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1.
Biochem Biophys Res Commun ; 524(4): 883-889, 2020 04 16.
Artículo en Inglés | MEDLINE | ID: mdl-32057365

RESUMEN

Disuse osteoporosis (DOP) is a common complication resulting from the lack of or disuse of mechanical loading and has been unsatisfactorily treated. We hypothesized that exosomes derived from human umbilical cord mesenchymal stem cells (HUCMSCs) could reduce bone marrow mesenchymal stem cell (BMSC) apoptosis in rat DOP via the miR-1263/Mob1/Hippo signaling pathway. To evaluate the function of exosomes derived from HUCMSCs (HUCMSC-Exos) in DOP, hind limb unloading (HLU)-induced DOP rat models were prepared. In vitro, the proliferation of BMSCs were evaluated using CCK-8 assays. Further, the apoptosis of BMSCs were evaluated using annexin V-FITC assay and Western blots. In vivo, the protective effects of HUCMSC-Exos were evaluated using HE staining and microCT analysis. The underlying molecular mechanism of exosome action on BMSC apoptosis through the miR-1263/Mob1/Hippo pathway was also investigated by high-throughput RNA sequencing, luciferase reporter assays, RNA-pull down assays and Western blots. The RNA-seq and q-PCR results showed that the level of miR-1263 was most abundant among differentially expressed microRNAs. Exosomal miR-1263 could bind to the 3'untranslated region (3' UTR) of Mob1 and exert its function by directly targeting Mob1 in recipient cells. The inhibition of Mob1 could activate YAP expression. Hippo inhibition reversed the in vitro HLU-induced apoptotic effect on BMSCs. The microCT and HE staining results indicated that HUCMSC-Exos ameliorated DOP in vivo. Exosomes derived from HUCMSCs are effective at inhibiting BMSC apoptosis and preventing rat DOP. This mechanism is mediated by the miR-1263/Mob1/Hippo signaling pathway.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/genética , Exosomas/trasplante , Células Madre Mesenquimatosas/metabolismo , MicroARNs/genética , Osteoporosis/prevención & control , Proteínas Serina-Treonina Quinasas/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Animales , Apoptosis/genética , Proteínas Reguladoras de la Apoptosis/genética , Proteínas Reguladoras de la Apoptosis/metabolismo , Proliferación Celular , Exosomas/genética , Exosomas/metabolismo , Regulación de la Expresión Génica , Suspensión Trasera/efectos adversos , Suspensión Trasera/métodos , Humanos , Células Madre Mesenquimatosas/citología , MicroARNs/metabolismo , Osteoporosis/etiología , Osteoporosis/genética , Osteoporosis/patología , Proteínas Serina-Treonina Quinasas/metabolismo , Ratas , Ratas Sprague-Dawley , Transducción de Señal , Cordón Umbilical/citología , Cordón Umbilical/metabolismo , Proteínas Señalizadoras YAP
2.
Calcif Tissue Int ; 106(5): 486-493, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-31897529

RESUMEN

Ossification of the ligamentum flavum (OLF) is characterized by a process of ectopic bone formation in the ligamentum flavum. The definitive pathophysiology of OLF still remains unclear, but the epigenetic m6A modification plays an important role in OLF. In addition, no studies have reported the function of ALKBH5 in OLF development. In this study, we investigated the function of the m6A demethylation enzyme ALKBH5 in OLF. To evaluate the function of ALKBH5, OLF tissues and normal ligamentum flavum tissues were collected. In vitro methods, including HE, IHC and western blotting assays, were used to evaluate the association of ALKBH5 with OLF. In addition, we verified the effects of ALKBH5 on osteogenesis using alizarin red and ALP staining. MeRIP q-PCR was performed to investigate the methylation level of BMP2. Moreover, the mechanism of ALKBH5-mediated regulation of the ossification of the ligamentum flavum cells through the AKT signaling pathway was also verified. The present study showed that the expression of ALKBH5 increased in OLF tissues. The overexpression of ALKBH5 increased the expression of osteogenic genes and promoted the ossification of ligamentum flavum cells. Furthermore, BMP2 was significantly enriched in the ligamentum flavum cells of the anti-m6A group compared with those of the IgG group. The overexpression of ALKBH5 led to the activation of p-AKT, and BMP2 was regulated by ALKBH5 through the AKT signaling pathway. ALKBH5 promoted the osteogenesis of the ligamentum flavum cells through BMP2 demethylation and AKT activation. ALKBH5 was shown to be an important demethylation enzyme in OLF development.


Asunto(s)
Desmetilasa de ARN, Homólogo 5 de AlkB , Proteína Morfogenética Ósea 2 , Ligamento Amarillo , Osificación Heterotópica , Proteínas Proto-Oncogénicas c-akt , Desmetilasa de ARN, Homólogo 5 de AlkB/metabolismo , Proteína Morfogenética Ósea 2/metabolismo , Células Cultivadas , Desmetilación , Humanos , Ligamento Amarillo/metabolismo , Ligamento Amarillo/patología , Osificación Heterotópica/metabolismo , Osteogénesis , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , Vértebras Torácicas
3.
Biochem Biophys Res Commun ; 509(1): 255-261, 2019 01 29.
Artículo en Inglés | MEDLINE | ID: mdl-30579595

RESUMEN

PURPOSE: large doses of glucocorticoids (GCs) are the most common cause of glucocorticoid-induced osteonecrosis of femoral head (GIONFH). Although awareness of GIONFH among patients with GCs history has increased over recent years, several studies indicate that its mechanism remains unclear. METHODS: To evaluate the function of circUSP45 in GIONFH, femoral heads in GIONFH patients or femoral heads in fracture patients were collected. In vitro, RT-PCR, FISH, RNA pull down and Western blotting assay were used to evaluate the function of circUSP45. In addition, we also verified the effects of circUSP45 on osteogenesis using alizarin red staining. In vivo, we used HE staining and microCT analysis to evaluate the bone mass. Moreover, the mechanism of circUSP45 regulating osteogenesis through the miR-127-5p/PTEN/AKT pathway was also investigated. RESULTS: The results showed that expression of circUSP45 increased in GIONFH patients. The overexpression of circUSP45 decreases osteogenic gene expression and inhibits the proliferation of BMSCs. Furthermore, circUSP45 was located mainly in the cytoplasm and directly interacted with miR-127-5p. MiR-127-5p acts with its targets PTEN to regulate the osteogenesis. MicroCT and HE staining verify the function of circUSP45 in GIONFH rat model. CONCLUSION: CircUSP45 decreases osteogenesis in bone GIONFH by sponging miR-127-5p through PTEN/AKT signal pathway.


Asunto(s)
Necrosis de la Cabeza Femoral/genética , MicroARNs/genética , Osteogénesis , Fosfohidrolasa PTEN/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , ARN/genética , Animales , Células Cultivadas , Femenino , Necrosis de la Cabeza Femoral/inducido químicamente , Necrosis de la Cabeza Femoral/metabolismo , Necrosis de la Cabeza Femoral/patología , Regulación de la Expresión Génica , Glucocorticoides , Humanos , ARN Circular , Ratas Sprague-Dawley , Transducción de Señal
5.
J Arthroplasty ; 33(6): 1972-1978.e4, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29455938

RESUMEN

BACKGROUND: Total knee arthroplasty (TKA) is accompanied by moderate-to-severe postoperative pain. Postoperative pain will hamper functional recovery and lower patients' satisfaction with surgery. Recently, periarticular local infiltration analgesia (LIA) has been widely used in TKA. However, there is no definite answer as to the efficacy and safety of LIA compared with femoral nerve block (FNB). METHOD: Randomized controlled trials about relevant studies were searched from PubMed (1996 to July 2017), Embase (1980 to July 2017), and Cochrane Library (CENTRAL, July 2017). Ten studies which compared LIA with FNB methods were included in our meta-analysis. RESULTS: Ten studies containing 950 patients met the inclusion criteria. Our pooled data indicated that LIA was as effective as the FNB in terms of visual analog scale score for pain at 24 hours (P = .52), 48 hours (P = .36), and 72 hours (P = .27), and total morphine consumption (P = .27), range of motion (P = .45), knee society score (P = .51), complications (P = .81), and length of hospital stay (P = .75). CONCLUSIONS: Our current meta-analysis results demonstrated that there were no differences in efficacy between the FNB and LIA method.


Asunto(s)
Analgesia/métodos , Artroplastia de Reemplazo de Rodilla/efectos adversos , Nervio Femoral/cirugía , Bloqueo Nervioso/efectos adversos , Bloqueo Nervioso/métodos , Dolor Postoperatorio/tratamiento farmacológico , Anciano , Anestesia de Conducción , Anestésicos Locales/uso terapéutico , Femenino , Humanos , Hipoestesia , Inyecciones , Articulación de la Rodilla , Tiempo de Internación , Masculino , Persona de Mediana Edad , Morfina/uso terapéutico , Manejo del Dolor/métodos , Satisfacción del Paciente , Ensayos Clínicos Controlados Aleatorios como Asunto , Rango del Movimiento Articular
6.
J Arthroplasty ; 32(10): 3238-3248.e3, 2017 10.
Artículo en Inglés | MEDLINE | ID: mdl-28606458

RESUMEN

BACKGROUND: Total knee arthroplasty (TKA) is associated with intense postoperative pain with a need for early ambulation to gain function and prevent postoperative complications. Compared with femoral nerve block (FNB), adductor canal block (ACB) can relieve postoperative pain and preserve quadriceps muscle strength. This meta-analysis was conducted to investigate which analgesic method provides better pain relief and functional recovery after TKA. METHOD: We conducted a meta-analysis to identify relevant randomized controlled trials involving ACB and FNB after TKA in electronic databases, including Web of Science, Embase, PubMed, and the Cochrane Library, up to November 2016. Finally, 9 randomized controlled trials involving 609 patients (668 knees) were included in our study. Review Manager Software and Grading of Recommendations Assessment, Development, and Evaluation profiler were used to perform the meta-analysis. RESULTS: Compared with FNB, ACB resulted in better quadriceps muscle strength and mobilization ability. There were no significant differences in the visual analog scale at rest, visual analog scale with mobilization, rescue opioid consumption, patient satisfaction, and length of hospital stay. CONCLUSION: Compared with FNB, ACB shows similar pain control after TKA. However, ACB can better preserve quadriceps muscle strength and improve mobilization ability. In conclusion, ACB showed better functional recovery after TKA without compromising pain control. Therefore, ACB is recommended as an alternative analgesic method for early ambulation after TKA.


Asunto(s)
Artroplastia de Reemplazo de Rodilla , Nervio Femoral , Bloqueo Nervioso/métodos , Manejo del Dolor/métodos , Dolor Postoperatorio/prevención & control , Analgésicos Opioides/administración & dosificación , Anestesia de Conducción , Ambulación Precoz , Humanos , Tiempo de Internación , Fuerza Muscular , Músculo Esquelético , Dimensión del Dolor , Satisfacción del Paciente , Complicaciones Posoperatorias , Músculo Cuádriceps/fisiología , Ensayos Clínicos Controlados Aleatorios como Asunto , Recuperación de la Función , Muslo , Escala Visual Analógica
7.
J Arthroplasty ; 32(4): 1395-1402, 2017 04.
Artículo en Inglés | MEDLINE | ID: mdl-28082044

RESUMEN

BACKGROUND: Total knee arthroplasty (TKA) is gradually emerging as the treatment of choice for end-stage osteoarthritis. In the past, the method of liposomal bupivacaine by periarticular injection (PAI) showed better effects on pain reduction and opioid consumption after surgery. However, some recent studies have reported that liposomal bupivacaine by PAI did not improve pain control and functional recovery in patients undergoing TKA. Therefore, this meta-analysis was conducted to determine whether liposomal bupivacaine provides better pain relief and functional recovery after TKA. METHODS: Web of Science, PubMed, Embase, and the Cochrane Library were comprehensively searched. Randomized controlled trials, controlled clinical trials, and cohort studies were included in our meta-analysis. Eleven studies that compared liposomal bupivacaine using the PAI technique with the conventional PAI method were included in our meta-analysis. The preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines and Cochrane Handbook were applied to assess the quality of the results published in all included studies to ensure that the results of our meta-analysis were reliable and veritable. RESULTS: Our pooled data analysis demonstrated that liposomal bupivacaine was as effective as the control group in terms of visual analog scale score at 24 hours (P = .46), 48 hours (P = .43), 72 hours (P = .21), total amount of opioid consumption (P = .25), range of motion (P = .28), length of hospital stay (P = .53), postoperative nausea (P = .34), and ambulation distance (P = .07). CONCLUSION: Compared with the conventional PAI method, liposomal bupivacaine shows similar pain control and functional recovery after TKA. Considering the cost for pain control, liposomal bupivacaine is not worthy of being recommended as a long-acting alternative analgesic agent using the PAI method.


Asunto(s)
Anestésicos Locales/administración & dosificación , Artroplastia de Reemplazo de Rodilla/efectos adversos , Bupivacaína/administración & dosificación , Dolor Postoperatorio/tratamiento farmacológico , Recuperación de la Función/efectos de los fármacos , Analgésicos/administración & dosificación , Analgésicos Opioides/administración & dosificación , Humanos , Inyecciones Intraarticulares , Tiempo de Internación , Liposomas , Manejo del Dolor/métodos , Dimensión del Dolor , Dolor Postoperatorio/etiología , Náusea y Vómito Posoperatorios , Rango del Movimiento Articular
9.
Otolaryngol Head Neck Surg ; 170(4): 999-1008, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38124278

RESUMEN

OBJECTIVE: Olfactory disturbance is one of the main symptoms of coronavirus disease-2019 (COVID-19). Various olfactory disorders caused by viral infections are treated with nasal corticosteroids. This study aimed to evaluate the safety and efficacy of nasal corticosteroids in the treatment of olfactory disorders caused by the severe acute respiratory syndrome coronavirus 2. DATA SOURCES: We searched the Web of Science, Embase, PubMed, and Cochrane Library databases for clinical trials of nasal corticosteroids for treating COVID-19 olfactory dysfunction. REVIEW METHODS: We assessed the effect of nasal corticosteroids on olfactory function in COVID-19-affected individuals using a Meta-analysis of published studies, considering the number of patients who fully recovered from olfactory dysfunction, olfactory scores following treatment, and olfactory recovery time. RESULTS: Seven studies involving 930 patients were analyzed. The Meta-analysis results revealed that the olfactory score of the experimental group was 1.40 points higher than that of the control group (standardized mean difference [MD]: 1.40, 95% confidence interval [95% CI]: 0.34-2.47, P < .00001). However, the differences in the outcomes of cure rate (risk ratio: 1.18, 95% CI: 0.89-1.69, P = .21) and recovery time (MD: -1.78, 95% CI: -7.36 to 3.81, P = .53) were not statistically significant. Only 1 study reported adverse effects of nasal steroid treatment, namely tension, anger, and stomach irritation. CONCLUSION: Although nasal steroid therapy does not result in significant adverse effects, it proves ineffective in the treatment of COVID-19 olfactory dysfunction.


Asunto(s)
COVID-19 , Trastornos del Olfato , Rinitis , Humanos , Rinitis/tratamiento farmacológico , COVID-19/complicaciones , Corticoesteroides/uso terapéutico , Esteroides , Trastornos del Olfato/tratamiento farmacológico , Trastornos del Olfato/etiología
10.
Front Immunol ; 14: 1344990, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38239367

RESUMEN

[This corrects the article DOI: 10.3389/fimmu.2022.923286.].

11.
Int J Surg ; 109(11): 3566-3577, 2023 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-37534687

RESUMEN

BACKGROUND: Propofol is the most widely used intravenous anesthetic in endoscopic surgery, but is associated with several adverse reactions. Public research has shown that remimazolam, a safe general anesthetic, is increasingly being used as a substitute for propofol in clinical operations. Our meta-analysis aimed to analyze whether the adverse reaction rate of remimazolam in endoscopic surgery is acceptable and whether the surgical success rate is not lower than that of propofol. AIM: This meta-analysis examined the adverse events and efficacy of remimazolam vs. propofol during endoscopic surgery. METHOD: MEDLINE, Embase, ClinicalTrials.gov, and Google Scholar were comprehensively searched. Seven studies comparing remimazolam and propofol were included in our meta-analysis. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and Cochrane manual were used to assess the quality of the results published in all included studies to ensure that our meta-analysis results are reliable and worthwhile. RESULTS: Compared to propofol, the use of remimazolam reduced postoperative injection pain [relative risk (RR)=0.06, 95% confidence interval (CI): 0.03-0.12, P <0.00001], postoperative hypotension (RR=0.45, 95% CI: 0.28-0.73, P =0.001), and postoperative respiratory depression (RR=0.20, 95% CI: 0.08-0.47, P =0.0002); however, it also slightly reduced the success rate of the operation [risk difference (RD)=-0.02, 95% CI: -0.04 to -0.01, P =0.0007]. There were no significant differences in the occurrence of bradycardia symptoms after the operation (RD=-0.01, 95% CI: -0.03 to 0.01, P =0.35), recovery time after the operation [standardized mean difference (SMD)=0.68, 95% CI: -0.43 to 1.80, P =0.23] or discharge time (SMD=0.17, 95% CI: -0.58 to 0.23, P =0.41). We also performed a subgroup analysis of each corresponding outcome. CONCLUSION: Our analysis showed that remimazolam may be a safer shock option than propofol for endoscopic surgery. However, further research is required to determine their utility.


Asunto(s)
Propofol , Humanos , Propofol/efectos adversos , Anestesia Intravenosa/efectos adversos , Endoscopía , Dolor Postoperatorio
12.
Front Immunol ; 13: 923286, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36105796

RESUMEN

Objectives: A major challenge for COVID-19 therapy is dysregulated immune response associated with the disease. Umbilical cord mesenchymal stromal cells (UC-MSCs) may be a promising candidate for COVID-19 treatment owing to their immunomodulatory and anti-inflammatory functions. Therefore, this study aimed to evaluate the effectiveness of UC-MSCs inpatients with COVID-19. Method: Medline, Embase, PubMed, Cochrane Library, and Web of Science databases were searched to collect clinical trials concerning UC-MSCs for the treatment of COVID-19. After literature screening, quality assessment, and data extraction, a systematic review and meta-analysis of the included study were performed. Results: This systematic review and meta-analysis were prospectively registered on PROSPERO, and the registration number is CRD42022304061. After screening, 10 studies involving 293 patients with COVID-19 were eventually included. Our meta-analysis results showed that UC-MSCs can reduce mortality (relative risk [RR] =0.60, 95% confidence interval [CI]: [0.38, 0.95], P=0.03) in COVID-19 patients. No significant correlation was observed between adverse events and UC-MSC treatment (RR=0.85, 95% CI: [0.65, 1.10], P=0.22; RR=1.00, 95%CI: [0.64, 1.58], P=1.00). In addition, treatment with UC-MSCs was found to suppress inflammation and improve pulmonary symptoms. Conclusions: UC-MSCs hold promise as a safe and effective treatment for COVID-19. Systematic Review Registartion: PROSPERO, identifier CRD42022304061.


Asunto(s)
Tratamiento Farmacológico de COVID-19 , COVID-19 , Células Madre Mesenquimatosas , COVID-19/terapia , Humanos , Inmunomodulación , Cordón Umbilical
13.
Mol Ther Nucleic Acids ; 23: 565-576, 2021 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-33510944

RESUMEN

The pathogenesis of glucocorticoid (GC)-induced osteonecrosis of the femoral head (GIONFH) is still disputed, and abnormal bone metabolism caused by GCs may be an important factor. In vitro, Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) staining were used to evaluate cellular proliferation, and western blotting was used to investigate osteogenesis. In vivo, we used micro-computed tomography (micro-CT), H&E staining, Masson staining, and immunohistochemistry (IHC) analysis to evaluate the impact of exosomes. In addition, the mechanism by which exosomes regulate osteogenesis through the miR-365a-5p/Hippo signaling pathway was investigated using RNA sequencing (RNA-seq), luciferase reporter assays, fluorescence in situ hybridization (FISH), and western blotting. The results of western blotting verified that the relevant genes in osteogenesis, including BMP2, Sp7, and Runx2, were upregulated. RNA-seq and qPCR of the exosome and Dex-treated exosome groups showed that miR-365a-5p was upregulated in the exosome group. Furthermore, we verified that miR-365a-5p promoted osteogenesis by targeting SAV1. Additional in vivo experiments revealed that exosomes prevented GIONFH in a rat model, as shown by micro-CT scanning and histological and IHC analysis. We concluded that exosomal miR-365a-5p was effective in promoting osteogenesis and preventing the development of GIONFH via activation of the Hippo signaling pathway in rats.

14.
Stem Cell Res Ther ; 11(1): 295, 2020 07 17.
Artículo en Inglés | MEDLINE | ID: mdl-32680565

RESUMEN

BACKGROUND: The oral cavity is a complex environment in which periodontal tissue is constantly stimulated by external microorganisms and mechanical forces. Proper mechanical force helps maintain periodontal tissue homeostasis, and improper inflammatory response can break the balance. Periodontal ligament (PDL) cells play crucial roles in responding to these challenges and maintaining the homeostasis of periodontal tissue. However, the mechanisms underlying PDL cell property changes induced by inflammatory and mechanical force microenvironments are still unclear. Recent studies have shown that exosomes function as a means of cell-cell and cell-matrix communication in biological processes. METHODS: Human periodontal ligament stem cells (HPDLSCs) were tested by the CCK8 assay, EdU, alizarin red, and ALP staining to evaluate the functions of exosomes induced by a mechanical strain. MicroRNA sequencing was used to find the discrepancy miRNA in exosomes. In addition, real-time PCR, FISH, luciferase reporter assay, and western blotting assay were used to investigate the mechanism of miR-181b-5p regulating proliferation and osteogenic differentiation through the PTEN/AKT pathway. RESULTS: In this study, the exosomes secreted by MLO-Y4 cells exposed to mechanical strain (Exosome-MS) contributed to HPDLSC proliferation and osteogenic differentiation. High-throughput miRNA sequencing showed that miR181b-5p was upregulated in Exosome-MS compared to the exosomes derived from MLO-Y4 cells lacking mechanical strain. The luciferase reporter assay demonstrated that miR-181b-5p may target phosphatase tension homolog deletion (PTEN). In addition, PTEN was negatively regulated by overexpressing miR-181b-5p. Real-time PCR and western blotting assay verified that miR-181b-5p enhanced the protein kinase B (PKB, also known as AKT) activity and improved downstream factor transcription. Furthermore, miR-181b-5p effectively ameliorated the inhibition of HPDLSC proliferation and promoted HPDLSC induced by inflammation. CONCLUSIONS: This study concluded that exosomes induced by mechanical strain promote HPDLSC proliferation via the miR-181b-5p/PTEN/AKT signaling pathway and promote HPDLSC osteogenic differentiation by BMP2/Runx2, suggesting a potential mechanism for maintaining periodontal homeostasis.


Asunto(s)
Fenómenos Biológicos , Exosomas , MicroARNs , Diferenciación Celular , Proliferación Celular , Exosomas/genética , Exosomas/metabolismo , Humanos , MicroARNs/genética , Osteocitos/metabolismo , Osteogénesis/genética , Fosfohidrolasa PTEN/genética , Ligamento Periodontal/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal
15.
Chem Biol Interact ; 304: 97-105, 2019 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-30878453

RESUMEN

PURPOSE: Glucocorticoid-induced osteonecrosis of the femoral head (GIONFH) is a common disease following long-term use or large doses of glucocorticoids. The pathogenesis of GIONFH remains controversial, and abnormal bone metabolism caused by glucocorticoids(GCs) may be one of the important factors. Due to its positive effect on bone remodeling, naringin shows potential therapeutic effects in bone metabolism-related diseases. In this study, we hypothesized that naringin regulated bone metabolism in rat GIONFH via the Akt/Bad signal cascades. METHODS: In vitro, a dexamethasone (Dex)- or naringin-treated cell model was used to evaluate the function of naringin. In vivo, methylprednisolone (MPS)-treated rat model was used to evaluate the function of naringin in GIONFH. In vitro, Cell Counting Kit-8 (CCK-8) and Edu staining was used to evaluate the proliferation of osteocytes, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, Annexin V-FITC-PI, and western blotting were used to evaluate the apoptosis of osteocytes. We also verified the effects of naringin on osteogenesis and osteoclastogenesis. In vivo, we used micro-CT (computed tomography), histological, and immunohistochemical analysis to evaluate the effect of naringin. Moreover, the mechanism of naringin regulating the bone metabolism through the Akt/Bad pathway was also investigated using bioinformatics analysis and western blotting. RESULTS: The results of in vitro study showed that Akt activated by naringin promoted osteogenesis and osteocyte proliferation; in addition, osteocyte apoptosis and osteoclastogenesis was inhibited by Akt activation and Bad suppression. According to the in vivo study, naringin prevented GIONFH in a rat model as shown by micro-CT scanning and histological and immunohistochemical analysis. CONCLUSIONS: Therefore, we concluded that naringin is an effective compound for promoting bone repair and preventing bone loss in rats with GIONFH through Akt/Bad signal cascades.


Asunto(s)
Cabeza Femoral/efectos de los fármacos , Flavanonas/farmacología , Glucocorticoides/farmacología , Osteogénesis/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/antagonistas & inhibidores , Células 3T3 , Animales , Apoptosis/efectos de los fármacos , Células Cultivadas , Relación Dosis-Respuesta a Droga , Cabeza Femoral/metabolismo , Ratones , Estructura Molecular , Proteínas Proto-Oncogénicas c-akt/metabolismo , Células RAW 264.7 , Transducción de Señal/efectos de los fármacos , Relación Estructura-Actividad
16.
Int J Biol Sci ; 15(9): 1861-1871, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31523188

RESUMEN

Purpose: Glucocorticoid-induced osteonecrosis of the femoral head (GIONFH) is a common disease after long-term or high-dose glucocorticoid use. The pathogenesis of GIONFH is still controversial, and abnormal bone metabolism caused by glucocorticoids may be one of the important factors. Exosomes, owing to their positive effect on bone repair, show promising therapeutic effects on bone-related diseases. In this study, we hypothesised that exosomes reduce osteocyte apoptosis in rat GIONFH via the miR-21-PTEN-AKT signalling pathway. Methods: To evaluate the effects of exosomes in GIONFH, a dexamethasone-treated or exosome-treated in vitro cell model and a methylprednisolone-treated in vivo rat model were set up. In vitro, a CCK-8 assay and 5-ethynyl-2'-deoxyuridine staining were performed to evaluate the proliferation of osteocytes. Further, a terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay, annexin V-fluorescein isothiocyanate-propidium iodide staining, and western blotting were conducted to evaluate the apoptosis of osteocytes. In vivo, we used micro-computed tomography and histological and immunohistochemical analyses to assess the effects of exosomes. Moreover, the mechanism of exosome action on osteocyte apoptosis through the miR-21-PTEN-AKT pathway was investigated by high-throughput RNA sequencing, fluorescence in situ hybridisation, luciferase reporter assays, and western blotting. Results: High-throughput RNA sequencing results showed that the AKT signalling pathway was up-regulated in the exosome group. Quantitative PCR and western blotting confirmed that the relative expression of genes in the AKT pathway was up-regulated. Western blotting revealed that AKT activated by exosomes inhibited osteocyte apoptosis. RNA fluorescence in situ hybridisation and luciferase reporter assays were performed to confirm the interaction between miR-21 and PTEN. According to the experiment in vivo, exosomes prevented GIONFH in a rat model as evidenced by micro-computed tomography scanning and histological and immunohistochemical analyses. Conclusions: Exosomes are effective at inhibiting osteocyte apoptosis (in MLO-Y4 cells) and at preventing rat GIONFH. These beneficial effects are mediated by the miR-21-PTEN-AKT signalling pathway.


Asunto(s)
Exosomas/metabolismo , Glucocorticoides/farmacología , Células Madre Mesenquimatosas/citología , Osteocitos/citología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Cordón Umbilical/citología , Gelatina de Wharton/citología , Animales , Apoptosis/efectos de los fármacos , Western Blotting , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Exosomas/ultraestructura , Femenino , Humanos , Células Madre Mesenquimatosas/ultraestructura , Microscopía Electrónica de Transmisión , Osteocitos/efectos de los fármacos , Osteocitos/ultraestructura , Ratas , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos
17.
Int J Surg ; 51: 205-212, 2018 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-29367046

RESUMEN

OBJECTIVE: A meta-analysis to evaluate the efficacy of preoperative training on functional recovery in patients undergoing total knee arthroplasty. METHOD: Randomized controlled trials (RCTs) about relevant studies were searched from PubMed (1996-2017.4), Embase (1980-2017.4), and the Cochrane Library (CENTRAL 2017.4). Nine studies which evaluated the effect of preoperative training on functional recovery in patients undergoing TKA were included in our meta-analysis. Meta-analysis results were collected and analyzed by Review Manager 5.3 (Copenhagen: The Nordic Cochrane Center the Collaboration 2014). RESULTS: Nine studies containing 777 patients meet the inclusion criteria. Our pooled data analysis indicated that preoperative training was as effective as the control group in terms of visual analogue scale(VAS) score at ascend stairs (P = 0.41) and descend stars (P = 0.80), rang of motion (ROM) of flexion (P = 0.86) and extension (P = 0.60), short form 36 (SF-36) of physical function score (P = 0.07) and bodily pain score (P = 0.39), western Ontario and Macmaster universities osteoarthritis index (WOMAC) function score (P = 0.10), and time up and go (P = 0.28). While differences were found in length of stay (P < 0.05). CONCLUSIONS: Our meta-analysis demonstrated that preoperative training have the similar efficacy on functional recovery in patients following total knee arthroplasty compared with control group. However, high quality studies with more patients were needed in future.


Asunto(s)
Artroplastia de Reemplazo de Rodilla , Recuperación de la Función , Humanos , Cuidados Preoperatorios , Rango del Movimiento Articular , Escala Visual Analógica
18.
Int J Surg ; 52: 89-97, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-29471156

RESUMEN

OBJECTIVE: Femoral neck fracture is considered a difficult fracture to treat and often gives rise to unsatisfactory treatment results. Cannulated cancellous screws (CCS) or a sliding hip screw (SHS) are the mainstream internal fixations used for osteosynthesis of femoral neck fractures. There is a need to integrate existing data through a meta-analysis to investigate the safety and effectiveness of CCS and SHS in the treatment of femoral neck fractures. METHOD: According to the Cochrane Handbook for Systematic Reviews of Interventions, we screened for the relevant studies by searching Google Scholar, the Cochrane Controlled Trials Register, the Cochrane Library, Web of Science, EMBASE, and PubMed. The PICOS criteria was used to make sure the included studies fulfilled the inclusion criteria. RESULTS: Pooled data showed that there were no significant differences between the SHS and CCS groups for the Harris Hip Score. Significant differences were found between the SHS and CCS groups in terms of union time, postoperative complications, blood loss, operation time, incision length and length of hospital stay. CONCLUSIONS: Although the SHS and CCS groups showed similar functional recovery in treatment of femoral neck fracture in terms of the Harris Hip Score, the SHS group showed fewer postoperative complications and faster union time for patients with femoral neck fractures. Therefore, compared with CCS, the use of SHS may be a more effective treatment of femoral neck fractures.


Asunto(s)
Tornillos Óseos/efectos adversos , Fracturas del Cuello Femoral/cirugía , Fijación Interna de Fracturas/métodos , Adulto , Anciano , Femenino , Fijación Interna de Fracturas/efectos adversos , Humanos , Tiempo de Internación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Tempo Operativo , Complicaciones Posoperatorias/etiología , Recuperación de la Función , Resultado del Tratamiento
19.
Pain Physician ; 20(7): 649-661, 2017 11.
Artículo en Inglés | MEDLINE | ID: mdl-29149144

RESUMEN

BACKGROUND: Pain management after spinal surgery has been studied for years. Gabapentin is a third-generation antiepileptic drug that selectively affects the nociceptive process and has been used for pain relief after surgery. However, the relationship between gabapentin and postoperative pain in spinal surgery is still controversial. OBJECTIVE: To assess the efficacy of the pre-emptive use of gabapentin in spinal surgery. STUDY DESIGN: A meta-analysis of randomized controlled studies. SETTING: The MEDLINE, EMBASE, ClinicalTrials.gov, and Web of Science databases were systematically searched. METHODS: This meta-analysis of randomized controlled trials (RCTs) was performed to compare the use of gabapentin with placebo in spinal surgery regarding to the following: the mean difference (MD) of postoperative opioid requirements, the changes of visual analog scale (VAS) scores in 2 groups, and the incidence rate of adverse effects. An electronic-based search of all related literatures was conducted, and only RCTs for spinal surgery were included. The MD of postoperative opioid requirements and VAS scores and the relative risk (RR) of the incidence rate of adverse effects in the gabapentin group versus the placebo group were extracted throughout the study. RESULTS: Ten trials, involving 827 patients, met the inclusion criteria and were included in this meta-analysis. The total morphine consumption was significantly lower over the first 24 hours postoperatively in the gabapentin group (P < 0.05). The VAS scores at 2, 4, 6, 12, and 24 hours were less in the gabapentin group (P < 0.05). The incidence rate of vomiting, pruritus, and urinary retention was significantly less in the gabapentin groups (RR = 0.53, 95% CI 0.32-0.86, P < 0.05; RR = 0.38, 95% CI 0.22-0.66, P < 0.05; RR = 0.57, 95% CI 0.34-0.98, P < 0.05, respectively). LIMITATIONS: All of the studies we screened were published online except for unpublished articles. Only 10 RCTs met our inclusion criteria, so the sample size was still relatively small. CONCLUSION: This meta-analysis suggests that the administration of gabapentin is effective in reducing postoperative opioid consumption, VAS scores, and some side effects after spinal surgery. KEY WORDS: Gabapentin, analgesia, spinal surgery, meta-analysis, randomized controlled trials, visual analog scale score, side effect.


Asunto(s)
Aminas/uso terapéutico , Analgésicos/uso terapéutico , Ácidos Ciclohexanocarboxílicos/uso terapéutico , Dolor Postoperatorio/tratamiento farmacológico , Cuidados Preoperatorios , Columna Vertebral/cirugía , Ácido gamma-Aminobutírico/uso terapéutico , Aminas/efectos adversos , Analgésicos/efectos adversos , Ácidos Ciclohexanocarboxílicos/efectos adversos , Gabapentina , Humanos , Dimensión del Dolor , Náusea y Vómito Posoperatorios/epidemiología , Ensayos Clínicos Controlados Aleatorios como Asunto , Ácido gamma-Aminobutírico/efectos adversos
20.
Medicine (Baltimore) ; 96(26): e6947, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28658096

RESUMEN

BACKGROUND: Pain management after total knee arthroplasty (TKA) varies and has been investigated for years. Pregabalin as an anticonvulsant agent that selectively affects the nociceptive process has been used for pain relief after operation. This meta-analysis was conducted to examine the evidence of pregabalin in TKA. METHODS: Systematic searches of all related literatures were conducted using the following databases: MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials. Only randomized-controlled trials (RCTs) for TKA were included. The postoperative narcotic requirements, visual analog scale scores, knee flexion range, and relative risk of incidence rate of adverse effects in the pregabalin group versus placebo group were extracted throughout the study. RESULTS: Seven placebo-controlled RCTs met the inclusion criteria. The use of pregabalin significantly decrease the postoperative total morphine consumption (P < .05) and increase the passive knee flexion range (P < .05). Compared with the control group, the incidence of some side effects (nausea, vomiting, pruritus, and constipation) was less in the pregabalin group (P < .05). CONCLUSIONS: The administration of pregabalin is not only efficacious in the reduction of narcotic requirements and incidence of some adverse effect, but also workable for the improvement of passive knee flexion range after TKA.


Asunto(s)
Analgésicos/efectos adversos , Analgésicos/uso terapéutico , Artroplastia de Reemplazo de Rodilla , Dolor Postoperatorio/tratamiento farmacológico , Pregabalina/efectos adversos , Pregabalina/uso terapéutico , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto
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