RESUMO
The osteonecrotic area of steroid-induced avascular necrosis of the femoral head (SANFH) is a hypoxic microenvironment that leads to apoptosis of transplanted bone marrow mesenchymal stem cells (BMSCs). However, the underlying mechanism remains unclear. Here, we explore the mechanism of hypoxic-induced apoptosis of BMSCs, and use the mechanism to improve the transplantation efficacy of BMSCs. Our results show that the long non-coding RNA AABR07053481 (LncAABR07053481) is downregulated in BMSCs and closely related to the degree of hypoxia. Overexpression of LncAABR07053481 could increase the survival rate of BMSCs. Further exploration of the downstream target gene indicates that LncAABR07053481 acts as a molecular "sponge" of miR-664-2-5p to relieve the silencing effect of miR-664-2-5p on the target gene Notch1. Importantly, the survival rate of BMSCs overexpressing LncAABR07053481 is significantly improved after transplantation, and the repair effect of BMSCs in the osteonecrotic area is also improved. This study reveal the mechanism by which LncAABR07053481 inhibits hypoxia-induced apoptosis of BMSCs by regulating the miR-664-2-5p/Notch1 pathway and its therapeutic effect on SANFH.
Assuntos
Necrose da Cabeça do Fêmur , Células-Tronco Mesenquimais , MicroRNAs , Humanos , Necrose da Cabeça do Fêmur/induzido quimicamente , Necrose da Cabeça do Fêmur/genética , Necrose da Cabeça do Fêmur/terapia , Células-Tronco Mesenquimais/metabolismo , Apoptose/genética , Hipóxia/metabolismo , Esteroides/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismoRESUMO
BACKGROUND/AIMS: Avascular necrosis of the femoral head (ANFH) is the focus and difficulty of orthopedic diseases. Recently, tissue engineering bone for this disease has shown a good therapeutic effect. The aim of the present study was to investigate the therapeutic effect of basic fibroblast growth factor (FGF-2) as cytokines transfected bone marrow mesenchymal stem cells (BMSCs) in constructing tissue-engineered bone for avascular necrosis of the femoral head. METHODS: The FGF-2 gene overexpressed lentivirus-transfected rBMSCs with xenogeneic antigen-extracted cancellous bone (XACB) to construct tissue engineered bone, and the model of early avascular necrosis of the femoral head was established by lipopolysaccharide (LPS) combined with hormone. The models were randomly divided into five groups: A (control), B (XACB), C (XACB+rBMSCs), D (XACB+rBMSCs+Lv-GFP), and E (XACB+rBMSCs+Lv-FGF-2/GFP) groups. The therapeutic effect of the tissue engineered bone for the avascular necrosis of the femoral head was evaluated by gross anatomy, X-ray examination, immunohistochemistry and H&E staining. RESULTS: The FGF-2 gene was transfected into rBMSCs (Multiplicity of infection [MOI] = 100) by lentivirus, and its efficiency was above 95%. The rBMSCs were successfully transfected overexpressing FGF-2 by qPCR and western blot. After tissue engineering bone implantation, X-ray examination and gross specimen observation revealed that the repair area in the E group was > 80% at six weeks, the defect was completely repaired at 12 weeks, and osteogenesis was stronger, when compared with the other groups. For the X-ray score, vascular area density and new bone formation area were higher, when compared with the other groups, and the difference was statistically significant (P< 0.05). CONCLUSION: FGF-2 gene overexpression lentivirus transfection BMSCs combined with XACB to construct tissue engineered bone can effectively promote vascular regeneration, and improve the repair effect of avascular necrosis of the femoral head.
Assuntos
Osso e Ossos/patologia , Necrose da Cabeça do Fêmur/patologia , Fator 2 de Crescimento de Fibroblastos/metabolismo , Animais , Células da Medula Óssea/citologia , Regeneração Óssea/fisiologia , Osso e Ossos/diagnóstico por imagem , Células Cultivadas , Modelos Animais de Doenças , Feminino , Necrose da Cabeça do Fêmur/etiologia , Necrose da Cabeça do Fêmur/metabolismo , Fator 2 de Crescimento de Fibroblastos/genética , Vetores Genéticos/genética , Vetores Genéticos/metabolismo , Lentivirus/genética , Lipopolissacarídeos/toxicidade , Masculino , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Osteogênese , Coelhos , Engenharia TecidualRESUMO
AIM: To evaluate the safety and efficacy profile of 27-gauge (27G) pars plana vitrectomy (PPV) for the treatment of various vitreoretinal diseases. METHODS: The clinical outcomes of 61 eyes (58 patients) with various vitreoretinal diseases following 27G PPV were retrospectively reviewed. RESULTS: Surgical indications included rhegmatogenous retinal detachment (n=24), full-thickness macular hole (n=12), diabetic retinopathy (n=11), vitreous hemorrhage (n=6), Eales disease (n=4), pathological myopia-related vitreous floater (n=2), and macular epiretinal membrane (n=2). The mean follow-up was 166.4±61.3d (range 98-339d). The mean logMAR best-corrected visual acuity (BCVA) improved from 1.7±1.1 [0.02 decimal visual acuity (VA) equivalent] preoperatively to 1.2±1.0 (0.06 decimal VA equivalent) at the last postoperative visit (P<0.001). The mean operative time was 49.9min. With the exception of complicated cataract in one eye, no intraoperative complications were encountered. No case required conversion to conventional 20-, 23- or 25G instrumentation in all surgical maneuvers except for silicone oil infusion, which required a 25G oil injection syringe. Postoperative complications included transient ocular hypertension, vitreous hemorrhage, persistent intraocular pressure elevation, subconjunctival oil leakage, and recurrent retinal detachment. No cases of hypotony, endophthalmitis, and sclerotomy-related tears were observed. CONCLUSION: The current results suggest that 27G PPV system is a safe and effective treatment for various vitreoretinal diseases. When learning to perform 27G PPV, surgeons may encounter a learning curve and should gradually expand surgical indications from easy to pathologically complicated cases.
RESUMO
The study aims to investigate the effect of microRNA-34a (miR-34a) targeting Tgif2 on steroid-induced avascular necrosis of femoral head (SANFH) by regulating OPG/RANK/RANKL signaling pathway. SD rats were divided into normal control and model (RNAKL rat models) groups. The model group was further assigned into model control, negative control, miR-34a mimics and miR-34a inhibitors groups. QRT-PCR was applied to detect miR-34a, Tgif2, OPG, RANK and RNAKL mRNA expressions. Femoral head tissues were collected for Micro-CT scanning and HE staining. QRT-PCR and Western blotting were used to detect expressions of miR-34a, Tgif2, OPG, RANK, RANKL and Runx2, OPN and OC in bone tissues. Dual-luciferase reporter gene assay was used to testify the target relationship between miR-34a and Tgif2. Compared with the normal control group, the model group showed increased Tgif2, RANK and RANKL mRNA expressions, but decreased miR-34a and OPG mRNA expressions. Tgif2 mRNA expression was negatively correlated with miR-34a and OPG mRNA expressions. Micro-CT showed cystic degeneration of femoral head, with decreased bone volume/total volume (BV/TV), bone surface area/bone volume and trabecular number in the model control group compared with the normal control group. Compared with the model control group, the miR-34a mimics group showed increased BV/TV and trabecular thickness and Runx2, OPN and OC expressions, while the parameters decreased in the miR-34a inhibitors group. Compared with the normal control group, the other groups showed increased Tgif2, RANK and RANKL expressions but decreased miR-34a and OPG expressions. Compared with the model control group, Tgif2, RANK and RANKL expressions decreased and miR-34a and OPG expressions increased in the miR-34a mimics group, while the miR-34a inhibitors group had a reverse trend in contrast to the miR-34a mimics group. Tgif2 is a target gene of miR-34a. In conclusion, miR-34a can alleviate SANFH through targeting Tgif2 and further regulating OPG/RANK/RANKL signaling pathway. Impact statement miR-34a can alleviate SANFH through targeting Tgif2 and further regulating OPG/RANK/RANKL signaling pathway, which can be used as a new theoretical basis for SANFH treatment.
Assuntos
Necrose da Cabeça do Fêmur/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Proteínas de Homeodomínio/metabolismo , MicroRNAs/metabolismo , Proteínas Repressoras/metabolismo , Animais , Necrose da Cabeça do Fêmur/induzido quimicamente , Glucocorticoides/toxicidade , Masculino , Metilprednisolona/toxicidade , MicroRNAs/farmacologia , Osteoprotegerina/metabolismo , Ligante RANK/metabolismo , Ratos , Ratos Sprague-Dawley , Receptor Ativador de Fator Nuclear kappa-B/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
BACKGROUND AND PURPOSE: The vascular morphology in crowd with family history of stroke remains unclear. The present study clarified the characteristics of the intracranial vascular CoW and prevalence of intracranial aneurysms in subjects with family history of stroke. METHODS: A stratified cluster, random sampling method was used for subjects with family history of stroke among rural residents in Jixian, Tianjin, China. All the subjects underwent a physical examination, head computed tomography (CT) scan, and cephalic and cervical computed tomography angiography (CTA) scan. Anatomic variations in the Circle of Willis and cerebrovascular disease in this population were analyzed. RESULTS: In the crowd with similar living environment, stable genetic background, and family history of stroke and without obvious nerve function impairment (1) hypoplasia or absence of A1 segment was significantly different in gender (male versus female: 9.8% versus 18.8%, p = 0.031), especially the right-side A1 (male versus female: 5.9% versus 16.4%, p = 0.004). (2) Hypoplasia or absence of bilateral posterior communicating arteries was more common in men than women (58.2% versus 45.3%, p = 0.032). Unilateral fetal posterior cerebral artery was observed more often in women than men (17.2% versus 8.5%, p = 0.028). (3) The percentage of subjects with incomplete CoW did not increase significantly with age. Compared to healthy Chinese people, the crowd had a higher percentage of incomplete CoW (p < 0.001). (4) No obvious correlation between risk factors and CoW was found. (5) The prevalence of aneurysm was 10.3% in the special crowd. CONCLUSIONS: The certain variations of CoW showed significant relation to gender, but not to age in people with family history of stroke. The incomplete circle may be a dangerous factor that is independent of common risk factors for stroke and tend to lead to cerebral ischemia in the crowd with family history of stroke. The prevalence of intracranial aneurysm is comparatively high in the present subjects compared to other people.
Assuntos
Transtornos Cerebrovasculares/patologia , Círculo Arterial do Cérebro/diagnóstico por imagem , Aneurisma Intracraniano/patologia , Acidente Vascular Cerebral/patologia , Adulto , Idoso , Angiografia Cerebral , Transtornos Cerebrovasculares/diagnóstico por imagem , Transtornos Cerebrovasculares/epidemiologia , China , Feminino , Humanos , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/epidemiologia , Masculino , Pessoa de Meia-Idade , Linhagem , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Inquéritos e Questionários , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVE: To explore the prevalence of cataract and measure the outcomes after cataract surgery in patients aged ≥ 50 years and to evaluate the validity of Rapid Assessment of Avoidable Blindness (RAAB). METHODS: A total of 76 clusters of 50 patients aged ≥ 50 years were selected through probability proportionate to size sampling. The measurements of visual acuity (VA) were made with a tumbling-E chart and the diagnosis of the principal cause of visual impairment by an ophthalmologist. RESULTS: A total of 3288 patients were examined with a response rate of 86.5%. There were 271 males (38.7%) and 2017 females (61.3%). Among 832 cataract patients, 175 (5.3%) had blindness due to cataract. The prevalence of cataract was 9.2%, 25.2%, 47.6%, 70.1% in 50, 60, 70, 80 years old respectively. And 109 eyes underwent cataract surgery. Among 88 pseudophakic eyes (80.7%), 59 eyes achieved excellent outcomes (VA ≥ 0.3) after surgery (54.1%). CONCLUSION: The major cause of blindness in Anyue is due to cataract. Attention needs to be paid to improving outcomes after surgery. RAAB provides information about the magnitude and cause of avoidable blindness so that it may be used for planning and monitoring cataract.