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1.
Int J Biol Sci ; 16(9): 1604-1615, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32226305

RESUMO

The roles of long non-coding RNAs (lncRNAs) and micro RNAs (miRNAs) as regulators of mRNA expression in various diseases have recently been reported. Osteoblast differentiation is the vital process which mediates bone formation and fracture healing. In present study, we found microRNA-6979-5p (miR-6979-5p) to be the most differentially expressed miRNA between normal bone and calluses of mice, and overexpression of miR-6979-5p was negatively associated with osteoblast differentiation. Through luciferase assays, we found evidence that bone morphogenetic protein 2 (BMP2) is a miR-6979-5p target gene that positively regulates osteoblast differentiation. We further identified the lncRNA Rhno1 as a competing endogenous RNA (ceRNA) of miR-6979-5p, and we verified that it was able to influence osteoblast differentiation both in vitro and in vivo. In summary, our data indicates that the lncRNA Rhno1/miR-6979-5p/BMP2 axis is a significant regulatory mechanism controlling osteoblast differentiation, and it may thus offer a novel therapeutic strategy for fracture healing.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32213082

RESUMO

Background: Atherosclerosis is one of the leading causes of morbidity and mortality worldwide. A variety of long noncoding RNAs (lncRNAs) have been reported to be significantly involved in vascular smooth muscle cell (VSMC) proliferation, which is an essential process for atherosclerotic plaque formation. The aim of this study was to investigate the mechanism of lncRNA urothelial cancer associated 1 (UCA1) involvement in atherosclerosis. Method: The effects of oxidized low-density lipoprotein (oxLDL) and UCA1 on VSMC proliferation and colony-forming ability was measured by 3-(4,5-dimethylthiazol-2-yl) -2,5-diphenyl-2H-tetrazolium bromide (MTT) assays, real-time polymerase chain reaction (PCR), and western blots, as well as to determine the effect that oxLDL has on UCA1 expression, and the effect of oxLDL and UCA1 on the expression of cyclin-dependent kinase 2 (CDK2). Results: oxLDL treatment increased the proliferation rate of VSMCs in a concentration-dependent manner. Importantly, UCA1 apparently increased the viability of VSMCs as the VSMCs exhibited a significantly reduced growth rate when UCA1 expression was knocked down by specific small interfering RNAs (siRNAs). In conjunction with increasing cell viability, oxLDL also enhanced the colony-forming ability of VSMCs while UCA1 siRNA decreased the colony-forming ability of VSMCs. Furthermore, UCA1 significantly decreased the percentage of VSMCs in G1 phase, while increasing their percentage in S phase. In contract siRNA knockdown of UCA1 caused an increased percentage of cell in G1 phase, and a reduction in the percentage of cells in S phase. Using real-time PCR and western blot assays, we showed that oxLDL significantly increased the expression levels of UCA1 and CDK2. Furthermore, UCA1 siRNA and CDK2 siRNA almost abolished the positive effect of oxLDL on CDK2 expression. Finally, overexpression of UCA1 induced an increase in CDK2 levels, and knockdown of UCA1 caused inhibition of CDK2 expression. Conclusion: Upregulation of UCA1 enhances abnormal proliferation of VSMC by promoting G1/S transition through modulating the expression of CDK2.

3.
FASEB J ; 2020 Feb 14.
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.

4.
BMC Cardiovasc Disord ; 20(1): 24, 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31952504

RESUMO

BACKGROUND: Longitudinal stent deformation (LSD) is an infrequent complication of percutaneous coronary intervention (PCI), and it may lead to catastrophic clinical outcomes. However, reports of cardiac adverse events associated with LSD are rare. CASE PRESENTATION: A 55-year-old man with chest pain was treated for a severe left anterior descending branch (LAD)-diagonal 1 (D1) bifurcation lesion by PCI with two stents in the proximal LAD. LSD occurred during the withdrawal of the trapped D1 wire. High-pressure balloon dilatation was performed in the deformed stent, and the end-angiographic appearance was acceptable, but no additional corrective measures were implemented. Ten months later, the patient represented with acute coronary syndrome. Severe in-stent restenosis (ISR) had suboccluded the proximal LAD, and optical coherence tomography (OCT) visualized multilayered stent struts protruding into the lumen at the compressed segment of the stent. Following complete apposition with balloon dilation, a drug-coated balloon (DCB) was used to avoid an additional permanent metallic layer. He remained angina free, and the angiographic result demonstrated no residual stenosis at the six-month follow-up. To our knowledge, this case demonstrates the first report of ISR triggered by LSD in patients treated with DCBs under the guidance of OCT. CONCLUSIONS: The current report underscores the importance of awareness of LSD, and OCT seems to be the preferred modality to confirm complete apposition. If left without performing additional corrective measures, LSD may be associated with a risk of ISR. Complete apposition with balloon dilation followed by a DCB is a feasible treatment option.

5.
J Orthop Surg (Hong Kong) ; 28(1): 2309499019887660, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31895000

RESUMO

Osteoarthritis (OA) is an extremely common form of chronic joint disease which can affect the knees and other joints of older adults, leading to debilitating disability in the knee and consequent reduction in quality of life. Intra-articular platelet-rich plasma (PRP) or hyaluronic acid (HA) injections are effective for maintaining long-term beneficial effects without increasing the risk of intra-articular infection. However, few studies have compared the relative value of HA and PRP for OA treatment. PRP is more effective than HA for OA treatment in recent studies of this topic. We systematically searched Medline, SpringerLink, Embase, Pubmed, Clinical Trials.gov, the Cochrane Library, and OVID for all articles published through May 2018. Any study was included that compared the effect of HA and PRP (consistent treatment cycle and frequency of injection) on patient's pain levels and functionality improvements. Review Manager 5.3 was used to analyze data regarding these two primary outcomes. We included 10 total studies in the present meta-analysis. International Knee Documentation Committee (IKDC; MD: 10.37, 95% confidence interval (CI): 9.13 to 11.62, p < 0.00001), Western Ontario and MacMaster Universities Osteoarthritis Index (WOMAC; MD: -20.69, 95% CI: -24.50 to -16.89, p < 0.00001, I2 = 94%), and Visual Analogue Scale (VAS; MD: -1.50, 95% CI: -1.61 to -1.38, p < 0.00001, I2 = 90%) differed significantly between the PRP and HA groups. Knee Osteoarthritis Outcome Scores (KOOSs) did not differ significantly (χ2 = 23.53, I2 = 41%, p = 0.11). Our hypothesis appears not to be confirmed because PRP and HA did not differ significantly with respect to KOOS score. However, the IKDC, WOMAC, and VAS scores differed significantly. Thus, based on the current evidence, PRP appears to be better than HA at achieving pain relief and self-reported functional improvement. Ia, meta-analyses of randomized clinical trials.

6.
J Cell Mol Med ; 24(1): 1076-1086, 2020 Jan.
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.

7.
Injury ; 51(2): 466-472, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31839426

RESUMO

PURPOSE: To evaluate intraoperative and early postoperative clinical outcomes using the Nice knot as an auxiliary reduction technique in displaced comminuted patellar fractures. METHODS: Thirty-nine patients with unilateral closed displaced comminuted patellar fractures received open reduction and internal fixation (ORIF), utilizing either Nice knot (the NK group, 24 patients) or traditional reduction (the TR group, 23 patients) techniques, were retrospectively reviewed in this study. Intra-operative surgical time and peri-operative hemoglobin were recorded. Post-operative clinical outcomes were measured using visual analgesic score, range of motion of the knee joint and the Böstman scales, and radiographic outcomes were used to evaluate fracture healing. Complications including infection, bone non-union, implant loosening, fragment displacement and painful hardware were also assessed. RESULTS: In-hospital records indicated significantly shorter surgical duration (32.6 min) in the NK group than in the TR group (63.9 min). Intraoperative blood loss was also significantly decreased in the NK group (64.7 ml) compared to the TR group (189.1 ml). Patients in the NK and TR groups were followed for mean of 12.9 months and 12.5 months respectively. The union rate was 100% (24/24) in the NK group and 91.3% (21/23) in the TR group. In the TR group, there were two non-unions, including one infected non-union. There was no difference in the visual analgesic score, the range of motion of the knee joint or the Böstman scale at last follow-up between the two groups. CONCLUSION: The sliding, self-stabilizing Nice knot was associated with reduced surgical time, decreased intraoperative blood loss, and satisfactory postoperative outcomes in the treatment of displaced patellar fractures. Future studies are needed to ensure the generalizability of these findings to additional patient populations at other institutions.

8.
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.

9.
Small ; 16(3): e1904044, 2020 Jan.
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.

10.
Mol Cell Biol ; 40(5)2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-31871129

RESUMO

Osteomyelitis, an infection of the bone and bone marrow, imposes a heavy burden on public health care systems owing to its progressive bone destruction and sequestration. Human bone mesenchymal stem cells (hBMSCs) play a key role in the process of bone formation, and mounting evidence has confirmed that long noncoding RNAs (lncRNAs) are involved in hBMSC osteogenic differentiation. Nevertheless, the exact function and molecular mechanism of lncRNAs in osteogenic differentiation during osteomyelitis development remain to be explored. In this study, hBMSCs were treated with staphylococcal protein A (SpA) during osteogenic differentiation induction to mimic osteomyelitis in vitro The results of lncRNA microarray analysis revealed that FAM83H-AS1 presented the lowest expression among the significantly downregulated lncRNAs. Functionally, ectopic expression of FAM83H-AS1 contributed to osteogenic differentiation of SpA-induced hBMSCs. Additionally, our findings revealed that FAM83H-AS1 negatively regulated microRNA 541-3p (miR-541-3p), and WNT3A was validated as a target gene of miR-541-3p. Mechanically, FAM83H-AS1 elevated WNT3A expression by competitively binding with miR-541-3p. Lastly, it was demonstrated that FAM83H-AS1/miR-541-3p/WNT3A ameliorated SpA-mediated inhibition of the osteogenic differentiation of hBMSCs, which provided a novel therapeutic strategy for patients with osteomyelitis.

11.
Ecotoxicol Environ Saf ; 188: 109920, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31733937

RESUMO

This study aimed to investigate the influences of mercuric chloride (HgCl2, 250 ppm, drink water) on the growth performance, cecal morphology and microbiota of chickens (n = 60) after 30, 60, and 90 days of exposure. A control group of sixty chickens received water free of HgCl2. Our results suggested that mercury exposure reduced the body weight and changed the cecal morphology of chickens after the 90-day treatment. Furthermore, sequence analysis of 16 S rRNA gene revealed that the diversity and composition of cecal microbiota in chickens differed between the control and exposure group. At the phylum level, Proteobacteria and Tenericutes phyla both significantly increased in mercury exposure groups on day 30 while only Tenericutes phyla significantly increased on day 60. At the genus level, we observed that the change in microbial populations are most dramatic on day 30. Besides, compared with the control group, the genus Prevotellaceae_UCG-001 significantly increased in exposure group on day 30 but showed no significant difference on day 60, whereas there was a significant decrease on day 90. PICRUSt analysis revealed potential metabolic changes, such as Bacterial invasion of epithelial cells and Metabolism of xenobiotics, associated with mercury exposure in chickens. Taken together, the data show that subchronic exposure to mercury not only affected the growth and development but also caused the dysbiosis of gut microbiota, which may further induced metabolic disorders in chickens.


Assuntos
Ceco/efeitos dos fármacos , Galinhas , Poluentes Ambientais/toxicidade , Microbioma Gastrointestinal , Cloreto de Mercúrio/toxicidade , Microbiota , Animais , Bacteroidetes/isolamento & purificação , Ceco/microbiologia , Ceco/patologia , Galinhas/microbiologia , Relação Dose-Resposta a Droga , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/genética , Masculino , Microbiota/genética , Proteobactérias/isolamento & purificação , RNA Ribossômico 16S/genética
12.
Analyst ; 145(3): 1047-1055, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-31845651

RESUMO

It is important to further improve the electrophysiology and electrochemistry techniques of neurotransmitter detection. Here, we report the development of multifunctional nanopipette-based integrated approaches for the detection of neurotransmitters. We successfully fabricated a nanopipette with two independent functional units at the apex, a nanopore and a gold nanoelectrode (GNE). The GNE shows good electrochemical response to dopamine (DA). Furthermore, both the nanopore and nanoelectrode can effectively enrich DA but not ascorbic acid by electrical means. The enriched DA is then detected and analysed with an obviously improved signal-to-noise ratio by electrochemical methods and surface-enhanced Raman spectroscopy (SERS). In addition, with the addition of silver nanoparticles during enrichment, up to 10 times increase of the Raman intensity of DA can be observed.

13.
Oxid Med Cell Longev ; 2019: 4764071, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31885796

RESUMO

Excessive compression, the main cause of intervertebral disc (IVD) degeneration, affected endogenous repair of the intervertebral disc. Pioglitazone (PGZ) is the agonist of peroxisome proliferator-activated receptor γ, which has been widely used in the treatment of diabetes mellitus. The present study aim at investigating whether pioglitazone has protective effects on compression-mediated cell apoptosis in nucleus pulposus mesenchymal stem cells (NP-MSCs) and further exploring the possible underlying mechanism. Our results indicated that the isolated cells satisfied the criteria of MSC stated by the International Society for Cellular Therapy. Besides, our research revealed that pioglitazone could protect cell viability, cell proliferation of NP-MSCs and alleviated the toxic effects caused by compression. The actin stress fibers was suppressed obviously under compression, and pioglitazone alleviated the adverse outcomes. Pioglitazone exerted protective effects on compression-induced NP-MSCs apoptosis according to annexin V/PI double-staining and TUNEL assays. Pioglitazone suppressed compression-induced NP-MSCs oxidative stress, including decreasing compression-induced overproduction of reactive oxygen species (ROS) and malondialdehyde (MDA), and alleviated compression-induced mitochondrial membrane potential (MMP) decrease. Ultrastructure collapse of the mitochondria exhibited a notable improvement by pioglitazone in compression-induced NP-MSCs according to transmission electron microscopy (TEM). Furthermore, the molecular results showed that pioglitazone significantly decreased the expression of apoptosis-associated proteins, including cyto.cytochrome c, Bax, cleaved caspase-9, and cleaved caspase-3, and promoted Bcl-2 expression. These results indicated that pioglitazone alleviated compression-induced NP-MSCs apoptosis by suppressing oxidative stress and the mitochondrial apoptosis pathway, which may be a valuable candidate for the treatment of IVD degeneration.

14.
Aging (Albany NY) ; 11(24): 11988-12001, 2019 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-31848327

RESUMO

Fracture healing is a complex process involving various cell types, cytokines, and mRNAs. Here, we report the roles of the circRNA AFF4/miR-7223-5p/PIK3R1 axis during fracture healing. We found that increased expression of PIK3R1 during fracture healing is directly associated with augmented proliferation and decreased apoptosis of MC3T3-E1 cells. Furthermore, miR-7223-5p targeted PI3KR1 and inhibited MC3T3-E1 proliferation while promoting apoptosis. CircRNA AFF4 acted as a sponge of miR-7223-5p, thereby promoting MC3T3-E1 cell proliferation and inhibiting apoptosis. Local injection of circRNA AFF4 into femoral fracture sites promoted fracture healing in vivo while the injection of miR-7223-5p delayed healing. These findings suggest that CircRNA AFF4 promotes fracture healing by targeting the miR-7223-5p/PIK3R1 axis, and suggests miR-7223-5p, CircRNA AFF4, and the miR-7223-5p/PIK3R1 axis are potential therapeutic targets for improving fracture healing.

15.
BMC Pharmacol Toxicol ; 20(1): 61, 2019 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-31661009

RESUMO

BACKGROUND: In recent years, targeted therapy has received widespread attention. Among these therapies, anti-angiogenic targeted drugs have become one of the hotspots of research. Apatinib is a novel oral small molecule anti-angiogenic agent that has been clinically tested in a variety of solid tumours. The aim of this study was to investigate the efficacy of apatinib in patients with advanced malignant tumours and failure of standard therapy. METHODS: We collected 41 patients with advanced malignant tumours in our department; all tumours were pathologically confirmed as malignant. All patients received apatinib after failure of standard therapy: 500 mg/dose, one dose/d, orally 30 min after a meal, until progressive disease or intolerable adverse reactions occurred. When there was a second- or third-degree adverse reaction associated with apatinib during treatment, apatinib treatment could be suspended or reduced to 250 mg/dose. Clinical efficacy and progression-free survival were assessed according to RECIST1.1, and adverse reactions were observed. RESULTS: Efficacy assessment was available for 31 patients with a median progression-free survival time of 2.66 months; the objective response rate and disease control rates were 16.1 and 64.5%, respectively. The disease control rates of the patients with lower Eastern Cooperative Oncology Group scores (1-2 points) and with fewer metastatic sites (< 3 sites) were higher than those of the patients with higher scores (3 points) and with more metastatic sites (≥3 sites), respectively (all P < 0.05). The most common adverse reactions were hypertension, neutropenia and hand-foot syndrome. CONCLUSION: For patients with advanced malignant tumours with failure of standard therapy, administration of apatinib can still result in good efficacy. The efficacy of apatinib is better in patients with a higher performance status and lower degree of tumour progression.

16.
Carbohydr Polym ; 226: 115302, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31582049

RESUMO

Hydrogels could be promising wound healing dressings that maintain a moist environment in the wound site and accelerate wound healing. However, the lack of antibacterial effect, suitable mechanical property and adhesiveness limits their applications. Here, we designed a quaternized chitosan-Matrigel-polyacrylamide (QCS-M-PAM) hydrogel with multi-functions. The morphology, swelling ratio, mechanical test, antimicrobial property, hemostatic performance and biocompatibility of the hybrid hydrogel were investigated in vitro and vivo. The hybrid hydrogel showed a three-dimensional (3D) microporous structure, high swelling ratio, excellent stretchable and compressive property, similar modulus to human skin, good adhesiveness, and low cytotoxicity. The results of histology and molecular testing in vivo demonstrated that the hybrid hydrogel could significantly enhance wound healing, collagen deposition, and induce skin adnexal regeneration by upregulating anti-inflammatory factors, and downregulating proinflammatory factors. Together, the present antibacterial hydrogels with hemostatic and adhesive properties are considered to have promising potential used as wound dressings for full-thickness skin defect.


Assuntos
Resinas Acrílicas/farmacologia , Curativos Hidrocoloides , Quitosana/farmacologia , Colágeno/farmacologia , Hidrogéis/farmacologia , Laminina/farmacologia , Proteoglicanas/farmacologia , Cicatrização/efeitos dos fármacos , Resinas Acrílicas/química , Adesividade , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Antifúngicos/química , Antifúngicos/farmacologia , Células Cultivadas , Quitosana/química , Colágeno/química , Combinação de Medicamentos , Humanos , Hidrogéis/química , Laminina/química , Camundongos , Proteoglicanas/química , Cicatrização/fisiologia
17.
Exp Ther Med ; 18(4): 2933-2941, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31572536

RESUMO

Traumatic soft tissue defects such as bedsores, chronic skin ulcers, limb necrosis, osteonecrosis and other ischemic orthopedic diseases are the most clinically intractable and common problems in orthopedics due to unsatisfactory conventional treatments. The present study designed poly(ethylene glycol; PEG) hydrogels with covalently binded arginylglycylaspartic acid (RGD). Endothelial progenitor cells (EPCs) were encapsulated in the modified hydrogel along with vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). Results demonstrated that the modified hydrogel displayed good mechanical properties appropriate for a sustained release carrier. RGD modification significantly promoted EPC biocompatibility. VEGF and bFGF encapsulation enhanced the adhesion of EPCs, promoted the production of extracellular matrix and facilitated EPC proliferation. In addition, bFGF and VEGF induced angiogenesis. The combination of growth factors and EPCs in the hydrogel displayed a strong synergy to improve biocompatibility. The present results provided a potential novel treatment approach for soft tissue defects such as bone exposure, chronic skin ulcers, bedsores, limb necrosis, osteonecrosis and other ischemic diseases.

18.
BMC Pulm Med ; 19(1): 174, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31533673

RESUMO

BACKGROUND: Chronic kidney disease (CKD) is a common comorbidity of chronic obstructive pulmonary disease (COPD). Although high hemoglobin (Hb) is detrimental to CKD patients, its relationship with poor outcomes in the COPD population has not been reported. This study aimed to investigate the relationship between high Hb and in-hospital mortality and to explore reference Hb intervals in patients with COPD and CKD. METHODS: This retrospective study was multicenter population-based. A total of 47,209 patients who presented with COPD between January 2012 and December 2016 were included. The average Hb level during hospitalization was used as the Hb level. CKD and advanced CKD were defined as estimated glomerular filtration rates < 60 and < 30 ml/min/1.73 m2, respectively. The association between Hb level (measured in 1 g/dL intervals) and in-hospital mortality was analyzed in different multivariable logistic regression models by CKD stratification. RESULTS: The Hb level was decreased in the CKD subgroup. In the non-CKD group, a higher Hb level was not associated with an increased risk of in-hospital death. However, the Hb level and mortality showed a U-shaped relationship in the CKD group. After adjusting for age and Charlson Comorbidity Index, multivariable regression analysis showed that an Hb level > 17 g/dL was associated with an increased risk of death in the CKD group with an odds ratio (OR) of 2.085 (95% CI, 1.019-4.264). Hb > 14 g/dL was related to an increased risk of death in advanced CKD patients (OR, 4.579 (95% CI, 1.243-16.866)). CONCLUSIONS: High Hb is associated with an increased risk of in-hospital death in COPD patients with CKD, especially among those with advanced CKD. In this group of patients, attention should be paid to those with high Hb levels.

19.
Int Immunopharmacol ; 76: 105907, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31525636

RESUMO

Sepsis disrupts innate and adaptive immune response, and immune disorders may also impact clinical course of sepsis. Notch signaling pathway plays a vital role in T cell modulation and differentiation. The aim of current study was to investigate the immunoregulatory function of Notch signaling pathway to T cells in patients with sepsis and septic shock. Twenty-seven sepsis patients, twenty-five septic shock patients, and twenty-one normal controls (NCs) were enrolled. Notch receptors mRNA levels were semi-quantified by real-time PCR. The absolute numbers of CD3+, CD4+, and CD8+ T cells were measured by flow cytometry. Key transcriptional factors of CD4+ T cells, cytotoxic molecules in CD8+ T cells, and cytotoxicity of CD8+ T cells were investigated. The regulatory activities of Notch signaling inhibition by γ-secretase inhibitor (GSI) on purified CD4+ and CD8+ T cells from sepsis and septic shock patients were also assessed. Notch1 mRNA relative level was significantly elevated in sepsis and septic shock patients when compared with NCs. CD4+ and CD8+ T cells were dysfunctional in sepsis and septic shock, which presented as decreased cell accounts, down-regulation of Th1/Th17 transcriptional factors and cytotoxic molecules (perforin, granzyme B, and FasL), and reduced cytotoxicity of CD8+ T cells. Notch signaling inhibition by GSI increased Th1 and Th17 differentiation of CD4+ T cells. Moreover, GSI stimulation not only promoted perforin, granzyme B, and FasL mRNA expression in CD8+ T cells, but also elevated CD8+ T cell-induced target cell death and IFN-γ/TNF-α production in sepsis and septic shock. The current data suggest that Notch signaling pathway contributes to T cell dysfunction and limited immune response in sepsis.

20.
Am J Transl Res ; 11(8): 4746-4760, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31497196

RESUMO

Patients who suffered a traumatic brain injury (TBI) show a faster fracture healing than patients with isolated fractures. Prior studies have suggested that this process may be accelerated through the inhibition of key microRNAs. In this study, we aimed to explore the mechanisms underlying this phenomenon, with a special focus on miR-16-5p, which is markedly decreased in patients with TBI. In vitro, miR-16-5p over-expression significantly inhibited cell proliferation in MC3T3-E1 cells transfected with agomiR-16-5p. Flow cytometry analysis further demonstrated that the overexpression of miR-16-5p induced cell cycle G1/S phase arrest and apoptosis. Moreover, target prediction and luciferase reporter assay demonstrated that miR-16-5p could negatively regulate Bcl-2 and Cyclin-D1 expression. Meanwhile, Bcl-2 and Cyclin-D1 were up-regulated after osteogenic differentiation while the down-regulation of endogenous Bcl-2 and Cyclin-D suppressed the osteogenic differentiation of MC3T3-E1 cells. In vivo, PBS, agomiR-16-5p and antagomiR-16-5p were injected into fracture sites to assess any improvements in fracture healing, which further confirmed the negative effect of miR-16-5p on fracture healing. Together, these results demonstrate miR-16-5p downregulation may accelerate fracture healing by enhancing the proliferation and inhibiting the apoptosis of osteoblasts in patients with both fractures and TBI. These phenomena may be exploited in the treatment of fractures.

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