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1.
J Clin Exp Dent ; 16(4): e503-e515, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38725825

RESUMO

Background: To evaluate the influence of chemotherapy on the prevalence of trismus in irradiated head and neck cancer patients. Material and Methods: This systematic review guided by PRISMA-2020 and registered in PROSPERO (CRD42021255377) screened 963 articles in 7 scientific-databases (PubMed, Lilacs, Livivo, Scopus, Embase, Web of Science, EBSCO) and 3 grey-literature databases (Open Grey, Google Scholar, ProQuest) and eight articles were included for qualitative synthesis, meta-analysis (combined odds ratio, inverse variance method plus random effects), heterogeneity analysis (I² and Tau²), one-of-out evaluation and publication bias analysis (Eggs' and Begg's tests) (RevMan®, p<0.05). The Newcastle-Ottawa Quality Assessment Scale Cohort Studies was used to assess the risk of bias (RoB). The classification assessment, development, and recommendations (GRADE) approach was used to assess the certainty of evidence. Results: The eight articles evaluated 1474 patients treated with chemoradiotherapy and 858 patients treated with radiotherapy. Five articles had low RoB, and three had high RoB. Chemoradiotherapy significantly (p=0.0003) increased the prevalence of trismus (OR=2.55, 95% CI = 1.53-4.23) compared to radiotherapy, with significant (p=0.010) but low heterogeneity (I²=59%;Tau²=0.29). There was no significant risk of publication bias, one-out analysis showed no significant difference between studies, and GRADE showed a moderate level of evidence. Trismus was directly associated to worse quality of life. Conclusions: The incidence of trismus increases when chemotherapy is combined with radiotherapy for head and neck cancer, which negatively impacts the quality of life. Key words:Radiotherapy, Chemoradiotherapy, Head and Neck Neoplasms, Trismus, Quality of Life.

2.
Int Arch Otorhinolaryngol ; 28(2): e326-e331, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38618584

RESUMO

Introduction Smell is one of the senses of the human body, and it can be affected by several factors, such as viral infections, traumatic brain injury, iatrogenesis, smoking, and neurodegenerative and systemic diseases. Objectives The main goal of the present study is to describe the epidemiology of olfactory disorders in Rio Grande do Norte (RN). More specifically, to determine the prevalence of olfactory dysfunction and to identify the main risk factors related to these dysfunctions in the state's population. Methods A total of 180 volunteers living in the RN underwent the Connecticut Clinical Research Center (CCCRC) smell test and a clinical and demographic questionnaire. Results A total of 58.89% of the patients presented normosmia and 87.78% were classified as having between normal and mild hyposmia. A statistically significant relationship was found between worse performance in the test and nasal surgery ( p = 0.041) and the subjective feeling of not having an accurate sense of smell ( p = 0.006 on the right nostril). There was no statistical relationship between the olfactory status and the report of coronavirus disease 2019 (COVID-19) infection ( p = 0.254). Conclusion The occurrence of altered sense of smell in our study was different from that reported in other studies that used the same test. The relationship with COVID-19 was not clear.

3.
Curr Top Med Chem ; 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38523516

RESUMO

BACKGROUND: Inflammation is a series of complex defense-related reactions. The inflammation cascade produces various pro-inflammatory mediators. Unregulated production of these pro-inflammatory mediators can lead to a wide range of diseases, including rheumatoid arthritis, sepsis, and inflammatory bowel disease. In the literature, the anti-inflammatory action of quinoline and thiazolidinedione nuclei are well established, alone, and associated with other nuclei. The synthesis of hybrid molecules is a strategy for obtaining more efficient molecules due to the union of pharmacophoric nuclei known to be related to pharmacological activity. OBJECTIVE: Based on this, this work presents the synthesis of thiazolidinedione-quinoline molecular hybrids and their involvement in the modulation of cytokines involved in the inflammatory reaction cascade. METHODS: After synthesis and characterization, the compounds were submitted to cell viability test (MTT), ELISA IFN-γ and TNF-α, adipogenic differentiation, and molecular docking assay with PPARy and COX-2 targets. RESULTS: LPSF/ZKD2 and LPSF/ZKD7 showed a significant decrease in the concentration of IFN- γ and TNF-α, with a dose-dependent behavior. LPSF/ZKD4 at a concentration of 50 µM significantly reduced IL-6 expression. LPSF/ZKD4 demonstrates lipid accumulation with significant differences between the untreated and negative control groups, indicating a relevant agonist action on the PPARγ receptor. Molecular docking showed that all synthesized compounds have good affinity with PPARγ e COX-2, with binding energy close to -10,000 Kcal/mol. CONCLUSION: These results demonstrate that the synthesis of quinoline-thiazolidinedione hybrids may be a useful strategy for obtaining promising candidates for new anti-inflammatory agents.

4.
JTO Clin Res Rep ; 5(3): 100646, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38434771

RESUMO

Introduction: Stage III NSCLC is a heterogeneous disease, representing approximately one-third of newly diagnosed lung cancers. Brazil lacks detailed information regarding stage distribution, treatment patterns, survival, and prognostic variables in locally advanced NSCLC. Methods: RELANCE/LACOG 0118 is an observational, retrospective cohort study assessing sociodemographic and clinical data of patients diagnosed with having stage III NSCLC from January 2015 to June 2019, regardless of treatment received. The study was conducted across 13 cancer centers in Brazil. Disease status and survival data were collected up to June 2021. Descriptive statistics, survival analyses, and a multivariable Cox regression model were performed. p values less than 0.05 were considered significant. Results: We recruited 403 patients with stage III NSCLC. Most were male (64.0%), White (31.5%), and smokers or former smokers (86.1%). Most patients had public health insurance (67.5%), had stage IIIA disease (63.2%), and were treated with concurrent chemoradiation (53.1%). The median follow-up time was 33.83 months (95% confidence interval [CI]: 30.43-37.50). Median overall survival (OS) was 27.97 months (95% CI: 21.57-31.73), and median progression-free survival was 11.23 months (95% CI: 10.70-12.77). The type of treatment was independently associated with OS and progression-free survival, whereas the types of health insurance and histology were independent predictors of OS only. Conclusions: Brazilian patients with stage III NSCLC with public health insurance are diagnosed later and have poorer OS. Nevertheless, patients with access to adequate treatment have outcomes similar to those reported in the pivotal trials. Health policy should be improved to make lung cancer diagnosis faster and guarantee prompt access to adequate treatment in Brazil.

5.
Data Brief ; 53: 110112, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38328288

RESUMO

The dataset aims to examine the prior and acquired knowledge in an Escape Room (ER) experience on sustainable mobility. In addition, the data could also be used to identify possible correspondences between some mobility behaviors and the predisposition to learn sustainable mobility concepts to foster attitude change. To meet these objectives, an ER on sustainable mobility was conducted and a questionnaire was given before and after the activity to 173 students from various schools between 5th grade of primary school and 1st year of compulsory secondary school (10-13 years old). The questionnaire was divided into two parts. The first part included social demographics questions (gender, family members, place of residence) and mobility habits (number of cars in the family, bus use, cycling). The second part included questions related to sustainable mobility topics with 14 items. Data was collected between December 2022 and February 2023.

6.
Chembiochem ; 25(6): e202300679, 2024 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-38205937

RESUMO

The connection between 3d (Cu) and 4d (Mo) via the "Mo-S-Cu" unit is called Mo-Cu antagonism. Biology offers case studies of such interactions in metalloproteins such as Mo/Cu-CO Dehydrogenases (Mo/Cu-CODH), and Mo/Cu Orange Protein (Mo/Cu-ORP). The CODH significantly maintains the CO level in the atmosphere below the toxic level by converting it to non-toxic CO2 for respiring organisms. Several models were synthesized to understand the structure-function relationship of these native enzymes. However, this interaction was first observed in ruminants, and they convert molybdate (MoO4 2- ) into tetrathiomolybdate (MoS4 2- ; TTM), reacting with cellular Cu to yield biological unavailable Mo/S/Cu cluster, then developing Cu-deficiency diseases. These findings inspire the use of TTM as a Cu-sequester drug, especially for treating Cu-dependent human diseases such as Wilson diseases (WD) and cancer. It is well known that a balanced Cu homeostasis is essential for a wide range of biological processes, but negative consequence leads to cell toxicity. Therefore, this review aims to connect the Mo-Cu antagonism in metalloproteins and anti-copper therapy.


Assuntos
Cobre , Metaloproteínas , Humanos , Cobre/metabolismo , Molibdênio/farmacologia , Molibdênio/uso terapêutico
7.
J Physiother ; 70(1): 16-24, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38036402

RESUMO

QUESTIONS: What is the effect of preoperative respiratory muscle training (RMT) on the incidence of postoperative pulmonary complications (PPCs) after open cardiac surgery? What is the effect of RMT on the duration of mechanical ventilation, postoperative length of stay and respiratory muscle strength? DESIGN: Systematic review of randomised trials with meta-analysis. PARTICIPANTS: Adults undergoing elective open cardiac surgery. INTERVENTION: The experimental groups received preoperative RMT and the comparison groups received no intervention. OUTCOME MEASURES: The primary outcomes were PPCs, length of hospital stay, respiratory muscle strength, oxygenation and duration of mechanical ventilation. The methodological quality of studies was assessed using the PEDro scale and the overall certainty of the evidence was assessed using the GRADE approach. RESULTS: Eight trials involving 696 participants were included. Compared with the control group, the respiratory training group had fewer PPCs (RR 0.51, 95% CI 0.38 to 0.70), less pneumonia (RR 0.44, 95% CI 0.25 to 0.78), shorter hospital stay (MD -1.7 days, 95% CI -2.4 to -1.1) and higher maximal inspiratory pressure values at the end of the training protocol (MD 12 cmH2O, 95% CI 8 to 16). The mechanical ventilation time was similar in both groups. The quality of evidence was high for pneumonia, length of hospital stay and maximal inspiratory pressure. CONCLUSION: Preoperative RMT reduced the risk of PPCs and pneumonia after cardiac surgery. The training also improved the maximal inspiratory pressure and reduced hospital stay. The effects on PPCs were large enough to warrant use of RMT in this population. REGISTRATION: CRD42021227779.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Pneumonia , Adulto , Humanos , Tempo de Internação , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Exercícios Respiratórios/métodos , Pneumonia/prevenção & controle , Músculos Respiratórios/fisiologia , Complicações Pós-Operatórias/prevenção & controle
8.
Crit Rev Toxicol ; 53(10): 658-701, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38050998

RESUMO

Tobacco use is a major cause of preventable morbidity and mortality globally. Tobacco products, including smokeless tobacco (ST), generally contain tobacco-specific N-nitrosamines (TSNAs), such as N'-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-butanone (NNK), which are potent carcinogens that cause mutations in critical genes in human DNA. This review covers the series of biochemical and chemical transformations, related to TSNAs, leading from tobacco cultivation to cancer initiation. A key aim of this review is to provide a greater understanding of TSNAs: their precursors, the microbial and chemical mechanisms that contribute to their formation in ST, their mutagenicity leading to cancer due to ST use, and potential means of lowering TSNA levels in tobacco products. TSNAs are not present in harvested tobacco but can form due to nitrosating agents reacting with tobacco alkaloids present in tobacco during certain types of curing. TSNAs can also form during or following ST production when certain microorganisms perform nitrate metabolism, with dissimilatory nitrate reductases converting nitrate to nitrite that is then released into tobacco and reacts chemically with tobacco alkaloids. When ST usage occurs, TSNAs are absorbed and metabolized to reactive compounds that form DNA adducts leading to mutations in critical target genes, including the RAS oncogenes and the p53 tumor suppressor gene. DNA repair mechanisms remove most adducts induced by carcinogens, thus preventing many but not all mutations. Lastly, because TSNAs and other agents cause cancer, previously documented strategies for lowering their levels in ST products are discussed, including using tobacco with lower nornicotine levels, pasteurization and other means of eliminating microorganisms, omitting fermentation and fire-curing, refrigerating ST products, and including nitrite scavenging chemicals as ST ingredients.


Assuntos
Neoplasias , Nitrosaminas , Tabaco sem Fumaça , Humanos , Carcinógenos/toxicidade , Mutagênicos , Neoplasias/induzido quimicamente , Nitratos , Nitritos , Nitrosaminas/toxicidade , Nitrosaminas/química , Nitrosaminas/metabolismo , Tabaco sem Fumaça/toxicidade
9.
Lasers Med Sci ; 38(1): 259, 2023 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-37935876

RESUMO

This study evaluated photobiomodulation therapy (PBMT) for treatment of trismus in patients undergoing radiotherapy for head and neck cancer (HNC). Sixteen patients, 10 men and 6 women, who had a mouth opening < 35 mm and underwent RT were included. The patients were evaluated daily before and after the PBMT application, measuring mouth opening and performing pain scores for the masticatory muscles using the visual analog scale (VAS). We used the infrared laser (~ 808 nm) extraorally, 0.1 W power, 3 J energy, 30 s (107 J/cm2) per point, applied to temporalis anterior, masseter muscles, and temporomandibular joints (TMJ). An intraoral point was made in the trigonoretromolar region towards the medial pterygoid muscle. The mean mouth opening of the patients increased by more than 7 mm throughout the treatment. The pain scores on the initial days showed an immediate reduction after PBMT on the ipsilateral side in the muscles and TMJ. Throughout PBMT applications, there was a significant reduction in pain scores in all muscles and the TMJ. The radiation dose of all patients was above 40 Gy, which is the threshold dose for the risk of developing trismus. SPSS software was used and adopted a confidence of 95%. The Kolmogorov-Smirnov normality test, Wilcoxon test, and Spearman correlation were performed. PBMT controls muscular pain and reduced mouth opening limitation in HNC during radiotherapy. Further studies are needed to evaluate the preventive capacity of PBMT protocols for RT trismus-related HNC.


Assuntos
Neoplasias de Cabeça e Pescoço , Terapia com Luz de Baixa Intensidade , Masculino , Humanos , Feminino , Trismo/etiologia , Trismo/radioterapia , Terapia com Luz de Baixa Intensidade/métodos , Neoplasias de Cabeça e Pescoço/radioterapia , Músculos da Mastigação , Dor
10.
Support Care Cancer ; 31(8): 480, 2023 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-37477721

RESUMO

OBJECTIVE: The objective of this systematic review was to determine whether oral and dental hygiene protocols (DHPs) reduce the incidence and severity of oral mucositis (OM) during antineoplastic treatment. MATERIALS AND METHODS: This PROSPERO-registered systematic review (CRD42021295322) was based on searches of publicly accessible databases, including PubMed, Scopus, Web of Science, LILACS, EBSCOhost, LIVIVO, Embase, and gray literature (Google Scholar, ProQuest, and Energy) until December 2021. Twenty-five articles from these searches and 14 articles retrieved from the references therein were evaluated in this systematic review and meta-analysis. The risk of bias (RoB) was assessed using RoB-2 and ROBINS-I for randomized (RCT) and non-randomized (n-RCT) clinical trials, respectively. A meta-analysis was performed on RCTs and n-RCTs in two subgroups to evaluate oral mouth rinses or DHP. GRADE-pro was used to assess the degree of certainty of the evidence. RESULTS: Of the 3367 articles retrieved, 25 RCTs and 14 n-RCTs involving 2109 and 754 patients, respectively, were included in the analyses. RoB was low for RCTs and moderate-to-very severe for n-RCTs. High heterogeneity and publication RoB were identified. In RCTs, mouth rinses (p = 0.830) and DHP (p = 0.100) did not reduce the incidence of OM. However, mouth rinses strongly reduced the severity of OM (p < 0.001; Cohen's d = - 1.87, 95% confidence interval [CI] = - 2.49 to - 1.24). In non-RCTs, mouth rinses (p < 0.001) and DHP (p < 0.001) reduced the relative risk of OM 0.38 (95% CI = 0.24 to 0.59) and 0.64 (95% CI = 0.53 to 0.70) times, respectively. In addition, DHP strongly reduced OM severity (Cohen's d = - 0.81, 95% CI = - 1.03 to - 0.59). GRADE-pro showed high certainty of OM severity and incidence in RCTs and non-RCTs, respectively, and low (OM incidence in RCTs) to very low (OM severity in non-RCTs) certainty in other outcomes. CONCLUSION: DHPs strongly reduce the severity and moderately reduce the incidence of OM. However, further studies with low heterogeneity are needed to validate these findings.


Assuntos
Antineoplásicos , Higiene Bucal , Estomatite , Humanos , Antineoplásicos/efeitos adversos , Incidência , Antissépticos Bucais/uso terapêutico , Estomatite/induzido quimicamente , Estomatite/epidemiologia , Estomatite/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto , Neoplasias/complicações , Neoplasias/tratamento farmacológico
11.
J Perinat Med ; 51(7): 896-903, 2023 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-37163520

RESUMO

OBJECTIVES: Analyze the diagnostic and prognostic value of the sFlt-1/PlGF ratio in pregnant women with at least one sign/symptom of suspected/diagnosed pre-eclampsia. METHODS: This retrospective observational study included 170 pregnant women with at least one sign/symptom of pre-eclampsia, who had sFlt-1/PlGF ratio values. The following information was evaluated: pregnant women's demographic data and clinical history; laboratory data (urine protein/creatinine ratio; sFlt-1/PlGF ratio); signs and symptoms presented; clinical outcome; fetal complications; data related to childbirth. Statistical analysis was performed by R Software Version 3.5.2. RESULTS: Among the 170 patients, 78 presented pre-eclampsia. The median sFlt-1/PlGF ratio was significantly higher [143.1 (2.2-2,927.1)] for women who presented pre-eclampsia than for women without pre-eclampsia [33.5 (0.8-400.2)]. The negative predictive value of sFlt-1/PlGF ratio <38 was 83.9 % (95 % CI, 71.7-92.4 %) and the positive predictive value of sFlt-1/PlGF ratio >85 or 110 (for late onset pre-eclampsia) was 76.4 % (95 % CI, 66.2-84.8 %). sFlt-1/PlGF >85 or 110 was associated with pre-eclampsia clinical development, fetal complications, shorter gestational age at birth, higher number of caesarean deliveries and lower birth weight. CONCLUSIONS: The sFlt-1/PlGF ratio, together with the standard diagnostic criteria, can be used to rule out pre-eclampsia, identify high-risk patients and predict the occurrence of adverse outcomes.


Assuntos
Pré-Eclâmpsia , Feminino , Humanos , Recém-Nascido , Gravidez , Biomarcadores/metabolismo , Obstetrícia , Fator de Crescimento Placentário , Pré-Eclâmpsia/diagnóstico , Pré-Eclâmpsia/metabolismo , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Receptor 1 de Fatores de Crescimento do Endotélio Vascular
12.
Rev Port Cardiol ; 42(10): 861-872, 2023 Oct.
Artigo em Inglês, Português | MEDLINE | ID: mdl-37172761

RESUMO

Cardiovascular (CV) guidelines stress the need for global intervention to manage risk factors and reduce the risk of major vascular events. Growing evidence supports the use of polypill as a strategy to prevent cerebral and cardiovascular disease, however it is still underused in clinical practice. This paper presents an expert consensus aimed to summarize the data regarding polypill use. The authors consider the benefits of polypill and the significant claims for clinical applicability. Potential advantages and disadvantages, data regarding several populations in primary and secondary prevention, and pharmacoeconomic data are also addressed.

13.
Molecules ; 28(10)2023 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-37241969

RESUMO

A story going back almost 40 years is presented in this manuscript. This is a different and more challenging way of reporting my research and I hope it will be useful to and target a wide-ranging audience. When preparing the manuscript and collecting references on the subject of this paper-aldehyde oxidoreductase from Desulfovibrio gigas-I felt like I was travelling back in time (and space), bringing together the people that have contributed most to this area of research. I sincerely hope that I can give my collaborators the credit they deserve. This study is not presented as a chronologic narrative but as a grouping of topics, the development of which occurred over many years.


Assuntos
Aldeído Oxirredutases , Desulfovibrio , Humanos , Desulfovibrio gigas , Molibdênio , Aldeído Desidrogenase
14.
Sensors (Basel) ; 23(5)2023 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-36904964

RESUMO

The fast growth of Internet-connected embedded devices demands new system capabilities at the network edge, such as provisioning local data services on both limited network and computational resources. The current contribution addresses the previous problem by enhancing the usage of scarce edge resources. It designs, deploys, and tests a new solution that incorporates the positive functional advantages offered by software-defined networking (SDN), network function virtualization (NFV), and fog computing (FC). Our proposal autonomously activates or deactivates embedded virtualized resources, in response to clients' requests for edge services. Complementing existing literature, the obtained results from extensive tests on our programmable proposal show the superior performance of the proposed elastic edge resource provisioning algorithm, which also assumes an SDN controller with proactive OpenFlow behavior. According to our results, the maximum flow rate for the proactive controller is 15% higher; the maximum delay is 83% smaller; and the loss is 20% smaller compared to when the non-proactive controller is in operation. This improvement in flow quality is complemented by a reduction in control channel workload. The controller also records the time duration of each edge service session, which can enable the accounting of used resources per session.

15.
Cureus ; 15(1): e33841, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36819439

RESUMO

Paraneoplastic neurologic syndromes (PNS) are neurologic disorders that can affect any part of the nervous system, occur in association with cancer, and have an immune-mediated mechanism that produces direct damage to the neural tissue. Neurological symptoms frequently precede, in months to years, the symptoms directly attributed to the primary tumor, requiring a high clinical suspicion for adequate investigation. We report the case of a man in his early 80s admitted for an altered level of consciousness, alternating between periods with stupor and drowsiness, short-term waking states and psychomotor agitation, respiratory failure and dysautonomia, resembling a Morvan's syndrome. Anti-leucine-rich glioma-inactivated 1 and anti-contactin-associated protein-like 2 antibodies were both positive and, after exclusion of infectious and autoimmune systemic causes, the possibility of PNS was raised. Screening for the primary tumor was pursued, and an 18F-fluorodeoxyglucose (18F-FDG)/PET showed only an intensely hypermetabolic, apparent parietal thickening of the lower rectum. Due to the frequent association of Morvan's syndrome to thymoma, a review of the CT of the thorax images was requested and a mediastinal image with features of thymoma was identified. PNS treatment and prognosis depend on finding and treating the underlying tumor, with benefits in both resolution of neurological symptoms and in the prognosis of the underlying tumor itself. Therefore, clinicians should be aware of this frequent but underdiagnosed and underreported condition, in order to improve the chances of better outcomes.

16.
J Inorg Biochem ; 240: 112096, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36603242

RESUMO

The rational design and functionalization of small, simple, and stable peptides scaffolds is an attractive avenue to mimic catalytic metal-centres of complex proteins, relevant for the design of metalloenzymes with environmental, biotechnological and health impacts. The de novo designed α3DIV-L21C framework has a rubredoxin-like metal binding site and was used in this work to incorporate a Mo-atom. Thermostability studies using differential scanning calorimetry showed an increase of 4 °C in the melting temperature of the Mo-α3DIV-L21C when compared to the apo-α3DIV-L21C. Circular dichroism in the visible and far-UV regions corroborated these results showing that Mo incorporation provides stability to the peptide even though there were almost no differences observed in the secondary structure. A formal reduction potential of ∼ -408 mV vs. NHE, pH 7.6 was determined. Combining electrochemical results, EPR and UV-visible data we discuss the oxidation state of the molybdenum centre in Mo-α3DIV-L21C and propose that is mainly in a Mo (VI) oxidation state.


Assuntos
Metaloproteínas , Molibdênio , Molibdênio/química , Rubredoxinas/metabolismo , Metaloproteínas/química , Oxirredução , Peptídeos/metabolismo
17.
J Inorg Biochem ; 238: 112056, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36332410

RESUMO

Research on enzymes for lignocellulose biomass degradation has progressively increased in recent years due to the interest in taking advantage of this natural resource. Among these enzymes are the lytic polysaccharide monooxygenases (LPMOs) that oxidatively depolymerize crystalline cellulose using a reactive oxygen species generated in a reduced mono­copper active site. The copper site comprises of a highly conserved histidine-brace, providing three equatorial nitrogen ligands, whereas less conserved residues close to the copper contribute to shaping and confining the site. The catalytic copper site is exposed to the solvent and to the crystalline substrates, and as so, the influence of the copper environment on LPMO properties, including the redox potential, is of great interest. In the current work, a direct electrochemical study of an LPMO (ScLPMO10C) was conducted allowing to retrieve kinetic and thermodynamic data associated with the redox transition in the catalytic centre. Moreover, two residues that do not bind to the copper but shape the copper sites were mutated, and the properties of the mutants were compared with those of the wild-type enzyme. The direct electrochemical studies, using cyclic voltammetry, yielded redox potentials in the +200 mV range, well in line with LPMO redox potentials determined by other methods. Interestingly, while the mutations hardly affected the formal redox potential of the enzyme, they drastically affected the reactivity of the copper site and enzyme functionality.


Assuntos
Cobre , Oxigenases de Função Mista , Cobre/química , Oxigenases de Função Mista/metabolismo , Domínio Catalítico , Polissacarídeos/metabolismo , Celulose
18.
Molecules ; 29(1)2023 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-38202704

RESUMO

Living organisms use selenium mainly in the form of selenocysteine in the active site of oxidoreductases. Here, selenium's unique chemistry is believed to modulate the reaction mechanism and enhance the catalytic efficiency of specific enzymes in ways not achievable with a sulfur-containing cysteine. However, despite the fact that selenium/sulfur have different physicochemical properties, several selenoproteins have fully functional cysteine-containing homologues and some organisms do not use selenocysteine at all. In this review, selected selenocysteine-containing proteins will be discussed to showcase both situations: (i) selenium as an obligatory element for the protein's physiological function, and (ii) selenium presenting no clear advantage over sulfur (functional proteins with either selenium or sulfur). Selenium's physiological roles in antioxidant defence (to maintain cellular redox status/hinder oxidative stress), hormone metabolism, DNA synthesis, and repair (maintain genetic stability) will be also highlighted, as well as selenium's role in human health. Formate dehydrogenases, hydrogenases, glutathione peroxidases, thioredoxin reductases, and iodothyronine deiodinases will be herein featured.


Assuntos
Selênio , Humanos , Cisteína , Selenocisteína , Enxofre , Oxirredução , Biologia
19.
Int J Mol Sci ; 23(23)2022 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-36499524

RESUMO

Caveolin-2 is a protein suitable for the study of interactions of caveolins with other proteins and lipids present in caveolar lipid rafts. Caveolin-2 has a lower tendency to associate with high molecular weight oligomers than caveolin-1, facilitating the study of its structural modulation upon association with other proteins or lipids. In this paper, we have successfully expressed and purified recombinant human caveolin-2 using E. coli. The structural changes of caveolin-2 upon interaction with a lipid bilayer of liposomes were characterized using bioinformatic prediction models, circular dichroism, differential scanning calorimetry, and fluorescence techniques. Our data support that caveolin-2 binds and alters cholesterol-rich domains in the membranes through a CARC domain, a type of cholesterol-interacting domain in its sequence. The far UV-CD spectra support that the purified protein keeps its folding properties but undergoes a change in its secondary structure in the presence of lipids that correlates with the acquisition of a more stable conformation, as shown by differential scanning calorimetry experiments. Fluorescence experiments using egg yolk lecithin large unilamellar vesicles loaded with 1,6-diphenylhexatriene confirmed that caveolin-2 adsorbs to the membrane but only penetrates the core of the phospholipid bilayer if vesicles are supplemented with 30% of cholesterol. Our study sheds light on the caveolin-2 interaction with lipids. In addition, we propose that purified recombinant caveolin-2 can provide a new tool to study protein-lipid interactions within caveolae.


Assuntos
Caveolina 1 , Escherichia coli , Humanos , Escherichia coli/metabolismo , Caveolina 1/metabolismo , Caveolina 2/metabolismo , Cavéolas/metabolismo , Colesterol/metabolismo , Microdomínios da Membrana/metabolismo , Bicamadas Lipídicas/metabolismo
20.
Artigo em Inglês | MEDLINE | ID: mdl-36078229

RESUMO

(1) Background: Maternal syphilis (MS) and congenital syphilis (CS) are serious public health problems worldwide due to their high morbidity and mortality rates. (2) Objective: Evaluating the applicability of Clinical Protocols and Treatment Guidelines on case incidence trends in Brazil and Portugal. (3) Methods: The review was done through bibliographic research in two public databases and government websites from both countries, published between 2007 and 2022. All guidelines that contained CS and MS were selected. (4) Results and discussion: After evaluation, we found that Brazil and Portugal have adequate protocols for screening and treating congenital and maternal syphilis. (5) Conclusion: The results suggest that CS and MS incidence are notably higher in Brazil than in Portugal due to economic, cultural, and social disparities and the differences in territory size. Therefore, these demographic and socioeconomic factors could strongly influence efforts to fight against syphilis and thus control the infection.


Assuntos
Complicações Infecciosas na Gravidez , Sífilis Congênita , Sífilis , Brasil/epidemiologia , Protocolos Clínicos , Feminino , Humanos , Portugal/epidemiologia , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Sífilis/epidemiologia , Sífilis/prevenção & controle , Sífilis Congênita/diagnóstico , Sífilis Congênita/epidemiologia , Sífilis Congênita/prevenção & controle
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