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1.
Artigo em Inglês | MEDLINE | ID: mdl-38814483

RESUMO

PURPOSE: This study aimed to investigate the clinical and histopathological characteristics of sinonasal seromucinous hamartomas (SHs). METHODS: Eight patients with sinonasal SH and treated at a tertiary hospital between November 2005 and September 2023 were included. Additionally, a systematic review of published articles was conducted, analyzing 48 cases of SH described in the literature. RESULTS: Among the eight patients treated at our institution, tumors originated from the posterior nasal cavity in four patients and middle turbinate and middle meatus were the primary origin in two patients each. Coexistence of inflammatory nasal polyps (NPs) was observed in four cases. Histopathologically, four patients exhibited focal respiratory epithelial adenomatoid hamartoma (REAH) features, and low-grade dysplasia was found in one patient. A combined analysis with previous literature revealed that 46.3% of all cases originated in the anterior nasal cavity. The proportions of cases accompanied by NPs and those with focal REAH features were 20.5% and 39.1%, respectively. Additionally, the frequencies of cases exhibiting dysplastic features (5.4%) and recurrence (2.1%) were low. Remarkably, tumors originating from the anterior region tended to have a higher frequency of dysplasia than those originating from the posterior region, although this difference was not statistically significant (p = 0.0996). CONCLUSION: Patients with sinonasal SH showed favorable treatment outcomes following surgical resection. Focal REAH features and accompanying NPs were frequently observed. A substantial proportion of cases originate in the anterior nasal cavity, and these tumors may exhibit a high tendency for dysplasia.

2.
Biochem Biophys Res Commun ; 571: 125-130, 2021 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-34325127

RESUMO

This study investigated the properties of Latilactobacillus curvatus MS2 isolated from Korean traditional fermented seafood as probiotics and the effect of reducing cholesterol as a synbiotic with isomalto-oligosaccharide (IMO) in BALB/c mice. The isolated strain showed high resistance to acids and bile acids and exhibited a high DPPH scavenging capacity of 72.27 ± 0.38 %. In the intestinal adhesion test using HT-29 cells, the adhesion rate of MS2 was 17.10 ± 1.78 %, which was higher than the adhesion rate of the other investigated probiotics. MS2 showed good antimicrobial activity against food-borne pathogens, especially Staphylococcus aureus, S. epidermidis, Escherichia coli, and Vibrio vulnificus. This strain had high availability for IMO among the prebiotics of fructo-oligosaccharide, inulin and IMO. Oral administration of MS2 and IMO to BALB/c mice for 5 weeks resulted in a significant reduction in blood cholesterol levels by regulating liver lipid metabolism. These results suggest that the combination of MS2 and IMO has potential for application in functional foods.


Assuntos
Colesterol/metabolismo , Fermentação , Lactobacillaceae/isolamento & purificação , Oligossacarídeos/metabolismo , Prebióticos/microbiologia , Alimentos Marinhos/microbiologia , Animais , Masculino , Camundongos , Camundongos Endogâmicos BALB C , República da Coreia , Simbióticos
3.
Int J Mol Sci ; 21(11)2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-32485896

RESUMO

Maternal genes are important in directing early development and determining egg quality in fish. We here report the de novo transcriptome from four tissue libraries of the cyprinid loach, Misgurnus anguillicaudatus, and for the first time identified maternal gene transcripts in unfertilized eggs and suggest their immune system involvement. Expression profiles and functional enrichment revealed a total 24,116 transcripts were expressed as maternal transcripts in unfertilized eggs, which were involved in a wide range of biological functions and pathways. Comparison expression profiles and analysis of tissue specificity revealed that the large numbers of maternal transcripts were stored in unfertilized eggs near the late phase of ovarian maturation and before ovulation. Functional classification showed a total of 279 maternal immune-related transcripts classified with immune system process GO term and immune system KEGG pathway. qPCR analysis showed that transcript levels of identified maternal immune-related candidate genes were dynamically modulated during development and early ontogeny of M. anguillicaudatus. Taken together, this study could not only provide knowledge on the protective roles of maternal immune-related genes during early life stage of M. anguillicaudatus but could also be a valuable transcriptomic/genomic resource for further analysis of maternally provisioned genes in M. anguillicaudatus and other related teleost fishes.


Assuntos
Cipriniformes/genética , Oócitos/metabolismo , Transcriptoma , Animais , Quimiocinas/genética , Quimiocinas/metabolismo , Cipriniformes/imunologia , Feminino , Proteínas de Peixes/genética , Proteínas de Peixes/metabolismo , Masculino , Herança Materna , Fagocitose/genética
4.
Medicina (Kaunas) ; 57(1)2020 12 30.
Artigo em Inglês | MEDLINE | ID: mdl-33396839

RESUMO

Background and objectives: To perform a updated systematic review and meta-analysis comparing effectiveness of percutaneous nephrolithotomy (PCNL), retrograde intrarenal surgery (RIRS), and extracorporeal shock wave lithotripsy (ESWL) for treatment of renal stones (RS). Materials and Methods: A total of 37 studies were included in this systematic review and meta-analysis about effectiveness to treat RS. Endpoints were stone-free rates (SFR), incidence of auxiliary procedure, retreatment, and complications. We also conducted a sub-analysis of ≥2 cm stones. Results: First, PCNL had the highest SFR than others regardless of stone sizes and RIRS showed a higher SFR than ESWL in <2 cm stones. Second, auxiliary procedures were higher in ESWL than others, and it did not differ between PCNL and RIRS. Finally, in <2 cm stones, the retreatment rate of ESWL was higher than others. RIRS required significantly more retreatment procedures than PCNL in ≥2 cm stones. Complication was higher in PCNL than others, but there was no statistically significant difference in complications between RIRS and PCNL in ≥2 cm stones. For ≥2 cm stones, PCNL had the highest SFR, and auxiliary procedures and retreatment rates were significantly lower than others. Conclusions: We suggest that PCNL is a safe and effective treatment, especially for large RS.


Assuntos
Cálculos Renais , Litotripsia , Nefrolitotomia Percutânea , Humanos , Cálculos Renais/cirurgia , Litotripsia/efeitos adversos , Nefrolitotomia Percutânea/efeitos adversos , Retratamento , Resultado do Tratamento
5.
Fish Shellfish Immunol ; 93: 161-173, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31319209

RESUMO

Two liver-expressed antimicrobial peptide 2 (LEAP2) isoforms were characterized in a primitive chondrostean sturgeon species, Acipenser baerii (Acipenseriformes). A. baerii LEAP2 isoforms represented essentially common structures shared by their vertebrate orthologs at both genomic (i.e., tripartite organization) and peptide (two conserved disulfide bonds) levels. A. baerii LEAP2 isoforms (designed LEAP2AB and LEAP2C, respectively) phylogenetically occupy the most basal position in the actinopterygian lineage and represent an intermediate character between teleostean and tetrapodian LEAP2s in the sequence alignment. Molecular phylogenetic analysis including LEAP2s from extant primitive fish species indicated that the evolutionary origin of ancestral LEAP2 in vertebrate groups should date back to earlier than the actinopterygian-sarcopterygian split. Gene expression assays under both basal and stimulated conditions suggested that A. baerii LEAP2 isoforms have undergone substantial subfunctionalization in tissue distribution pattern, developmental/ontogenetic expression, and immune responses. LEAP2AB showed a predominant liver expression, while LEAP2C exhibited the highest level of expression in the intestine. LEAP2C was a more dominantly expressed isoform during embryonic development and prelarval ontogeny. The LEAP2AB isoform is more closely associated with innate immune response to microbial invasion, compared with LEAP2C, as evidenced by results from LPS, poly(I:C) and Aeromonas hydrophila challenges. Synthetic mature peptides of LEAP2AB displayed a more potent antimicrobial activity than did LEAP2C. Data from this study could be useful not only to provide deeper insights into the evolutionary mechanism of LEAP2 in the actinopterygian lineage but also to better understand the innate immunity of this commercially important chondrostean species.


Assuntos
Doenças dos Peixes/imunologia , Peixes/genética , Peixes/imunologia , Regulação da Expressão Gênica/imunologia , Hepcidinas/genética , Hepcidinas/imunologia , Imunidade Inata/genética , Aeromonas hydrophila/fisiologia , Sequência de Aminoácidos , Animais , Feminino , Proteínas de Peixes/química , Proteínas de Peixes/genética , Proteínas de Peixes/imunologia , Perfilação da Expressão Gênica/veterinária , Infecções por Bactérias Gram-Negativas/imunologia , Infecções por Bactérias Gram-Negativas/veterinária , Hepcidinas/química , Lipopolissacarídeos/farmacologia , Filogenia , Poli I-C/farmacologia , Alinhamento de Sequência/veterinária
6.
Fish Shellfish Immunol ; 88: 117-125, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30802630

RESUMO

Hepcidin, a cysteine-rich antimicrobial peptide (AMP), plays key roles as a regulatory hormone in iron homeostasis, providing a link between iron metabolism and innate immunity. Unlike many other AMPs displaying a high degree of sequence variability among closely related organisms, hepcidin is highly conserved from teleosts to mammals. However, little is known about the early ancestry of hepcidins in the vertebrate lineage. Here, we first report potential a prototype hepcidin from the Siberian sturgeon Acipenser baerii, a primitive chondrostean species. The A. baerii hepcidin (AbHAMP) gene showed a tripartite exon-intron organization, which encoded a precursor protein comprised of three structural signatures containing eight cysteine residues, a common structure in vertebrate hepcidin genes and proteins. mRNA expression by iron-overloading and bacterial infection and antibacterial activity revealed that AbHAMP might play a role in iron metabolism regulator in the liver, and in direct and/or indirect host immune response in the kidney against invading pathogen. Comparison of gene and protein sequences reveled that AbHAMP possesses intermediate characteristics between tetrapodian and teleostean hepcidins (HAMP1s). Phylogenetically, AbHAMP had a closer genetic affiliation to tetrapodian orthologs than to teleostean orthologs, suggesting that the structures of this chondrostean hepcidin may closely reflect the structures of an evolutionarily ancestral form that might have evolved into extant hepcidins in tetrapods and teleosts, respectively. Based on the identification of hepcidin from the chondrostean group, the emergence of the common ancestral hepcidin should be traced back to in early Osteichthyes: no later than sarcopterygian (lobe-finned fishes) - actinopterygian (ray-finned fishes) split.


Assuntos
Peixes/genética , Sequência de Aminoácidos , Animais , Bactérias , Infecções Bacterianas/imunologia , Infecções Bacterianas/veterinária , Evolução Biológica , Proteínas de Peixes , Peixes/metabolismo , Peixes/microbiologia , Hepcidinas , Imunidade Inata/genética , Ferro/metabolismo , Fígado/metabolismo , Filogenia , Alinhamento de Sequência
7.
Fish Shellfish Immunol ; 93: 683-693, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31408729

RESUMO

Fish skin mucus is considered to act as the first line of defense against waterborne pathogens and to be potential source of novel antimicrobial components. Here we report the purification and characterization of a novel hepcidin type 2-like antimicrobial peptide (TpHAMP2) from the skin mucus of the pufferfish Takifugu pardalis. The purified TpHAMP2 comprised of 23 amino acids (AAs) with eight Cys residues that form four intramolecular disulfide bonds. The TpHAMP2 gene shared overall structural characteristics with all known hepcidins, which have a tripartite exon-intron gene organization and three structural signatures in the precursor protein. Phylogenetically, TpHAMP2 was classified as HAMP2 class in acanthopterygian fish. Interestingly, the AA sequence of TpHAMP2 did not contain a proprotein cleavage site (RXXR motif) that conserved in most hepcidins and showed a highly positive charged (RKR-) short N-terminus and Val18 and Gly22 residues, which are distinctive structures compared to other known active hepcidins. Recombinant TpHAMP2 identical to the native form exhibited a broad spectrum and potent antimicrobial activity against tested gram-positive and -negative bacteria. Expression of TpHAMP2 mRNA was predominant in the liver and was upregulated in the liver, the spleen, the intestine, and the skin of T. pardalis post immune challenge. Thus, our findings suggests that TpHAMP2 might be of importance in the framework of discovering the fish hepcidins, especially type 2s, and provide noteworthy insight into its gene structure and expression and in the innate immunity as well as the mucosal immunity in regard to hepcidins' evolutionary history in fish species.


Assuntos
Doenças dos Peixes/imunologia , Regulação da Expressão Gênica/imunologia , Hepcidinas/genética , Hepcidinas/imunologia , Imunidade Inata/genética , Takifugu/genética , Takifugu/imunologia , Sequência de Aminoácidos , Animais , Sequência de Bases , Feminino , Proteínas de Peixes/química , Proteínas de Peixes/genética , Proteínas de Peixes/imunologia , Perfilação da Expressão Gênica/veterinária , Hepcidinas/química , Imunidade nas Mucosas/genética , Masculino , Filogenia , Alinhamento de Sequência/veterinária
8.
Fish Shellfish Immunol ; 79: 351-362, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29753144

RESUMO

Invertebrates, unlike vertebrates which have adaptive immune system, rely heavily on the innate immune system for the defense against pathogenic bacteria. Lysozymes, along with other immune effectors, are regarded as an important group in this defense. An invertebrate-type (i-type) lysozyme, designated Urechis unicinctus invertebrate-type lysozyme, Uu-ilys, has been isolated from nephridia of Urechis unicinctus using a series of high performance liquid chromatography (HPLC), and ultrasensitive radial diffusion assay (URDA) as a bioassay system. Analyses of the primary structure and cDNA cloning revealed that Uu-ilys was approximately 14 kDa and composed of 122 amino acids (AAs) of which the precursor had a total of 160 AAs containing a signal peptide of 18 AAs and a pro-sequence of 20 AAs encoded by the nucleotide sequence of 714 bp that comprises a 5' untranslated region (UTR) of 42 bp, an open reading frame (ORF) of 483 bp, and a 3' UTR of 189 bp. Multiple sequence alignment showed Uu-ilys has high homology to i-type lysozymes from several annelids. Relatively high transcriptional expression levels of Uu-ilys was detected in nephridia, anal vesicle, and intestine. The native Uu-ilys exhibited comparable lysozyme enzymatic and antibacterial activities to hen egg white lysozyme. Collectively, these data suggest that Uu-ilys, the isolated antibacterial protein, plays a role in the immune defense mechanism of U. unicinctus. Recombinant Uu-ilys (rUu-ilys) produced in a bacterial expression system showed significantly decreased lysozyme lytic activity from that of the native while its potency on radial diffusion assay detecting antibacterial activity was retained, which may indicate the non-enzymatic antibacterial capacity of Uu-ilys.


Assuntos
Anelídeos/genética , Anelídeos/imunologia , Regulação da Expressão Gênica/imunologia , Imunidade Inata/genética , Muramidase/genética , Muramidase/imunologia , Sequência de Aminoácidos , Animais , Anelídeos/enzimologia , Proteínas de Artrópodes/química , Proteínas de Artrópodes/genética , Proteínas de Artrópodes/imunologia , Sequência de Bases , Perfilação da Expressão Gênica , Muramidase/química , Filogenia , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Alinhamento de Sequência
9.
J Biol Chem ; 290(34): 21042-21053, 2015 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-26116716

RESUMO

The molecular characterization of symbionts is pivotal for understanding the cross-talk between symbionts and hosts. In addition to valuable knowledge obtained from symbiont genomic studies, the biochemical characterization of symbionts is important to fully understand symbiotic interactions. The bean bug (Riptortus pedestris) has been recognized as a useful experimental insect gut symbiosis model system because of its cultivatable Burkholderia symbionts. This system is greatly advantageous because it allows the acquisition of a large quantity of homogeneous symbionts from the host midgut. Using these naïve gut symbionts, it is possible to directly compare in vivo symbiotic cells with in vitro cultured cells using biochemical approaches. With the goal of understanding molecular changes that occur in Burkholderia cells as they adapt to the Riptortus gut environment, we first elucidated that symbiotic Burkholderia cells are highly susceptible to purified Riptortus antimicrobial peptides. In search of the mechanisms of the increased immunosusceptibility of symbionts, we found striking differences in cell envelope structures between cultured and symbiotic Burkholderia cells. The bacterial lipopolysaccharide O antigen was absent from symbiotic cells examined by gel electrophoretic and mass spectrometric analyses, and their membranes were more sensitive to detergent lysis. These changes in the cell envelope were responsible for the increased susceptibility of the Burkholderia symbionts to host innate immunity. Our results suggest that the symbiotic interactions between the Riptortus host and Burkholderia gut symbionts induce bacterial cell envelope changes to achieve successful gut symbiosis.


Assuntos
Burkholderia/química , Parede Celular/química , Heterópteros/microbiologia , Antígenos O/química , Simbiose , Animais , Peptídeos Catiônicos Antimicrobianos/farmacologia , Burkholderia/efeitos dos fármacos , Burkholderia/metabolismo , Burkholderia/fisiologia , Membrana Celular/química , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Parede Celular/efeitos dos fármacos , Parede Celular/metabolismo , Trato Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/imunologia , Trato Gastrointestinal/metabolismo , Trato Gastrointestinal/microbiologia , Heterópteros/imunologia , Heterópteros/metabolismo , Antígenos O/metabolismo
10.
J Neurochem ; 137(1): 33-45, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26801824

RESUMO

Neuropeptides that act as muscle relaxants have been identified in chordates and protostomian invertebrates but little is known about the molecular identity of neuropeptides that act as muscle relaxants in deuterostomian invertebrates (e.g. echinoderms) that are 'evolutionary intermediates' of chordates and protostomes. Here, we have used the apical muscle of the starfish Patiria pectinifera to assay for myorelaxants in extracts of this species. A hexadecapeptide with the amino acid sequence Phe-Gly-Lys-Gly-Gly-Ala-Tyr-Asp-Pro-Leu-Ser-Ala-Gly-Phe-Thr-Asp was identified and designated starfish myorelaxant peptide (SMP). Cloning and sequencing of a cDNA encoding the SMP precursor protein revealed that it comprises 12 copies of SMP as well as 3 peptides (7 copies in total) that are structurally related to SMP. Analysis of the expression of SMP precursor transcripts in P. pectinifera using qPCR revealed the highest expression in the radial nerve cords and lower expression levels in a range of neuromuscular tissues, including the apical muscle, tube feet and cardiac stomach. Consistent with these findings, SMP also caused relaxation of tube foot and cardiac stomach preparations. Furthermore, SMP caused relaxation of apical muscle preparations from another starfish species - Asterias amurensis. Collectively, these data indicate that SMP has a general physiological role as a muscle relaxant in starfish. Interestingly, comparison of the sequence of the SMP precursor with known neuropeptide precursors revealed that SMP belongs to a bilaterian family of neuropeptides that include molluscan pedal peptides (PP) and arthropodan orcokinins (OK). This is the first study to determine the function of a PP/OK-type peptide in a deuterostome. Pedal peptide/orcokinin (PP/OK)-type peptides are a family of structurally related neuropeptides that were first identified and functionally characterised in protostomian invertebrates. Here, we report the discovery of starfish myorelaxant peptide (SMP), a novel member of the PP/OK-type neuropeptide identified in the starfish Patiria pectinifera (phylum Echinodermata). SMP is the first PP/OK-type neuropeptide to be functionally characterised in a deuterostome.


Assuntos
Relaxamento Muscular/efeitos dos fármacos , Fármacos Neuromusculares/isolamento & purificação , Neuropeptídeos/isolamento & purificação , Estrelas-do-Mar/química , Sequência de Aminoácidos , Animais , Asterias , Sequência de Bases , Clonagem Molecular , DNA Complementar/genética , Dados de Sequência Molecular , Músculos/efeitos dos fármacos , Neuropeptídeos/genética , Neuropeptídeos/farmacologia , Neuropeptídeos/fisiologia , Precursores de Proteínas/genética , RNA Mensageiro/biossíntese , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos
11.
EMBO J ; 31(12): 2770-83, 2012 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-22549468

RESUMO

Caspases have been extensively studied as critical initiators and executioners of cell death pathways. However, caspases also take part in non-apoptotic signalling events such as the regulation of innate immunity and activation of nuclear factor-κB (NF-κB). How caspases are activated under these conditions and process a selective set of substrates to allow NF-κB signalling without killing the cell remains largely unknown. Here, we show that stimulation of the Drosophila pattern recognition protein PGRP-LCx induces DIAP2-dependent polyubiquitylation of the initiator caspase DREDD. Signal-dependent ubiquitylation of DREDD is required for full processing of IMD, NF-κB/Relish and expression of antimicrobial peptide genes in response to infection with Gram-negative bacteria. Our results identify a mechanism that positively controls NF-κB signalling via ubiquitin-mediated activation of DREDD. The direct involvement of ubiquitylation in caspase activation represents a novel mechanism for non-apoptotic caspase-mediated signalling.


Assuntos
Proteínas de Transporte/metabolismo , Caspases/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila/imunologia , Regulação da Expressão Gênica , Bactérias Gram-Negativas/imunologia , Proteínas Inibidoras de Apoptose/metabolismo , Ubiquitinação , Animais , Peptídeos Catiônicos Antimicrobianos/biossíntese , Drosophila/genética , Drosophila/microbiologia , Imunidade Inata , Modelos Biológicos , NF-kappa B/metabolismo , Fatores de Transcrição/metabolismo
12.
Fish Shellfish Immunol ; 52: 289-97, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27033467

RESUMO

A 4.7 kDa antimicrobial peptide was purified from the acidified gill extract of the Abalone, Haliotis discus, by cation-exchange and C18 reversed-phase high performance liquid chromatography (HPLC). Comparison of the amino acid sequences and molecular weight of this peptide with those of other known antimicrobial peptides revealed that this antimicrobial peptide have high sequence homology with that of cgMolluscidin and was designated hdMolluscidin. hdMolluscidin is composed of 46 amino acid residues containing several dibasic residue repeats like KK or K-R. hdMolluscidin showed potent antimicrobial activity against both Gram-positive bacteria including Bacillus subtilis and Staphylococcus aureus (minimal effective concentrations [MECs]; 0.8-19.0 µg/mL) and Gram-negative bacteria including Aeromonas hydrophila, Escherichia coli, Pseudomonas aeruginosa, Salmonella enterica, Shigella flexneri, and Vibrio parahemolyticus ([MECs]; 1.0-4.0 µg/mL) without hemolytic activity. However, hdMolluscidin did not show any significant activity against Candida albicans. The secondary structural prediction suggested that hdMolluscidin might not form an ordered or an amphipathic structure. hdMolluscidin did not show membrane permeabilization or leakage ability. The full-length hdMolluscidin cDNA contained 566-bp, including a 5'-untranslated region (UTR) of 63-bp, a 3'-UTR of 359-bp, and an open reading frame of 144-bp encoding 47 amino acids (containing Met). cDNA study of hdMolluscidin suggests that it is expressed as a mature peptide. Our results indicate that hdMolluscidin could relate to the innate immune defenses in abalone and it may not act directly on bacterial membrane.


Assuntos
Peptídeos Catiônicos Antimicrobianos/genética , Gastrópodes/genética , Gastrópodes/imunologia , Sequência de Aminoácidos , Animais , Peptídeos Catiônicos Antimicrobianos/química , Peptídeos Catiônicos Antimicrobianos/metabolismo , Sequência de Bases , Candida albicans/fisiologia , Clonagem Molecular , DNA Complementar/genética , DNA Complementar/metabolismo , Gastrópodes/metabolismo , Gastrópodes/microbiologia , Brânquias/química , Brânquias/imunologia , Brânquias/microbiologia , Bactérias Gram-Negativas/fisiologia , Bactérias Gram-Positivas/fisiologia , Estrutura Secundária de Proteína , Alinhamento de Sequência
13.
J Pept Sci ; 22(10): 628-635, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27506561

RESUMO

A bioactive peptide mimicking peptide-signaling molecules has been isolated from the skin extract of fish Channa argus which caused contraction of the apical muscle of a starfish Patiria pectinifera, a deuterostomian invertebrate. The primary structure of the isolated pentapeptide comprises amino acid sequence of H-Pro-Ala-Leu-Ala-Leu-OH (PALAL) with a molecular mass of 483.7 Da. Pharmacological activity of PALAL, dosage ranging from 10-9 to 10-5 M, revealed concentration-dependent contraction of the apical muscles of P. pectinifera and Asterias amurensis. However, PALAL was not active on the intestinal smooth muscle of the goldfish Carassius auratus and has presumably other physiological roles in fish skin. Investigation of structure-activity relationship using truncated and substituted analogs of PALAL demonstrated that H-Ala-Leu-Ala-Leu-OH was necessary and should be sufficient to constrict apical muscle of P. pectinifera. Furthermore, the second alanine residue was required to display the activity, and the fifth leucine residue was responsible for its potency. Comparison with PALAL's primary structure with those of other known bioactive peptides from fish and starfish revealed that PALAL does not have any significant homology. Consequently, PALAL is a bioactive peptide that elicits a muscle contraction in starfish, and the isolation of PALAL may lead to develop other bioactive peptides sharing its similar sequence and/or activity. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.


Assuntos
Proteínas de Peixes/farmacologia , Contração Muscular/efeitos dos fármacos , Músculos/efeitos dos fármacos , Oligopeptídeos/farmacologia , Pele/química , Sequência de Aminoácidos , Animais , Relação Dose-Resposta a Droga , Proteínas de Peixes/síntese química , Proteínas de Peixes/isolamento & purificação , Peixes/metabolismo , Peso Molecular , Contração Muscular/fisiologia , Músculos/fisiologia , Oligopeptídeos/síntese química , Oligopeptídeos/isolamento & purificação , Estrelas-do-Mar/efeitos dos fármacos , Estrelas-do-Mar/fisiologia , Relação Estrutura-Atividade
14.
J Biol Chem ; 289(29): 20092-101, 2014 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-24891502

RESUMO

In Drosophila, the Imd pathway is activated by diaminopimelic acid-type peptidoglycan and triggers the humoral innate immune response, including the robust induction of antimicrobial peptide gene expression. Imd and Relish, two essential components of this pathway, are both endoproteolytically cleaved upon immune stimulation. Genetic analyses have shown that these cleavage events are dependent on the caspase-8 like Dredd, suggesting that Imd and Relish are direct substrates of Dredd. Among the seven Drosophila caspases, we find that Dredd uniquely promotes Imd and Relish processing, and purified recombinant Dredd cleaves Imd and Relish in vitro. In addition, interdomain cleavage of Dredd is not required for Imd or Relish processing and is not observed during immune stimulation. Baculovirus p35, a suicide substrate of executioner caspases, is not cleaved by purified Dredd in vitro. Consistent with this biochemistry but contrary to earlier reports, p35 does not interfere with Imd signaling in S2* cells or in vivo.


Assuntos
Caspases/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila/metabolismo , Fatores de Transcrição/metabolismo , Proteínas Virais/metabolismo , Sequência de Aminoácidos , Substituição de Aminoácidos , Animais , Animais Geneticamente Modificados , Caspase 8/metabolismo , Caspases/química , Caspases/genética , Linhagem Celular , Drosophila/genética , Drosophila/imunologia , Proteínas de Drosophila/química , Proteínas de Drosophila/genética , Feminino , Dados de Sequência Molecular , Mutagênese Sítio-Dirigida , Domínios e Motivos de Interação entre Proteínas , Processamento de Proteína Pós-Traducional , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Transdução de Sinais , Especificidade por Substrato
15.
J Immunol ; 191(6): 3319-27, 2013 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-23966633

RESUMO

The human pathogen Staphylococcus aureus is responsible for many community-acquired and hospital-associated infections and is associated with high mortality. Concern over the emergence of multidrug-resistant strains has renewed interest in the elucidation of host mechanisms that defend against S. aureus infection. We recently demonstrated that human serum mannose-binding lectin binds to S. aureus wall teichoic acid (WTA), a cell wall glycopolymer--a discovery that prompted further screening to identify additional serum proteins that recognize S. aureus cell wall components. In this report, we incubated human serum with 10 different S. aureus mutants and determined that serum amyloid P component (SAP) bound specifically to a WTA-deficient S. aureus ΔtagO mutant, but not to tagO-complemented, WTA-expressing cells. Biochemical characterization revealed that SAP recognizes bacterial peptidoglycan as a ligand and that WTA inhibits this interaction. Although SAP binding to peptidoglycan was not observed to induce complement activation, SAP-bound ΔtagO cells were phagocytosed by human polymorphonuclear leukocytes in an FcγR-dependent manner. These results indicate that SAP functions as a host defense factor, similar to other peptidoglycan recognition proteins and nucleotide-binding oligomerization domain-like receptors.


Assuntos
Proteínas de Transporte/imunologia , Fagocitose/imunologia , Componente Amiloide P Sérico/imunologia , Infecções Estafilocócicas/imunologia , Staphylococcus aureus/imunologia , Western Blotting , Citometria de Fluxo , Humanos
16.
Appl Environ Microbiol ; 80(14): 4374-82, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24814787

RESUMO

The Riptortus-Burkholderia symbiotic system is an experimental model system for studying the molecular mechanisms of an insect-microbe gut symbiosis. When the symbiotic midgut of Riptortus pedestris was investigated by light and transmission electron microscopy, the lumens of the midgut crypts that harbor colonizing Burkholderia symbionts were occupied by an extracellular matrix consisting of polysaccharides. This observation prompted us to search for symbiont genes involved in the induction of biofilm formation and to examine whether the biofilms are necessary for the symbiont to establish a successful symbiotic association with the host. To answer these questions, we focused on purN and purT, which independently catalyze the same step of bacterial purine biosynthesis. When we disrupted purN and purT in the Burkholderia symbiont, the ΔpurN and ΔpurT mutants grew normally, and only the ΔpurT mutant failed to form biofilms. Notably, the ΔpurT mutant exhibited a significantly lower level of cyclic-di-GMP (c-di-GMP) than the wild type and the ΔpurN mutant, suggesting involvement of the secondary messenger c-di-GMP in the defect of biofilm formation in the ΔpurT mutant, which might operate via impaired purine biosynthesis. The host insects infected with the ΔpurT mutant exhibited a lower infection density, slower growth, and lighter body weight than the host insects infected with the wild type and the ΔpurN mutant. These results show that the function of purT of the gut symbiont is important for the persistence of the insect gut symbiont, suggesting the intricate biological relevance of purine biosynthesis, biofilm formation, and symbiosis.


Assuntos
Biofilmes , Trato Gastrointestinal/microbiologia , Heterópteros/microbiologia , Purinas/biossíntese , Simbiose , Animais , Burkholderia/genética , Burkholderia/metabolismo , GMP Cíclico/metabolismo , Escherichia coli/crescimento & desenvolvimento , Genes Bacterianos , Microscopia Eletrônica de Transmissão , Mutação , Polissacarídeos/metabolismo
17.
Appl Environ Microbiol ; 79(23): 7229-33, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24038695

RESUMO

Many insects possess symbiotic bacteria that affect the biology of the host. The level of the symbiont population in the host is a pivotal factor that modulates the biological outcome of the symbiotic association. Hence, the symbiont population should be maintained at a proper level by the host's control mechanisms. Several mechanisms for controlling intracellular symbionts of insects have been reported, while mechanisms for controlling extracellular gut symbionts of insects are poorly understood. The bean bug Riptortus pedestris harbors a betaproteobacterial extracellular symbiont of the genus Burkholderia in the midgut symbiotic organ designated the M4 region. We found that the M4B region, which is directly connected to the M4 region, also harbors Burkholderia symbiont cells, but the symbionts therein are mostly dead. A series of experiments demonstrated that the M4B region exhibits antimicrobial activity, and the antimicrobial activity is specifically potent against the Burkholderia symbiont but not the cultured Burkholderia and other bacteria. The antimicrobial activity of the M4B region was detected in symbiotic host insects, reaching its highest point at the fifth instar, but not in aposymbiotic host insects, which suggests the possibility of symbiont-mediated induction of the antimicrobial activity. This antimicrobial activity was not associated with upregulation of antimicrobial peptides of the host. Based on these results, we propose that the M4B region is a specialized gut region of R. pedestris that plays a critical role in controlling the population of the Burkholderia gut symbiont. The molecular basis of the antimicrobial activity is of great interest and deserves future study.


Assuntos
Burkholderia/fisiologia , Insetos/microbiologia , Simbiose , Animais , Burkholderia/crescimento & desenvolvimento , Trato Gastrointestinal/microbiologia , Viabilidade Microbiana
18.
Genes (Basel) ; 14(9)2023 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-37761822

RESUMO

Aquaculture assumes a pivotal role in meeting the escalating global food demand, and shrimp farming, in particular, holds a significant role in the global economy and food security, providing a rich source of nutrients for human consumption. Nonetheless, the industry faces formidable challenges, primarily attributed to disease outbreaks and the diminishing efficacy of conventional disease management approaches, such as antibiotic usage. Consequently, there is an urgent imperative to explore alternative strategies to ensure the sustainability of the industry. In this context, the field of epigenetics emerges as a promising avenue for combating infectious diseases in shrimp aquaculture. Epigenetic modulations entail chemical alterations in DNA and proteins, orchestrating gene expression patterns without modifying the underlying DNA sequence through DNA methylation, histone modifications, and non-coding RNA molecules. Utilizing epigenetic mechanisms presents an opportunity to enhance immune gene expression and bolster disease resistance in shrimp, thereby contributing to disease management strategies and optimizing shrimp health and productivity. Additionally, the concept of epigenetic inheritability in marine animals holds immense potential for the future of the shrimp farming industry. To this end, this comprehensive review thoroughly explores the dynamics of epigenetic modulations in shrimp aquaculture, with a particular emphasis on its pivotal role in disease management. It conveys the significance of harnessing advantageous epigenetic changes to ensure the long-term viability of shrimp farming while deliberating on the potential consequences of these interventions. Overall, this appraisal highlights the promising trajectory of epigenetic applications, propelling the field toward strengthening sustainability in shrimp aquaculture.


Assuntos
Aquicultura , Doenças Transmissíveis , Animais , Humanos , Alimentos Marinhos , Agricultura , Crustáceos/genética , Epigênese Genética
19.
Antibiotics (Basel) ; 12(8)2023 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-37627706

RESUMO

The incidence of carbapenem-resistant Enterobacteriaceae (CRE) has been increasing since 2008, with Gyeonggi Province in South Korea being particularly vulnerable due to its large number of healthcare facilities. This study examines the trends of CRE occurrence in Gyeonggi Province over the past four years and the epidemiological characteristics of the infected patients. Patients with positive CRE blood cultures admitted to healthcare facilities in Gyeonggi Province from January 2018 to December 2021 were evaluated in this study. Risk factors for CRE-related death were analyzed using data from patients who died within 30 days of the last blood sampling. Older adults aged 70 years and above constituted the majority of patients with CRE bacteremia. Antibiotic use did not significantly affect mortality risk. Non-survivors were more common in tertiary hospitals and intensive care units and included patients with hypertension, malignant tumors, and multiple underlying diseases. Klebsiella pneumoniae was the most common CRE strain, with Klebsiella pneumoniae carbapenemase being the predominant carbapenemase. Our study suggests the endemicity of CRE in Gyeonggi Province and highlights the increasing isolation of CRE strains in South Korean long-term care hospitals within the province. Further, infection control measures and government support specific to each healthcare facility type are crucial.

20.
Proc Natl Acad Sci U S A ; 106(24): 9779-84, 2009 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-19497884

RESUMO

The Drosophila NF-kappaB transcription factor Relish is an essential regulator of antimicrobial peptide gene induction after gram-negative bacterial infection. Relish is a bipartite NF-kappaB precursor protein, with an N-terminal Rel homology domain and a C-terminal IkappaB-like domain, similar to mammalian p100 and p105. Unlike these mammalian homologs, Relish is endoproteolytically cleaved after infection, allowing the N-terminal NF-kappaB module to translocate to the nucleus. Signal-dependent activation of Relish, including cleavage, requires both the Drosophila IkappaB kinase (IKK) and death-related ced-3/Nedd2-like protein (DREDD), the Drosophila caspase-8 like protease. In this report, we show that the IKK complex controls Relish by direct phosphorylation on serines 528 and 529. Surprisingly, these phosphorylation sites are not required for Relish cleavage, nuclear translocation, or DNA binding. Instead they are critical for recruitment of RNA polymerase II and antimicrobial peptide gene induction, whereas IKK functions noncatalytically to support Dredd-mediated cleavage of Relish.


Assuntos
Anti-Infecciosos , Proteínas de Drosophila/metabolismo , Proteínas de Drosophila/fisiologia , Regulação da Expressão Gênica , Quinase I-kappa B/fisiologia , Peptídeos/genética , Fatores de Transcrição/metabolismo , Animais , Drosophila , Proteínas de Drosophila/química , Epistasia Genética , Quinase I-kappa B/química , Fosforilação , Regiões Promotoras Genéticas , Serina/metabolismo
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