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1.
J Sep Sci ; 47(2): e2300201, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38286733

RESUMO

WenDanTang (WDT) is a Chinese herbal formula used to treat various diseases, including neurodegenerative diseases. However, the neuroprotective metabolic pathways and the components involved in this process are not fully understood. In this study, we examined the neuroprotective metabolic pathways of WDT in rat brains using cerebrospinal fluid metabolomics and ultra-high-performance liquid chromatography-high-resolution mass spectrometry. Twelve rats were randomly divided into a WDT (administrated with WDT solution) and a control group. The ultra-high-performance liquid chromatography technique was used to explore the components of the WDT solution and cerebrospinal fluid, and secondary mass spectra of cerebrospinal fluid were used to identify possible brain-incorporating components after WDT. The results of the differential metabolism analysis showed that eight metabolites were typically altered (all p < 0.05). By comparing the secondary mass spectra of the cerebrospinal fluid of rats and WDT solution, two possible brain-incorporating components of WDT, stachydrine and α-methoxyphenylacetic acid, were identified. The data also suggested that WDT affects nucleotide metabolism, glutathione metabolism, and B-vitamin metabolic pathways, the central differential metabolic pathways. These data suggest that WDT protects neurons through its active components, such as stachydrine, and regulates biochemical metabolism to affect the brain's energy metabolism and antioxidant capacity.


Assuntos
Medicamentos de Ervas Chinesas , Metabolômica , Ratos , Animais , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas/métodos , Metabolômica/métodos , Espectrometria de Massa com Cromatografia Líquida , Medicamentos de Ervas Chinesas/análise
2.
Ann Hematol ; 102(9): 2317-2327, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37421506

RESUMO

B cell hyper-function plays an important role in the pathogenesis of immune thrombocytopenia (ITP), but the molecular mechanisms underlying such changes remain unclear. We sought to identify regulators of B cell dysfunction in ITP patients through transcriptome sequencing and the use of inhibitors. B cells were isolated from PBMC of 25 ITP patients for B cell function test and transcriptome sequencing. For the potential regulatory factors identified by transcriptome sequencing, the corresponding protein inhibitors were used to explore the regulatory effect of the regulatory factors on B cell dysfunction in vitro. In this study, increased antibody production, enhanced terminal differentiation and highly expressed costimulatory molecules CD80 and CD86 were found in B cells of patients with ITP. In addition, RNA sequencing revealed highly activated mTOR pathway in these pathogenic B cells, indicating that the mTOR pathway may be involved in B cell hyper-function. Furthermore, mTOR inhibitors rapamycin or Torin1 effectively blocked the activation of mTORC1 in B cells, resulting in reduce antibody secretion, impaired differentiation of B cells into plasmablasts and downregulation of costimulatory molecules. Interestingly, as an unspecific inhibitor of mTORC2 besides mTORC1, Torin1 did not show a stronger capacity to modulate B cell function than rapamycin, suggesting that the regulation of B cells by Torin1 may depend on blockade of mTORC1 rather than mTORC2 pathway. These results indicated that the activation of mTORC1 pathway is involved in B cell dysfunction in patients with ITP, and inhibition of mTORC1 pathway might be a potential therapeutic approach for ITP.


Assuntos
Púrpura Trombocitopênica Idiopática , Trombocitopenia , Humanos , Alvo Mecanístico do Complexo 1 de Rapamicina/genética , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Transdução de Sinais , Púrpura Trombocitopênica Idiopática/genética , Leucócitos Mononucleares/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Sirolimo , Alvo Mecanístico do Complexo 2 de Rapamicina/genética , Alvo Mecanístico do Complexo 2 de Rapamicina/metabolismo , Fatores de Transcrição
3.
J Oral Rehabil ; 50(7): 548-554, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36959731

RESUMO

BACKGROUND: This study aimed at investigating the effect of loose teeth on the accuracy of occlusal records by comparing the differences in the number of occlusal contact points, occlusal contact area and the centre of the occlusal contact region under different occlusal forces in patients with periodontitis. OBJECTIVE: The effects of different occlusal forces on the occlusal contact point (OCP), occlusal contact area (OCA) and the centre of occlusal contact region (OCC) of loose teeth. METHODS: Occlusal training was performed on the 30 patients who completed periodontal serial treatment. One doctor took the occlusal records with silicone rubber and the T-scan system; the patients were digitally scanned intraorally by a technician. The data of the healthy teeth were recorded as the control group, and the data of the loose teeth were recorded as the experimental group. Then, we used Image J to measure the numbers of OCP and OCA and Auto CAD to calculate the coordinates of OCC. A paired t test was used to analyse whether the differences in OCP, OCA and OCC were statistically significant when the occlusal forces were different. RESULTS: The OCA of all three experimental methods increased under heavy occlusal force (p < .01), and the silicone rubber OCA increased the most. The OCC of all three experimental methods was shifted in the buccal and mesial (p < .01). And the occlusal records obtained by the T-scan system showed a low correlation between the differences of OCA and OCC. CONCLUSION: Whether the teeth were loose or not, the OCA increased under heavy occlusal forces. For patients with loose teeth, the OCC was shifted towards the buccal under heavy occlusal force.


Assuntos
Periodontite , Doenças Dentárias , Humanos , Força de Mordida , Elastômeros de Silicone
4.
Br J Haematol ; 197(3): 367-372, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35288929

RESUMO

Primary immune thrombocytopenia (ITP) is an autoimmune haemorrhagic disease that could manifest with comorbid type 2 diabetes mellitus (T2DM). However, the exact impact of T2DM in patients with ITP remains uncertain. In this study, we performed a retrospective cohort study of 458 participants with ITP. The prevalence of T2DM was 7.6% in this population (35 patients), which was slightly lower than the Chinese nationwide prevalence of T2DM, calculated to be approximately 10.9%. The participants with pre-existing T2DM displayed a significantly higher response to therapy than those without T2DM (71% vs. 53%). Furthermore, in the T2DM cohort, the response rate reached 88% when metformin was included in the treatment regimen. This clinical evidence suggests that metformin therapy might improve the clinical outcomes of ITP.


Assuntos
Diabetes Mellitus Tipo 2 , Metformina , Adulto , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Humanos , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento
5.
Gastrointest Endosc ; 96(2): 250-261, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35381230

RESUMO

BACKGROUND AND AIMS: Disposable gastroscopes have recently been developed to eliminate the risk of infection transmission from contaminated reusable gastroscopes. We compared the performance of disposable and reusable gastroscopes in patients undergoing gastroscopy. METHODS: Patients requiring gastroscopy were randomized to either the disposable or reusable digital gastroscope group. The primary endpoint was the success rate of photographing customary anatomic sites, with a noninferiority margin of -8%. Secondary endpoints were technical performance factors such as gastroscope imaging quality, maneuverability, gastroscopy completion rate, device failure/defect rate, operating time, and safety. Data were analyzed using the Newcombe-Wilson score method and Fisher exact 2-tailed t test. RESULTS: Of 110 patients, 55 were treated using disposable gastroscopes and 55 using reusable gastroscopes. The success rate for capturing images of customary anatomic sites was 100% in both groups. The average imaging quality score was significantly lower (37.02 ± 3.09 vs 39.47 ± 1.92, P < .001) and the operating time significantly longer (P < .001) in the disposable gastroscope group. No significant differences in maneuverability, gastroscopy completion rate, device failure/defect rate, operating time, or safety were found between the 2 groups. CONCLUSIONS: Given the overall safety profile and similar technical performance, disposable gastroscopes represent an alternative to reusable gastroscopes for routine examination, bedside first aid, and some certain circumstances.


Assuntos
Equipamentos Descartáveis , Gastroscópios , Gastroscopia , Humanos , Estudos Prospectivos
6.
Scand J Gastroenterol ; 57(11): 1296-1303, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35645153

RESUMO

OBJECTIVES: The presence of autoimmune metaplastic atrophic gastritis (AMAG) may lead to an increased risk of associated gastric neoplastic lesions. This study aims to investigate the prevalence of gastric neoplasia in AMAG patients and to explore the possibility of PGI/II ratio as a predictor for AMAG diagnosis. PATIENTS AND METHODS: Retrospective audit of 135 patients diagnosed with AMAG on endoscopic gastric biopsy between January 2017 and December 2020 at Beijing Friendship Hospital. The study was registered in Chinese Clinical Trial Registry (ChiCTR2000041163). RESULTS: A total of 135 patients (the mean age 61.9 ± 10.9 years,109 female) had histologically confirmed AMAG. 31.1% (42/135) had AMAG without neoplasia on the initial biopsy; 37% (50/135) had multiple type 1 gastric neuroendocrine tumors (g-NETs), 36 grade 1 and 14 grade 2, the median diameter was 5 mm (range 1-25); 31.9% (43/135) had multiple gastric hyperplastic polyps (GHPs), including 15 cases of GHPs with neoplastic transformation, the median diameter was 14.5 mm (range 3-50). 3.7% (5/135) had single gastric low-grade dysplasia/adenoma, the median diameter was 5 mm (range 3-15). 5.9% (8/135) had single or double gastric high-grade dysplasia or adenocarcinoma, the median diameter was 15 mm (range 8-43). 40.7% (55/135) had pepsinogen (PG) I< 10 ng/ml, 45.9% (62/135) had PG I/II ratio ≤1 and each group had a median of PG I/II ratio <1. CONCLUSIONS: Lower serum PG I level and PGI/II ratio may be a predictor to indicate the diagnosis of AMAG. It's necessary to perform regular endoscopic surveillance for AMAG patients to recognize associated gastric neoplasia timely.


Assuntos
Doenças do Tecido Conjuntivo , Gastrite Atrófica , Gastrite , Helicobacter pylori , Lesões Pré-Cancerosas , Neoplasias Gástricas , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Atrofia/patologia , Mucosa Gástrica/patologia , Gastrite/patologia , Gastrite Atrófica/patologia , Gastroscopia , Hiperplasia/patologia , Metaplasia/patologia , Pepsinogênio A , Lesões Pré-Cancerosas/patologia , Estudos Retrospectivos , Neoplasias Gástricas/diagnóstico , Masculino
7.
Br J Haematol ; 194(6): 1045-1052, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34337736

RESUMO

Exosomes are released into extracellular fluids and have emerged as vital biological mediators in autoimmune diseases. Plasma-derived exosomes have been reported to take part in the pathogenesis of primary immune thrombocytopenia (ITP), but the protein and miRNA cargoes have not been entirely elucidated. Via proteomic analysis and RNA sequencing on plasma-derived exosomes from ITP patients and healthy controls, we found one upregulated exosomal protein (apolipoprotein E, ApoE), six downregulated exosomal miRNAs (miR-584-5p, miR-4433a-5p, miR-4433b-3p, miR-6842-3p, miR-130b-5p and miR-222-3p), and 10 upregulated exosomal miRNAs (miR-29a-3p, miR-142-5p, miR-16-2-3p, miR-29b-3p, miR-501-3p, miR-144-5p, miR-192-5p, miR-182-5p, miR-363-3p and miR-96-5p) in ITP patients. The elevated exosomal protein candidate ApoE in the ITP cohort was further validated using western blot. Via quantitative real-time polymerase chain reaction assays, three differentially expressed miRNAs (miR-584-5p, miR-142-5p and miR-29b-3p) were identified. This study provides direct evidence for a restricted signature of exosomal protein and miRNAs which distinguishes ITP from healthy controls. The results require further validation in larger independent ITP cohorts, which will provide insights into the potential pathophysiological significance of circulating exosomes in ITP.


Assuntos
Exossomos/genética , MicroRNAs/genética , Púrpura Trombocitopênica Idiopática/genética , Transcriptoma , Adolescente , Adulto , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Proteômica , Púrpura Trombocitopênica Idiopática/sangue , Adulto Jovem
8.
Haematologica ; 106(3): 770-781, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-32079695

RESUMO

Human leukocyte antigen-G (HLA-G) is a non-classical major histocompatibility complex class I antigen with potent immune-inhibitory function. HLA-G benefit patients in allotransplantation and autoimmune diseases by interacting with its receptors, immunoglobulinlike transcripts. Here we observed significantly less HLA-G in plasma from immune thrombocytopenia (ITP) patients positive for anti-platelet autoantibodies compared with autoantibodies-negative patients or healthy controls, while we found that HLA-G is positively correlated with platelet counts in both patients and healthy controls. We also found less membranebound HLA-G and immunoglobulin-like transcripts on CD4+ and CD14+ cells in patients. Recombinant HLA-G upregulated immunoglobulin-like transcript 2 expression on CD4+ and immunoglobulin-like transcript 4 on CD14+ cells. HLA-G upregulated IL-4 and IL-10, and downregulated tumor necrosis factor-a, IL-12 and IL-17 secreted by patient peripheral blood mononuclear cells, suggesting a stimulation of Th2 differentiation and downregulation of Th1 and Th17 immune response. HLA-G-modulated dendritic cells from ITP patients showed decreased expression of CD80 and CD86, and suppressed CD4+ T-cell proliferation compared to unmodulated cells. Moreover, HLA-G-modulated cells from patients induced less platelet apoptosis. HLA-G administration also significantly alleviated thrombocytopenia in a murine model of ITP. In conclusion, our data demonstrated that impaired expression of HLA-G and immunoglobulin-like transcripts is involved in the pathogenesis of ITP; recombinant HLA-G can correct this abnormality via upregulation of immunoglobulin-like transcripts, indicating that HLA-G can be a diagnostic marker and a therapeutic option for ITP.


Assuntos
Púrpura Trombocitopênica Idiopática , Trombocitopenia , Animais , Antígenos de Histocompatibilidade Classe I , Humanos , Imunoglobulinas , Leucócitos Mononucleares , Camundongos , Púrpura Trombocitopênica Idiopática/genética
9.
Platelets ; 32(8): 1108-1112, 2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33400601

RESUMO

Congenital macrothrombocytopenia is a genetically heterogeneous group of rare disorders. We herein report a large Chinese family presented with phenotypic variability involving thrombocytopenia and/or giant platelets. Whole genome sequencing (WGS) of the proband and one of his affected brothers identified a potentially pathogenic c.952 C > T heterozygous variant in the TUBB1 gene. This p.R318W ß1-tubulin variant was also identified in three additional siblings and five members of the next generation. These findings were consistent with an autosomal dominant inheritance with incomplete penetrance. Moreover, impaired platelet agglutination in response to ristocetin was detected in the patient's brother. Half of the family members harboring the p.R318W mutation displayed significantly decreased external release of p-selectin by stimulated platelets. The p.R318W ß1-tubulin mutation was identified for the first time in a Chinese family with congenital macrothrombocytopenia using WGS as an unbiased sequencing approach. Affected individuals within the family demonstrated impaired platelet aggregation and/or release functions.


Assuntos
Trombocitopenia/congênito , Trombocitopenia/genética , Tubulina (Proteína)/metabolismo , Adolescente , Povo Asiático , Humanos , Masculino , Sequenciamento Completo do Genoma
10.
FASEB J ; 33(1): 264-274, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-29985646

RESUMO

Helicobacter pylori infection is a major risk factor for the development of gastric cancer. Aberrant expression of microRNAs is strongly implicated in gastric tumorigenesis; however, their contribution in response to H. pylori infection has not been fully elucidated. In this study, we evaluated the expression of miR-135b-5p and its role in gastric cancer. We describe the overexpression of miR-135b-5p in human gastric cancer tissue samples compared with normal tissue samples. Furthermore, we found that miR-135b-5p is also up-regulated in gastric tumors from the trefoil factor 1-knockout mouse model. Infection with H. pylori induced the expression of miR-135b-5p in the in vitro and in vivo models. miR-135b-5p induction was mediated by NF-κB. Treatment of gastric cancer cells with TNF-α induced miR-135b-5p in a NF-κB-dependent manner. Mechanistically, we found that miR-135b-5p targets Krüppel-like factor 4 (KLF4) and binds to its 3' UTR, leading to reduced KLF4 expression. Functionally, high levels of miR-135b-5p suppress apoptosis and induce cisplatin resistance. Our results uncovered a mechanistic link between H. pylori infection and miR-135b-5p-KLF4, suggesting that targeting miR-135b-5p could be a potential therapeutic approach to circumvent resistance to cisplatin.-Shao, L., Chen, Z., Soutto, M., Zhu, S., Lu, H., Romero-Gallo, J., Peek, R., Zhang, S., El-Rifai, W. Helicobacter pylori-induced miR-135b-5p promotes cisplatin resistance in gastric cancer.


Assuntos
Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos , Regulação Neoplásica da Expressão Gênica , Infecções por Helicobacter/complicações , Fatores de Transcrição Kruppel-Like/metabolismo , MicroRNAs/genética , Neoplasias Gástricas/patologia , Animais , Antineoplásicos/farmacologia , Apoptose , Proliferação de Células , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/patologia , Helicobacter pylori/isolamento & purificação , Humanos , Fator 4 Semelhante a Kruppel , Fatores de Transcrição Kruppel-Like/genética , Camundongos , Camundongos Knockout , NF-kappa B/genética , NF-kappa B/metabolismo , Prognóstico , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Neoplasias Gástricas/microbiologia , Taxa de Sobrevida , Fator Trefoil-1/fisiologia , Células Tumorais Cultivadas
11.
Arch Pharm (Weinheim) ; 353(10): e2000143, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32667714

RESUMO

The emergence and worldwide spread of drug-resistant bacteria have already posed a serious threat to human life, creating the urgent need to develop potent and novel antibacterial drug candidates with high efficacy. Indole and isatin (indole-2,3-dione) present a wide structural and mechanistic diversity, so their derivatives possess various pharmacological properties and occupy a salient place in the development of new drugs. Indole/isatin-containing hybrids, which demonstrate a promising activity against a panel of clinically important Gram-positive and Gram-negative bacteria, are privileged scaffolds for the discovery of novel antibacterial candidates. This review, covering articles published between January 2015 and May 2020, focuses on the development and structure-activity relationship (SAR) of indole/isatin-containing hybrids with potential application for fighting bacterial infections, to facilitate further rational design of novel drug candidates.


Assuntos
Antibacterianos/farmacologia , Indóis/farmacologia , Isatina/farmacologia , Animais , Antibacterianos/química , Desenvolvimento de Medicamentos , Descoberta de Drogas , Farmacorresistência Bacteriana , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Humanos , Indóis/química , Isatina/análogos & derivados , Isatina/química , Relação Estrutura-Atividade
12.
Blood ; 130(9): 1097-1103, 2017 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-28630121

RESUMO

The aim of this study was to determine the safety and efficacy of recombinant human thrombopoietin (rhTPO) for the management of immune thrombocytopenia (ITP) during pregnancy. Pregnant patients with ITP were enrolled in the study if they had a platelet count less than 30 × 109/L, were experiencing bleeding manifestations, had failed to respond to corticosteroids and/or intravenous immunoglobulin (IVIG), and had developed refractoriness to platelet transfusion. Thirty-one patients received rhTPO at an initial dose of 300 U/kg once daily for 14 days. Twenty-three patients responded (74.2%), including 10 complete responders (>100 × 109/L) and 13 responders (30-100 × 109/L). It appears that rhTPO ameliorated the bleeding symptoms remarkably, even in the nonresponders. rhTPO was well tolerated. Dizziness, fatigue, and pain at an injection site were reported in 1 patient each. No congenital disease or developmental delays were observed in the infants in a median follow-up of 53 (range, 39-68) weeks. In conclusion, rhTPO is a potentially safe and effective treatment choice for patients with ITP during pregnancy. Our work has paved the way for further study on the clinical application of rhTPO and other thrombopoietic agents for the management of ITP during pregnancy. This study is registered at www.clinicaltrials.gov as NCT02391272.


Assuntos
Complicações Hematológicas na Gravidez/tratamento farmacológico , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Proteínas Recombinantes/uso terapêutico , Trombopoetina/uso terapêutico , Adulto , Feminino , Hemorragia/tratamento farmacológico , Humanos , Recém-Nascido , Contagem de Plaquetas , Gravidez , Complicações Hematológicas na Gravidez/sangue , Púrpura Trombocitopênica Idiopática/sangue , Proteínas Recombinantes/efeitos adversos , Trombopoetina/efeitos adversos , Trombopoetina/sangue
13.
Mol Biol Rep ; 46(3): 3233-3246, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30945068

RESUMO

The sustained activation of Angiotensin II (Ang II) induces the remodelling of neurovascular units, inflammation and oxidative stress reactions in the brain. Long non-coding RNAs (lncRNAs) play a crucial regulatory role in the pathogenesis of hypertensive neuronal damage. The present study aimed to substantially extend the list of potential candidate genes involved in Ang II-related neuronal damage. This study assessed apoptosis and energy metabolism with Annexin V/PI staining and a Seahorse assay after Ang II exposure in SH-SY5Y cells. The expression of mRNA and lncRNA was investigated by transcriptome sequencing. The integrated analysis of mRNA and lncRNAs and the molecular mechanism of Ang II on neuronal injury was analysed by bioinformatics. Ang II increased the apoptosis rate and reduced the energy metabolism of SH-SY5Y cells. The data showed that 702 mRNAs and 821 lncRNAs were differentially expressed in response to Ang II exposure (244 mRNAs and 432 lncRNAs were upregulated, 458 mRNAs and 389 lncRNAs were downregulated) (fold change ≥ 1.5, P < 0.05). GO and KEGG analyses showed that both DE mRNA and DE lncRNA were enriched in the metabolism, differentiation, apoptosis and repair of nerve cells. This is the first report of the lncRNA-mRNA integrated profile of SH-SY5Y cells induced by Ang II. The novel targets revealed that the metabolism of the vitamin B group, the synthesis of unsaturated fatty acids and glycosphingolipids are involved in the Ang II-related cognitive impairment. Sphingolipid metabolism, the Hedgehog signalling pathway and vasopressin-regulated water reabsorption play important roles in nerve damage.


Assuntos
Angiotensina II/metabolismo , Hipertensão/genética , Neurônios/metabolismo , Apoptose , Linhagem Celular , Biologia Computacional , Perfilação da Expressão Gênica , Proteínas Hedgehog/metabolismo , Humanos , Hipertensão/metabolismo , Metabolismo dos Lipídeos/genética , Mitocôndrias/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , RNA Longo não Codificante/genética , RNA Mensageiro/genética , Transcriptoma/genética
14.
Blood ; 127(12): 1587-97, 2016 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-26744458

RESUMO

Myeloid-derived suppressor cells (MDSCs) are heterogeneous immature cells and natural inhibitors of adaptive immunity. In this study, the MDSC population was evaluated in adult patients with primary immune thrombocytopenia (ITP), where cell-mediated immune mechanisms are involved in platelet destruction. Our data demonstrated that both the numbers and suppressive functions of MDSCs were impaired in the peripheral blood and spleens of patients with ITP compared with healthy control patients. High-dose dexamethasone (HD-DXM) treatment rescued MDSC numbers in patients with ITP. And DXM modulation promoted the suppressive function of MDSCs induced in vitro. Moreover, the expression of interleukin 10 and transforming growth factor ß was significantly upregulated in DXM-modulated MDSCs compared with the unmodulated cultures. DXM-modulated MDSCs inhibited autologous CD4(+)T-cell proliferation and significantly attenuated cytotoxic T lymphocyte-mediated platelet lysis, further indicating enhanced control over T-cell responses. Elevated expression of the transcription factor Ets1 was identified in DXM-modulated MDSCs. Transfection of Ets-1 small interfering RNA efficiently blocked regulatory effects of MDSCs, which almost offset the augmentation of MDSC function by DXM. Meanwhile, splenocytes from CD61 knockout mice immunized with CD61(+)platelets were transferred into severe combined immunodeficient (SCID) mouse recipients (C57/B6 background) to induce a murine model of severe ITP. We passively transferred the DXM-modulated MDSCs induced from bone marrow of wild-type C57/B6 mice into the SCID mouse recipients, which significantly increased platelet counts in vivo compared with those receiving splenocyte engraftment alone. These findings suggested that impaired MDSCs are involved in the pathogenesis of ITP, and that HD-DXM corrected MDSC functions via a mechanism underlying glucocorticoid action and Ets1.


Assuntos
Anti-Inflamatórios/uso terapêutico , Dexametasona/uso terapêutico , Células Mieloides/efeitos dos fármacos , Proteína Proto-Oncogênica c-ets-1/imunologia , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Imunidade Adaptativa/efeitos dos fármacos , Adolescente , Adulto , Idoso , Animais , Citocinas/imunologia , Feminino , Humanos , Masculino , Camundongos Endogâmicos C57BL , Camundongos SCID , Pessoa de Meia-Idade , Células Mieloides/imunologia , Células Mieloides/patologia , Púrpura Trombocitopênica Idiopática/imunologia , Púrpura Trombocitopênica Idiopática/patologia , Adulto Jovem
15.
Blood ; 122(10): 1789-92, 2013 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-23869085

RESUMO

Immune thrombocytopenia (ITP) is an autoimmune disease where platelets are destroyed prematurely. In the majority of children the disease resolves, but in some it becomes chronic. To investigate whether these 2 phases of the disease are molecularly similar or separate entities we performed DNA microarray analysis (GEO accession number: GSE46922) of T-cells from newly diagnosed children and children with chronic ITP. We found complete separation of the gene expression profiles between the 2 phases of the disease. Furthermore, the gene expression levels of several cytokines differed between the 2 phases of the disease. This was also reflected in plasma with increased levels of interleukin (IL)-16 and TNF-related weak inducer of apoptosis and lower levels of IL-4 in newly diagnosed compared with chronic ITP. Thus, our data indicate that chronic ITP in childhood is a separate disease entity, dissimilar in many aspects to the newly diagnosed phase.


Assuntos
Citocinas/sangue , Citocinas/genética , Perfilação da Expressão Gênica , Púrpura Trombocitopênica Idiopática/sangue , Púrpura Trombocitopênica Idiopática/genética , Criança , Doença Crônica , Análise por Conglomerados , Regulação da Expressão Gênica , Genoma Humano/genética , Humanos , Púrpura Trombocitopênica Idiopática/diagnóstico , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
16.
Blood ; 122(12): 2074-82, 2013 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-23926306

RESUMO

Thalidomide (THD) is an immunomodulatory agent used to treat immune-mediated diseases. Immune thrombocytopenia (ITP) is an autoimmune disorder in which impaired mesenchymal stem cells (MSCs) are potentially involved. We demonstrated that MSCs in ITP patients had reduced proliferative capacity and lost their immunosuppressive function, which could be corrected with THD treatment. According to the gene profile, the downregulation of caspase-8 and caspase-10, and upregulation of oct3/4 and tgf-ß1, may be associated with THD modulation. Dendritic cells (DCs) played an important role in mediating the inhibitory activity of MSCs. To study the functional alteration of DCs elicited by MSCs, we sorted DCs after incubation with MSCs and performed T-lymphocyte reaction assays. The THD-modulated MSCs from ITP patients induced mature DCs to become tolerogenic DCs, whereas unmodulated MSCs had no effect. The induction of tolerogenicity in DCs by MSCs was dependent on the expression of TIEG1 in DCs. The study reveals the inability of MSCs from ITP patients to induce tolerogenic ability in DCs. THD could restore the regulatory effect of MSCs on DCs. These findings will help us understand the pathogenesis of ITP, and with appropriate safeguards, THD may benefit patients with ITP.


Assuntos
Células Dendríticas/imunologia , Tolerância Imunológica/efeitos dos fármacos , Imunossupressores/farmacologia , Células-Tronco Mesenquimais/metabolismo , Púrpura Trombocitopênica Idiopática/imunologia , Púrpura Trombocitopênica Idiopática/metabolismo , Talidomida/farmacologia , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Proliferação de Células/efeitos dos fármacos , Fatores de Transcrição de Resposta de Crescimento Precoce/genética , Fatores de Transcrição de Resposta de Crescimento Precoce/metabolismo , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Fatores de Transcrição Kruppel-Like/genética , Fatores de Transcrição Kruppel-Like/metabolismo , Masculino , Pessoa de Meia-Idade , Púrpura Trombocitopênica Idiopática/genética , Interferência de RNA , Adulto Jovem
17.
Platelets ; 26(5): 495-7, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25166956

RESUMO

The management of chronic immune thrombocytopenia (ITP) remains to be a challenge. Oseltamivir phosphate is a sialidase inhibitor agent used to treat influenza in the conventional sense. At present, we demonstrate for the first time that an adult chronic ITP patient with anti-GP Ib/IX autoantibody, who was resistant to corticosteroids, IVIG, recombinant human thrombopoietin, rituximab, danazol and vindesine, but was successfully treated with oseltamivir phosphate. Through flow cytometric analysis of ß-galactose and ß-GlcNAc exposure on platelet surfaces, we showed that oseltamivir phosphate could reduce the desialylation level of platelet glycoproteins in ITP patient. The substantial alleviation of thrombocytopenia in this case, though not leading to conclusions, lays a foundation for a novel approach for the treatment of ITP.


Assuntos
Autoanticorpos/imunologia , Oseltamivir/uso terapêutico , Complexo Glicoproteico GPIb-IX de Plaquetas/imunologia , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Púrpura Trombocitopênica Idiopática/imunologia , Idoso , Autoanticorpos/sangue , Humanos , Masculino , Contagem de Plaquetas , Púrpura Trombocitopênica Idiopática/diagnóstico , Resultado do Tratamento
18.
Platelets ; 26(6): 589-92, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25806433

RESUMO

Immune thrombocytopenia (ITP) is an autoimmune disease where platelets are destroyed prematurely. In the majority of children, the disease resolves, but in some, it becomes chronic. Cytokines are important mediators of the immune response and are known to be dysregulated in autoimmune diseases. Therefore, our aim was to investigate differences in plasma levels of cytokines between children with ITP and healthy controls. We had two cohorts of children: one Swedish with 18 children with ITP and seven healthy children and a second Chinese one with 58 children with ITP and 30 healthy children. Plasma levels of chemokine (C-X3-C motif) ligand 1 (CX3CL1), transforming growth factor ß1 (TGF-ß1), and interleukin 22 (IL-22) were analyzed in both cohorts using enzyme-linked immunosorbent assays (ELISAs). We found lower plasma levels of TGF-ß1 and elevated levels of CX3CL1 and IL-22 in children with ITP compared with controls in both the Swedish and the Chinese cohort. In conclusion, all three cytokines differ between pediatric ITP and healthy controls and may, therefore, be potential biomarkers for the disease.


Assuntos
Citocinas/sangue , Púrpura Trombocitopênica Idiopática/sangue , Adolescente , Adulto , Quimiocinas/sangue , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Masculino , Adulto Jovem
19.
Int J Mol Sci ; 15(2): 1927-45, 2014 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-24473142

RESUMO

Acute myeloid leukemia (AML) is a hematological tumor in which progress T helper (Th) subsets including Th22, Th17, and Th1 cells play a pivotal role. However, the role of T helper (Th) subsets in the immune pathogenesis of AML remains unclear. Here, we investigated frequencies of Th22, Th17, pure Th17, and Th1 cells in the peripheral blood (PB) of AML patients. We demonstrated that Th22, Th17, and pure Th17 in newly-diagnosed (ND) and non-complete remission (Non-CR) AML patients and plasma IL-22 in ND AML patients were significantly increased. Retinoid-related orphan receptor C (RORC) expression was significantly elevated in CR and Non-CR AML patients. However, Th1 in ND AML patients and IL-17 in ND, Non-CR or CR AML patients was significantly decreased compared with controls. Moreover, Th22 and IL-22 showed positive correlation with pure Th17, but Th22 showed negative correlation with Th1 in ND AML patients. RORC showed positive correlation with Th22 and approximately positive correlation with pure Th17 in Non-CR patients. PB blast cell showed positive correlation with Th22 and negative correlation with Th1 in ND AML patients. Our results indicate that Th22 and pure Th17 cells conjointly contribute to the pathogenesis of AML and might be promising novel clinical index for AML.


Assuntos
Leucemia Mieloide Aguda/sangue , Leucemia Mieloide Aguda/imunologia , Contagem de Linfócitos , Subpopulações de Linfócitos T/imunologia , Células Th17/imunologia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Estudos de Casos e Controles , Citocinas/sangue , Feminino , Regulação Leucêmica da Expressão Gênica , Humanos , Imunofenotipagem , Interleucinas/sangue , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Masculino , Pessoa de Meia-Idade , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/genética , Indução de Remissão , Subpopulações de Linfócitos T/metabolismo , Células Th1/imunologia , Células Th17/metabolismo , Adulto Jovem , Interleucina 22
20.
Waste Manag Res ; 32(6): 519-26, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24951551

RESUMO

This study explored the amount and composition of pyrolysis gas and oil derived from wet material or dried material during the preparation of sludge-corncob activated carbon, and evaluated the physicochemical and surface properties of the obtained two types of sludge-corncob-activated carbons. For wet material, owing to the presence of water, the yields of sludge-corncob activated carbon and the oil fraction slightly decreased while the yield of gases increased. The main pyrolysis gas compounds were H2 and CO2, and more H2 was released from wet material than dried material, whereas the opposite holds for CO2 Heterocyclics, nitriles, organic acids, and steroids were the major components of pyrolysis oil. Furthermore, the presence of water in wet material reduced the yield of polycyclic aromatic hydrocarbons from 6.76% to 5.43%. The yield of furfural, one of heterocyclics, increased sharply from 3.51% to 21.4%, which could be explained by the enhanced hydrolysis of corncob. In addition, the surface or chemical properties of the two sludge-corncob activated carbons were almost not affected by the moisture content of the raw material, although their mesopore volume and diameter were different. In addition, the adsorption capacities of the two sludge-corncob activated carbons towards Pb and nitrobenzene were nearly identical.


Assuntos
Carvão Vegetal/química , Óleos/química , Esgotos/química , Gerenciamento de Resíduos/métodos , Dióxido de Carbono , Cromatografia Gasosa , Furaldeído/química , Cromatografia Gasosa-Espectrometria de Massas , Hidrogênio , Hidrólise , Hidrocarbonetos Policíclicos Aromáticos/química , Espectroscopia de Infravermelho com Transformada de Fourier , Gerenciamento de Resíduos/instrumentação , Água/química , Zea mays
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