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1.
Immunity ; 55(3): 494-511.e11, 2022 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-35263568

RESUMO

Interleukin (IL)-22 is central to immune defense at barrier sites. We examined the contributions of innate lymphoid cell (ILC) and T cell-derived IL-22 during Citrobacter rodentium (C.r) infection using mice that both report Il22 expression and allow lineage-specific deletion. ILC-derived IL-22 activated STAT3 in C.r-colonized surface intestinal epithelial cells (IECs) but only temporally restrained bacterial growth. T cell-derived IL-22 induced a more robust and extensive activation of STAT3 in IECs, including IECs lining colonic crypts, and T cell-specific deficiency of IL-22 led to pathogen invasion of the crypts and increased mortality. This reflected a requirement for T cell-derived IL-22 for the expression of a host-protective transcriptomic program that included AMPs, neutrophil-recruiting chemokines, and mucin-related molecules, and it restricted IFNγ-induced proinflammatory genes. Our findings demonstrate spatiotemporal differences in the production and action of IL-22 by ILCs and T cells during infection and reveal an indispensable role for IL-22-producing T cells in the protection of the intestinal crypts.


Assuntos
Citrobacter rodentium , Infecções por Enterobacteriaceae , Animais , Antibacterianos , Imunidade Inata , Interleucinas/metabolismo , Mucosa Intestinal , Linfócitos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Linfócitos T/metabolismo , Interleucina 22
2.
Brief Bioinform ; 25(2)2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38446739

RESUMO

Antimicrobial peptides (AMPs), short peptides with diverse functions, effectively target and combat various organisms. The widespread misuse of chemical antibiotics has led to increasing microbial resistance. Due to their low drug resistance and toxicity, AMPs are considered promising substitutes for traditional antibiotics. While existing deep learning technology enhances AMP generation, it also presents certain challenges. Firstly, AMP generation overlooks the complex interdependencies among amino acids. Secondly, current models fail to integrate crucial tasks like screening, attribute prediction and iterative optimization. Consequently, we develop a integrated deep learning framework, Diff-AMP, that automates AMP generation, identification, attribute prediction and iterative optimization. We innovatively integrate kinetic diffusion and attention mechanisms into the reinforcement learning framework for efficient AMP generation. Additionally, our prediction module incorporates pre-training and transfer learning strategies for precise AMP identification and screening. We employ a convolutional neural network for multi-attribute prediction and a reinforcement learning-based iterative optimization strategy to produce diverse AMPs. This framework automates molecule generation, screening, attribute prediction and optimization, thereby advancing AMP research. We have also deployed Diff-AMP on a web server, with code, data and server details available in the Data Availability section.


Assuntos
Aminoácidos , Peptídeos Antimicrobianos , Antibacterianos , Difusão , Cinética
3.
Exp Cell Res ; 439(1): 114092, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38754617

RESUMO

Asymmetric stem cell divisions play instrumental roles in the maintenance, growth and differentiation of organs. Failure of asymmetric stem cell divisions may result in an array of developmental disorders, including cancer. It is well established that the gene, inscuteable, acts as the upstream component of asymmetric cell divisions. In Drosophila larval midgut, a founder adult midgut precursor (AMP) experiences an asymmetric division to instruct its first daughter to become a peripheral cell that serves as a niche where the AMP and its future daughters can remain undifferentiated. The present study demonstrates that inscuteable expressing stem cells require Rab11, a conserved small Ras-like GTPase, for proper proliferation and differentiation. As insc-GAL4 mediated Rab11RNAi in Drosophila larval and adult midguts show the disruption of the niche microenvironment of adult midgut precursors as well as elevated DPP signalling at the larval stage, which is associated with aberrant over-proliferation and early differentiation of larval AMPs and adult intestinal stem cells. The observed connections between Rab11, larval AMP proliferation, niche establishment, and DPP signalling highlight the potential for Rab11 to serve as a key regulatory factor in maintaining tissue homeostasis and balanced cellular growth.


Assuntos
Diferenciação Celular , Proteínas de Drosophila , Larva , Transdução de Sinais , Proteínas rab de Ligação ao GTP , Animais , Diferenciação Celular/genética , Proteínas de Drosophila/metabolismo , Proteínas de Drosophila/genética , Proteínas rab de Ligação ao GTP/metabolismo , Proteínas rab de Ligação ao GTP/genética , Larva/crescimento & desenvolvimento , Larva/metabolismo , Larva/genética , Proliferação de Células , Células-Tronco/metabolismo , Células-Tronco/citologia , Drosophila melanogaster/metabolismo , Drosophila melanogaster/genética , Drosophila melanogaster/crescimento & desenvolvimento , Nicho de Células-Tronco
4.
Biol Chem ; 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38766708

RESUMO

Amphibians are well-known for their ability to produce and secrete a mixture of bioactive substances in specialized skin glands for the purpose of antibiotic self-protection and defense against predators. Some of these secretions contain various small molecules, such as the highly toxic batrachotoxin, tetrodotoxin, and samandarine. For some time, the presence of peptides in amphibian skin secretions has attracted researchers, consisting of a diverse collection of - to the current state of knowledge - three to 104 amino acid long sequences. From these more than 2000 peptides many are known to exert antimicrobial effects. In addition, there are some reports on amphibian skin peptides that can promote wound healing, regulate immunoreactions, and may serve as antiparasitic and antioxidative substances. So far, the focus has mainly been on skin peptides from frogs and toads (Anura), eclipsing the research on skin peptides of the ca. 700 salamanders and newts (Caudata). Just recently, several novel observations dealing with caudate peptides and their structure-function relationships were reported. This review focuses on the chemistry and bioactivity of caudate amphibian skin peptides and their potential as novel agents for clinical applications.

5.
Arch Microbiol ; 206(6): 280, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38805035

RESUMO

Antimicrobial resistance poses a significant global health threat, necessitating innovative approaches for combatting it. This review explores various mechanisms of antimicrobial resistance observed in various strains of bacteria. We examine various strategies, including antimicrobial peptides (AMPs), novel antimicrobial materials, drug delivery systems, vaccines, antibody therapies, and non-traditional antibiotic treatments. Through a comprehensive literature review, the efficacy and challenges of these strategies are evaluated. Findings reveal the potential of AMPs in combating resistance due to their unique mechanisms and lower propensity for resistance development. Additionally, novel drug delivery systems, such as nanoparticles, show promise in enhancing antibiotic efficacy and overcoming resistance mechanisms. Vaccines and antibody therapies offer preventive measures, although challenges exist in their development. Non-traditional antibiotic treatments, including CRISPR-Cas systems, present alternative approaches to combat resistance. Overall, this review underscores the importance of multifaceted strategies and coordinated global efforts to address antimicrobial resistance effectively.


Assuntos
Antibacterianos , Bactérias , Farmacorresistência Bacteriana , Bactérias/efeitos dos fármacos , Bactérias/genética , Humanos , Antibacterianos/farmacologia , Peptídeos Antimicrobianos/farmacologia , Peptídeos Antimicrobianos/genética , Sistemas de Liberação de Medicamentos , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/microbiologia , Sistemas CRISPR-Cas , Animais
6.
Fish Shellfish Immunol ; 152: 109772, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39019125

RESUMO

Aquaculture is a prosperous economic sector threatened by viral infections. Among the viruses threatening fish culture, Betanodavirus (NNV) is extremely important in the Mediterranean Sea affecting to highly traded species as European sea bass. In this context, application of antimicrobial peptides (AMPs) has arisen as a potential biotechnological tool. The aim of this work was to evaluate the therapeutic application of two European sea bass-derived AMPs, NK-lysin (Nkl) and dicentracin (Dic), against NNV infections. Synthetic Dic peptide was able to significantly reduce NNV-induced mortalities while Nkl failed to do so. Although neither Dic nor Nkl peptides were able to alter the transcriptional levels of NNV and the number of infected cells, Nkl seemed to increase the viral load per cell. Interestingly, both Nkl and Dic peptides showed immunomodulatory roles. For instance, our data revealed an interplay among different AMPs, at both gene and protein levels. Otherwise, Nkl and Dic peptides provoked an anti-inflammatory balance upon NNV infection, as well as the recruitment of macrophages and B cells to the target site of the infection, the brain. In conclusion, Dic can be proposed as a therapeutic candidate to combat NNV.


Assuntos
Bass , Doenças dos Peixes , Nodaviridae , Infecções por Vírus de RNA , Nodaviridae/fisiologia , Animais , Bass/imunologia , Doenças dos Peixes/imunologia , Doenças dos Peixes/tratamento farmacológico , Doenças dos Peixes/virologia , Infecções por Vírus de RNA/imunologia , Infecções por Vírus de RNA/veterinária , Infecções por Vírus de RNA/tratamento farmacológico , Proteolipídeos/farmacologia , Proteolipídeos/imunologia , Proteínas de Peixes/imunologia , Proteínas de Peixes/genética , Proteínas de Peixes/farmacologia , Proteínas de Peixes/química , Peptídeos Antimicrobianos/farmacologia , Peptídeos Antimicrobianos/química , Agentes de Imunomodulação/farmacologia , Agentes de Imunomodulação/química
7.
J Pept Sci ; 30(7): e3593, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38471710

RESUMO

In recent decades, the global rise of viral emerging infectious diseases has posed a substantial threat to both human and animal health worldwide. The rapid spread and accumulation of mutations into viruses, and the limited availability of antiviral drugs and vaccines, stress the urgent need for alternative therapeutic strategies. Antimicrobial peptides (AMPs) derived from natural sources present a promising avenue due to their specificity and effectiveness against a broad spectrum of pathogens. The present study focuses on investigating the antiviral potential of oreochromicin-1 (oreoch-1), a fish-derived AMP obtained from Nile tilapia, against a wide panel of animal viruses including canine distemper virus (CDV), Schmallenberg virus (SBV), caprine herpesvirus 1 (CpHV-1), and bovine herpesvirus 1 (BoHV-1). Oreoch-1 exhibited a strong antiviral effect, demonstrating an inhibition of infection at concentrations in the micromolar range. The mechanism of action involves the interference with viral entry into host cells and a direct interaction between oreoch-1 and the viral envelope. In addition, we observed that the peptide could also interact with the cell during the CDV infection. These findings not only highlight the efficacy of oreoch-1 in inhibiting viral infection but also emphasize the potential of fish-derived peptides, specifically oreoch-1, as effective antiviral agents against viral infections affecting animals, whose potential to spill into humans is high. This research contributes valuable insights to the ongoing quest for novel antiviral drugs with the potential to mitigate the impact of infectious diseases on a global scale.


Assuntos
Antivirais , Animais , Antivirais/farmacologia , Antivirais/química , Peptídeos Antimicrobianos/farmacologia , Peptídeos Antimicrobianos/química , Humanos , Testes de Sensibilidade Microbiana , Chlorocebus aethiops , Internalização do Vírus/efeitos dos fármacos
8.
Mar Drugs ; 22(2)2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38393057

RESUMO

Antimicrobial peptides (AMPs) are promising molecules in diverse fields, including aquaculture. AMPs possess lytic effects on a wide range of pathogens, resulting in a potential replacement for traditional antimicrobials in aquaculture. In addition, they also have modulatory effects on host immune responses. Thus, the objective of this work was to evaluate the immunomodulatory capability of three known synthetic AMPs derived from European sea bass, NK-lysin (Nkl), hepcidin (Hamp), and dicentracin (Dic), in head-kidney cell suspensions from European sea bass and gilthead seabream. The tested peptides were neither cytotoxic for European sea bass nor gilthead seabream cells and failed to modulate the respiratory burst and phagocytosis activities. However, they modified the pattern of transcription of immune-related genes differently in both species. Peptides were able to promote the expression of marker genes for anti-inflammatory (il10), antiviral (mx, irf3), cell-mediated cytotoxicity (nccrp1, gzmb), and antibody responses (ighm) in European sea bass, with the Nkl peptide being the most effective. Contrary to this, the effects of those peptides on gilthead seabream mainly resulted in the suppression of immune responses. To conclude, European sea bass-derived peptides can be postulated as potential tools for immunostimulation in European sea bass fish farms, but more efforts are required for their universal use in other species.


Assuntos
Bass , Doenças dos Peixes , Dourada , Animais , Peptídeos Antimicrobianos , Bass/genética , Dourada/genética , Imunidade , Perfilação da Expressão Gênica , Imunidade Inata
9.
Int J Mol Sci ; 25(8)2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38673881

RESUMO

Interstitial lung diseases (ILDs) are characterized by inflammation or fibrosis of the pulmonary parenchyma. Despite the involvement of immune cells and soluble mediators in pulmonary fibrosis, the influence of antimicrobial peptides (AMPs) remains underexplored. These effector molecules display a range of activities, which include immunomodulation and wound repair. Here, we investigate the role of AMPs in the development of fibrosis in ILD. We compare the concentration of different AMPs and different cytokines in 46 fibrotic (F-ILD) and 17 non-fibrotic (NF-ILD) patients by ELISA and using peripheral blood mononuclear cells from in vitro stimulation in the presence of lysozyme or secretory leukocyte protease inhibitor (SLPI) from 10 healthy donors. We observed that bronchoalveolar lavage (BAL) levels of AMPs were decreased in F-ILD patients (lysozyme: p < 0.001; SLPI: p < 0.001; LL-37: p < 0.001; lactoferrin: p = 0.47) and were negatively correlated with levels of TGF-ß (lysozyme: p = 0.02; SLPI: p < 0.001) and IL-17 (lysozyme: p < 0.001; SLPI: p < 0.001). We observed that lysozyme increased the percentage of CD86+ macrophages (p < 0.001) and the production of TNF-α (p < 0.001). We showed that lysozyme and SLPI were associated with clinical parameters (lysozyme: p < 0.001; SLPI: p < 0.001) and disease progression (lysozyme: p < 0.001; SLPI: p = 0.01). These results suggest that AMPs may play an important role in the anti-fibrotic response, regulating the effect of pro-fibrotic cytokines. In addition, levels of lysozyme in BAL may be a potential biomarker to predict the progression in F-ILD patients.


Assuntos
Líquido da Lavagem Broncoalveolar , Doenças Pulmonares Intersticiais , Muramidase , Inibidor Secretado de Peptidases Leucocitárias , Humanos , Muramidase/metabolismo , Masculino , Feminino , Pessoa de Meia-Idade , Inibidor Secretado de Peptidases Leucocitárias/metabolismo , Líquido da Lavagem Broncoalveolar/química , Doenças Pulmonares Intersticiais/metabolismo , Doenças Pulmonares Intersticiais/patologia , Idoso , Citocinas/metabolismo , Adulto , Biomarcadores , Lavagem Broncoalveolar , Leucócitos Mononucleares/metabolismo
10.
Curr Issues Mol Biol ; 45(4): 3674-3704, 2023 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-37185763

RESUMO

Antimicrobial peptides (AMPs) are short polypeptide molecules produced by multicellular organisms that are involved in host defense and microbiome preservation. In recent years, AMPs have attracted attention as novel drug candidates. However, their successful use requires detailed knowledge of the mode of action and identification of the determinants of biological activity. In this review, we focused on structure-function relationships in the thionins, α-hairpinins, hevein-like peptides, and the unique Ib-AMP peptides isolated from Impatiens balsamina. We summarized the available data on the amino acid sequences and 3D structure of peptides, their biosynthesis, and their biological activity. Special attention was paid to the determination of residues that play a key role in the activity and the identification of the minimal active cores. We have shown that even subtle changes in amino acid sequences can affect the biological activity of AMPs, which opens up the possibility of creating molecules with improved properties, better therapeutic efficacy, and cheaper large-scale production.

11.
Development ; 147(4)2020 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-32001438

RESUMO

Despites several decades of studies on the neuromuscular system, the relationship between muscle stem cells and motor neurons remains elusive. Using the Drosophila model, we provide evidence that adult muscle precursors (AMPs), the Drosophila muscle stem cells, interact with the motor axons during embryogenesis. AMPs not only hold the capacity to attract the navigating intersegmental (ISN) and segmental a (SNa) nerve branches, but are also mandatory to the innervation of muscles in the lateral field. This so-far-ignored AMP role involves their filopodia-based interactions with nerve growth cones. In parallel, we report the previously undetected expression of the guidance molecule-encoding genes sidestep and side IV in AMPs. Altogether, our data support the view that Drosophila muscle stem cells represent spatial landmarks for navigating motor neurons and reveal that their positioning is crucial for the muscles innervation in the lateral region. Furthermore, AMPs and motor axons are interdependent, as the genetic ablation of SNa leads to a specific loss of SNa-associated lateral AMPs.


Assuntos
Axônios/fisiologia , Neurônios Motores/fisiologia , Músculos/embriologia , Músculos/inervação , Mioblastos/fisiologia , Animais , Apoptose , Orientação de Axônios , Movimento Celular , Proteínas de Drosophila/fisiologia , Drosophila melanogaster/embriologia , Genótipo , Proteínas de Fluorescência Verde , Cones de Crescimento/fisiologia , Imuno-Histoquímica , Hibridização In Situ , Proteínas de Membrana/fisiologia , Microscopia de Fluorescência , Pseudópodes/fisiologia , Transdução de Sinais , Células-Tronco/citologia
12.
Microb Ecol ; 87(1): 8, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38036921

RESUMO

Changes in the structure and function of the microbiota are associated with various human diseases. These microbial changes can be mediated by antimicrobial peptides (AMPs), small peptides produced by the host and their microbiota, which play a crucial role in host-bacteria co-evolution. Thus, by studying AMPs produced by the microbiota (microbial AMPs), we can better understand the interactions between host and bacteria in microbiome homeostasis. Additionally, microbial AMPs are a new source of compounds against pathogenic and multi-resistant bacteria. Further, the growing accessibility to metagenomic and metatranscriptomic datasets presents an opportunity to discover new microbial AMPs. This review examines the structural properties of microbiota-derived AMPs, their molecular action mechanisms, genomic organization, and strategies for their identification in any microbiome data as well as experimental testing. Overall, we provided a comprehensive overview of this important topic from the microbial perspective.


Assuntos
Peptídeos Catiônicos Antimicrobianos , Microbiota , Humanos , Peptídeos Catiônicos Antimicrobianos/genética , Peptídeos Catiônicos Antimicrobianos/farmacologia , Peptídeos Antimicrobianos , Bactérias/genética , Microbiota/genética , Antibacterianos
13.
Fish Shellfish Immunol ; 141: 109061, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37683807

RESUMO

Vibrio harveyi is the primary pathogenic bacteria affecting Nibea albiflora aquaculture. In a previous phase, our laboratory intentionally exposed N. albiflora to V. harveyi and analyzed the outcomes using a combination of genome-wide association study (GWAS) and RNA-seq. The results revealed that the antimicrobial peptide NK-lysin (YdNkl-1) was a candidate gene for resistance to V. harveyi disease in N. albiflora. To investigate the role of the antimicrobial peptide NK-lysin in N. albiflora's antimicrobial immunity, we screened the YdNkl-1 gene from the transcriptome database. The full-length cDNA of YdNkl-1 gene is 508 bp, with an open reading frame (ORF) of 477 bp, encoding 158 amino acids. The deduced amino acid sequence of YdNkl-1 contains a signal peptide (1st-22nd amino acids) and a Saposin B domain (50th-124th amino acids), akin to mammalian NK-lysin. Phylogenetic tree analysis confirmed that the NK-lysin of teleost fish clustered into a single species, and YdNkl-1 was most closely related to Larimichthys crocea. Subcellular localization showed that YdNkl-1 was distributed in cytoplasm and nucleus of yellow drum kidney cells. Furthermore, YdNkl-1 mRNA transcripts were significantly up-regulated in the skin, gill, intestine, head-kidney, liver, and spleen after V. harveyi infection, suggesting a critical role in N. albiflora's defense against V. harveyi infection. Additionally, we purified and observed the YdNkl-1 protein, which exhibited a potent membrane-disrupting effect on V. harveyi, Pseudomonas plecoglossicida, Vibrio parahaemolyticus, Escherichia coli and Bacillus subtilis. These findings underscore the significance of NK-lysin in N. albiflora's resistance to V. harveyi infection and provide new insights into the crucial role of NK-lysin in the innate immunity of teleost fishes.


Assuntos
Doenças dos Peixes , Perciformes , Vibrio parahaemolyticus , Animais , Filogenia , Estudo de Associação Genômica Ampla , Sequência de Bases , Proteínas de Peixes/química , Perciformes/genética , Perciformes/metabolismo , Antibacterianos , Peixes/genética , Vibrio parahaemolyticus/genética , Imunidade Inata/genética , Clonagem Molecular , Peptídeos Antimicrobianos , Mamíferos/metabolismo
14.
Fish Shellfish Immunol ; 135: 108691, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36924911

RESUMO

Antimicrobial peptides (AMPs) play important roles in the immune defense against pathogenic microorganisms. For instance, histone 2A (H2A)-derived AMPs is an antimicrobial peptide involved in the host's innate immune defense and immunoregulation. AMPs have been isolated from the pearl oyster Pinctada fucata martensii but their role in host defense remains poorly understood. To elucidate the structural features of P. f. martensii H2A (PmH2A)-derived AMPs and their potential immune functions, we synthesized a series of laboratory-designed synthetic analogs of PmH2A and examined their antimicrobial properties, as well as their mechanisms of action. This analysis revealed inhibitory effects on the growth of Gram-positive and Gram-negative bacteria. Further assessment by transmission electron microscopy (TEM) of two of the three peptides, PmH2A-AMP and PmH2A-AMP(5-13)[KLLK]3, confirmed that it exerted an anti-bacterial activity through membrane lysis. Finally, we found that the hemocytes and gills of P. f. martensii released antimicrobial H2A histones in response to LPS exposure, mimicking tissue damage and infection. This immune response is reminiscent of the neutrophil extracellular traps (NETs) recently described in oysters. Thus, the LPS challenge is sufficient to induce histone-derived peptide accumulation in pearl oyster P.f. martensii.


Assuntos
Pinctada , Animais , Histonas , Peptídeos Antimicrobianos , Lipopolissacarídeos/farmacologia , Antibacterianos/farmacologia , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Peptídeos/farmacologia
15.
Fish Shellfish Immunol ; 134: 108649, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36849046

RESUMO

With the antibiotics prohibition in feedstuffs worldwide, antimicrobial peptides (AMPs) are considered a more promising substitute for antibiotics to be used as feed additives, and positive results have been reported in livestock feeding studies. However, whether dietary supplementation of AMPs could promote the growth of mariculture animals such as fish and the underlying mechanism has not been elucidated yet. In the study, a recombinant AMP product of Scy-hepc was used as a dietary supplement (10 mg/kg) to feed mariculture juvenile large yellow croaker (Larimichthys crocea) with an average initial body weight (BW) of 52.9 g for 150 days. During the feeding trial, the fish fed with Scy-hepc showed a significant growth-promoting performance. Especially at 60 days after feeding, fish fed with Scy-hepc weighed approximately 23% more than the control group. It was further confirmed that the growth-related signaling pathways such as the GH-Jak2-STAT5-IGF1 growth axis, the PI3K-Akt and Erk/MAPK pathways were all activated in the liver after Scy-hepc feeding. Furthermore, a second repeated feeding trial was scheduled for 30 days using much smaller juvenile L. crocea with an average initial BW of 6.3 g, and similar positive results were observed. Further investigation revealed that the downstream effectors of the PI3K-Akt pathway, such as p70S6K and 4EBP1, were significantly phosphorylated, suggesting that Scy-hepc feeding might promote translation initiation and protein synthesis processes in the liver. Taken together, as an effector of innate immunity, AMP Scy-hepc played a role in promoting the growth of L. crocea and the underlying mechanism was associated with the activation of the GH-Jak2-STAT5-IGF1 axis, as well as the PI3K-Akt and Erk/MAPK signaling pathways.


Assuntos
Perciformes , Fator de Transcrição STAT5 , Animais , Peptídeos Antimicrobianos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Perciformes/metabolismo , Peixes/metabolismo , Antibacterianos/metabolismo , Proteínas de Peixes/metabolismo
16.
J Appl Microbiol ; 134(2)2023 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-36626757

RESUMO

AIMS: A rapid rise in resistance to conventional antibiotics for Shigella spp. has created a problem in treating shigellosis. Hence, there is an urgent need for new and non-conventional anti-bacterial agents. The aim of this study is to show how Asiatic acid, a plant-derived compound, inhibits the intracellular growth of Shigella flexneri. METHODS AND RESULTS: Shigella flexneri sensitive and resistant strains were used for checking antimicrobial activity of Asiatic acid by gentamicin protection assay. Asiatic acid inhibited the intracellular growth of all strains. Gene expression analysis showed antimicrobial peptide (AMP) up-regulation by Asiatic acid in intestinal cells. Further western blot analysis showed that ERK, p38, and JNK are activated by Asiatic acid. ELISA was performed to check IL-8, IL-6, and cathelicidin secretion. The antibacterial effect of Asiatic acid was further verified in an in vivo mouse model. CONCLUSIONS: The reason behind the antibacterial activities of Asiatic acid is probably over-expression of antimicrobial peptide genes. Besides, direct antimicrobial activities, antimicrobial peptides also carry immunomodulatory activities. Here, Asiatic acid increased IL-6 and IL-8 secretion to induce inflammation. Overall, Asiatic acid up-regulates antimicrobial peptide gene expression and inhibits intracellular S. flexneri growth. Moreover, Asiatic acid reduced bacterial growth and recovered intestinal tissue damages in in vivo mice model.


Assuntos
Disenteria Bacilar , Shigella , Animais , Camundongos , Antibacterianos/farmacologia , Disenteria Bacilar/tratamento farmacológico , Disenteria Bacilar/microbiologia , Expressão Gênica , Interleucina-6/genética , Interleucina-8/genética , Testes de Sensibilidade Microbiana , Shigella/genética , Shigella flexneri/genética , Peptídeos Antimicrobianos/farmacologia
17.
Mar Drugs ; 21(10)2023 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-37888440

RESUMO

Golden pompano, Trachinotus ovatus, as a highly nutritious commercially valuable marine fish, has become one of the preferred species for many fish farmers due to its rapid growth, wide adaptability, and ease of feeding and management. However, with the expansion of aquaculture scale, bacterial and parasitic diseases have also become major threats to the golden pompano industry. This study, based on comparative genomics, shows the possibility of preferential evolution of freshwater fish over marine fish by analyzing the phylogenetic relationships and divergence times of 14 marine fish and freshwater fish. Furthermore, we identified antimicrobial peptide genes from 14 species at the genomic level and found that the number of putative antimicrobial peptides may be related to species evolution. Subsequently, we classified the 341 identified AMPs from golden pompano into 38 categories based on the classification provided by the APD3. Among them, TCP represented the highest proportion, accounting for 23.2% of the total, followed by scolopendin, lectin, chemokine, BPTI, and histone-derived peptides. At the same time, the distribution of AMPs in chromosomes varied with type, and covariance analysis showed the frequency of its repeat events. Enrichment analysis and PPI indicated that AMP was mainly concentrated in pathways associated with disease immunity. In addition, our transcriptomic data measured the expression of putative AMPs of golden pompano in 12 normal tissues, as well as in the liver, spleen, and kidney infected with Streptococcus agalactiae and skin infected with Cryptocaryon irritans. As the infection with S. agalactiae and C. irritans progressed, we observed tissue specificity in the number and types of responsive AMPs. Positive selection of AMP genes may participate in the immune response through the MAPK signaling pathway. The genome-wide identification of antimicrobial peptides in the golden pompano provided a complete database of potential AMPs that can contribute to further understanding the immune mechanisms in pathogens. AMPs were expected to replace traditional antibiotics and be developed into targeted drugs against specific bacterial and parasitic pathogens for more precise and effective treatment to improve aquaculture production.


Assuntos
Peptídeos Antimicrobianos , Doenças dos Peixes , Animais , Filogenia , Peixes/genética , Peixes/metabolismo , Genoma/genética , Imunidade , Proteínas de Peixes/metabolismo , Doenças dos Peixes/microbiologia , Imunidade Inata/genética
18.
Brain Inj ; : 1-6, 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36597272

RESUMO

BACKGROUND: The Functional Independence Measure (FIM) is a well-established predictor of length of stay (LOS) for rehabilitation. The Assessment of Motor and Process Skills (AMPS) is a more in-depth construct for measuring activities of daily living (ADL) and may therefore be a valuable adjunct when predicting LOS. This paper aimed to investigate AMPS as a candidate predictor of LOS in a statistical model including FIM. METHODS: A cohort study of 647 patients with acquired brain injuries admitted for rehabilitation. LOS was analyzed in a multiple regression model with the motor and process/cognitive domains of AMPS and FIM. RESULTS: Independence in ADL process ability and FIM cognition were associated with 31% (p < 0.001) and 38% (p < 0.001) shorter LOS, respectively, relative to patients needing total assistance. Independence in ADL motor ability was associated with a 26% (p = 0.002) shorter LOS, whereas FIM motor was not a predictor. CONCLUSIONS: The AMPS predicts LOS for rehabilitation at a level that is at least as good as that of FIM. Conducting the AMPS early in the course of inpatient rehabilitation provides clinicians and managers with valuable information for planning LOS.

19.
Bioprocess Biosyst Eng ; 46(6): 813-828, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36997801

RESUMO

Nowadays, the abuse of antibiotics has led to the rise of multi-drug-resistant bacteria. Antimicrobial peptides (AMPs), with broad-spectrum antimicrobial activity have attracted considerable attention as possible alternatives to traditional antibiotics. In this work, we aimed to evaluate the antimicrobial and anti-biofilm activity of an antimicrobial peptide designed as YS12 derived from Bacillus velezensis CBSYS12. The strain CBSYS12 was isolated from Korean food kimchi and purified followed by ultrafiltration and sequential chromatographic methodology. Hereafter, Tricine SDS-PAGE revealed a single protein band of around 3.3 kDa that was further confirmed in situ inhibitory activity of the gel. A similar molecular weight (~ 3348.4 Da) protein also appeared in MALDI-TOF confirming the purity and homogeneity of peptide YS12. Intriguingly, YS12 revealed a strong antimicrobial activity with a minimum inhibitory concentration (MIC) value ranging from 6 to 12 µg/ml for both Gram-positive and Gram-negative bacteria, such as E. coli, P. aeruginosa, MRSA 4-5, VRE 82, and M. smegmatis. We also determined the mode of action of the peptide against pathogenic microorganisms using different fluorescent dyes. In addition, the anti-biofilm assay demonstrated that peptide YS12 was able to inhibit biofilm formation  around 80% for both bacterial strains E. coli and P. aeruginosa at 80 µg/ml. Notably, YS12 exhibited a greater biofilm eradication activity than commercial antibiotics. In summary, our study proposed that peptide YS12 may be used as a promising therapeutic agent to overcome drug and biofilm-related infections.


Assuntos
Anti-Infecciosos , Bacillus , Antibacterianos/química , Peptídeos Antimicrobianos , Peptídeos Catiônicos Antimicrobianos/química , Peptídeos Catiônicos Antimicrobianos/farmacologia , Escherichia coli , Bactérias Gram-Negativas , Bactérias , Anti-Infecciosos/farmacologia , Testes de Sensibilidade Microbiana , Biofilmes
20.
Neuropsychol Rehabil ; 33(7): 1262-1277, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35679176

RESUMO

This study investigated the ADL performances of people with VFL after an acute stroke using an observation-based evaluation of ADL skills, the Assessment of Motor and Process Skills. The AMPS was administered on initial assessment and at ≥11 weeks follow-up on 58 adults with a mild stroke, with (n = 16) and without VFL (n = 42), over a 13-month period. The AMPS guidelines on clinically relevant difference of 0.30 logits were used to determine the differences of the groups' ADL performance on initial assessment and follow-up. The study found that the ADL motor and process scores did not differ significantly on initial assessment. The study observed no clinically relevant difference between the ADL motor and process scores of between the VFL and non-VFL on initial assessment and follow-up but demonstrated clinically relevant improvements in ADL motor and process scores of both groups from initial assessment to follow-up. VFL does not have an additional negative impact on ADL performance of those with a mild stroke and does not impede improvement of ADL performance over time.


Assuntos
Atividades Cotidianas , Acidente Vascular Cerebral , Adulto , Humanos , Estudos Prospectivos , Campos Visuais
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