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1.
Gen Psychiatr ; 37(5): e101613, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39314264

RESUMO

Background: The research findings on the topological properties of functional connectomes (TP-FCs) in patients with schizophrenia (SZPs) exhibit inconsistencies and contradictions, which can be attributed to limitations such as small sample sizes and heterogeneous data processing techniques. Aims: To address these limitations, we conducted a large-scale study. Uniform data processing flows were employed to investigate the aberrant TP-FCs and the associations between TP-FCs and symptoms or cognitions (A-TP-SCs) in SZPs. Methods: The large-scale study included six datasets from four sites, involving 497 SZPs and 374 healthy controls (HCs). A uniform process for imaging data preprocessing and functional connectivity matrix configuration was used. ComBat was employed for data harmonisation, and various TPs were calculated. We explored between-group differences in brain functional integration (FI) and functional segregation (FS) measured with TP-FCs, and conducted partial correlation analyses, with adjustments for age, gender and educational level, to identify A-TP-SCs. Results: Compared with random networks and HCs, SZPs maintained small-worldness and global FI capacity despite their compromised global FS capacity and resilience. A decline in nodal FI and FS capacity was observed in sensory areas, whereas an increase in nodal FI capacity was found in regions associated with cognition and information integration. In addition, associations between TP-FCs and positive symptoms, negative symptoms or cognitive functions including speed of processing, visual learning and the ability to inhibit cognitive interference were identified in SZPs. Conclusions: The identified A-TP-SCs verified that reductions in FS and resilience indicated pathological impairments in schizophrenia. The A-TP-SCs or TP-FCs, which measured the same attributes of the functional connectomes, exhibited high internal consistency, robustly reinforcing these findings.

2.
Front Biosci (Landmark Ed) ; 29(8): 278, 2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39206914

RESUMO

BACKGROUND: Bone tissue engineering offers a new approach for the treatment of bone defects, with angiogenesis being critical to the survival and development of tissue-engineered bone. Mineralized osteoblasts (MOBs) have been reported to promote vascular formation by endothelial cells (ECs) through the secretion of exosomes containing a variety of angiogenic factors. The aim of the present study was to investigate the effect of miR-423-5p contained within exosomes derived from MOBs (MOB-Exos) on EC angiogenesis. METHODS: The Cell Counting Kit-8 (CCK-8), scratch wound healing, Transwell migration, and tube formation assays were conducted to assess the in vitro effects of MOB-Exos on EC proliferation, migration, and tubule-forming capabilities. The miR-423-5p level in MOB-Exos was quantified using quantitative polymerase chain reaction (qPCR). Co-culture experiments were used to study the exosomal transport of miR-423-5p and its angiogenic effects. High-throughput sequencing was used to identify differentially expressed genes, and a dual luciferase reporter assay to determine whether CXCL10 was a direct target gene for miR-423-5p. Furthermore, the in vivo effect of MOB-Exos-derived miR-423-5p on angiogenesis was evaluated using a subcutaneous xenograft model. RESULTS: MOB-Exos significantly promoted the in vitro proliferation, migration, and tubule formation of ECs. A high level of miR-423-5p was found in MOB-Exos and promoted the angiogenesis of ECs. The CXCL10 gene was significantly downregulated in ECs upon miR-423-5p mimic transfection. Dual luciferase reporter assay confirmed the direct binding of miR-423-5p to the CXCL10 gene. miR-423-5p derived from MOB-Exos upregulated expression of the vascular markers CD31 and vascular endothelial growth factor (VEGF) in vivo, thus underscoring its angiogenic potential. CONCLUSION: This study found that miR-423-5p derived from MOB-Exos could potentially enhance EC angiogenesis via the regulation of CXCL10. Therefore, exosomes are promising therapeutic candidates for clinical bone defects.


Assuntos
Quimiocina CXCL10 , Exossomos , MicroRNAs , Neovascularização Fisiológica , Osteoblastos , MicroRNAs/genética , MicroRNAs/metabolismo , Humanos , Osteoblastos/metabolismo , Osteoblastos/citologia , Exossomos/metabolismo , Exossomos/genética , Animais , Neovascularização Fisiológica/genética , Quimiocina CXCL10/metabolismo , Quimiocina CXCL10/genética , Células Endoteliais/metabolismo , Proliferação de Células/genética , Movimento Celular , Células Endoteliais da Veia Umbilical Humana/metabolismo , Camundongos , Camundongos Nus , Angiogênese
3.
J Org Chem ; 89(14): 9853-9860, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-38822472

RESUMO

An efficient and chemodivergent synthesis of highly functionalized 1,4-dihydropyridazines and pyrazoles has been accomplished via base-promoted annulation between hydrazones and alkyl 2-aroyl-1-chlorocyclopropanecarboxylates, respectively. This transition-metal-free domino reaction proceeded rapidly under mild basic conditions, affording potentially bioactive 1,4-dihydropyridazine and pyrazole derivatives in moderate yields. The conversion of 1,4-dihydropyridazine to pyrazole was confirmed by adjusting the quantity of the base.

4.
Stem Cells Int ; 2024: 5512423, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38765936

RESUMO

Exosomes secreted from osteoblasts (OBs) can regulate the angiogenesis of endothelial cells (ECs); however, whether cerebrospinal fluid pulsation (CSFP) stress, a special mechanical stimulation, can influence the cell's communication in the context of angiogenesis remains unknown. In this study, the effect of exosomes derived from CSFP stress-stimulated OBs on facilitating the angiogenesis of ECs was investigated. First, OBs were cultured in a CSFP bioreactor, and exosomes derived from OBs were isolated and identified. Cell Counting Kit 8 assay, transwell migration assay, wound healing migration assay, and tube formation assay were conducted to assess the effects of CSFP stress-stimulated OBs-derived exosomes (CSFP-Exos) on the angiogenesis of ECs. Then high-throughput RNA sequencing was used to determine the miRNA profiles of Non-CSFP stress-stimulated OBs-derived exosomes (NCSFP-Exos) and CSFP-Exos, and the luciferase reporter gene assay was performed to confirm the binging of miR-423-5p to DUSP8. In addition, the Matrigel plug assay was performed to explore whether exosomal miR-423-5p has the same effects in vivo. Our results suggested that CSFP-Exos can promote the angiogenesis of ECs, and miR-423-5p was enriched in CSFP-Exos. Moreover, miR-423-5p could promote the effect of angiogenesis via directly targeting dual-specificity phosphatase 8 (DUSP8), which inhibited the ERK1/2 signaling pathway. In conclusion, exosomal miR-423-5p derived from CSFP stress-stimulated OBs could promote the angiogenesis of ECs by the DUSP8/ERK1/2 signaling pathway.

5.
Comput Biol Med ; 158: 106830, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37011432

RESUMO

BACKGROUND: Recently, a novel approach axis-blade angle (ABA) was developed to measure implant positions during trochanteric hip fracture surgery. It was defined as the sum of two angles α and ß measured between the femoral neck axis and helical blade axis in anteroposterior and lateral X-ray films, respectively. Although its clinical practicability has been confirmed, the mechanism is yet to be investigated by means of finite element (FE) analysis. METHODS: Computed tomography images of four femurs and dimensions of one implant at three angles were obtained to construct FE models. For each femur, 15 FE models in an arrangement (intramedullary nails at three angles multiplying five blade positions) were established. Under the simulation of normal walking loads, the ABA, von Mises stress (VMS), maximum/minimum principal strain and displacement were analyzed. RESULTS: When the ABA increased, all outcome indicators initially decreased till reaching inferior-middle site and then increased while the blade positions within the femoral head shifted from the superior-anterior quadrant toward the inferior-posterior quadrant, where the ABA were higher. Only the peak VMS of implant models in the inferior-posterior quadrant (particularly the inferior-middle site within) with blades in did not reach the yielding (risky) cut-off. CONCLUSIONS: From the perspective of angles, ABA, this study demonstrated the inferior-posterior quadrant as the relatively stable and safe regions, especially the inferior-middle site within. This was similar but more elaborate compared with previous studies and clinical practice. Therefore, ABA could be employed as a promising approach to anchor the implants into the optimal region.


Assuntos
Fixação Intramedular de Fraturas , Fraturas do Quadril , Humanos , Análise de Elementos Finitos , Fraturas do Quadril/diagnóstico por imagem , Fraturas do Quadril/cirurgia , Fêmur/diagnóstico por imagem , Fêmur/cirurgia , Fixação Intramedular de Fraturas/métodos , Próteses e Implantes
6.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 39(12): 1406-1409, 2022 Dec 10.
Artigo em Chinês | MEDLINE | ID: mdl-36453969

RESUMO

OBJECTIVE: To explore the phenotypic characteristics of paternal chromosomal simplex 3q microduplication syndrome. METHODS: Amniotic fluid samples of 3 fetuses from a same couple were subjected to prenatal diagnosis through combined high-resolution chromosomal G-banding karyotyping and chromosomal microarray analysis (CMA). Peripheral blood samples were also collected the couple for the determination of parental origin. RESULTS: The karyotypes of all three fetuses were 46,XN,dup(3)(q25q26.1), and their CMA results were arr[hg19]3q25.33q26.1(159 336 333-166 924 969)×3. The duplication in the three fetuses have all derived from their father. No anomaly with found with the mother by CMA . CONCLUSION: Through combined G-banded chromosomal karyotyping and CMA assay, a paternally derived 3q25.33-q26.1 microduplication has been identified, which has enabled genetic counseling for this couple.


Assuntos
Testes Genéticos , Diagnóstico Pré-Natal , Feminino , Gravidez , Humanos , Masculino , Feto , Síndrome , Mães , Pai
7.
J Tissue Eng Regen Med ; 16(12): 1184-1195, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36348261

RESUMO

Blood vessel formation is the prerequisite for the survival and growth of tissue-engineered bone. Mineralized osteoblasts (MOBs) have been shown to regulate angiogenesis through the secretion of exosomes containing various pro-angiogenic factors. However, whether the mineralized osteoblast-derived exosomes (MOB-Exos) containing let-7f-5p can regulate the angiogenesis of endothelial cells (ECs) is still unknown. In this study, the angiogenic capabilities of ECs respectively treated with MOB-Exos, let-7f-5p mimicked MOB-Exos (miR mimic group), and let-7f-5p inhibited MOB-Exos (miR inhibitor group) were compared through in vitro and in vivo studies. Moreover, the potential mechanism of MOB-Exo let-7f-5p regulating angiogenesis was explored by verifying the role of the Erk1/2 signaling pathway and target gene DUSP1. The results showed that MOB-Exos could significantly promote the angiogenesis of ECs, which could be enhanced by mimicked exosomal let-7f-5p and attenuated by inhibited exosomal let-7f-5p. Let-7f-5p could suppress the luciferase activity of wide-type DUSP1, and the mutation of DUSP1 could abrogate the repressive ability of let-7f-5p. Furthermore, the expression of DUSP1 exhibited a reversed trend to that of pErk1/2. The expression of pErk1/2 was significantly higher in the miR mimic group and lower in the miR inhibitor group than that in the MOB-Exos group, while inhibition of pErk1/2 could partly impair the angiogenic capabilities of ECs. In conclusion, we concluded that exosomal let-7f-5p derived from MOBs could promote the angiogenesis of ECs via activating the DUSP1/Erk1/2 signaling pathway, which might be a promising target for promoting the angiogenesis of tissue-engineered bone.


Assuntos
Exossomos , MicroRNAs , Fosfatase 1 de Especificidade Dupla/metabolismo , Células Endoteliais/metabolismo , Exossomos/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Neovascularização Patológica , Osteoblastos/metabolismo , Transdução de Sinais , Animais
8.
Mol Cytogenet ; 15(1): 32, 2022 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-35927742

RESUMO

BACKGROUND: The mosaic forms and clinical phenotypes of fetuses with isochromosome Y are difficult to predict. Therefore, we summarized the cases of nine fetuses with isochromosome Y identified in prenatal diagnosis with a combination of molecular cytogenetic techniques, providing clinical evidence for prenatal genetic counseling. METHODS: The prenatal diagnosis and pregnancy outcomes of nine fetuses with isochromosome Y were obtained by a  retrospective analysis. Isochromosome Y was identified prenatally by different approaches, such as conventional karyotyping, chromosomal microarray analysis (CMA), quantitative fluorescent polymerase chain reaction (QF-PCR) and fluorescence in situ hybridization (FISH). RESULTS: Seven idic(Y) fetuses and two i(Y) fetuses were identified. One fetus was complete for i(Y)(p10), and the rest with 45,X had mosaic forms. A break and fusion locus was identified in Yp11.3 in one fetus, in Yq11.22 in six fetuses and in Yp10 in two fetuses. The CMA results suggested that different deletions and duplications were found on the Y chromosome. The deletion fragments ranged from 4.7 Mb to the entire Y chromosome, and the duplication fragments ranged from 10.4 to 18.0 Mb. QF-PCR analysis suggested that the AZF region was intact in one fetus, four fetuses had AZFb+c+d deletion, one fetus had AZFa+b+c+d deletion, and one fetus had AZFc+d deletion. Finally, four healthy male neonates were delivered successfully, but the parents of the remaining five fetuses, including three healthy and two unhealthy fetuses, chose to terminate their pregnancies. CONCLUSION: The fetus and neonate phenotype of prenatally detected isochromosome Y usually is that of a normally developed male, ascertained in the absence of other indicators of a fetal structural anomaly. Our study provides clinical reference materials for risk assessment and permits better prenatally counseling and preparation of parents facing the birth of isochromosome Y fetuses.

9.
Front Surg ; 9: 855851, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35402493

RESUMO

Purpose: To systematically evaluate the benefits of reducing and fixing displaced lesser trochanter (LT) of trochanteric fractures and when this procedure is worth the effect. Methods: From database establishment through March 2021, four online databases (PubMed, Cochrane, Embase, and Web of Science) were searched for relevant literature that investigated reduction and fixation for displaced LT of trochanteric fractures. The papers were then screened by two reviewers independently and in duplicate according to prior inclusion and exclusion criteria. Demographic data as well as data on fracture types, surgical protocols, and surgical outcomes were recorded, analyzed, and interpreted. Results: Total 10 clinical studies with 928 patients were included, in which 48 cases had intact LT and 880 cases involved the displaced LT, of which 196 (22.27%) cases underwent reduction and fixation for LT while the rest of 684 (77.73%) cases not. In these studies, complications were evaluated as a more applicable predictive parameter for operation than postoperative hip function. Conclusion: It was beneficial to reduce and fix the displaced LT when one of the conditions below occurred: displacement distance of LT ≥2 cm, quantity of comminuted LT fragments ≥2, and range of LT fragments in medial wall ≥75%; the fracture line of LT fragments reaching or exceeding the midline of the posterior wall.

10.
Tissue Eng Part A ; 28(7-8): 366-372, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34569267

RESUMO

Laminectomy can effectively decompress the spinal cord and expand the vertebral canal. However, the fibrosis that appears may cause adherence and recompression of the spinal cord or/and nerve root, which may cause failed back syndrome (FBS) and make the reexposure process more difficult. Reconstruction of the epidural fat may be an ideal method to achieve satisfactory results. Thirty-six New Zealand rabbits were randomly divided into three groups: control, extracellular matrix (ECM), and ECM+aMSCs groups. Saline, ECM gel, and ECM+aMSC complex were placed, respectively, at the fifth lumbar vertebrate of the rabbits. Epidural fat and fibrosis formation were detected by magnetic resonance imaging (MRI) and histologically at the 4th, 8th, and 12th weeks. Quantitative RT-PCR was used to detect the expression of interleukin 6 (IL-6) and transforming growth factor ß (TGF-ß). MRI and Oil Red O staining revealed epidural fat formation at the 12th week in the ECM+aMSCs group. Hematoxylin and eosin staining showed that the numbers of fibroblasts in the ECM gel and ECM+aMSCs groups were less than the control group at the 4th and 8th weeks (p < 0.05). Masson's trichrome staining showed that the proportion of collagen fibers in the ECM gel and ECM+aMSCs group was lower than the control group (p < 0.05). Quantitative RT-PCR showed the expressions of TGF-ß and IL-6 were lower in the ECM gel and ECM+aMSCs group than those in the control group (p < 0.05) at the 4th week, but higher at the 8th week. We successfully reconstructed the epidural fat with ECM gel and aMSC complex; additionally, IL-6 and TGF-ß cytokines were lower at early stage after laminectomy. Impact statement Our study revealed that epidural fat formed at the 12th week in the extracellular matrix (ECM) plus mesenchymal stem cell (MSC) group after laminectomy in rabbits; additionally, transforming growth factor ß (TGF-ß) (fibrosis) and interleukin 6 (IL-6) (inflammation) expression was reduced. Thus, we believe that our study makes a significant contribution to the literature because we were able to successfully reconstruct the epidural fat with an ECM gel combined with MSCs and reduce local inflammation.


Assuntos
Interleucina-6 , Laminectomia , Animais , Fibrose , Inflamação , Laminectomia/efeitos adversos , Coelhos , Fator de Crescimento Transformador beta
11.
Schizophr Bull Open ; 3(1): sgac024, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-39144775

RESUMO

Objective: Cognitive symptoms are associated with significant dysfunction in schizophrenia. Oxidative stress and inflammation involving histone deacetylase (HDAC) have been implicated in the pathophysiology of schizophrenia. Sulforaphane has antioxidant properties and is an HDAC inhibitor. The objective of this study was to determine the efficacy of sulforaphane on cognition dysfunction for patients with schizophrenia. Methods: This double-blind randomized 22-week trial of patients with first-episode schizophrenia was conducted in four psychiatric institutions in China. Patients were randomized to three groups (two doses of sulforaphane vs. placebo) and symptomatic and cognitive assessments were completed at multiple times. The primary outcome measure was change in the MATRICS Composite score. The secondary outcomes were change in MATRICS Domain scores, PANSS Total Scores and change in side-effects. Results: A total of 172 patients were randomized and 151 patients had at least one follow up evaluation. There were no significant effects of sulforaphane, on the primary outcome, MATRICS overall composite score. However, on secondary outcomes, sulforaphane did significantly improve performance scores on MATRICS battery Domains of spatial working memory (F = 5.68, P = 0.004), reasoning-problem solving (F = 2.82, P = 0.063), and verbal learning (F = 3.56, P = 0.031). There were no effects on PANSS symptom scores. Sulforaphane was well tolerated. Conclusion: Although the primary outcome was not significant, improvement in three domains of the MATRICS battery, suggests a positive cognitive effect on some cognitive functions, which warrants further clinical trials to further assess whether sulforaphane may be a useful adjunct for treating some types of cognitive deficits in schizophrenia.

12.
Neural Plast ; 2021: 9954547, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34512748

RESUMO

Background: Previous studies have revealed the abnormalities in homotopic connectivity in schizophrenia. However, the relationship of these deficits to antipsychotic treatment in schizophrenia remains unclear. This study explored the effects of antipsychotic therapy on brain homotopic connectivity and whether the homotopic connectivity of these regions might predict individual treatment response in schizophrenic patients. Methods: A total of 21 schizophrenic patients and 20 healthy controls were scanned by the resting-state functional magnetic resonance imaging. The patients received olanzapine treatment and were scanned at two time points. Voxel-mirrored homotopic connectivity (VMHC) and pattern classification techniques were applied to analyze the imaging data. Results: Schizophrenic patients presented significantly decreased VMHC in the temporal and inferior frontal gyri, medial prefrontal cortex (MPFC), and motor and low-level sensory processing regions (including the fusiform gyrus and cerebellum lobule VI) relative to healthy controls. The VMHC in the superior/middle MPFC was significantly increased in the patients after eight weeks of treatment. Support vector regression (SVR) analyses revealed that VMHC in the superior/middle MPFC at baseline can predict the symptomatic improvement of the positive and negative syndrome scale after eight weeks of treatment. Conclusions: This study demonstrated that olanzapine treatment may normalize decreased homotopic connectivity in the superior/middle MPFC in schizophrenic patients. The VMHC in the superior/middle MPFC may predict individual response for antipsychotic therapy. The findings of this study conduce to the comprehension of the therapy effects of antipsychotic medications on homotopic connectivity in schizophrenia.


Assuntos
Antipsicóticos/uso terapêutico , Imageamento por Ressonância Magnética/métodos , Rede Nervosa/diagnóstico por imagem , Olanzapina/uso terapêutico , Córtex Pré-Frontal/diagnóstico por imagem , Esquizofrenia/diagnóstico por imagem , Adolescente , Adulto , Antipsicóticos/farmacologia , Feminino , Humanos , Masculino , Rede Nervosa/efeitos dos fármacos , Olanzapina/farmacologia , Valor Preditivo dos Testes , Córtex Pré-Frontal/efeitos dos fármacos , Esquizofrenia/tratamento farmacológico , Resultado do Tratamento , Adulto Jovem
13.
NPJ Regen Med ; 6(1): 51, 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34489466

RESUMO

Mechanical loads are fundamental regulators of bone formation and remodeling. However, the molecular regulation of mechanotransduction during vertebral laminae regeneration remains poorly understood. Here, we found that cerebrospinal fluid pulsation (CSFP) stress-cyclic pulsation stress-could promote the osteogenic and angiogenic abilities of rat mesenchymal stromal cells (MSC), thereby promoting tissue-engineered laminae's bone and blood vessel formation. In the process, F-actin relayed CSFP stress to promote the nuclear translocation of YAP1, which then decreased the degradation and promoted the nuclear translocation of ß-Catenin. In turn, the nuclear translocation of ß-Catenin promoted the osteogenic differentiation and angiogenic abilities of MSC, thereby promoting tissue-engineered laminae's bone and blood vessel formation. Thus, we conclude that CSFP promotes the osteogenesis and angiogenesis of tissue-engineered laminae through the F-actin/YAP-1/ß-Catenin signaling axis. This study advances our understanding of vertebral laminae regeneration and provides potential therapeutic approaches for spinal degeneration after spinal laminectomy.

14.
Stem Cells Int ; 2021: 8359582, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34552633

RESUMO

Tissue engineering provides a promising way for the regeneration of artificial vertebral laminae. Previous studies have confirmed the feasibility of reconstructing vertebral laminae via hydroxyapatite-collagen I scaffolds and mesenchymal stromal cells. However, there were no studies exploring the degradation of hydroxyapatite-collagen I scaffolds and the function of Wnt/ß-catenin pathway in the process. In this study, tissue-engineered laminae (TEL) were constructed by nanohydroxyapatite/collagen I scaffolds and umbilical cord Wharton's Jelly mesenchymal stromal cells (WJ-MSCs). Cell attachment was observed by scanning electron microscopy, and cell viability was confirmed by Live/Dead staining. The rat models were randomly divided into control and ß-catenin inhibition groups. Vertebral lamina defect rat models were made on the fifth lumbar vertebrate, and TEL was implanted into the defect site. After 14 weeks, the newborn laminae were harvested for microcomputed tomography, histology, or transcriptional profile analysis. We found that, for the control group, the newborn lamina formation matched with the scaffold degradation and complete newborn laminae formed at the 14th week; for the ß-catenin inhibition group, the scaffold degradation rate overrated the lamina formation and no complete artificial laminae were formed at the 14th week. In addition, the osteoclastic genes, such as Cathepsin K or RANKL, in the control groups were significantly lower than the ß-catenin inhibition group, and the antiosteoclastic gene, OPG, in the control group was significantly higher than the ß-catenin inhibition group. In conclusion, inhibition of Wnt/ß-catenin pathway led to speedy scaffold degradation and deferred artificial lamina formation. Wnt/ß-catenin pathway played a critical role in maintaining the balance between scaffold degradation and bone formation in the process of vertebral lamina reconstruction.

15.
Eur Arch Psychiatry Clin Neurosci ; 271(4): 783-798, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32215727

RESUMO

Previous studies have demonstrated the efficacy of metacognitive training (MCT) in schizophrenia. However, the underlying mechanisms related to therapeutic effect of MCT remain unknown. The present study explored the treatment effects of MCT on brain regional neural activity using regional homogeneity (ReHo) and whether these regions' activities could predict individual treatment response in schizophrenia. Forty-one patients with schizophrenia and 20 healthy controls were scanned using resting-state functional magnetic resonance imaging. Patients were randomly divided into drug therapy (DT) and drug plus psychotherapy (DPP) groups. The DT group received only olanzapine treatment, whereas the DPP group received olanzapine and MCT for 8 weeks. The results revealed that ReHo in the right precuneus, left superior medial prefrontal cortex (MPFC), right parahippocampal gyrus and left rectus was significantly increased in the DPP group after 8 weeks of treatment. Patients in the DT group showed significantly increased ReHo in the left ventral MPFC/anterior cingulate cortex (ACC), left superior MPFC/middle frontal gyrus (MFG), left precuneus, right rectus and left MFG, and significantly decreased ReHo in the bilateral cerebellum VIII and left inferior occipital gyrus (IOG) after treatment. Support vector regression analyses showed that high ReHo levels at baseline in the right precuneus and left superior MPFC could predict symptomatic improvement of Positive and Negative Syndrome Scale (PANSS) after 8 weeks of DPP treatment. Moreover, high ReHo levels at baseline and alterations of ReHo in the left ventral MPFC/ACC could predict symptomatic improvement of PANSS after 8 weeks of DT treatment. This study suggests that MCT is associated with the modulation of ReHo in schizophrenia. ReHo in the right precuneus and left superior MPFC may predict individual therapeutic response for MCT in patients with schizophrenia.


Assuntos
Esquizofrenia , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Humanos , Imageamento por Ressonância Magnética , Olanzapina , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/tratamento farmacológico
16.
Stem Cells Int ; 2020: 8026362, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32714396

RESUMO

BACKGROUND: Angiogenesis is a prerequisite step to achieve the success of bone regeneration by tissue engineering technology. Previous studies have shown the role of cerebrospinal fluid pulsation (CSFP) stress in the reconstruction of tissue-engineered laminae. In this study, we investigated the role of CSFP stress in the angiogenesis of tissue-engineered laminae. METHODS: For the in vitro study, a CSFP bioreactor was used to investigate the impact of CSFP stress on the osteogenic mesenchymal stem cells (MSCs). For the in vivo study, forty-eight New Zealand rabbits were randomly divided into the CSFP group and the Non-CSFP group. Tissue-engineered laminae (TEL) was made by hydroxyapatite-collagen I scaffold and osteogenic MSCs and then implanted into the lamina defect in the two groups. The angiogenic and osteogenic abilities of newborn laminae were examined with histological staining, qRT-PCR, and radiological analysis. RESULTS: The in vitro study showed that CSFP stress could promote the vascular endothelial growth factor A (VEGF-A) expression levels of osteogenic MSCs. In the animal study, the expression levels of angiogenic markers in the CSFP group were higher than those in the Non-CSFP group; moreover, in the CSFP group, their expression levels on the dura mater surface, which are closer to the CSFP stress stimulation, were also higher than those on the paraspinal muscle surface. The expression levels of osteogenic markers in the CSFP group were also higher than those in the Non-CSFP group. CONCLUSION: CSFP stress could promote the angiogenic ability of osteogenic MSCs and thus promote the angiogenesis of tissue-engineered laminae. The pretreatment of osteogenic MSC with a CSFP bioreactor may have important implications for vertebral lamina reconstruction with a tissue engineering technique.

17.
Front Psychiatry ; 11: 234, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32292360

RESUMO

BACKGROUND: Previous studies have revealed the efficacy of metacognitive training for schizophrenia. However, the underlying mechanisms of metacognitive training on brain function alterations, including the default-mode network (DMN), remain unknown. The present study explored treatment effects of metacognitive training on functional connectivity of the brain regions in the DMN. METHODS: Forty-one patients with schizophrenia and 20 healthy controls were scanned using resting-state functional magnetic resonance imaging. Patients were randomly assigned to drug plus psychotherapy (DPP) and drug therapy (DT) groups. The DPP group received olanzapine and metacognitive training, and the DT group received only olanzapine for 8 weeks. Network homogeneity (NH) was applied to analyze the imaging data, and pattern classification techniques were applied to test whether abnormal NH deficits at baseline might be used to discriminate patients from healthy controls. Abnormal NH in predicting treatment response was also examined in each patient group. RESULTS: Compared with healthy controls, patients at baseline showed decreased NH in the bilateral ventral medial prefrontal cortex (MPFC), right posterior cingulate cortex (PCC)/precuneus, and bilateral precuneus and increased NH in the right cerebellum Crus II and bilateral superior MPFC. NH values in the right PCC/precuneus increased in the DPP group after 8 weeks of treatment, whereas no substantial difference in NH value was observed in the DT group. Support vector machine analyses showed that the accuracy, sensitivity, and specificity for distinguishing patients from healthy controls were more than 0.7 in the NH values of the right PCC/precuneus, bilateral ventral MPFC, bilateral superior MPFC, and bilateral precuneus regions. Support vector regression analyses showed that high NH levels at baseline in the bilateral superior MPFC could predict symptomatic improvement of positive and negative syndrome scale (PANSS) after 8 weeks of DPP treatment. No correlations were found between alterations in the NH values and changes in the PANSS scores/cognition parameters in the patients. CONCLUSION: This study provides evidence that metacognitive training is related to the modulation of DMN homogeneity in schizophrenia.

18.
J Org Chem ; 85(4): 2202-2212, 2020 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-31904976

RESUMO

A synthesis of the 2-azatricyclo[4.3.2.04,9]undecane ring system-a hitherto unreported bridged azatricyclic ring system-beginning from tricarbonyl(tropone)iron and allylamine was accomplished in three steps: (1) aza-Michael addition of allylamine to tricarbonyl(tropone)iron; (2) Boc-protection of the resulting secondary amine; and (3) oxidative demetallation leading to a spontaneous intramolecular Diels-Alder reaction. The effect of a variety of parameters on the intramolecular Diels-Alder reaction was investigated, including diene and dienophile substitution patterns and dienophile tether length.

19.
Connect Tissue Res ; 61(6): 537-545, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-31185754

RESUMO

Purpose: To investigate the proliferative, adipogenic, and immunological properties of rabbit Mesenchymal stromal cells (MSCs) derived from bone marrow and umbilical cord Wharton's jelly.Materials and Methods: We extracted rabbit MSCs from bone marrow (BMSCs) and umbilical cord Wharton's jelly (WJ-MSCs). Both BMSCs and WJ-MSCs underwent adipogenic differentiation for 2 weeks, and then were transferred to non-inductive complete medium. Their adipogenic capacities were examined by histomorphometry and quantitative RT-PCR (qRT-PCR). The immunological markers were determined by mRNA expression of MHC-Ia, MHC-II, and RLA-DRA by qRT-PCR and protein expression of MHC-II by immunofluorescent staining. The proliferative capacities of adipogenic MSCs were also examined by counting kit-8 experiment and cell population doubling time.Results: We found that adipogenic differentiation increased the mRNA expression levels of adipogenic and immunological markers. The protein expression levels of MHC-II also increased after adipogenic differentiation in both groups. The adipogenic BMSCs showed higher mRNA expression levels of adipogenic and immunological markers. Removal of adipogenic agents after 2 weeks of adipo-differentiation inversely decreased the expression of immunological and adipogenic markers. The adipo-differentiation could decreased the proliferative capacities of both MSCs, but the adipogenic WJ-MSCs showed significantly higher proliferative capacities than BMSCs.Conclusions: Adipogenic differentiation increased the immunogenicity of both BMSCs and WJ-MSCs, and dedifferentiation inversely decreased their immunogenicity. Adipogenic WJ-MSCs showed significantly higher proliferative and immunoprivileged capacities than BMSCs, and the dedifferentiated BMSCs showed almost the same adipogenic capacity as WJ-MSCs. WJ-MSCs were more suitable than BMSCs for adipose tissue engineering.


Assuntos
Tecido Adiposo/fisiologia , Células da Medula Óssea/citologia , Células-Tronco Mesenquimais/citologia , Engenharia Tecidual , Geleia de Wharton/citologia , Adipogenia/genética , Animais , Antígenos de Superfície/metabolismo , Células da Medula Óssea/imunologia , Diferenciação Celular/genética , Proliferação de Células/genética , Forma Celular , Feminino , Regulação da Expressão Gênica , Células-Tronco Mesenquimais/metabolismo , Coelhos
20.
Bone Joint Res ; 8(10): 502-508, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31728190

RESUMO

OBJECTIVES: Different criteria for assessing the reduction quality of trochanteric fractures have been reported. The Baumgaertner reduction quality criteria (BRQC) are relatively common and the Chang reduction quality criteria (CRQC) are relatively new. The objectives of the current study were to compare the reliability of the BRQC and CRQC in predicting mechanical complications and to investigate the clinical implications of the CRQC. METHODS: A total of 168 patients were assessed in a retrospective observational study. Clinical information including age, sex, fracture side, American Society of Anesthesiologists (ASA) classification, tip-apex distance (TAD), fracture classification, reduction quality, blade position, BRQC, CRQC, bone quality, and the occurrence of mechanical complications were used in the statistical analysis. RESULTS: A total of 127 patients were included in the full analysis, and mechanical complications were observed in 26 patients. The TAD, blade position, BRQC and CRQC were significantly associated with mechanical complications in the univariate analysis. Only the TAD (p = 0.025) and the CRQC (p < 0.001) showed significant results in the multivariate analysis. In the comparison of the receiver operating characteristic curves, the CRQC also performed better than the BRQC. CONCLUSION: The CRQC are reliable in predicting mechanical complications and are more reliable than the BRQC. Future studies could use the CRQC to assess fracture reduction quality. Intraoperatively, the surgeon should refer to the CRQC to achieve good reduction in trochanteric fractures.Cite this article: Bone Joint Res 2019;8:502-508.

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