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1.
Mater Sci Eng C Mater Biol Appl ; 128: 112306, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34474857

RESUMO

Osteomyelitis is caused by Staphylococcus aureus (S. aureus), with associated progressive bone loss. This study developed for the first time a calcium phosphate cement (CPC) for delivery of doxycycline (DOX) and human platelet lysate (hPL) to fight against S. aureus infection and enhance the osteogenesis of human periodontal ligament stem cells (hPDLSCs). Chitosan-containing CPC scaffolds were fabricated in the absence (CPCC) or presence of DOX (CPCC+DOX). In addition, hPL was encapsulated in alginate microbeads and incorporated into CPCC+DOX (CPCC+DOX+ hPL). Flexural strength of CPCC+DOX + hPL was (5.56 ± 0.55) MPa, lower than (8.26 ± 1.6) MPa of CPCC+DOX (p < 0.05), but exceeding the reported strength of cancellous bone. CPCC+DOX and CPCC+DOX + hPL exhibited strong antibacterial activity against S. aureus, reducing biofilm CFU by 4 orders of magnitude. The hPDLSCs encapsulated in microbeads were co-cultured with the CPCs. The hPDLSCs were able to be released from the microbeads and showed a high proliferation rate, increasing by about 8 folds at 14 days for all groups. The hPL was released from the scaffold and promoted the osteogenic differentiation of hPDLSCs. ALP activity was 28.07 ± 5.15 mU/mg for CPCC+DOX + hPL, higher than 17.36 ± 2.37 mU/mg and 1.34 ± 0.37 mU/mg of CPCC+DOX and CPCC, respectively (p < 0.05). At 7 days, osteogenic genes (ALP, RUNX2, COL-1, and OPN) in CPCC+DOX + hPL were 3-10 folds those of control. The amount of hPDLSC-synthesized bone mineral with CPCC+DOX + hPL was 3.8 folds that of CPCC (p < 0.05). In summary, the novel CPC + DOX + hPL-hPDLSCs scaffold exhibited strong antibacterial activity, excellent cytocompatibility and hPDLSC osteogenic differentiation, showing a promising approach for treatment and prevention of bone infection and enhancement of bone regeneration.


Assuntos
Osteogênese , Ligamento Periodontal , Biofilmes , Fosfatos de Cálcio/farmacologia , Diferenciação Celular , Células Cultivadas , Humanos , Staphylococcus aureus , Células-Tronco
2.
EMBO Mol Med ; 13(10): e11668, 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34542937

RESUMO

Loss of ß-cell number and function is a hallmark of diabetes. ß-cell preservation is emerging as a promising strategy to treat and reverse diabetes. Here, we first found that Pdia4 was primarily expressed in ß-cells. This expression was up-regulated in ß-cells and blood of mice in response to excess nutrients. Ablation of Pdia4 alleviated diabetes as shown by reduced islet destruction, blood glucose and HbA1c, reactive oxygen species (ROS), and increased insulin secretion in diabetic mice. Strikingly, this ablation alone or in combination with food reduction could fully reverse diabetes. Conversely, overexpression of Pdia4 had the opposite pathophysiological outcomes in the mice. In addition, Pdia4 positively regulated ß-cell death, dysfunction, and ROS production. Mechanistic studies demonstrated that Pdia4 increased ROS content in ß-cells via its action on the pathway of Ndufs3 and p22phox . Finally, we found that 2-ß-D-glucopyranosyloxy1-hydroxytrideca 5,7,9,11-tetrayne (GHTT), a Pdia4 inhibitor, suppressed diabetic development in diabetic mice. These findings characterize Pdia4 as a crucial regulator of ß-cell pathogenesis and diabetes, suggesting Pdia4 is a novel therapeutic and diagnostic target of diabetes.

3.
Int Immunopharmacol ; 98: 107699, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34147911

RESUMO

Severe traumatic brain injury (sTBI)-induced acute lung injury (sTBI-ALI) is regarded as the most common complication of sTBI that is an independent predictor of poor outcomes in patients with sTBI and strongly increases sTBI mortality. Polydatin (PD) has been shown to have a potential therapeutic effect on sTBI-induced neurons injury and sepsis-induced acute lung injury (ALI), therefore, it is reasonable to believe that PD has a protective effect on sTBI-ALI. Here, to clarify the PD protective effect following sTBI-ALI, a rat brain injury model of lateral fluid percussion was established to mimic sTBI. As a result, sTBI induced ALI, and caused an increasing of wet/dry weight ratio and lung vascular permeability, as well as sTBI promoted oxidative stress response in the lung; sTBI caused inflammatory cytokines release, such as IL-6, IL-1ß, TNF-α and MCP-1; and sTBI promoted NETs formation, mainly including an increasing expression of MPO, NE and CitH3. Simultaneously, sTBI induced a significant increase in the level of S100B; however, when inhibition of S100B, the expression of MPO, NE and CITH3 were significantly inhibited following sTBI. Inhibition of S100B also promoted lung vascular permeability recovery and alleviated oxidative stress response. Furthermore, PD treatmentreduced the pathological lung damage, promoted lung vascular permeability recovery, alleviated oxidative stress response and inflammatory cytokines release; more importantly, PD inhibited the expression of S100B, and NETs formation in the lung following sTBI. These results indicate that PD alleviates sTBI-ALI by inhibiting S100B mediated NETs formation. Thus, PD may be valuable in sTBI-ALI treatment.

4.
J Tissue Eng Regen Med ; 15(3): 232-243, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33434402

RESUMO

Infectious bone defects remain a significant challenge in orthopedics and dentistry. Calcium phosphate cement (CPC) have attracted significant interest in use as local drug delivery system, which with great potential to control release of antibiotics for the treatment of infectious bone defects. Within the current study, a novel antibacterial scaffold of chitosan-reinforced calcium phosphate cement delivering doxycycline hyclate (CPCC + DOX) was developed. Furthermore, the capacity of CPCC + DOX scaffolds for bone regeneration was enhanced by the human periodontal ligament stem cells (hPDLSCs) encapsulated in alginate beads. CPCC + DOX scaffolds were fabricated to contain different concentrations of DOX. Flexural strength of CPCC + DOX ranged from 5.56 ± 0.70 to 6.2 ± 0.72 MPa, which exceeded the reported strength of cancellous bone. Scaffolds exhibited continual DOX release, reaching 80% at 21 days. Scaffold with 5 mg/ml DOX (CPCC + DOX5mg) had a strong antibacterial effect, with a 4-log colony forming unit reduction against S. aureus and P. gingivalis. The proliferation and osteogenic differentiation of hPDLSCs encapsulated in alginate hydrogel microbeads were investigated in culture with CPCC + DOX scaffolds. CPCC + DOX5mg had no negative effect on proliferation of hPDLSCs. Alkaline phosphatase activity, mineral synthesis, and osteogenic gene expressions for CPCC + DOX5mg group were much higher than control group. DOX did not compromise the osteogenic induction. In summary, the novel CPCC + DOX scaffold exhibited excellent mechanical properties and strong antibacterial activity, while supporting the proliferation and osteogenic differentiation of hPDLSCs. The CPCC + DOX + hPDLSCs construct is promising to enhance bone regeneration and combat bone infections in dental, craniofacial, and orthopedic applications.

5.
Anim Biotechnol ; : 1-6, 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33146068

RESUMO

With the advent of global climate change, heat-tolerance is becoming more and more important to the sustainability of animal husbandry production systems. Previous studies have shown that MYO1A gene associated with pigmentation may be closely related to heat-tolerance in cattle. In this study, a novel missense mutation (NC_037332.1 g.56390345 A > G) was first detected in MYO1A in 891 individuals of 35 cattle breeds, which transformed the amino acid isoleucine into valine. The purpose of this study was to determine the allele frequencies distribution of this locus in Chinese indigenous cattle and to analyze the relationship between this locus and heat-tolerance. Further analysis showed that frequency of wild allele A decreased gradually from northern cattle to southern cattle, whereas frequency of mutant type allele G showed the opposite pattern, which was consistent with the distribution of various climatic conditions of China. Additionally, association analysis was carried out between genotypes and four climatic conditions (annual mean temperature (T), relative humidity (H), temperature-humidity index (THI) and average annual sunshine hours (100-cloudiness) (SR)). Analysis results showed that genotypes were significantly correlated with climatic conditions. Therefore, our results suggest that the novel SNP (rs209559414) is related to heat-tolerance trait of Chinese indigenous cattle.

6.
Animals (Basel) ; 9(8)2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31416175

RESUMO

The small heat shock proteins (HSPB) are expressed in response to heat stress, and the heat shock protein family B (small) member 7 (HSPB7) gene has been reported to play an important role in heat tolerance pathways. Only a missense mutation (NC_037329.1: g.136054902 C > G: p.Ala69Gly) was identified in the HSPB7 gene in indicine cattle, which might be a candidate mutation associated with the heat tolerance. Here, we explore the allele frequency of this mutation in 774 individuals belonging to 32 Chinese indigenous cattle breeds using polymerase chain reaction (PCR) and DNA sequencing methods. The distribution of alleles of NC_037329.1: g.136054902 C > G displays significant geographical difference across native Chinese cattle breeds that the allele C was dominant in northern cattle groups, while allele G was dominant in southern indicine cattle groups. Additionally, the association analysis indicated that the G allele was significantly associated with mean annual temperature (T), relative humidity (RH), and temperature humidity index (THI) (p < 0.01), suggesting that cattle carrying allele G were distributed in regions with higher T, RH, and THI. Our results demonstrate that the mutation of the HSPB7 gene in Chinese indicine cattle might be a candidate gene associated with the heat tolerance.

7.
Oncol Rep ; 41(4): 2518-2528, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30720130

RESUMO

Chromatin assembly factor 1 subunit B (CHAF1B) participates in DNA synthesis and repair. High CHAF1B expression has been associated with a poor prognosis in several types of cancers. However, no study has evaluated the clinical significance and biological function of CHAF1B in non­small cell lung cancer (NSCLC). In the present study, we aimed to investigate CHAF1B expression and its role in NSCLC. In the present study, it was revealed that CHAF1B was highly expressed in NSCLC lung tissues and 95­D cells. Kaplan­Meier survival analysis indicated that high CHAF1B expression in tumour tissue was associated with poor clinical outcomes in NSCLC patients. Multivariate Cox analyses revealed that lymph node metastasis, tumour­node­metastasis (TNM) stage and CHAF1B expression were independent prognostic factors in NSCLC patients. Moreover, CHAF1B knockdown in 95­D cells markedly inhibited tumour proliferation, reduced colony formation, induced cell cycle arrest and promoted apoptosis. In vivo studies demonstrated that CHAF1B knockdown inhibited the growth of transplanted tumours. Furthermore, our results revealed that the mechanism by which CHAF1B induced apoptosis was mediated by the activation of the p53­dependent apoptotic signalling pathway (BAK/Bcl­2/caspase­3) in 95­D cells. These data indicated that CHAF1B plays an important role in tumourigenesis and may be a therapeutic molecular target to counter NSCLC progression.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Fator 1 de Modelagem da Cromatina/metabolismo , Neoplasias Pulmonares/patologia , Animais , Apoptose/genética , Carcinogênese/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Linhagem Celular Tumoral , Proliferação de Células/genética , Fator 1 de Modelagem da Cromatina/genética , Progressão da Doença , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Prognóstico , RNA Interferente Pequeno/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
8.
Br J Radiol ; 90(1072): 20150772, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28257237

RESUMO

OBJECTIVE: This study aims to investigate the curative effects and mechanism of radiofrequency ablation nucleoplasty in the treatment of cervical vertigo. METHODS: A total of 27 patients diagnosed with cervical vertigo from January 2012 to October 2014 received treatment of radiofrequency ablation nucleoplasty. The narrow-side vertebral artery diameters were examined by using Philips 1.5-T body dual-gradient MRI system. The haemodynamic parameters were detected by using transcranial Doppler sonography. Both of the vertebral artery diameters and haemodynamic parameters were recorded and compared before and after treatment. The curative effects in early post-operative application were evaluated according to the Nagashima standards. RESULTS: Radiofrequency ablation nucleoplasty was performed in a total of 59 cervical discs in 27 patients. The average operation time was 42.7 min, and the symptoms of 92.6% patients were alleviated after radiofrequency ablation nucleoplasty post-operation application. There was no significant difference in the narrow-side vertebral artery diameters before and after treatment in both Group A (p = 0.12) and Group B (p = 0.48); however, the blood flow velocity was significantly higher than that before treatment in both Group A (p = 0.01) and Group B (p = 0.03), respectively. CONCLUSION: Radiofrequency ablation nucleoplasty improves the blood flow in the narrow-side vertebral artery and illustrates the therapeutic effect on cervical vertigo in patients who have no direct compression of the vertebral artery. Advances in knowledge: Radiofrequency intradiscal nucleoplasty can be used as a minimally invasive procedure for treating cervical vertigo.


Assuntos
Ablação por Cateter/métodos , Vértebras Cervicais/cirurgia , Vertigem/cirurgia , Idoso , Velocidade do Fluxo Sanguíneo , Vértebras Cervicais/diagnóstico por imagem , Feminino , Humanos , Disco Intervertebral/diagnóstico por imagem , Disco Intervertebral/cirurgia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Ultrassonografia Doppler Transcraniana , Artéria Vertebral/diagnóstico por imagem
9.
Di Yi Jun Yi Da Xue Xue Bao ; 23(8): 784-5, 2003 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-12919897

RESUMO

OBJECTIVE: To investigate the therapeutic effects of different skin flaps for repairing severe complex hand injuries with burns and compression. METHODS: From January 1990 to December 2000, 39 patients with severe complex injuries due to burns and compression in the hand were treated with different skin flaps, followed by early-stage postoperative comprehensive rehabilitation therapy. RESULTS: All the patients were followed up for 6 to 12 months, and significant differences were observed in the appearance and function of the repaired hands with different skin flaps. CONCLUSION: The medial skin flap taken from the lower leg and the reverse-flow island flap from the anterior aspect of the forearm, when combined with early postoperative rehabilitation treatment, can achieve good recovery of function and appearance of the injured hand.


Assuntos
Queimaduras/cirurgia , Traumatismos da Mão/cirurgia , Retalhos Cirúrgicos , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
10.
Artigo em Chinês | MEDLINE | ID: mdl-11826655

RESUMO

OBJECTIVE: To evaluate the clinical effect of total hip joint replacement and hemiarthroplasty in treatment of fracture of femoral neck in old patients. METHODS: One hundred and ten cases with femoral neck fracture in the aged, 70 to 106 years old, from Aug 1990 to Aug 1999 were reviewed, 96 cases were followed up, among which 52 cases received total hip joints replacement and the other 44 cases received hemiarthroplasty. All of the 96 cases were followed up for 15 to 112 months, averaged 51 months, and were evaluated in operation procedures, post-operative recovery and joint function according to Harris Scoring. RESULTS: The operation time of total hip joints replacement was 20 minutes longer, bleeding volume was 120 ml larger, and post-operative drainage was 140 ml more, in average, than those in hemiarthroplasty. There was no obvious difference between the two types of operation in bed-resting time, length of stay and hospitalizing costs. According to Harris Scoring, there were 38 cases of excellent in hemiarthroplasty (86.4%) and 48 cases of excellent in total hip joints replacement (92.3%). CONCLUSION: Both of the artificial joint replacements are reasonable choices for treatment of fracture of femoral neck in old patients, but total hip joints replacement is recommendable for those comparatively younger patients with good systematic status, and hemiarthroplasty is a good option for those elderly with some systematic diseases.


Assuntos
Artroplastia de Quadril/métodos , Fraturas do Colo Femoral/cirurgia , Idoso , Idoso de 80 Anos ou mais , Feminino , Fraturas do Colo Femoral/diagnóstico por imagem , Seguimentos , Humanos , Masculino , Radiografia
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