Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 108.490
Filtrar
1.
J Biomed Nanotechnol ; 16(6): 985-996, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33187593

RESUMO

Cetuximab-conjugated gold nanoparticles are known to target cancer cells, but display toxicity towards normal kidney, liver and endothelial cells in vitro. In this study, we investigated their pharmacokinetics, biodistribution and toxicity after intravenous administration in healthy mice. Our data showed that these nanoparticles were rapidly cleared from the blood and accumulated mainly in the liver and spleen with long-term retention. Acute liver injury, inflammatory activity and vascular damage were transient and negligible, as confirmed by the liver functionality tests and serum marker analysis. There was no sign of altered liver, kidney, lung and spleen morphology up to 4 weeks post-injection. After 6 months, kidney casts and splenic apoptosis appeared to be more prevalent than in the controls. Furthermore, occasional immune cell infiltration was observed in the lungs. Therefore, we recommend additional in vivo studies, in order to investigate the long-term toxicity and elimination of gold nanoparticles after multiple dosing in their preclinical validation as new targeted anti-cancer therapies.


Assuntos
Nanopartículas Metálicas , Nanopartículas , Animais , Células Endoteliais , Ouro/metabolismo , Ouro/toxicidade , Nanopartículas Metálicas/toxicidade , Camundongos , Baço/metabolismo , Distribuição Tecidual
2.
Acta Cir Bras ; 35(9): e202000902, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33084734

RESUMO

PURPOSE: To evaluate the viability of the upper (UP) and lower pole (LP) of the spleen from a macro and microscopic point of view, after subtotal splenectomy with preservation (SSP) of the UP and the LP. METHODS: Seventeen male Wistar rats, two months old, were submitted to SSPUP and SSPLP and 5 to simulated operation (SG). After 80 days, the rats were euthanized, and the remaining LP and UP and intact spleens were evaluated macroscopically and microscopically. RESULTS: Two rats died during the operation. Macroscopic analysis showed that in 15 LP, one of them was not viable and in 15 UP and in 5 spleens in the SG, all were viable. In the statistical analysis, there was no difference in relation to viability. The LP and UP analyzed showed variation. As for the length, the UP increased significantly; however, in relation to the width, there was a significant increase in the LP in relation to the UP. In addition, the weight of the UP was significantly greater than that of the LP. Microscopic analysis attested viability of the splenic remnants. CONCLUSION: There was no significant difference regarding the viability of UP and LP, in macroscopy and microscopy.


Assuntos
Baço , Esplenectomia , Animais , Humanos , Lactente , Masculino , Período Pós-Operatório , Ratos , Ratos Wistar , Baço/cirurgia
3.
Nat Commun ; 11(1): 5091, 2020 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-33037195

RESUMO

Sialic acid-binding immunoglobulin-type lectins (Siglecs) are immunomodulatory receptors that are regulated by their glycan ligands. The connections between Siglecs and human disease motivate improved methods to detect Siglec ligands. Here, we describe a new versatile set of Siglec-Fc proteins for glycan ligand detection. Enhanced sensitivity and selectivity are enabled through multimerization and avoiding Fc receptors, respectively. Using these Siglec-Fc proteins, Siglec ligands are systematically profiled on healthy and cancerous cells and tissues, revealing many unique patterns. Additional features enable the production of small, homogenous Siglec fragments and development of a quantitative ligand-binding mass spectrometry assay. Using this assay, the ligand specificities of several Siglecs are clarified. For CD33 (Siglec-3), we demonstrate that it recognizes both α2-3 and α2-6 sialosides in solution and on cells, which has implications for its link to Alzheimer's disease susceptibility. These soluble Siglecs reveal the abundance of their glycan ligands on host cells as self-associated molecular patterns.


Assuntos
Polissacarídeos/análise , Lectinas Semelhantes a Imunoglobulina de Ligação ao Ácido Siálico/química , Lectinas Semelhantes a Imunoglobulina de Ligação ao Ácido Siálico/metabolismo , Animais , Antígenos CD/genética , Antígenos CD/metabolismo , Neoplasias da Mama/metabolismo , Células CHO , Cricetulus , Feminino , Células HEK293 , Humanos , Fragmentos Fc das Imunoglobulinas/genética , Fragmentos Fc das Imunoglobulinas/metabolismo , Imunoglobulina G/genética , Imunoglobulina G/metabolismo , Células K562 , Espectrometria de Massas , Polissacarídeos/metabolismo , Lectina 3 Semelhante a Ig de Ligação ao Ácido Siálico/metabolismo , Lectinas Semelhantes a Imunoglobulina de Ligação ao Ácido Siálico/genética , Lectinas Semelhantes a Imunoglobulina de Ligação ao Ácido Siálico/isolamento & purificação , Ácidos Siálicos/metabolismo , Sialiltransferases/genética , Sialiltransferases/metabolismo , Baço/citologia , Baço/metabolismo , Estreptavidina/metabolismo
4.
PLoS One ; 15(9): e0238164, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32877416

RESUMO

PURPOSE: Haematological toxicities occur in patients receiving oxaliplatin. Mild anaemia (grade 1-2) is a common side effect and approximately 90% of recipients develop measurable spleen enlargement. Although generally asymptomatic, oxaliplatin-induced splenomegaly is independently associated with complications following liver resection for colorectal liver metastasis and separately with poorer patient outcomes. Here, we investigated oxaliplatin-induced haematological toxicities and splenomegaly in mice treated with escalating dosages comparable to those prescribed to colorectal cancer patients. METHODS: Blood was analysed, and smears assessed using Wright-Giemsa staining. Paw coloration was quantified as a marker of anaemia. Spleen weight and morphology were assessed for abnormalities relating to splenomegaly and a flow cytometry and multiplex cytokine array assessment was performed on splenocytes. The liver was assessed for sinusoidal obstructive syndrome. RESULTS: Blood analysis showed dose dependent decreases in white and red blood cell counts, and significant changes in haematological indices. Front and hind paws exhibited dose dependent and dramatic discoloration indicative of anaemia. Spleen weight was significantly increased indicating splenomegaly, and red pulp tissue exhibited substantial dysplasia. Cytokines and chemokines within the spleen were significantly affected with temporal upregulation of IL-6, IL-1α and G-CSF and downregulation of IL-1ß, IL-12p40, MIP-1ß, IL-2 and RANTES. Flow cytometric analysis demonstrated alterations in splenocyte populations, including a significant reduction in CD45+ cells. Histological staining of the liver showed no evidence of sinusoidal obstructive syndrome but there were signs suggestive of extramedullary haematopoiesis. CONCLUSION: Chronic oxaliplatin treatment dose dependently induced haematological toxicity and splenomegaly characterised by numerous physiological and morphological changes, which occurred independently of sinusoidal obstructive syndrome.


Assuntos
Testes Hematológicos , Oxaliplatina/efeitos adversos , Esplenomegalia/induzido quimicamente , Animais , Citocinas/metabolismo , Relação Dose-Resposta a Droga , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Camundongos , Tamanho do Órgão/efeitos dos fármacos , Fenótipo , Baço/efeitos dos fármacos , Baço/patologia , Esplenomegalia/metabolismo , Esplenomegalia/patologia , Fatores de Tempo
5.
PLoS Pathog ; 16(9): e1008765, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32970777

RESUMO

Tilapia is one of the most important economic and fastest-growing species in aquaculture worldwide. In 2015, an epidemic associated with severe mortality occurred in adult tilapia in Hubei, China. The causative pathogen was identified as Tilapia parvovirus (TiPV) by virus isolation, electron microscopy, experimental challenge, In situ hybridization (ISH), indirect immunofluorescence (IFA), and viral gene sequencing. Electron microscopy revealed large numbers of parvovirus particles in the organs of diseased fish, including kidney, spleen, liver, heart, brain, gill, intestine, etc. The virions were spherical in shape, non-enveloped and approximately 30nm in diameter. The TiPV was isolated and propagated in tilapia brain cells (TiB) and induced a typical cytopathic effect (CPE) after 3 days post-infection (dpi). This virus was used to experimentally infect adult tilapia and clinical disease symptoms similar to those observed naturally were replicated. Additionally, the results of ISH and IFA showed positive signals in kidney and spleen tissues from TiPV-infected fish. To identify TiPV-specific sequences, the near complete genome of TiPV was obtained and determined to be 4269 bp in size. Phylogenetic analysis of the NS1 sequence revealed that TiPV is a novel parvovirus, forms a separate branch in proposed genus Chapparvovirus of Parvoviridae. Results presented here confirm that TiPV is a novel parvovirus pathogen that can cause massive mortality in adult tilapia. This provides a basis for the further studies to define the epidemiology, pathology, diagnosis, prevention and treatment of this emerging viral disease.


Assuntos
Doenças dos Peixes/virologia , Infecções por Parvoviridae/virologia , Parvovirus/patogenicidade , Tilápia/virologia , Animais , China , Efeito Citopatogênico Viral/efeitos dos fármacos , Baço/virologia
6.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 36(9): 802-808, 2020 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-32967764

RESUMO

Objective To study the expression and significance of myeloid-derived suppressor cell (MDSC)-associated chemokines in the spleen of hepatoma H22-bearing mice. Methods The percentage of splenic MDSCs was examined by flow cytometry. Splenic MDSCs were sorted using flow cytometry and co-cultured with activated splenocytes, and then the level of IFN-γ in the supernatant of co-cultured cells was assayed by ELISA. The murine orthotopic hepatoma model was established. The differential cytokine expression in the spleens of normal and tumor-bearing mice was assayed by protein chip, and splenic MDSC-associated chemokines were verified using ELISA. The chemokine receptors on splenic MDSCs were also detected by flow cytometry. Results The percentage of splenic MDSCs was markedly raised in the tumor-bearing mice, and splenic MDSCs exhibited immune-inhibitory function. Ten up-regulated cytokines and nine down-regulated ones were found out using protein chip. Among the up-regulated cytokines, 5 cytokines were chemokines, namely B lymphocyte chemoattractant (BLC), chemokine (C-X-C motif) ligand 16 (CXCL16), macrophage/monocyte chemotactic protein-5 (MCP-5), macrophage inflammatory protein 1γ (MIP-1γ) and MIP-2. The level of splenic MDSC-associated chemokine MIP-1γ significantly increased in the spleen of tumor-bearing mice, and its receptor CCR1 was also expressed on the cell surface of splenic MDSCs. Conclusion Splenic MDSC-associated chemokine MIP-1γ and its receptor CCR1 were obtained by protein chip, and they might be associated with the accumulation of splenic MDSCs in hepatoma H22-bearing mice.


Assuntos
Carcinoma Hepatocelular , Células Supressoras Mieloides , Animais , Linhagem Celular Tumoral , Quimiocinas , Quimiocinas CC , Neoplasias Hepáticas , Proteínas Inflamatórias de Macrófagos , Camundongos , Receptores CCR1 , Baço
7.
Cell ; 183(1): 143-157.e13, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32877699

RESUMO

Humoral responses in coronavirus disease 2019 (COVID-19) are often of limited durability, as seen with other human coronavirus epidemics. To address the underlying etiology, we examined post mortem thoracic lymph nodes and spleens in acute SARS-CoV-2 infection and observed the absence of germinal centers and a striking reduction in Bcl-6+ germinal center B cells but preservation of AID+ B cells. Absence of germinal centers correlated with an early specific block in Bcl-6+ TFH cell differentiation together with an increase in T-bet+ TH1 cells and aberrant extra-follicular TNF-α accumulation. Parallel peripheral blood studies revealed loss of transitional and follicular B cells in severe disease and accumulation of SARS-CoV-2-specific "disease-related" B cell populations. These data identify defective Bcl-6+ TFH cell generation and dysregulated humoral immune induction early in COVID-19 disease, providing a mechanistic explanation for the limited durability of antibody responses in coronavirus infections, and suggest that achieving herd immunity through natural infection may be difficult.


Assuntos
Infecções por Coronavirus/imunologia , Centro Germinativo/imunologia , Pneumonia Viral/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Idoso , Idoso de 80 Anos ou mais , Linfócitos B/imunologia , Feminino , Centro Germinativo/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Proteínas Proto-Oncogênicas c-bcl-6/genética , Proteínas Proto-Oncogênicas c-bcl-6/metabolismo , Baço/imunologia , Baço/patologia , Fator de Necrose Tumoral alfa/metabolismo
8.
Proc Natl Acad Sci U S A ; 117(38): 23626-23635, 2020 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-32883883

RESUMO

Hematopoietic stem and progenitor cell (HSPC) formation and lineage differentiation involve gene expression programs orchestrated by transcription factors and epigenetic regulators. Genetic disruption of the chromatin remodeler chromodomain-helicase-DNA-binding protein 7 (CHD7) expanded phenotypic HSPCs, erythroid, and myeloid lineages in zebrafish and mouse embryos. CHD7 acts to suppress hematopoietic differentiation. Binding motifs for RUNX and other hematopoietic transcription factors are enriched at sites occupied by CHD7, and decreased RUNX1 occupancy correlated with loss of CHD7 localization. CHD7 physically interacts with RUNX1 and suppresses RUNX1-induced expansion of HSPCs during development through modulation of RUNX1 activity. Consequently, the RUNX1:CHD7 axis provides proper timing and function of HSPCs as they emerge during hematopoietic development or mature in adults, representing a distinct and evolutionarily conserved control mechanism to ensure accurate hematopoietic lineage differentiation.


Assuntos
Subunidade alfa 2 de Fator de Ligação ao Core , Proteínas de Ligação a DNA , Hematopoese , Animais , Diferenciação Celular , Linhagem Celular , Subunidade alfa 2 de Fator de Ligação ao Core/química , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Subunidade alfa 2 de Fator de Ligação ao Core/metabolismo , Proteínas de Ligação a DNA/química , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Feminino , Células-Tronco Hematopoéticas , Humanos , Masculino , Camundongos , Baço/citologia , Peixe-Zebra
9.
PLoS One ; 15(9): e0239668, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32970762

RESUMO

We developed an approach for substantial attenuation of Mycobacterium tuberculosis by prolonged culturing under gradually acidifying conditions. Bacteria subjected to acidification lost the capacity to form colonies on solid media, but readily resuscitated their growth in the murine host, providing a useful model to study in vivo development of infection mimicking latent and reactivation tuberculosis (TB) in humans. Here we characterize biomarkers of lung pathology and immune responses triggered by such attenuated bacteria in genetically TB-susceptible and resistant mice. In susceptible I/St mice, CFU counts in lungs and spleens were ~1.5-log higher than in resistant B6 mice, accompanied by diffuse pneumonia and excessive lung infiltration with highly activated CD44+CD62L- T-lymphocytes resulting in death between months 7-9 post challenge. B6 mice were characterized by development of local inflammatory foci, higher production of pro-inflammatory IL-6 and IL-11 cytokines and a more balanced T-cell activation in their lungs. CFU counts remained stable in B6 mice during the whole 18-mo observation period, and all mice survived. Thus, we established a mouse model of fatal reactivation TB vs. indefinite mycobacterial possession after identical challenge and characterized the features of immune responses in the lung tissue underlining these polar phenotypes.


Assuntos
Predisposição Genética para Doença , Interleucinas/metabolismo , Pulmão/imunologia , Ativação Linfocitária , Tuberculose Pulmonar/imunologia , Tuberculose Esplênica/imunologia , Animais , Carga Bacteriana , Células Cultivadas , Feminino , Receptores de Hialuronatos/genética , Receptores de Hialuronatos/metabolismo , Interleucinas/genética , Selectina L/genética , Selectina L/metabolismo , Pulmão/microbiologia , Camundongos , Camundongos Endogâmicos C57BL , Mycobacterium tuberculosis/patogenicidade , Baço/imunologia , Baço/microbiologia , Linfócitos T/imunologia , Tuberculose Pulmonar/genética , Tuberculose Esplênica/genética
10.
Medicine (Baltimore) ; 99(33): e20021, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32871968

RESUMO

To evaluate the diagnostic performance of net influx rate (Ki) values from a whole-body dynamic (WBD) Ga-DOTATOC-PET/CT acquisition to differentiate pancreatic neuroendocrine tumors (pNETs) from physiological uptake of pancreatic uncinate process (UP).Patients who were benefited from a WBD acquisition for the assessment of a known well-differentiated neuroendocrine tumor (NET)/suspicion of disease in the prospective GAPET-NET cohort were screened. Only patients with a confirmed pNET/UP as our gold standard were included. The positron emission tomography (PET) procedure consisted in a single-bed dynamic acquisition centered on the heart, followed by a whole-body dynamic acquisition and then a static acquisition. Dynamic (Ki calculated according to Patlak method), static (SUVmax, SUVmean, SUVpeak) parameters, and tumor-to-liver and tumor-to-spleen ratio (TLRKi and TSRKi (according to hepatic/splenic Ki)), tumor SUVmax to liver SUVmax (TM/LM), tumor SUVmax to liver SUVmean (TM/Lm), tumor SUVmax to spleen SUVmax (TM/SM), and tumor SUVmax to spleen SUVmean (TM/Sm) (according to hepatic/splenic SUVmax and SUVmean respectively) were calculated. A Receiver Operating Characteristic (ROC) analysis was performed to evaluate their diagnostic performance to distinguish UP from pNET.One hundred five patients benefited from a WBD between July 2018 and July 2019. Eighteen (17.1%) had an UP and 26 (24.8%) a pNET. For parameters alone, the Ki and SUVpeak had the best sensitivity (88.5%) while the Ki, SUVmax, and SUVmean had the best specificity (94.4%). The best diagnostic accuracy was obtained with Ki (90.9%). For ratios, the TLRKi and the TSRKi had the best sensitivity (95.7%) while the TM/SM and TM/Sm the best specificity (100%). TLRKi had the best diagnostic accuracy (95.1%) and the best area under the curve (AUC) (0.990).Our study is the first one to evaluate the interest of a WBD acquisition to differentiate UP from pNETs and shows excellent diagnostic performances of the Ki approach.


Assuntos
Tumores Neuroendócrinos/diagnóstico por imagem , Pâncreas/diagnóstico por imagem , Neoplasias Pancreáticas/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Imagem Corporal Total , Diagnóstico Diferencial , Feminino , Humanos , Fígado/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Octreotida/análogos & derivados , Compostos Organometálicos , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Estudos Prospectivos , Compostos Radiofarmacêuticos , Sensibilidade e Especificidade , Baço/diagnóstico por imagem , Imagem Corporal Total/métodos
11.
Nat Commun ; 11(1): 4596, 2020 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-32929083

RESUMO

Earlier studies indicate that either the canonical or non-canonical pathways of inflammasome activation have a limited role on malaria pathogenesis. Here, we report that caspase-8 is a central mediator of systemic inflammation, septic shock in the Plasmodium chabaudi-infected mice and the P. berghei-induced experimental cerebral malaria (ECM). Importantly, our results indicate that the combined deficiencies of caspases-8/1/11 or caspase-8/gasdermin-D (GSDM-D) renders mice impaired to produce both TNFα and IL-1ß and highly resistant to lethality in these models, disclosing a complementary, but independent role of caspase-8 and caspases-1/11/GSDM-D in the pathogenesis of malaria. Further, we find that monocytes from malaria patients express active caspases-1, -4 and -8 suggesting that these inflammatory caspases may also play a role in the pathogenesis of human disease.


Assuntos
Caspase 8/metabolismo , Inflamação/patologia , Malária Cerebral/enzimologia , Animais , Encéfalo/patologia , Caspase 1/metabolismo , Células Dendríticas/metabolismo , Ativação Enzimática , Matriz Extracelular/metabolismo , Regulação da Expressão Gênica , Humanos , Interferon gama/metabolismo , Interleucina-1beta/metabolismo , Lipopolissacarídeos , Malária Cerebral/genética , Camundongos Endogâmicos C57BL , Monócitos/metabolismo , Plasmodium chabaudi/fisiologia , Baço/metabolismo , Receptores Toll-Like/metabolismo
12.
PLoS One ; 15(9): e0239450, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32970714

RESUMO

BACKGROUND: Bone abnormality and leg disease in commercial broiler flocks are increasingly prominent, causing serious economic losses to the broiler breeding industry. Valgus-varus deformity (VVD) is a common deformity of the long bone in broilers that manifests as an outward or inward deviation of the tibiotarsus or tarsometatarsus. There is a paucity of studies on the molecular mechanisms of VVD. RESULTS: In this study, 6 cDNA libraries were constructed from spleen samples from VVD birds and normal birds. A total of 1951 annotated lncRNAs, 7943 novel lncRNAs and 30252 mRNAs were identified by RNA-sequencing. In addition, 420 differentially expressed (DE) mRNAs and 124 differentially expressed lncRNAs (adjusted P-value < 0.05) were obtained. A total of 16 dysregulated genes were confirmed by qPCR to be consistent with the results of the RNA-Seq. The functional lncRNA-mRNA co-expression network was constructed using differentially expressed mRNAs and target genes of the differentially expressed lncRNAs. 11 DE genes were obtained from the analysis. In order to gain insight into the interactions of genes, lncRNAs and pathways associated with VVD, we focused on the following pathways, which are involved in immunity and bone development: the Jak-stat signaling pathway, Toll-like receptor signaling pathway, Wnt-signaling pathway, mTOR signaling pathway, VEGF signaling pathway, Notch signaling pathway, TGF-beta signaling pathway and Fanconi anemia pathway. All together, 30 candidate DE genes were obtained from these pathways. We then analyzed the interaction between the DE genes and their corresponding lncRNAs. From these interaction network analyses we found that GARS, NFIC, PIK3R1, BMP6, NOTCH1, ACTB and CREBBP were the key core nodes of these networks. CONCLUSION: This study showed that differentially expressed genes and signaling pathways were related to immunity or bone development. These results increase the understanding of the molecular mechanisms of VVD and provide some reference for the etiology and pathogenesis of VVD.


Assuntos
Doenças Ósseas/genética , Doenças das Aves Domésticas/genética , RNA Longo não Codificante/metabolismo , RNA Mensageiro/metabolismo , Animais , Desenvolvimento Ósseo/genética , Doenças Ósseas/patologia , Galinhas/genética , Cromossomos/genética , Análise por Conglomerados , Regulação para Baixo , Biblioteca Gênica , Redes Reguladoras de Genes , Doenças das Aves Domésticas/patologia , RNA Longo não Codificante/química , RNA Mensageiro/química , Análise de Sequência de RNA , Baço/metabolismo , Transcriptoma , Regulação para Cima
13.
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi ; 32(4): 405-408, 2020 Jun 10.
Artigo em Chinês | MEDLINE | ID: mdl-32935518

RESUMO

OBJECTIVE: To assess the value of shear-wave elastography (SWE) of the liver and spleen for predicting the risk of esophageal-gastric varices (EGV) and the bleeding from EGV (EGVB) in patients with advanced schistosomiasis. METHODS: The medical records of 90 patients with definitive diagnosis of advanced schistosomiasis in Wuxi People's Hospital Affiliated to Nanjing Medical University from January 2017 through January 2020 were retrospectively reviewed. The severity of EGV was graded in the 90 patients with advanced schistosomiasis using gastroscopic findings as a golden standard. Then, the subjects were assigned to the non-EGV and EGV groups, and the low- and high-risk EGVB groups according to the grading. The SWE elastic moduli of the liver and spleen were measured and compared between groups. In addition, the receiver operating characteristic (ROC) curve was plotted, and the area under the ROC curve (AUC) was estimated to evaluate the diagnostic efficiency of the SWE elastic moduli of the liver and spleen for predicting the high risk of EGV and EGVB. RESULTS: The 90 patients with advanced schistosomiasis included 61 men and 29 women, and had a mean age of (74.3 ± 8.6) years (range, 62 to 83 years). If gastroscopic findings were employed as a golden standard, there were 32 cases with grade 0 (35.5%), 17 cases with grade 1 (18.9%), 15 cases with grade 2 (16.7%) and 26 cases with grade 3 EGV (28.9%). There were 32 cases in the non-EGV group (35.6%) and 58 cases in the EGV group (64.4%), and 41 cases in the high-risk EGV group (45.6%) and 49 cases in the low-risk EGV group (54.4%), respectively. The SWE elastic moduli of the liver and spleen were both significantly greater in the EGV group than in the non-EGV group (t = 5.73 and 7.26, both P values < 0.05). The SWE elastic moduli of the liver and spleen had AUCs of 0.70 and 0.75, optimal cut-off of 16.1 kPa and 22.6 kPa, sensitivities of 80.6% and 83.9% and specificities of 71.4% and 78.6% for the prediction of EGV, respectively. In addition, the SWE elastic moduli of the liver and spleen were significantly greater in the high-risk EGVB groups than in the low-risk EGVB group (t = 7.35 and 9.61, both P values < 0.05), and the SWE elastic moduli of the liver and spleen had AUCs of 0.68 and 0.71, optimal cut-off of 22.7 kPa and 33.8 kPa, sensitivities of 70.4% and 73.6% and specificities of 89.3% and 93.1% for the prediction of high-risk EGV, respectively. CONCLUSIONS: SWE is useful to predict the risk of EGV and EGVB in patients with advanced schistosomiasis.


Assuntos
Técnicas de Imagem por Elasticidade , Varizes Esofágicas e Gástricas , Hemorragia , Esquistossomose , Idoso , Idoso de 80 Anos ou mais , Técnicas de Imagem por Elasticidade/normas , Varizes Esofágicas e Gástricas/diagnóstico por imagem , Varizes Esofágicas e Gástricas/etiologia , Feminino , Hemorragia/diagnóstico por imagem , Hemorragia/etiologia , Humanos , Fígado/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Esquistossomose/complicações , Esquistossomose/diagnóstico por imagem , Baço/diagnóstico por imagem
14.
Exp Parasitol ; 218: 107970, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32828829

RESUMO

Visceral leishmaniasis (VL) is an anthropozoonosis endemic in Brazil. We included 20 patients with confirmed diagnosis of VL and 20 healthy individuals to evaluate the expression levels of complement receptor 1 (CR1)/CD35 and CR3/CD11b on leukocytes in the peripheral blood and determine their correlation with the clinical state of patients. CR1/CD35 expression increased on CD11b+CD35+granulocytes of patients, while CR1/CD35 and CR3/CD11b expression levels increased on CD14+CD11b+CD35+ monocytes. Among patients, those with severe clinical state had higher expression of CR3/CD11b on CD14+monocytes. The count of CD19+CD35+B lymphocytes reduced in the blood samples from patients. These observed changes may indicate the modulation in CR1/CD35 and CR3/CD11b complement receptor expressionlevels on granulocyte and monocyte populations in response to Leishmania sp.


Assuntos
Antígeno CD11b/metabolismo , Leishmaniose Visceral/imunologia , Leucócitos/metabolismo , Antígeno de Macrófago 1/metabolismo , Receptores de Complemento 3b/metabolismo , Adolescente , Adulto , Idoso , Brasil/epidemiologia , Doenças Endêmicas/estatística & dados numéricos , Feminino , Citometria de Fluxo , Granulócitos/imunologia , Granulócitos/patologia , Humanos , Hipertrofia , Leishmaniose Visceral/sangue , Leishmaniose Visceral/epidemiologia , Leucócitos/imunologia , Fígado/patologia , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Monócitos/imunologia , Monócitos/patologia , Pancitopenia , População Rural , Baço/patologia , População Urbana , Adulto Jovem
15.
Life Sci ; 259: 118218, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32784057

RESUMO

AIMS: The balance between various CD4+ T cell subsets through highly regulated differentiation of naïve T cells is critical to ensure proper immune response, disruption of which may cause autoimmunity and cancers. miR-10a has been reported to regulate the fate of naïve T cells. Mesenchymal stem cells (MSC) derived exosomes are known effective immunomodulators and ideal vehicles for delivery of microRNAs. This study was aimed to examine the impacts of miR-10a on CD4+ cell fate upon exosomal delivery in combination with immunomodulatory effects of MSCs. MAIN METHODS: Exosomes isolated form adipose tissue derived mesenchymal stem cells (AD-MSC-Exo) were transfected with miR-10a and added to naïve T cells purified from mouse spleen. AD-MSC-Exos were characterized and the efficacy of miR-10a delivery was evaluated. The expression levels of T-bet, GATA3, RORγt, and Foxp3 and the secreted levels of IFN-γ, IL-4, IL-17, and TGF-ß respectively specific to Th1, Th2, Th17 and Treg, were assessed by qPCR and ELISA. KEY FINDINGS: Being transferred by AD-MSC-Exo, miR-10a was effectively induced in CD4+ T cells. Upon treatment with miR-10a loaded exosomes, the expression levels of RORγt and Foxp3 were enhanced and that of T-bet was reduced. Similarly, the secreted levels of IL-17, and TGF-ß were increased and that of IFN-γ was decreased. SIGNIFICANCE: Our data indicate that miR-10a loaded exosomes, promote Th17 and Tregs response while reduce that of Th1. Promotion of both Th17 and Tregs in concert, mediated by the combined effect of miR-10a and MSC-Exo, indicate new therapeutic potentials, particularly in line with novel anti-tumor immunotherapeutic strategies.


Assuntos
Exossomos/imunologia , Células-Tronco Mesenquimais/imunologia , MicroRNAs/imunologia , Linfócitos T Reguladores/imunologia , Células Th17/imunologia , Adiposidade/fisiologia , Adulto , Animais , Diferenciação Celular/fisiologia , Técnicas de Cocultura , Exossomos/genética , Feminino , Humanos , Células-Tronco Mesenquimais/citologia , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/genética , Baço/citologia , Baço/imunologia , Linfócitos T Reguladores/citologia , Células Th17/classificação
16.
Life Sci ; 260: 118258, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32818542

RESUMO

Inflammation is a sophisticated biological tissue response to both extrinsic and intrinsic stimuli. Although the pathological aspects of inflammation are well appreciated, there are still rooms for understanding the physiological functions of the inflammation. Recent studies have focused on mechanisms, context and the role of physiological inflammation. Besides, there have been progress in the comprehension of commensal microbiota, immunometabolism, cancer and intracellular signaling events' roles that impact on the regulation of inflammation. Despite the fact that inflammatory responses are vital through tissue damage, understanding the mechanisms to turn off the finished or unnecessary inflammation is crucial for restoring homeostasis. Inflammation seems to be a smart process that acts like two edges of a sword, meaning that it has both protective and deleterious consequences. Knowing both edges and the regulation processes will help the future understanding and therapy for various diseases.


Assuntos
Inflamação/fisiopatologia , Animais , Homeostase , Humanos , Imunidade Inata/fisiologia , Inflamassomos/fisiologia , Microbiota/fisiologia , Fenômenos Fisiológicos da Nutrição , Transdução de Sinais , Baço/fisiopatologia
17.
Crit Care ; 24(1): 495, 2020 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-32787909

RESUMO

BACKGROUND: Post-mortem studies can provide important information for understanding new diseases and small autopsy case series have already reported different findings in COVID-19 patients. METHODS: We evaluated whether some specific post-mortem features are observed in these patients and if these changes are related to the presence of the virus in different organs. Complete macroscopic and microscopic autopsies were performed on different organs in 17 COVID-19 non-survivors. Presence of SARS-CoV-2 was evaluated with immunohistochemistry (IHC) in lung samples and with real-time reverse-transcription polymerase chain reaction (RT-PCR) test in the lung and other organs. RESULTS: Pulmonary findings revealed early-stage diffuse alveolar damage (DAD) in 15 out of 17 patients and microthrombi in small lung arteries in 11 patients. Late-stage DAD, atypical pneumocytes, and/or acute pneumonia were also observed. Four lung infarcts, two acute myocardial infarctions, and one ischemic enteritis were observed. There was no evidence of myocarditis, hepatitis, or encephalitis. Kidney evaluation revealed the presence of hemosiderin in tubules or pigmented casts in most patients. Spongiosis and vascular congestion were the most frequently encountered brain lesions. No specific SARS-CoV-2 lesions were observed in any organ. IHC revealed positive cells with a heterogeneous distribution in the lungs of 11 of the 17 (65%) patients; RT-PCR yielded a wide distribution of SARS-CoV-2 in different tissues, with 8 patients showing viral presence in all tested organs (i.e., lung, heart, spleen, liver, colon, kidney, and brain). CONCLUSIONS: In conclusion, autopsies revealed a great heterogeneity of COVID-19-associated organ injury and the remarkable absence of any specific viral lesions, even when RT-PCR identified the presence of the virus in many organs.


Assuntos
Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/virologia , Pneumonia Viral/virologia , Idoso , Autopsia , Encéfalo/virologia , Colo/virologia , Infecções por Coronavirus/terapia , Feminino , Coração/virologia , Humanos , Rim/virologia , Fígado/virologia , Pulmão/virologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/terapia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Baço/virologia
18.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(4): 1177-1182, 2020 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-32798395

RESUMO

OBJECTIVE: To investigate the mechanism of hematopoietic reconstruction in mice treated with Danggui Buxue Decoction (DBD) combined with the muscle-derived stem cell transplantation (MDSCT). METHODS: Female Kunming mice were randomly divided into the 6 groups: irradiation model, the bone marrow transplantation, the MDSC transplantation, the DBD 1 (4.5 g/kg), 2 (13.5 g/kg), and 3 (22.5 g/kg) + MDSC transplantation. After a week of oral administration of normal saline or different doses of DBD, The mice were exposied to 8 Gy 137Cs γ ray and were followed by bone marrow or MDSC transplantation. The expression levels of Notch1, Jagged1 and Hes1 in bone marrow, thymus and spleen were measured at 3 and 8 weeks after irradiation and transplantation. RESULTS: In the bone marrow, 3 weeks after above-mentioned treatment, the expression of Notch1 mRNA increased obviously and the expression of Jagged1, Hes1 mRNA decreased obviously in each intervention group, compared with the irradiation model group. 8th week after treatment, the expression of Notch1 mRNA decreased obviously in each intervention group, the Jagged1 mRNA expression decreased obviously except the bone marrow group, and Hes1 mRNA expression increased (P<0.05) in each intervention group. 3 weeks after treatment, compared with the irradiation model group, the expression of Notch1 mRNA in the thymocytes increased only in DBD1+MDSC group, Jagged1, Hes1 mRNA was increased in the MDSC transplantation group and the DBD1、2+MDSC group. 8th week after treatment, the expression of Notch1, Jagged1 mRNA expression decreased in each intervention group, the expression of Hes1 mRNA increased obviously in the MDSC transplantation group and the DBD1、2+MDSC group (P<0.05). In the spleen, 3 weeks after treatment, the expression of Notch1, Jagged1 mRNA in the spleen of each intervention group decreased obviously, compared with the irradiation model group. The expression of Jagged1, Hes1 mRNA in each intervention group were increased obviously 8th week after treatment (P<0.05). CONCLUSION: MDSC transplantation after pretreatment of DBD can improve the hematopoietic reconstitution in mice with lethal dose radiation damage. Notch1、Jagged1 and Hes1 play different roles in this process, but the concrete mechanism needs to be further studied.


Assuntos
Medicamentos de Ervas Chinesas , Transplante de Células-Tronco Hematopoéticas , Sistema Hematopoético , Animais , Feminino , Camundongos , Baço
19.
Ecotoxicol Environ Saf ; 202: 110903, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32800238

RESUMO

Cadmium (Cd) is a type of toxic metal, in most cases, coming from fuel burning and aquatic plants. The cells of organisms can be caused serious damage, including pyroptosis, exposure to low concentrations of Cd in long-term. Pyroptosis is a recently discovered Caspase-1-mediated cell death. In this study, lymphocytes were extracted from the pronephros and spleens in carps, respectively. After treating cells with low concentration of Cd, the mRNA and protein expression levels of pyroptosis-related genes, NLRP3, Caspase-1, and pro-inflammatory cytokines, increased obviously. And the content of reactive oxygen species (ROS) and mitochondria reactive oxygen species (mtROS) increased significantly, we also found the activities of CAT, GSH-px and T-SOD reduce significantly, and the content of MDA have a clear upward trend. We then added NLRP3 inhibitor, Glyburide, to the Cd-treated group, further confirming that NLRP3 is a key gene in pyroptosis pathways by detecting the mRNA and protein expression levels. Besides, the rupture of the cell membrane was also confirmed by Hoechst/PI double staining, red fluorescence increased obviously in the Cd treatment group. The experiment revealed that Cd exposure induces pyroptosis of lymphocytes in carp pronephros and spleens by activating NLRP3. Inhibition of NLRP3 activity can slow down the degree of lymphocytes pyroptosis. Thus, the above information provides a new avenue toward understanding the partial mechanism of Cd exposure-induced pyroptosis.


Assuntos
Cádmio/toxicidade , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Pronefro/metabolismo , Poluentes Químicos da Água/toxicidade , Animais , Cádmio/metabolismo , Carpas/metabolismo , Carpas/fisiologia , Caspase 1 , Inflamassomos/metabolismo , Linfócitos , Mitocôndrias/metabolismo , Piroptose/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Baço/metabolismo
20.
PLoS Biol ; 18(8): e3000807, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32760056

RESUMO

Radiotherapy is a commonly used conditioning regimen for bone marrow transplantation (BMT). Cytotoxicity limits the use of this life-saving therapy, but the underlying mechanisms remain poorly defined. Here, we use the syngeneic mouse BMT model to test the hypothesis that lethal radiation damages tissues, thereby unleashing signals that indiscriminately activate the inflammasome pathways in host and transplanted cells. We find that a clinically relevant high dose of radiation causes severe damage to bones and the spleen through mechanisms involving the NLRP3 and AIM2 inflammasomes but not the NLRC4 inflammasome. Downstream, we demonstrate that gasdermin D (GSDMD), the common effector of the inflammasomes, is also activated by radiation. Remarkably, protection against the injury induced by deadly ionizing radiation occurs only when NLRP3, AIM2, or GSDMD is lost simultaneously in both the donor and host cell compartments. Thus, this study reveals a continuum of the actions of lethal radiation relayed by the inflammasome-GSDMD axis, initially affecting recipient cells and ultimately harming transplanted cells as they grow in the severely injured and toxic environment. This study also suggests that therapeutic targeting of inflammasome-GSDMD signaling has the potential to prevent the collateral effects of intense radiation regimens.


Assuntos
Células da Medula Óssea/efeitos da radiação , Transplante de Medula Óssea , Proteínas de Ligação a DNA/genética , Inflamassomos/efeitos da radiação , Peptídeos e Proteínas de Sinalização Intracelular/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteínas de Ligação a Fosfato/genética , Animais , Células da Medula Óssea/citologia , Células da Medula Óssea/metabolismo , Proteínas de Ligação a DNA/deficiência , Feminino , Fêmur/citologia , Fêmur/metabolismo , Regulação da Expressão Gênica , Inflamassomos/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/deficiência , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteína 3 que Contém Domínio de Pirina da Família NLR/deficiência , Proteínas de Ligação a Fosfato/deficiência , Piroptose/genética , Piroptose/efeitos da radiação , Transdução de Sinais , Baço/metabolismo , Baço/patologia , Baço/efeitos da radiação , Transplante Isogênico , Irradiação Corporal Total , Raios X
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA