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1.
Cancer Invest ; 37(9): 453-462, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31469000

RESUMO

Cancer is a proficient evader of the immune system and is responsible for a high number of deaths annually. Most of these cancer cases are associated with genetic mutations, viruses, radiations or other carcinogenic substances like tobacco smoke. However, a significant number of cases arise as a result of infection by certain parasitic organisms other than viruses. This review tries to explore various less studied mechanisms by which these parasites induce cancer and lead to its progression. The changes brought by organisms in the genetic makeup are enumerated along with the effects of various protein products synthesised by these organisms.


Assuntos
Infecções Bacterianas/complicações , Micoses/complicações , Neoplasias/etiologia , Doenças Parasitárias/complicações , Animais , Infecções Bacterianas/genética , Carcinogênese , Progressão da Doença , Redes Reguladoras de Genes , Humanos , Micoses/genética , Neoplasias/genética , Doenças Parasitárias/genética
2.
Biochim Biophys Acta Rev Cancer ; 1872(1): 1-10, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31059737

RESUMO

Pyroptosis, a type of inflammatory programmed cell death, is mediated by multiple inflammasomes which can recognize danger signals and activate the secretion of pro-inflammatory cytokines like IL-181 and IL-1ß2. It can induce cancer cell death within the gastrointestinal tract. NLRs3, AIM24, GSDM5 family play important roles in pyroptosis signaling pathways in intestinal cancer such as gastric cancer, colitis-associated colorectal cancer and esophageal cancer, etc. Furthermore, several inflammasomes are elucidated to be involved in mucosal innate immune responses and modulate specific enteric pathogens infection. Precise modulation of inflammasome activation and exploration of potential diagnostic markers can contribute to the diagnosis, prevention and treatment of intestinal tumors and inflammatory or infectious disorders in human patients in the near future.


Assuntos
Infecções Bacterianas/genética , Neoplasias Gastrointestinais/genética , Intestinos/microbiologia , Piroptose/genética , Infecções Bacterianas/complicações , Infecções Bacterianas/imunologia , Infecções Bacterianas/microbiologia , Neoplasias Gastrointestinais/complicações , Neoplasias Gastrointestinais/imunologia , Neoplasias Gastrointestinais/microbiologia , Humanos , Imunidade Inata/genética , Inflamassomos/genética , Interleucina-18/genética , Interleucina-1beta/genética , Intestinos/patologia
3.
ACS Appl Mater Interfaces ; 11(19): 17177-17183, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-30997794

RESUMO

Because of the abuse of antibiotics and threats of antibiotic resistance, bacterial infection is still one of the most difficult issues to be resolved. Thus, it is of great significance to explore novel antibacterial agents. In this paper, we investigated a type of silica-coated gold-silver nanocages (Au-Ag@SiO2 NCs) as antibacterial candidates. Their intrinsic characteristics of photothermal property and sustained release of Ag ions were fully exploited for near-infrared (NIR)-induced combined anti-infective therapy. The broad-spectrum antibacterial property of the as-prepared Au-Ag@SiO2 NCs was confirmed in vitro against Gram-positive Staphylococcus aureus ( S. aureus) and Gram-negative bacteria Escherichia coli ( E. coli). In addition, Au-Ag@SiO2 NCs exhibit effective treatment of the S. aureus biofilm with the assistance of NIR irradiation. More importantly, we assessed the in vivo antibacterial efficacy of Au-Ag@SiO2 NCs against S. aureus, which demonstrated sustainably enhanced therapeutic effects on a rat model with wound infection.


Assuntos
Antibacterianos/farmacologia , Infecções Bacterianas/tratamento farmacológico , Biofilmes/efeitos dos fármacos , Prata/química , Animais , Antibacterianos/química , Infecções Bacterianas/genética , Infecções Bacterianas/microbiologia , Farmacorresistência Bacteriana/genética , Escherichia coli/efeitos dos fármacos , Escherichia coli/patogenicidade , Ouro/química , Humanos , Testes de Sensibilidade Microbiana , Ratos , Dióxido de Silício/química , Dióxido de Silício/farmacologia , Prata/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/patogenicidade
4.
PLoS Comput Biol ; 15(4): e1006866, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30986219

RESUMO

Investigating the emergence of a particular cell type is a recurring theme in models of growing cellular populations. The evolution of resistance to therapy is a classic example. Common questions are: when does the cell type first occur, and via which sequence of steps is it most likely to emerge? For growing populations, these questions can be formulated in a general framework of branching processes spreading through a graph from a root to a target vertex. Cells have a particular fitness value on each vertex and can transition along edges at specific rates. Vertices represent cell states, say genotypes or physical locations, while possible transitions are acquiring a mutation or cell migration. We focus on the setting where cells at the root vertex have the highest fitness and transition rates are small. Simple formulas are derived for the time to reach the target vertex and for the probability that it is reached along a given path in the graph. We demonstrate our results on several scenarios relevant to the emergence of drug resistance, including: the orderings of resistance-conferring mutations in bacteria and the impact of imperfect drug penetration in cancer.


Assuntos
Evolução Biológica , Resistência a Múltiplos Medicamentos , Modelos Biológicos , Bactérias/efeitos dos fármacos , Bactérias/genética , Bactérias/crescimento & desenvolvimento , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/genética , Infecções Bacterianas/microbiologia , Biologia Computacional , Resistência a Múltiplos Medicamentos/genética , Farmacorresistência Bacteriana Múltipla/genética , Resistencia a Medicamentos Antineoplásicos/genética , Evolução Molecular , Humanos , Mutação , Neoplasias/tratamento farmacológico , Neoplasias/genética , Neoplasias/patologia , Fenótipo , Probabilidade , Processos Estocásticos
5.
Cell Mol Life Sci ; 76(11): 2031-2042, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30877336

RESUMO

Pyroptosis is a caspase-1 or caspase-4/5/11-dependent programmed cell death associated with inflammation, which is initiated by inflammasomes or cytosolic LPS in innate immunity. Sepsis is a life-threatening organ dysfunction caused by an imbalance in the body's response to infection. It is a complex interaction between the pathogen and the host's immune system. Neutrophils play the role of a double-edged sword in sepsis, and a number of studies have previously shown that regulation of neutrophils is the most crucial part of sepsis treatment. Pyroptosis is one of the important forms for neutrophils to function, which is increasingly understood as a host active immune response. There is ample evidence that neutrophil pyroptosis may play an important role in sepsis. In recent years, a breakthrough in pyroptosis research has revealed the main mechanism of pyroptosis. However, the potential value of neutrophil pyroptosis in the treatment of sepsis did not draw enough attention. A literature review was performed on the main mechanism of pyroptosis in sepsis and the potential value of neutrophils pyroptosis in sepsis, which may be suitable targets for sepsis treatment in future.


Assuntos
Infecções Bacterianas/imunologia , Caspases/imunologia , Inflamassomos/imunologia , Neutrófilos/imunologia , Piroptose/imunologia , Sepse/imunologia , Animais , Anti-Inflamatórios/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/genética , Infecções Bacterianas/patologia , Proteínas Adaptadoras de Sinalização CARD/genética , Proteínas Adaptadoras de Sinalização CARD/imunologia , Caspases/genética , Regulação da Expressão Gênica , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imunidade Inata , Inflamassomos/efeitos dos fármacos , Interleucina-18/genética , Interleucina-18/imunologia , Interleucina-1beta/genética , Interleucina-1beta/imunologia , Lipopolissacarídeos/farmacologia , Neutrófilos/efeitos dos fármacos , Neutrófilos/microbiologia , Piroptose/efeitos dos fármacos , Sepse/tratamento farmacológico , Sepse/genética , Sepse/patologia
6.
Expert Rev Mol Diagn ; 19(2): 161-173, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30640566

RESUMO

INTRODUCTION: Bloodstream infections (BSIs) remain a major public health burden worldwide, particularly in high-income countries as they are associated with a significant mortality rate. As early administration of appropriate antimicrobial therapy is a major prognostic factor, there remain unmet needs for shortening BSI diagnosis. Current blood cultures (BC) processing to identify pathogens involved in BSI is not compatible with such delays, although it remains the gold standard. Areas covered: Herein, we review and discuss emerging or ongoing assessed methodologies dedicated to shorten the identification of microorganisms involved in BSI and published since 2015. A particular focus on the economical and clinical impact of these approaches is provided when hindsight is sufficient. Methods to shorten antibiotic susceptibility testing are also reviewed. Expert commentary: Post-culture approaches have encountered a huge success as they are reliable, fast and easy to implement in the laboratory. In particular, the MALDI-TOF MS was shown to be a cost-effective method when combined with antimicrobial stewardship policies. However, further research is needed to optimize methods performed on whole blood in particular next-generation sequencing methods, as they represent an opportunity to substantially improve management of high-risk patients.


Assuntos
Antibacterianos/uso terapêutico , Bacteriemia , Infecções Bacterianas , Hemocultura/métodos , Sequenciamento de Nucleotídeos em Larga Escala , Bacteriemia/sangue , Bacteriemia/tratamento farmacológico , Bacteriemia/genética , Bacteriemia/microbiologia , Infecções Bacterianas/sangue , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/genética , Infecções Bacterianas/microbiologia , Humanos
7.
Bull Exp Biol Med ; 166(3): 334-338, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30627903

RESUMO

Activities of MMP-2 and MMP-9 in the cytoplasm and mitochondria of kidney cells were evaluated on the models of acute renal pathologies: pyelonephritis, rhabdomyolysis, and ischemia/reperfusion of the kidney. In acute pyelonephritis, a significant increase in the level of MMP-2 and MMP-9 in kidney cells and the appearance of mitochondrial MMP-2 isoform with a lower molecular weight, but still exhibiting proteolytic activity were observed. A direct correlation between the level of MMP-2 and MMP-9 in the kidney and the severity of inflammation in pyelonephritis was revealed. Obviously, the appearance of active protease in the mitochondria of the kidney cells could have an impact on their functioning and, generally, on the fate of renal cells in this pathology.


Assuntos
Infecções Bacterianas/genética , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 9 da Matriz/genética , Mitocôndrias/genética , Pielonefrite/genética , Traumatismo por Reperfusão/genética , Rabdomiólise/genética , Doença Aguda , Animais , Animais não Endogâmicos , Infecções Bacterianas/enzimologia , Infecções Bacterianas/patologia , Modelos Animais de Doenças , Células Epiteliais , Regulação da Expressão Gênica , Isoenzimas/genética , Isoenzimas/metabolismo , Rim/enzimologia , Rim/patologia , Rim/cirurgia , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Mitocôndrias/enzimologia , Mitocôndrias/patologia , Nefrectomia/métodos , Pielonefrite/enzimologia , Pielonefrite/patologia , Ratos , Traumatismo por Reperfusão/enzimologia , Traumatismo por Reperfusão/patologia , Rabdomiólise/enzimologia , Rabdomiólise/patologia , Índice de Gravidade de Doença
8.
Congenit Anom (Kyoto) ; 59(3): 81-87, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30592100

RESUMO

The rapid rise in the prevalence of autism spectrum disorders (ASD) and other psychiatric disorders displaying similar traits has increased the need to elucidate their molecular mechanisms. Epidemiological studies have shown that maternal infection during mid-pregnancy is associated with increased risk of neurodevelopmental disorders such as ASD in offspring. Using maternal infection models, researchers have gathered evidence relevant to such disorders. A comprehensive summary of the changes in the brain structure, function, and behavior in offspring induced by maternal immune activation (MIA) has been reported. However, the molecular mechanisms underlying the association between MIA and improper brain development, which ultimately lead to neurodevelopmental disorders, have not been fully reviewed. This paper summarizes the currently known molecular mechanisms associated with the MIA model, with a special focus on the role of the placenta in fetal brain development.


Assuntos
Infecções Bacterianas/genética , Encéfalo/imunologia , Interleucina-6/genética , Transtornos do Neurodesenvolvimento/genética , Complicações Infecciosas na Gravidez/genética , Viroses/genética , Animais , Infecções Bacterianas/complicações , Infecções Bacterianas/imunologia , Infecções Bacterianas/fisiopatologia , Encéfalo/efeitos dos fármacos , Encéfalo/crescimento & desenvolvimento , Encéfalo/fisiopatologia , Modelos Animais de Doenças , Feminino , Feto , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Imunidade Inata/efeitos dos fármacos , Interleucina-6/imunologia , Lipopolissacarídeos/farmacologia , Transtornos do Neurodesenvolvimento/complicações , Transtornos do Neurodesenvolvimento/imunologia , Transtornos do Neurodesenvolvimento/fisiopatologia , Placenta , Poli I-C/farmacologia , Gravidez , Complicações Infecciosas na Gravidez/imunologia , Complicações Infecciosas na Gravidez/fisiopatologia , Transdução de Sinais , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia , Viroses/complicações , Viroses/imunologia , Viroses/fisiopatologia
9.
Methods Mol Biol ; 1898: 163-171, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30570731

RESUMO

Alternative infection models of bacterial pathogenesis are useful because they reproduce some of the disease characteristics observed in higher animals. Insect models are especially useful for modeling bacterial infections, as they are inexpensive, generally less labor-intensive, and more ethically acceptable than experimentation on higher organisms. Similar to animals, insects have been shown to possess innate immune systems that respond to pathogenic bacteria.


Assuntos
Alternativas aos Testes com Animais/métodos , Infecções Bacterianas/microbiologia , Larva/microbiologia , Mariposas/microbiologia , Animais , Bactérias/genética , Bactérias/patogenicidade , Infecções Bacterianas/genética , Modelos Animais de Doenças , Humanos , Larva/genética , Mariposas/genética , Virulência/genética
10.
Dev Comp Immunol ; 90: 21-28, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30165084

RESUMO

In mammals, the TNF family is important inflammatory cytokines. Eiger, the invertebrate ortholog of TNF identified firstly in Drosophila, has been implicated in immune response with an unknown molecular mechanism. The present work reports a novel eiger like gene (Mdeiger) from Musca domestica. Mdeiger was significantly up-regulated upon challenge with either Escherichia coli or Staphylococcus aureus. Silencing Mdeiger led to higher mortalities of larvae post either E. coli or S. aureus infection, enhanced the expressions of attacin and diptericin, but blocked the induction of ceropin and muscin, and inhibited the activation of phenoloxidase following bacterial challenge. Meanwhile, the expression of dorsal and JNK was inhibited while that of relish was enhanced in Mdeiger-depleted larvae. We suppose that, by coordinating with the Imd, Toll and JNK pathways, Mdeiger be involved in regulating the innate immune response through controlling the capacity of phenoloxidase and the expression of antimicrobial peptide genes synergistically.


Assuntos
Infecções Bacterianas/imunologia , Escherichia coli/fisiologia , Moscas Domésticas/imunologia , Staphylococcus aureus/fisiologia , Fator de Necrose Tumoral alfa/genética , Animais , Infecções Bacterianas/genética , Células Cultivadas , Clonagem Molecular , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Regulação da Expressão Gênica , Imunidade Inata , MAP Quinase Quinase 4/metabolismo , Mamíferos , Proteínas de Membrana/genética , RNA Interferente Pequeno/genética , Transdução de Sinais , Receptores Toll-Like/metabolismo
11.
Iran J Immunol ; 15(4): 309-320, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30593745

RESUMO

BACKGROUND: Primary complement deficiencies are rare diseases. OBJECTIVE: To retrospectively evaluate the clinical and laboratory findings and complications of patients to increase awareness of pediatricians about complement deficiencies, which are rarely encountered. METHODS: In this study, the clinical and immunological characteristics of 21 patients who consulted the Immunology Department of our hospital between 2003 and 2017 and were diagnosed with classical or alternative pathway complement deficiency were obtained from the file records. RESULTS: Ten patients with C1 inhibitor deficiency, four patients with factor I deficiency, three patients with properdin deficiency, two patients with C8 deficiency, one patient with C1q deficiency, and one patient with C4B deficiency were assessed. The mean age of the patients at diagnosis was 11.4±4.7 years, the age of onset of symptoms was 7.9±3.9 years, and the follow-up period was 6.7±3.9 years. Fourteen cases had a similar medical history in the family. All patients with C1q, factor I, properdin, C8, and C4B deficiencies presented with an infection, and vasculitic rash was present in two patients with factor I deficiency. In addition, immune complex glomerulonephritis was present in one patient with factor I deficiency. Meningococcal, Haemophilus influenzae type B, and pneumococcal vaccines were administered and prophylactic antibiotic treatment was initiated in all patients except patients with C1 inhibitor deficiency. CONCLUSIONS: Early diagnosis of complement deficiencies can facilitate prevention of life-threatening complications such as severe bacterial infections by considering prophylactic antibiotics and vaccines. In patients with C1 inhibitor deficiency, achieving an acurate early diagnosis will assist in the management and timely treatment of life-threatening attacks such as upper airway obstruction and improve outcomes.


Assuntos
Infecções Bacterianas/genética , Via Alternativa do Complemento/genética , Via Clássica do Complemento/genética , Síndromes de Imunodeficiência/genética , Adolescente , Antibioticoprofilaxia , Infecções Bacterianas/diagnóstico , Criança , Proteína Inibidora do Complemento C1/genética , Complemento C1q/genética , Complemento C8/genética , Diagnóstico Precoce , Feminino , Fibrinogênio/genética , Seguimentos , Humanos , Síndromes de Imunodeficiência/diagnóstico , Masculino , Properdina/genética , Estudos Retrospectivos
12.
Nature ; 564(7736): 434-438, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30542152

RESUMO

The annotation of the mammalian protein-coding genome is incomplete. Arbitrary size restriction of open reading frames (ORFs) and the absolute requirement for a methionine codon as the sole initiator of translation have constrained the identification of potentially important transcripts with non-canonical protein-coding potential1,2. Here, using unbiased transcriptomic approaches in macrophages that respond to bacterial infection, we show that ribosomes associate with a large number of RNAs that were previously annotated as 'non-protein coding'. Although the idea that such non-canonical ORFs can encode functional proteins is controversial3,4, we identify a range of short and non-ATG-initiated ORFs that can generate stable and spatially distinct proteins. Notably, we show that the translation of a new ORF 'hidden' within the long non-coding RNA Aw112010 is essential for the orchestration of mucosal immunity during both bacterial infection and colitis. This work expands our interpretation of the protein-coding genome and demonstrates that proteinaceous products generated from non-canonical ORFs are crucial for the immune response in vivo. We therefore propose that the misannotation of non-canonical ORF-containing genes as non-coding RNAs may obscure the essential role of a multitude of previously undiscovered protein-coding genes in immunity and disease.


Assuntos
Imunidade nas Mucosas/genética , Fases de Leitura Aberta/genética , Biossíntese de Proteínas , RNA Longo não Codificante/genética , Animais , Infecções Bacterianas/genética , Infecções Bacterianas/imunologia , Infecções Bacterianas/metabolismo , Infecções Bacterianas/microbiologia , Colite/genética , Colite/imunologia , Colite/metabolismo , Imunidade nas Mucosas/efeitos dos fármacos , Interleucina-12/biossíntese , Lipopolissacarídeos/farmacologia , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos , Biossíntese de Proteínas/efeitos dos fármacos , Biossíntese de Proteínas/genética , RNA Longo não Codificante/metabolismo , Ribossomos/efeitos dos fármacos , Ribossomos/metabolismo , Salmonella typhimurium/imunologia , Transcriptoma/efeitos dos fármacos , Transcriptoma/genética
13.
DNA Cell Biol ; 37(8): 708-723, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29905492

RESUMO

The high-mobility group box 1 (HMGB1) protein is a highly conserved nonhistone chromosomal protein ubiquitously present in almost all cell types. In the nucleus, it facilitates DNA repair and replication, V(D)J recombination, stabilization of nucleosome, and in the cytoplasm, it regulates autophagy and apoptosis. In addition to these intracellular functions, HMGB1 also facilitates activation of innate immune responses and plays key roles in host defense. To investigate its role in fish, we cloned and characterized HMGB1 in Labeo rohita (LrHMGB1), the most important freshwater fish species in the Indian subcontinent. The full-length cDNA sequence of LrHMGB1 consisted of 787 bp having an open reading frame of 618 bp encoding 205 amino acids (aa) polypeptide, with an estimated molecular mass of 23.61 kDa and isoelectric point (pI) of 5.96. Motif search of LrHMGB1 revealed two homologous DNA-binding domains, the A-box and B-box comprising 8-78 aa and 94-162 aa, respectively, and a negatively charged acidic C-terminal tail (179-204) that consisted of 26 consecutive aspartic and glutamic acid residues. The amino acids sequence of LrHMGB1 protein and the secondary structure having helix (H) and coils (C) in tandem in the A- and B-box region and only coils in the acidic tail region shared significant similarity with mouse and human HMGB1. In addition to the three prominent motifs (A-box, B-box, and the acidic tail), the site of acetylation (lys27-29), phosphorylation (serine38,41,45,52), methylation (lys43), and oxidation (cysteine44,105) in LrHMGB1 was also conserved across the fish species, mouse, and human. LrHMGB1 was expressed during embryogenesis and was widely expressed in various organs/tissues having highest expression in blood. In response to bacterial infection, antiviral vaccination, and pathogen-associated molecular patterns stimulations, LrHMGB1 gene expression was significantly (p < 0.05) induced in various organs and tissues. These results together suggest an evolutionary conserved structure and function of HMGB1 from fish to human.


Assuntos
Antivirais/farmacologia , Infecções Bacterianas/genética , Carpas/genética , Doenças dos Peixes/genética , Proteínas de Peixes/genética , Proteína HMGB1/genética , Padrões Moleculares Associados a Patógenos/farmacologia , Aeromonas hydrophila/fisiologia , Sequência de Aminoácidos , Animais , Infecções Bacterianas/veterinária , Sequência de Bases , Carpas/microbiologia , Clonagem Molecular , Sequência Conservada , DNA Complementar/análise , Regulação da Expressão Gênica/efeitos dos fármacos , Proteína HMGB1/análise , Imunidade Inata/genética , Vacinação/veterinária
14.
Biochem Biophys Res Commun ; 497(4): 1104-1109, 2018 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-29499195

RESUMO

As a protein with complex domain structure and roles in kinase, GTPase and scaffolding, LRRK2 is believed to be an important orchestration node leading to several cascades of signal transduction rather than one specific pathway. LRRK2 variants were found to be associated with Parkinson's disease, Crohn's disease and leprosy. Here we disrupt LRRK2 in zebrafish and found hyperactivity rather than hypoactivity in adult zebrafish mutants. By RNA-seq we found genes involved in infectious disease and immunological disease were notably affected. Functional studies also revealed a weakened antibacterial response in LRRK2 mutant. This mutant can be further explored for revealing molecular mechanisms and modeling of LRRK2 related diseases.


Assuntos
Hipercinese/etiologia , Imunidade/genética , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/genética , Proteínas de Peixe-Zebra/genética , Animais , Infecções Bacterianas/genética , Infecções Bacterianas/imunologia , Comportamento Animal , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/imunologia , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/fisiologia , Atividade Motora/genética , Mutagênese Sítio-Dirigida , Análise de Sequência de RNA , Peixe-Zebra , Proteínas de Peixe-Zebra/imunologia , Proteínas de Peixe-Zebra/fisiologia
15.
APMIS ; 126(4): 275-283, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29508438

RESUMO

Inflammatory bowel disease (IBD) is a general term used for the ulcerative colitis (UC) and Crohn's disease (CD); in addition, IBD principally refers to a chronic disease of the gastrointestinal tract in which mediated by immune system. Consequently, IBD could progress in individuals who are genetically prone. Infections role in the development of inflammatory disease of the gastrointestinal tract has been studied by quite many clinical studies; furthermore, the possible role of some pathogens in the development and exacerbation of the inflammatory disease of the gastrointestinal tract have been described. Evidently, the most indispensable pathogens that could be associated with the IBD disease, Mycobacterium avium subspecies paratuberculosis, Clostridium difficile, Escherichia coli, Listeria monocytogenes, Campylobacter concisus; as well as viruses, such as, cytomegalovirus, Epstein-Barr Virus, and measles virus are notable. A number of pathogenic parasites may also be involved in the development and progression of the disease. As a matter of fact, overexposure of immune system in the presence of excessive bacterial substances could also lead to the loss of immunological tolerance to the bacteria, which are commonly considered as the normal flora in the intestine; furthermore, it may subsequently elicit bowel inflammation and IBD development. In the current study, we discussed the most common bacterial pathogens that may be involved in the development of IBD; as well as, a comprehensive narrative review related to the evidences which support or ignore the possible role of bacteria in progression of IBD, indeed.


Assuntos
Infecções Bacterianas/microbiologia , Fenômenos Fisiológicos Bacterianos , Doenças Inflamatórias Intestinais/microbiologia , Animais , Bactérias/genética , Bactérias/isolamento & purificação , Infecções Bacterianas/genética , Infecções Bacterianas/imunologia , Humanos , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/imunologia
16.
Rev Invest Clin ; 70(1): 18-28, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29513298

RESUMO

Nucleotide-binding domain (NBD) leucine-rich repeat (LRR)-containing receptors or NLRs are a family of receptors that detect both, molecules associated to pathogens and alarmins, and are located mainly in the cytoplasm. NOD2 belongs to the NLR family and is a dynamic receptor capable of interacting with multiple proteins and modulate immune responses in a stimuli-dependent manner. The experimental evidence shows that interaction between NOD2 structural domains and the effector proteins shape the overall response against bacterial or viral infections. Other reports have focused on the importance of NOD2 not only in infection but also in maintaining tissue homeostasis. However, not only protein interactions relate to function but also certain polymorphisms in the gene that encodes NOD2 have been associated with inflammatory diseases, such as Crohn's disease. Here, we review the importance and general characteristics of NOD2, discussing its participation in infections caused by bacteria and viruses as well as its interaction with other pathogen recognition receptors or effectors to induce antibacterial and antiviral responses. Finally, the role of NOD2 in chronic inflammatory conditions and its potential to be targeted therapeutically are examined.


Assuntos
Infecções Bacterianas/metabolismo , Proteína Adaptadora de Sinalização NOD2/metabolismo , Viroses/metabolismo , Animais , Infecções Bacterianas/genética , Infecções Bacterianas/terapia , Humanos , Proteína Adaptadora de Sinalização NOD2/genética , Polimorfismo Genético , Viroses/genética , Viroses/terapia
17.
Crit Rev Microbiol ; 44(4): 465-486, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29345518

RESUMO

Interleukin-17 (IL-17) is a pro-inflammatory cytokine involved in the control of many different disorders, including autoimmune, oncogenic, and diverse infectious diseases. In the context of infectious diseases, IL-17 protects the host against various classes of microorganisms but, intriguingly, can also exacerbate the severity of some infections. The regulation of IL-17 expression stems, in part, from the activity of Interleukin-23 (IL-23), which drives the maturation of different classes of IL-17-producing cells that can alter the course of infection. In this review, we analyze IL-17/IL-23 signalling in bacterial infection, and examine the interconnecting mechanisms that link immune regulation, host genetics, and microbial virulence in the context of bacterial pathogenesis. We consider the roles of IL-17 in both acute and chronic bacterial infections, with a focus on mouse models of human bacterial disease that involve infection of mucosal surfaces in the lungs, urogenital, and gastrointestinal tracts. Polymorphisms in IL-17-encoding genes in humans, which have been associated with heightened host susceptibility to some bacterial pathogens, are discussed. Finally, we examine the implications of IL-17 biology in infectious diseases for the development of novel therapeutic strategies targeted at preventing bacterial infection.


Assuntos
Bactérias/patogenicidade , Infecções Bacterianas/genética , Infecções Bacterianas/imunologia , Interleucina-17/genética , Animais , Bactérias/genética , Bactérias/metabolismo , Infecções Bacterianas/microbiologia , Infecções Bacterianas/fisiopatologia , Interações Hospedeiro-Patógeno , Humanos , Interleucina-17/imunologia , Virulência
18.
Sci Rep ; 8(1): 896, 2018 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-29343758

RESUMO

The exciting discovery of the semiconducting-like properties of deoxyribonucleic acid (DNA) and its potential applications in molecular genetics and diagnostics in recent times has resulted in a paradigm shift in biophysics research. Recent studies in our laboratory provide a platform towards detecting charge transfer mechanism and understanding the electronic properties of DNA based on the sequence-specific electronic response, which can be applied as an alternative to identify or detect DNA. In this study, we demonstrate a novel method for identification of DNA from different shrimp viruses and bacteria using electronic properties of DNA obtained from both negative and positive bias regions in current-voltage (I-V) profiles. Characteristic electronic properties were calculated and used for quantification and further understanding in the identification process. Aquaculture in shrimp industry is a fast-growing food sector throughout the world. However, shrimp culture in many Asian countries faced a huge economic loss due to disease outbreaks. Scientists have been using specific established methods for detecting shrimp infection, but those methods do have their significant drawbacks due to many inherent factors. As such, we believe that this simple, rapid, sensitive and cost-effective tool can be used for detection and identification of DNA from different shrimp viruses and bacteria.


Assuntos
DNA/genética , Penaeidae/genética , Animais , Aquicultura/métodos , Ásia , Bactérias/genética , Infecções Bacterianas/genética , Infecções Bacterianas/microbiologia , Penaeidae/microbiologia , Penaeidae/virologia , Alimentos Marinhos/microbiologia , Viroses/genética , Viroses/virologia , Vírus/genética
19.
Cancer Sci ; 109(1): 24-32, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29143406

RESUMO

Chronic infection is one of the major causes of cancer, and there are several mechanisms for infection-mediated oncogenesis. Some pathogens encode gene products that behave like oncogenic factors, hijacking cellular pathways to promote the survival and proliferation of infected cells in vivo. Some of these viral oncoproteins trigger a cellular damage defense response leading to senescence; however, other viral factors hinder this suppressive effect, suggesting that cooperation of those viral factors is important for malignant transformation. Coinfection with multiple agents is known to accelerate cancer development in certain cases. For example, parasitic or bacterial infection is a risk factor for adult T-cell leukemia-lymphoma induced by human T-cell leukemia virus type 1, and Epstein-Barr virus and malaria are closely associated with endemic Burkitt lymphoma. Human immunodeficiency virus type 1 infection is accompanied by various types of infection-related cancer. These findings indicate that these oncogenic pathogens can cooperate to overcome host barriers against cancer development. In this review, the authors focus on the collaborative strategies of pathogens for oncogenesis from two different points of view: (i) the cooperation of two or more different factors encoded by a single pathogen; and (ii) the acceleration of oncogenesis by coinfection with multiple agents.


Assuntos
Infecções Bacterianas/genética , Transformação Celular Neoplásica/patologia , Doenças Parasitárias/genética , Viroses/genética , Infecções Bacterianas/complicações , Proliferação de Células , Transformação Celular Neoplásica/genética , Senescência Celular , Coinfecção , Humanos , Proteínas Oncogênicas Virais/metabolismo , Doenças Parasitárias/complicações , Viroses/complicações
20.
J Craniomaxillofac Surg ; 46(1): 128-134, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29198578

RESUMO

Bacterial resistance against conventional antibiotics is increasing. This introduces challenges, for example, in the treatment of infected surgical wounds. Host defence peptides (HDP), which are endogenous peptide antibiotics, show broad-spectrum antimicrobial effectiveness. They protect the organism against pathological microorganisms. Synthetic HDP might supplement or even become alternatives to conventional antibiotics. Knowledge of their quantities under physiological and pathophysiological conditions is therefore required. The influence of gender on HDP expression is unknown. This study evaluates whether gender influences HDP expression in infected or healthy epithelium. Expression levels of HDP human beta-defensin (hBD)-1, -2 and -3 and psoriasin (S100A7) were analysed, by using real-time polymerase chain reaction, in samples of epithelium from infected surgical wounds (n = 20) and healthy epithelium (n = 14) from the neck in a basic medical research study (analytic observational design). The results demonstrated a significantly elevated expression of hBD-2, hBD-3 and psoriasin (P = 0.001 each) in infected epithelium compared with healthy epithelium. No difference in HDP expression levels was evident between samples from female and male patients, either within infected samples or within healthy epithelium samples. Thus, gender does not affect the cutaneous expression of the investigated HDP. This is fundamental knowledge for the study and potential use of HDP derivates as alternative antibiotic substances.


Assuntos
Infecções Bacterianas/metabolismo , Epitélio/metabolismo , Proteína A7 Ligante de Cálcio S100/biossíntese , beta-Defensinas/biossíntese , Adolescente , Adulto , Idoso , Infecções Bacterianas/genética , Pesquisa Biomédica , Feminino , Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Proteína A7 Ligante de Cálcio S100/genética , Fatores Sexuais , Adulto Jovem , beta-Defensinas/genética
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