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1.
Annu Rev Cell Dev Biol ; 37: 43-63, 2021 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-34314592

RESUMO

The centrosome is a main orchestrator of the animal cellular microtubule cytoskeleton. Dissecting its structure and assembly mechanisms has been a goal of cell biologists for over a century. In the last two decades, a good understanding of the molecular constituents of centrosomes has been achieved. Moreover, recent breakthroughs in electron and light microscopy techniques have enabled the inspection of the centrosome and the mapping of its components with unprecedented detail. However, we now need a profound and dynamic understanding of how these constituents interact in space and time. Here, we review the latest findings on the structural and molecular architecture of the centrosome and how its biogenesis is regulated, highlighting how biophysical techniques and principles as well as quantitative modeling are changing our understanding of this enigmatic cellular organelle.


Assuntos
Centrossomo , Organelas , Animais
2.
Nat Immunol ; 23(10): 1470-1483, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36138183

RESUMO

Traditionally viewed as poorly plastic, neutrophils are now recognized as functionally diverse; however, the extent and determinants of neutrophil heterogeneity in humans remain unclear. We performed a comprehensive immunophenotypic and transcriptome analysis, at a bulk and single-cell level, of neutrophils from healthy donors and patients undergoing stress myelopoiesis upon exposure to growth factors, transplantation of hematopoietic stem cells (HSC-T), development of pancreatic cancer and viral infection. We uncover an extreme diversity of human neutrophils in vivo, reflecting the rates of cell mobilization, differentiation and exposure to environmental signals. Integrated control of developmental and inducible transcriptional programs linked flexible granulopoietic outputs with elicitation of stimulus-specific functional responses. In this context, we detected an acute interferon (IFN) response in the blood of patients receiving HSC-T that was mirrored by marked upregulation of IFN-stimulated genes in neutrophils but not in monocytes. Systematic characterization of human neutrophil plasticity may uncover clinically relevant biomarkers and support the development of diagnostic and therapeutic tools.


Assuntos
Mielopoese , Neutrófilos , Biomarcadores/metabolismo , Humanos , Interferons/genética , Interferons/metabolismo , Neutrófilos/metabolismo , Plásticos/metabolismo
3.
Proc Natl Acad Sci U S A ; 121(14): e2308132121, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38551841

RESUMO

Tumor necrosis factor (TNF) receptor 1 (TNFR1) plays a pivotal role in mediating TNF induced downstream signaling and regulating inflammatory response. Recent studies have suggested that TNFR1 activation involves conformational rearrangements of preligand assembled receptor dimers and targeting receptor conformational dynamics is a viable strategy to modulate TNFR1 signaling. Here, we used a combination of biophysical, biochemical, and cellular assays, as well as molecular dynamics simulation to show that an anti-inflammatory peptide (FKCRRWQWRMKK), which we termed FKC, inhibits TNFR1 activation allosterically by altering the conformational states of the receptor dimer without blocking receptor-ligand interaction or disrupting receptor dimerization. We also demonstrated the efficacy of FKC by showing that the peptide inhibits TNFR1 signaling in HEK293 cells and attenuates inflammation in mice with intraperitoneal TNF injection. Mechanistically, we found that FKC binds to TNFR1 cysteine-rich domains (CRD2/3) and perturbs the conformational dynamics required for receptor activation. Importantly, FKC increases the frequency in the opening of both CRD2/3 and CRD4 in the receptor dimer, as well as induces a conformational opening in the cytosolic regions of the receptor. This results in an inhibitory conformational state that impedes the recruitment of downstream signaling molecules. Together, these data provide evidence on the feasibility of targeting TNFR1 conformationally active region and open new avenues for receptor-specific inhibition of TNFR1 signaling.


Assuntos
Receptores Tipo I de Fatores de Necrose Tumoral , Transdução de Sinais , Camundongos , Humanos , Animais , Ligantes , Células HEK293 , Fator de Necrose Tumoral alfa/metabolismo , Peptídeos/farmacologia
4.
N Engl J Med ; 387(12): 1089-1098, 2022 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-36027570

RESUMO

BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of hospitalization for heart failure and cardiovascular death among patients with chronic heart failure and a left ventricular ejection fraction of 40% or less. Whether SGLT2 inhibitors are effective in patients with a higher left ventricular ejection fraction remains less certain. METHODS: We randomly assigned 6263 patients with heart failure and a left ventricular ejection fraction of more than 40% to receive dapagliflozin (at a dose of 10 mg once daily) or matching placebo, in addition to usual therapy. The primary outcome was a composite of worsening heart failure (which was defined as either an unplanned hospitalization for heart failure or an urgent visit for heart failure) or cardiovascular death, as assessed in a time-to-event analysis. RESULTS: Over a median of 2.3 years, the primary outcome occurred in 512 of 3131 patients (16.4%) in the dapagliflozin group and in 610 of 3132 patients (19.5%) in the placebo group (hazard ratio, 0.82; 95% confidence interval [CI], 0.73 to 0.92; P<0.001). Worsening heart failure occurred in 368 patients (11.8%) in the dapagliflozin group and in 455 patients (14.5%) in the placebo group (hazard ratio, 0.79; 95% CI, 0.69 to 0.91); cardiovascular death occurred in 231 patients (7.4%) and 261 patients (8.3%), respectively (hazard ratio, 0.88; 95% CI, 0.74 to 1.05). Total events and symptom burden were lower in the dapagliflozin group than in the placebo group. Results were similar among patients with a left ventricular ejection fraction of 60% or more and those with a left ventricular ejection fraction of less than 60%, and results were similar in prespecified subgroups, including patients with or without diabetes. The incidence of adverse events was similar in the two groups. CONCLUSIONS: Dapagliflozin reduced the combined risk of worsening heart failure or cardiovascular death among patients with heart failure and a mildly reduced or preserved ejection fraction. (Funded by AstraZeneca; DELIVER ClinicalTrials.gov number, NCT03619213.).


Assuntos
Insuficiência Cardíaca , Inibidores do Transportador 2 de Sódio-Glicose , Volume Sistólico , Função Ventricular Esquerda , Compostos Benzidrílicos/efeitos adversos , Compostos Benzidrílicos/uso terapêutico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glucosídeos/efeitos adversos , Glucosídeos/uso terapêutico , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Humanos , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Volume Sistólico/efeitos dos fármacos , Função Ventricular Esquerda/efeitos dos fármacos
5.
Eur J Immunol ; : e2350716, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38837757

RESUMO

Immune mediators affect multiple biological functions of intestinal epithelial cells (IECs) and, like Paneth and Paneth-like cells, play an important role in intestinal epithelial homeostasis. IFN-γ a prototypical proinflammatory cytokine disrupts intestinal epithelial homeostasis. However, the mechanism underlying the process remains unknown. In this study, using in vivo and in vitro models we demonstrate that IFN-γ is spontaneously secreted in the small intestine. Furthermore, we observed that this cytokine stimulates mitochondrial activity, ROS production, and Paneth and Paneth-like cell secretion. Paneth and Paneth-like secretion downstream of IFN-γ, as identified here, is mTORC1 and necroptosis-dependent. Thus, our findings revealed that the pleiotropic function of IFN-γ also includes the regulation of Paneth cell function in the homeostatic gut.

6.
Nucleic Acids Res ; 51(D1): D337-D344, 2023 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-36399486

RESUMO

The 5' and 3' untranslated regions of eukaryotic mRNAs (UTRs) play crucial roles in the post-transcriptional regulation of gene expression through the modulation of nucleo-cytoplasmic mRNA transport, translation efficiency, subcellular localization, and message stability. Since 1996, we have developed and maintained UTRdb, a specialized database of UTR sequences. Here we present UTRdb 2.0, a major update of UTRdb featuring an extensive collection of eukaryotic 5' and 3' UTR sequences, including over 26 million entries from over 6 million genes and 573 species, enriched with a curated set of functional annotations. Annotations include CAGE tags and polyA signals to label the completeness of 5' and 3'UTRs, respectively. In addition, uORFs and IRES are annotated in 5'UTRs as well as experimentally validated miRNA targets in 3'UTRs. Further annotations include evolutionarily conserved blocks, Rfam motifs, ADAR-mediated RNA editing events, and m6A modifications. A web interface allowing a flexible selection and retrieval of specific subsets of UTRs, selected according to a combination of criteria, has been implemented which also provides comprehensive download facilities. UTRdb 2.0 is accessible at http://utrdb.cloud.ba.infn.it/utrdb/.


Assuntos
Bases de Dados de Ácidos Nucleicos , Eucariotos , RNA Mensageiro , Regiões não Traduzidas , Regiões 3' não Traduzidas/genética , Regiões 5' não Traduzidas , Eucariotos/genética , Células Eucarióticas/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
7.
Curr Issues Mol Biol ; 46(6): 6199-6222, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38921041

RESUMO

Human papillomavirus 16 (HPV 16) infection is associated with several types of cancer, such as head and neck, cervical, anal, and penile cancer. Its oncogenic potential is due to the ability of the E6 and E7 oncoproteins to promote alterations associated with cell transformation. HPV 16 E6 and E7 oncoproteins increase metabolic reprogramming, one of the hallmarks of cancer, by increasing the stability of hypoxia-induced factor 1 α (HIF-1α) and consequently increasing the expression levels of their target genes. In this report, by bioinformatic analysis, we show the possible effect of HPV 16 oncoproteins E6 and E7 on metabolic reprogramming in cancer through the E6-E7-PHD2-VHL-CUL2-ELOC-HIF-1α axis. We proposed that E6 and E7 interact with VHL, CUL2, and ELOC in forming the E3 ubiquitin ligase complex that ubiquitinates HIF-1α for degradation via the proteasome. Based on the information found in the databases, it is proposed that E6 interacts with VHL by blocking its interaction with HIF-1α. On the other hand, E7 interacts with CUL2 and ELOC, preventing their binding to VHL and RBX1, respectively. Consequently, HIF-1α is stabilized and binds with HIF-1ß to form the active HIF1 complex that binds to hypoxia response elements (HREs), allowing the expression of genes related to energy metabolism. In addition, we suggest an effect of E6 and E7 at the level of PHD2, VHL, CUL2, and ELOC gene expression. Here, we propose some miRNAs targeting PHD2, VHL, CUL2, and ELOC mRNAs. The effect of E6 and E7 may be the non-hydroxylation and non-ubiquitination of HIF-1α, which may regulate metabolic processes involved in metabolic reprogramming in cancer upon stabilization, non-degradation, and translocation to the nucleus.

8.
Electrophoresis ; 45(1-2): 35-54, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37946578

RESUMO

This review covers the know-how of the Grupo de Química Analítica e Quimiometria regarding the analysis of fatty acids by capillary electrophoresis acquired over its 20 years of existence. Therefore, the fundamentals, advantages, and applications of this technique for analyzing different fatty acids in samples such as food, oils, cosmetics, and biological matrices are presented and discussed. Capillary electrophoresis is, thus, shown as an interesting and valuable separation technique for the target analysis of these analytes as an alternative to the gas chromatography coupled to flame ionization detection, as it offers advantages over the latter such as low analysis times, low sample and reagent consumption, the use of a nondedicated column, and simpler sample preparation. In addition, the methods shown in this literature review can be useful for quality control, adulteration, and health-related research by regulatory agencies.


Assuntos
Eletroforese Capilar , Ácidos Graxos , Ácidos Graxos/análise , Eletroforese Capilar/métodos , Cromatografia Gasosa/métodos , Óleos , Contaminação de Medicamentos
9.
Psychol Sci ; 35(3): 250-262, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38289294

RESUMO

Fundamental frequency ( fo) is the most perceptually salient vocal acoustic parameter, yet little is known about how its perceptual influence varies across societies. We examined how fo affects key social perceptions and how socioecological variables modulate these effects in 2,647 adult listeners sampled from 44 locations across 22 nations. Low male fo increased men's perceptions of formidability and prestige, especially in societies with higher homicide rates and greater relational mobility in which male intrasexual competition may be more intense and rapid identification of high-status competitors may be exigent. High female fo increased women's perceptions of flirtatiousness where relational mobility was lower and threats to mating relationships may be greater. These results indicate that the influence of fo on social perceptions depends on socioecological variables, including those related to competition for status and mates.


Assuntos
Voz , Adulto , Humanos , Masculino , Feminino , Homicídio , Percepção Social , Parceiros Sexuais
10.
Mov Disord ; 39(6): 1048-1053, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38477413

RESUMO

BACKGROUND: Gait disorders in patients with Parkinson's disease (PD) can become disabling with disease progression without effective treatment. OBJECTIVES: To investigate the efficacy of intermittent θ burst trans-spinal magnetic stimulation (TsMS) in PD patients with gait and balance disorders. METHODS: This was a randomized, parallel, double-blind, controlled trial. Active or sham TsMS was applied at third thoracic vertebra with 100% of the trans-spinal motor threshold, during 5 consecutive days. Participants were evaluated at baseline, immediately after last session, 1 and 4 weeks after last session. Primary outcome was Total Timed Up and Go (TUG) values comparing active versus sham phases 1 week after intervention. The secondary outcome measurements consisted of motor, gait and balance scales, and questionnaires for quality of life and cognition. RESULTS: Thirty-three patients were included, average age 68.5 (6.4) years in active group and 70.3 (6.3) years in sham group. In active group, Total TUG mean baseline was 107.18 (95% CI, 52.1-116.1), and 1 week after stimulation was 93.0 (95% CI, 50.7-135.3); sham group, Total TUG mean baseline was 101.2 (95% CI, 47.1-155.3) and 1 week after stimulation 75.2 (95% CI 34.0-116.4), P = 0.54. Similarly, intervention had no significant effects on secondary outcome measurements. During stimulation period, five patients presented with mild side effects (three in active group and two in sham group). DISCUSSION: TsMS did not significantly improve gait or balance analysis in patients with PD and gait disorders. The protocol was safe and well tolerated. © 2024 International Parkinson and Movement Disorder Society.


Assuntos
Transtornos Neurológicos da Marcha , Doença de Parkinson , Humanos , Doença de Parkinson/complicações , Doença de Parkinson/terapia , Doença de Parkinson/fisiopatologia , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Transtornos Neurológicos da Marcha/etiologia , Transtornos Neurológicos da Marcha/terapia , Transtornos Neurológicos da Marcha/fisiopatologia , Método Duplo-Cego , Equilíbrio Postural/fisiologia , Resultado do Tratamento , Qualidade de Vida , Estimulação da Medula Espinal/métodos , Estimulação Magnética Transcraniana/métodos , Marcha/fisiologia , Magnetoterapia/métodos
11.
Cerebellum ; 23(2): 363-373, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36806980

RESUMO

Ataxia-telangiectasia (A-T) is a disease caused by mutations in the ATM gene (11q22.3-23.1) that induce neurodegeneration Sasihuseyinoglu AS et al.  Pediatr Allergy Immunol Pulmonol 31(1):9-14, 2018, Teive HAG et al. Parkinsonism Relat Disord 46:3-8, 2018. Clinically, A-T is characterized by ataxia, mucocutaneous telangiectasia, immunodeficiency, and malignancy. Movement disorders have been the most described and well-studied symptoms of A-T. Other studies have reported visuospatial processing disorders, executive function disorders and emotional regulation disorders, which are clinical manifestations that characterize cerebellar cognitive affective syndrome (CCAS) Choy KR et al. Dev Dyn 247(1):33-46, 2018. To describe the neurocognitive and emotional state of pediatric patients with ataxia-telangiectasia and to discuss whether they have cerebellar cognitive affective syndrome. This observational, cross-sectional, and descriptive study included 9 patients with A-T from May 2019 to May 2021. A complete medical history was retrieved, and tests were applied to assess executive functions, visual-motor integration and abilities, language, psychological disorders, and ataxia. Six girls and 3 boys agreed to participate. The age range was 6 to 14 years. The participants included five schoolchildren and four teenagers. Eight patients presented impaired executive functioning. All patients showed some type of error in copying and tracing (distortion) in the performance of visual perceptual abilities. Emotional disorders such as anxiety and depression were observed in six patients. Eight patients presented with dyslalia and impairments in word articulation, all patients presented with ataxia, and seven patients used a wheelchair. All patients presented symptoms consistent with CCAS and had variable cognitive performance.


Assuntos
Ataxia Telangiectasia , Ataxia Cerebelar , Doenças Cerebelares , Masculino , Feminino , Adolescente , Humanos , Criança , Ataxia Telangiectasia/complicações , Estudos Transversais , Ataxia Cerebelar/genética , Cognição/fisiologia
12.
Gastrointest Endosc ; 100(1): 1-16.e20, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38432492

RESUMO

BACKGROUND AND AIMS: Substantial differences exist in pancreatic cancer outcomes across ethnoracial stratifications. We sought to assess racial, ethnic, sex, and age reporting and inclusion of participants in pancreatic cancer screening studies. METHODS: A systematic search of Cochrane Library, Ovid Embase, Google Scholar, Ovid MEDLINE, PubMed, Scopus, and Web of Science Core Collection from inception to 2022 was conducted. Original studies on pancreatic cancer screening were identified and assessed for reporting and inclusion on race, ethnicity, sex, and age. The pooled proportions of study participants for these characteristics were calculated and compared with population-based benchmarks. RESULTS: Among 27 eligible pancreatic cancer screening studies, 26 reported data on either sex, race, or ethnicity, with a total of 5273 participants. Information on participant sex was reported by 26, race by 12, and ethnicity by 8 studies. Participants in these studies were almost all white (pooled proportion, 93.1%; 95% confidence interval [CI], 89.7-96.4) and non-Latino (pooled proportion, 97.4%; 95% CI, 94.0-100), and these groups were over-represented when compared with the general population. Female participants were well represented, with a pooled proportion of 63.2% (95% CI, 59.9-66.6). When reported, mean or median participant age was <60 years. Meta-regression revealed higher proportions of female participants in studies from the United States (P = .002). No association between increasing participation of racial or ethnic under-represented populations and study quality, ascending year of publication, or source of study funding was noted. CONCLUSIONS: Substantial disparities in race, ethnicity, sex, and age reporting and inclusion in pancreatic cancer studies were noted, even among high-quality and publicly funded studies.


Assuntos
Detecção Precoce de Câncer , Etnicidade , Neoplasias Pancreáticas , Grupos Raciais , Humanos , Neoplasias Pancreáticas/etnologia , Detecção Precoce de Câncer/estatística & dados numéricos , Fatores Etários , Fatores Sexuais , Etnicidade/estatística & dados numéricos , Grupos Raciais/estatística & dados numéricos , Disparidades em Assistência à Saúde/etnologia , Feminino , Seleção de Pacientes , Masculino
13.
J Theor Biol ; 585: 111781, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38432504

RESUMO

This paper aims to present a comprehensive framework for coupling tumor-bone remodeling processes in a 2-dimensional geometry. This is achieved by introducing a bio-inspired damage that represents the growing tumor, which subsequently affects the main populations involved in the remodeling process, namely, osteoclasts, osteoblasts, and bone tissue. The model is constructed using a set of differential equations based on the Komarova's and Ayati's models, modified to incorporate the bio-inspired damage that may result in tumor mass formation. Three distinct models were developed. The first two models are based on the Komarova's governing equations, with one demonstrating an osteolytic behavior and the second one an osteoblastic model. The third model is a variation of Ayati's model, where the bio-inspired damage is induced through the paracrine and autocrine parameters, exhibiting an osteolytic behavior. The obtained results are consistent with existing literature, leading us to believe that our in-silico experiments will serve as a cornerstone for paving the way towards targeted interventions and personalized treatment strategies, ultimately improving the quality of life for those affected by these conditions.


Assuntos
Neoplasias , Qualidade de Vida , Humanos , Osteoclastos , Osteoblastos , Osso e Ossos , Remodelação Óssea
14.
Pediatr Allergy Immunol ; 35(2): e14073, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38351896

RESUMO

PURPOSE: We aimed to describe the clinical, immunological, and genetic features of patients with DOCK8 deficiency (DOCK8-Def) in a tertiary care center for children. METHODS: Retrospective chart review of patients' clinical, immunological, and genetic characteristics with DOCK8-Def. Genetic analysis was performed with targeted- or whole-exome sequencing; we also assessed DOCK8 protein expression and a lymphoproliferation assay and analyzed survival by the Kaplan-Meier method. RESULTS: We described 11 patients from 8 unrelated kindreds. The median age at symptoms' onset was 10 months (range 1-54 months). The median follow-up time was 53.4 months (4.8-118.8). All patients presented eczema and recurrent sinopulmonary and cutaneous infections. Besides those symptoms, the most frequent manifestations were bronchiectases (8/11), food allergies (6/11), and severe infections (6/11). Infrequent characteristics were detection of CMV in bronchial lavage, C. parvum-driven sclerosing cholangitis, Takayasu vasculitis, neurological syndromes, pulmonary tuberculosis, and lymphomatoid granulomatosis. CONCLUSION: DOCK8-Def has a broad spectrum of manifestations, including allergy, autoimmunity, inflammation, infection, and cancer. The hallmark of this inborn error of immunity is IEI-associated eczema with eosinophilia and increased IgE. Here, we report six new mutations causing human DOCK8 deficiency and symptoms previously unrecognized to occur in DOCK8-Def. Therefore, an early diagnosis of DOCK8-Def is essential to facilitate an adequate treatment such as HSCT.


Assuntos
Eczema , Hipersensibilidade , Síndrome de Job , Criança , Humanos , Lactente , Pré-Escolar , Estudos Retrospectivos , Síndrome de Job/genética , Eczema/epidemiologia , Eczema/genética , Mutação , Fatores de Troca do Nucleotídeo Guanina/genética
15.
Cell Biol Int ; 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38894528

RESUMO

Ecto-5'-nucleotidase (CD73) hydrolyses 5'AMP to adenosine and inorganic phosphate. Breast cancer cells (MDA-MB-231) express high CD73 levels, and this enzyme has been found to play a tumour-promoting role in breast cancer. However, no studies have sought to investigate whether CD73 has differential affinity or substrate preferences between noncancerous and cancerous breast cells. In the present study, we aimed to biochemically characterise ecto-5'-nucleotidase in breast cancer cell lines and assess whether its catalytic function and tumour progression are correlated in breast cancer cells. The results showed that compared to nontumoral breast MCF-10A cells, triple-negative breast cancer MDA-MB-231 cells had a higher ecto-5'-nucleotidase expression level and enzymatic activity. Although ecto-5'-nucleotidase activity in the MDA-MB-231 cell line showed no selectivity among monophosphorylated substrates, 5'AMP was preferred by the MCF-10A cell line. Compared to the MCF-10A cell line, the MDA-MB-231 cell line has better hydrolytic ability, lower substrate affinity, and high inhibitory potential after treatment with a specific CD73 inhibitor α,ß­methylene ADP (APCP). Therefore, we demonstrated that a specific inhibitor of the ecto-5-nucleotidase significantly reduced the migratory and invasive capacity of MDA-MB-231 cells, suggesting that ecto-5-nucleotidase activity might play an important role in metastatic progression.

16.
Fish Shellfish Immunol ; 151: 109687, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38866348

RESUMO

Meningitis caused by Gram-negative bacteria is a serious public health problem, causing morbidity and mortality in both children and adults. Here, we propose a novel experimental model using Nile tilapia (Oreochromis niloticus) to study neuroinflammation. The fish were infected with Aeromonas hydrophila, and the course of infection was monitored in the peripheral blood. Septicemia was obvious in the blood, while in the brain tissue, infection of the meninges was present. The histopathological examination showed suppurative meningitis, and the cellular immune response in the brain tissue during infection was mediated by microglia. These cells were morphologically characterized and phenotyped by MHC class II markers and CD68. The increased production of TNF-α, IL-1ß and iNOS supported the infiltration of these cells during the neuroinflammatory process. In the proteomic analysis of A. hydrophila isolated from brain tissue, we found chemotactic and transport proteins, proteolytic enzymes and enzymes associated with the dismutation of nitric oxide (NO), as well as motor proteins and those responsible for cell division. After characterizing the most abundant proteins during the course of infection, we investigated the druggability index of these proteins and identified promising peptide sequences as molecular targets that are similar among bacteria. Thus, these findings deepened the understanding of the pathophysiology of meningitis caused by A. hydrophila. Moreover, through the proteomics analysis, important mechanisms and pathways used by the pathogen to subvert the host response were revealed, providing insights for the development of novel antibiotics and vaccines.

17.
Rev Med Virol ; 33(3): e2432, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36807958

RESUMO

According to the World Health Organisation, as of October 2022, there have been 55,560,329 reported cases of SARS-COV-2 in patients under 19 years old. It is estimated that about 0.06% of these patients may develop MIS-C, representing more than 2 million children worldwide. This systematic review and meta-analysis examined the pooled prevalence of cardiovascular manifestation and cardiac complications in children hospitalised with MIS-C. The PROSPERO register number is CRD42022327212. We included case-report studies, case-control studies, cohort studies, and cross-sectional studies, as well as clinical trials or studies describing cardiac manifestations of MIS-C and its sequelae in a paediatric population. Initially, 285 studies were selected, but there were 154 duplicates, and 81 were excluded because they did not fit the eligibility criteria. Thus, 50 studies were selected for review, and 30 were included in the meta-analysis. A total sample size of 1445 children was included. The combined prevalence of myocarditis or pericarditis was 34.3% (95% CI: 25.0%-44.2%). The combined prevalence for echocardiogram anomalies was 40.8% (95% CI: 30.5%-51.5%), that of Kawasaki disease presentation was 14.8% (95% CI: 7.5%-23.7%), and that of coronary dilation was 15.2% (95% CI: 11.0%-19.8%). The rate of electrocardiogram anomalies was 5.3% (95% CI: 0.8%-12.3%), and the mortality rate was 0.5% (CI 95%: 0%-1.2%). Furthermore, 186 children still had complications at discharge, with a combined prevalence of such long-lasting manifestations of 9.3% (95% CI: 5.6%-13.7%). Studies that assess whether these children will have an increased cardiovascular risk with a greater chance of acute myocardial infarction, arrhythmias, or thrombosis will be essential for healthcare planning.


Assuntos
COVID-19 , Miocardite , Adulto , Criança , Humanos , Adulto Jovem , COVID-19/complicações , Miocardite/complicações , SARS-CoV-2
18.
BMC Infect Dis ; 24(1): 584, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38867165

RESUMO

BACKGROUND: Natural infection and vaccination against SARS-CoV-2 is associated with the development of immunity against the structural proteins of the virus. Specifically, the two most immunogenic are the S (spike) and N (nucleocapsid) proteins. Seroprevalence studies performed in university students provide information to estimate the number of infected patients (symptomatic or asymptomatic) and generate knowledge about the viral spread, vaccine efficacy, and epidemiological control. Which, the aim of this study was to evaluate IgG antibodies against the S and N proteins of SARS-CoV-2 at university students from Southern Mexico. METHODS: A total of 1418 serum samples were collected from eighteen work centers of the Autonomous University of Guerrero. Antibodies were detected by Indirect ELISA using as antigen peptides derived from the S and N proteins. RESULTS: We reported a total seroprevalence of 39.9% anti-S/N (positive to both antigens), 14.1% anti-S and 0.5% anti-N. The highest seroprevalence was reported in the work centers from Costa Grande, Acapulco and Centro. Seroprevalence was associated with age, COVID-19, contact with infected patients, and vaccination. CONCLUSION: University students could play an essential role in disseminating SARS-CoV-2. We reported a seroprevalence of 54.5% against the S and N proteins, which could be due to the high population rate and cultural resistance to safety measures against COVID-19 in the different regions of the state.


Assuntos
Anticorpos Antivirais , COVID-19 , Proteínas do Nucleocapsídeo de Coronavírus , Imunoglobulina G , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Estudantes , Humanos , México/epidemiologia , Masculino , Feminino , Estudos Transversais , Glicoproteína da Espícula de Coronavírus/imunologia , Imunoglobulina G/sangue , COVID-19/epidemiologia , COVID-19/imunologia , Adulto Jovem , Anticorpos Antivirais/sangue , SARS-CoV-2/imunologia , Estudos Soroepidemiológicos , Adulto , Universidades , Proteínas do Nucleocapsídeo de Coronavírus/imunologia , Adolescente , Fosfoproteínas/imunologia
19.
J Periodontal Res ; 59(2): 237-248, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38135675

RESUMO

BACKGROUND AND OBJECTIVE: As elsewhere in the world, the prevalence of periodontitis in stages I-II is high in the Latin American population, this scenario emphasizes the need for identification of urgent needs for allocating adequate resources to provide diagnosis, prevention, and treatment of these diseases. The aim of this Delphi study was to predict the trends in periodontology/periodontics in the Latin American region by the year 2030. METHODS: A steering committee and an advisory group of experts in periodontology/periodontics were selected from 16 countries. An open questionnaire of 60 questions was validated and used following the Delphi methodology. RESULTS: Two hundred and twenty-five experts from Latin America answered the two rounds of the questionnaire. Moderate to strong consensus was reached on 45 questions (75%). The prediction was that the prevalence of gingivitis and periodontitis in stages I and II will be maintained, the importance of the link with systemic diseases will increase, and the impact of prevention and periodontal treatment will also increase, mainly in the private sector. There was a strong consensus that plastic and regenerative surgical procedures will increase, as well as the demand for training in the specialty of periodontology. CONCLUSIONS: The present study has provided relevant and useful information on predictions in periodontology/periodontics in Latin America, with important level of consensus among experts. It has been predicted that periodontitis will still be a highly prevalent disease, and its links with other medical conditions should demand more attention by health authorities to develop adequate prevention and management policies and strategies.


Assuntos
Doenças Periodontais , Periodontite , Humanos , Periodontia , Doenças Periodontais/epidemiologia , Doenças Periodontais/terapia , América Latina/epidemiologia , Consenso , Técnica Delphi , Periodontite/epidemiologia , Periodontite/terapia
20.
Mol Biol Rep ; 51(1): 582, 2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38678168

RESUMO

BACKGROUND: Hybridization associated with polyploidy studies is rare in the tropics. The genus Zygopetalum (Orchidaceae) was investigated here as a case study of Neotropical plants. In the rocky highlands of the Ibitipoca State Park (ISP), southeast Brazil, individuals with intermediate colors and forms between the species Z. maculatum and Z. triste were commonly identified. METHODS AND RESULTS: Chromosomal analysis and DNA quantity showed a uniform population. Regardless of the aspects related to the color and shape of floral structures, all individuals showed 2n = 96 chromosomes and an average of 14.05 pg of DNA. Irregularities in meiosis associated with chromosome number and C value suggest the occurrence of polyploidy. The genetic distance estimated using ISSR molecular markers revealed the existence of genetic variability not related to morphological clusters. Morphometric measurements of the flower pieces revealed that Z. maculatum shows higher variation than Z. triste although lacking a defined circumscription. CONCLUSION: The observed variation can be explained by the polyploid and phenotypic plasticity resulting from the interaction of the genotypes with the heterogeneous environments observed in this habitat.


Assuntos
Variação Genética , Orchidaceae , Fenótipo , Poliploidia , Orchidaceae/genética , Variação Genética/genética , Brasil , Cromossomos de Plantas/genética , Genótipo , Flores/genética , Flores/anatomia & histologia , Repetições de Microssatélites/genética , Hibridização Genética/genética
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