Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.925
Filtrar
1.
Cells ; 10(12)2021 11 25.
Artigo em Inglês | MEDLINE | ID: mdl-34943813

RESUMO

Acute respiratory distress syndrome (ARDS) is a serious lung condition characterized by severe hypoxemia leading to limitations of oxygen needed for lung function. In this study, we investigated the effect of anandamide (AEA), an endogenous cannabinoid, on Staphylococcal enterotoxin B (SEB)-mediated ARDS in female mice. Single-cell RNA sequencing data showed that the lung epithelial cells from AEA-treated mice showed increased levels of antimicrobial peptides (AMPs) and tight junction proteins. MiSeq sequencing data on 16S RNA and LEfSe analysis demonstrated that SEB caused significant alterations in the microbiota, with increases in pathogenic bacteria in both the lungs and the gut, while treatment with AEA reversed this effect and induced beneficial bacteria. AEA treatment suppressed inflammation both in the lungs as well as gut-associated mesenteric lymph nodes (MLNs). AEA triggered several bacterial species that produced increased levels of short-chain fatty acids (SCFAs), including butyrate. Furthermore, administration of butyrate alone could attenuate SEB-mediated ARDS. Taken together, our data indicate that AEA treatment attenuates SEB-mediated ARDS by suppressing inflammation and preventing dysbiosis, both in the lungs and the gut, through the induction of AMPs, tight junction proteins, and SCFAs that stabilize the gut-lung microbial axis driving immune homeostasis.


Assuntos
Ácidos Araquidônicos/uso terapêutico , Endocanabinoides/uso terapêutico , Microbioma Gastrointestinal , Trato Gastrointestinal/patologia , Pulmão/patologia , Alcamidas Poli-Insaturadas/uso terapêutico , Síndrome do Desconforto Respiratório/tratamento farmacológico , Síndrome do Desconforto Respiratório/microbiologia , Animais , Ácidos Araquidônicos/farmacologia , Butiratos/metabolismo , Ceco/patologia , Separação Celular , Colo/efeitos dos fármacos , Colo/patologia , Análise Discriminante , Disbiose/complicações , Disbiose/microbiologia , Endocanabinoides/farmacologia , Enterotoxinas , Feminino , Trato Gastrointestinal/efeitos dos fármacos , Linfonodos/efeitos dos fármacos , Linfonodos/patologia , Ativação Linfocitária/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Pneumonia/tratamento farmacológico , Pneumonia/microbiologia , Alcamidas Poli-Insaturadas/farmacologia , Síndrome do Desconforto Respiratório/complicações , Linfócitos T/efeitos dos fármacos
2.
Int J Mol Sci ; 22(17)2021 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-34502521

RESUMO

BACKGROUND: Sepsis is a serious, heterogeneous clinical entity produced by a severe and systemic host inflammatory response to infection. Methotrexate (MTX) is a folate-antagonist that induces the generation of adenosine and also inhibits JAK/STAT pathway; MTX it is widely used as an anti-inflammatory drug to control the immune system. OBJECTIVE: The aim of this study was to assess the beneficial effects of a single and low dose of MTX in the systemic response and acute lung injury (ALI) induced by sepsis. As in the clinics, we treated our animals with antibiotics and fluids and performed the source control to mimic the current clinic treatment. METHODS AND MAIN RESULTS: Sepsis was induced in rats by a cecal ligation puncture (CLP) procedure. Six hours after induction of sepsis, we proceeded to the source control; fluids and antibiotics were administered at 6 h and 24 h after CLP. MTX (2.5 mg/Kg) was administered 6 h after the first surgery in one CLP experimental group and to one Sham group. A protective effect of MTX was observed through a significant reduction of pro-inflammatory cytokines and a decrease infiltration of inflammatory cells in the lung. In addition, we found a regulation in adenosine receptor A2aR and the metalloproteinases by MTX. CONCLUSION: A single, low dose of MTX attenuates sepsis lung-associated damage by decreasing pro-inflammatory response, infiltration of pro-inflammatory cells and avoiding defective tissue lung remodeling.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Metotrexato/farmacologia , Sepse/tratamento farmacológico , Animais , Anti-Inflamatórios/uso terapêutico , Ceco/patologia , Modelos Animais de Doenças , Inflamação/tratamento farmacológico , Inflamação/fisiopatologia , Ligadura , Pulmão/efeitos dos fármacos , Masculino , Metotrexato/metabolismo , Punções , Ratos , Ratos Sprague-Dawley , Sepse/fisiopatologia
3.
Life Sci ; 284: 119882, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34384829

RESUMO

AIMS: Sepsis is a life-threatening organ dysfunction syndrome arising from infection-induced uncontrolled systemic inflammatory responses. Patients surviving severe sepsis also exhibit increased mortality due to enhanced vulnerability to infections. In this study, we examined whether (R)-ketamine could prevent against lethal sepsis-induced systemic inflammation and inflammatory organ injury. MAIN METHODS: Septic model was induced by cecal ligation and puncture (CLP) surgery on adult mice. (R)-ketamine (10 or 15 mg/kg) was administrated intraperitoneally (i.p.) 24 h before and/or immediately after CLP. KEY FINDINGS: Combined prophylactic and therapeutic use of (R)-ketamine (10 mg/kg), as well as either prophylactic or therapeutic use of (R)-ketamine at a single dose of 15 mg/kg did not reduce 14-day mortality after CLP. However, combined prophylactic and therapeutic use of (R)-ketamine (15 mg/kg) significantly increased 14-day survival rate, attenuated sepsis-induced marked drop in the rectal temperature and increase in the plasma levels of inflammatory cytokines [i.e., interleukin (IL)-6, IL-17A, tumor necrosis factor (TNF)-α, IL-1ß, and IL-10] 12 h after CLP. Furthermore, (R)-ketamine alleviated sepsis-induced increase in the organ injury markers such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), myocardial kinase (CK-MB), and creatinine 24 h after CLP. Moreover, the increased lung wet/dry weight ratio, pulmonary morphological injury and the pulmonary levels of inflammatory cytokines were also attenuated by (R)-ketamine. SIGNIFICANCE: Combined prophylactic and therapeutic use of (R)-ketamine could attenuate systemic inflammation and inflammatory multi-organ injury in mice after CLP-induced lethal sepsis. Therefore, (R)-ketamine would be a potential prophylactic and therapeutic drug for patients prone to sepsis.


Assuntos
Ceco/patologia , Inflamação/tratamento farmacológico , Inflamação/patologia , Ketamina/uso terapêutico , Insuficiência de Múltiplos Órgãos/tratamento farmacológico , Insuficiência de Múltiplos Órgãos/patologia , Animais , Biomarcadores/metabolismo , Citocinas/sangue , Modelos Animais de Doenças , Inflamação/sangue , Mediadores da Inflamação/sangue , Ketamina/farmacologia , Ligadura , Pulmão/metabolismo , Pulmão/patologia , Masculino , Camundongos Endogâmicos C57BL , Insuficiência de Múltiplos Órgãos/sangue , Tamanho do Órgão/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Substâncias Protetoras/uso terapêutico , Punções , Sepse/sangue , Sepse/tratamento farmacológico
4.
Proc Natl Acad Sci U S A ; 118(28)2021 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-34244427

RESUMO

Although inflammation is critical for the clearance of pathogens, uncontrolled inflammation also contributes to the development of multiple diseases such as cancer and sepsis. Since NF-κB-mediated transactivation in the nucleus is pivotal downstream of various stimuli to induce inflammation, searching the nuclear-localized targets specifically regulating NF-κB activation will provide important therapeutic application. Here, we have identified that homeodomain-interacting protein kinase 2 (HIPK2), a nuclear serine/threonine kinase, increases its expression in inflammatory macrophages. Importantly, HIPK2 deficiency or overexpression could enhance or inhibit inflammatory responses in LPS-stimulated macrophages, respectively. HIPK2-deficient mice were more susceptible to LPS-induced endotoxemia and CLP-induced sepsis. Adoptive transfer of Hipk2 +/- bone marrow cells (BMs) also aggravated AOM/DSS-induced colorectal cancer. Mechanistically, HIPK2 bound and phosphorylated histone deacetylase 3 (HDAC3) at serine 374 to inhibit its enzymatic activity, thus reducing the deacetylation of p65 at lysine 218 to suppress NF-κB activation. Notably, the HDAC3 inhibitors protected wild-type or Hipk2 -/- BMs-reconstituted mice from LPS-induced endotoxemia. Our findings suggest that the HIPK2-HDAC3-p65 module in macrophages restrains excessive inflammation, which may represent a new layer of therapeutic mechanism for colitis-associated colorectal cancer and sepsis.


Assuntos
Colite/complicações , Neoplasias Colorretais/etiologia , Histona Desacetilases/metabolismo , NF-kappa B/metabolismo , Sepse/etiologia , Acetilação , Animais , Ceco/patologia , Neoplasias Colorretais/metabolismo , Citocinas/biossíntese , Endotoxemia/complicações , Inibidores de Histona Desacetilases/farmacologia , Humanos , Inflamação/patologia , Mediadores da Inflamação/metabolismo , Ligadura , Lipopolissacarídeos , Lisina/metabolismo , Macrófagos/metabolismo , Macrófagos/patologia , Camundongos , Fosforilação/efeitos dos fármacos , Fosfosserina/metabolismo , Punções , Sepse/metabolismo , Receptor 4 Toll-Like/metabolismo , Receptor Toll-Like 9/metabolismo , Fator de Transcrição RelA/metabolismo , Regulação para Cima
5.
Cell Physiol Biochem ; 55(4): 400-412, 2021 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-34214389

RESUMO

BACKGROUND/AIMS: Postoperative adhesions may induce adverse outcomes in patients. Adhesion formation is initiated by fibrin accumulation at the surgical site which is followed by local neutrophilia and the establishment of neutrophil extracellular traps (NET). Previous reports have suggested that the preventive efficacy of reagents designed to reduce postoperative adhesion is inversely correlated with neutrophilia and NET production. Antithrombin (AT) is a natural inhibitor of thrombin, a key factor in coagulation. Here, we evaluate whether treatment with AT and/or NET inhibitors prevent or reduce postoperative adhesion formation in mice. METHODS: Mice were treated with AT and/or NET inhibitors before and/or after cecum cauterization and their adhesion scores were evaluated on day 7 post-operation. Immunochemistry/ immunofluorescence analyses were also performed and we used GSK484, an inhibitor of peptidyl arginine deiminase 4 (PAD4), as the NET inhibitor. RESULTS: AT or GSK484 partially rescued postoperative adhesion formation in mice. AT prevented thrombin-induced plasminogen activator inhibitor 1 and interleukin-6 expression in mesothelial cells in vitro. However, AT could not prevent neutrophilia or NETs formation around the injured serosa. Finally, we investigated a combination of AT and a PAD4 inhibitor and found that this could inhibit almost all adhesion formation in these animals. Since AT-inactivating proteases are liberated following NET release, they might dampen the biological action of the AT treatment. This suggests that NET inhibitors might allow AT to exert its full action in the surgically injured serosa. CONCLUSION: Combined treatment with AT and GSK484 may effectively attenuate postoperative adhesion production in mice.


Assuntos
Antitrombinas/farmacologia , Armadilhas Extracelulares/metabolismo , Aderências Teciduais , Animais , Ceco/metabolismo , Ceco/patologia , Ceco/cirurgia , Feminino , Interleucina-6/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Proteína-Arginina Desiminase do Tipo 4/antagonistas & inibidores , Proteína-Arginina Desiminase do Tipo 4/metabolismo , Serpina E2/metabolismo , Aderências Teciduais/metabolismo , Aderências Teciduais/patologia , Aderências Teciduais/prevenção & controle
6.
Elife ; 102021 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-34085924

RESUMO

The composition of gut-associated microbial communities changes during intestinal inflammation, including an expansion of Enterobacteriaceae populations. The mechanisms underlying microbiota changes during inflammation are incompletely understood. Here, we analyzed previously published metagenomic datasets with a focus on microbial hydrogen metabolism. The bacterial genomes in the inflamed murine gut and in patients with inflammatory bowel disease contained more genes encoding predicted hydrogen-utilizing hydrogenases compared to communities found under non-inflamed conditions. To validate these findings, we investigated hydrogen metabolism of Escherichia coli, a representative Enterobacteriaceae, in mouse models of colitis. E. coli mutants lacking hydrogenase-1 and hydrogenase-2 displayed decreased fitness during colonization of the inflamed cecum and colon. Utilization of molecular hydrogen was in part dependent on respiration of inflammation-derived electron acceptors. This work highlights the contribution of hydrogenases to alterations of the gut microbiota in the context of non-infectious colitis.


Assuntos
Ceco/microbiologia , Colite/induzido quimicamente , Colite/microbiologia , Colo/microbiologia , Infecções por Escherichia coli/microbiologia , Escherichia coli/metabolismo , Microbioma Gastrointestinal , Hidrogênio/metabolismo , Animais , Ceco/metabolismo , Ceco/patologia , Colite/metabolismo , Colite/patologia , Colo/metabolismo , Colo/patologia , Bases de Dados Genéticas , Sulfato de Dextrana , Modelos Animais de Doenças , Disbiose , Escherichia coli/genética , Escherichia coli/crescimento & desenvolvimento , Infecções por Escherichia coli/metabolismo , Infecções por Escherichia coli/patologia , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Feminino , Humanos , Hidrogenase/genética , Hidrogenase/metabolismo , Interleucina-10/genética , Interleucina-10/metabolismo , Masculino , Metagenoma , Metagenômica , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Piroxicam
7.
Methods Mol Biol ; 2321: 137-154, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34048013

RESUMO

Mice are a suitable animal model for sepsis studies because they recapitulate many aspects of the pathophysiology observed in septic human patients. It is ethically preferable to use mice for research over higher sentient species, when scientifically appropriate. Mice are also advantageous for research due to their small size, modest housing needs, the availability of genetically modified strains, and the broad range of reagents available for scientific assays on this species. Nevertheless, there are some intrinsic differences between mice and humans that should be recognized when considering the translational potential of sepsis therapies. It is often wise to complement traditional mouse studies with animal models that exhibit even greater similarity to humans, and in particular, models that better recapitulate the human immune response. Humanized mice are a promising tool to bridge this interspecies research gap. Herein, we provide a protocol to generate BLT humanized mice and describe their sepsis phenotype after cecal ligation and puncture (CLP).


Assuntos
Sepse/patologia , Animais , Ceco/imunologia , Ceco/metabolismo , Ceco/patologia , Citocinas/imunologia , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Imunidade/imunologia , Ligadura/métodos , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Punções/métodos , Sepse/imunologia , Sepse/metabolismo
8.
Cell Death Dis ; 12(6): 526, 2021 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-34023853

RESUMO

Thymic atrophy in sepsis is a critical disadvantage because it induces immunosuppression and increases the mortality rate as the disease progresses. However, the exact mechanism of thymic atrophy has not been fully elucidated. In this study, we discovered a novel role for VSIG4-positive peritoneal macrophages (V4(+) cells) as the principal cells that induce thymic atrophy and thymocyte apoptosis. In CLP-induced mice, V4(+) cells were activated after ingestion of invading microbes, and the majority of these cells migrated into the thymus. Furthermore, these cells underwent a phenotypic shift from V4(+) to V4(-) and from MHC II(low) to MHC II(+). In coculture with thymocytes, V4(+) cells mainly induced apoptosis in DP thymocytes via the secretion of TNF-α. However, there was little effect on CD4 or CD8 SP and DN thymocytes. V4(-) cells showed low levels of activity compared to V4(+) cells. Thymic atrophy in CLP-induced V4(KO) mice was much less severe than that in CLP-induced wild-type mice. In addition, V4(KO) peritoneal macrophages also showed similar activity to V4(-) cells. Taken together, the current study demonstrates that V4(+) cells play important roles in inducing immunosuppression via thymic atrophy in the context of severe infection. These data also suggest that controlling the function of V4(+) cells may play a crucial role in the development of new therapies to prevent thymocyte apoptosis in sepsis.


Assuntos
Macrófagos Peritoneais/fisiologia , Receptores de Complemento/metabolismo , Sepse/patologia , Timócitos/fisiologia , Animais , Apoptose/genética , Ceco/patologia , Ceco/cirurgia , Modelos Animais de Doenças , Feminino , Ligadura , Macrófagos Peritoneais/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Punções , Receptores de Complemento/genética , Sepse/genética , Sepse/metabolismo , Timócitos/metabolismo , Timócitos/patologia , Fator de Necrose Tumoral alfa/metabolismo
10.
Nutrients ; 13(5)2021 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-33922242

RESUMO

As a natural active substance that can effectively improve blood lipid balance in the body, hypolipidemic active peptides have attracted the attention of scholars. In this study, the effect of walnut meal peptides (WMP) on lipid metabolism was investigated in rats fed a high-fat diet (HFD). The experimental results show that feeding walnut meal peptides counteracted the high-fat diet-induced increase in body, liver and epididymal fat weight, and reduce the serum concentrations of total cholesterol, triglycerides, and LDL-cholesterol and hepatic cholesterol and triglyceride content. Walnut meal peptides also resulted in increased HDL-cholesterol while reducing the atherosclerosis index (AI). Additionally, the stained pathological sections of the liver showed that the walnut meal peptides reduced hepatic steatosis and damage caused by HFD. Furthermore, walnut meal peptide supplementation was associated with normalization of elevated apolipoprotein (Apo)-B and reduced Apo-A1 induced by the high-fat diet and with favorable changes in the expression of genes related to lipid metabolism (LCAT, CYP7A1, HMGR, FAS). The results indicate that walnut meal peptides can effectively prevent the harmful effects of a high-fat diet on body weight, lipid metabolism and liver fat content in rats, and provide, and provide a reference for the further development of walnut meal functional foods.


Assuntos
Dieta Hiperlipídica , Hiperlipidemias/tratamento farmacológico , Juglans/química , Metabolismo dos Lipídeos , Fígado/metabolismo , Peptídeos/uso terapêutico , Adipócitos/efeitos dos fármacos , Adipócitos/patologia , Aminoácidos/análise , Animais , Apolipoproteínas/metabolismo , Peso Corporal/efeitos dos fármacos , Ceco/efeitos dos fármacos , Ceco/patologia , Colesterol/metabolismo , Ingestão de Energia/efeitos dos fármacos , Epididimo/efeitos dos fármacos , Epididimo/patologia , Regulação da Expressão Gênica/efeitos dos fármacos , Hidrólise , Hipolipemiantes/farmacologia , Hipolipemiantes/uso terapêutico , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/enzimologia , Fígado/patologia , Masculino , Tamanho do Órgão/efeitos dos fármacos , Peptídeo Hidrolases/metabolismo , Peptídeos/farmacologia , Ratos Sprague-Dawley
11.
Sci Rep ; 11(1): 6460, 2021 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-33742067

RESUMO

We developed a magnetic-assisted capsule colonoscope system with integration of computer vision-based object detection and an alignment control scheme. Two convolutional neural network models A and B for lumen identification were trained on an endoscopic dataset of 9080 images. In the lumen alignment experiment, models C and D used a simulated dataset of 8414 images. The models were evaluated using validation indexes for recall (R), precision (P), mean average precision (mAP), and F1 score. Predictive performance was evaluated with the area under the P-R curve. Adjustments of pitch and yaw angles and alignment control time were analyzed in the alignment experiment. Model D had the best predictive performance. Its R, P, mAP, and F1 score were 0.964, 0.961, 0.961, and 0.963, respectively, when the area of overlap/area of union was at 0.3. In the lumen alignment experiment, the mean degrees of adjustment for yaw and pitch in 160 trials were 21.70° and 13.78°, respectively. Mean alignment control time was 0.902 s. Finally, we compared the cecal intubation time between semi-automated and manual navigation in 20 trials. The average cecal intubation time of manual navigation and semi-automated navigation were 9 min 28.41 s and 7 min 23.61 s, respectively. The automatic lumen detection model, which was trained using a deep learning algorithm, demonstrated high performance in each validation index.


Assuntos
Colonoscópios/normas , Automação , Ceco/diagnóstico por imagem , Ceco/patologia , Colonoscopia/instrumentação , Colonoscopia/métodos , Diagnóstico por Computador/métodos , Diagnóstico por Computador/normas , Desenho de Equipamento , Humanos , Fenômenos Magnéticos , Sensibilidade e Especificidade
13.
Vet Res ; 52(1): 24, 2021 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-33596990

RESUMO

Avian coccidiosis caused by Eimeria leads to huge economic losses on the global poultry industry. In this study, microneme adhesive repeat regions (MARR) bc1 of E. tenella microneme protein 3 (EtMIC3-bc1) was used as ligand, and peptides binding to EtMIC3 were screened from a phage display peptide library. The positive phage clones were checked by enzyme-linked immunosorbent assay (ELISA). Competitive ELISA was applied to further verify the binding capability between the positive phages and recombinant EtMIC3-bc1 protein or sporozoites protein. The inhibitory effects of target peptides on sporozoites invasion of MDBK cells were measured in vitro. Chickens were orally administrated with target positive phages and the protective effects against homologous challenge were evaluated. The model of three-dimensional (3D) structure for EtMIC3-bc1 was conducted, and molecular docking between target peptides and EtMIC3-bc1 model was analyzed. The results demonstrated that three selected positive phages specifically bind to EtMIC3-bc1 protein. The three peptides A, D and W effectively inhibited invasion of MDBK cells by sporozoites, showing inhibited ratio of 71.8%, 54.6% and 20.8%, respectively. Chickens in the group orally inoculated with phages A displayed more protective efficacies against homologous challenge than other groups. Molecular docking showed that amino acids in three peptides, especially in peptide A, insert into the hydrophobic groove of EtMIC3-bc1 protein, and bind to EtMIC3-bc1 through intermolecular hydrogen bonds. Taken together, the results suggest EtMIC3-binding peptides inhibit sporozoites entry into host cells. This study provides new idea for exploring novel strategies against coccidiosis.


Assuntos
Galinhas , Coccidiose/veterinária , Eimeria tenella/imunologia , Doenças das Aves Domésticas/prevenção & controle , Proteínas de Protozoários/imunologia , Esporozoítos/imunologia , Animais , Bacteriófagos , Ceco/patologia , Coccidiose/prevenção & controle , Simulação de Acoplamento Molecular , Doenças das Aves Domésticas/parasitologia , Ligação Proteica , Conformação Proteica
14.
Ned Tijdschr Geneeskd ; 1652021 01 13.
Artigo em Holandês | MEDLINE | ID: mdl-33560609

RESUMO

A 37-year-old male presented with acute lower right abdominal pain. A CT-scan showed a cecal mass. During laparoscopic right colectomy, multiple liver lesions and peritoneal deposits were seen. Histology confirmed pT4aN0 cecum carcinoma, but the liver lesions were consistent with sarcoidosis, and the peritoneal deposits were suggestive of benign mesothelioma.


Assuntos
Carcinoma/secundário , Neoplasias do Ceco/patologia , Neoplasias Hepáticas/secundário , Neoplasias Peritoneais/secundário , Dor Abdominal/etiologia , Adulto , Neoplasias do Ceco/complicações , Ceco/patologia , Colectomia , Humanos , Fígado/patologia , Masculino , Peritônio/patologia , Tomografia Computadorizada por Raios X
15.
Yonsei Med J ; 62(3): 262-273, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33635017

RESUMO

PURPOSE: This study aimed to explore the role of the long non-coding RNA (lncRNA) RNA component of mitochondrial RNAase P (RMRP) in sepsis-induced acute kidney injury (AKI). MATERIALS AND METHODS: Venous blood was collected from septic patients and healthy people. C57BL/6 mice who underwent cecal ligation and puncture (CLP) were used as in vivo models of septic AKI. Lipopolysaccharide (LPS)-induced HK-2 cells were employed as in vitro models of AKI. Flow cytometry analysis was conducted to detect cell apoptosis. Enzyme-linked immunosorbent assay and Western blot assays were used to detect levels of pro-inflammatory cytokines. RESULTS: RMRP was upregulated in sera from patients with AKI and in LPS-induced cells. Knockdown of RMRP inhibited cell apoptosis and reduced production of inflammatory factors in LPS-induced cells, as well as alleviated AKI in CLP mice. RMRP facilitated inflammation by activating NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome. We found that microRNA 206 (miR-206) binds with and is negatively regulated by RMRP: miR-206 directly targets the 3' untranslated region of DEAD-box helicase 5 (DDX5) and negatively regulates DDX5 expression. By binding with miR-206, RMRP upregulated DDX5 expression. Rescue assays revealed that overexpression of DDX5 counteracted the effect of RMRP inhibition on cell apoptosis and inflammatory response in LPS-induced cells. CONCLUSION: The lncRNA RMRP contributes to sepsis-induced AKI through upregulation of DDX5 in a miR-206 dependent manner and through activation of NLRP3 inflammasome. This novel discovery may provide a potential strategy for treating AKI.


Assuntos
Injúria Renal Aguda/etiologia , Injúria Renal Aguda/genética , RNA Longo não Codificante/metabolismo , Sepse/complicações , Animais , Apoptose/genética , Sequência de Bases , Ceco/patologia , Citocinas/metabolismo , RNA Helicases DEAD-box/genética , RNA Helicases DEAD-box/metabolismo , Técnicas de Silenciamento de Genes , Humanos , Inflamassomos/metabolismo , Inflamação/genética , Ligadura , Lipopolissacarídeos , Masculino , Camundongos Endogâmicos C57BL , MicroRNAs/genética , MicroRNAs/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Punções , RNA Longo não Codificante/genética , Regulação para Cima/genética
16.
Oxid Med Cell Longev ; 2021: 6647258, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33628372

RESUMO

Sepsis may lead to sleep deprivation, which will promote the development of neuroinflammation and mediate the progression of sepsis-associated encephalopathy (SAE). Senkyunolide I, an active component derived from an herb medicine, has been shown to provide a sedative effect to improve sleep. However, its role in sepsis is unclear. The present study was performed to investigate whether Senkyunolide I protected against SAE in a murine model of cecal ligation and puncture (CLP). Here, we showed that Senkyunolide I treatment improved the 7-day survival rate and reduced the excessive release of cytokines including TNF-α, IL-6, and IL-1ß. A fear conditioning test was performed, and the results showed that Senkyunolide I attenuated CLP-induced cognitive dysfunction. Senkyunolide I treatment also decreased the phosphorylation levels of inflammatory signaling proteins, including p-ERK, p-JNK, p-P38, and p-P65, and the level of inflammatory cytokines, including TNF-α, IL-6, and IL-1ß, in the hippocampus homogenate. Sleep deprivation was attenuated by Senkyunolide I administration, as demonstrated by the modification of the BDNF and c-FOS expression. When sleep deprivation was induced manually, the protective effect of Senkyunolide I against inflammatory responses and cognitive dysfunction was reversed. Our data demonstrated that Senkyunolide I could protect against sepsis-associated encephalopathy in a murine model of sepsis via relieving sleep deprivation.


Assuntos
Benzofuranos/uso terapêutico , Ceco/patologia , Fármacos Neuroprotetores/uso terapêutico , Encefalopatia Associada a Sepse/tratamento farmacológico , Privação do Sono/tratamento farmacológico , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Apoptose/efeitos dos fármacos , Benzofuranos/administração & dosagem , Benzofuranos/química , Benzofuranos/farmacologia , Disfunção Cognitiva/complicações , Disfunção Cognitiva/tratamento farmacológico , Modelos Animais de Doenças , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Inflamação/complicações , Inflamação/patologia , Ligadura , Masculino , Transtornos da Memória/complicações , Transtornos da Memória/tratamento farmacológico , Camundongos Endogâmicos C57BL , Microglia/efeitos dos fármacos , Microglia/patologia , Fármacos Neuroprotetores/farmacologia , Punções , Encefalopatia Associada a Sepse/complicações , Encefalopatia Associada a Sepse/patologia , Transdução de Sinais/efeitos dos fármacos , Privação do Sono/complicações , Privação do Sono/patologia , Análise de Sobrevida
17.
J Leukoc Biol ; 109(5): 877-890, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33438263

RESUMO

Neutrophil-macrophage interplay is a fine-tuning mechanism that regulates the innate immune response during infection and inflammation. Cell surface receptors play an essential role in neutrophil and macrophage functions. The same receptor can provide different outcomes within diverse leukocyte subsets in different inflammatory conditions. Understanding the variety of responses mediated by one receptor is critical for the development of anti-inflammatory treatments. In this study, we evaluated the role of a leukocyte adhesive receptor, integrin αD ß2 , in the development of acute inflammation. αD ß2 is mostly expressed on macrophages and contributes to the development of chronic inflammation. In contrast, we found that αD -knockout dramatically increases mortality in the cecal ligation and puncture sepsis model and LPS-induced endotoxemia. This pathologic outcome of αD -deficient mice is associated with a reduced number of monocyte-derived macrophages and an increased number of neutrophils in their lungs. However, the tracking of adoptively transferred fluorescently labeled wild-type (WT) and αD -/- monocytes in WT mice during endotoxemia demonstrated only a moderate difference between the recruitment of these two subsets. Moreover, the rescue experiment, using i.v. injection of WT monocytes to αD -deficient mice followed by LPS challenge, showed only slightly reduced mortality. Surprisingly, the injection of WT neutrophils to the bloodstream of αD -/- mice markedly increased migration of monocyte-derived macrophage to lungs and dramatically improves survival. αD -deficient neutrophils demonstrate increased necrosis/pyroptosis. αD ß2 -mediated macrophage accumulation in the lungs promotes efferocytosis that reduced mortality. Hence, integrin αD ß2 implements a complex defense mechanism during endotoxemia, which is mediated by macrophages via a neutrophil-dependent pathway.


Assuntos
Endotoxemia/imunologia , Cadeias alfa de Integrinas/metabolismo , Neutrófilos/metabolismo , Sepse/imunologia , Transferência Adotiva , Animais , Ceco/patologia , Contagem de Células , Movimento Celular , Citocinas/sangue , Modelos Animais de Doenças , Endotoxemia/sangue , Endotoxemia/complicações , Cadeias alfa de Integrinas/deficiência , Ligadura , Lipopolissacarídeos , Pulmão/patologia , Macrófagos/patologia , Masculino , Camundongos Endogâmicos C57BL , Monócitos/patologia , Necrose , Neutrófilos/patologia , Fagocitose , Punções , Piroptose , Sepse/sangue , Sepse/complicações , Análise de Sobrevida , Regulação para Cima
18.
Indian J Pathol Microbiol ; 64(1): 168-170, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33433433

RESUMO

Lymphomas are hematological malignancies with a wide variety of histological subtypes, varied clinical manifestations and behaviour and have a wide range of organ involvement. About 40 per cent of lymphomas are extra nodal. The most common extra nodal site is gastrointestinal tract (GIT). In the GIT, stomach is the most common organ involved accounting for 50-60 per cent of the lesions. Colorectal lymphomas are rare and account for 15-20 per cent of GIT lymphomas. They constitute 1 per cent of colorectal malignancies. Most common histological type of lymphoma involving GIT is diffuse large B-cell lymphoma, followed by MALT lymphoma; T-cell lymphomas are very rare and have an incidence of 3 per cent of Non Hodgkins Lymphoma (NHL). We report a case of anaplastic large cell lymphoma in the caecum and ascending colon with review of literature.


Assuntos
Ceco/patologia , Colo Ascendente/patologia , Neoplasias Colorretais/diagnóstico por imagem , Linfoma Anaplásico de Células Grandes/diagnóstico , Colo Ascendente/diagnóstico por imagem , Neoplasias Colorretais/classificação , Neoplasias Colorretais/tratamento farmacológico , Tratamento Farmacológico , Feminino , Técnicas Histológicas , Humanos , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Adulto Jovem
20.
PLoS One ; 16(1): e0244503, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33444337

RESUMO

INTRODUCTION: Adhesions are often considered to be an inevitable consequence of abdominal and pelvic surgery, jeopardizing the medium and long-term success of these procedures. Numerous strategies have been tested to reduce adhesion formation, however, to date, no surgical or medical therapeutic approaches have been successful in its prevention. This study demonstrates the safety and efficacy of Chitogel with Deferiprone and/or antibacterial Gallium Protoporphyrin in different concentrations in preventing adhesion formation after abdominal surgery. MATERIALS AND METHODS: 112 adult (8-10 week old) male Wistar albino rats were subjected to midline laparotomy and caecal abrasion, with 48 rats having an additional enterotomy and suturing. Kaolin (0.005g/ml) was applied to further accelerate adhesion formation. The abrasion model rats were randomized to receive saline, Chitogel, or Chitogel plus Deferiprone (5, 10 or 20 mM), together with Gallium Protoporphyrin (250µg/mL). The abrasion with enterotomy rats were randomised to receive saline, Chitogel or Chitogel with Deferiprone (1 or 5 mM). At day 21, rats were euthanised, and adhesions graded macroscopically and microscopically; the tensile strength of the repaired caecum was determined by an investigator blinded to the treatment groups. RESULTS: Chitogel with Deferiprone 5 mM significantly reduced adhesion formation (p<0.01) when pathologically assessed in a rat abrasion model. Chitogel with Deferiprone 5 mM and 1 mM also significantly reduced adhesions (p<0.05) after abrasion with enterotomy. Def-Chitogel 1mM treatment did not weaken the enterotomy site with treated sites having significantly better tensile strength compared to control saline treated enterotomy rats. CONCLUSIONS: Chitogel with Deferiprone 1 mM constitutes an effective preventative anti-adhesion barrier after abdominal surgery in a rat model. Moreover, this therapeutic combination of agents is safe and does not weaken the healing of the sutured enterotomy site.


Assuntos
Abdome/cirurgia , Deferiprona/uso terapêutico , Géis/química , Aderências Teciduais/prevenção & controle , Animais , Ceco/patologia , Ceco/cirurgia , Quitosana/química , Deferiprona/química , Modelos Animais de Doenças , Enterostomia , Caulim/química , Caulim/uso terapêutico , Protoporfirinas/química , Ratos , Ratos Wistar , Resistência à Tração
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...