Proteomic analysis of peripheral blood mononuclear cells in first episode psychosis - Protein and peptide-centered approaches to elucidate potential diagnostic biomarkers.

Diagnosing patients suffering from psychotic disorders is far from being achieved with molecular support, despite all the efforts to study these disorders from different perspectives. Characterizing the proteome of easily obtainable blood specimens, such as the peripheral blood mononuclear cells (PBMCs), has particular interest in biomarker discovery and generating pathophysiological knowledge. This approach has been explored in psychiatry, and while generating valuable information, it has not translated into meaningful biomarker discovery. In this project, we report the proof-of-concept of a methodology that aims to explore further information obtained with classical proteomics approaches that is easily overlooked. PBMC samples from first-episode psychosis and control subjects were subjected to a SWATH-MS approach, and the classical protein relative quantification was performed, where 389 proteins were found to be important to distinguish the two groups. Individual analysis of the quantified peptides was also performed, highlighting peptides of unchanged proteins that were significantly altered. With the combination of protein- and peptide-centered proteomics approaches, it is possible to highlight that information about proteoforms, namely regulation at the peptide level possibly due to post-translational modifications, is routinely overlooked and that its diagnostic potential should be further explored. SIGNIFICANCE: Our exploratory findings highlight the potential of MS-based proteomics strategies, combining protein- and peptide-centered approaches, to aid clinical decision-making in first-episode psychosis, helping to establish early biomarkers for schizophrenia and other psychotic disorders. Particularly, the less popular peptide-centered approach allows the identification/measurement of overlooked modulated peptides that may have potential biomarker characteristics. The application in parallel of protein- and peptide-centered strategies is transversal to research of other diseases, potentially allowing a more comprehensive characterization of the metabolic/pathophysiological alterations related to a specific disease.

A Comparative Analysis of the Venom System between Two Morphotypes of the Sea Anemone Actinia equina.

The current study investigates the venom-delivery system of green and red morphotypes of the sea anemone Actinia equina to disclose its potential as a source of bioactive compounds. We compared the two morphotypes using electron and optical microscopy, proteomics, and toxicity assessment on zebrafish embryos. Specialized venom-injecting cells (nematocysts) are equally distributed and found in the tentacles of both varieties. Proteomics revealed proteins of interest in both red and green Actinia, yielding the three most abundant Gene Ontology (GO) terms related to the biological processes "proteolysis", "hemolysis in another organism" and "lipid catabolic process". Neurotoxins and cytolytic toxins similar to known cnidarian toxins like PsTX-60A and AvTX-60A, for instance, were identified in both types. Extracts from green and red anemones were toxic to zebrafish embryos, with green anemone venom appearing to be more potent. The findings highlight the presence of proteinaceous toxins in A. equina and the potential for different varieties to possess distinct bioactive compounds. Notably, pore-forming toxins are suggested for molecular probes and immunotoxins, making them valuable assets for potential biotechnological and biomedical purposes.

Dental caries in the permanent dentition and health-related quality of life among children and adolescents with sickle cell disease.

The aim was to associate living, health and oral health conditions with the quality of life (QL) of children and adolescents (CA) with sickle cell disease (SCD). Of the 120 eligible users of a public hematological service, 106 CA with SCD from 6 to 18 years of age, and their caregivers, answered semi-structured questions about socio-demographic, health and oral health conditions. For QL, we used the validated instrument PedsQLSCD™. The oral clinical examination occurred according to the guidelines of WHO and SB Brazil 2010. The majority of CA were non-white people (88%), mean age of 10.4 (±2.9) years, family income of up to two monthly minimum wages, for 03 to 05 members, with diagnosis of sickle cell anemia by neonatal screening, hospitalizations were due allergic crises, polypharmacy and dental caries (51%) were present. "About the Impact of My Pain" was the best-fit model for the QLSCD (adjusted R²=56%; AIC=28.67; p=0.04). Dental caries in permanent dentition worsened the QLSCD (OR=0.53; IC95%=0.35-0.78; p<0.05) and was associated with the type of school, car ownership, number of family members, of complications and of the medications. To overcome this scenario, programmatic actions are required, and implementation of public policies specifically directed towards these groups.

The secretome of macrophages has a differential impact on spinal cord injury recovery according to the polarization protocol.

Introduction: The inflammatory response after spinal cord injury (SCI) is an important contributor to secondary damage. Infiltrating macrophages can acquire a spectrum of activation states, however, the microenvironment at the SCI site favors macrophage polarization into a pro-inflammatory phenotype, which is one of the reasons why macrophage transplantation has failed. Methods: In this study, we investigated the therapeutic potential of the macrophage secretome for SCI recovery. We investigated the effect of the secretome in vitro using peripheral and CNS-derived neurons and human neural stem cells. Moreover, we perform a pre-clinical trial using a SCI compression mice model and analyzed the recovery of motor, sensory and autonomic functions. Instead of transplanting the cells, we injected the paracrine factors and extracellular vesicles that they secrete, avoiding the loss of the phenotype of the transplanted cells due to local environmental cues. Results: We demonstrated that different macrophage phenotypes have a distinct effect on neuronal growth and survival, namely, the alternative activation with IL-10 and TGF-ß1 (M(IL-10+TGF-ß1)) promotes significant axonal regeneration. We also observed that systemic injection of soluble factors and extracellular vesicles derived from M(IL-10+TGF-ß1) macrophages promotes significant functional recovery after compressive SCI and leads to higher survival of spinal cord neurons. Additionally, the M(IL-10+TGF-ß1) secretome supported the recovery of bladder function and decreased microglial activation, astrogliosis and fibrotic scar in the spinal cord. Proteomic analysis of the M(IL-10+TGF-ß1)-derived secretome identified clusters of proteins involved in axon extension, dendritic spine maintenance, cell polarity establishment, and regulation of astrocytic activation. Discussion: Overall, our results demonstrated that macrophages-derived soluble factors and extracellular vesicles might be a promising therapy for SCI with possible clinical applications.

Dental caries in the permanent dentition and health-related quality of life among children and adolescents with sickle cell disease / Cáries dentárias na dentição permanente e qualidade de vida relacionada à saúde entre crianças e adolescentes com doença falciforme

Abstract The aim was to associate living, health and oral health conditions with the quality of life (QL) of children and adolescents (CA) with sickle cell disease (SCD). Of the 120 eligible users of a public hematological service, 106 CA with SCD from 6 to 18 years of age, and their caregivers, answered semi-structured questions about socio-demographic, health and oral health conditions. For QL, we used the validated instrument PedsQLSCD™. The oral clinical examination occurred according to the guidelines of WHO and SB Brazil 2010. The majority of CA were non-white people (88%), mean age of 10.4 (±2.9) years, family income of up to two monthly minimum wages, for 03 to 05 members, with diagnosis of sickle cell anemia by neonatal screening, hospitalizations were due allergic crises, polypharmacy and dental caries (51%) were present. "About the Impact of My Pain" was the best-fit model for the QLSCD (adjusted R²=56%; AIC=28.67; p=0.04). Dental caries in permanent dentition worsened the QLSCD (OR=0.53; IC95%=0.35-0.78; p<0.05) and was associated with the type of school, car ownership, number of family members, of complications and of the medications. To overcome this scenario, programmatic actions are required, and implementation of public policies specifically directed towards these groups.

Resumo Objetivou-se associar condições de vida, de saúde e de saúde bucal à qualidade de vida (QLV) de crianças e adolescentes (CA) com Doença Falciforme (DF). Dos 120 usuários elegíveis de um serviço público hematológico, 106 CA entre 6 e 18 anos de idade, e seus cuidadores, responderam questões semiestruturadas sobre condições sociodemográficas, de saúde e saúde bucal. Para a QLV, o instrumento validado PedsQL DF® foi aplicado. Na sequência, realizou-se o exame clínico bucal nas CA segundo diretrizes da OMS e do SB Brasil 2010. A maioria das CA era negra (88%), idade média de 10,4 (±2.9) anos, renda familiar de até dois salários mínimos, para 03 a 05 membros, diagnosticadas na triagem neonatal com anemia falciforme, internadas por crises álgicas, em uso de polifarmácia e com cárie dental (51%). O domínio "Sobre o Impacto da Minha Dor" foi preditivo da QLVDF (R² ajustado =56%; AIC=28.67; p=0,04). Nele, a cárie dental na dentição permanente piorou a QLVDF das CA (OR=0.53; IC95%=0.35-0.78; p<0,05), associando-se ao tipo de escola, posse de carro e do número de membros na família, de complicações da DF e de medicamentos. Os achados ratificam a dor como marca da DF e mostram a importância da saúde bucal na QLDF das CA. A implementação de políticas públicas específicas pode superar esse cenário.

An Exploration of Novel Bioactives from the Venomous Marine Annelid Glycera alba.

The immense biodiversity of marine invertebrates makes them high-value targets for the prospecting of novel bioactives. The present study investigated proteinaceous toxins secreted by the skin and proboscis of Glycera alba (Annelida: Polychaeta), whose congenerics G. tridactyla and G. dibranchiata are known to be venomous. Proteomics and bioinformatics enabled the detection of bioactive proteins that hold potential for biotechnological applications, including toxins like glycerotoxins (GLTx), which can interfere with neuromuscular calcium channels and therefore have value for the development of painkillers, for instance. We also identified proteins involved in the biosynthesis of toxins. Other proteins of interest include venom and toxin-related bioactives like cysteine-rich venom proteins, many of which are known to interfere with the nervous system. Ex vivo toxicity assays with mussel gills exposed to fractionated protein extracts from the skin and proboscis revealed that fractions potentially containing higher-molecular-mass venom proteins can exert negative effects on invertebrate prey. Histopathology, DNA damage and caspase-3 activity suggest significant cytotoxic effects that can be coadjuvated by permeabilizing enzymes such as venom metalloproteinases M12B. Altogether, these encouraging findings show that venomous annelids are important sources of novel bioactives, albeit illustrating the challenges of surveying organisms whose genomes and metabolisms are poorly understood.

Chronic treatment with D2-antagonist haloperidol leads to inhibitory/excitatory imbalance in striatal D1-neurons.

Striatal dysfunction has been implicated in the pathophysiology of schizophrenia, a disorder characterized by positive symptoms such as hallucinations and delusions. Haloperidol is a typical antipsychotic medication used in the treatment of schizophrenia that is known to antagonize dopamine D2 receptors, which are abundantly expressed in the striatum. However, haloperidol's delayed therapeutic effect also suggests a mechanism of action that may go beyond the acute blocking of D2 receptors. Here, we performed proteomic analysis of striatum brain tissue and found more than 400 proteins significantly altered after 30 days of chronic haloperidol treatment in mice, namely proteins involved in glutamatergic and GABAergic synaptic transmission. Cell-type specific electrophysiological recordings further revealed that haloperidol not only reduces the excitability of striatal medium spiny neurons expressing dopamine D2 receptors (D2-MSNs) but also affects D1-MSNs by increasing the ratio of inhibitory/excitatory synaptic transmission (I/E ratio) specifically onto D1-MSNs but not D2-MSNs. Therefore, we propose the slow remodeling of D1-MSNs as a mechanism mediating the delayed therapeutic effect of haloperidol over striatum circuits. Understanding how haloperidol exactly contributes to treating schizophrenia symptoms may help to improve therapeutic outcomes and elucidate the molecular underpinnings of this disorder.

Proteomic and Metabolic Analysis of Pinus halepensis Mill. Embryonal Masses Induced under Heat Stress.

Understanding the physiological and molecular adjustments occurring during tree stress response is of great importance for forest management and breeding programs. Somatic embryogenesis has been used as a model system to analyze various processes occurring during embryo development, including stress response mechanisms. In addition, "priming" plants with heat stress during somatic embryogenesis seems to favor the acquisition of plant resilience to extreme temperature conditions. In this sense, Pinus halepensis somatic embryogenesis was induced under different heat stress treatments (40 °C for 4 h, 50 °C for 30 min, and 60 °C for 5 min) and its effects on the proteome and the relative concentration of soluble sugars, sugar alcohols and amino acids of the embryonal masses obtained were assessed. Heat severely affected the production of proteins, and 27 proteins related to heat stress response were identified; the majority of the proteins with increased amounts in embryonal masses induced at higher temperatures consisted of enzymes involved in the regulation of metabolism (glycolysis, the tricarboxylic acid cycle, amino acid biosynthesis and flavonoids formation), DNA binding, cell division, transcription regulation and the life-cycle of proteins. Finally, significant differences in the concentrations of sucrose and amino acids, such as glutamine, glycine and cysteine, were found.

Self-recycling and partially conservative replication of mycobacterial methylmannose polysaccharides.

The steep increase in nontuberculous mycobacteria (NTM) infections makes understanding their unique physiology an urgent health priority. NTM synthesize two polysaccharides proposed to modulate fatty acid metabolism: the ubiquitous 6-O-methylglucose lipopolysaccharide, and the 3-O-methylmannose polysaccharide (MMP) so far detected in rapidly growing mycobacteria. The recent identification of a unique MMP methyltransferase implicated the adjacent genes in MMP biosynthesis. We report a wide distribution of this gene cluster in NTM, including slowly growing mycobacteria such as Mycobacterium avium, which we reveal to produce MMP. Using a combination of MMP purification and chemoenzymatic syntheses of intermediates, we identified the biosynthetic mechanism of MMP, relying on two enzymes that we characterized biochemically and structurally: a previously undescribed α-endomannosidase that hydrolyses MMP into defined-sized mannoligosaccharides that prime the elongation of new daughter MMP chains by a rare α-(1→4)-mannosyltransferase. Therefore, MMP biogenesis occurs through a partially conservative replication mechanism, whose disruption affected mycobacterial growth rate at low temperature.

Enrichment of hepatic glycogen and plasma glucose from H218 O informs gluconeogenic and indirect pathway fluxes in naturally feeding mice.

Deuterated water (2 H2 O) is a widely used tracer of carbohydrate biosynthesis in both preclinical and clinical settings, but the significant kinetic isotope effects (KIE) of 2 H can distort metabolic information and mediate toxicity. 18 O-water (H2 18 O) has no significant KIE and is incorporated into specific carbohydrate oxygens via well-defined mechanisms, but to date it has not been evaluated in any animal model. Mice were given H2 18 O during overnight feeding and 18 O-enrichments of liver glycogen, triglyceride glycerol (TG), and blood glucose were quantified by 13 C NMR and mass spectrometry (MS). Enrichment of oxygens 5 and 6 relative to body water informed indirect pathway contributions from the Krebs cycle and triose phosphate sources. Compared with mice fed normal chow (NC), mice whose NC was supplemented with a fructose/glucose mix (i.e., a high sugar [HS] diet) had significantly higher indirect pathway contributions from triose phosphate sources, consistent with fructose glycogenesis. Blood glucose and liver TG 18 O-enrichments were quantified by MS. Blood glucose 18 O-enrichment was significantly higher for HS versus NC mice and was consistent with gluconeogenic fructose metabolism. TG 18 O-enrichment was extensive for both NC and HS mice, indicating a high turnover of liver triglyceride, independent of diet. Thus H2 18 O informs hepatic carbohydrate biosynthesis in similar detail to 2 H2 O but without KIE-associated risks.

Peptidomics Unveils Distinct Acetylation Patterns of Histone and Annexin A1 in Differentiated Thyroid Cancer.

Thyroid cancer is a common malignancy of the endocrine system. Nodules are routinely evaluated for malignancy risk by fine needle aspiration biopsy (FNAB), and in cases such as follicular lesions, differential diagnosis between benign and malignant nodules is highly uncertain. Therefore, the discovery of new biomarkers for this disease could be helpful in improving diagnostic accuracy. Thyroid nodule biopsies were subjected to a precipitation step with both the insoluble and supernatant fractions subjected to proteome and peptidome profiling. Proteomic analysis identified annexin A1 as a potential biomarker of thyroid cancer malignancy, with its levels increased in malignant samples. Also upregulated were the acetylated peptides of annexin A1, revealed by the peptidome analysis of the supernatant fraction. In addition, supernatant peptidomic analysis revealed a number of acetylated histone peptides that were significantly elevated in the malignant group, suggesting higher gene transcription activity in malignant tissue. Two of these peptides were found to be robust malignancy predictors, with an area under the receiver operating a characteristic curve (ROC AUC) above 0.95. Thus, this combination of proteomics and peptidomics analyses improved the detection of malignant lesions and also provided new evidence linking thyroid cancer development to heightened transcription activity. This study demonstrates the importance of peptidomic profiling in complementing traditional proteomics approaches.

COVID-19 Salivary Protein Profile: Unravelling Molecular Aspects of SARS-CoV-2 Infection.

COVID-19 is the most impacting global pandemic of all time, with over 600 million infected and 6.5 million deaths worldwide, in addition to an unprecedented economic impact. Despite the many advances in scientific knowledge about the disease, much remains to be clarified about the molecular alterations induced by SARS-CoV-2 infection. In this work, we present a hybrid proteomics and in silico interactomics strategy to establish a COVID-19 salivary protein profile. Data are available via ProteomeXchange with identifier PXD036571. The differential proteome was narrowed down by the Partial Least-Squares Discriminant Analysis and enrichment analysis was performed with FunRich. In parallel, OralInt was used to determine interspecies Protein-Protein Interactions between humans and SARS-CoV-2. Five dysregulated biological processes were identified in the COVID-19 proteome profile: Apoptosis, Energy Pathways, Immune Response, Protein Metabolism and Transport. We identified 10 proteins (KLK 11, IMPA2, ANXA7, PLP2, IGLV2-11, IGHV3-43D, IGKV2-24, TMEM165, VSIG10 and PHB2) that had never been associated with SARS-CoV-2 infection, representing new evidence of the impact of COVID-19. Interactomics analysis showed viral influence on the host immune response, mainly through interaction with the degranulation of neutrophils. The virus alters the host's energy metabolism and interferes with apoptosis mechanisms.

Optimization of a Protocol for Protein Extraction from Calcified Aortic Valves for Proteomics Applications: Development of a Standard Operating Procedure.

The comprehension of the pathophysiological mechanisms, the identification of druggable targets, and putative biomarkers for aortic valve stenosis can be pursued through holistic approaches such as proteomics. However, tissue homogenization and protein extraction are made difficult by tissue calcification. The reproducibility of proteome studies is key in clinical translation of the findings. Thus, we aimed to optimize a protocol for aortic valve homogenization and protein extraction and to develop a standard operating procedure (SOP), which researchers can use to maximize protein yield while reducing inter-laboratory variability. We have compared the protein yield between conventional tissue grinding in nitrogen followed by homogenization with a Potter apparatus with a more advanced bead-beating system. Once we confirmed the superiority of the latter, we further optimized it by testing the effect of beads size, the number of homogenization cycles, tube capacity, lysis buffer/tissue mass ratio, and two different lysis buffers. Optimal protein extraction was achieved with 2.8 mm zirconium dioxide beads, in two homogenization cycles, in the presence of 20 µL RIPA buffer/mg tissue, using 2 mL O-ring cryotubes. As a proof of concept of the usefulness of this SOP for proteomics, the AV proteome of men and women with aortic stenosis was characterized, resulting in the quantification of proteins across six orders of magnitude and uncovering some putative proteins dysregulated by sex.

O processo de monitoramento, controle e avaliação do Programa Mais Médicos no estado da Bahia / The monitoring, control and evaluation process of the Mais Médicos Program in Bahia / El proceso de seguimiento, control y evaluación del Programa Más Médicos EN EL ESTADO DE Bahía

Este artigo tem o objetivo de avaliar o processo de aprimoramento e acompanhamento das variáveis envolvidas na consolidação do Progama Mais Médicos para o Brasil (PMMB) na Bahia, bem como a gestão da informação associada aos avanços tecnológicos. A pesquisa é de natureza qualitativa e do tipo estudo de caso. Os dados pertinentes ao monitoramento e planejamento estratégico do PMMB, no estado da Bahia, foram coletados mensalmente, a partir das bases de dados do Ministério da Saúde, Ministério da Educação e municípios, para serem agrupados em uma planilha eletrônica do Microsoft Excel, por meio do recurso Power Business Intelligence (Power BI), programa que está em constante modificação, permitindo visualizar a qualquer momento as variáveis desejadas. Assim, a distribuição de médicos atuantes no PMMB, no território baiano, corrobora os estudos que apontam o crescimento do provimento de médicos, sobretudo nas regiões mais isoladas, pobres e vulneráveis. A construção dos painéis, realizada pela captação e sistematização de diferentes fontes de dados relativos à gestão do PMMB na Bahia, permitiu avaliar: a distribuição dos médicos atuantes no PMMB na Bahia, as regiões de maior concentração de médicos, a porcentagem dos municípios contemplados pelo programa, a distribuição da rede de apoio no estado da Bahia, a distribuição dos cursos de medicina no estado e as regiões que realizam teleconsultorias. Por meio desta pesquisa, foi possível concluir que o número de médicos destinados à atenção de saúde nas populações mais carentes e isoladas vem aumentando gradativamente, embora ainda seja insufuciente. Além disso, pode-se concluir que a gestão da informação associada aos avanços tecnológicos podem servir como instrumento de monitoramento e avaliação na área da saúde.

Este estudio tiene como objetivo evaluar el proceso de mejora y seguimiento de las variables involucradas en la consolidación del Programa Más Médicos (PMM) en Bahía (Brasil), así como la gestión de la información asociada a los avances tecnológicos. La investigación es de carácter cualitativo, de tipo estudio de caso. Los datos relevantes para el seguimiento y la planificación estratégica del PMM en el estado de Bahía fueron recopilados mensualmente de las bases de datos del Ministerio de Salud, del Ministerio de Educación y municipios, para ser agrupados en una hoja de cálculo de Microsoft Excel, a través del recurso Power BI que se modifica constantemente, lo que permite ver las variables en cualquier momento. Así, la distribución de los médicos que actúan en el PMM en el amplio territorio de Bahía corrobora estudios que apuntan al crecimiento de la oferta de médicos, especialmente en las regiones más aisladas, pobres y vulnerables. La construcción de los paneles, realizada a partir de la captura y sistematización de diferentes fuentes de datos, relacionados con la gestión del PMM de Bahía, permitió evaluar: la distribución de los médicos que actúan en el PMM de Bahía, las regiones con mayor concentración de médicos, el porcentaje de municipios cubiertos por el programa, la distribución de la red de apoyo en el estado de Bahía, la distribución de los cursos de medicina en el estado, y las regiones que realizan teleconsultas. Esta investigación permite concluir que el número de médicos dedicados a la atención de la salud en las poblaciones más necesitadas y aisladas ha ido aumentando paulatinamente, aunque aún es insuficiente. Además, se concluye que el manejo de la información asociada a los avances tecnológicos puede servir como una herramienta de seguimiento y evaluación en salud.

This qualitative case study evaluates the improvement and monitoring processes concerning the variables involved in the consolidation of the More Doctors Program (PMM) in Bahia, Brazil, as well as the management of information associated with technological advances. Data relevant for monitoring and strategic planning the PMM in the state were collected monthly from the Ministry of Health, Ministry of Education and municipalities databases, and then grouped in a Microsoft Excel spreadsheet using power BI, an everchanging software that allow us to view the desired variables at any time. The results on the distribution of PMM doctors in the broad territory of Bahia corroborate studies that point to an increased supply of physicians, especially in more isolated, poorer and vulnerable regions. The panels developed by capturing and systematizing different data sources regarding PMM management in Bahia allowed to evaluate: the distribution of PMM doctors in the state, the regions with the highest concentration, the percentage of municipalities covered by the program, the distribution of the support network within the state, the distribution of medical undergraduate programs in the state; the regions that offer teleconsultations. In conclusion, the number of physicians offering health care to the poorest and most isolated populations has been increasing gradually, but remains insufficient. Moreover, the management of information associated with technological advances can serve as a monitoring and evaluation instrument in health care.

A importância da inserção da odontologia na residência multiprofissional do hemorio / The importance of the insertion of dentistry in the multiprofessional residence of hemoriola / Importancia de la inserción de la odontología en la residencia multiprofesional de hemorio

O Instituto Estadual de Hematologia Arthur de Siqueira Cavalcanti ­ HEMORIO, é o Hemocentro coordenador do Estado do RJ responsável pelo abastecimento de sangue de cerca de 180 unidades de saúde pública conveniadas ao SUS, e pelo tratamento hematológico em nível primário à terciário de baixa a alta complexidade. A Instituição oferece uma formação diferenciada que qualifica profissionais para um olhar especializado sobre a produção de novos conhecimentos quanto ao processo saúde-doença, com atenção integral à saúde, nas respectivas áreas de atuação.

Fascite necrosante cervical após extração dentária em paciente com leucemia eosinofílica crônica: relato de caso / Cervical necrotizing fasciitis after tooth extraction in a patient with chronic eosinophilic leukemia: case report / Fascitis necrotizante cervical posterior a exodoncia en paciente con leucemia eosinofílica crónica: reporte de caso

A fascite necrosante cervical (FNC)é uma infecção rara e grave, que acomete o tecido celular subcutâneo e a fáscia muscular, resultando em necrose. A maioria dos casos tem origem odontogênica ou faríngea, evoluindo com extensa necrose e formação gasosa no tecido subcutâneo e fáscia subjacente, com elevado índice de mortalidade. A FNC ocorre com mais frequência em pacientes com doenças crônicas ou supressão imunológica, podendo manifestar-se de forma mais grave nesses casos. Nopresente trabalho é relatado o caso de um paciente diagnosticado com Leucemia Eosinofílica Crônica (LEC), que após uma extração dentária, evoluiu com um quadro de extensa lesão em região submandibular/cervical direita com necrose, liquefação, exsudato necrolizado, e exposição de tecido muscularcompatível ­aspecto clínico que, estando associado aos dados da tomografia computadorizada, possibilitou o diagnóstico de FNC. O paciente foi hospitalizado e acompanhado por uma equipe multiprofissional. Este artigo pretende relatar que a FNC é uma infecção de progressão rápida, potencialmente fatal, que requer diagnóstico e intervenção imediatos, podendo ocorrer como complicação de uma extração dentária, principalmente em pacientes portadores de doenças crônicas ousupressão imunológica. Portanto, o cirurgião dentista deve incluir esta condição no diagnóstico diferencial de infecções pós-extração, sendo a abordagem multidisciplinar fundamental para o estabelecimento do diagnóstico e tratamento adequado.

Cervical necrotizing fasciitis (CNF)is a rare and severe infection that affects subcutaneous tissue and muscle fascia, causing necrosis. Most cases arise from odontogenic or pharyngeal infections, evolving into extensive necrosis and gas formation in the subcutaneous tissue and underlying fascia, with a high mortality rate. CNF is more common among patients with chronic diseases or immune suppression, possibly being more severe in these cases. This work reports the case of a patient diagnosedwith chronic eosinophilic leukemia (CEL) who developed a condition of extensive lesion in the right submandibular/cervical region after a tooth extraction, presenting necrosis, liquefaction, necrolized exudate, and compatible muscle tissue exposure­clinical aspect that, associated with data on computed tomography, enabled CNF diagnosis. The patient was hospitalized and followed-up by a multidisciplinary team. This article aims to report that CNF is a rapidly progressing, potentially fatal infection, requiring immediate diagnosis and intervention. The infection may arise from a complication following tooth extraction, especially in patients with chronic diseases or immunological suppression. Considering that, the oral surgeon must include this condition within post-extraction infections differential diagnosis, where a multidisciplinary approach is fundamental for diagnosing and establishing an appropriate treatment.

La fascitis necrosante cervical (FNC) es una infección rara y grave que afecta el tejido subcutáneo y la fascia muscular, causando necrosis. La mayoría de los casos surgen de infecciones odontogénicas o faríngeas, evolucionando hacia una extensa necrosis y formación de gas en el tejido subcutáneo y la fascia subyacente, con unaalta tasa de mortalidad. La FNC es más frecuente en pacientes con enfermedades crónicas oinmunosupresión, pudiendo ser más grave en estos casos. Este trabajo reporta el caso de un paciente diagnosticado de leucemia eosinofiliacrónica (LEC) que desarrolló una condición de lesión extensa en la región submandibular/cervical derecha después de una extracción dental,presentando necrosis, licuefacción, exudado necrolizado y exposición de tejido muscular compatible -aspecto clínico que, asociado a los datos de la tomografía computarizada, permitió la FNC diagnóstico. El paciente fue hospitalizado y seguido por un equipo multidisciplinario. Este artículo tiene como objetivo informar que la FNC es una infección potencialmente mortal que progresa rápidamente y que requiere un diagnóstico e intervención inmediatos. La infección puede surgir de una complicación posterior a la extracción dental, especialmente en pacientes con enfermedades crónicas o inmunológicas supresión. Por ello, el cirujano oral debe incluir esta condición dentro del diagnóstico diferencial de las infecciones post exodoncia, donde el abordaje multidisciplinario es fundamental para diagnosticar y establecer un tratamiento adecuado.

Thermopriming-associated proteome and sugar content responses in Pinus radiata embryogenic tissue.

Improving the capacity of plants to face adverse environmental conditions requires a deep understanding of the molecular mechanisms governing stress response and adaptation. Proteomics, combined with metabolic analyses, offers a wide resource of information to be used in plant breeding programs. Previous studies have shown that somatic embryogenesis in Pinus spp. is a suitable tool not only to investigate stress response processes but also to modulate the behaviour of somatic plants. Based on this, the objective of this study was to analyse the protein and soluble sugar profiles of Pinus radiata embryonal masses after the application of high temperatures to unravel the mechanisms involved in thermopriming and memory acquisition at early stages of the somatic embryogenesis process. Results confirmed that heat provokes deep readjustments in the life cycle of proteins, together with a significant reduction in the carbon-flux of central-metabolism pathways. Heat-priming also promotes the accumulation of proteins involved in oxidative stress defence, in the synthesis of specific amino acids such as isoleucine, influences cell division, the organization of the cytoskeleton and cell-walls, and modifies the levels of free soluble sugars like glucose or fructose. All this seems to be regulated by proteins linked with epigenetic, transcriptional and post-transcriptional mechanisms.

Effects of microplastics alone and with adsorbed benzo(a)pyrene on the gills proteome of Scrobicularia plana.

Microplastics (MPs) are globally present in the marine environment, but the biological effects on marine organisms at the molecular and cellular levels remain scarce. Due to their lipophilic nature, MPs can adsorb other contaminants present in the marine environment, which may increase their detrimental effects once ingested by organisms. This study investigates the effects of low-density polyethylene (PE) MPs with and without adsorbed benzo[a]pyrene (BaP) in the gills proteome of the peppery furrow shell clam, Scrobicularia plana. Clams were exposed to PE MPs (11-13 µm; 1 mg L-1) for 14 days. BaP was analyzed in whole clams' soft tissues, and a proteomic approach was applied in the gills using SWATH/DIA analysis. Proteomic responses suggest that virgin MPs cause disturbance by altering cytoskeleton and cell structure, energy metabolism, conformational changes, oxidative stress, fatty acids, DNA binding and, neurotransmission highlighting the potential risk of this type of MPs for the clam health. Conversely, when clam gills were exposed to MPs adsorbed with BaP a higher differentiation of protein expression was observed that besides changes in cytoskeleton and cell structure, oxidative stress, energy metabolism and DNA binding also induce changes in glucose metabolism, RNA binding and apoptosis. These results indicate that the presence of both stressors (MPs and BaP) have a higher toxicological risk to the health of S. plana.

Posttranslational modifications of proteins are key features in the identification of CSF biomarkers of multiple sclerosis.

BACKGROUND: Multiple sclerosis is an inflammatory and degenerative disease of the central nervous system (CNS) characterized by demyelination and concomitant axonal loss. The lack of a single specific test, and the similarity to other inflammatory diseases of the central nervous system, makes it difficult to have a clear diagnosis of multiple sclerosis. Therefore, laboratory tests that allows a clear and definite diagnosis, as well as to predict the different clinical courses of the disease are of utmost importance. Herein, we compared the cerebrospinal fluid (CSF) proteome of patients with multiple sclerosis (in the relapse-remitting phase of the disease) and other diseases of the CNS (inflammatory and non-inflammatory) aiming at identifying reliable biomarkers of multiple sclerosis. METHODS: CSF samples from the discovery group were resolved by 2D-gel electrophoresis followed by identification of the protein spots by mass spectrometry. The results were analyzed using univariate (Student's t test) and multivariate (Hierarchical Cluster Analysis, Principal Component Analysis, Linear Discriminant Analysis) statistical and numerical techniques, to identify a set of protein spots that were differentially expressed in CSF samples from patients with multiple sclerosis when compared with other two groups. Validation of the results was performed in samples from a different set of patients using quantitative (e.g., ELISA) and semi-quantitative (e.g., Western Blot) experimental approaches. RESULTS: Analysis of the 2D-gels showed 13 protein spots that were differentially expressed in the three groups of patients: Alpha-1-antichymotrypsin, Prostaglandin-H2-isomerase, Retinol binding protein 4, Transthyretin (TTR), Apolipoprotein E, Gelsolin, Angiotensinogen, Agrin, Serum albumin, Myosin-15, Apolipoprotein B-100 and EF-hand calcium-binding domain-containing protein. ELISA experiments allowed validating part of the results obtained in the proteomics analysis and showed that some of the alterations in the CSF proteome are also mirrored in serum samples from multiple sclerosis patients. CSF of multiple sclerosis patients was characterized by TTR oligomerization, thus highlighting the importance of analyzing posttranslational modifications of the proteome in the identification of novel biomarkers of the disease. CONCLUSIONS: The model built based on the results obtained upon analysis of the 2D-gels and in the validation phase attained an accuracy of about 80% in distinguishing multiple sclerosis patients and the other two groups.