RESUMO
BACKGROUND: The shortcomings of plaster in water resistance, air permeability, skin comfort, fixed stability and weight of wearing are still to be solved. 3D printed cast can overcome the above shortcomings. At present, there is a relative lack of data on the clinical application of 3D printed cast, probably due to its complexity, relatively long operating time, and high price. We aimed to compare and evaluate the short-term effectiveness, safety and advantages of 3D printed wrist cast versus polymer orthosis in the treatment of Colles fracture. METHODS: Forty patients with Colles fracture in our hospital from June to December 2022 were selected and divided into an observation group (20 patients, treated with instant 3D printed cast) and a control group (20 cases, treated with polymer orthosis). Both groups treated with manual reduction and external fixation. The visual analogue scale (VAS), immobilization effectiveness and satisfaction scores, Disability of the Arm, Shoulder and Hand (DASH) score, complications and imaging data were collected and compared before immobilization and at 2, 6 and 12 weeks after the fracture. RESULTS: VAS at 2 weeks after the fracture was significantly lower in the observation group than in the control group ( P < 0.05). The immobilization effectiveness and satisfaction scores at 6 weeks after the fracture were significantly higher in the observation group than in the control group (all P < 0.05). The DASH scores at 2 and 6 weeks after the fracture were significantly lower in the observation group than in the control group (all P < 0.05). There wasn't rupture of the printed cast or orthosis in both groups. There were 2 cases of skin irritation in the control group, and no skin irritation occurred in the observation group. The palmar tilt angle and ulnar inclination angle at 2 weeks and 12 weeks after the fracture were significantly higher in the observation group than in the control group (all P < 0.05). CONCLUSIONS: Both instant 3D printed cast and polymer orthosis are effective in the treatment of Colles fracture. But instant 3D printed cast is better than polymer orthosis in areas of good clinical and imaging performance, and high patient satisfaction and comfort.
Assuntos
Fratura de Colles , Fraturas do Rádio , Humanos , Fratura de Colles/cirurgia , Aparelhos Ortopédicos , Braquetes , Fixação de Fratura/métodos , Impressão Tridimensional , Resultado do Tratamento , Fraturas do Rádio/cirurgia , Moldes CirúrgicosRESUMO
BACKGROUND: Runt-related transcription factor-2 (Runx2) has been considered an inducer to improve bone repair ability of mesenchymal stem cells (MSCs). METHODS AND RESULTS: Twenty-four rabbits were used to establish Osteonecrosis of the femoral head (ONFH) and randomly devided into four groups: Adenovirus Runx2 (Ad-Runx2) group, Runx2-siRNA group, MSCs group and Model group. At 1 week after model establishment, the Ad-Runx2 group was treated with 5 × 107 MSCs transfected through Ad-Runx2, the Runx2-siRNA group was treated with 5 × 107 MSCs transfected through Runx2-siRNA, the MSCs group was injected with 5 × 107 untreated MSCs, and the Model group was treated with saline. The injection was administered at 1 week and 3 weeks after model establishment. The expression of bone morphogenetic protein 2 (BMP-2), Runx2 and Osterix from the femoral head was detected at 3 and 6 weeks after MSCs being injected, and Masson Trichrome Staining, Gross Morphology, X-ray and CT images observation were used to evaluate the repair effect of ONFH. The data revealed that the expression of BMP-2, Runx2 and Osterix in the Runx2-siRNA group was reduced at 3 weeks compared with the MSCs group, and then the expression further reduced at 6 weeks, but was still higher than the Model group besides Osterix; The expression of these three genes in the Ad-Runx2 group was higher than in the MSCs group. Masson Trichrome Staining, Gross Morphology and X-ray and CT images observation revealed that necrotic femoral head of the MSCs group was more regular and smooth than the Runx2-siRNA group, which has a collapsed and irregular femoral head. In the Ad-Runx2 group, necrotic femoral head was basically completely repaired and covered by rich cartilage and bone tissue. CONCLUSIONS: Overexpression of Runx2 can improve osteoblastic phenotype maintenance of MSCs and promote necrotic bone repair of ONFH.
Assuntos
Necrose da Cabeça do Fêmur , Células-Tronco Mesenquimais , Animais , Coelhos , Necrose da Cabeça do Fêmur/genética , Necrose da Cabeça do Fêmur/terapia , Necrose da Cabeça do Fêmur/metabolismo , Cabeça do Fêmur , Células-Tronco Mesenquimais/metabolismo , RNA Interferente Pequeno/farmacologiaRESUMO
Disruption of bone homeostasis is the pathological basis of bone diseases. Multiple cells work together to maintain homeostasis and bone health. As a natural flavonoid compound, Naringin (NG) can positively affect the maintenance of bone homeostasis by acting on different types of cells. In this review, we discuss the direct and indirect osteoprotective effects of NG as well as the underlying mechanisms, and we provide a critical perspective on its clinical translation.
Assuntos
Flavanonas , Flavanonas/farmacologia , Flavonoides , HomeostaseRESUMO
BACKGROUND: Several observational studies have reported an association between hand grip strength (HGS) and pulmonary function (PF). However, causality is unclear. To investigate whether HGS and PF are causally associated, we performed Mendelian randomization (MR) analyses. METHODS: We identified 110 independent single nucleotide polymorphisms (SNPs) for right-hand grip strength (RHGS) and 103 independent SNPs for left-hand grip strength (LHGS) at the genome-wide significant threshold (P < 5 × 10-8) from MRC-IEU Consortium and evaluated these related to PF. MR estimates were calculated using the inverse-variance weighted (IVW) method and multiple sensitivity analyses were further performed. RESULTS: Genetical liability to HGS was positively causally associated with forced vital capacity (FVC) and forced expiratory volume in one second (FEV1), but not with FEV1/FVC. In addition, there was positive causal association between RHGS and FVC (OR=1.519; 95% CI, 1.418-1.627; P=8.96E-33), and FEV1 (OR=1.486; 95% CI, 1.390-1.589; P=3.19E-31); and positive causal association between LHGS and FVC (OR=1.464; 95% CI, 1.385-1.548; P=2.83E-41) and FEV1 (OR=1.419; 95% CI, 1.340-1.502; P=3.19E-33). Nevertheless, no associations were observed between RHGS and FEV1/FVC (OR=0.998; 95% CI, 0.902-1.103; P=9.62E-01) and between LHGS and FEV1/FVC (OR=0.966; 95% CI, 0.861-1.083; P=5.52E-01). Similar results were shown in several sensitivity analyses. CONCLUSION: Our study provides support at the genetic level that HGS is positively causally associated with FVC and FEV1, but not with FEV1/FVC. Interventions for HGS in PF impairment deserve further exploration as potential indicators of PF assessment.
Assuntos
Força da Mão , Análise da Randomização Mendeliana , Humanos , Pulmão , Volume Expiratório Forçado , Capacidade Vital/genética , Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Traumatic osteonecrosis of the femoral head (ONFH) is a condition leading to the collapse of the femoral head, and the primary treatment is a total hip replacement, which has a poor prognosis. The current study was conducted with the aim of investigating the role of exosomes from bone marrow-derived mesenchymal stem cells (BM-MSCs) carrying microRNA-224-3p (miR-224-3p) in traumatic ONFH. Initially, a microarray analysis was performed to screen the differentially expressed genes and miRs associated with traumatic ONFH. Patients with traumatic and nontraumatic ONFH were enrolled, and HUVECs were obtained. The BM-MSCs-derived exosomes were purified and characterized, after which HUVECs were cocultured with exosomes. The functional role of miR-224-3p in traumatic ONFH was determined using ectopic expression, depletion, and reporter assay experiments. Endothelial cell proliferation, migration, invasion abilities, and angiogenesis were evaluated. Based on microarray analysis, miR-224-3p was found to be down-regulated, whereas focal adhesion kinase family interacting protein of 200 kDa (FIP200) was up-regulated in ONFH. Traumatic ONFH exosomes resulted in the up-regulation of FIP200 and down-regulation of miR-224-3p. FIP200 was confirmed to be a target gene of miR-224-3p. Exosomes were internalized by vascular endothelial cells. The down-regulation of exosomal miR-224-3p was observed to promote endothelial cell proliferation, migration, invasion abilities, angiogenesis, and FIP200 expression. In addition, FIP200 overexpression promoted angiogenesis. In summary, the results highly indicated that lower miR-224-3p levels in exosomes derived from BM-MSCs promote angiogenesis of traumatic ONFH by up-regulating FIP200. The present study provides a potential strategy for the treatment of traumatic ONFH.-Xu, H.-J., Liao, W., Liu, X.-Z., Hu, J., Zou, W.-Z., Ning, Y., Yang, Y., Li, Z.-H. Down-regulation of exosomal microRNA-224-3p derived from bone marrow-derived mesenchymal stem cells potentiates angiogenesis in traumatic osteonecrosis of the femoral head.
Assuntos
Células da Medula Óssea/metabolismo , Regulação para Baixo , Cabeça do Fêmur/metabolismo , Células-Tronco Mesenquimais/metabolismo , MicroRNAs/biossíntese , Neovascularização Fisiológica , Osteonecrose/metabolismo , Artroplastia de Quadril , Proteínas Relacionadas à Autofagia/biossíntese , Células da Medula Óssea/patologia , Técnicas de Cocultura , Feminino , Cabeça do Fêmur/patologia , Células Endoteliais da Veia Umbilical Humana/metabolismo , Células Endoteliais da Veia Umbilical Humana/patologia , Humanos , Masculino , Células-Tronco Mesenquimais/patologia , Osteonecrose/patologiaRESUMO
Mesenchymal stem cells (MSCs) with multipotential differentiation capacity can differentiate into bone cells under specific conditions and can be used to treat osteonecrosis (ON) of the femoral head (ONFH) through cell transplantation. The current study aims to explore the role of bone marrow (BM) MSCs (BMSCs)-derived exosomes carrying microRNA-122-5p (miR-122-5p) in ONFH rabbit models.First, rabbit models with ONFH were established. ONFH-related miRNAs were screened using the Gene Expression Omnibus (GEO) database. A gain-of-function study was performed to investigate the effect of miR-122-5p on osteoblasts and BMSCs and effects of exosomes carrying miR-122-5p on ONFH. Co-culture experiments for osteoblasts and BMSCs were performed to examine the role of exosomal miR-122-5p in osteoblast proliferation and osteogenesis. The target relationship between miR-122-5p and Sprouty2 (SPRY2) was tested.MiR-122, significantly decreased in ONFH in the GSE89587 expression profile, was screened. MiR-122-5p negatively regulated SPRY2 and elevated the activity of receptor tyrosine kinase (RTK), thereby promoting the proliferation and differentiation of osteoblasts. In vivo experiments indicated that bone mineral density (BMD), trabecular bone volume (TBV), and mean trabecular plate thickness (MTPT) of femoral head were increased after over-expressing miR-122-5p in exosomes. Significant healing of necrotic femoral head was also observed.Exosomes carrying over-expressed miR-122-5p attenuated ONFH development by down-regulating SPRY2 via the RTK/Ras/mitogen-activated protein kinase (MAPK) signaling pathway. Findings in the present study may provide miR-122-5p as a novel biomarker for ONFH treatment.
Assuntos
Exossomos/metabolismo , Necrose da Cabeça do Fêmur/patologia , Células-Tronco Mesenquimais/metabolismo , Osteoblastos/patologia , Adipogenia/efeitos dos fármacos , Adipogenia/genética , Compostos de Anilina/farmacologia , Animais , Sequência de Bases , Compostos de Benzilideno/farmacologia , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/genética , Exossomos/efeitos dos fármacos , Exossomos/ultraestrutura , Necrose da Cabeça do Fêmur/diagnóstico por imagem , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas de Membrana/metabolismo , Células-Tronco Mesenquimais/efeitos dos fármacos , MicroRNAs/genética , MicroRNAs/metabolismo , Neovascularização Fisiológica/efeitos dos fármacos , Neovascularização Fisiológica/genética , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Osteogênese/efeitos dos fármacos , Osteogênese/genética , Coelhos , Transdução de Sinais , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/genética , Cicatrização/efeitos dos fármacos , Cicatrização/genéticaRESUMO
Overload-exercise (OE) causes myocardial injury through inducing autophagy and apoptosis. In this study we examined whether an autophagy inhibitor 3-methyladenine (3-MA) could alleviate OE-induced cardiac injury. Rats were injected with 3-MA (15 mg/kg, iv) or saline before subjected to various intensities of OE, including no swim (control), 2 h swim (mild-intensity exercise, MIE), 2 h swim with 2.5% body weight overload (moderate OE; MOE), 5% overload (intensive OE; IOE) or 2.5% overload until exhausted (exhaustive OE; EOE). After OE, the hearts were harvested for morphological and biochemiacal analysis. The cardiac morphology, autophagosomes and apoptosis were examined with H&E staining, transmission electron microscopy and TUNEL analysis, respectively. Autophagy-related proteins to (LC3-II/I and Beclin-1) and apoptosis-related proteins (Bcl-2/Bax) were assessed using Western blotting. Our results showed that compared with the control, MIE did not change the morphological structures of the heart tissues that exhibited intact myocardial fibers and neatly arranged cardiomyocytes. However, IOE resulted in irregular arrangement of cardiomyocytes and significantly increased width of cardiomyocytes, whereas EOE caused more swollen and even disrupted cardiomyocytes. In parallel with the increased OE intensity (MOE, IOE, EOE), cardiomyocyte autophagy and apoptosis became more and more prominent, evidenced by the increasing number of autophagosomes and expression levels of LC3-II/I and Beclin-1 as well as the increasing apoptotic cells and decreasing Bcl-2/Bax ratio. 3-MA administration significantly attenuated OE-induced morphological changes of cardiomyocytes as well as all the autophagy- and apoptosis-related abnormalities in MOE, IOE and EOE rats. Thus, the autophagy inhibitor 3-MA could alleviate OE-induced heart injury in rats.
Assuntos
Adenina/análogos & derivados , Autofagia/efeitos dos fármacos , Traumatismos Cardíacos/tratamento farmacológico , Condicionamento Físico Animal , Adenina/farmacologia , Animais , Modelos Animais de Doenças , Traumatismos Cardíacos/patologia , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
A 12-week Wheelchair Tai Chi 10 Form (WTC10) intervention was conducted among elderly with disability to examine the effect of this WTC10 intervention on selected physical and mental health variables. Thirteen (age 87.23 ± 6.71) in the WTC10 intervention group and 15 (age 89.73 ± 6.31) in the control group completed the study. Independent t-tests and paired t-tests were employed to examine the differences between groups and within groups, respectively, at pretest and post-test. The WTC10 intervention group showed significant improvements in systolic and diastolic blood pressure, shoulder external rotation, left trunk rotation and total trunk rotation after the intervention. A 12-week WTC10 intervention had positive effects on blood pressure, range of motion at the shoulder and trunk, physical activity, and mental health among the elderly with disability. WTC10 is a feasible and safe exercise for the elderly with disability.
Assuntos
Pessoas com Deficiência/psicologia , Exercício Físico/fisiologia , Saúde Mental , Tai Chi Chuan , Cadeiras de Rodas , Idoso de 80 Anos ou mais , Pressão Sanguínea , Feminino , Nível de Saúde , Humanos , Masculino , Amplitude de Movimento Articular , Rotação , Articulação do Ombro/fisiologia , Tai Chi Chuan/psicologia , Tronco/fisiologiaRESUMO
The causal association of educational attainment (EA) with intervertebral disc degeneration (IVDD) or low back pain (LBP), and the mediating effect of metabolic syndrome (MetS) in this association, is not studied to date. In this study, using summary statistics of genome-wide association studies primarily conducted in the individuals of European ancestry, Mendelian randomization (MR) analyses were performed to investigate: (1) the total and direct effects of EA on IVDD and LBP, (2) bidirectional associations of EA with MetS or the components of MetS, (3) causal effects of MetS or its components on IVDD and LBP, and (4) mediating effects of MetS or its components on the causal associations of EA with IVDD and LBP. Univariable MR analysis demonstrated that genetically proxied EA was inversely associated with IVDD (ORIVW: 0.90; 95 % CI: 0.87-0.92) and LBP (ORIVW: 0.86; 95 % CI: 0.84-0.89). Consistent results were obtained after adjusting for potential confounders (cognition, economic level, smoking traits, and metabolic factors). Mediation analysis proved that the effect of EA on IVDD mediated by MetS, waist circumference, and high-density lipoprotein cholesterol was 11.38 %, 9.22 %, and 2.17 %, respectively. Besides, MetS mediated 8.42 % and waist circumference mediated 5.81 % of the EA effects on LBP, respectively. Our findings provided support for MetS mediating the causal protective effects of EA on IVDD and LBP, which provided causal evidence to the etiology and intervention targets of IVDD and LBP.
RESUMO
The development of numerous diseases is significantly influenced by inflammation. Macrophage-derived exosomes (M-Exos) play a role in controlling inflammatory reactions in various conditions, including chronic inflammatory pain, hypertension, and diabetes. However, the specific targets and roles of M-Exos in regulating inflammation in diseases remain largely unknown. This review summarizes current knowledge on M-Exos biogenesis and provides updated information on M-Exos' biological function in inflammation modulation. Furthermore, this review highlights the functionalization and engineering strategies of M-Exos, while providing an overview of cutting-edge approaches to engineering M-Exos and advancements in their application as therapeutics for inflammation modulation. Finally, multiple engineering strategies and mechanisms are presented in this review along with their perspectives and challenges, and the potential contribution that M-Exos may have in diseases through the modulation of inflammation is discussed.
Assuntos
Exossomos , MicroRNAs , Humanos , Macrófagos , Inflamação/terapiaRESUMO
AIM: To explore the feasibility of allogeneic mesenchymal stem cells (MSCs) transplanted intravenously for angiogenesis and bone repair in a rabbit model of avascular necrosis of femoral head (ANFH). MATERIALS AND METHODS: Forty-five rabbits were randomized into three groups: a blank control group (without treatment), a necrotic control group (ANFH induced but without therapy), and an MSC transplantation group (ANFH induced and treated with MSC transplantation). The biopsies, blood sampling, and imaging examinations were performed on each animal at different time points (2, 4, and 6 wk). To monitor angiogenesis and bone repair progress, examinations included real-time polymerase chain reaction, Western blot analysis, x-ray, computed tomography, Masson trichrome staining, picrosirius red staining, and immunohistochemical staining. RESULTS: Necrosis and bone collapse were observed in bilateral femoral heads of necrotic rabbits of the necrotic control group, whereas the femoral head morphology was generally restored in the MSC transplantation group. The mRNA levels of Cbfa1, BMP, VEGF, and OPN in bone tissue were significantly higher in the MSC transplantation group than in the necrotic control group. In addition, the total protein amount of Cbfa1 in the MSC transplantation group was also significantly higher than that in the necrotic control group (P < 0.05). CONCLUSION: Intravenous transplantation of allogeneic MSCs can promote vascular and bone regeneration in the necrotic region of the femoral head in a rabbit model of ANFH. The results of our study suggest that the intravenous transplantation of MSCs could be a potential and minimally invasive treatment option for ANFH patients.
Assuntos
Regeneração Óssea , Necrose da Cabeça do Fêmur/terapia , Transplante de Células-Tronco Mesenquimais , Neovascularização Fisiológica , Animais , Colágeno/metabolismo , Modelos Animais de Doenças , Expressão Gênica , Injeções Intravenosas , Osteócitos/fisiologia , Osteogênese , Coelhos , Distribuição Aleatória , Transplante Homólogo , CicatrizaçãoRESUMO
The effects of tacrolimus postconditioning on protein-serine-threonine kinases (Akt) phosphorylation and apoptotic cell death in rats after spinal cord ischemia-reperfusion injury were investigated. Ninety male SD rats were randomly divided into sham operation group, ischemia-reperfusion group and tacrolimus postconditioning group. The model of spinal cord ischemia was established by means of catheterization through femoral artery and balloon dilatation. The spinal cord was reperfused 20 min after ischemia via removing saline out of balloon. The corresponding spinal cord segments were excised and determined for Akt activity in spinal cord tissue by using Western blotting at 5, 15, and 60 min after reperfusion respectively. Spinal cord tissue sections were stained immunohistochemically for detection of the phosphorylated Akt expression at 15 min after reperfusion. Flow cytometry was applied to assess apoptosis of neural cells, and dry-wet weights method was employed to measure water content in spinal cord tissue at 24 h after reperfusion. The results showed that the activities of Akt in tarcolimus postconditioning group were significantly higher than those in ischemia-reperfusion group at 5, 15, and 60 min after reperfusion (P<0.05, P<0.01). The Akt activities reached the peak at 15 min after reperfusion in ischemia-reperfusion group and tacrolimus postconditioning group. The percentage of apoptotic cells and water content in spinal cord tissue were significantly reduced (P<0.01) in tacrolimus postconditioning group as compared with those in ischemia-reperfusion group at 24 h after reperfusion. It is concluded that tacrolimus post-conditioning can increase Akt activity in spinal cord tissue of rats, inhibit apoptosis of neural cells as well as tissue edema, and thereby alleviate spinal cord ischemia-reperfusion injury.
Assuntos
Apoptose/efeitos dos fármacos , Imunossupressores/uso terapêutico , Proteínas Serina-Treonina Quinases/metabolismo , Traumatismo por Reperfusão/tratamento farmacológico , Isquemia do Cordão Espinal/tratamento farmacológico , Tacrolimo/uso terapêutico , Animais , Imunossupressores/farmacologia , Masculino , Fosforilação , Proteínas Serina-Treonina Quinases/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/metabolismo , Medula Espinal/efeitos dos fármacos , Medula Espinal/metabolismo , Medula Espinal/patologia , Isquemia do Cordão Espinal/metabolismo , Tacrolimo/farmacologia , Regulação para CimaRESUMO
OBJECTIVE: To investigate whether protective effect of tacrolimus postconditioning on rats' spinal cord ischemia-reperfusion injury is mediated by up-regulation of activity of endogenous antioxidant enzymes and down-regulation of production of oxygen free radicals. METHODS: Ninety male Sprague-Dawley rats were randomly divided into ischemia-reperfusion (IR) group, tacrolimus postconditioning (TP) group and sham operation (SO) group. The model of spinal cord ischemia was prepared by means of catheterization through femoral artery and balloon dilatation. IR group underwent reperfusion 20 min after spinal cord ischemia. TP group experienced a single injection of tacrolimus (0.5 mg/kg) through the left common carotid artery at the onset of reperfusion. SO group received femoral artery catheterization only. Fluoro spectro photometry was employed to detect the level of reactive oxygen species (ROS) in injured spinal cord segment at 15 minutes after reperfusion. The content of malondialdehyde (MDA) and activity of antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-PX) were determined at 15 minutes, 1, 6, and 24 hours after reperfusion respectively. BBB scale was conducted to evaluate hindlimb motor function at 14 days after reperfusion. RESULTS: The level of ROS in TP group was significantly lower than that in IR group at 15 minutes after reperfusion. The activity of SOD was significantly higher in TP group than in IR group at all observational time points, while the activities of CAT and GSH-PX were significantly higher in TP group than in IR group at 1 and 6 hours after reperfusion. The content of MDA in TP group was significantly less than that in IR group at all observational time points. The motor function score of TP group was significantly superior to that of IR group at 14 days after reperfusion. CONCLUSION: Tacrolimus post conditioning can improve activity of endogenous antioxidant enzymes, decrease production of oxygen free radicals, suppress lipid peroxidation, and thereby promote functional recovery after spinal cord ischemia-reperfusion injury in rats.
Assuntos
Pós-Condicionamento Isquêmico , Estresse Oxidativo/efeitos dos fármacos , Traumatismo por Reperfusão/metabolismo , Isquemia do Cordão Espinal/metabolismo , Tacrolimo/farmacologia , Animais , Modelos Animais de Doenças , Glutationa Peroxidase/metabolismo , Masculino , Malondialdeído/metabolismo , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismoRESUMO
Aptamers are single-stranded nucleic acids (DNA, short RNA, or other artificial molecules) produced by the Systematic Evolution of Ligands by Exponential Enrichment (SELEX) technology, which can be tightly and specifically combined with desired targets. As a comparable alternative to antibodies, aptamers have many advantages over traditional antibodies such as a strong chemical stability and rapid bulk production. In addition, aptamers can bind targets in various ways, and are not limited like the antigen-antibody combination. Studies have shown that aptamers have tremendous potential to diagnose and treat clinical diseases. However, only a few aptamer-based drugs have been used because of limitations of the aptamers and SELEX technology. To promote the development and applications of aptamers, we present a review of the methods optimizing the SELEX technology and modifying aptamers to boost the selection success rate and improve aptamer characteristics. In addition, we review the application of aptamers to treat bone diseases.
Assuntos
Aptâmeros de Nucleotídeos , Doenças Ósseas , Humanos , Aptâmeros de Nucleotídeos/uso terapêutico , Aptâmeros de Nucleotídeos/química , Aptâmeros de Nucleotídeos/genética , Técnica de Seleção de Aptâmeros/métodos , Ligantes , Doenças Ósseas/diagnóstico , Doenças Ósseas/terapiaRESUMO
Partial-thickness cartilage defects (PTCDs) of the articular surface is the most common problem in cartilage degeneration, and also one of the main pathogenesis of osteoarthritis (OA). Due to the lack of a clear diagnosis, the symptoms are often more severe when full-thickness cartilage defect (FTCDs) is present. In contrast to FTCDs and osteochondral defects (OCDs), PTCDs does not injure the subchondral bone, there is no blood supply and bone marrow exudation, and the nearby microenvironment is unsuitable for stem cells adhesion, which completely loses the ability of self-repair. Some clinical studies have shown that partial-thickness cartilage defects is as harmful as full-thickness cartilage defects. Due to the poor effect of conservative treatment, the destructive surgical treatment is not suitable for the treatment of partial-thickness cartilage defects, and the current tissue engineering strategies are not effective, so it is urgent to develop novel strategies or treatment methods to repair PTCDs. In recent years, with the interdisciplinary development of bioscience, mechanics, material science and engineering, many discoveries have been made in the repair of PTCDs. This article reviews the current status and research progress in the treatment of PTCDs from the aspects of diagnosis and modeling of PTCDs, drug therapy, tissue transplantation repair technology and tissue engineering ("bottom-up").
Assuntos
Cartilagem Articular , Cartilagem Articular/patologia , Engenharia Tecidual/métodos , Medula Óssea , Células-Tronco , Células CultivadasRESUMO
In this study, we investigated the feasibility and safety of intravenous transplantation of allogeneic bone marrow mesenchymal stem cells (MSCs) for femoral head repair, and observed the migration and distribution of MSCs in hosts. MSCs were labeled with green fluorescent protein (GFP) in vitro and injected into nude mice via vena caudalis, and the distribution of MSCs was dynamically monitored at 0, 6, 24, 48, 72 and 96 h after transplantation. Two weeks after the establishment of a rabbit model of femoral head necrosis, GFP labeled MSCs were injected into these rabbits via ear vein, immunological rejection and graft versus host disease were observed and necrotic and normal femoral heads, bone marrows, lungs, and livers were harvested at 2, 4 and 6 w after transplantation. The sections of these tissues were observed under fluorescent microscope. More than 70 % MSCs were successfully labeled with GFP at 72 h after labeling. MSCs were uniformly distributed in multiple organs and tissues including brain, lungs, heart, kidneys, intestine and bilateral hip joints of nude mice. In rabbits, at 6 w after intravenous transplantation, GFP labeled MSCs were noted in the lungs, liver, bone marrow and normal and necrotic femoral heads of rabbits, and the number of MSCs in bone marrow was higher than that in the, femoral head, liver and lungs. Furthermore, the number of MSCs peaked at 6 w after transplantation. Moreover, no immunological rejection and graft versus host disease were found after transplantation in rabbits. Our results revealed intravenously implanted MSCs could migrate into the femoral head of hosts, and especially migrate directionally and survive in the necrotic femoral heads. Thus, it is feasible and safe to treat femoral head necrosis by intravenous transplantation of allogeneic MSCs.
Assuntos
Transplante de Medula Óssea/métodos , Movimento Celular , Necrose da Cabeça do Fêmur/terapia , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/fisiologia , Animais , Movimento Celular/fisiologia , Células Cultivadas , Necrose da Cabeça do Fêmur/imunologia , Necrose da Cabeça do Fêmur/patologia , Necrose da Cabeça do Fêmur/fisiopatologia , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/imunologia , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/imunologia , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/farmacocinética , Humanos , Infusões Intravenosas , Masculino , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/imunologia , Coelhos , Coloração e Rotulagem/métodos , Transplante HomólogoRESUMO
The study aimed to compare the clinical characteristics and outcomes of patients with different types (ordinary, severe, and critical) of COVID-19. A total of 1280 patients diagnosed with COVID-19 were retrospectively studied, including 793 ordinary patients, 363 severe patients and 124 critical patients. The impact of comorbidities on prognosis in ordinary, severe, and critical patients were compared and analyzed. The most common comorbidities were hypertension (33.0%), followed by diabetes (14.4%). The length of hospital stay and time from the onset to discharge were significantly longer in ordinary patients with comorbidities compared with those without comorbidities. Critical patients with comorbidities had significantly lower cure rate (19.3% vs 38.9%, p<0.05) and significantly higher mortality rate (53.4% vs 33.3%, p<0.05) compared with those without comorbidities. The time from onset to discharge was significantly longer in ordinary patients with hypertension compared with those without hypertension. The mortality rate of critical patients with diabetes was higher than that of patients without diabetes (71.4% vs 42.7%, p<0.05). Men had a significantly increased risk of death than women (OR=4.395, 95% CI 1.896 to 10.185, p<0.05); patients with diabetes had higher risk of death (OR=3.542, 95% CI 1.167 to 10.750, p<0.05). Comorbidities prolonged treatment time in ordinary patients, increased the mortality rate and reduced the cure rate of critical patients; hypertension and diabetes may be important factors affecting the clinical course and prognosis of ordinary and critical patients, respectively.
Assuntos
COVID-19/complicações , COVID-19/diagnóstico , Adulto , Idoso , COVID-19/mortalidade , Comorbidade , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de SobrevidaRESUMO
BACKGROUND: Recruitment of gene modifying bone marrow mesenchymal stem cells (BMSCs) has been considered an alternative to single-cell injection in articular cartilage repair. PURPOSE: This study aimed to investigate whether the effect of runt-related transcription factor 2(Runx2) overexpression bone marrow mesenchymal stem cells in vivo could improve the quality of repaired tissue of a knee cartilage defect in a rabbit model. METHODS: Thirty-two New Zealand rabbits were randomly divided into four groups. The blank group (Con) did not receive anything, the model group (Mo) was administered saline, the simple stem cell group (MSCs) received MSCs injection, and the Runx2 transfection group (R-MSCs) received Runx2 overexpression MSCs injection. After adapting to the environment for a week, a 5 mm diameter cylindrical osteochondral defect was created in the center of the medial femoral condyle. Cell and saline injections were performed in the first and third weeks after surgery. The cartilage repair was evaluated by macroscopically and microscopically at 4 and 8 weeks. RESULTS: Macroscopically, defects were filled and surfaces were smoother in the MSCs groups than in the Mo group at 4th week. Microscopically, the R-MSCs group showed coloration similar to surrounding normal articular cartilage tissue at 8 weeks in masson trichrome staining. The COL-II, SOX9, and Aggrecan mRNA expressions of MSCs were enhanced at 4 weeks compared with R-MSCs, then the expression reduced at 8 weeks, but was still higher than Mo group level (P<0.05). The western blot examination revealed that the COL-IIand SOX9 expression of MSCs was higher than R-MSCs at 4 weeks, then the expression reduced at 8 weeks, but was still higher than the Mo level (P<0.05). The IL-1ß content in the joint fluid also revealed that cartilage repair with R-MSCs was better than that with MSCs at 8 weeks (P<0.05). CONCLUSION: The R-MSCs group showed cellular morphology and arrangement similar to surrounding normal articular cartilage tissue, and Runx2 overexpression of MSCs resulted in overall superior cartilage repair as compared with MSCs at 8 weeks.
Assuntos
Doenças das Cartilagens/terapia , Cartilagem Articular/metabolismo , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/metabolismo , Animais , Doenças das Cartilagens/genética , Cartilagem Articular/crescimento & desenvolvimento , Fêmur/lesões , Fêmur/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/genética , Humanos , Interleucina-1beta/genética , Joelho/crescimento & desenvolvimento , Joelho/patologia , Coelhos , Engenharia TecidualRESUMO
Osteoporosis, femoral head necrosis, and congenital bone defects are orthopedic disorders characterized by reduced bone generation and insufficient bone mass. Bone regenerative therapy primarily relies on the bone marrow mesenchymal stem cells (BMSCs) and their ability to differentiate osteogenically. Icariin (ICA) is the active ingredient of Herba epimedii, a common herb used in traditional Chinese medicine (TCM) formulations, and can effectively enhance BMSC proliferation and osteogenesis. However, the underlying mechanism of ICA action in BMSCs is not completely clear. In this review, we provide an overview of the studies on the role and mechanism of action of ICA in BMSCs, to provide greater insights into its potential clinical use in bone regeneration.
RESUMO
OBJECTIVE: To evaluate whether EPC-MVs could promote bone regeneration by directly regulating osteoblast through miR-126. The underlying mechanisms were also explored. METHODS: EPCs were isolated from bone marrow mononuclear cells. EPC-MVs were collected from EPCs cultured medium. The lentivirus was used to induce miR-126 over-expression in EPCs and EPC-MVs. miR-126 expression was detected by qRT-PCR. The proliferation, migration, apoptosis and differentiation abilities of osteoblast cells MC3T3-E1 were analysed in the presence or absence of EPC-MVs or miR-126 overexpressed EPC-MVs (EPC-MVs-miR126). The proteins of Erk1/2 and Bcl-2 were analysed by western blot. Erk1/2 inhibitor was used for pathway exploration. RESULTS: EPC-MVs reduced apoptosis and promoted proliferation and migration of MC3T3-E1 cells, which could be enhanced by miR-126 enrichment (p< 0.05). Neither EPC-MVs nor EPC-MVs-miR126 had an effect on MC3T3-E1 cell osteogenic differentiation (p> 0.05). EPC-MVs-miR126 had better effects than EPC-MVs on upregulating the expressions of p-Erk1/2 and Bcl-2, which were abolished by Erk1/2 inhibitor. ERK1/2-Bcl-2 activity plays a crucial role in the regulation of EPC-MVs/EPC-MVs-miR126 on the effect of MC3T3-E1 cells. CONCLUSION: EPC-MVs promote proliferation and migration of MC3T3-E1 cell while reduced apoptosis via the miR-126/Erk1/2-Bcl-2 pathway. A combination of EPC-MVs and miR-126 might provide novel therapeutic targets for bone regeneration and fracture healing through regulating osteoblast.