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1.
Small ; 20(7): e2307058, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37806763

RESUMO

The severe quality of life and economic burden imposed by non-healing skin wounds, infection risks, and treatment costs are affecting millions of patients worldwide. To mitigate these challenges, scientists are relentlessly seeking effective treatment measures. In recent years, extracellular vesicles (EVs) have emerged as a promising cell-free therapy strategy, attracting extensive attention from researchers. EVs mediate intercellular communication, possessing excellent biocompatibility and stability. These features make EVs a potential tool for treating a plethora of diseases, including those related to wound repair. However, there is a growing focus on the engineering of EVs to overcome inherent limitations such as low production, relatively fixed content, and targeting capabilities of natural EVs. This engineering could improve both the effectiveness and specificity of EVs in wound repair treatments. In light of this, the present review will introduce the latest progress in the design methods and experimental paradigms of engineered EVs applied in wound repair. Furthermore, it will comprehensively analyze the current clinical research status and prospects of engineered EVs within this field.


Assuntos
Vesículas Extracelulares , Qualidade de Vida , Humanos , Comunicação Celular , Terapia Baseada em Transplante de Células e Tecidos , Cicatrização
2.
Zhongguo Yi Liao Qi Xie Za Zhi ; 48(2): 179-183, 2024 Mar 30.
Artigo em Chinês | MEDLINE | ID: mdl-38605618

RESUMO

Objective: To introduce a locating device for the entry point of intramedullary nail based on the inertial navigation technology, which utilizes multi-dimensional angle information to assist in rapid and accurate positioning of the ideal direction of femoral anterograde intramedullary nails' entry point, and to verify its clinical value through clinical tests. Methods: After matching the locating module with the developing board, which are the two components of the locating device, they were placed on the skin surface of the proximal femur of the affected side. Anteroposterior fluoroscopy was performed. The developing angle corresponding to the ideal direction of entry point was selected based on the X-ray image, and then the yaw angle of the locating module was reset to zero. After resetting, the locating module was combined with the surgical instrument to guide the insertion angle of the guide wire. The ideal direction of entry point was accurately located based on the angle guidance. By setting up an experimental group and a control group for clinical surgical operations, the number of guide wire insertion times, surgical time, fluoroscopy frequency, and intraoperative blood loss with or without the locating device was recorded. Results: Compared to the control group, the experimental group showed significant improvement in the number of guide wire insertion times, surgical time, fluoroscopy frequency, and intraoperative blood loss, with a statistically significant difference (P<0.01). Conclusion: The locating device can assist doctors in quickly locating the entry point of intramedullary nail, effectively reducing the fluoroscopy frequency and surgical time by improving the success rate of the guide wire insertion with one shot, improving surgical efficiency, and possessing certain clinical value.


Assuntos
Fixação Intramedular de Fraturas , Cirurgia Assistida por Computador , Humanos , Pinos Ortopédicos , Perda Sanguínea Cirúrgica , Fluoroscopia/métodos , Fixação Intramedular de Fraturas/métodos , Cirurgia Assistida por Computador/métodos
3.
Small ; 18(1): e2104229, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34791802

RESUMO

The treatment of diabetic wounds remains a major challenge in clinical practice, with chronic wounds characterized by multiple drug-resistant bacterial infections, angiopathy, and oxidative damage to the microenvironment. Herein, a novel in situ injectable HA@MnO2 /FGF-2/Exos hydrogel is introduced for improving diabetic wound healing. Through a simple local injection, this hydrogel is able to form a protective barrier covering the wound, providing rapid hemostasis and long-term antibacterial protection. The MnO2 /ε-PL nanosheet is able to catalyze the excess H2 O2 produced in the wound, converting it to O2 , thus not only eliminating the harmful effects of H2 O2 but also providing O2 for wound healing. Moreover, the release of M2-derived Exosomes (M2 Exos) and FGF-2 growth factor stimulates angiogenesis and epithelization, respectively. These in vivo and in vitro results demonstrate accelerated healing of diabetic wounds with the use of the HA@MnO2 /FGF-2/Exos hydrogel, presenting a viable strategy for chronic diabetic wound repair.


Assuntos
Diabetes Mellitus , Exossomos , Exossomos/metabolismo , Fatores de Crescimento de Fibroblastos/metabolismo , Humanos , Hidrogéis , Compostos de Manganês , Estresse Oxidativo , Óxidos , Cicatrização
4.
Cell Commun Signal ; 20(1): 165, 2022 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-36284303

RESUMO

BACKGROUND: Postmenopausal bone loss, mainly caused by excessive bone resorption mediated by osteoclasts, has become a global public health burden. Metformin, a hypoglycemic drug, has been reported to have beneficial effects on maintaining bone health. However, the role and underlying mechanism of metformin in ovariectomized (OVX)-induced bone loss is still vague. RESULTS: In this study, we demonstrated for the first time that metformin administration alleviated bone loss in postmenopausal women and ovariectomized mice, based on reduced bone resorption markers, increased bone mineral density (BMD) and improvement of bone microstructure. Then, osteoclast precursors administered metformin in vitro and in vivo were collected to examine the differentiation potential and autophagical level. The mechanism was investigated by infection with lentivirus-mediated BNIP3 or E2F1 overexpression. We observed a dramatical inhibition of autophagosome synthesis and osteoclast formation and activity. Treatment with RAPA, an autophagy activator, abrogated the metformin-mediated autophagy downregulation and inhibition of osteoclastogenesis. Additionally, overexpression of E2F1 demonstrated that reduction of OVX-upregulated autophagy mediated by metformin was E2F1 dependent. Mechanistically, metformin-mediated downregulation of E2F1 in ovariectomized mice could downregulate BECN1 and BNIP3 levels, which subsequently perturbed the binding of BECN1 to BCL2. Furthermore, the disconnect between BECN1 and BCL2 was shown by BNIP3 overexpression. CONCLUSION: In summary, we demonstrated the effect and underlying mechanism of metformin on OVX-induced bone loss, which could be, at least in part, ascribed to its role in downregulating autophagy during osteoclastogenesis via E2F1-dependent BECN1 and BCL2 downregulation, suggesting that metformin or E2F1 inhibitor is a potential agent against postmenopausal bone loss. Video abstract.


Assuntos
Reabsorção Óssea , Metformina , Osteoporose Pós-Menopausa , Humanos , Camundongos , Feminino , Animais , Osteoclastos , Osteoporose Pós-Menopausa/metabolismo , Metformina/farmacologia , Reabsorção Óssea/tratamento farmacológico , Autofagia , Hipoglicemiantes/metabolismo , Hipoglicemiantes/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Diferenciação Celular , Ligante RANK/metabolismo , Fator de Transcrição E2F1/metabolismo
5.
BMC Musculoskelet Disord ; 23(1): 350, 2022 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-35410232

RESUMO

BACKGROUND: We aimed to compare the intraoperative and early postoperative clinical outcomes of using an acromioclavicular joint hook plate (AJHP) versus a locking plate (LP) in the treatment of anterior sternoclavicular joint dislocation. METHODS: Seventeen patients with anterior sternoclavicular joint dislocation were retrospectively analyzed from May 2014 to September 2019. Six patients were surgically treated with an AJHP, and 11 were surgically treated with an LP. Five male and one female patients composed the AJHP group, and nine male and two female patients composed the LP group. The mean age of all patients was 49.5 years. RESULTS: Reduction and fixation were performed with AJHP or LP in all 17 patients. The mean operative blood loss, operative time, and length of incision in the AJHP group were significantly better than those in the LP group. Shoulder girdle movement of the AJHP group was significantly better than that of the LP group. CONCLUSIONS: This study revealed that AJHP facilitated glenohumeral joint motion, reduced the risk of rupture of mediastinal structures, required a shorter incision, and had lesser blood loss and a shorter duration of operation compared with LP. However, some deficiencies require further improvement.


Assuntos
Articulação Acromioclavicular , Luxações Articulares , Luxação do Ombro , Articulação Esternoclavicular , Traumatismos Torácicos , Articulação Acromioclavicular/diagnóstico por imagem , Articulação Acromioclavicular/cirurgia , Feminino , Humanos , Luxações Articulares/diagnóstico por imagem , Luxações Articulares/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Luxação do Ombro/cirurgia , Articulação Esternoclavicular/diagnóstico por imagem , Articulação Esternoclavicular/cirurgia , Resultado do Tratamento
6.
FASEB J ; 34(4): 5208-5222, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32060985

RESUMO

Emerging evidence highlights the role of the long noncoding RNA (lncRNA) KCNQ1OT1 in fracture healing. Osteoblast proliferation, migration, and survival are pivotal during this process. In this study, we aimed to improve our understanding of the regulatory role of lncRNA KCNQ1OT1 during osteoblast proliferation, migration, and survival. We searched the gene expression omnibus databases and LncBase Experimental V.2 to identify key microRNAs (miRNAs) targets of KCNQ1OT1. MiR-701-3p was selected as a differentially expressed miRNA and RNA immunoprecipitation assays were performed to verify its interaction with KCNQ1OT1. Fibroblast growth factor receptor 3 (FGFR3) was also identified as a target of miR-701-3p. We further identified KCNQ1OT1 as a competing endogenous RNA of miR-701-3p that could influence osteoblast proliferation, migration, and apoptosis in vitro and in vivo. Taken together, our results indicate that the KCNQ1OT1/miR-701-3p/FGFR3 axis is an important regulator of osteoblast proliferation, migration, and apoptosis, and provide a new therapeutic avenue for fracture healing.


Assuntos
Modelos Animais de Doenças , Fraturas do Fêmur/terapia , Consolidação da Fratura/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , RNA Longo não Codificante/genética , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/metabolismo , Animais , Apoptose , Proliferação de Células , Fraturas do Fêmur/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/genética , Transdução de Sinais
7.
J Nanobiotechnology ; 19(1): 150, 2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34020670

RESUMO

BACKGROUND: Enhanced angiogenesis can promote diabetic wound healing. Mesenchymal stem cells (MSCs)-derived exosomes, which are cell-free therapeutics, are promising candidates for the treatment of diabetic wound healing. The present study aimed to investigate the effect of exosomes derived from MSCs pretreated with pioglitazone (PGZ-Exos) on diabetic wound healing. RESULTS: We isolated PGZ-Exos from the supernatants of pioglitazone-treated BMSCs and found that PGZ-Exos significantly promote the cell viability and proliferation of Human Umbilical Vein Vascular Endothelial Cells (HUVECs) injured by high glucose (HG). PGZ-Exos enhanced the biological functions of HUVECs, including migration, tube formation, wound repair and VEGF expression in vitro. In addition, PGZ-Exos promoted the protein expression of p-AKT, p-PI3K and p-eNOS and suppressed that of PTEN. LY294002 inhibited the biological function of HUVECs through inhibition of the PI3K/AKT/eNOS pathway. In vivo modeling in diabetic rat wounds showed that pioglitazone pretreatment enhanced the therapeutic efficacy of MSCs-derived exosomes and accelerated diabetic wound healing via enhanced angiogenesis. In addition, PGZ-Exos promoted collagen deposition, ECM remodeling and VEGF and CD31 expression, indicating adequate angiogenesis in diabetic wound healing. CONCLUSIONS: PGZ-Exos accelerated diabetic wound healing by promoting the angiogenic function of HUVECs through activation of the PI3K/AKT/eNOS pathway. This offers a promising novel cell-free therapy for treating diabetic wound healing.


Assuntos
Diabetes Mellitus/metabolismo , Exossomos/metabolismo , Células-Tronco Mesenquimais/metabolismo , Pioglitazona/metabolismo , Pioglitazona/farmacologia , Cicatrização/efeitos dos fármacos , Indutores da Angiogênese/farmacologia , Animais , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Colágeno/metabolismo , Diabetes Mellitus Experimental , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Masculino , Fosfatidilinositol 3-Quinases/metabolismo , Ratos , Ratos Sprague-Dawley , Pele/efeitos dos fármacos
8.
Med Sci Monit ; 27: e928240, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33385316

RESUMO

BACKGROUND Traditional plaster (TP) is a widely used auxiliary fixation (AF) approach for postoperative fracture patients. However, patient discomfort and inconvenience to clinicians has limited its application. We introduce a novel instant 3-dimensional printing appliance system (3D-AS) to address such issues. MATERIAL AND METHODS Twenty-seven postoperative fracture patients were divided randomly between a TP group and a 3D-AS group, and analyzed retrospectively. Radiographic images during follow-up were evaluated for fracture healing and fracture reduction quality. The range of motion (ROM) was recorded to assess motor performance. Patient pain was assessed using the Visual Analogue Scale (VAS). Complications were also compared between the 2 groups. RESULTS The patients comprised 17 men and 10 women with ages ranging from 21 to 69 years (mean age: 47.35). All patients completed a follow-up visit (range: 14-19 months, mean: 13.59 months). Although no significant difference was found between general characteristics (P>0.05) and the time of fracture union (P>0.05), significant differences between groups were seen in complications (P<0.05), VAS (P<0.01), patient satisfaction (P<0.05), and ROM for the upper joints (P<0.05). CONCLUSIONS Our study suggests that 3D-AS provides better upper-limb ROM and more comfortable healing for postoperative fracture patients, indicating that it can be recommended for use in such patients.


Assuntos
Fraturas Ósseas/patologia , Fraturas Ósseas/cirurgia , Impressão Tridimensional , Estudos de Coortes , Feminino , Fraturas Ósseas/economia , Custos de Cuidados de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Impressão Tridimensional/economia , Inquéritos e Questionários , Resultado do Tratamento
9.
J Cell Mol Med ; 24(11): 6385-6396, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32307908

RESUMO

N6-methyladenosine (m6A) modification has been reported in various diseases and implicated in increasing numbers of biological processes. However, previous studies have not focused on the role of m6A modification in fracture healing. Here, we demonstrated that m6A modifications are decreased during fracture healing and that methyltransferase-like 3 (METTL3) is the main factor involved in the abnormal changes in m6A modifications. Down-regulation of METTL3 promotes osteogenic processes both in vitro and in vivo, and this effect is recapitulated by the suppression of miR-7212-5p maturation. Further studies have shown that miR-7212-5p inhibits osteoblast differentiation in MC3T3-E1 cells by targeting FGFR3. The present study demonstrated an important role of the METTL3/miR-7212-5p/FGFR3 axis and provided new insights on m6A modification in fracture healing.


Assuntos
Adenosina/análogos & derivados , Diferenciação Celular/genética , Consolidação da Fratura/genética , Metiltransferases/metabolismo , MicroRNAs/metabolismo , Osteoblastos/metabolismo , Osteoblastos/patologia , Adenosina/metabolismo , Animais , Linhagem Celular , Regulação da Expressão Gênica , Metilação , Metiltransferases/genética , Camundongos Endogâmicos C57BL , MicroRNAs/genética , Proteínas de Ligação a RNA/metabolismo , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/metabolismo
10.
J Cell Mol Med ; 24(1): 1076-1086, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31755174

RESUMO

Interleukin-10 (IL-10) displays well-documented anti-inflammatory effects, but its effects on osteoblast differentiation have not been investigated. In this study, we found IL-10 negatively regulates microRNA-7025-5p (miR-7025-5p), the down-regulation of which enhances osteoblast differentiation. Furthermore, through luciferase reporter assays, we found evidence that insulin-like growth factor 1 receptor (IGF1R) is a miR-7025-5p target gene that positively regulates osteoblast differentiation. In vivo studies indicated that the pre-injection of IL-10 leads to increased bone formation, while agomiR-7025-5p injection delays fracture healing. Taken together, these results indicate that IL-10 induces osteoblast differentiation via regulation of the miR-7025-5p/IGF1R axis. IL-10 therefore represents a promising therapeutic strategy to promote fracture healing.


Assuntos
Diferenciação Celular , Fibroblastos/citologia , Consolidação da Fratura/efeitos dos fármacos , Fraturas Ósseas/tratamento farmacológico , Interleucina-10/farmacologia , Osteoblastos/citologia , Osteogênese , Animais , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Fraturas Ósseas/metabolismo , Fraturas Ósseas/patologia , Regulação da Expressão Gênica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/genética , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Receptor IGF Tipo 1/genética , Receptor IGF Tipo 1/metabolismo
11.
Small ; 16(3): e1904044, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31867895

RESUMO

At present, developing therapeutic strategies to improve wound healing in individuals with diabetes remains challenging. Exosomes represent a promising nanomaterial from which microRNAs (miRNAs) can be isolated. These miRNAs have the potential to exert therapeutic effects, and thus, determining the potential therapeutic contributions of specific miRNAs circulating in exosomes is of great importance. In the present study, circulating exosomal miRNAs are identified in diabetic patients and assessed for their roles in the context of diabetic wound healing. A significant upregulation of miR-20b-5p is observed in exosomes isolated from patients with type 2 diabetes mellitus (T2DM), and this miRNA is able to suppress human umbilical vein endothelial cell angiogenesis via regulation of Wnt9b/ß-catenin signaling. It is found that the application of either miR-20b-5p or diabetic exosomes to wound sites is sufficient to slow wound healing and angiogenesis. In diabetic mice, it is found that knocking out miR-20b-5p significantly enhances wound healing and promotes wound angiogenesis. Together, these findings thus provide strong evidence that miR-20b-5p is highly enriched in exosomes from patients with T2DM and can be transferred to cells of the vascular endothelium, where it targets Wnt9b signaling to negatively regulate cell functionality and angiogenesis.


Assuntos
Diabetes Mellitus Tipo 2/fisiopatologia , Exossomos/metabolismo , MicroRNAs/antagonistas & inibidores , Proteínas Wnt/metabolismo , Cicatrização , Animais , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/metabolismo , Células Endoteliais da Veia Umbilical Humana , Humanos , Camundongos , MicroRNAs/sangue
12.
J Transl Med ; 18(1): 328, 2020 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-32867787

RESUMO

BACKGROUND: Patients with severe Coronavirus Disease 2019 (COVID-19) will progress rapidly to acute respiratory failure or death. We aimed to develop a quantitative tool for early predicting mortality risk of patients with COVID-19. METHODS: 301 patients with confirmed COVID-19 admitted to Main District and Tumor Center of the Union Hospital of Huazhong University of Science and Technology (Wuhan, China) between January 1, 2020 to February 15, 2020 were enrolled in this retrospective two-centers study. Data on patient demographic characteristics, laboratory findings and clinical outcomes was analyzed. A nomogram was constructed to predict the death probability of COVID-19 patients. RESULTS: Age, neutrophil-to-lymphocyte ratio, D-dimer and C-reactive protein obtained on admission were identified as predictors of mortality for COVID-19 patients by LASSO. The nomogram demonstrated good calibration and discrimination with the area under the curve (AUC) of 0.921 and 0.975 for the derivation and validation cohort, respectively. An integrated score (named ANDC) with its corresponding death probability was derived. Using ANDC cut-off values of 59 and 101, COVID-19 patients were classified into three subgroups. The death probability of low risk group (ANDC < 59) was less than 5%, moderate risk group (59 ≤ ANDC ≤ 101) was 5% to 50%, and high risk group (ANDC > 101) was more than 50%, respectively. CONCLUSION: The prognostic nomogram exhibited good discrimination power in early identification of COVID-19 patients with high mortality risk, and ANDC score may help physicians to optimize patient stratification management.


Assuntos
Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/mortalidade , Escore de Alerta Precoce , Nomogramas , Pneumonia Viral/diagnóstico , Pneumonia Viral/mortalidade , Adulto , Idoso , Betacoronavirus/fisiologia , COVID-19 , China/epidemiologia , Estudos de Coortes , Feminino , História do Século XXI , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Prognóstico , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , SARS-CoV-2
13.
J Nanobiotechnology ; 18(1): 68, 2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32375794

RESUMO

BACKGROUND: Enhancing angiogenesis is critical for accelerating wound healing. Application of different types of exosomes (Exos) to promote angiogenesis represents a novel strategy for enhanced wound repair. Saliva is known to accelerate wound healing, but the underlying mechanisms remain unclear. RESULTS: Our results have demonstrated that saliva-derived exosomes (saliva-Exos) induce human umbilical vein endothelial cells (HUVEC) proliferation, migration, and angiogenesis in vitro, and promote cutaneous wound healing in vivo. Further experiments documented that Ubiquitin-conjugating enzyme E2O (UBE2O) is one of the main mRNAs of saliva-Exos, and activation of UBE2O has effects similar to those of saliva-Exos, both in vitro and in vivo. Mechanistically, UBE2O decreases the level of SMAD family member 6 (SMAD6), thereby activating bone morphogenetic protein 2 (BMP2), which, in turn, induces angiogenesis. CONCLUSIONS: The present work suggests that administration of saliva-Exos and UBE2O represents a promising strategy for enhancing wound healing through promotion of angiogenesis.


Assuntos
Exossomos/enzimologia , Neovascularização Fisiológica/efeitos dos fármacos , Saliva/enzimologia , Proteína Smad6/metabolismo , Enzimas de Conjugação de Ubiquitina , Animais , Células Cultivadas , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Camundongos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Mensageiro/farmacologia , Saliva/citologia , Pele/lesões , Enzimas de Conjugação de Ubiquitina/genética , Enzimas de Conjugação de Ubiquitina/metabolismo , Enzimas de Conjugação de Ubiquitina/farmacologia , Cicatrização/efeitos dos fármacos
14.
J Nanobiotechnology ; 18(1): 66, 2020 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-32345321

RESUMO

BACKGROUND: Osteoblast differentiation is a vital process for fracture healing, and exosomes are nanosized membrane vesicles that can deliver therapeutic drugs easily and safely. Macrophages participate in the regulation of various biological processes in vivo, and macrophage-derived exosomes (MD-Exos) have recently been a topic of increasing research interest. However, few study has explored the link between MD-Exos and osteoblast differentiation. Herein, we sought to identify miRNAs differentially expressed between M1 and M2 macrophage-derived exosomes, and to evaluate their roles in the context of osteoblast differentiation. RESULTS: We found that microRNA-5106 (miR-5106) was significantly overexpressed in M2 macrophage-derived exosomes (M2D-Exos), while its expression was decreased in M1 macrophage-derived exosomes (M1D-Exos), and we found that this exosomal miRNA can induce bone mesenchymal stem cell (BMSC) osteogenic differentiation via directly targeting the Salt-inducible kinase 2 and 3 (SIK2 and SIK3) genes. In addition, the local injection of both a miR-5106 agonist or M2D-Exos to fracture sites was sufficient to accelerate healing in vivo. CONCLUSIONS: Our study demonstrates that miR-5106 is highly enriched in M2D-Exos, and that it can be transferred to BMSCs wherein it targets SIK2 and SIK3 genes to promote osteoblast differentiation.


Assuntos
Diferenciação Celular , Exossomos/metabolismo , MicroRNAs/metabolismo , Osteogênese , Proteínas Serina-Treonina Quinases/metabolismo , Regiões 3' não Traduzidas , Animais , Antagomirs/metabolismo , Técnicas de Cocultura , Exossomos/transplante , Fraturas do Fêmur/patologia , Fraturas do Fêmur/terapia , Macrófagos/citologia , Macrófagos/metabolismo , Masculino , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Osteoblastos/citologia , Osteoblastos/metabolismo , Osteocalcina/genética , Osteocalcina/metabolismo , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/química , Proteínas Serina-Treonina Quinases/genética , Interferência de RNA , RNA Interferente Pequeno/metabolismo
15.
Med Sci Monit ; 26: e927370, 2020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-33151913

RESUMO

BACKGROUND The surgical strategies for posterolateral tibial plateau fractures are still inconsistent. Although a number of operative approaches were previously reported for surgical treatment of fractures of the posterolateral column in the tibial plateau, some approaches fail to provide direct visualization of the articular surface and do not allow enough space to access the posterolateral area of the lateral tibial plateau, thereby leading to unsatisfactory reconstruction of the knee and poor articular activity. MATERIAL AND METHODS We retrospectively reviewed records of 21 patients who underwent fibular neck osteotomy approach for posterolateral fractures. Radiographs taken during follow-up were used to evaluate the quality of fracture reduction and lower-limb axis. The Tegner-Lysholm score was used to assess patient functional performance. Complications, including incision infection, osteotomy nonunion, peroneal nerve injury, and fragment displacement, were evaluated. RESULTS We included 12 males and 9 females, with an age range of 27-67 years (mean age, 42.43 years). No intraoperative complications or postoperative complications were found. The mean operative duration was 128.05 min (range: 86-167 min). No patients were lost to clinical or radiographic follow-up. All patients had complete follow-up (range: 13-28 months, mean: 19.57 months). Anatomical fracture reduction was achieved in 14 patients. Radiological limb alignment was restored in all patients. The mean Tegner-Lysholm score was 87.07 (range: 74-95) and the average knee society score (KSS) was 91.67 (range: 86-94) at the final follow-up. CONCLUSIONS In this retrospective study, the results suggest that the fibular neck osteotomy approach is a good choice for treatment of posterolateral tibial plateau fractures.


Assuntos
Fíbula/cirurgia , Osteotomia , Fraturas da Tíbia/cirurgia , Adulto , Idoso , Feminino , Fíbula/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fraturas da Tíbia/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Resultado do Tratamento
16.
Arch Orthop Trauma Surg ; 140(1): 11-17, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31127408

RESUMO

OBJECTIVE: To compare the clinical effect of 3D-printed template technology with X-ray fluoroscopy in assisting surgery for sacroiliac screws placement. DESIGN: Institutional review board-approved retrospective analysis. PATIENTS: The clinical data of 31 cases of sacroiliac complex injury between January 2015 and December 2016 were analyzed. There were 16 patients, males 11 and females 5, who underwent surgery assisted by 3D-printed template in template group, and that of contemporaneous 15 patients, males 11 and females 4, who underwent traditional surgery were gathered as fluoroscopy group. All those patients were followed up for more than 6 months. MAIN OUTCOME MEASURES: The operation time and X-ray fluoroscopy times for each screw placement, and the Matta and Majeed score were analyzed and the difference between the two group was tested. RESULTS: All cases were followed up for 6-20 months, average 11.4 ± 0.6 months. In template group, 19 screws were implanted. Each screw spent 25-38 min, average 27.2 ± 5.3 min, and need 2-5 times fluoroscopy, average 2.7 ± 0.5. The fracture reduction quality was evaluated by Matta score scale: excellent 10, well 4, fair 2, good rate 87.5%; and pelvic function were evaluated by Majeed score scale: excellent 11, well 3, fair 2, and good rate 87.5%. In fluoroscopy group, 17 screws were implanted. Each screw spent 45-70 min, average 60.3 ± 5.8 min, and needs 11-23 times fluoroscopy, average 15.4 ± 3.5. The fracture reduction quality was evaluated by Matta score scale: excellent 7, well 6, fair 2, and good rate 86.7%; and pelvic function was evaluated by Majeed score scale: excellent 6, well 6, fair 3, and good rate 80.0%. The difference in operation time, X-ray fluoroscopy times between template group and fluoroscopy group had statistical significance. But the Matta and Majeed score had no difference between two groups. CONCLUSION: Compared with traditional surgery, 3D-printed template technology-assisted surgery for sacroiliac screws placement in sacroiliac complex injury patients possesses advantage such as shortened operation time and reduced X-ray exposure times. This technology improves the safety profile of this operation and should be further studied in future clinical applications.


Assuntos
Parafusos Ósseos , Fluoroscopia/métodos , Ílio , Impressão Tridimensional , Sacro , Feminino , Fixação de Fratura/instrumentação , Fixação de Fratura/métodos , Fraturas Ósseas/diagnóstico por imagem , Fraturas Ósseas/cirurgia , Humanos , Ílio/diagnóstico por imagem , Ílio/lesões , Ílio/cirurgia , Masculino , Estudos Retrospectivos , Sacro/diagnóstico por imagem , Sacro/lesões , Sacro/cirurgia , Cirurgia Assistida por Computador/métodos
17.
Acta Orthop ; 91(6): 639-643, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32896189

RESUMO

Background and purpose - Following the outbreak of COVID-19 in December 2019, in China, many hip fracture patients were unable to gain timely admission and surgery. We assessed whether delayed surgery improves hip joint function and reduces major complications better than nonoperative therapy. Patients and methods - In this retrospective observational study, we collected data from 24 different hospitals from January 1, 2020, to July 20, 2020. 145 patients with hip fractures aged 65 years or older were eligible. Clinical data was extracted from electronic medical records. The primary outcomes were visual analogue scale (VAS) score and Harris Hip Score. Major complications, including deep venous thrombosis (DVT) and pneumonia within 1 month and 3 months, were collected for further analysis. Results - Of the 145 hip fracture patients 108 (median age 72; 70 females) received delayed surgery and 37 (median age 74; 20 females) received nonoperative therapy. The median time from hip fracture injury to surgery was 33 days (IQR 24-48) in the delayed surgery group. Hypertension, in about half of the patients in both groups, and cerebral infarction, in around a quarter of patients in both groups, were the most common comorbidities. Both VAS score and Harris Hip Score were superior in the delayed surgery group. At the 3-month follow-up, the median VAS score was 1 in the delayed surgery group and 2.5 in the nonoperative group (p < 0.001). Also, the percentage of complications was higher in the nonoperative group (p = 0.004 for DVT, p < 0.001 for pulmonary infection). Interpretation - In hip fracture patients, delayed surgery compared with nonoperative therapy significantly improved hip function and reduced various major complications.


Assuntos
Infarto Cerebral , Tratamento Conservador , Fixação de Fratura , Fraturas do Quadril , Hipertensão , Complicações Pós-Operatórias , Tempo para o Tratamento/estatística & dados numéricos , Idoso , COVID-19/epidemiologia , COVID-19/prevenção & controle , Infarto Cerebral/epidemiologia , Infarto Cerebral/etiologia , Infarto Cerebral/prevenção & controle , China/epidemiologia , Tratamento Conservador/efeitos adversos , Tratamento Conservador/métodos , Tratamento Conservador/estatística & dados numéricos , Registros Eletrônicos de Saúde/estatística & dados numéricos , Feminino , Fixação de Fratura/efeitos adversos , Fixação de Fratura/métodos , Fixação de Fratura/estatística & dados numéricos , Fraturas do Quadril/epidemiologia , Fraturas do Quadril/terapia , Humanos , Hipertensão/epidemiologia , Hipertensão/etiologia , Hipertensão/prevenção & controle , Masculino , Avaliação de Processos e Resultados em Cuidados de Saúde , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , SARS-CoV-2
18.
J Cell Biochem ; 120(5): 7741-7750, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30506715

RESUMO

The beneficial effects of icariin in the management of many diseases, such as chronic renal failure and heart failure, are well known. Icariin has also been shown to ameliorate osteoarthritis (OA) symptoms; however, the underlying mechanisms remain unclear. In this study, a bioinformatics analysis was performed to investigate the KEGG pathways of icariin-targeted genes involved in OA. Our study suggests that icariin plays a role in OA by regulating inflammatory cytokine production, insulin resistance, and cell survival through modulation of the NF-κB, MAPK, and Akt signaling pathways. Importantly, IKBKB, NFKBIA, MAPK8, MAPK9, and MAPK10 may be the hub genes affected by icariin when providing its beneficial effects on OA. In addition, we found that icariin decreases proinflammatory factors and inhibits chondrocyte apoptosis through suppression of the NF-κB pathway. Our study highlights a set of KEGG pathways that could explain the molecular mechanism of icariin's action on OA, suggesting that icariin could be considered as a promising therapeutic option for OA.

19.
Lab Invest ; 99(8): 1193-1202, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30837678

RESUMO

Hypoxia resulting in hypoxia-inducible factor-1 alpha (HIF-1α) induction is known to drive scar formation during cutaneous wound healing, and may be responsible for excessive fibrosis inherent to hypertrophic scars and keloids. Because epigenetic pathways play an important role in regulation of fibrosing processes, we evaluated patient scars for DNA hydroxymethylation (5-hydroxymethylcytosine; 5-hmC) status and documented a significant decrease in scar fibroblasts. To test this finding in vitro, human fibroblasts were cultured with cobalt chloride (CoCl2), a known stimulant of HIF-1α. HIF-1α induced so resulted in loss of 5-hmC similar to that seen in naturally occurring scars and was associated with significant downregulation of one of the 5-hmC converting enzymes-ten-eleven translocation 3 (TET3)-as well as increased expression of phosphorylated focal adhesion kinase (p-FAK), which is important in wound contracture. These changes were partially reversed by exposure to ascorbic acid, a recognized epigenetic regulator potentially capable of minimizing excessive scar formation and promoting a more regenerative healing response. Our results provide a novel and translationally relevant mechanism whereby epigenetic regulation of scar formation may be manipulated at the level of fibroblast DNA hydroxymethylation.


Assuntos
5-Metilcitosina/análogos & derivados , Ácido Ascórbico/farmacologia , Hipóxia Celular , Dioxigenases/metabolismo , Fibroblastos/metabolismo , 5-Metilcitosina/metabolismo , Células Cultivadas , Cicatriz/metabolismo , Metilação de DNA/efeitos dos fármacos , Epigênese Genética/efeitos dos fármacos , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Expressão Gênica/efeitos dos fármacos , Expressão Gênica/genética , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo
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