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1.
Eur J Trauma Emerg Surg ; 50(4): 1599-1609, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38483558

RESUMO

PURPOSE: Traumas cause great casualties, accompanied by heavy economic burdens every year. The study aimed to use ML (machine learning) survival algorithms for predicting the 8-and 24-hour survival of severe traumas. METHODS: A retrospective study using data from National Trauma Data Bank (NTDB) was conducted. Four ML survival algorithms including survival tree (ST), random forest for survival (RFS) and gradient boosting machine (GBM), together with a Cox proportional hazard model (Cox), were utilized to develop the survival prediction models. Following this, model performance was determined by the comparison of the C-index, integrated Brier score (IBS) and calibration curves in the test datasets. RESULTS: A total of 191,240 individuals diagnosed with severe trauma between 2015 and 2018 were identified. Glasgow Coma Scale (GCS), trauma type, age, SaO2, respiratory rate (RR), systolic blood pressure (SBP), EMS transport time, EMS on-scene time, pulse, and EMS response time were identified as the main predictors. For predicting the 8-hour survival with the complete cases, the C-indexes in the test sets were 0.853 (0.845, 0.861), 0.823 (0.812, 0.834), 0.871 (0.862, 0.879) and 0.857 (0.849, 0.865) for Cox, ST, RFS and GBM, respectively. Similar results were observed in the 24-hour survival prediction models. The prediction error curves based on IBS also showed a similar pattern for these models. Additionally, a free web-based calculator was developed for potential clinical use. CONCLUSION: The RFS survival algorithms provide non-parametric alternatives to other regression models to be of clinical use for estimating the survival probability of severe trauma patients.


Assuntos
Bases de Dados Factuais , Serviços Médicos de Emergência , Ferimentos e Lesões , Humanos , Masculino , Feminino , Estudos Retrospectivos , Ferimentos e Lesões/mortalidade , Ferimentos e Lesões/terapia , Adulto , Pessoa de Meia-Idade , Aprendizado de Máquina , Escala de Coma de Glasgow , Escala de Gravidade do Ferimento , Algoritmos , Idoso , Adolescente
2.
J Nanobiotechnology ; 22(1): 112, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38491475

RESUMO

The challenges posed by delayed atrophic healing and nonunion stand as formidable obstacles in osteoporotic fracture treatment. The processes of type H angiogenesis and osteogenesis emerge as pivotal mechanisms during bone regeneration. Notably, the preconditioning of adipose-derived stem cell (ADSC) exosomes under hypoxic conditions has garnered attention for its potential to augment the secretion and functionality of these exosomes. In the present investigation, we embarked upon a comprehensive elucidation of the underlying mechanisms of hypo-ADSC-Exos within the milieu of osteoporotic bone regeneration. Our findings revealed that hypo-ADSC-Exos harboured a preeminent miRNA, namely, miR-21-5p, which emerged as the principal orchestrator of angiogenic effects. Through in vitro experiments, we demonstrated the capacity of hypo-ADSC-Exos to stimulate the proliferation, migration, and angiogenic potential of human umbilical vein endothelial cells (HUVECs) via the mediation of miR-21-5p. The inhibition of miR-21-5p effectively attenuated the proangiogenic effects mediated by hypo-ADSC-Exos. Mechanistically, our investigation revealed that exosomal miR-21-5p emanating from hypo-ADSCs exerts its regulatory influence by targeting sprouly1 (SPRY1) within HUVECs, thereby facilitating the activation of the PI3K/AKT signalling pathway. Notably, knockdown of SPRY1 in HUVECs was found to potentiate PI3K/AKT activation and, concomitantly, HUVEC proliferation, migration, and angiogenesis. The culminating stage of our study involved a compelling in vivo demonstration wherein GelMA loaded with hypo-ADSC-Exos was validated to substantially enhance local type H angiogenesis and concomitant bone regeneration. This enhancement was unequivocally attributed to the exosomal modulation of SPRY1. In summary, our investigation offers a pioneering perspective on the potential utility of hypo-ADSC-Exos as readily available for osteoporotic fracture treatment.


Assuntos
Exossomos , Gelatina , Células-Tronco Mesenquimais , Metacrilatos , MicroRNAs , Fraturas por Osteoporose , Humanos , Fraturas por Osteoporose/metabolismo , Exossomos/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Angiogênese , Proteínas Proto-Oncogênicas c-akt/metabolismo , Neovascularização Fisiológica , MicroRNAs/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Hipóxia/metabolismo
3.
Open Med (Wars) ; 19(1): 20240898, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38463518

RESUMO

Photothermal therapy (PTT) of nanomaterials is an emerging novel therapeutic strategy for breast cancer. However, there exists an urgent need for appropriate strategies to enhance the antitumor efficacy of PTT and minimize damage to surrounding normal tissues. Piezo1 might be a promising novel photothermal therapeutic target for breast cancer. This study aims to explore the potential role of Piezo1 activation in the hyperthermia therapy of breast cancer cells and investigate the underlying mechanisms. Results showed that the specific agonist of Piezo1 ion channel (Yoda1) aggravated the cell death of breast cancer cells triggered by heat stress in vitro. Reactive oxygen species (ROS) production was significantly increased following heat stress, and Yoda1 exacerbated the rise in ROS release. GSK2795039, an inhibitor of NADPH oxidase 2 (NOX2), reversed the Yoda1-mediated aggravation of cellular injury and ROS generation after heat stress. The in vivo experiments demonstrate the well photothermal conversion efficiency of TiCN under the 1,064 nm laser irradiation, and Yoda1 increases the sensitivity of breast tumors to PTT in the presence of TiCN. Our study reveals that Piezo1 activation might serve as a photothermal sensitizer for PTT, which may develop as a promising therapeutic strategy for breast cancer.

5.
J Mater Chem B ; 11(29): 6922-6933, 2023 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-37381759

RESUMO

Absorbable polymers have attracted increasing attention in the field of bone regeneration in recent years for their degradation. Compared with other degradable polymers, polypropylene carbonate (PPC) has several advantages such as biodegradation and relatively cheap raw materials. Most importantly, PPC can degrade into water and carbon dioxide totally which does not give rise to local inflammation and bone resorption in vivo. However, pure PPC has not presented excellent osteoinductivity properties. In order to enhance the osteoinductivity of PPC, silicon nitride (SiN) was employed due to its excellent mechanical properties, biocompatibility and osteogenesis compared with the other common materials such as hydroxyapatite and calcium phosphate ceramics. In this study, composites of PPC mixed with different contents of SiN were prepared successfully (PSN10 with 10 wt% SiN content, and PSN20 with 20 wt% SiN content). The characterization of the composites suggested that PPC mixed with SiN evenly and PSN composites presented stable properties. The results in vitro revealed that the PSN20 composite possessed satisfactory biocompatibility and exerted better osteogenic differentiation effects on adipose-derived stem cells (ADSCs). In particular, the PSN20 composite accelerated the healing of bone defects better and degraded with the process of bone healing in vivo. Overall, the PSN20 composite exhibited better biocompatibility, induced osteogenic differentiation of ADSCs and promoted healing of bone defects, due to which the PSN composite is considered as a potential candidate for treating bone defects in the field of bone tissue engineering.


Assuntos
Osteogênese , Polímeros , Polímeros/farmacologia , Células-Tronco
6.
Am J Transl Res ; 14(7): 4698-4708, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35958510

RESUMO

BACKGROUND: Hip tumors often require tumor-type artificial joint replacement. The selection of the prosthesis stem (hip tumor prosthesis stem) implantation angle during the operation is important to prevent the complication of postoperative prosthesis dislocation. The aim of this study was to evaluate the role of a nickel-titanium (Ni-Ti) shape memory alloy embracing fixator in determination of the implantation angle of a hip tumor prosthesis stem and analyze its efficacy. METHODS: 36 patients with proximal femur tumor were treated with extended tumor resection and prosthetic replacement. 14 patients received prosthetic replacements with the embracing fixators fixing between the junction of the prosthesis stem and the femur temporarily, while the other 22 patients received the same replacements but without the fixators. The two groups were compared regarding occurrence of complications, limb function, and active hip range of motion (ROM). RESULTS: There was no case of hip dislocation in the group that received prosthetic replacements with the use of embracing fixators. Occurrence of deep infection had no difference between the two groups. However, better limb function and higher active (ROM) on abduction or flexion were observed in the group using embracing fixators. CONCLUSION: Ni-Ti shape memory alloy embracing fixator plays a key role in assisting the accurate implantation angle of the prosthesis stem in prosthetic replacement. The prosthesis stem can be adjusted to the optimal angle with the help of the embracing fixator. Patients have a lower risk of dislocation, better limb function, and higher active hip ROM.

7.
Ther Hypothermia Temp Manag ; 12(4): 223-228, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35605088

RESUMO

Lung injury occurring in the early stage of heat stroke (HS) leads to hypoxia and further aggravation of other organic damage. Lactoferrin (LF) is an iron binding protein with anti-inflammatory and antioxidant effects. This study focuses on the protection of preadministration of bovine lactoferrin (BLF) against lung injury in rats with HS. Sixty-four Sprague-Dawley male rats were divided into four groups randomly: control (CON)+phosphate-buffered saline (PBS) (n = 16), HS+PBS (n = 16), HS+low-dose BLF (LBLF) (n = 16), and HS+high-dose BLF (HBLF) (n = 16). CON+PBS and HS+PBS were preadministered 10 mL/kg PBS for 1 week. HS+LBLF and HS+HBLF were preadministered 100 and 200 mg/kg BLF for 1 week, respectively. The HS onset time and the survival rate were recorded, and bronchoalveolar lavage fluid was obtained to measure protein concentration. Lung was obtained for pathological analysis and wet/dry weight ratio measurement; later, the content of malondialdehyde (MDA), activity of myeloperoxidase (MPO), and superoxide dismutase (SOD) were measured in lung tissue homogenate. The results indicated that BLF preadministration could delay the HS onset time, enhance the survival rate, the levels of serum inflammatory cytokine and MDA content in HS+LBLF and HS+HBLF showed significant reduction compared with HS+PBS, while a significant elevation of SOD activity and reduction of MPO activity in HS+HBLF. Our results demonstrate that BLF preadministration could relieve lung injury in HS rats by enhancing thermal endurance, and alleviating serum inflammatory response and pulmonary oxidative stress damage.


Assuntos
Golpe de Calor , Hipotermia Induzida , Lesão Pulmonar , Animais , Masculino , Ratos , Golpe de Calor/complicações , Golpe de Calor/tratamento farmacológico , Golpe de Calor/metabolismo , Lactoferrina/farmacologia , Lactoferrina/uso terapêutico , Lactoferrina/química , Peroxidação de Lipídeos , Pulmão , Lesão Pulmonar/metabolismo , Ratos Sprague-Dawley , Superóxido Dismutase/metabolismo , Superóxido Dismutase/farmacologia
8.
Zhongguo Yi Liao Qi Xie Za Zhi ; 46(1): 38-41, 2022 Jan 30.
Artigo em Chinês | MEDLINE | ID: mdl-35150105

RESUMO

Cannulated Screw is a common internal fixation for the treatment of femoral neck fractures. However, the traditional implantation method has disadvantages such as inaccuracy and large radiation exposure. Based on the anatomical characteristics of the femoral neck and geometric principles, we develop a novel guide device for cannulated screws insertion. The cadaver experiment showed that it can improve the accuracy of cannulated screws implantation, reduce puncture attempts and the radiation exposure of doctors and patients.


Assuntos
Fraturas do Colo Femoral , Procedimentos Cirúrgicos Robóticos , Parafusos Ósseos , Fraturas do Colo Femoral/cirurgia , Fixação Interna de Fraturas , Humanos
10.
ACS Appl Mater Interfaces ; 13(16): 18472-18487, 2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-33856781

RESUMO

Repair of large bone defects represents a major challenge for orthopedic surgeons. The newly formed microvessels inside grafts play a crucial role in successful bone tissue engineering. Previously, an active role for mesenchymal stem cell (MSC)-derived exosomes in blood vessel development and progression was suggested in the repair of multiple tissues. However, the reports on the application of MSC-derived exosomes in the repair of large bone defects are sparse. In this study, we encapsulated umbilical MSC-derived exosomes (uMSCEXOs) in hyaluronic acid hydrogel (HA-Gel) and combined them with customized nanohydroxyapatite/poly-ε-caprolactone (nHP) scaffolds to repair cranial defects in rats. Imaging and histological evaluation indicated that the uMSCEXOs/Gel/nHP composites markedly enhanced bone regeneration in vivo, and the uMSCEXOs might play a key role in this process. Moreover, the in vitro results demonstrated that uMSCEXOs promoted the proliferation, migration, and angiogenic differentiation of endothelial progenitor cells (EPCs) but did not significantly affect the osteogenic differentiation of BMSCs. Importantly, mechanistic studies revealed that exosomal miR-21 was the potential intercellular messenger that promoted angiogenesis by upregulating the NOTCH1/DLL4 pathway. In conclusion, our findings exhibit a promising exosome-based strategy in repairing large bone defects through enhanced angiogenesis, which potentially regulated by the miR-21/NOTCH1/DLL4 signaling axis.


Assuntos
Exossomos/química , Hidrogéis/farmacologia , Células-Tronco Mesenquimais/citologia , Neovascularização Fisiológica/efeitos dos fármacos , Crânio/efeitos dos fármacos , Crânio/fisiologia , Cordão Umbilical/citologia , Animais , Regeneração Óssea/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Ácido Hialurônico/química , Ácido Hialurônico/farmacologia , Hidrogéis/química , Masculino , Osteogênese/efeitos dos fármacos , Ratos , Transdução de Sinais/efeitos dos fármacos
11.
Int J Med Robot ; 17(4): e2270, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33908164

RESUMO

BACKGROUND: Poor reduction can lead to complications such as deformity and delayed fracture healing. We introduce a 3D printed external fixator technology that can assist in fracture reduction and fixation. METHODS: A fractured long bone was first fixed by a temporary external fixator and then scanned with computed tomography. Three-dimensional reconstruction of the contour and bone fragments of the affected limb was performed using Mimics software, and the fracture reduction was simulated. Subsequently, data were imported into SolidWorks software for customized external fixator design and 3D printing. Through the precise assembly of the 3D printed external fixator and external fixation pins, automatic fracture reduction. RESULTS: The patient's fractures were well reduced, firmly fixed, and the postoperative fractures healed well with no complications. CONCLUSION: The technique we introduce not only assists in fracture reduction for temporary external fixation but can also be used as a definitive treatment for long bone fractures.


Assuntos
Fixação de Fratura , Fraturas Ósseas , Fixadores Externos , Fixação Interna de Fraturas , Fraturas Ósseas/cirurgia , Humanos , Impressão Tridimensional , Tomografia Computadorizada por Raios X , Resultado do Tratamento
12.
J Bone Miner Res ; 36(1): 186-198, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32866293

RESUMO

Smokers are at a higher risk of delayed union or nonunion after fracture repair. Few specific interventions are available for prevention because the molecular mechanisms that result in these negative sequelae are poorly understood. Murine models that mimic fracture healing in smokers are crucial in further understanding the local cellular and molecular alterations during fracture healing caused by smoking. We exposed three murine strains, C57BL/6J, 129X1/SvJ, and BALB/cJ, to cigarette smoke for 3 months before the induction of a midshaft transverse femoral osteotomy. We evaluated fracture healing 4 weeks after the osteotomy using radiography, micro-computed tomography (µCT), and biomechanical testing. Radiographic analysis demonstrated a significant decrease in the fracture healing capacity of smoking 129X1/SvJ mice. µCT results showed delayed remodeling of fracture calluses in all three strains after cigarette smoke exposure. Biomechanical testing indicated the most significant impairment in the functional properties of 129X1/SvJ in comparison with C57BL/6J and BALB/cJ mice after cigarette smoke exposure. Thus, the 129X1/SvJ strain is most suitable in simulating smoking-induced impaired fracture healing. Furthermore, in smoking 129X1/SvJ murine models, we investigated the molecular and cellular alterations in fracture healing caused by cigarette smoking using histology, flow cytometry, and multiplex cytokine/chemokine analysis. Histological analysis showed impaired chondrogenesis in cigarette smoking. In addition, the important reparative cell populations, including skeletal stem cells and their downstream progenitors, demonstrated decreased expansion after injury as a result of cigarette smoking. Moreover, significantly increased pro-inflammatory mediators and the recruitment of immune cells in fracture hematomas were demonstrated in smoking mice. Collectively, our findings demonstrate the significant cellular and molecular alterations during fracture healing impaired by smoking, including disrupted chondrogenesis, aberrant skeletal stem and progenitor cell activity, and a pronounced initial inflammatory response. © 2020 American Society for Bone and Mineral Research (ASBMR).


Assuntos
Consolidação da Fratura , Fumar , Animais , Inflamação , Camundongos , Camundongos Endogâmicos C57BL , Fumar/efeitos adversos , Células-Tronco , Microtomografia por Raio-X
13.
J Knee Surg ; 34(9): 987-996, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31896140

RESUMO

This study aims to compare the clinical outcomes of the nickel-titanium arched shape-memory alloy connector (hereafter referred to as the ASC) and tension band fixation for the treatment of transverse patellar fractures. We retrospectively analyzed a total of 257 patients with transverse patellar fractures who were treated at our emergency orthopaedics department from March 2010 to March 2017. Either an ASC or the Kirschner wire (K-wire) tension band had been used to treat these fractures according to surgeons' experience and preference. We compared operative details, postoperative recovery, and postoperative knee function at 6 months. In terms of surgical duration, blood loss, incision length, length of hospital stay, and postoperative complications, patients in the ASC group showed significantly better results than patients in the K-wire group (p < 0.05). There were no significant differences between the two groups in terms of fracture healing time, knee mobility, and the Boström score at the postoperative 6-month evaluation (p > 0.05). Though, there were similar functional outcomes between two groups whose transverse patellar fractures were different methods, we found that the ASC method was a more reliable, more minimally invasive, and safer treatment option than the tension band wiring method using K-wires, resulting in less tissue damage, shorter surgical duration, shorter length of hospital stay, and fewer complications.


Assuntos
Fraturas Ósseas , Ligas de Memória da Forma , Fios Ortopédicos , Fixação Interna de Fraturas , Humanos , Níquel , Patela/cirurgia , Estudos Retrospectivos , Titânio
14.
Neurochem Res ; 46(2): 349-357, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33211272

RESUMO

Currently, there is no cure for spinal cord injury (SCI), a heavy burden on patients physiology and psychology. We found that microRNA-139-5p (miR-139-5p) expression was significantly downregulated in damaged spinal cords in mice. So, we aimed to test the effect of treatment with miR-139-5p on functional recovery and neuropathic pain in mice with SCI and investigate the underlying mechanism. The luciferase reporter assay revealed that miR-139-5p directly targeted mammalian sterile 20-like kinase 1 (Mst1), and miR-139-5p treatment suppressed Mst1 protein expression in damaged spinal cords of mice. Wild-type mice and Mst1(-/-) mice were exposed to SCI and treated with miR-139-5p agomir via intrathecal infusion. Treatment of SCI mice with miR-139-5p accelerated locomotor functional recovery, reduced hypersensitivities to mechanical and thermal stimulations, and promoted neuronal survival in damaged spinal cords. Treatment with miR-139-5p enhanced phosphorylation of adenosine monophosphate-activated protein kinase alpha (AMPKα), improved mitochondrial function, and suppressed NF-κB-related inflammation in damaged spinal cords. Deficiency of Mst1 had similar benefits in mice with SCI. Furthermore, miR-139-5p treatment did not provide further protection in Mst1(-/-) mice against SCI. In conclusion, miR-139-5p treatment enhanced functional recovery and reduced pain hypersensitivity in mice with SCI, possibly through targeting Mst1.


Assuntos
MicroRNAs/uso terapêutico , Neuralgia/tratamento farmacológico , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Recuperação de Função Fisiológica/efeitos dos fármacos , Traumatismos da Medula Espinal/tratamento farmacológico , Animais , Regulação para Baixo , Técnicas de Inativação de Genes , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Locomoção/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , MicroRNAs/metabolismo , Mitocôndrias/efeitos dos fármacos , Neurônios Motores/efeitos dos fármacos , Neuralgia/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Medula Espinal/efeitos dos fármacos , Medula Espinal/metabolismo , Traumatismos da Medula Espinal/metabolismo
15.
J Orthop Surg Res ; 15(1): 453, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33008473

RESUMO

PURPOSE: Olecranon fracture is a common upper limb fracture, and several surgical approaches have been advocated for its fixation. To overcome the complications associated with common techniques, we present a novel shape-memory alloy concentrator, an alternative for tension band compression, to fix olecranon fracture. METHODS: Fifty-seven patients (26 men and 31 women) with olecranon fracture, with a mean age of 45 years, were included in this study. Each patient had undergone open reduction and internal fixation using the Nitinol (Ni-Ti) arched shape-memory connector (ASC). The clinical assessments were performed using the Disability of the Arm, Shoulder, and Hand (DASH) questionnaire and the Mayo Elbow Performance (MEP) score, which were both recorded at the final follow-up visit. RESULTS: The patients were followed up for 44 months on average (range, 31 to 56 months). No patients were lost to follow-up, and all of the olecranon fractures healed in an average of 15 weeks (range, 10 to 34 weeks). The mean DASH score was 8.6 (range, 0 to 32.4), and the mean MEP score was 92.5 (range, 74 to 100). Nine patients showed postoperative complications: prominent hardware (2), infection (1), loss of the range of functional motion (5), and heterotopic ossification (1). CONCLUSION: The ASC may serve as a favorable device for multi-fragmented and comminuted fractures with rare hardware irritation and may also provide continuous concentrative compression to accelerate osseous healing, thereby aiding the restoration and permitting an early rehabilitation with a low incidence of postoperative complications.


Assuntos
Fixação Interna de Fraturas/métodos , Fraturas Cominutivas/cirurgia , Olécrano/lesões , Olécrano/cirurgia , Ligas de Memória da Forma , Fraturas da Ulna/cirurgia , Adulto , Feminino , Seguimentos , Fixação Interna de Fraturas/reabilitação , Fraturas Cominutivas/reabilitação , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Resultado do Tratamento , Fraturas da Ulna/reabilitação , Adulto Jovem
16.
Theranostics ; 10(8): 3430-3450, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32206100

RESUMO

Reactive oxygen species (ROS) play a crucial role in cancer formation and development, especially cancer metastasis. However, lack of a precise tool, which could accurately distinguish specific types of ROS, restricts an in-depth study of ROS in cancer development and progression. Herein, we designed smart and versatile fluorescent Ag nanoclusters (AgNCs) for sensitive and selective detection of different species of ROS in cells and tissues. Methods: Firstly, dual-emission fluorescent AgNCs was synthesized by using bovine serum albumin (BSA) to sense different types of ROS (H2O2, O2•-, •OH). The responsiveness of the AgNCs to different species of ROS was explored by fluorescence spectrum, hydrodynamic diameter, and so on. Furthermore, dual-emission fluorescent AgNCs was used to sense ROS in tumor with different degrees of differentiation. Finally, the relationship between specific types of ROS and tumor cell invasion was explored by cell migration ability and the expression of cell adhesion and EMT markers. Results: This dual-emission fluorescent AgNCs possessed an excellent ability to sensitively and selectively distinguish highly reactive oxygen species (hROS, including O2•-and •OH) from moderate reactive oxygen species (the form of H2O2), and exhibited no fluoresence and green fluorescence, respectively. The emission of AgNCs is effective in detecting cellular and tissular ROS. When cultured with AgNCs, malignant tumor cells exhibit non-fluorescence, while the benign tumor emits green and reduced red light and the normal cells appear in weak green and bright red fluorescence. We further verified that not just H2O2 but specific species of ROS (O2•-and •OH) were involved in cell invasion and malignant transformation. Our study warrants further research on the role of ROS in physiological and pathophysiological processes. Conclusion: Taken together, AgNCs would be a promising approach for sensing ROS, and offer an intelligent tool to detect different kinds of ROS in tumors.


Assuntos
Técnicas Biossensoriais , Corantes Fluorescentes , Nanopartículas Metálicas , Neoplasias/diagnóstico , Neoplasias/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Prata , Animais , Linhagem Celular Tumoral , Humanos , Camundongos , Neoplasias/patologia , Fenótipo , Sensibilidade e Especificidade , Soroalbumina Bovina , Espectrometria de Fluorescência
17.
Mol Immunol ; 117: 168-179, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31812793

RESUMO

OBJECTIVE: This investigation was intended to elucidate lncRNA-miRNA networks that could explain inflammation underlying sepsis progression. METHODS: In the first place, four kinds of mice models were established, namely, SHAM group (n = 30), trauma (TH) group (n = 30), lipopolysaccharide (LPS) group (n = 30) and TH + LPS group (n = 30). Their lung, spleen and liver tissues were gathered for determination of TNF-α, IL-6, IL-10 and MCP-1 levels. Furthermore, mouse mononuclear macrophage leukemia cell line (RAW264.7) was stimulated by LPS to establish inflammation cell models. Then si-NEAT1s, pcDNA3.1-NEAT1, miR-495-3p mimic, miR-495-3p inhibitor, miR-NC, miR-211 mimic and miR-211 inhibitor were, respectively, transfected into the cells, so as to observe the impacts of NEAT1, miR-495-3p and miR-211 on cytokine levels released by the cells. RESULTS: The survival condition of mice in the TH + LPS group was undesirable, in relative to mice in the LPS group and SHAM group (both P < 0.05). High-level NEAT1 and low-level miR-495-3p/miR-211 were associated with poor survival of mice in the TH+LPS group (P < 0.05). Additionally, the correlation between NEAT1/miR-495-3p/miR-211 level and cytokine level was the strongest among TH+LPS-treated mice, in comparison to mice treated by TH or LPS. Furthermore, up-regulation of NEAT1 level and down-regulation of miR-495-3p/miR-211 level could aggravate inflammation in LPS-treated RAW264.7 cells. The miR-495-3p and miR-211 herein, were both subjected to sponging of NEAT1, possibly affected inflammation responses in RAW264.7 cells, respectively, through modulating STAT3 and PI3K/AKT signaling. CONCLUSION: LncRNA NEAT1 exhibited great potential sepsis diagnosis and treatment, considering its modifying miR-495-3p/STAT3 axis and miR-211/PI3K/AKT axis in inflammation cell models.


Assuntos
Inflamação/imunologia , RNA Longo não Codificante/imunologia , Sepse/imunologia , Transdução de Sinais/imunologia , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/imunologia , Fosfatidilinositol 3-Quinases/imunologia , Proteínas Proto-Oncogênicas c-akt/imunologia , Fator de Transcrição STAT3/imunologia
18.
Artif Cells Nanomed Biotechnol ; 47(1): 3720-3728, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31523993

RESUMO

Matrine derivative MASM (M19) is a quinolizine alkaloid with diverse pharmacological effects including preventing postmenopausal osteoporosis. In the current study, we observed that pretreatment with M19 inhibited cell apoptosis of murine osteoblastic MC3T3-E1 and primary osteoblasts induced by 1 µM dexamethasone in a dose-dependent manner. Our study also showed that pretreatment with M19 significantly prevented the upregulation of p53 that is caused by dexamethasone but had no effect on the p53 mRNA expression levels. Further immunoprecipitation (IP) experiments showed that M19 treatment increases the ubiquitination of p53 in dexamethasone-treated MC3T3-E1 cells. The expression of USP14, a deubiquitinating enzyme, increased with dexamethasone and decreased with M19 pretreatment. Co-IP experiments demonstrated the interaction between USP14 and p53, and the induced effect of a USP14 inhibitor (IU1) on p53 ubiquitination, which indicated that USP14 is a potential deubiquitinase for p53. Furthermore, pretreatment with IU1 or a p53 inhibitor (PFT-α) partially blocked dexamethasone-induced apoptosis of MC3T3-E1 cells. The overexpression of USP14 or p53 reversed the antiapoptotic effect of M19 in dexamethasone-treated MC3T3-E1 cells. In addition, PFT-α treatment remarkably blocked the effects of USP14 overexpression. In summary, our findings suggest that M19 exerts protective effects on dexamethasone-treated MC3T3-E1 cells by regulating USP14/p53.


Assuntos
Alcaloides/farmacologia , Apoptose/efeitos dos fármacos , Dexametasona/efeitos adversos , Osteoblastos/citologia , Osteoblastos/efeitos dos fármacos , Quinolizinas/farmacologia , Proteína Supressora de Tumor p53/metabolismo , Ubiquitina Tiolesterase/metabolismo , Células 3T3 , Animais , Citoproteção/efeitos dos fármacos , Camundongos , Osteoblastos/metabolismo , Ubiquitinação/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos , Matrinas
19.
Eur J Med Res ; 24(1): 27, 2019 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-31351486

RESUMO

PURPOSE: To summarize the techniques and clinical effectiveness in treating scaphoid nonunion with nickel-titanium (Ni-Ti) arched shape-memory alloy connector in combination with autologous iliac bone grafts. METHODS: This study retrospectively analyzed 18 scaphoid nonunion cases treated with arched connectors with autologous iliac bone grafts. Based on scaphoid nonunion, 2 cases were classified as type II (fibrous union), 4 cases as type III (mild sclerotic union), 6 cases as type IV (moderate resorption and sclerosis), 5 cases as type V (severe bone resorption and sclerosis), and 1 case as type VI (pseudarthrosis formation). At the first 4, 8 and 12 weeks after the surgery, wrist anteroposterior, lateral X-ray were obtained, respectively, to evaluate bone healing. Patients who had not yet reached the standard of healing at 12 weeks after surgery would continue to receive additional appointments for follow-up visits, such as 14 weeks, 16 weeks, 18 weeks after surgery, until their imaging studies had achieved satisfactory bone healing. Clinical effectiveness was evaluated comprehensively, based on bone union time, Mayo wrist score, and visual analog pain score. RESULTS: All 18 patients achieved satisfactory reduction and fixation with a mean union time of 4.2 months. Preoperative Mayo wrist score averaged 57.4 and average final postoperative follow-up was 91.4. On the other hand, mean preoperative VAS score was 6.8, and final postoperative follow-up average was 1.6. Mayo wrist score of the overall treatment effectiveness was excellent (90-100) in 12 cases, good (80-90) in 5 cases, and acceptable (60-80) in 1 case with zero poor (below 60) cases observed. Statistical analysis suggested that a statistically significant improvement in fracture healing, wrist function recovery and visual analog pain after surgery when compared to the scores of the patients before surgery. CONCLUSION: Using Ni-Ti arched shape-memory alloy connector in combination with autologous bone grafting provided a new modality to treat scaphoid nonunions in a less traumatic, convenient to operate and satisfactory manner in treatment outcomes, and thus is worthy of further application.


Assuntos
Transplante Ósseo , Fraturas não Consolidadas/cirurgia , Níquel/farmacologia , Osso Escafoide/cirurgia , Ligas de Memória da Forma/farmacologia , Titânio/farmacologia , Adulto , Fraturas não Consolidadas/fisiopatologia , Humanos , Masculino , Recuperação de Função Fisiológica/efeitos dos fármacos , Osso Escafoide/diagnóstico por imagem , Osso Escafoide/fisiopatologia , Resultado do Tratamento , Punho/fisiopatologia
20.
BMC Musculoskelet Disord ; 20(1): 311, 2019 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-31266474

RESUMO

BACKGROUND: The treatment of open tibial shaft fractures is challenging. External fixation (EF) is comparatively safe in treating these open injuries, meanwhile it has the advantages of easy application, minimal additional disruption, and convenient subsequent soft tissue repair. Nevertheless, its application is accompanied by a series of problems in alignment and bone healing. Therefore, limited internal fixation (LIF), such as cortical screws, has been used based on the external fixator for better therapeutic effect. The aim of this study is to compare the outcomes of EF combined with LIF and simple EF in the management of open tibial shaft fractures, evaluating the efficacy and safety of using the combined technique in treating such fractures. METHODS: From January 2012 to December 2016, patients with open tibial shaft fractures treated with EF with or without LIF augmentation were identified. A total of 152 patients were included in the analysis, and there were 85 patients in the simple external fixation group and 67 patients in the EF-LIF group. General assessment indicators included the direct cost of hospitalization and the times of first surgery, full weight bearing, and complete union. Infections and complications in union or limb alignment were compared as primary outcomes. Additionally, the number of patients who changed the fixation system for various reasons were analysed. RESULTS: Effective follow-up of all participants for statistical analysis was obtained. The follow-up time averaged 17.15 months (range: 12.00 to 24.00 months) in the EF group and 16.20 months (range: 12.00 to 19.00 months) in the EF-LIF group. Combined fixation provided shortened time to bear full weight and achieve complete bone union, while requiring additional first surgery time. No significant difference was found in infection rates or direct cost of hospitalization. Delayed union and non-union in the EF-LIF group were significantly decreased (20.9% versus 40.0, 1.5% versus 14.1%, p < 0.05). In limb alignment, patients with combined fixation exhibited reduced malreduction, loss of reduction, and malunion. In terms of secondary fixation, the EF-LIF group showed a markedly lower incidence (5.8% versus 34.1%, p < 0.001). CONCLUSION: Compared with simple EF, combined fixation is an effective and safe alternative for management of open tibial diaphyseal fractures. It provides superior initial reduction, better stability and decreases the risk of inferior alignment and delayed union without increasing the risk of infection.


Assuntos
Fixadores Externos , Fixação Interna de Fraturas/métodos , Consolidação da Fratura , Fraturas Expostas/cirurgia , Fraturas da Tíbia/cirurgia , Adulto , Idoso , Placas Ósseas , Parafusos Ósseos , Feminino , Seguimentos , Fixação Interna de Fraturas/efeitos adversos , Fixação Interna de Fraturas/instrumentação , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
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