Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 82
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Mol Med Rep ; 2020 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-32186751

RESUMO

Idiopathic membranous nephropathy (IMN) is one of the main types of chronic kidney disease in adults and one of the most common causes of end­stage renal disease. In recent years, the morbidity of IMN among primary glomerular diseases has markedly increased, while the pathogenesis of the disease remains unclear. To address this, a number of experimental models, including Heymann nephritis, anti­thrombospondin type­1 domain­containing 7A antibody­induced IMN, cationic bovine serum albumin, anti­human podocyte antibodies and zymosan­activated serum­induced C5b­9, have been established. This review comprehensively summarized the available animal and cell models for IMN. The limitations and advantages of the current models were discussed and two improved models were introduced to facilitate the selection of an appropriate model for further studies on IMN.

2.
Korean J Radiol ; 21(4): 505-508, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32174053

RESUMO

The epidemic of 2019 novel coronavirus, later named as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is still gradually spreading worldwide. The nucleic acid test or genetic sequencing serves as the gold standard method for confirmation of infection, yet several recent studies have reported false-negative results of real-time reverse-transcriptase polymerase chain reaction (rRT-PCR). Here, we report two representative false-negative cases and discuss the supplementary role of clinical data with rRT-PCR, including laboratory examination results and computed tomography features. Coinfection with SARS-COV-2 and other viruses has been discussed as well.

3.
JAMA Netw Open ; 3(3): e201226, 2020 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-32191330

RESUMO

Importance: There is currently no standard treatment strategy for patients with advanced non-small cell lung cancer (NSCLC) without driver gene variation after failure of 2 or more lines of chemotherapy. Objective: To assess the efficacy and safety of apatinib combined with oral vinorelbine. Design, Setting, and Participants: This phase 2 prospective nonrandomized clinical trial evaluating the efficacy and safety of apatinib plus vinorelbine recruited patients from Hunan Cancer Center, Hunan, China, from January 1, 2017, to November 30, 2018. Eligible patients were those with wild-type advanced NSCLC whose disease did not respond to at least 2 lines of chemotherapy. Patients were evaluated until December 31, 2019. Data were analyzed from July 2019 to December 2019. Intervention: Apatinib at an initial dose of 500 mg once daily and oral vinorelbine 60 mg/m2 once weekly were administered until disease progression, patient withdrawal, or occurrence of unacceptable toxic effects. Main Outcomes and Measures: The primary end point was overall response rate. Secondary end points were overall survival, progression-free survival, and safety. Results: The potential efficacy of apatinib plus vinorelbine was identified using drug susceptibility assay based on 3-dimensional coculture of tumor cells derived from 3 patients with lung adenocarcinoma. Among 30 patients enrolled, the median (range) age was 63 (34-78) years and 18 (60%) were men. Most patients (27 patients [90%]) had stage IV disease, and the median (range) number of prior unsuccessful treatments was 2 (2-5) lines of chemotherapy. Twenty-five patients (83%) completed the treatment, while 5 patients (17%) discontinued treatment owing to intolerable adverse events. The overall response rate was 36.7% (11 patients) and the disease control rate was 76.7% (23 patients). The median progression-free survival was 4.5 (95% CI, 2.4-6.6) months, and the median overall survival was 10.0 (95% CI, 4.8-17.1) months. Hand-foot syndrome was the most common adverse event observed, including grade 3 hand-foot syndrome observed in 5 patients (17%) and grade 4 hand-foot observed in 1 patient (3%). Grade 3 weakness was observed in 1 patient (3%). Conclusions and Relevance: These findings suggest that apatinib combined with oral vinorelbine is a potentially effective regimen with an acceptable safety profile. This regimen may have potential as a treatment option for patients with wild-type advanced NSCLC whose disease failed at least 2 prior lines of chemotherapy. Trial Registration: ClinicalTrials.gov Identifier: NCT03652857.

4.
Medicine (Baltimore) ; 99(12): e19496, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32195949

RESUMO

BACKGROUND: Dysmenorrhea seriously affects the ability of women to perform normal social activities and decreases their quality of life. Primary dysmenorrhea can be effectively treated with acupuncture. Based on the wrist-ankle acupuncture (WAA) theory, we designed a portable WAA point compression treatment strap that treats diseases by automatically applying pressure to acupuncture points. The proposed study aims to evaluate the immediate analgesic effect of the acupressure wrist-ankle strap in patients with primary dysmenorrhea. METHODS: The study will be a randomized controlled trial conducted from May 1, 2019 to May 30, 2020 that includes 78 students from Shanghai University of Traditional Chinese Medicine who have primary dysmenorrhea and meet the eligibility criteria. Participants will be randomly divided into 2 groups in a 1:1 allocation ratio. The intervention group will use the acupressure wrist-ankle strap equipped with tip compression component parts on the internal side; the control group will use the nonacupressure wrist-ankle strap with the tip compression parts removed. All participants will be treated for 30 minutes on the 1st day of menstruation. The primary outcome is the pain intensity score measured by the visual analog scale. The secondary outcomes are the onset time of analgesia, the pain threshold at Yinlingquan (SP 9), skin temperature at Guanyuan (CV 4), and expectations and satisfaction of patients as investigated via the expectation and treatment credibility scale. DISCUSSION: This trial will be the 1st study to evaluate the analgesic effect of the acupressure wrist-ankle strap in patients with primary dysmenorrhea. The quality of this study is ensured by the randomization, nonacupressure control, and blinded design. The results may provide evidence for a potential alternative treatment for primary dysmenorrhea and evidence-based proof of the analgesic effect of WAA.

5.
J Thorac Oncol ; 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-32112982

RESUMO

BACKGROUND: During non-reciprocal/reciprocal translocation process, 5'-ALK sometimes get retained in the genome and are detectable by next-generation sequencing (NGS); however, no report have investigated its clinical significance. Our study aimed to assess the impact of harboring 5'-ALK on the efficacy of crizotinib. PATIENTS AND METHODS: A total of 150 patients with NGS-identified ALK-rearranged NSCLC from March 2014 to July 2018 at the Hunan Cancer Hospital were enrolled in this study. The efficacy of crizotinib as first-line therapy was evaluated in 112 patients according to the retention of 5'-ALK. RESULTS: Among 150 NSCLC patients, non-reciprocal/reciprocal translocation was detected in 18.7% (28/150) and 3'-ALK fusion alone was detected in 81.3% (122/150). Among the 112 patients who received first-line crizotinib, 89 patients had 3'-ALK fusion alone (79 EML4-ALK and 10 non-EML4 ALK) and 23 patients had non-reciprocal/reciprocal ALK translocation. Among the patients with non-reciprocal/reciprocal ALK translocation, 3 patients harbored dual concurrent 3'-ALK fusions. Patients with non-reciprocal/reciprocal ALK translocation had higher incidence of brain metastasis at baseline than those with 3'-ALK fusion alone (39.1% vs. 13.4%, p=0.028). Crizotinib-treated patients with non-reciprocal/reciprocal ALK translocation had significantly shorter mPFS compared with patients carrying 3'-ALK fusion alone (6.1m vs. 12.0m, p=0.001) or with EML4-ALK fusion alone (6.1m vs. 12.6m, p=0.001). Multivariate analysis revealed that harboring non-reciprocal/reciprocal ALK translocation was an independent predictor of worse PFS for crizotinib-treated ALK-rearranged NSCLC (p=0.0046). CONCLUSIONS: Presence of non-reciprocal/reciprocal ALK translocation was predictive for worse PFS and greater likelihood of baseline brain metastases in patients with ALK-rearranged NSCLC who received first-line crizotinib.

7.
Lung Cancer ; 141: 82-88, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31982639

RESUMO

OBJECTIVES: We aimed to investigate the clinical efficacy of EGFR tyrosine kinase inhibitor (TKI, T) plus bevacizumab (an antiangiogenic therapy, A) in a real-world population and to provide insights into their mechanism of resistance. METHODS: This study included 256 NSCLC patients harboring EGFR sensitizing mutations (EGFR 19del and L858R) who underwent nextgeneration sequencing (NGS) with 168-gene panel prior to treatment between Jan 2015 to Aug 2018. Cohort A included 60 patients treated with A + T; while cohort B consisted of 120 patients treated with EGFR-TKI monotherapy with the patients identified using Propensity Score Matching (Ratio of 1:2). Clinical outcomes and potential resistance mechanism were evaluated. RESULTS: Baseline clinical characteristics were not significantly different between Cohort A and B. Compared with cohort B, cohort A had significantly better overall response rate (95% vs 74.2%, p = 0.001) and longer median progression-free survival (PFS, 16.5m vs.12.0 m, HR = 0.7, p = 0.001). Until Jan 2019, 31 and 103 patients in cohort A and B, respectively, were evaluated with progressive disease and underwent tissue re-biopsy and NGS profiling with 168-gene panel. In cohort B, T790M was the predominant acquired resistance mechanism, detected in 51.5% (53/103) of progressive tumors, followed by amplifications in EGFR (15.5%, 16/103) and MET (6.8%, 7/103). Contrastingly, cohort A had a significantly lower rate of T790 M mutation (35.5%, 11/31, p = 0.0003), followed by mutations in TP53 (29.0%, 9/31), RB1 (9.7%, 3/31), SMAD4 (3.2%, 1/31) and EGFR V834 L (3.2%, 1/31) and amplifications in EGFR (9.7%, 3/31), and MET(6.5%, 2/31). CONCLUSION: Treatment with first-line A + T significantly extends the time to progression and increases the response rate with acceptable safety profile. T790 M was the most common acquired resistance mechanism but it was less common in patients who received A + T.

8.
Biomed Pharmacother ; 121: 109599, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31707345

RESUMO

Diabetic nephropathy (DN) is a common but intractable diabetic microvascular complication. Tripterygium, a Chinses herb, has been proven to be effective for DN treatment. In this review, the efficacy and pharmacological mechanism of tripterygium and its extracts on DN is elucidated. Tripterygium and its extracts could effectively reduce urine protein and protect renal function. Its pharmacological mechanism involves anti-inflammation, anti-oxidation, anti-glomerulosclerosis and anti-fibrosis, which is achieved by balancing the Th1/Th2 cells, regulating macrophage infiltration, and regulating the following pathways: p38 MAPK, NF-κB, TGF-ß, Wnt/ß-catenin, Akt and Notch1. Although tripterygium and its extracts may result in some adverse effects, including liver-function damage, gastrointestinal reaction, menstrual disorders, and reproductive problems, they are considered good alternative medicines for DN if used with caution and in the proper manner.

9.
Parasit Vectors ; 12(1): 608, 2019 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-31881922

RESUMO

BACKGROUND: Cystic echinococcosis (CE) in humans and livestock is caused by Echinococcus granulosus (sensu lato). In China where CE is endemic, a number of studies have shown that Echinococcus granulosus (sensu stricto) is majorly responsible for CE. However, E. canadensis (G6) which is the second leading cause of CE is now being detected in most parts of the country. In this study, the species diversity and genetic variation of Echinococcus granulosus (s.l.) in four counties in Tibet Autonomous Region of China were investigated. METHODS: Infection with Echinococcus granulosus (s.s.) in yaks and sheep was identified using NADH dehydrogenase subunit 1 and 5 (nad1 and nad5) mitochondrial genes while the genotype G6 of E. canadensis initially diagnosed with NADH dehydrogenase subunit 1 (nad1) was further confirmed by analysis of the complete mitochondrial genome and a phylogenetic network constructed based on the nad2 and nad5 genes. RESULTS: Out of 85 hydatid cyst samples collected from slaughtered sheep (n = 54) and yaks (n = 31), 83 were identified as E. granulosus (s.s.) G1 (n = 77), G3 (n = 6) and 2 were identified as E. canadensis G6. Analysis of the nad1/nad5 genes revealed 16/17 mutations with 9/14 parsimony informative sites resulting in 15/14 haplotypes, respectively. Haplotype diversity (Hd) and nucleotide diversity (π) of E. granulosus (s.s.) population were 0.650 and 0.00127 for nad1 and 0.782 and 0.00306 for nad5, respectively, with an overall negative Tajima's D and Fu's Fs. A low FST indicated no genetic difference between isolates from sheep and yaks. CONCLUSION: Pockets of infection with E. canadensis (G6, G7, G8 and G10) have been previously reported in sheep, goats, yaks and/or humans in different parts of China. While the G6 genotype has been previously reported in sheep in the Tibet Autonomous Region, the detection in a yak in the present study represents the first to the best of our knowledge. Therefore, we recommend future surveys and control efforts to comprehensively investigate other potential intermediate hosts for the prevalence and genetic diversity of the E. canadensis group (G6, G7, G8 and G10) across the country and their inclusion into the existing CE control programme.

10.
Nanomedicine (Lond) ; 14(24): 3193-3212, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31855117

RESUMO

Aim: We aimed to investigate the proteomics of primary chondrocyte exosomes and the effect of exosomes in osteoarthritis (OA) treatment. Materials & methods: We isolated exosomes from primary chondrocytes cultured in normal (D0) and inflammatory environments induced by IL-1ß and determined the proteomics of these exosomes. Next, we investigated what effect and mechanism D0 chondrocytes exosomes have in OA treatment. Results: There were more proteins that belonged to mitochondrion and were involved in immune system processes in D0 exosomes. Notably, intra-articular administration of D0 exosomes successfully prevented the development of OA. D0 chondrocyte exosomes could restore mitochondrial dysfunction and polarize macrophage response toward an M2 phenotype. Conclusion: Our findings demonstrated that primary chondrocyte exosomes are efficient in OA treatment.

11.
ACS Appl Mater Interfaces ; 11(42): 38737-38745, 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31592677

RESUMO

Interface engineering holds huge potential for enabling exceptional physical properties in heterostructure materials via tuning properties at the atomic level. In this study, a heterostructure built by a new redox stable semiconductor SrFe0.75Ti0.25O3-δ (SFT) and an ionic conductor Sm0.25Ce0.75O2 (SDC) is reported. The SFT-SDC heterostructure exhibits a high ionic conductivity >0.1 S/cm at 520 °C, which is 1 order of magnitude higher than that of bulk SDC. When it was applied into the fuel cell, the SFT-SDC can realize favorable electrolyte functionality and result in an excellent power density of 920 mW cm-2 at 520 °C. The prepared SFT-SDC heterostructure materials possess both electronic and ionic conduction, where electron states modulate local electrical field to facilitate ion transport. Further investigations to calculate the structure and electronic structure/state of SFT and SDC are done using density functional theory (DFT). It is found that the reconstruction of the energy band at interfaces is responsible for such enhanced ionic conductivity and cell power output. The current study about the perovskite-based heterostructure presents a novel strategy for developing advanced ceramic fuel cells.

12.
Artif Intell Med ; 99: 101696, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31606115

RESUMO

The diagnosis of depression almost exclusively depends on doctor-patient communication and scale analysis, which have the obvious disadvantages such as patient denial, poor sensitivity, subjective biases and inaccuracy. An objective, automated method that predicts clinical outcomes in depression is essential for increasing the accuracy of depression recognition and treatments. This paper aims at better recognizing depression using the transformation of EEG features and machine learning methods. An experiment based on emotional face stimuli task was conducted, and twenty-eight subjects' EEG data were recorded from 128-channel HydroCel Geodesic Sensor Net (HCGSN) by Net Station software. The Mini International Neuropsychiatric Interview (MINI) was used by psychiatrists as the criterion for diagnosis of depression patients. The power spectral density and activity were respectively extracted as original features using Auto-regress model and Hjorth algorithm with different time windows. Two separate approaches processed the features: ensemble learning and deep learning. For the ensemble learning, a deep forest transformed the original features to new features that potentially improve feature engineering and a support vector machine (SVM) that was applied as classifier. For deep learning method, we added spatial information of EEG caps to both features by image conversion and adopted convolutional neural network (CNN) to recognize them. The performance of both methods was evaluated for separated and total frequency bands. As a result, the best accuracy obtained was 89.02% when we used the ensemble model and power spectral density. The best accuracy of deep learning method was 84.75% using the activity. These experimental results prove the efficiency of the proposed methods and show that EEG could be used as a reliable indicator for depression recognition, which makes it possible for EEG-based portable system design and application in auxiliary depression recognition in the future.

13.
Onco Targets Ther ; 12: 8319-8328, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31632081

RESUMO

Background: Gemcitabine is proven to be the first-line standard treatment of breast cancers. Yet, little is known involving gemcitabine resistance and remains largely to be elucidated. Materials and methods: We evaluated the expression of Cx43 in gemcitabine-resistant cells and parental cells by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot analyses. Dual-luciferase reporter assay was applied to examine the epigenetic regulator of Cx43. The role of miR-218-5p-Cx43 axis on cell cytotoxicity, cell proliferation, colony formation, chemoresistance and migration was detected via mammalian expression vector and small short RNA (shRNA) transfection in vitro. Results: In this study, we found that Cx43 expression levels were significantly lower in gemcitabine-resistant cells than in the parental cells. On deep investigation of the epigenetic regulation of Cx43, a few miRNA candidates targeting Cx43 were derived. Through dual-luciferase reporter assay, Cx43 was proved to be a direct target of miR-218-5p. Besides, qPCR, Western blot demonstrated an inverse correlation between miR-218-5p and Cx43 expression in breast cancer cells, thus forming the miR-218-5p-Cx43 axis. Notably, miR-218-5p-Cx43 axis was found to be involved in the process of gemcitabine chemoresistance, cell proliferation and migration in breast cancer cells. Conclusion: Our findings suggested that miR-218-5p-Cx43 axis was versatile and indicated significant potency in breast cancer cells. More importantly, miR-218-5p-Cx43 axis might be valuable in translational medicine, with therapeutic and prognostic information.

14.
Zhongguo Gu Shang ; 32(7): 653-657, 2019 Jul 25.
Artigo em Chinês | MEDLINE | ID: mdl-31382725

RESUMO

OBJECTIVE: To observe the repair effect of bone marrow mesenchymal stem cells (BMSCs) combined with basic fibroblast growth factor (bFGF) on spinal cord injury in rats and explore its mechanism. METHODS: SD rat BMSCs were obtained by serum culture technique. Eighty healthy 6-week-old male SD rats(weight about 240 g) were randomly divided into 4 groups with 20 each. The sham operation group underwent simple laminectomy without damaging spinal cord and was kept in the same condition as the other 3 groups. The other 3 groups underwent left T9 spinal cord hemisection to establish spinal cord injury model. After 9 days of modeling the local transplantation was performed. The Control group was implanted with gelatin sponge containing normal saline. The BMSCs transplantation group was implanted with gelatin sponge containing BMSCs. The bFGF+BMSCs transplantation group was implanted with gelatin sponge containing bFGF+BMSCs. After 4 and 8 weeks, the expression of NF-200 and GFAP in injured spinal cord tissue was analyzed by Western blotting and the recovery of hind limb function was evaluated by Basso Beattie Bresnahan(BBB) motor function score scale. RESULTS: The BBB scores of BMSCs transplantation group and bFGF+BMSCs transplantation group were better than control group at 4 and 8 weeks after operation (P<0.05) and there was significant difference between bFGF+BMSCs transplantation group and BMSCs transplantation group (P<0.05). After 4 and 8 weeks postoperatively, NF-200 expression was minimal in control group and only a small amount was expressed in BMSCs transplantation group while in bFGF+BMSCs transplantation group NF-200 was highly expressed(P<0.05). GFAP expression was high in control group, middle in BMSCs transplantation group and low in bFGF BMSCs transplantation group(P<0.05). There was significant difference between bFGF+BMSCs transplantation group, BMSCs transplantation group and control group(P<0.05). CONCLUSIONS: The combined transplantation of BMSCs and bFGF can repair the spinal cord injury in rats. The mechanism may be related to the decrease of GFAP expression and the increase of NF-200 expression.


Assuntos
Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Traumatismos da Medula Espinal , Animais , Células da Medula Óssea , Fator 2 de Crescimento de Fibroblastos , Masculino , Ratos , Ratos Sprague-Dawley , Medula Espinal
15.
Infect Genet Evol ; 75: 104019, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31470093

RESUMO

Enterocytozoon bieneusi and Giardia duodenalis are important opportunistic enteric zoonotic pathogens that cause diarrhoea and intestinal diseases in animals and humans. China is the largest producer of pigs, but whether Tibetan pigs, a unique pig breed in Tibet, are infected with E. bieneusi and G. duodenalis is unknown. Therefore, we conducted a molecular epidemiological survey to determine the prevalence of E. bieneusi and G. duodenalis in Tibetan pigs in Tibet, China, and identified the genotypes of these causative agents. A total of 345 faecal specimens were collected from Tibetan pigs from three Tibet counties (Milin, Cuona and Gongbujiangda), examined by nested PCR and sequenced utilizing genetic markers in the ribosomal internal transcribed spacer (ITS) region of the rRNA and glutamate dehydrogenase (gdh) gene for E. bieneusi and G. duodenalis, respectively. Moreover, using multilocus sequence typing, the subtypes of E. bieneusi were identified based on four loci (MS1, MS3, MS4 and MS7). A total of 41 (11.88%) faecal samples from Tibetan pigs were E. bieneusi-positive, and 2 (0.58%) were G. duodenalis-positive. The multivariate logistic regression analysis showed that age was considered a risk factor for Tibetan pig infection of E. bieneusi. Two novel (GB11, GB31) and four known E. bieneusi genotypes (EbpC, EbpD, PigEBITS5 and CHS12) were identified and were all classified as zoonotic group 1 according to the phylogenetic analysis. Two MLGs (MLGI and MLGII) were further identified in the E. bieneusi EbpC genotype by multilocus sequence typing analysis. In addition, two G. duodenalis assemblages (D and E) were found in the present study. To our knowledge, the current study is the first to detect the prevalence and perform genetic characterization of G. duodenalis in Tibetan pigs in Tibet, China. The results could provide essential data for controlling E. bieneusi and G. duodenalis infections in Tibetan pigs that are in contact with other animals and humans, as Tibetan pigs could be a potential source for human infection by these pathogens.

16.
Free Radic Biol Med ; 143: 1-15, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31351174

RESUMO

Excessive oxidative stress and inflammation are the key early events in the development of intervertebral disc degeneration (IVDD). The NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasome has been identified as the major source of oxidative stress and the inflammatory responses and thus is an attractive therapeutic target for IVDD. However, currently, there are no reports on the use of mesenchymal stem cell (MSC)-derived exosomes to reduce NLRP3 inflammasome expression for IVDD treatment. The present study aimed to investigate the therapeutic effect of exosomes for use as IVDD therapeutics. We first manufactured and evaluated the characteristics of exosomes. Then, we investigated the effects of exosomes on H2O2-induced nucleus pulposus (NP) cell inflammation. Third, we tested the function of exosomes with respect to H2O2-induced ROS production and mitochondrial dysfunction. Finally, the therapeutic effect of exosomes on IVDD was investigated using a rabbit IVDD model. Results showed that exosomes play an anti-inflammatory role in pathological NP cells by suppressing inflammatory mediators and NLRP3 inflammasome activation. Moreover, it was suggested that exosomes might supply mitochondrial proteins to NP cells, and that the damaged mitochondria could be restored with this supplement. Further, in the rabbit IVDD model, exosomes significantly prevented the progression of degenerative changes. Our results confirmed that the NLRP3 inflammasome is an effective target for IVDD treatment and that the injection of exosomes could be a promising therapeutic strategy.

17.
Theranostics ; 9(9): 2439-2459, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31131046

RESUMO

Mitochondrial dysfunction and oxidative stress damage are hallmarks of osteoarthritis (OA). Mesenchymal stem cell (MSC)-derived exosomes are important in intercellular mitochondria communication. However, the use of MSC exosomes for regulating mitochondrial function in OA has not been reported. This study aimed to explore the therapeutic effect of MSC exosomes in a three dimensional (3D) printed scaffold for early OA therapeutics. Methods: We first examined the mitochondria-related proteins in normal and OA human cartilage samples and investigated whether MSC exosomes could enhance mitochondrial biogenesis in vitro. We subsequently designed a bio-scaffold for MSC exosomes delivery and fabricated a 3D printed cartilage extracellular matrix (ECM)/gelatin methacrylate (GelMA)/exosome scaffold with radially oriented channels using desktop-stereolithography technology. Finally, the osteochondral defect repair capacity of the 3D printed scaffold was assessed using a rabbit model. Results: The ECM/GelMA/exosome scaffold effectively restored chondrocyte mitochondrial dysfunction, enhanced chondrocyte migration, and polarized the synovial macrophage response toward an M2 phenotype. The 3D printed scaffold significantly facilitated the cartilage regeneration in the animal model. Conclusion: This study demonstrated that the 3D printed, radially oriented ECM/GelMA/exosome scaffold could be a promising strategy for early OA treatment.

18.
Am J Sports Med ; 47(7): 1722-1733, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31100005

RESUMO

BACKGROUND: Mesenchymal stem cells (MSCs) can be isolated from various tissues and can present themselves as a promising cell source for cell-based therapies. Although adipose- and bone marrow-derived mesenchymal stem cells have already been used in a considerable number of clinical trials for osteoarthritis treatment, systematic analyses from single- to bulk-cell resolution as well as clinical outcomes of these 2 MSCs are still insufficient. PURPOSE: To explore the characteristics and differences of adipose-derived stem cells (ADSCs) and bone marrow MSCs (BMSCs) at single- and bulk-cell levels, to study the clinical outcomes of these 2 cells on the treatment of osteoarthritis, and to provide potential guidance on the more precise clinical application of these MSCs. STUDY DESIGN: Controlled laboratory study and meta-analysis. METHODS: Same donor-derived ADSCs and BMSCs were isolated and cultured. Single- and bulk-cell assays were used to identify the characteristics of these 2 cells. Meta-analysis of clinical trials was done to compare the clinical therapeutic effects in osteoarthritis treatment with ADSCs and BMSCs. RESULTS: Single-cell RNA sequencing analysis showed that the population of ADSCs showed lower transcriptomic heterogeneity when compared with BMSCs. Additionally, as compared with BMSCs, ADSCs were less dependent on mitochondrial respiration for energy production. Furthermore, ADSCs had a lower expression level of human leukocyte antigen class I antigen and higher immunosuppression capacity when compared with the BMSC population. Meta-analysis of current clinical trials of osteoarthritis treatment with MSCs consistently showed that ADSCs are more stable than BMSCs in their therapeutic effect. CONCLUSION: These results provide basic biological insights into human ADSCs and BMSCs at the single-cell resolution. Findings indicated that ADSCs may be a more controllable stem cell source, may be more adaptable to surviving in the hypoxic articular cavity niche, and may exhibit superiority in regulating inflammation. Based on the meta-analysis results of the different characteristics of ADSCs and BMSCs, ADSCs were implicated as being a better cell source for osteoarthritis treatment. CLINICAL RELEVANCE: These results guide a more precise clinical application of adipose and bone marrow mesenchymal stem cells.

19.
Mater Sci Eng C Mater Biol Appl ; 101: 588-595, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31029352

RESUMO

Articular cartilage lacks self-healing capacity, and there is no effective therapy facilitating cartilage repair. Osteoarthritis (OA) due to cartilage defects represents large and increasing healthcare burdens worldwide. Nowadays, the generation of scaffolds to preserve bioactive factors and the biophysical environment has received increasing attention. Furthermore, improved decellularization technology has provided novel insights into OA treatment. This review provides a comparative account of different cartilage defect therapies. Furthermore, some recent effective decellularization protocols have been discussed. In particular, this review focuses on the decellularization ratio of each protocol. Moreover, these protocols were compared particularly on the basis of immunogenicity and mechanical functionality. Further, various recellularization methods have been enlisted and the reparative capacity of decellularized cartilage scaffolds is evaluated herein. The advantages and limitations of different recellularization processes have been described herein. This provides a basis for the generation of decellularized cartilage scaffolds, thereby potentially promoting the possibility of decellularization as a clinical therapeutic target.


Assuntos
Cartilagem Articular/citologia , Engenharia Tecidual/métodos , Tecidos Suporte/química , Animais , Matriz Extracelular/química , Humanos , Estudos Prospectivos
20.
Nat Commun ; 10(1): 1707, 2019 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-30979875

RESUMO

Interest in low-temperature operation of solid oxide fuel cells is growing. Recent advances in perovskite phases have resulted in an efficient H+/O2-/e- triple-conducting electrode BaCo0.4Fe0.4Zr0.1Y0.1O3-δ for low-temperature fuel cells. Here, we further develop BaCo0.4Fe0.4Zr0.1Y0.1O3-δ for electrolyte applications by taking advantage of its high ionic conduction while suppressing its electronic conduction through constructing a BaCo0.4Fe0.4Zr0.1Y0.1O3-δ-ZnO p-n heterostructure. With this approach, it has been demonstrated that BaCo0.4Fe0.4Zr0.1Y0.1O3-δ can be applied in a fuel cell with good electrolyte functionality, achieving attractive ionic conductivity and cell performance. Further investigation confirms the hybrid H+/O2- conducting capability of BaCo0.4Fe0.4Zr0.1Y0.1O3-δ-ZnO. An energy band alignment mechanism based on a p-n heterojunction is proposed to explain the suppression of electronic conductivity and promotion of ionic conductivity in the heterostructure. Our findings demonstrate that BaCo0.4Fe0.4Zr0.1Y0.1O3-δ is not only a good electrode but also a highly promising electrolyte. The approach reveals insight for developing advanced low-temperature solid oxide fuel cell electrolytes.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA