryza/efeitos da radiação , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
3.
J Biol Chem ; 299(3): 102904, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36642177

RESUMO

Calcium (Ca2+) is a key regulator in diverse intracellular signaling pathways and has long been implicated in metabolic control and mitochondrial function. Mitochondria can actively take up large amounts of Ca2+, thereby acting as important intracellular Ca2+ buffers and affecting cytosolic Ca2+ transients. Excessive mitochondrial matrix Ca2+ is known to be deleterious due to opening of the mitochondrial permeability transition pore (mPTP) and consequent membrane potential dissipation, leading to mitochondrial swelling, rupture, and cell death. Moderate Ca2+ within the organelle, on the other hand, can directly or indirectly activate mitochondrial matrix enzymes, possibly impacting on ATP production. Here, we aimed to determine in a quantitative manner if extra- or intramitochondrial Ca2+ modulates oxidative phosphorylation in mouse liver mitochondria and intact hepatocyte cell lines. To do so, we monitored the effects of more modest versus supraphysiological increases in cytosolic and mitochondrial Ca2+ on oxygen consumption rates. Isolated mitochondria present increased respiratory control ratios (a measure of oxidative phosphorylation efficiency) when incubated with low (2.4 ± 0.6 µM) and medium (22.0 ± 2.4 µM) Ca2+ concentrations in the presence of complex I-linked substrates pyruvate plus malate and α-ketoglutarate, respectively, but not complex II-linked succinate. In intact cells, both low and high cytosolic Ca2+ led to decreased respiratory rates, while ideal rates were present under physiological conditions. High Ca2+ decreased mitochondrial respiration in a substrate-dependent manner, mediated by mPTP. Overall, our results uncover a Goldilocks effect of Ca2+ on liver mitochondria, with specific "just right" concentrations that activate oxidative phosphorylation.


Assuntos
Cálcio , Mitocôndrias , Fosforilação Oxidativa , Animais , Camundongos , Cálcio/metabolismo , Mitocôndrias/metabolismo
4.
J Bioenerg Biomembr ; 56(2): 87-99, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38374292

RESUMO

High-fat diet-induced metabolic changes are not restricted to the onset of cardiovascular diseases, but also include effects on brain functions related to learning and memory. This study aimed to evaluate mitochondrial markers and function, as well as cognitive function, in a rat model of metabolic dysfunction. Eight-week-old male Wistar rats were subjected to either a control diet or a two-hit protocol combining a high fat diet (HFD) with the nitric oxide synthase inhibitor L-NAME in the drinking water. HFD plus L-NAME induced obesity, hypertension, and increased serum cholesterol. These rats exhibited bioenergetic dysfunction in the hippocampus, characterized by decreased oxygen (O2) consumption related to ATP production, with no changes in H2O2 production. Furthermore, OPA1 protein expression was upregulated in the hippocampus of HFD + L-NAME rats, with no alterations in other morphology-related proteins. Consistently, HFD + L-NAME rats showed disruption of performance in the Morris Water Maze Reference Memory test. The neocortex did not exhibit either bioenergetic changes or alterations in H2O2 production. Calcium uptake rate and retention capacity in the neocortex of HFD + L-NAME rats were not altered. Our results indicate that hippocampal mitochondrial bioenergetic function is disturbed in rats exposed to a HFD plus L-NAME, thus disrupting spatial learning, whereas neocortical function remains unaffected.


Assuntos
Dieta Hiperlipídica , Memória Espacial , Ratos , Animais , Masculino , Dieta Hiperlipídica/efeitos adversos , Ratos Wistar , NG-Nitroarginina Metil Éster/farmacologia , NG-Nitroarginina Metil Éster/metabolismo , Peróxido de Hidrogênio/metabolismo , Aprendizagem em Labirinto , Hipocampo/metabolismo , Mitocôndrias/metabolismo
5.
Histopathology ; 84(3): 451-462, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37988282

RESUMO

AIMS: NTRK-rearranged sarcomas of the female genital tract mainly occur in the uterus (more commonly cervix than corpus) and are characterized by a "fibrosarcoma-like" morphology and NTRK gene rearrangements. These neoplasms may exhibit histological overlap with other entities and can present diagnostic difficulties without molecular confirmation. Pan-TRK immunohistochemistry was developed to identify tumours harbouring NTRK rearrangements. The aim of this study was to characterize pan-TRK immunohistochemical expression in a large cohort of gynaecological mesenchymal neoplasms and investigate the utility of pan-TRK immunohistochemistry to distinguish NTRK-rearranged sarcoma from its mimics. METHODS AND RESULTS: A total of 473 gynaecological mesenchymal tumours (461 without known NTRK fusions and 12 NTRK-rearranged sarcomas) were selected. Pan-TRK immunohistochemistry (EPR17341, Abcam) was performed on whole tissue sections and tissue microarrays. Molecular interrogation of pan-TRK positive tumours was performed by RNA sequencing or fluorescence in situ hybridization (FISH). Of the 12 NTRK-rearranged sarcomas, 11 (92%) exhibited diffuse (≥70%) cytoplasmic pan-TRK staining with moderate/marked intensity, while the other was negative. Eleven (2.4%) additional tumours also exhibited pan-TRK immunohistochemical expression: three low-grade endometrial stromal sarcomas, seven high-grade endometrial stromal sarcomas, and an undifferentiated uterine sarcoma. Molecular confirmation of the absence of NTRK rearrangements was possible in nine of these tumours. Of these nine neoplasms, seven exhibited focal/multifocal (<70%) pan-TRK cytoplasmic staining with weak/moderate intensity. CONCLUSION: Even though pan-TRK immunohistochemical expression is not entirely sensitive or specific for NTRK-rearranged sarcomas, these neoplasms tend to exhibit diffuse staining of moderate/strong intensity, unlike its mimics. Pan-TRK should be performed in monomorphic uterine (corpus and cervix) spindle cell neoplasms that are negative for smooth muscle markers and hormone receptors and positive for CD34 and/ or S100. Ultimately, the diagnosis requires molecular confirmation.


Assuntos
Neoplasias do Endométrio , Neoplasias de Tecido Conjuntivo e de Tecidos Moles , Sarcoma do Estroma Endometrial , Sarcoma , Neoplasias de Tecidos Moles , Feminino , Humanos , Biomarcadores Tumorais/genética , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Proteínas de Fusão Oncogênica/genética , Sarcoma/diagnóstico , Sarcoma/genética , Sarcoma/patologia , Receptor trkA
6.
J Am Acad Dermatol ; 90(6): 1200-1209, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38301923

RESUMO

INTRODUCTION: Solid organ transplant recipients (SOTRs) are believed to have an increased risk of metastatic cutaneous squamous cell carcinoma (cSCC), but reliable data are lacking regarding the precise incidence and associated risk factors. METHODS: In a prospective cohort study, including 19 specialist dermatology outpatient clinics in 15 countries, patient and tumor characteristics were collected using standardized questionnaires when SOTRs presented with a new cSCC. After a minimum of 2 years of follow-up, relevant data for all SOTRs were collected. Cumulative incidence of metastases was calculated by the Aalen-Johansen estimator. Fine and Gray models were used to assess multiple risk factors for metastases. RESULTS: Of 514 SOTRs who presented with 623 primary cSCCs, metastases developed in 37 with a 2-year patient-based cumulative incidence of 6.2%. Risk factors for metastases included location in the head and neck area, local recurrence, size > 2 cm, clinical ulceration, poor differentiation grade, perineural invasion, and deep invasion. A high-stage tumor that is also ulcerated showed the highest risk of metastasis, with a 2-year cumulative incidence of 46.2% (31.9%-68.4%). CONCLUSIONS: SOTRs have a high risk of cSCC metastases and well-established clinical and histologic risk factors have been confirmed. High-stage, ulcerated cSCCs have the highest risk of metastasis.


Assuntos
Carcinoma de Células Escamosas , Transplante de Órgãos , Neoplasias Cutâneas , Humanos , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/patologia , Carcinoma de Células Escamosas/epidemiologia , Estudos Prospectivos , Incidência , Pessoa de Meia-Idade , Masculino , Feminino , Europa (Continente)/epidemiologia , Transplante de Órgãos/efeitos adversos , Fatores de Risco , Idoso , Adulto , Transplantados/estatística & dados numéricos , Invasividade Neoplásica , Neoplasias de Cabeça e Pescoço/epidemiologia , Neoplasias de Cabeça e Pescoço/patologia , Estadiamento de Neoplasias , Recidiva Local de Neoplasia/epidemiologia
7.
Semin Dial ; 37(2): 85-90, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37026486

RESUMO

Management of vascular access is a challenge for the dialysis team, particularly to keep the arteriovenous access working. The vascular access coordinator can positively contribute to increase the number of arteriovenous fistulas and reduce central venous catheters. In this article, we introduce a new approach to vascular access management centered on (the results of setting up) the role of vascular access coordinator. We described the three-level model (3Level_M) for vascular access management organized in three levels: vascular access nurse manager, vascular access coordinator, and vascular access consultant. We defined the instrumental skills and training required to be developed by each element and clarify the articulation between the model and all members of the dialysis team related to vascular access.


Assuntos
Fístula Arteriovenosa , Derivação Arteriovenosa Cirúrgica , Cateterismo Venoso Central , Cateteres Venosos Centrais , Humanos , Diálise Renal/métodos , Cateterismo Venoso Central/métodos
8.
Eur J Clin Pharmacol ; 80(5): 677-684, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38372756

RESUMO

PURPOSE: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, though uncertainty exists regarding their immune-related safety. The objective of this study was to assess the comparative safety profile (odds ratio) of ICIs and estimate the absolute rate of immune-related serious adverse events (irSAEs) in cancer patients undergoing treatment with ICIs. METHODS: We searched for randomized trials till February 2021, including all ICIs for all cancers. Primary outcome was overall irSAEs, and secondary outcomes were pneumonitis, colitis, hepatitis, hypophysitis, myocarditis, nephritis, and pancreatitis. We conducted Bayesian network meta-analyses, estimated absolute rates and ranked treatments according to the surface under the cumulative ranking curve (SUCRA). RESULTS: We included 96 trials (52,811 participants, median age 62 years). Risk of bias was high in most trials. Most cancers were non-small cell lung cancer (28 trials) and melanoma (15 trials). The worst-ranked ICI was ipilimumab (SUCRA 14%; event rate 848/10,000 patients) while the best-ranked ICI was atezolizumab (SUCRA 82%; event rate 119/10,000 patients). CONCLUSION: Each ICI showed a unique safety profile, with certain events more frequently observed with specific ICIs, which should be considered when managing cancer patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Pessoa de Meia-Idade , Inibidores de Checkpoint Imunológico/efeitos adversos , Metanálise em Rede , Teorema de Bayes
9.
PLoS Genet ; 17(6): e1009612, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34143770

RESUMO

Wolbachia is one of the most prevalent bacterial endosymbionts, infecting approximately 40% of terrestrial arthropod species. Wolbachia is often a reproductive parasite but can also provide fitness benefits to its host, as, for example, protection against viral pathogens. This protective effect is currently being applied to fight arboviruses transmission by releasing Wolbachia-transinfected mosquitoes. Titre regulation is a crucial aspect of Wolbachia biology. Higher titres can lead to stronger phenotypes and fidelity of transmission but can have a higher cost to the host. Since Wolbachia is maternally transmitted, its fitness depends on host fitness, and, therefore, its cost to the host may be under selection. Understanding how Wolbachia titres are regulated and other aspects of Wolbachia biology has been hampered by the lack of genetic tools. Here we developed a forward genetic screen to identify new Wolbachia over-proliferative mutant variants. We characterized in detail two new mutants, wMelPop2 and wMelOctoless, and show that the amplification or loss of the Octomom genomic region lead to over-proliferation. These results confirm previous data and expand on the complex role of this genomic region in the control of Wolbachia proliferation. Both new mutants shorten the host lifespan and increase antiviral protection. Moreover, we show that Wolbachia proliferation rate in Drosophila melanogaster depends on the interaction between Octomom copy number, the host developmental stage, and temperature. Our analysis also suggests that the life shortening and antiviral protection phenotypes of Wolbachia are dependent on different, but related, properties of the endosymbiont; the rate of proliferation and the titres near the time of infection, respectively. We also demonstrate the feasibility of a novel and unbiased experimental approach to study Wolbachia biology, which could be further adapted to characterize other genetically intractable bacterial endosymbionts.


Assuntos
Drosophila melanogaster/microbiologia , Genoma Bacteriano , Longevidade/imunologia , Simbiose/genética , Wolbachia/genética , Animais , Carga Bacteriana , Dicistroviridae/crescimento & desenvolvimento , Dicistroviridae/patogenicidade , Drosophila melanogaster/imunologia , Drosophila melanogaster/virologia , Feminino , Edição de Genes/métodos , Ilhas Genômicas , Masculino , Fenótipo , Wolbachia/crescimento & desenvolvimento , Wolbachia/metabolismo
10.
J Dairy Sci ; 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38608945

RESUMO

The objective of this randomized controlled trial was to evaluate the efficacy of supplementing bovine colostrum replacer during weaning to reduce intestinal permeability and improve gain. For this experiment, 65 calves were enrolled and housed individually until 70 d of age. Calves were fed milk replacer (150 g/L) 3 times daily with 9 L/d, 10.5 L/d, 11.25 L/d, and 12 L/d offered from d 1-7, d 8-14, d 15-21, d 22-56, respectively. Calves were weaned over 8 d from d 57-64, receiving a total of 7.8 L in 2 meals/d from d 57-60 and 3.8 L/d in one feeding from d 61-64. At d 57, calves were blocked by birth weight and randomly assigned to one of 2 treatments, equal in metabolizable energy, which were fed once daily during weaning from d 57-64: control (CON; n = 31 calves): 3.8 L milk replacer (150 g/L) fed by nipple bottle, or colostrum supplementation (COL; n = 34): a mixture of 1 L bovine colostrum replacer (125 g/L) and 3 L milk replacer (150 g/L) with 3.8 L of the mixture fed by nipple bottle. Serum IgG was measured within 48 h of birth and body weight was taken at d 0, 57, 60, 64, 70, 77, and 84. Starter intake and bovine respiratory disease (BRD) score were measured daily from d 50-70 and fecal consistency was examined daily from d 56-70. Serum ß-hydroxybutyrate (BHB) and lung consolidation were evaluated at d 57, 64, and 70 and intestinal permeability was assessed by recovery of chromium-EDTA, lactulose, and d-mannitol from plasma after oral administration at d 56 and 65. There was no difference in body weight between treatment groups at the start of weaning, but COL were 2.79 kg (95% CI: 0.90-4.68) and 2.76 kg (95% CI: 0.86-4.65) heavier than CON at d 77 and 84, respectively. Additionally, COL tended to gain 100.00 g/d more than CON calves (95% CI: -10.41-207.13) from d 57-84. There were no differences in any of the other variables measured. Supplementation of bovine colostrum replacer during weaning may improve weight gain, but the mechanism of action is not clear.

11.
Chem Biodivers ; 21(3): e202301641, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38358043

RESUMO

This study shows the profile of volatile organic compounds (VOCs) from pupae and larvae of Melipona quadrifasciata anthidioides Lepeletier subjected to three death induction techniques for hygienic behavior (HB) studies: freezing in liquid nitrogen (LN2), freezing in a freezer (FRZ) and piercing of offspring with an entomological pin (PIN). The VOCs from larvae and pupae were obtained through headspace solid-phase microextraction and characterized using gas chromatography coupled to mass spectrometry. In addition, an HB test was performed on the colonies. The main classes of VOCs were hydrocarbons, terpenes and alcohols. Multivariate analysis was applied and showed that there was a separation in the compound profiles between the different treatments. The HB test in the colonies showed that 24 hours after the application of the techniques, the bees removed more dead larvae in LN2 treatment (83.5 %), while after 48 hours more larvae were removed in the LN2 and FRZ treatments (92.3 %). When compared to pupae removal, larvae removal was significantly faster in LN2.


Assuntos
Compostos Orgânicos Voláteis , Abelhas , Animais , Compostos Orgânicos Voláteis/análise , Escala de Avaliação Comportamental , Cromatografia Gasosa-Espectrometria de Massas , Larva , Espectrometria de Massas , Pupa , Microextração em Fase Sólida
12.
Bioprocess Biosyst Eng ; 47(1): 145-157, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38103079

RESUMO

Global environmental concerns drive research toward the development of new eco-friendly compounds to replace pollutant chemicals. This study focuses on optimizing the production of trehalose lipids (TLs), which are glycolipid biosurfactants (BS) with various applications like antimicrobial or surface tension reduction. New microorganism sources, growth conditions, medium composition, purification conditions, and physicochemical properties of TLs are studied. Addressing a microscale approach, TLs production was successfully achieved using Rhodotorula sp. and Rhodococcus erythropolis to compare, with different media compositions including glucose-based and salt media supplemented with glycerol, glucose, n-hexadecane, n-dodecane. Liquid-liquid extraction using ethyl acetate and methanol was employed for compound extraction, followed by characterization using analytical methods such as Thin layer chromatography (TLC), High performance liquid chromatography (HPLC), and UHPLC. The produced TLs exhibited a minimum surface tension of 47 mN/m and a critical micellar concentration of 4.4 mg/mL. This study also identified Rhodotorula sp. as a new sustainable producer of TLs with improved productivity.


Assuntos
Rhodotorula , Trealose , Glicolipídeos , Micelas , Glucose , Tensoativos/química
13.
Molecules ; 29(2)2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38257246

RESUMO

Although the impacts of plastic pollution have long been recognized, the presence, pervasiveness, and ecotoxicological consequences of microplastic-i.e., plastic particles < 5 mm-contamination have only been explored over the last decade. Far less focus has been attributed to the role of these materials and, particularly, microplastics, as vectors for a multitude of chemicals, including those (un)intentionally added to plastic products, but also organic pollutants already present in the environment. Owing to the ubiquitous presence of microplastics in all environmental matrices and to the diverse nature of their chemical and physical characteristics, thoroughly understanding the mechanistic uptake/release of these compounds is inherently complex, but necessary in order to better assess the potential impacts of both microplastics and associated chemicals on the environment. Herein, we delve into the known processes and factors affecting these mechanisms. We center the discussion on microplastics and discuss some of the most prominent ecological implications of the sorption of this multitude of chemicals. Moreover, the key limitations of the currently available literature are described and a prospective outlook for the future research on the topic is presented.

14.
J Neurochem ; 165(4): 521-535, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36563047

RESUMO

Intracellular Ca2+ concentrations are strictly controlled by plasma membrane transporters, the endoplasmic reticulum, and mitochondria, in which Ca2+ uptake is mediated by the mitochondrial calcium uniporter complex (MCUc), while efflux occurs mainly through the mitochondrial Na+ /Ca2+ exchanger (NCLX). RNAseq database repository searches led us to identify the Nclx transcript as highly enriched in astrocytes when compared with neurons. To assess the role of NCLX in mouse primary culture astrocytes, we inhibited its function both pharmacologically or genetically. This resulted in re-shaping of cytosolic Ca2+ signaling and a metabolic shift that increased glycolytic flux and lactate secretion in a Ca2+ -dependent manner. Interestingly, in vivo genetic deletion of NCLX in hippocampal astrocytes improved cognitive performance in behavioral tasks, whereas hippocampal neuron-specific deletion of NCLX impaired cognitive performance. These results unveil a role for NCLX as a novel modulator of astrocytic glucose metabolism, impacting on cognition.


Assuntos
Astrócitos , Cálcio , Camundongos , Animais , Astrócitos/metabolismo , Cálcio/metabolismo , Trocador de Sódio e Cálcio/genética , Mitocôndrias/metabolismo , Glicólise , Cognição , Sódio/metabolismo , Sinalização do Cálcio/fisiologia
15.
Biochem Biophys Res Commun ; 687: 149185, 2023 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-37951047

RESUMO

Metacaspases are cysteine proteases belonging to the CD clan of the C14 family. They possess important characteristics, such as specificity for cleavage after basic residues (Arg/Lys) and dependence on calcium ions to exert their catalytic activity. They are defined by the presence of a large subunit (p20) and a small subunit (p10) and are classified into types I, II, and III. Type I metacaspases have a characteristic pro-domain at the N-terminal of the enzyme, preceding a region rich in glutamine and asparagine. In the yeast Saccharomyces cerevisiae, a type I metacaspase is found. This organism encodes a single metacaspase that participates in the process of programmed cell death by apoptosis. The study focuses on cloning, expressing, and mutating Saccharomyces cerevisiae metacaspase (ScMCA-Ia). Mutations in Cys155 and Cys276 were introduced to investigate autoprocessing mechanisms. Results revealed that Cys155 plays a crucial role in autoprocessing, initiating a conformational change that activates ScMCA-Ia. Comparative analysis with TbMCA-IIa highlighted the significance of the N-terminal region in substrate access to the active site. The study proposes a two-step processing mechanism for type I metacaspases, where an initial processing step generates the active form, followed by a distinct intermolecular processing step. This provides new insights into ScMCA-Ia's activation and function. The findings hold potential implications for understanding cellular processes regulated by metacaspases. Overall, this research significantly advances knowledge in metacaspase biology.


Assuntos
Caspases , Saccharomyces cerevisiae , Caspases/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Cisteína/genética , Apoptose , Domínio Catalítico
16.
Eur J Neurol ; 30(2): 305-320, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36263630

RESUMO

BACKGROUND AND PURPOSE: The development of high-quality clinical practice guidelines (CPGs) takes substantial time, effort, and resources. During the past years, the European Academy of Neurology (EAN) guideline production was significantly increased, so the need to develop clear, transparent, and methodologically solid criteria for prioritizing guideline topics became apparent. With this paper, we aim to define a set of criteria to be applied for prioritizing topics for future EAN guidelines, as well as the procedure for their implementation. METHODS: After review of the literature, we identified a recent systematic review that reported on the main prioritization criteria used by health organizations. Based on these, we developed a list of 20 preliminary criteria, which were voted on through a Delphi consensus procedure, including 160 stakeholders. Finally, we established a working procedure on how to submit and select new guideline topic proposals within the EAN. This procedure was reviewed by the EAN Scientific Committee and the Board. RESULTS: The first round, 61.3% of the participants voted, and 86% of them participated in the second round. Seven criteria were approved with this procedure. After the selection of the criteria, a prioritization procedure was launched, and the first 30 topics are reported in this paper. This bottom-up process that involved the whole EAN community was followed by a top-down process, using additional criteria for further selection by the EAN board members. CONCLUSIONS: We describe the development of prioritization criteria to be applied in the process of topic selection for future EAN CPGs. We will perform regular reviews and adjustments of the process.


Assuntos
Neurologia , Humanos , União Europeia
17.
BMC Cardiovasc Disord ; 23(1): 249, 2023 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-37173636

RESUMO

BACKGROUND: Renal denervation (RDN) has emerged in recent years as a possible treatment for hypertension. The first sham-controlled trial showed a small magnitude and non-significant in the blood pressure (BP) lowering effect, also due to a substantial decrease of BP in sham arm. Considering this, we aimed to quantify the magnitude of BP decrease within the sham arm of Randomized Controlled Trials (RCT) with RDN in patients with hypertension. METHODS: Electronic databases were searched since inception until January 2022 for randomized sham-controlled trials which assessed the efficacy in lowering BP of the sham intervention for catheter-based RDN in adult patients with hypertension. The outcomes were change in ambulatory/office systolic and diastolic BP. RESULTS: A total of 9 RCT were included in the analysis enrolling a total of 674 patients. Sham intervention showed a decrease in all evaluated outcomes. Office systolic BP had a reduction of -5.52 mmHg [95%CI -7.91, -3.13] and office diastolic BP of -2.13 mmHg [95%CI -3.08, -1.17]. Sham procedure for RDN also showed a reduction of -3.41 mmHg [95%CI -5.08, -1.75] in ambulatory systolic BP and - 2.44 mmHg [95%CI -3.31, -1.57] in ambulatory diastolic BP. CONCLUSION: Despite recent data indicating that RDN might be an effective treatment for patients with resistant hypertension when compared to a sham intervention, our results indicate that the sham intervention for RDN also has a significant effect on lowering Office and Ambulatory (24-h) Blood Pressure in adult patients with hypertension. This highlights that BP itself might be sensitive to placebo-like effect and also brings further difficulties in establishing the BP lowering efficacy of invasive interventions due to the magnitude of the sham effect.


Assuntos
Hipertensão , Adulto , Humanos , Hipertensão/diagnóstico , Hipertensão/cirurgia , Hipertensão/tratamento farmacológico , Rim , Pressão Sanguínea , Resultado do Tratamento , Simpatectomia/efeitos adversos , Simpatectomia/métodos , Anti-Hipertensivos/uso terapêutico , Monitorização Ambulatorial da Pressão Arterial
18.
J Thromb Thrombolysis ; 56(3): 474-484, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37405677

RESUMO

Oral anticoagulation significantly reduces the incidence of dementia in atrial fibrillation patients. However, this protective effect has not been compared between Direct Oral Anticoagulants (DOAC) and Vitamin K antagonists' anticoagulants (VKA). We conducted an electronic search for potentially eligible studies through the bibliographic databases MEDLINE, CENTRAL, ClinicalTrials.gov, EMBASE and Web of Science. The outcome of interest was dementia. Random-effects meta-analysis was performed. Nine observational studies were included and 1,175,609 atrial fibrillation patients were enrolled. DOAC therapy was associated with a significant reduction when compared with patients under VKA therapy (hazard ratio 0.89; 95% confidence interval 0.80-0.99). The grade of confidence of our results was very low due to the risk of bias. DOAC therapy is associated with a significant decrease in the risk of dementia when compared with VKA therapy. However, the low certainty of the evidence along with the paucityof clinical trials dedicated to answering this important question underscores a need for global clinical research initiatives.


Assuntos
Fibrilação Atrial , Demência , Acidente Vascular Cerebral , Humanos , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Anticoagulantes/efeitos adversos , Fibrinolíticos/uso terapêutico , Vitamina K , Demência/prevenção & controle , Administração Oral , Acidente Vascular Cerebral/prevenção & controle , Acidente Vascular Cerebral/complicações
19.
Mar Drugs ; 21(12)2023 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-38132941

RESUMO

The growing understanding and knowledge of the potential of marine species, as well as the application of "blue biotechnology" have been motivating new innovative solutions in cosmetics. It is widely noted that that marine species are important sources of compounds with several biological activities that are yet to be discovered. This review explores various biological properties of marine-derived molecules and briefly outlines the main extraction methods. Alongside these, it is well known the legislative and normative framework of cosmetics is increasingly being developed. In this research segment, there is a growing concern with sustainability. In this sense, "blue biotechnology", together with the use of invasive species or marine waste products to obtain new active ingredients, haven been emerging as innovative and sustainable solutions for the future's cosmetics industry. This review also examines the regulatory framework and focus on the recent advancements in "blue biotechnology" and its relevance to the sustainable development of innovative cosmetics.


Assuntos
Cosméticos , Biotecnologia , Indústrias
20.
Sensors (Basel) ; 23(13)2023 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-37447812

RESUMO

Due to the increase in the number of mobile stations in recent years, cooperative relaying systems have emerged as a promising technique for improving the quality of fifth-generation (5G) wireless networks with an extension of the coverage area. In this paper, we propose a two-hop orthogonal frequency division multiplexing and code-division multiple-access (OFDM-CDMA) multiple-input multiple-output (MIMO) relay system, which combines, both at the source and relay nodes, a tensor space-time-frequency (TSTF) coding with a multiple symbol matrices Kronecker product (MSMKron), called TSTF-MSMKron coding, aiming to increase the diversity gain. It is first established that the signals received at the relay and the destination satisfy generalized Tucker models whose core tensors are the coding tensors. Assuming the coding tensors are known at both nodes, tensor models are exploited to derive two semi-blind receivers, composed of two steps, to jointly estimate symbol matrices and individual channels. Necessary conditions for parameter identifiability with each receiver are established. Extensive Monte Carlo simulation results are provided to show the impact of design parameters on the symbol error rate (SER) performance, using the zero-forcing (ZF) receiver. Next, Monte Carlo simulations illustrate the effectiveness of the proposed TSTF-MSMKron coding and semi-blind receivers, highlighting the benefit of exploiting the new coding to increase the diversity gain.


Assuntos
Algoritmos , Simulação por Computador , Método de Monte Carlo
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