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1.
Eur Respir Rev ; 29(157)2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33004527

RESUMO

The respiratory tract and its resident immune cells face daily exposure to stress, both from without and from within. Inhaled pathogens, including severe acute respiratory syndrome coronavirus 2, and toxins from pollution trigger a cellular defence system that reduces protein synthesis to minimise viral replication or the accumulation of misfolded proteins. Simultaneously, a gene expression programme enhances antioxidant and protein folding machineries in the lung. Four kinases (PERK, PKR, GCN2 and HRI) sense a diverse range of stresses to trigger this "integrated stress response". Here we review recent advances identifying the integrated stress response as a critical pathway in the pathogenesis of pulmonary diseases, including pneumonias, thoracic malignancy, pulmonary fibrosis and pulmonary hypertension. Understanding the integrated stress response provides novel targets for the development of therapies.


Assuntos
Inflamação/metabolismo , Pneumopatias/metabolismo , Estresse Oxidativo/fisiologia , Biomarcadores/metabolismo , Humanos
2.
J Environ Pathol Toxicol Oncol ; 39(3): 247-260, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32865916

RESUMO

The anticancer activity of malvidin was studied in Dalton's lymphoma ascites (DLA)-induced solid and ascitic tumor mice models. Malvidin is a natural compound belonging to the family of O-methylated anthocyanidin and plays a predominant role in regulating both short- and long-term cellular activities. Animals were injected with DLA cells (1.5 × 106 cells/animal) to induce solid and ascitic tumors. The administration of malvidin (5 mg/kg bw and 10 mg/kg bw) was carried out for 10 consecutive days from the day of tumor induction for both solid and ascitic tumors. Cyclophosphamide, CTX (25 mg/kg bw), used as the standard drug, was also administered for 10 consecutive days. Treatment with malvidin showed a significant reduction in tumor volume and elevated white blood cell (WBC) count when compared to the DLA-bearing control animals. The treatment also maintained the body weight and hemoglobin level, and decreases in aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT) were also noted. This investigation also reported the decreased levels of cellular glutathione (GSH) in ascitic tumor groups. Malvidin reduced inflammatory mediator and cytokine levels, such as tumor necrosis factor level alpha (TNF-α) and interleukin-6 (IL-6), which serve as molecular targets for cancer prevention. A decrease in the level of reactive oxygen species (ROS), like nitric oxide (NO), was observed. Histopathological examination revealed altered morphological changes in tumor tissue and the alleviation of hepatic architecture due to DLA. Immunohistochemical analysis revealed the inhibition of iNOS. This study demonstrated that malvidin exhibited significant in vivo antitumor activity and that it was reasonably imputable to its increasing endogenous mechanism. We accent the pertinence of malvidin as a potential naturally derived drug target for tumor control.


Assuntos
Antocianinas/uso terapêutico , Antineoplásicos Fitogênicos/uso terapêutico , Ascite/tratamento farmacológico , Citocinas/sangue , Linfoma/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Animais , Antocianinas/administração & dosagem , Antineoplásicos Fitogênicos/administração & dosagem , Ascite/metabolismo , Ascite/patologia , Biomarcadores/sangue , Biomarcadores/metabolismo , Linhagem Celular Tumoral , Citocinas/metabolismo , Linfoma/metabolismo , Linfoma/patologia , Masculino , Camundongos , Transplante de Neoplasias , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Estresse Oxidativo/imunologia
3.
Aquat Toxicol ; 227: 105590, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32891021

RESUMO

The aim of the present study was to investigate effects of defined mixtures of polycyclic aromatic hydrocarbons (PAHs) and perfluoroalkyl substances (PFASs), at low, environmentally relevant (1× = L), or high (20× = H) doses, on biological responses in Atlantic cod (Gadus morhua). To this end, farmed juvenile cod were exposed at day 0 and day 7 via intraperitoneal (i.p.) injections, in a two-week in vivo experiment. In total, there were 10 groups of fish (n = 21-22): two control groups, four separate exposure groups of PAH and PFAS mixtures (L, H), and four groups combining PAH and PFAS mixtures (L/L, H/L, L/H, H/H). Body burden analyses confirmed a dose-dependent accumulation of PFASs in cod liver and PAH metabolites in bile. The hepatosomatic index (HSI) was significantly reduced for three of the combined PAH/PFAS exposure groups (L-PAH/H-PFAS, H-PAH/L-PFAS, H-PAH/H-PFAS). Analysis of the hepatic proteome identified that pathways related to lipid degradation were significantly affected by PFAS exposure, including upregulation of enzymes in fatty acid degradation pathways, such as fatty acid ß-oxidation. The increased abundances of enzymes in lipid catabolic pathways paralleled with decreasing levels of triacylglycerols (TGs) in the H-PFAS exposure group, suggest that PFAS increase lipid catabolism in Atlantic cod. Markers of oxidative stress, including catalase and glutathione S-transferase activities were also induced by PFAS exposure. Only minor and non-significant differences between exposure groups and control were found for cyp1a and acox1 gene expressions, vitellogenin concentrations in plasma, Cyp1a protein synthesis and DNA fragmentation. In summary, our combined proteomics and lipidomics analyses indicate that PFAS may disrupt lipid homeostasis in Atlantic cod.


Assuntos
Fluorcarbonetos/toxicidade , Gadus morhua/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Bile/metabolismo , Biomarcadores/metabolismo , Fluorcarbonetos/análise , Lipidômica , Fígado/metabolismo , Hidrocarbonetos Policíclicos Aromáticos/análise , Proteoma/metabolismo , Proteômica , Vitelogeninas/metabolismo , Poluentes Químicos da Água/análise
4.
Ecotoxicol Environ Saf ; 205: 111314, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32956866

RESUMO

Brazilian freshwater ecosystems are continuously exposed to pesticides and domestic sewage. The Uruguay River was chosen for this study because of its international importance, as it flows through Brazil, Argentina, and Uruguay. It receives contaminants such as pesticides and domestic residues. Thus, the aim of this study to assess the accumulation of pesticides in muscle of the fish Astyanax jacuhiensis, its biochemical responses, and the presence of pesticides in water. In total, seven pesticides were registered in water from both river sites. Eight pesticides were detected in fish muscle. The biochemical responses showed that brain lipid peroxidation (LPO) and protein carbonyl (PC) in A. jacuhiensis were higher in the summer. Muscle showed the highest LPO levels in the spring and the highest PC in the summer. Liver LPO and PC levels were higher in the spring and summer. In the gills, the PC was higher in the spring and the LPO in the spring and winter. In the brain and in the gills, glutathione-S-transferase activity was high in the summer and autumn. Catalase activity was lower during the winter and spring. Non-protein thiol (NPSH) levels were lower in the brain in the winter and spring. Muscle tissue showed lower NPSH in the winter (site 1). Liver NPSH showed increased levels in liver in the spring and winter (site 2). The biochemical results clearly is related to pesticides and/or to the presence of other contaminants in the water such as metals or domestic sewage. The accumulation of pesticides in fish muscle added evidence that pesticides have been used in the area surrounding the Uruguay River. In conclusion, the biomarkers assayed in the present study could be used in future investigations considering other sampling sites along Uruguay River.


Assuntos
Characidae/fisiologia , Monitoramento Ambiental , Praguicidas/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Biomarcadores/metabolismo , Brasil , Characidae/metabolismo , Caraciformes/metabolismo , Caraciformes/fisiologia , Ecossistema , Brânquias/metabolismo , Peroxidação de Lipídeos , Metais/metabolismo , Praguicidas/análise , Rios/química , Estações do Ano , Poluentes Químicos da Água/análise
5.
BMC Bioinformatics ; 21(1): 396, 2020 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-32894041

RESUMO

BACKGROUND: MicroRNAs are a class of important small noncoding RNAs, which have been reported to be involved in the processes of tumorigenesis and development by targeting a few genes. Existing studies show that the imbalance between cell proliferation and apoptosis is closely related to the initiation and development of cancers. However, the impact of miRNAs on this imbalance has not been studied systematically. RESULTS: In this study, we first construct a cell fate miRNA-gene regulatory network. Then, we propose a systematical method for calculating the global impact of miRNAs on cell fate genes based on the shortest path. Results on breast cancer and liver cancer datasets show that most of the cell fate genes are perturbed by the differentially expressed miRNAs. Most of the top-identified miRNAs are verified in the Human MicroRNA Disease Database (HMDD) and are related to breast and liver cancers. Function analysis shows that the top 20 miRNAs regulate multiple cell fate related function modules and interact tightly based on their functional similarity. Furthermore, more than half of them can promote sensitivity or induce resistance to some anti-cancer drugs. Besides, survival analysis demonstrates that the top-ranked miRNAs are significantly related to the overall survival time in the breast and liver cancers group. CONCLUSION: In sum, this study can help to systematically study the important role of miRNAs on proliferation and apoptosis and thereby uncover the key miRNAs during the process of tumorigenesis. Furthermore, the results of this study will contribute to the development of clinical therapy based miRNAs for cancers.


Assuntos
Apoptose/genética , Proliferação de Células/genética , MicroRNAs/metabolismo , Biomarcadores/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Bases de Dados Genéticas , Feminino , Redes Reguladoras de Genes , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , MicroRNAs/genética , RNA Mensageiro/metabolismo , Análise de Sobrevida
6.
Am J Mens Health ; 14(5): 1557988320954021, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32936693

RESUMO

Coronaviruses are single-stranded ribonucleic acid viruses that can cause illnesses in humans ranging from the common cold to severe respiratory disease and even death.In March 2020, the World Health Organization declared the 2019 novel coronavirus disease (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as the first pandemic. Compared to women, most countries with available data report that men with COVID-19 have greater disease severity and higher mortality. Lab and animal data indicate that men respond differently to the SARS-CoV-2 infection, offering possible explanations for the epidemiologic observations. The plausible theories underlying these observations include sex-related differences in angiotensin-converting enzyme 2 receptors, immune function, hormones, habits, and coinfection rates.In this review we examine these factors and explore the rationale as to how each may impact COVID-19. Understanding why men are more likely to experience severe disease can help in developing effective treatments, public health policies, and targeted strategies such as early recognition and aggressive testing in subgroups.


Assuntos
Infecções por Coronavirus/epidemiologia , Pandemias/estatística & dados numéricos , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/epidemiologia , Síndrome Respiratória Aguda Grave/epidemiologia , Biomarcadores/metabolismo , Feminino , Marcadores Genéticos/fisiologia , Saúde Global , Humanos , Masculino , Prevalência , Medição de Risco , Fatores Sexuais , Análise de Sobrevida , Organização Mundial da Saúde
7.
Medicine (Baltimore) ; 99(38): e22091, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32957329

RESUMO

Inflammatory, angiogenic, and immune processes have been associated with uveal melanoma (UM). The aim of the present study was to evaluate the presence of some specific aqueous humor (AH) soluble biomarkers in eyes affected by UM. Thirty-five eyes affected by primary UM and 35 control eyes, scheduled for cataract surgery, underwent full ophthalmic examination and AH sampling at time of surgery (brachytherapy or cataract surgery, respectively). AH samples were analyzed by means of ELISA, to detect the concentration of selected cytokines, chemokines, and growth factors. Compared with the control group, higher levels of IL-6 (P = .049), IL-8 (P = .006), RANTES (P = .008), EGF (P = .032), bFGF (P = .016), MIF (P = .007), and MCP (P = .020) were detected in eyes with UM. VEGF concentration between the two groups was statistically borderline (P = .058). Comparison between clinical characteristics and cytokine concentrations showed a positive correlation between tumor thickness and IL-8 (P = .032), and degree of serous retinal detachment and IL-6 (P = .021). UM is characterized by the presence of retinal neuroinflammatory, angiogenic, and immune biomarkers in AH. The proteomic analysis of AH could characterize UM microenvironment, allowing to better understand its pathophysiology.


Assuntos
Humor Aquoso/metabolismo , Biomarcadores/metabolismo , Quimiocinas/metabolismo , Citocinas/metabolismo , Melanoma/metabolismo , Neoplasias Uveais/metabolismo , Estudos de Casos e Controles , Estudos Transversais , Feminino , Humanos , Masculino , Melanoma/cirurgia , Pessoa de Meia-Idade , Proteômica , Neoplasias Uveais/cirurgia
8.
Aquat Toxicol ; 227: 105625, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32927179

RESUMO

Here we report the molecular networks associated with the mucosal and systemic responses to peracetic acid (PAA), a candidate oxidative chemotherapeutic in Atlantic salmon (Salmo salar). Smolts were exposed to different therapeutic doses (0, 0.6 and 2.4 mg/L) of PAA for 5 min, followed by a re-exposure to the same concentrations for 30 min 2 weeks later. PAA-exposed groups have higher external welfare score alterations, especially 2 weeks after the re-exposure. Cases of fin damage and scale loss were prevalent in the PAA-exposed groups. Transcriptomic profiling of mucosal tissues revealed that the skin had 12.5 % more differentially regulated genes (DEGs) than the gills following PAA exposure. The largest cluster of DEGs, both in the skin and gills, were involved in tissue extracellular matrix and metabolism. There were 22 DEGs common to both mucosal tissues, which were represented primarily by genes involved in the biophysical integrity of the mucosal barrier, including cadherin, collagen I α 2 chain, mucin-2 and spondin 1a. The absence of significant clustering in the plasma metabolomes amongst the three treatment groups indicates that PAA treatment did not induce any global metabolomic disturbances. Nonetheless, five metabolites with known functions during oxidative stress were remarkably affected by PAA treatments such as citrulline, histidine, tryptophan, methionine and trans-4-hydroxyproline. Collectively, these results indicate that salmon were able to mount mucosal and systemic adaptive responses to therapeutic doses of PAA and that the molecules identified are potential markers for assessing the health and welfare consequences of oxidant exposure.


Assuntos
Metaboloma , Transcriptoma , Poluentes Químicos da Água/toxicidade , Animais , Biomarcadores/metabolismo , Doenças dos Peixes/genética , Perfilação da Expressão Gênica , Brânquias/efeitos dos fármacos , Membrana Mucosa/metabolismo , Oxidantes/metabolismo , Estresse Oxidativo , Salmo salar/metabolismo
9.
DNA Cell Biol ; 39(10): 1895-1906, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32882141

RESUMO

Acute aortic dissection (AD) is one of the most severe and highly mortality vascular disease. Its actual prevalence may be seriously underestimated. We studied different expression genes to understand gene profile change between acute AD and nondiseased individuals, and then discover potential biomarkers and therapeutic targets of acute AD. In our study, acute AD differentially expressed mRNAs and miRNAs were identified through bioinformatics analysis on Gene Expression Omnibus data sets GSE52093, GSE98770, and GSE92427. Then, comprehensive target prediction and network analysis methods were used to evaluate protein-protein interaction networks and to identify Gene Ontology terms for differentially expressed mRNAs. Differentially expressed mRNAs-miRNAs involved in acute AD were assessed as well. Finally, the quantitative real-time PCR and in vitro experiment was used to validate the results. We found Integral Membrane Protein 2C (ITM2C) was low expressed and miR-107-5p was highly expressed in acute AD tissues. Meanwhile, overexpression miR-107-5p promoted the cell proliferation and inhibited the cell apoptosis in RASMC cells. miR-107-5p inhibited the progression of acute AD through targeted ITM2C.


Assuntos
Aneurisma Dissecante/genética , MicroRNAs/genética , Aneurisma Dissecante/metabolismo , Aneurisma Dissecante/patologia , Animais , Apoptose , Biomarcadores/metabolismo , Proliferação de Células , Células Cultivadas , Redes Reguladoras de Genes , Humanos , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , MicroRNAs/metabolismo , Miócitos de Músculo Liso/metabolismo , Mapas de Interação de Proteínas , Ratos , Transcriptoma
10.
Int J Mol Sci ; 21(17)2020 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-32867310

RESUMO

Traumatic brain injury (TBI) represents an important problem of global health. The damage related to TBI is first due to the direct injury and then to a secondary phase in which neuroinflammation plays a key role. NLRP3 inflammasome is a component of the innate immune response and different diseases, such as neurodegenerative diseases, are characterized by NLRP3 activation. This review aims to describe NLRP3 inflammasome and the consequences related to its activation following TBI. NLRP3, caspase-1, IL-1ß, and IL-18 are significantly upregulated after TBI, therefore, the use of nonspecific, but mostly specific NLRP3 inhibitors is useful to ameliorate the damage post-TBI characterized by neuroinflammation. Moreover, NLRP3 and the molecules associated with its activation may be considered as biomarkers and predictive factors for other neurodegenerative diseases consequent to TBI. Complications such as continuous stimuli or viral infections, such as the SARS-CoV-2 infection, may worsen the prognosis of TBI, altering the immune response and increasing the neuroinflammatory processes related to NLRP3, whose activation occurs both in TBI and in SARS-CoV-2 infection. This review points out the role of NLRP3 in TBI and highlights the hypothesis that NLRP3 may be considered as a potential therapeutic target for the management of neuroinflammation in TBI.


Assuntos
Betacoronavirus/imunologia , Lesões Encefálicas Traumáticas/fisiopatologia , Infecções por Coronavirus/complicações , Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Pneumonia Viral/complicações , Biomarcadores/metabolismo , Lesões Encefálicas Traumáticas/diagnóstico , Lesões Encefálicas Traumáticas/tratamento farmacológico , Humanos , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Pandemias , Prognóstico , Piroptose
11.
Ecotoxicol Environ Saf ; 203: 110982, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32888624

RESUMO

Freshwater ecosystems are constantly threatened by the advance of agricultural activities. Abiotic variables (such as temperature, ammonia, and nitrite) and contaminants (e.g. pesticides) can potentially interact, increasing metabolism and the absorption of toxic substances, which can alter the ability of organisms to establish adequate stress responses. This study aimed to verify which pesticides were most frequently found and in the greatest quantities in low-order streams, and whether the combination of these pesticides with the abiotic variables altered the biological metabolism of aeglids. These freshwater crustaceans are important shredders that inhabit low-order streams and are sensitive to disturbances and/or abrupt environmental variations. The animals were exposed in situ in four streams (reference site and sites 1, 2, and 3). The reference site is a preserved stream with no apparent anthropogenic interference where aeglids still occur, while the other sites no longer exhibit populations of these animals and are influenced by agricultural activities. The exposure was performed bimonthly from November 2017 to September 2018 and lasted 96 h. Measured abiotic data and water samples were collected through all days of exposure. The analyzed biochemical parameters were acetylcholinesterase activity in muscle; and glutathione S-transferase, lipid peroxidation, protein carbonylation, non-protein thiols, antioxidant capacity against peroxides, and reactive oxygen species (ROS) in muscle, gills, and hepatopancreas. We found 24 active principles of pesticides, the most frequently being clomazone, atrazine, and propoxur. Bentazone was present at the highest amounts. The parameters evaluated in this study, including biochemical biomarkers and abiotic factors measured from the water, provided a separation of the months as a function of environmental conditions. There was a difference in activity and biomarker levels throughout the year within the same site and in some months between sites. The greater concentration or variety of pesticides associated with extreme abiotic (very high temperatures) data generated increased oxidative stress, with high levels of protein damage and considerable lipid damage in all tissues, as well as elevation in ROS, even with high levels of antioxidant capacity and non-protein thiols. With these data, we intend to warn about the risks of exposure to these environmental conditions by trying to contribute to the preservation of limnic fauna, especially aeglid crabs, because most species are under some degree of threat.


Assuntos
Anomuros/efeitos dos fármacos , Biomarcadores/metabolismo , Exposição Ambiental/efeitos adversos , Praguicidas/efeitos adversos , Animais , Anomuros/metabolismo
12.
Hypertension ; 76(5): 1526-1536, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32981365

RESUMO

ACE2 (angiotensin-converting enzyme 2) is a key component of the renin-angiotensin-aldosterone system. Yet, little is known about the clinical and biologic correlates of circulating ACE2 levels in humans. We assessed the clinical and proteomic correlates of plasma (soluble) ACE2 protein levels in human heart failure. We measured plasma ACE2 using a modified aptamer assay among PHFS (Penn Heart Failure Study) participants (n=2248). We performed an association study of ACE2 against ≈5000 other plasma proteins measured with the SomaScan platform. Plasma ACE2 was not associated with ACE inhibitor and angiotensin-receptor blocker use. Plasma ACE2 was associated with older age, male sex, diabetes mellitus, a lower estimated glomerular filtration rate, worse New York Heart Association class, a history of coronary artery bypass surgery, and higher pro-BNP (pro-B-type natriuretic peptide) levels. Plasma ACE2 exhibited associations with 1011 other plasma proteins. In pathway overrepresentation analyses, top canonical pathways associated with plasma ACE2 included clathrin-mediated endocytosis signaling, actin cytoskeleton signaling, mechanisms of viral exit from host cells, EIF2 (eukaryotic initiation factor 2) signaling, and the protein ubiquitination pathway. In conclusion, in humans with heart failure, plasma ACE2 is associated with various clinical factors known to be associated with severe coronavirus disease 2019 (COVID-19), including older age, male sex, and diabetes mellitus, but is not associated with ACE inhibitor and angiotensin-receptor blocker use. Plasma ACE2 protein levels are prominently associated with multiple cellular pathways involved in cellular endocytosis, exocytosis, and intracellular protein trafficking. Whether these have a causal relationship with ACE2 or are relevant to novel coronavirus-2 infection remains to be assessed in future studies.


Assuntos
Infecções por Coronavirus/epidemiologia , Surtos de Doenças/estatística & dados numéricos , Progressão da Doença , Insuficiência Cardíaca/enzimologia , Insuficiência Cardíaca/fisiopatologia , Peptidil Dipeptidase A/sangue , Pneumonia Viral/epidemiologia , Centros Médicos Acadêmicos , Análise de Variância , Biomarcadores/metabolismo , Estudos de Coortes , Infecções por Coronavirus/prevenção & controle , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Prognóstico , Modelos de Riscos Proporcionais , Proteômica/métodos , Estudos Retrospectivos , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Estados Unidos
13.
Medicine (Baltimore) ; 99(36): e21463, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32898995

RESUMO

Non-alcoholic fatty liver disease (NAFLD) is a common chronic condition caused by the accumulation of fat in the liver. NAFLD may range from simple steatosis to advanced cirrhosis, and affects more than 1 billion people around the world. To date, there has been no effective treatment for NAFLD. In this study, we evaluated the expression of 4 candidate NAFLD biomarkers to assess their possible applicability in the classification and treatment of the disease.Twenty-six obese subjects, who underwent bariatric surgery, were recruited and their liver biopsies obtained. Expression of 4 candidate biomarker genes, PNPLA3, COL1A1, PPP1R3B, and KLF6 were evaluated at gene and protein levels by RT-qPCR and enzyme-linked immunosorbent assay (ELISA), respectively.A significant increase in the levels of COL1A1 protein (P = .03) and PNPLA3 protein (P = .03) were observed in patients with fibrosis-stage NAFLD compared to that in patients with steatosis-stage NAFLD. However, no significant differences were found in abundance of PPP1R3B and KLF6 proteins or at the gene level for any of the candidate.This is the first study, to our knowledge, to report on the expression levels of candidate biomarker genes for NAFLD in the Saudi population. Although PNPLA3 and PPP1R3B had been previously suggested as biomarkers for steatosis and KLF6 as a possible marker for the fibrosis stage of NAFLD, our results did not support these findings. However, other studies that had linked PNPLA3 to fibrosis in advanced NAFLD supported our current finding of high PNPLA3 protein in patients with fibrosis. Additionally, our results support COL1A1 protein as a potential biomarker for the fibrosis stage of NAFLD, and indicate its use in the screening of patients with NAFLD. Further studies are required to validate the use of COL1A1 as a biomarker for advanced NAFLD in a larger cohort.


Assuntos
Biomarcadores/metabolismo , Colágenos Fibrilares , Lipase , Proteínas de Membrana , Hepatopatia Gordurosa não Alcoólica/genética , Adulto , Estudos de Casos e Controles , Progressão da Doença , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/classificação , Obesidade , Reação em Cadeia da Polimerase em Tempo Real , Arábia Saudita , Adulto Jovem
14.
Medicine (Baltimore) ; 99(33): e21706, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32872046

RESUMO

MicroRNAs (miRNAs) have been suggested to act critical roles in the pathophysiology of traumatic osteonecrosis of the femoral head (TONFH). Unfortunately, their roles in the development of TONFH are still ambiguous. The purpose of this study is to identify promising miRNA biomarkers in traumatic osteonecrosis development.We conducted a comprehensive bioinformatics analysis using microarray datasets downloaded from the Gene Expression Omnibus database, and compared the expression of miRNAs in the serum of TONFH patients with controls. Next, we performed target prediction, function enrichment analysis, and protein-protein interaction network analysis based on differentially expressed (DE) miRNAs.We identified 26 DE miRNAs that may contribute to the pathophysiology of TONFH. The miRNAs were linked to ubiquitin proteasome system including conjugating protein ligase activity, ubiquitin-protein ligase activity and ubiquitin mediated proteolysis 5 pathway, and we exposed miR-181a-5p and miR-140-5p as promising biomarkers in TONFH.A predicting model consisting of 5 miRNAs may help discriminating high-risk patients who might develop TONFH after femur neck fracture. Among DE miRNAs, MiR-181a-5p and miR-140-5p may contribute to the development femoral head osteonecrosis after femur neck fracture via ubiquitin proteasome system.


Assuntos
Fraturas do Colo Femoral/genética , Necrose da Cabeça do Fêmur/genética , MicroRNAs/análise , Ubiquitina/genética , Biomarcadores/metabolismo , Biologia Computacional , Feminino , Fraturas do Colo Femoral/cirurgia , Perfilação da Expressão Gênica , Humanos , Masculino , MicroRNAs/genética
15.
Medicine (Baltimore) ; 99(38): e22363, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32957411

RESUMO

BACKGROUND: Neurofilament light (NfL) level was obviously increased in traumatic brain injury (TBI) individuals. But, no comprehensive meta-analysis has ever been conducted to assess the diagnostic performance of NfL. This study aims to evaluate the relationship between NfL level and TBI through a meta-analysis. METHODS: Studies were selected from Pubmed, Web of science, Embase, Google Scholar, PMC and Chinese National Knowledge Infrastructure (CNKI), and the Chinese Biomedical Literature Database (CBM) through inclusion and exclusion criteria. The standard mean difference (SMD) and 95% confidence interval (CI) were calculated using the random-effect model or fixed-effect model to assess the association between NfL level and TBI. Subgroup analysis according to sample collection time, sample type and detection method was performed. The influence analysis and publication bias was also conducted. All analyses were performed using the RevMan 5.3 and Stata 12 software. RESULTS: A total of 9 studies were included. Results indicated that TBI individuals had a higher NfL expression level compared with the non-TBI individuals (SMD = 2.48, 95% CI = 1.52-3.43, I = 96%, P < .01). Similar NfL increasing was also observed in Caucasian population, 0-48 hour and 6-10 days sample collection time, as well as cerebrospinal fluid (CSF), serum, plasma sample subgroup analysis. Moreover, the NfL increasing still existed no matter the NfL expression level was detected by ELISA or Simoa assay. CONCLUSION: NfL expression level was increased in TBI individuals, which indicated that NfL could be a potential biomarker in the diagnosis of TBI and other neurodegenerative diseases.


Assuntos
Lesões Encefálicas Traumáticas/metabolismo , Proteínas de Neurofilamentos/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/metabolismo , Análise Química do Sangue , Lesões Encefálicas Traumáticas/diagnóstico , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoensaio , Masculino , Pessoa de Meia-Idade , Adulto Jovem
16.
PLoS One ; 15(9): e0238037, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32886703

RESUMO

Spectral Counts approaches (SpCs) are largely employed for the comparison of protein expression profiles in label-free (LF) differential proteomics applications. Similarly, to other comparative methods, also SpCs based approaches require a normalization procedure before Fold Changes (FC) calculation. Here, we propose new Complexity Based Normalization (CBN) methods that introduced a variable adjustment factor (f), related to the complexity of the sample, both in terms of total number of identified proteins (CBN(P)) and as total number of spectral counts (CBN(S)). Both these new methods were compared with the Normalized Spectral Abundance Factor (NSAF) and the Spectral Counts log Ratio (Rsc), by using standard protein mixtures. Finally, to test the robustness and the effectiveness of the CBNs methods, they were employed for the comparative analysis of cortical protein extract from zQ175 mouse brains, model of Huntington Disease (HD), and control animals (raw data available via ProteomeXchange with identifier PXD017471). LF data were also validated by western blot and MRM based experiments. On standard mixtures, both CBN methods showed an excellent behavior in terms of reproducibility and coefficients of variation (CVs) in comparison to the other SpCs approaches. Overall, the CBN(P) method was demonstrated to be the most reliable and sensitive in detecting small differences in protein amounts when applied to biological samples.


Assuntos
Biomarcadores/metabolismo , Córtex Cerebral/metabolismo , Modelos Animais de Doenças , Doença de Huntington/metabolismo , Proteoma/análise , Animais , Biomarcadores/análise , Córtex Cerebral/patologia , Proteínas de Escherichia coli/metabolismo , Doença de Huntington/patologia , Camundongos , Camundongos Endogâmicos C57BL , Modelos Teóricos , Padrões de Referência , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem
17.
Chaos ; 30(8): 081104, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32872802

RESUMO

The coronavirus 2019 (COVID-19) respiratory disease is caused by the novel coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), which uses the enzyme ACE2 to enter human cells. This disease is characterized by important damage at a multi-organ level, partially due to the abundant expression of ACE2 in practically all human tissues. However, not every organ in which ACE2 is abundant is affected by SARS-CoV-2, which suggests the existence of other multi-organ routes for transmitting the perturbations produced by the virus. We consider here diffusive processes through the protein-protein interaction (PPI) network of proteins targeted by SARS-CoV-2 as an alternative route. We found a subdiffusive regime that allows the propagation of virus perturbations through the PPI network at a significant rate. By following the main subdiffusive routes across the PPI network, we identify proteins mainly expressed in the heart, cerebral cortex, thymus, testis, lymph node, kidney, among others of the organs reported to be affected by COVID-19.


Assuntos
Betacoronavirus , Infecções por Coronavirus/fisiopatologia , Modelos Biológicos , Pneumonia Viral/fisiopatologia , Mapeamento de Interação de Proteínas , Mapas de Interação de Proteínas , Proteoma , Biomarcadores/metabolismo , Infecções por Coronavirus/metabolismo , Difusão , Humanos , Pandemias , Pneumonia Viral/metabolismo , Fatores de Tempo
18.
Plast Reconstr Surg ; 146(2): 309-320, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32740581

RESUMO

BACKGROUND: Adipose-derived stem cells are considered as candidate cells for regenerative plastic surgery. Measures to influence cellular properties and thereby direct their regenerative potential remain elusive. Hyperbaric oxygen therapy-the exposure to 100% oxygen at an increased atmospheric pressure-has been propagated as a noninvasive treatment for a multitude of indications and presents a potential option to condition cells for tissue-engineering purposes. The present study evaluates the effect of hyperbaric oxygen therapy on human adipose-derived stem cells. METHODS: Human adipose-derived stem cells from healthy donors were treated with hyperbaric oxygen therapy at 2 and 3 atm. Viability before and after each hyperbaric oxygen therapy, proliferation, expression of surface markers and protein contents of transforming growth factor (TGF)-ß, tumor necrosis factor-α, hepatocyte growth factor, and epithelial growth factor in the supernatants of treated adipose-derived stem cells were measured. Lastly, adipogenic, osteogenic, and chondrogenic differentiation with and without use of differentiation-inducing media (i.e., autodifferentiation) was examined. RESULTS: Hyperbaric oxygen therapy with 3 atm increased viability, proliferation, and CD34 expression and reduced the CD31/CD34/CD45 adipose-derived stem cell subset and endothelial progenitor cell population. TGF-ß levels were significantly decreased after two hyperbaric oxygen therapy sessions in the 2-atm group and decreased after three hyperbaric oxygen therapy sessions in the 3-atm group. Hepatocyte growth factor secretion remained unaltered in all groups. Although the osteogenic and chondrogenic differentiation were not influenced, adipogenic differentiation and autodifferentiation were significantly enhanced, with osteogenic autodifferentiation significantly alleviated by hyperbaric oxygen therapy with 3 atm. CONCLUSION: Hyperbaric oxygen therapy with 3 atm increases viability and proliferation of adipose-derived stem cells, alters marker expression and subpopulations, decreases TGF-ß secretion, and skews adipose-derived stem cells toward adipogenic differentiation. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.


Assuntos
Adipogenia/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Engenharia Celular/métodos , Células-Tronco Mesenquimais/efeitos dos fármacos , Oxigênio/administração & dosagem , Tecido Adiposo/citologia , Adulto , Biomarcadores/metabolismo , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Citocinas/metabolismo , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Masculino , Células-Tronco Mesenquimais/fisiologia , Pessoa de Meia-Idade , Pressão , Cultura Primária de Células/métodos
19.
Stem Cell Res Ther ; 11(1): 356, 2020 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-32795359

RESUMO

BACKGROUND: The outbreak of a new virus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has now become the main health concern all over the world. Since effective antiviral treatments have not been developed until now, SARS-CoV-2 is severely affecting countries and territories around the world. METHODS: At the present review, articles in PubMed were searched with the following terms: mesenchymal stem cells, exosomes, coronavirus, and SARS-CoV-2, either alone or in a combination form. The most relevant selected functions were mesenchymal stem cell-derived exosomes and SARS-CoV-2 virus infection. RESULTS: SARS-CoV-2 could damage pulmonary cells and induce secretion of different types of inflammatory cytokines. In the following, these cytokines trigger inflammation that damages the lungs and results in lethal acute respiratory distress syndrome (ARDS). The main characteristic of ARDS is the onset of inflammation in pulmonary, hyaline formation, pulmonary fibrosis, and edema. Mesenchymal stem cell-derived exosomes (MSC-Exo) are believed to have anti-inflammatory effects and immune-modulating capacity as well as the ability to induce tissue regeneration, suggesting a significant therapeutic opportunity that could be used to SARS-CoV-2 pneumonia treatment. Besides, exosomes may serve as a biomarker, drug delivery system, and vaccine for the management of the patient with SARS-CoV-2. CONCLUSION: MSC-Exo may serve as a promising tool in the treatment of SARS-CoV-2 pneumonia. However, further work needs to be carried out to confirm the efficacy of exosomes in the treatment of SARS-CoV-2 pneumonia.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/terapia , Exossomos/transplante , Pneumonia Viral/terapia , Betacoronavirus/isolamento & purificação , Biomarcadores/metabolismo , Coronavirus/isolamento & purificação , Coronavirus/patogenicidade , Infecções por Coronavirus/virologia , Citocinas/metabolismo , Humanos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Pandemias , Pneumonia Viral/virologia
20.
Clin Immunol ; 219: 108555, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32771488

RESUMO

Respiratory failure and acute kidney injury (AKI) are associated with high mortality in SARS-CoV-2-associated Coronavirus disease 2019 (COVID-19). These manifestations are linked to a hypercoaguable, pro-inflammatory state with persistent, systemic complement activation. Three critical COVID-19 patients recalcitrant to multiple interventions had skin biopsies documenting deposition of the terminal complement component C5b-9, the lectin complement pathway enzyme MASP2, and C4d in microvascular endothelium. Administration of anti-C5 monoclonal antibody eculizumab led to a marked decline in D-dimers and neutrophil counts in all three cases, and normalization of liver functions and creatinine in two. One patient with severe heart failure and AKI had a complete remission. The other two individuals had partial remissions, one with resolution of his AKI but ultimately succumbing to respiratory failure, and another with a significant decline in FiO2 requirements, but persistent renal failure. In conclusion, anti-complement therapy may be beneficial in at least some patients with critical COVID-19.


Assuntos
Lesão Renal Aguda/imunologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Betacoronavirus/patogenicidade , Inativadores do Complemento/uso terapêutico , Infecções por Coronavirus/imunologia , Síndrome da Liberação de Citocina/imunologia , Pneumonia Viral/imunologia , Síndrome Respiratória Aguda Grave/imunologia , Lesão Renal Aguda/complicações , Lesão Renal Aguda/tratamento farmacológico , Lesão Renal Aguda/virologia , Adulto , Betacoronavirus/imunologia , Biomarcadores/metabolismo , Ativação do Complemento/efeitos dos fármacos , Complemento C4b/antagonistas & inibidores , Complemento C5/antagonistas & inibidores , Complexo de Ataque à Membrana do Sistema Complemento/antagonistas & inibidores , Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/virologia , Síndrome da Liberação de Citocina/complicações , Síndrome da Liberação de Citocina/tratamento farmacológico , Síndrome da Liberação de Citocina/virologia , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Humanos , Imunidade Humoral/efeitos dos fármacos , Masculino , Serina Proteases Associadas a Proteína de Ligação a Manose/genética , Serina Proteases Associadas a Proteína de Ligação a Manose/imunologia , Pessoa de Meia-Idade , Neutrófilos/imunologia , Neutrófilos/patologia , Pandemias , Fragmentos de Peptídeos/antagonistas & inibidores , Pneumonia Viral/complicações , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/virologia , Síndrome Respiratória Aguda Grave/complicações , Síndrome Respiratória Aguda Grave/tratamento farmacológico , Síndrome Respiratória Aguda Grave/virologia
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