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1.
Front Psychiatry ; 11: 559729, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33101081

RESUMO

Objective: Decreased homotopic connectivity of brain networks such as the cortico-striato-thalamo-cortical (CSTC) circuits may contribute to the pathophysiology of obsessive-compulsive disorder (OCD). However, little is known about interhemispheric functional connectivity (FC) at rest in OCD. In this study, the voxel-mirrored homotopic connectivity (VMHC) method was applied to explore interhemispheric coordination at rest in OCD. Methods: Forty medication-free patients with OCD and 38 sex-, age-, and education level-matched healthy controls (HCs) underwent a resting-state functional magnetic resonance imaging. The VMHC and support vector machine (SVM) methods were used to analyze the data. Results: Patients with OCD had remarkably decreased VMHC values in the orbitofrontal cortex, thalamus, middle occipital gyrus, and precentral and postcentral gyri compared with HCs. A combination of the VMHC values in the thalamus and postcentral gyrus could optimally distinguish patients with OCD from HCs. Conclusions: Our findings highlight the contribution of decreased interhemispheric FC within and outside the CSTC circuits in OCD and provide evidence to the pathophysiology of OCD.

2.
Exp Ther Med ; 20(2): 1557-1565, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32742387

RESUMO

The present study aimed to explore the expression of microribonucleic acid (microRNA) (miR)-205 in bone tissues and serum of elderly female patients with type 2 diabetes mellitus (T2DM) complicated with osteoporosis (OP), and to investigate the effect of miR-205 on osteogenesis/adipogenesis of bone marrow mesenchymal stem cells (BMSCs) and its mechanism in elderly female mice with T2DM + OP. The bone tissues and serum of 24 female patients with T2DM + OP at the Third Affiliated Hospital of Qiqihar Medical University were collected as the research group, while those of 24 healthy people were collected as the control group. The expression level of miR-205 was detected in both groups via reverse transcription-polymerase chain reaction (RT-PCR). Then the elderly female mouse model of T2DM + OP was established as a model group, while normal mice of the same age were used as the control group. The mice in the model and control groups were transfected with miR-205 mimic, negative control (NC)-mimic, miR-205-inhibitor and NC-inhibitor. Alizarin red S (ARS) staining and RT-PCR were conducted after osteogenic induction for 21 days, and oil red O (ORO) staining and RT-PCR were performed after adipogenic induction for 24 days. The overexpression of miR-205 inhibited osteogenic differentiation and promoted adipogenic differentiation of BMSCs in elderly female mice with T2DM + OP, while knockdown of miR-205 promoted osteogenic differentiation and inhibited adipogenic differentiation of BMSCs in elderly female mice with T2DM + OP. In addition, miR-205 was able to directly suppress the expression of its target gene RUNX family transcription factor 2 (Runx2). The expression level of miR-205 was obviously increased in female patients with T2DM + OP and the elderly female mouse model of T2DM + OP. In addition, miR-205 was able to regulate the osteogenic/adipogenic differentiation of BMSCs, and miR-205/Runx2 may be a new method and target for the treatment of female patients with T2DM + OP.

3.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 36(7): 634-639, 2020 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-32727649

RESUMO

Objective To investigate the role of circular RNA hsa_circ_0017247 in osteosarcoma cell invasion and migration. Methods Real-time quantitative PCR (qRT-PCR) was used to detect the expression of hsa_circ_0017247 in the matched osteosarcoma and adjacent tissues, as well as in Saos-2 and hFOB1.19 cells. The correlation between its expression and the clinicopathological parameters of osteosarcoma was analyzed using Fisher exact probability test. After knockdown of hsa_circ_0017247 by siRNA in Saos-2 cells, qRT-PCR was conducted to detect the transfection efficiency. TranswellTM invasion and migration assays were performed to evaluate the changes in cell invasion and migration. The mRNA and protein levels of E-cadherin and N-cadherin in the Saos-2 cells were tested by qRT-PCR and Western blotting, respectively. Results Compared with the adjacent tissues, hsa_circ_0017247 was highly expressed in the osteosarcoma tissues. Osteosarcoma with high expression of hsa_circ_0017247 had a higher clinical stage and metastasis rate. Highly expressed hsa_circ_0017247 was found in the Saos-2 cells as compared with the hFOB1.19 cells. The hsa_circ_0017247 significantly decreased after siRNA transfection in the Saos-2 cells, and silencing hsa_circ_0017247 inhibited the invasion and migration of the Saos-2 cells. Moreover, silencing hsa_circ_0017247 also promoted the expression of E-cadherin, but inhibited the expression of N-cadherin. Conclusion High expression of hsa_circ_0017247 enhances osteosarcoma cell invasion and migration through accelerating epithelial mesenchymal transformation.


Assuntos
Neoplasias Ósseas , Osteossarcoma , Neoplasias Ósseas/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células , Humanos , Osteossarcoma/genética , RNA/genética , RNA Circular
4.
Fetal Diagn Ther ; : 1-13, 2020 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-32663823

RESUMO

BACKGROUND: Defective lung development resulting in lung hypoplasia and an attenuated and hypermuscularized pulmonary vasculature contributes to significant postnatal mortality in congenital diaphragmatic hernia (CDH). We hypothesize that deficient embryonic pulmonary blood flow contributes to defective lung development in CDH, which may therefore be ameliorated via enhancement of embryonic pulmonary blood flow. METHODS: The mouse nitrofen model of CDH was utilized to measure embryonic pulmonary blood flow by in utero intracardiac injection of FITC-labeled tomato lectin and color-flow Doppler ultrasound. The effect of prenatal intra-amniotic treatment with sildenafil on survival, lung growth, and vascular morphology in the nitrofen model was determined. RESULTS: Nitrofen-treated embryos exhibited decreased blood flow in the lung periphery compared to controls, and intra-amniotic sildenafil significantly improved embryonic pulmonary blood flow. Similar to nitrofen alone, pups delivered after nitrofen treatment and intra-amniotic injection of dextrose control exhibited respiratory distress and never survived beyond 6 h. Intra-amniotic sildenafil ameliorated respiratory distress in nitrofen-treated pups and improved postnatal survival to 82%. Following intra-amniotic sildenafil treatment at embryonic day (E)10.5, nitrofen-treated P0 lungs were larger with increased left lobe weight, reduced small pulmonary arterial wall muscularization, and increased airway branching complexity compared to controls. Intra-amniotic sildenafil treatment later at E15.5 also resulted in improved survival, lung growth, and attenuation of vascular remodeling in nitrofen-treated embryos. CONCLUSIONS: Defective embryonic pulmonary blood flow may contribute to lung maldevelopment in CDH. Enhancement of embryonic pulmonary blood flow via intra-amniotic sildenafil results in lung growth and attenuation of pulmonary vascular remodeling and may have therapeutic potential for CDH.

5.
Adv Med Sci ; 65(2): 338-347, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32590154

RESUMO

PURPOSE: Pulmonary fibrosis (PF) is a severe lung disease causing significant morbidity and mortality. PF pathogenesis is attributed to the fibroblast-to-myofibroblast transition (FMT) driven by the most potent pro-fibrogenic factor TGF-ß1 activating the Smad3-dependent TGF-ß1 canonical pathway. Iguratimod (IGU) is a novel anti-rheumatic drug that suppresses the secretion of inflammatory factors, but is also able to modulate the differentiation of multiple cells. Therefore, the aim of this work was to investigate the effect of IGU on FMT. MATERIALS/METHODS: PF mouse model was induced in C57BL/6 male mice by bleomycin. The effect of IGU was assessed through the evaluation of lung morphology by H&E and through the collagen accumulation in the lung by Masson staining. Primary human lung fibroblasts (pHLFs) were also used to evaluate the effect of IGU in vitro on TGF-ß1-stimulated cells, and proliferation, migration and invasion were measured, together with genes and proteins involved in FMT. RESULTS: IGU attenuated bleomycin-induced PF in mice and improved the pathological changes in their lungs. In addition, IGU significantly inhibited proliferation, migration and invasion in TGF-ß1-stimulated pHLFs without causing apoptosis. Moreover, IGU significantly reduced TGF-ß1-induced increase of collagen I and III mRNA expression, thus reducing lung function impairment, and α-SMA, Smad2 and Smad3 phosphorylation, fibronectin expression and F-actin microfilament formation, thus attenuating FMT through the inhibition of the Smad3 pathway. CONCLUSIONS: Our results collectively revealed the beneficial effect of IGU on the inhibition of FMT, thus suggesting that it might act as an effective anti-fibrotic agent in preventing the progression of PF.

6.
Gastroenterol Res Pract ; 2020: 8493707, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32411204

RESUMO

Aim: Assess the risk of synchronous metastasis and establish a nomogram in patients with GISTs. Methods: Surveillance, Epidemiology and End Results database (2004-2014) was accessed. With the logistic regression model as the basis, a nomogram was constructed. Results: 7,256 target patients were contained in our study. The nomogram discrimination for mGIST prediction revealed that tumor size contributed most to synchronous metastasis, followed by lymph nodes, extension, pathologic grade, tumor location, and mitotic count. C-index values of predictions were 0.821 (95% CI, 0.805-0.836) and 0.815 (95% CI, 0.800-0.831), and Brier score were 0.109 and 0.112 in training and validation group, respectively. The value of area under the ROCs were 0.813 (p < 0.001) in the primary cohort and 0.819 (p < 0.001) in the validation cohort. Through the calibration curves (as seen in the figures), nomogram prediction proved to have excellent agreement with actual metastatic diseases. Conclusion: A new nomogram was created that can evaluate synchronous metastatic diseases in patients with GISTs.

7.
Eur Arch Psychiatry Clin Neurosci ; 270(8): 1015-1024, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31570980

RESUMO

Abnormalities of the cerebellum and default-mode network (DMN) in patients with obsessive-compulsive disorder (OCD) have been widely reported. However, alterations of reciprocal functional connections between the cerebellum and DMN at rest in OCD remain unclear. Forty patients with OCD and 38 gender-, age-, and education-matched healthy controls (HCs) underwent resting-state functional magnetic resonance imaging scan. Seed-based functional connectivity (FC) and support vector machine (SVM) were applied to analyze the imaging data. Compared with HCs, patients with OCD exhibited increased FCs between the left Crus I-left superior medial prefrontal cortex (MPFC) and between the right Crus I-left superior MPFC, left middle MPFC, and left middle temporal gyrus (MTG). A significantly negative correlation was observed between the right Crus I-left MTG connectivity and the Yale-Brown Obsessive-Compulsive Scale compulsion subscale scores in the OCD group (r = - 0.476, p = 0.002, Bonferroni corrected). SVM classification analysis indicated that a combination of the left Crus I-left superior MPFC connectivity and the right Crus I-left middle MPFC connectivity can be used to discriminate patients with OCD from HCs with a sensitivity of 85.00%, specificity of 68.42%, and accuracy of 76.92%. Our study highlights the contribution of the cerebellar-DMN connectivity in OCD pathophysiology and provides new findings to OCD research.

9.
Clin Rev Allergy Immunol ; 59(3): 295-303, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31440948

RESUMO

Diffuse alveolar hemorrhage (DAH) is a rare but potentially deadly manifestation of systemic lupus erythematosus (SLE). The aim of this study was to investigate the clinical characteristics and risk factors of DAH in SLE. A systematic review and meta-analysis of previous observational studies compared the clinical characteristics and risk factors between DAH-SLE and SLE patients without DAH. A total of 5 observational studies were included in this meta-analysis. Compared with the SLE patients without DAH, DAH-SLE patients had a significantly higher incidence of neuropsychiatric events (OR = 4.321, 95% CI (1.686-11.073), P = 0.002, I2 = 49.2%), nephritis (OR = 3.146, 95% CI (1.663-5.955,), P = 0.000, I2 = 0.0%), serositis (OR = 6.028, 95% CI (1.418-25.635), P = 0.015, I2 = 80.3%), dyspnea (OR = 31.241,95% CI (0.202-4833.203), P = 0.181, I2 = 94.6%), and a significantly lower level of C3 (SMD = - 1.358, 95% CI - 1.685, - 1.031), P = 0.000, I2 = 98.0%), C4 (SMD = - 1.251, 95% CI (- 1.648, - 0.855), P = 0.000, I2 = 87.7%), hemoglobin (SMD = - 2.074, 95% CI (- 2.433, - 1.715), P = 0.000, I2 = 94.2%), and a higher SLEDAI-2K score (SMD = 1.284, 95% CI (0.959, 1.608), P = 0.000, I2 = 98.2%). However, due to significant heterogeneity, some of these results should be interpreted cautiously. Nevertheless, when the above abnormal indicators are found, especially neuropsychiatric involvement and nephritis, besides the existed diagnostic criteria for DAH in SLE patients, a diagnosis for DAH should be considered and relevant treatment timely initiated. Further prospective multi-center SLE studies with a large cohort of patients and long-term follow-up are needed to clarify further or find out the specific clinical indexes for DAH in SLE patients.

10.
Int J Rheum Dis ; 22(9): 1686-1694, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31328410

RESUMO

AIM: Inflammatory joint diseases (IJDs) are chronic arthritis, but frequently present with co-morbidities of other organs and systems, which is known as extra-articular manifestations (EAMs). It is still unclear which clinical characteristics or bio-markers can predict the development of EAMs. The aim of this study was to estimate the proportion of EAMs in southern Chinese patients with IJDs and to explore the risk factors. METHODS: This was a retrospective cohort study of a total 1135 IJDs patients, including 788 rheumatoid arthritis (RA) patients, 307 ankylosing spondylitis (AS) patients and 40 psoriatic arthritis (PsA) patients. Demographic data, disease characteristics, laboratory blood tests, medical imaging, and the presence of EAMs were recorded. RESULTS: We found 459 (40.44%) patients presented with EAMs: 30.84% had cardiovascular involvement, 7.67% had pulmonary involvement, 5.29% had osteoporosis/low bone mineral density, 2.29% had ocular, 0.79% had gastrointestinal and 0.26% had renal involvements. Multivariate logistic regression showed older age (odds ratio [OR] 1.06, P < .001) and higher anti-cyclic citrullinated peptide antibody (anti-CCP) levels (OR 1.003, P = .019) were independent risks of EAMs in RA patients. In the AS group, older age (OR 1.07, P < .001) and higher disease activity (OR 3.24-7.42, both P < .05), were independent risks of EAMs. In the PsA group, longer disease duration (OR 1.01, P = .036) and higher disease activity (OR 1.15, P = .004) were univariate associated factors. CONCLUSION: These results suggested the high prevalence of EAMs, and it is important to regularly screen for EAMs, as they influence treatment decisions and impact on patients' quality of life.


Assuntos
Artrite Psoriásica/epidemiologia , Artrite/epidemiologia , Doenças Cardiovasculares/epidemiologia , Pneumopatias/epidemiologia , Espondilite Anquilosante/epidemiologia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Artrite/diagnóstico , Artrite Psoriásica/diagnóstico , Doenças Cardiovasculares/diagnóstico , China/epidemiologia , Progressão da Doença , Oftalmopatias/diagnóstico , Oftalmopatias/epidemiologia , Feminino , Gastroenteropatias/diagnóstico , Gastroenteropatias/epidemiologia , Humanos , Incidência , Nefropatias/diagnóstico , Nefropatias/epidemiologia , Pneumopatias/diagnóstico , Masculino , Pessoa de Meia-Idade , Osteoporose/diagnóstico , Osteoporose/epidemiologia , Prevalência , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Espondilite Anquilosante/diagnóstico , Adulto Jovem
11.
Radiology ; 290(1): 157-164, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30351251

RESUMO

Purpose To determine the diagnostic performance of dual-energy virtual noncalcium (VNCa) CT in the detection of bone marrow edema in study participants with sacroiliitis associated with axial spondyloarthritis. Materials and Methods In this prospective study, 47 consecutive participants (mean age, 27 years; age range, 14-41 years [28 male; mean age, 24 years; age range, 14-37 years] [19 female; mean age, 29 years; age range, 17-41 years]) underwent dual-energy CT and 3.0-T MRI between April 2016 and December 2017. Two independent readers visually evaluated all sacroiliac joints for the presence of abnormal marrow attenuation on dual-energy VNCa images using a four-point classification system (0, no edema; 1, mild edema; 2, moderate edema; 3, severe edema). CT numbers on VNCa images were determined with region-of-interest-based quantitative analysis. MRI was the reference standard for presence of bone marrow edema. Results Sensitivity, specificity, and accuracy of readers 1 and 2, respectively, in the identification of bone edema at CT were 87% and 93% (48 and 51 of 55), 94% and 91% (32 and 31 of 34), and 90% and 92% (80 and 82 of 89). Interobserver agreement was excellent (κ = 0.81). CT numbers from VNCa images increased from no edema to severe edema (P < .001). The area under the receiver operating characteristic curve was 0.93 for reader 1 and 0.91 for reader 2 in differentiation of the presence of bone marrow edema from no edema. A cutoff value of -33 HU derived from reader 1 yielded overall sensitivity, specificity, and accuracy of 90% (49 of 55), 83% (28 of 34), and 87% (77 of 89) in the detection of any extent of edema in the sacroiliac joints. Conclusion Dual-energy VNCa CT images had excellent diagnostic performance in evaluation of the extent of bone marrow edema in study participants with sacroiliitis associated with axial spondyloarthritis. © RSNA, 2018 See also the editorial by Guggenberger in this issue.


Assuntos
Doenças da Medula Óssea/diagnóstico por imagem , Articulação Sacroilíaca/diagnóstico por imagem , Espondilartrite/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adolescente , Adulto , Edema/diagnóstico por imagem , Feminino , Humanos , Masculino , Estudos Prospectivos , Adulto Jovem
13.
Forensic Sci Res ; 4(4): 364-366, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-32002497

RESUMO

We employed our previously developed 27-plex ancestry-informative single nucleotide polymorphism (SNP) panel to infer the ancestral components of bone remains of a possible foreign pilot found in south-western China. For ancestry assignment of this unknown individual, we first obtained the 27-SNP genotype of the individual. Then, based on a reference database of 3081 individuals from 33 populations, we calculated the match probability and likelihood ratio using the self-developed software program Forensic Intelligence. Inferred ancestral components of this individual were calculated by structure at K = 3. A complete profile was obtained for the individual using our multiplexed SNP assay. The European population was within one order of magnitude of the highest likelihood. The major ancestral component of this individual was 97.6% European.

14.
Medicine (Baltimore) ; 97(51): e13733, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30572513

RESUMO

INTRODUCTION: To assess the association between growth differentiation factor-15 (GDF15) and radiographic features including bone marrow edema and bone erosion in Spondyloarthritis (SpA). METHODS: Patients with SpA (n = 120) receiving treatment in the Guangdong General Hospital, China, between August 2012 and December 2016 were retrospectively included. Serum of patients and healthy controls (n = 30) were collected and GDF15 levels were measured using ELISA. Inflammation was assessed by C-reactive protein (CRP), and magnetic resonance imaging (MRI) of the sacroiliac joint using Spondyloarthritis Research Consortium of Canada score and a method of dichotomy to assess fat metaplasia, bone erosion, and ankylosis. Radiographs of the pelvis were scored using the modified New York (mNY) score. RESULTS: Serum GDF15 levels were higher in SpA patients compared to controls (503.52 ±â€Š222.92 vs. 190.86 ±â€Š104.18 pg/mL, P < .0001). Patients who suffered from bone erosion on MRI had higher levels of GDF15 (525.72 [186.33, 801.62]vs. 428.06 [255.15, 670.98] pg/mL, P = .0375). There was a positive correlation between serum GDF15 and CRP (r = 0.5442, P < .0001). Moreover, GDF15 levels were related to CRP levels (r = 0.5658, P < .0001) in those X-ray scores were III, according to 1984mNY criteria. Receiver operating characteristic (ROC) analysis showed that GDF15 levels above 501.98pg/mL could predict presence of bone erosion on MRI. CONCLUSION: The present study suggested that serum GDF15 levels are higher in SpA patients than in healthy controls. The GDF15 level was correlated with CRP and may be a surrogate biomarker in bone erosion.


Assuntos
Reabsorção Óssea/sangue , Reabsorção Óssea/etiologia , Fator 15 de Diferenciação de Crescimento/sangue , Espondilartrite/sangue , Espondilartrite/complicações , Adolescente , Adulto , Biomarcadores/sangue , Doenças da Medula Óssea/sangue , Doenças da Medula Óssea/diagnóstico por imagem , Doenças da Medula Óssea/etiologia , Reabsorção Óssea/diagnóstico por imagem , Proteína C-Reativa/metabolismo , Edema/sangue , Edema/diagnóstico por imagem , Edema/etiologia , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Projetos Piloto , Estudos Retrospectivos , Espondilartrite/diagnóstico por imagem , Adulto Jovem
15.
Sci Rep ; 8(1): 17668, 2018 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-30518769

RESUMO

The etiology of pulmonary vascular abnormalities in CDH is incompletely understood. Studies have demonstrated improvement in pulmonary vasculature with prenatal therapy in animal models. We hypothesize that prenatal sildenafil may attenuate defective pulmonary vascular development via modulation of vSMC phenotype from undifferentiated, proliferative phenotype to differentiated, contractile phenotype. We utilized the nitrofen model of CDH to examine the effect of IA sildenafil on pulmonary vSMC phenotype during lung development. Timed-pregnant CD-1 mice were gavage fed 25 mg nitrofen or olive oil (control) at E8.5 of gestation. Single IA injections of Sildenafil (Revatio; 10 µL of 4 mg/4 ml solution) or dextrose control were performed at E12.5. Mice were sacrificed on various gestational days for embryonic lung harvest. Markers of vSMC development of undifferentiated and differentiated phenotypes were analyzed by immunostaining and western blot. Across all time points in gestation, nitrofen-treated embryonic lungs demonstrated increased vSMC expression of NOTCH3, Hes-5, PDGFR-ß, desmin and α-SMA and decreased expression of calponin and SMMHC, compared to oil controls. IA dextrose treatment had no effect on expression levels. However, IA Sildenafil treatment resulted in down-regulation of NOTCH3, Hes-5, PDGFR-ß, desmin and α-SMA and upregulation of calponin and SMMHC, comparable to oil controls. In the nitrofen model, vSMC express markers consistent with more undifferentiated proliferative phenotype, resulting in hypermuscularization of intrapulmonary arterioles in CDH. A single dose of IA Sildenafil treatment early in gestation, results in sustained normalization of vSMC phenotype. Pharmacologic modulation of the vSMC phenotype at key gestational points may have therapeutic potential.


Assuntos
Hérnias Diafragmáticas Congênitas/tratamento farmacológico , Músculo Liso Vascular/efeitos dos fármacos , Citrato de Sildenafila/uso terapêutico , Vasodilatadores/uso terapêutico , Âmnio , Animais , Feminino , Hérnias Diafragmáticas Congênitas/induzido quimicamente , Hérnias Diafragmáticas Congênitas/etiologia , Injeções , Pulmão/irrigação sanguínea , Pulmão/efeitos dos fármacos , Pulmão/embriologia , Camundongos , Músculo Liso Vascular/embriologia , Fenótipo , Éteres Fenílicos , Gravidez , Citrato de Sildenafila/administração & dosagem , Vasodilatadores/administração & dosagem
16.
Front Immunol ; 9: 2407, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30425709

RESUMO

Recombinant human growth differentiation factor 15 (rhGDF15) affects dendritic cell (DC) maturation. However, whether GDF15 is expressed in DCs and its roles and signaling in DCs remain largely unknown. It is unclear whether GDF15-DCs can induce immune tolerance in heart transplantation (HT). This study aims to understand the impact of endogenous GDF15 on DC's development, function, underlying molecular mechanism including circular RNA (circRNA). This study will also explore GDF15-DC-mediated immune modulation in HT. Bone marrow (BM) derived DCs were cultured and treated to up- or down regulate GDF15 expression. Phenotype and function of DCs were detected. Expression of genes and circRNAs was determined by qRT-PCR. The signaling pathways activated by GDF15 were examined. The impact of GDF15 treated DCs on preventing allograft immune rejection was assessed in a MHC full mismatch mouse HT model. Our results showed that GDF15 was expressed in DCs. Knockout of GDF15 promoted DC maturation, enhanced immune responsive functions, up-regulated malat-1 circular RNA (circ_Malat 1), and activated the nuclear factor kappa B (NFκB) pathway. Overexpression of GDF15 in DCs increased immunosuppressive/inhibitory molecules, enhanced DCs to induce T cell exhaustion, and promoted Treg generation through IDO signaling. GDF15 utilized transforming growth factor (TGF) ß receptors I and II, not GFAL. Administration of GDF15 treated DCs prevented allograft rejection and induced immune tolerance in transplantation. In conclusion, GDF15 induces tolerogenic DCs (Tol-DCs) through inhibition of circ_Malat-1 and the NFκB signaling pathway and up-regulation of IDO. GDF15-DCs can prevent alloimmune rejection in HT.


Assuntos
Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Rejeição de Enxerto/genética , Rejeição de Enxerto/imunologia , Fator 15 de Diferenciação de Crescimento/metabolismo , Tolerância Imunológica , NF-kappa B/metabolismo , RNA Longo não Codificante/genética , Animais , Diferenciação Celular/genética , Diferenciação Celular/imunologia , Células Dendríticas/citologia , Regulação da Expressão Gênica , Técnicas de Silenciamento de Genes , Fator 15 de Diferenciação de Crescimento/farmacologia , Transplante de Coração/efeitos adversos , Humanos , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Transplante Homólogo
17.
Rev Sci Instrum ; 89(8): 083103, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30184661

RESUMO

Raman imaging has a great advantage in characterizing inhomogeneous systems. A practical wide-field Raman imaging platform is developed that shows major improvements on imaging speed, sensitivity, and resolution. Different from the traditional Raman imaging systems using the wavelength-fixed lasers and the chromatic dispersion devices, this system adopts an inverted architecture, integrated with a tunable laser and the wavelength-fixed filters. Owing to the high transmission of the fixed filters, the imaging sensitivity can be improved 5-10 times in comparison to the present wide-field Raman imaging setups using liquid-crystal tunable filters. Via combining with the high-power tunable laser, Raman images could be obtained in minutes and the Raman shift of the images could be tuned easily and accurately. The resolution of this system can reach 1.5 cm-1 in the spectrum and 490 nm in space, which could provide more fingerprint details of the analytes. This effective Raman imaging method allowing us to see chemical spatial variations on microscale is anticipated to be widely applied in scientific research fields.

18.
J Forensic Sci ; 63(6): 1692-1703, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29494760

RESUMO

Next-generation sequencing (NGS) has been used to genotype forensic short tandem repeat (STR) markers for individual identification and kinship analysis. STR data from several NGS platforms have been published, but forensic application trials using the Ion S5™ XL system have not been reported. In this work, we report sensitivity, reproducibility, mixture, simulated degradation, and casework sample data on the Ion Chef™ and S5™ XL systems using an early access 25-plex panel. Sensitivity experiments showed that over 97% of the alleles were detectable with down to 62 pg input of genomic DNA. In mixture studies, alleles from minor contributors were correctly assigned at 1:9 and 9:1 ratios. NGS successfully gave 12 full genotype results from 13 challenging casework samples, compared with five full results using the CE platform. In conclusion, the Ion Chef™ and the Ion S5™ XL systems provided an alternative and promising approach for forensic STR genotyping.


Assuntos
Sequenciamento de Nucleotídeos em Larga Escala/instrumentação , Repetições de Microssatélites , Análise de Sequência de DNA , Alelos , Impressões Digitais de DNA , Genética Forense , Genótipo , Humanos , Reprodutibilidade dos Testes
19.
Int J Rheum Dis ; 21(2): 477-486, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29316328

RESUMO

AIM: To determine whether pirfenidone attenuates lung fibrosis by interfering with the hedgehog (Hh) signalling pathway in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD). METHODS: Twenty-five SSc-ILD patients (20 first visit, five who underwent pirfenidone treatment for 6 months) and 10 healthy controls were recruited. Lung tissues were obtained by open-chest surgery, and primary lung fibroblasts were isolated, cultured and stimulated with pirfenidone. The levels of the proteins glioma-associated oncogene 1 (GLI1), suppressor of fused (Sufu), α-smooth muscle actin, and fibronectin in lung tissues or fibroblasts were determined by Western blotting. The messenger RNA levels of GLI1, glioma-associated oncogene 2, protein patched homolog 1, and Sufu in lung tissues or fibroblasts were determined by quantitative reverse-transcription polymerase chain reaction. Meanwhile, the levels of phosphorylation glycogen synthase kinasep-3ß (pGSK-3ß), phosphorylation SMAD2 (pSMAD2), and phosphorylation c-Jun N-terminal kinase (pJNK) in fibroblasts were determined by Western blotting. RESULTS: Hh pathway activation was increased in the lung tissue of SSc-ILD patients and was decreased by pirfenidone, Sufu was upregulated in lung fibroblasts isolated from SSc-ILD patients after pirfenidone challenge, and pirfenidone inhibited the phosphorylation of GSK-3ß signalling. CONCLUSION: Pirfenidone has anti-fibrotic effects in SSc-ILD patients by interfering with both the Hh signalling pathway and the GSK-3ß signalling pathway via the regulation of Sufu expression. These results might promote its use in other Hh driven lung diseases such as idiopathic pulmonary fibrosis and especially the interstitial lung disease associated with connective tissue diseases.


Assuntos
Fibroblastos/efeitos dos fármacos , Proteínas Hedgehog/metabolismo , Doenças Pulmonares Intersticiais/tratamento farmacológico , Pulmão/efeitos dos fármacos , Fibrose Pulmonar/tratamento farmacológico , Piridonas/farmacologia , Escleroderma Sistêmico/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Actinas/metabolismo , Adulto , Estudos de Casos e Controles , Células Cultivadas , Feminino , Fibroblastos/metabolismo , Fibroblastos/patologia , Fibronectinas/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Humanos , Pulmão/metabolismo , Pulmão/patologia , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/metabolismo , MAP Quinase Quinase 4/metabolismo , Masculino , Pessoa de Meia-Idade , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Receptor Patched-1/genética , Receptor Patched-1/metabolismo , Fosforilação , Fibrose Pulmonar/diagnóstico , Fibrose Pulmonar/metabolismo , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Escleroderma Sistêmico/diagnóstico , Escleroderma Sistêmico/metabolismo , Proteína Smad2/metabolismo , Tomografia Computadorizada por Raios X , Proteína GLI1 em Dedos de Zinco/genética , Proteína GLI1 em Dedos de Zinco/metabolismo , Proteína Gli2 com Dedos de Zinco/genética , Proteína Gli2 com Dedos de Zinco/metabolismo
20.
Plant Biotechnol J ; 16(1): 86-99, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28499064

RESUMO

Maize is a globally important food, feed crop and raw material for the food and energy industry. Plant architecture optimization plays important roles in maize yield improvement. PIN-FORMED (PIN) proteins are important for regulating auxin spatiotemporal asymmetric distribution in multiple plant developmental processes. In this study, ZmPIN1a overexpression in maize increased the number of lateral roots and inhibited their elongation, forming a developed root system with longer seminal roots and denser lateral roots. ZmPIN1a overexpression reduced plant height, internode length and ear height. This modification of the maize phenotype increased the yield under high-density cultivation conditions, and the developed root system improved plant resistance to drought, lodging and a low-phosphate environment. IAA concentration, transport capacity determination and application of external IAA indicated that ZmPIN1a overexpression led to increased IAA transport from shoot to root. The increase in auxin in the root enabled the plant to allocate more carbohydrates to the roots, enhanced the growth of the root and improved plant resistance to environmental stress. These findings demonstrate that maize plant architecture can be improved by root breeding to create an ideal phenotype for further yield increases.


Assuntos
Ácidos Indolacéticos/metabolismo , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/metabolismo , Zea mays/crescimento & desenvolvimento , Zea mays/metabolismo , Regulação da Expressão Gênica de Plantas/fisiologia , Melhoramento Vegetal , Proteínas de Plantas/metabolismo
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