Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 37.563
Filtrar
1.
Med Gas Res ; 13(1): 33-38, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35946221

RESUMO

In a previous study, in silico screening of the binding of almost all proteins in the Protein Data Bank to each of the five noble gases xenon, krypton, argon, neon, and helium was reported. This massive and rich data set requires analysis to identify the gas-protein interactions that have the best binding strengths, those where the binding of the noble gas occurs at a site that can modulate the function of the protein, and where this modulation might generate clinically relevant effects. Here, we report a preliminary analysis of this data set using a rational, heuristic score based on binding strength and location. We report a partial prioritized list of xenon protein targets and describe how these data can be analyzed, using arginase and carbonic anhydrase as examples. Our aim is to make the scientific community aware of this massive, rich data set and how it can be analyzed to accelerate future discoveries of xenon-induced biological activity and, ultimately, the development of new "atomic" drugs.


Assuntos
Proteoma , Xenônio , Criptônio/química , Criptônio/farmacologia , Neônio/farmacologia , Gases Nobres/química , Gases Nobres/metabolismo , Xenônio/química , Xenônio/farmacologia
2.
Braz. j. biol ; 83: e249424, 2023. graf
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1345538

RESUMO

Abstract Hypoxia is a prominent feature of head and neck cancer. However, the oxygen element characteristics of proteins and how they adapt to hypoxia microenvironments of head and neck cancer are still unknown. Human genome sequences and proteins expressed data of head and neck cancer were retrieved from pathology atlas of Human Protein Atlas project. Then compared the oxygen and carbon element contents between proteomes of head and neck cancer and normal oral mucosa-squamous epithelial cells, genome locations, pathways, and functional dissection associated with head and neck cancer were also studied. A total of 902 differentially expressed proteins were observed where the average oxygen content is higher than that of the lowly expressed proteins in head and neck cancer proteins. Further, the average oxygen content of the up regulated proteins was 2.54% higher than other. None of their coding genes were distributed on the Y chromosome. The up regulated proteins were enriched in endocytosis, apoptosis and regulation of actin cytoskeleton. The increased oxygen contents of the highly expressed and the up regulated proteins might be caused by frequent activity of cytoskeleton and adapted to the rapid growth and fast division of the head and neck cancer cells. The oxygen usage bias and key proteins may help us to understand the mechanisms behind head and neck cancer in targeted therapy, which lays a foundation for the application of stoichioproteomics in targeted therapy and provides promise for potential treatments for head and neck cancer.


Resumo A hipóxia é uma característica proeminente do câncer de cabeça e pescoço. No entanto, as características do elemento oxigênio das proteínas e como elas se adaptam aos microambientes de hipóxia do câncer de cabeça e pescoço ainda são desconhecidas. Sequências do genoma humano e dados expressos de proteínas de câncer de cabeça e pescoço foram recuperados do atlas de patologia do projeto Human Protein Atlas. Em seguida, comparou o conteúdo do elemento de oxigênio e carbono entre proteomas de câncer de cabeça e pescoço, e células epiteliais escamosas da mucosa oral normal, localizações do genoma, vias e dissecção funcional associada ao câncer de cabeça e pescoço também foram estudadas. Um total de 902 proteínas expressas diferencialmente foi observado onde o conteúdo médio de oxigênio é maior do que as proteínas expressas de forma humilde em proteínas de câncer de cabeça e pescoço. Além disso, o conteúdo médio de oxigênio das proteínas reguladas positivamente foi 2,54% maior do que das outras. Nenhum de seus genes codificadores foi distribuído no cromossomo Y. As proteínas reguladas positivamente foram enriquecidas em endocitose, apoptose e regulação do citoesqueleto de actina. O conteúdo aumentado de oxigênio das proteínas altamente expressas e reguladas pode ser causado pela atividade frequente do citoesqueleto e adaptado ao rápido crescimento e divisão das células cancerosas de cabeça e pescoço. O viés do uso de oxigênio e as proteínas-chave podem nos ajudar a entender os mecanismos por trás do câncer de cabeça e pescoço na terapia direcionada, o que estabelece uma base para a aplicação da estequioproteômica na terapia direcionada e oferece uma promessa para potenciais tratamentos para o câncer de cabeça e pescoço.


Assuntos
Humanos , Neoplasias de Cabeça e Pescoço/genética , Oxigênio , Carbono , Proteoma/genética , Microambiente Tumoral
3.
NPJ Syst Biol Appl ; 8(1): 31, 2022 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-36068227

RESUMO

Autism spectrum disorders (ASD) are a set of complex neurodevelopmental diseases characterized with repetitive behavioral patterns and communication disabilities. Using a systems biology method called MAPSD (Markov Affinity-based Proteogenomic Signal Diffusion) for joint modeling of proteome dynamics and a wide array of omics datasets, we identified a list of candidate ASD risk genes. Leveraging the collected biological signals as well as a large-scale protein-protein interaction network adjusted based on single cell resolution proteome properties in four brain regions, we observed an agreement between the known and the newly identified candidate genes that are spatially enriched in neuronal cells within cerebral cortex at the protein level. Moreover, we created a detailed subcellular localization enrichment map of the known and the identified genes across 32 micro-domains and showed that neuronal cells and neuropils share the largest fraction of signal enrichment in cerebral cortex. Notably, we showed that the identified genes are among the transcriptional biomarkers of inhibitory and excitatory neurons in human frontal cortex. Intersecting the identified genes with a single cell RNA-seq data on ASD brains further evidenced that 20 candidate genes, including GRIK1, EMX2, STXBP6, and KCNJ3 are disrupted in distinct cell-types. Moreover, we showed that ASD risk genes are predominantly distributed in certain human interactome modules, and that the identified genes may act as the regulator for some of the known ASD loci. In summary, our study demonstrated how tissue-wide cell-specific proteogenomic modeling can reveal candidate genes for brain disorders that can be supported by convergent lines of evidence.


Assuntos
Transtorno do Espectro Autista , Proteogenômica , Transtorno do Espectro Autista/genética , Transtorno do Espectro Autista/metabolismo , Encéfalo/metabolismo , Humanos , Mapas de Interação de Proteínas/genética , Proteoma/metabolismo
4.
Arch Microbiol ; 204(10): 604, 2022 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-36069945

RESUMO

The protozoa Leishmania donovani causes visceral leishmaniasis (kala-azar), the third most common vector-borne disease. The visceral organs, particularly the spleen, liver, and bone marrow, are affected by the disease. The lack of effective treatment regimens makes curing and eradicating the disease difficult. The availability of complete L. donovani genome/proteome data allows for the development of specific and efficient vaccine candidates using the reverse vaccinology method, while utilizing the unique sequential and structural features of potential antigenic proteins to induce protective T cell and B cell responses. Such shortlisted candidates may then be tested quickly for their efficacy in the laboratory and later in clinical settings. These antigens will also be useful for designing antigen-based next-generation sero-diagnostic assays. L. donovani's cell surface-associated proteins and secretory proteins are among the first interacting entities to be exposed to the host immune machinery. As a result, potential antigenic epitope peptides derived from these proteins could serve as competent vaccine components. We used a stepwise filtering-based in silico approach to identify the entire surface-associated and secretory proteome of L. donovani, which may provide rationally selected most exposed antigenic proteins. Our study identified 12 glycosylphosphatidylinositol-anchored proteins, 45 transmembrane helix-containing proteins, and 73 secretory proteins as potent antigens unique to L. donovani. In addition, we used immunoinformatics to identify B and T cell epitopes in them. Out of the shortlisted surface-associated and secretory proteome, 66 protein targets were found to have the most potential overlapping B cell and T cell epitopes (linear and conformational; MHC class I and MHC class II).


Assuntos
Leishmania donovani , Leishmaniose Visceral , Vacinas , Epitopos de Linfócito T , Humanos , Leishmania donovani/genética , Leishmaniose Visceral/diagnóstico , Leishmaniose Visceral/prevenção & controle , Proteoma
5.
Med Oncol ; 39(12): 190, 2022 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-36071279

RESUMO

Prostate cancer is the most common type of cancer among men, and there is still no definitively effective drug treatment. Thus, the search for novel drug agents that may be used for the effective treatment continues. Meclofenamic acid (MA), a non-steroidal anti-inflammatory drug, with anti-tumor effects in various types of cancers was used to investigate its effects on LNCaP cells, a prostate cancer cell line, at the proteome level. The cells were treated with 80 µM MA for 24 h and a comparative proteomic analysis was performed with their untreated control cells. Proteins were extracted from the cells and then were subjected to two-dimensional gel electrophoresis. Protein spots displaying changes in their regulation ratios for more than two-fold were excised from the gels and identified with MALDI-TOF/TOF mass spectrometry. Bioinformatics analysis of the differentially regulated proteins that we identified showed that they were all associated with and took part in related pathways. Glycolytic pathway, cytoskeletal formation, transport activity, protein metabolism, and most notably an mRNA processing pathway were affected by the MA treatment. In addition to presenting a detailed information for what is happening inside the cells upon MA treatment, the proteins affected by MA treatment hold the potential to be novel targets for prostate cancer treatment provided that further in vivo experiments are carried out.


Assuntos
Neoplasias da Próstata , Proteoma , Humanos , Masculino , Ácido Meclofenâmico , Poliadenilação , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/metabolismo , Proteoma/análise , Proteoma/metabolismo , Proteômica/métodos
6.
BMC Genomics ; 23(1): 635, 2022 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-36071374

RESUMO

BACKGROUND: Tandem mass tag spectrometry (TMT labeling-LC-MS/MS) was utilized to examine the global proteomes of Atlantic halibut eggs at the 1-cell-stage post fertilization. Comparisons were made between eggs judged to be of good quality (GQ) versus poor quality (BQ) as evidenced by their subsequent rates of survival for 12 days. Altered abundance of selected proteins in BQ eggs was confirmed by parallel reaction monitoring spectrometry (PRM-LC-MS/MS). Correspondence of protein levels to expression of related gene transcripts was examined via qPCR. Potential mitochondrial differences between GQ and BQ eggs were assessed by transmission electron microscopy (TEM) and measurements of mitochondrial DNA (mtDNA) levels. RESULTS: A total of 115 proteins were found to be differentially abundant between GQ and BQ eggs. Frequency distributions of these proteins indicated higher protein folding activity in GQ eggs compared to higher transcription and protein degradation activities in BQ eggs. BQ eggs were also significantly enriched with proteins related to mitochondrial structure and biogenesis. Quantitative differences in abundance of several proteins with parallel differences in their transcript levels were confirmed in egg samples obtained over three consecutive reproductive seasons. The observed disparities in global proteome profiles suggest impairment of protein and energy homeostasis related to unfolded protein response and mitochondrial stress in BQ eggs. TEM revealed BQ eggs to contain significantly higher numbers of mitochondria, but differences in corresponding genomic mtDNA (mt-nd5 and mt-atp6) levels were not significant. Mitochondria from BQ eggs were significantly smaller with a more irregular shape and a higher number of cristae than those from GQ eggs. CONCLUSION: The results of this study indicate that BQ Atlantic halibut eggs are impaired at both transcription and translation levels leading to endoplasmic reticulum and mitochondrial disorders. Observation of these irregularities over three consecutive reproductive seasons in BQ eggs from females of diverse background, age and reproductive experience indicates that they are a hallmark of poor egg quality. Additional research is needed to discover when in oogenesis and under what circumstances these defects may arise. The prevalence of this suite of markers in BQ eggs of diverse vertebrate species also begs investigation.


Assuntos
Linguado , Animais , Cromatografia Líquida , DNA Mitocondrial/genética , Feminino , Linguado/genética , Homeostase , Dobramento de Proteína , Proteoma , Espectrometria de Massas em Tandem
7.
PLoS One ; 17(9): e0273843, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36054185

RESUMO

INTRODUCTION: Liver sinusoidal endothelial cells (LSECs) are specialized fenestrated scavenger endothelial cells involved in the elimination of modified plasma proteins and tissue turnover waste macromolecules from blood. LSECs also participate in liver immune responses. A challenge when studying LSEC biology is the rapid loss of the in vivo phenotype in culture. In this study, we have examined biological processes and pathways affected during early-stage primary culture of rat LSECs and checked for cell responses to the pro-inflammatory cytokine interleukin (IL)-1ß and the anti-inflammatory drug dexamethasone. METHODS: LSECs from male Sprague Dawley rats were cultured on type I collagen in 5% oxygen atmosphere in DMEM with serum-free supplements for 2 and 24 h. Quantitative proteomics using tandem mass tag technology was used to examine proteins in cells and supernatants. Validation was done with qPCR, ELISA, multiplex immunoassay, and caspase 3/7 assay. Cell ultrastructure was examined by scanning electron microscopy, and scavenger function by quantitative endocytosis assays. RESULTS: LSECs cultured for 24 h showed a characteristic pro-inflammatory phenotype both in the presence and absence of IL-1ß, with upregulation of cellular responses to cytokines and interferon-γ, cell-cell adhesion, and glycolysis, increased expression of fatty acid binding proteins (FABP4, FABP5), and downregulation of several membrane receptors (STAB1, STAB2, LYVE1, CLEC4G) and proteins in pyruvate metabolism, citric acid cycle, fatty acid elongation, amino acid metabolism, and oxidation-reduction processes. Dexamethasone inhibited apoptosis and improved LSEC viability in culture, repressed inflammatory and immune regulatory pathways and secretion of IL-1ß and IL-6, and further upregulated FABP4 and FABP5 compared to time-matched controls. The LSEC porosity and endocytic activity were reduced at 24 h both with and without dexamethasone but the dexamethasone-treated cells showed a less stressed phenotype. CONCLUSION: Rat LSECs become activated towards a pro-inflammatory phenotype during early culture. Dexamethasone represses LSEC activation, inhibits apoptosis, and improves cell viability.


Assuntos
Células Endoteliais , Proteoma , Animais , Dexametasona/metabolismo , Dexametasona/farmacologia , Células Endoteliais/metabolismo , Fígado/metabolismo , Masculino , Proteoma/metabolismo , Ratos , Ratos Sprague-Dawley , Secretoma
8.
Gigascience ; 112022 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-36056732

RESUMO

BACKGROUND: Maternal proteins have important roles during early embryonic development. However, our understanding of maternal proteins is still very limited. The integrated analysis of mouse uniparental (parthenogenetic) and biparental (fertilized) embryos at the protein level creates a protein expression landscape that can be used to explore preimplantation mouse development. RESULTS: Using label-free quantitative mass spectrometry (MS) analysis, we report on the maternal proteome of mouse parthenogenetic embryos at pronucleus, 2-cell, 4-cell, 8-cell, morula, and blastocyst stages and highlight dynamic changes in protein expression. In addition, comparison of proteomic profiles of parthenogenotes and fertilized embryos highlights the different fates of maternal proteins. Enrichment analysis uncovered a set of maternal proteins that are strongly correlated with the subcortical maternal complex, and we report that in parthenogenotes, some of these maternal proteins escape the fate of protein degradation. Moreover, we identified a new maternal factor-Fbxw24, and highlight its importance in early embryonic development. We report that Fbxw24 interacts with Ddb1-Cul4b and may regulate maternal protein degradation in mouse. CONCLUSIONS: Our study provides an invaluable resource for mechanistic analysis of maternal proteins and highlights the role of the novel maternal factor Fbw24 in regulating maternal protein degradation during preimplantation embryo development.


Assuntos
Partenogênese , Proteômica , Animais , Blastocisto/metabolismo , Desenvolvimento Embrionário , Feminino , Camundongos , Gravidez , Proteoma/metabolismo
9.
Nihon Yakurigaku Zasshi ; 157(5): 384, 2022.
Artigo em Japonês | MEDLINE | ID: mdl-36047159

Assuntos
Proteoma
10.
Acta Neuropathol Commun ; 10(1): 134, 2022 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-36076304

RESUMO

BACKGROUND: The molecular drivers of early sporadic Parkinson's disease (PD) remain unclear, and the presence of widespread end stage pathology in late disease masks the distinction between primary or causal disease-specific events and late secondary consequences in stressed or dying cells. However, early and mid-stage Parkinson's brains (Braak stages 3 and 4) exhibit alpha-synuclein inclusions and neuronal loss along a regional gradient of severity, from unaffected-mild-moderate-severe. Here, we exploited this spatial pathological gradient to investigate the molecular drivers of sporadic PD. METHODS: We combined high precision tissue sampling with unbiased large-scale profiling of protein expression across 9 brain regions in Braak stage 3 and 4 PD brains, and controls, and verified these results using targeted proteomic and functional analyses. RESULTS: We demonstrate that the spatio-temporal pathology gradient in early-mid PD brains is mirrored by a biochemical gradient of a changing proteome. Importantly, we identify two key events that occur early in the disease, prior to the occurrence of alpha-synuclein inclusions and neuronal loss: (i) a metabolic switch in the utilisation of energy substrates and energy production in the brain, and (ii) perturbation of the mitochondrial redox state. These changes may contribute to the regional vulnerability of developing alpha-synuclein pathology. Later in the disease, mitochondrial function is affected more severely, whilst mitochondrial metabolism, fatty acid oxidation, and mitochondrial respiration are affected across all brain regions. CONCLUSIONS: Our study provides an in-depth regional profile of the proteome at different stages of PD, and highlights that mitochondrial dysfunction is detectable prior to neuronal loss, and alpha-synuclein fibril deposition, suggesting that mitochondrial dysfunction is one of the key drivers of early disease.


Assuntos
Doença de Parkinson , alfa-Sinucleína , Humanos , Mitocôndrias/metabolismo , Doença de Parkinson/patologia , Proteoma/metabolismo , Proteômica , alfa-Sinucleína/metabolismo
11.
Int J Mol Sci ; 23(17)2022 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-36076961

RESUMO

Plukenetia volubilis is a highly promising plant with high nutritional and economic values. In our previous studies, the expression levels of ricin encoded transcripts were the highest in the maturation stage of P. volubilis seeds. The present study investigated the transcriptome and proteome profiles of seeds at two developmental stages (Pv-1 and Pv-2) using RNA-Seq and iTRAQ technologies. A total of 53,224 unigenes and 6026 proteins were identified, with functional enrichment analyses, including GO, KEGG, and KOG annotations. At two development stages of P. volubilis seeds, 8815 unique differentially expressed genes (DEGs) and 4983 unique differentially abundant proteins (DAPs) were identified. Omics-based association analysis showed that ribosome-inactivating protein (RIP) transcripts had the highest expression and abundance levels in Pv-2, and those DEGs/DAPs of RIPs in the GO category were involved in hydrolase activity. Furthermore, 21 RIP genes and their corresponding amino acid sequences were obtained from libraries produced with transcriptome analysis. The analysis of physicochemical properties showed that 21 RIPs of P. volubilis contained ricin, the ricin_B_lectin domain, or RIP domains and could be divided into three subfamilies, with the largest number for type II RIPs. The expression patterns of 10 RIP genes indicated that they were mostly highly expressed in Pv-2 and 4 transcripts encoding ricin_B_like lectins had very low expression levels during the seed development of P. volubilis. This finding would represent valuable evidence for the safety of oil production from P. volubilis for human consumption. It is also notable that the expression level of the Unigene0030485 encoding type I RIP was the highest in roots, which would be related to the antiviral activity of RIPs. This study provides a comprehensive analysis of the physicochemical properties and expression patterns of RIPs in different organs of P. volubilis and lays a theoretical foundation for further research and utilization of RIPs in P. volubilis.


Assuntos
Proteínas Inativadoras de Ribossomos , Ricina , Humanos , Proteínas de Plantas/química , Proteoma/metabolismo , Proteínas Inativadoras de Ribossomos/genética , Ricina/química , Sementes/metabolismo , Transcriptoma
12.
Front Cell Infect Microbiol ; 12: 934321, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36118030

RESUMO

Assessment of serological Plasmodium falciparum-specific antibodies in highly endemic areas provides valuable information about malaria status and parasite exposure in the population. Although serological evidence of Plasmodium exposure is commonly determined by Plasmodium-specific immunoglobulin G (IgG) levels; IgM and IgA are likely markers of malaria status that remain relatively unexplored. Previous studies on IgM and IgA responses have been based on their affinity for single antigens with shortage of immune responses analysis against the whole Plasmodium proteome. Here, we provide evidence of how P. falciparum infection triggers the production of specific IgM and IgA in plasma and its relationship with parasite density and changes in hematological parameters. A total of 201 individuals attending a hospital in Breman Asikuma, Ghana, were recruited into this study. Total and P. falciparum-specific IgM, IgA, and IgG were assessed by ELISA and examined in relation to age (0-5, 14-49, and ≥50 age ranges); infection (submicroscopic vs. microscopic malaria); pregnancy and hematological parameters. Well-known IgG response was used as baseline control. P. falciparum-specific IgM and IgA levels increased in the population with the age, similarly to IgG. These data confirm that acquired humoral immunity develops by repeated infections through the years endorsing IgM and IgA as exposure markers in endemic malaria regions. High levels of specific IgA and IgM in children were associated with microscopic malaria and worse prognosis, because most of them showed severe anemia. This new finding shows that IgM and IgA may be used as diagnostic markers in this age group. We also found an extremely high prevalence of submicroscopic malaria (46.27% on average) accompanied by IgM and IgA levels indistinguishable from those of uninfected individuals. These data, together with the observed lack of sensitivity of rapid diagnostic tests (RDTs) compared to PCR, invoke the urgent need to implement diagnostic markers for submicroscopic malaria. Overall, this study opens the potential use of P. falciparum-specific IgM and IgA as new serological markers to predict malaria status in children and parasite exposure in endemic populations. The difficulties in finding markers of submicroscopic malaria are highlighted, emphasizing the need to explore this field in depth.


Assuntos
Malária Falciparum , Malária , Plasmodium , Anticorpos Antiprotozoários , Biomarcadores , Criança , Humanos , Imunoglobulina A , Imunoglobulina G , Imunoglobulina M , Malária Falciparum/diagnóstico , Plasmodium falciparum , Proteoma
13.
PLoS One ; 17(9): e0273925, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36048851

RESUMO

Skeletal muscle unloading due to joint immobilization induces muscle atrophy, which has primarily been attributed to reductions in protein synthesis in humans. However, no study has evaluated the skeletal muscle proteome response to limb immobilization using SWATH proteomic methods. This study characterized the shifts in individual muscle protein abundance and corresponding gene sets after 3 and 14 d of unilateral lower limb immobilization in otherwise healthy young men. Eighteen male participants (25.4 ±5.5 y, 81.2 ±11.6 kg) underwent 14 d of unilateral knee-brace immobilization with dietary provision and following four-weeks of training to standardise acute training history. Participant phenotype was characterized before and after 14 days of immobilization, and muscle biopsies were obtained from the vastus lateralis at baseline (pre-immobilization) and at 3 and 14 d of immobilization for analysis by SWATH-MS and subsequent gene-set enrichment analysis (GSEA). Immobilization reduced vastus group cross sectional area (-9.6 ±4.6%, P <0.0001), immobilized leg lean mass (-3.3 ±3.9%, P = 0.002), unilateral 3-repetition maximum leg press (-15.6 ±9.2%, P <0.0001), and maximal oxygen uptake (-2.9 ±5.2%, P = 0.044). SWATH analyses consistently identified 2281 proteins. Compared to baseline, two and 99 proteins were differentially expressed (FDR <0.05) after 3 and 14 d of immobilization, respectively. After 14 d of immobilization, 322 biological processes were different to baseline (FDR <0.05, P <0.001). Most (77%) biological processes were positively enriched and characterized by cellular stress, targeted proteolysis, and protein-DNA complex modifications. In contrast, mitochondrial organization and energy metabolism were negatively enriched processes. This study is the first to use data independent proteomics and GSEA to show that unilateral lower limb immobilization evokes mitochondrial dysfunction, cellular stress, and proteolysis. Through GSEA and network mapping, we identify 27 hub proteins as potential protein/gene candidates for further exploration.


Assuntos
Força Muscular , Músculo Esquelético , Proteoma , Humanos , Imobilização/fisiologia , Extremidade Inferior/fisiologia , Masculino , Mitocôndrias/metabolismo , Força Muscular/fisiologia , Músculo Esquelético/metabolismo , Atrofia Muscular/patologia , Proteólise , Proteoma/metabolismo , Proteômica , Músculo Quadríceps/fisiologia , Estresse Fisiológico
14.
Int J Mol Sci ; 23(17)2022 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-36077129

RESUMO

Osteoarthritis (OA) is a joint degenerative disease that most affects old age. The study of proteomics in synovial fluid (SF) has the task of providing additional elements to diagnose and predict the progress of OA. This review aims to identify the most significant biomarkers in the study of OA and to stimulate their routine use. Some of the major components of the ECM, such as proteoglycan aggrecan and decorin, were found considerably reduced in OA. Some biomarkers have proved useful for staging the temporality of OA: Periostin was found to be increased in early OA, while CRTA1 and MMPs were found to be increased in late OA. In its natural attempt at tissue regeneration, Collagen III was found to be increased in early OA while decreased in late OA. Some molecules studied in other areas, such as ZHX3 (oncological marker), LYVE1, and VEGF (lymph and angiogenesis markers), also have been found to be altered in OA. It also has been recorded that alteration of the hormonal pathway, using a dosage of PPAR-γ and RETN, can influence the evolution of OA. IL-1, one of the most investigated biomarkers in OA-SF, is not as reliable as a target of OA in recent studies. The study of biomarkers in SF appears to be, in combination with the clinical and radiological aspects, an additional weapon to address the diagnosis and staging of OA. Therefore, it can guide us more appropriately towards the indication of arthroplasty in patients with OA.


Assuntos
Osteoartrite , Líquido Sinovial , Biomarcadores/metabolismo , Humanos , Osteoartrite/diagnóstico , Osteoartrite/metabolismo , Medicina de Precisão , Proteoma/metabolismo , Líquido Sinovial/metabolismo
15.
Int J Mol Sci ; 23(17)2022 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-36077137

RESUMO

Due to a lack of novel therapies and biomarkers, the clinical outcomes of osteosarcoma patients have not significantly improved for decades. The advancement of mass spectrometry (MS), peptide quantification, and downstream pathway analysis enables the investigation of protein profiles across a wide range of input materials, from cell culture to long-term archived clinical specimens. This can provide insight into osteosarcoma biology and identify candidate biomarkers for diagnosis, prognosis, and stratification of chemotherapy response. In this review, we provide an overview of proteomics studies of osteosarcoma, indicate potential biomarkers that might be promising therapeutic targets, and discuss the challenges and opportunities of mass spectrometric-based proteomics in future osteosarcoma research.


Assuntos
Neoplasias Ósseas , Osteossarcoma , Biomarcadores/análise , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/metabolismo , Humanos , Espectrometria de Massas/métodos , Osteossarcoma/diagnóstico , Osteossarcoma/metabolismo , Proteoma/análise , Proteômica/métodos
16.
Int J Mol Sci ; 23(17)2022 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-36077305

RESUMO

Neofusicoccum parvum can cause twig blight of the walnut (Juglans spp.), resulting in great economic losses and ecological damage. We performed proteomic tandem mass tags (TMT) quantification of two Neofusicoccum parvum strains with different substrates, BH01 in walnut substrate (SW) and sterile water (SK), and BH03 in walnut substrate (WW) and sterile water (WK), in order to identify differentially expressed proteins. We identified 998, 95, and 489 differentially expressed proteins (DEPs) between the SK vs. WK, SW vs. SK, and WW vs. WK comparison groups, respectively. A phylogenetic analysis was performed to classify the ABC transporter proteins annotated in the TMT protein quantification into eight groups. Physicochemical and structural analyses of the 24 ATP-binding cassette (ABC) transporter proteins revealed that 14 of them had transmembrane structures. To elucidate the functions of these transmembrane proteins, we determined the relative expression levels of ABC transporter genes in strains cultured in sodium chloride, hydrogen peroxide, copper sulfate, and carbendazim mediums, in comparison with pure medium; analysis revealed differential upregulation. To verify the expression results, we knocked out the NpABC2 gene and compared the wild-type and knockout mutant strains. The knockout mutant strains exhibited a higher sensitivity to antifungal drugs. Furthermore, the virulence of the knockout mutant strains was significantly lower than the wild-type strains, thus implying that NpABC2 plays a role in the drug resistance of N. parvum and affects its virulence.


Assuntos
Transportadores de Cassetes de Ligação de ATP , Proteoma , Transportadores de Cassetes de Ligação de ATP/metabolismo , Ascomicetos , Filogenia , Proteoma/metabolismo , Proteômica , Água/metabolismo
17.
J Phys Chem B ; 126(36): 6820-6834, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36048731

RESUMO

Recently, we presented a whole-cell kinetic model of the genetically minimal bacterium JCVI-syn3A that described the coupled metabolic and genetic information processes and predicted behaviors emerging from the interactions among these networks. JCVI-syn3A is a genetically reduced bacterial cell that has the fewest number and smallest fraction of genes of unclear function, with approximately 90 of its 452 protein-coding genes (that is less than 20%) unannotated. Further characterization of unclear JCVI-syn3A genes strengthens the robustness and predictive power of cell modeling efforts and can lead to a deeper understanding of biophysical processes and pathways at the cell scale. Here, we apply computational analyses to elucidate the functions of the products of several essential but previously uncharacterized genes involved in integral cellular processes, particularly those directly affecting cell growth, division, and morphology. We also suggest directed wet-lab experiments informed by our analyses to further understand these "missing puzzle pieces" that are an essential part of the mosaic of biological interactions present in JCVI-syn3A. Our workflow leverages evolutionary sequence analysis, protein structure prediction, interactomics, and genome architecture to determine upgraded annotations. Additionally, we apply the structure prediction analysis component of our work to all 452 protein coding genes in JCVI-syn3A to expedite future functional annotation studies as well as the inverse mapping of the cell state to more physical models requiring all-atom or coarse-grained representations for all JCVI-syn3A proteins.


Assuntos
Bactérias , Proteoma , Bactérias/genética , Bactérias/metabolismo , Proteoma/metabolismo
18.
Front Cell Infect Microbiol ; 12: 942334, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36061859

RESUMO

Herpes simplex virus type 2 (HSV-2) is a common human pathogen that establishes lifelong latency in neurons of the nervous system. The number of severe central nervous system infections caused by the virus has increased recently. However, the pathogenesis of HSV-2 infection in the nervous system is not fully understood. Here, we demonstrated global proteomic changes in the brain tissue in BALB/c mice vaginally infected with HSV-2. Data are available via ProteomeXchange with identifier PXD034186. A total of 249 differentially expressed proteins were identified in infected brain tissue. The GO and KEGG enrichment analysis of these proteins indicated that they were mainly involved in the regulation of synapse formation and synaptic excitability. In addition, genes affecting autophagy, the development of other neurodegenerative diseases, and signaling pathways relevant to other neurologic diseases were identified. Additional experiments, comparing the brain tissue of asymptomatic and symptomatic mice showed a differential expression of proteins involved in synapse formation and synaptic transmission. Others were involved in autophagy, addiction, and signaling pathways of other neurologic diseases. These results suggest that changes in synaptic structure and function, as well as autophagy, may be related to the development of neurologic abnormalities that follow HSV-2 infection. We also identified a protein GluN2A encoded by Grin2a was continuously expressed at high levels after infection. We propose that GluN2A may be a key molecule in the pathogenesis of HSV-2-induced neurologic diseases.


Assuntos
Herpes Simples , Herpesvirus Humano 1 , Animais , Encéfalo/patologia , Feminino , Herpes Simples/metabolismo , Herpesvirus Humano 2 , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Proteoma/metabolismo , Proteômica
19.
Food Res Int ; 160: 111647, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36076379

RESUMO

The oyster protein hydrolysate (OPH) possesses various biological activities that have the potential to ameliorate alcoholic liver disease (ALD). This study aimed to assess the protective effects of OPH on liver injury in mice induced by chronic alcohol treatment and the underlying mechanism was further explored by transcriptome and proteome from a global view. Compared with the Model group, OPH treatment significantly decreased the liver weight (p < 0.01) and reduced the content of liver injury markers alanine aminotransferase (ALT, by 34.14%, p < 0.01), aspartate aminotransferase (AST, by 35.31%, p < 0.01) and alkaline phosphatase (ALP, by 17.18%, p < 0.05) while increased the content of hepatic function marker total protein (TP, by 17.30%, p < 0.05) in serum. Meanwhile, only mild hepatocyte injury accompanied by less lipid droplet accumulation was observed in OPH treated ALD mice. The transcriptome and proteome results indicated that 482 target genes and 111 target proteins were involved in the ameliorative effect of OPH on ALD. After data integration, 43 co-regulated targets were identified, which were mainly related to lipid metabolism (reduction of cholesterol and triglyceride accumulation) and inflammatory response [inhibition of inflammatory responses through toll-like receptors (TLRs), nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs), and tumor necrosis factor (TNF) signaling pathways]. Consistent with omics data, the hepatic levels of total lipid, total cholesterol, triglyceride, interleukin 1ß (IL-1ß), tumor necrosis factor α (TNF-α), and transforming growth factor ß (TGF-ß) were declined by OPH treatment in ALD mice. Collectively, our results prove that OPH possesses potent hepatoprotective activities and has the potential to be used as a novel functional ingredient for the management of ALD.


Assuntos
Doença Hepática Crônica Induzida por Substâncias e Drogas , Hepatopatias Alcoólicas , Ostreidae , Animais , Colesterol , Etanol/efeitos adversos , Inflamação/tratamento farmacológico , Metabolismo dos Lipídeos , Hepatopatias Alcoólicas/tratamento farmacológico , Hepatopatias Alcoólicas/metabolismo , Hepatopatias Alcoólicas/prevenção & controle , Camundongos , Ostreidae/metabolismo , Hidrolisados de Proteína/metabolismo , Hidrolisados de Proteína/farmacologia , Proteoma/metabolismo , Triglicerídeos , Fator de Necrose Tumoral alfa/metabolismo
20.
Food Res Int ; 160: 111670, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36076383

RESUMO

Only a few species of swiftlets in the Aerodramus and Collocalia genera can produce edible bird's nests (EBN). These saliva-cemented nests have been consumed as delicacies for centuries in Asia. Many researches have reported the aqueous extract of EBN has epidermal growth factor-like (EGF-like) activity. However, no standalone EGF has been identified in EBN. Moreover, proteome of EBN remained unclear due to lack of genomic data base of an EBN-producing swiftlet to support proteomic analysis of EBN. To address this, the first genome of the EBN-producing swiftlet, Aerodramus fuciphagus, was constructed. Orthology comparison of A. fuciphagus with 10 other avian species were conducted. The results revealed that the number of predicted paralogous coiled-coil domain-containing protein 63 (CCDC63) coding sequences (CDSs) in A. fuciphagus was found to be significantly expanded in comparison to Gallus gallus. There were 3 paralogous CCDC63 genes in the genome of A.fuciphagus. The CDSs predicted from the genome of A. fuciphagus were used to construct a database for proteomic analysis of EBN. In total, 398 proteins have been identified in EBN. The proteome of EBN was significant enriched with extracellular proteins as well as proteins related to extracellular matrix (ECM) organization and immune response. A few proteins with Ca2+-binding EGF-like domains were found in the proteome of EBN, like fibrillin-1, protocadherin fat 4 and coagulation factor X. No standalone EGF protein was identified. This indicated that the proteins with EGF-like domains might be responsible for the EGF-like activity of EBN. In addition, acidic mammalian chitinase and lysyl oxidase in EBN were found to be active when extracting with distilled water at room temperature. The current study has not just revealed the species-specific genotype of the EBN-producing swiftlet, A. fuciphagus, but also revealed the proteome of EBN. This established an important foundation for subsequently studies on efficacies of EBN.


Assuntos
Proteoma , Proteômica , Animais , Aves/genética , Aves/metabolismo , Fator de Crescimento Epidérmico/genética , Fator de Crescimento Epidérmico/metabolismo , Genótipo , Mamíferos , Proteoma/genética , Proteoma/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...