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1.
Adv Sci (Weinh) ; 7(6): 2000588, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32195106

RESUMO

[This corrects the article DOI: 10.1002/advs.201900099.].

2.
Mater Sci Eng C Mater Biol Appl ; 110: 110691, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32204116

RESUMO

Calcium phosphates (CaPs) in the form of blocks are typically not satisfied for administration to osteoporotic patients because of their rapid resorption rate in vivo. However, injectable CaP powders have not been investigated for their potential in osteoporotic hosts. Herein, CaPs in the form of nanoparticles was reported can inhibit RANKL-stimulated osteoclastic differentiation (OC) and bone resorption, as evidenced by suppressed TRAP-positive cells, disintegrated F-actin rings and downregulated expression of markers for OC. CaP powders also significantly inhibited nuclear factor-κB (NF-κB) and nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1) activation. Furthermore, injectable CaPs reversed bone loss in a mouse model induced by lipopolysaccharide (LPS) and promoted osteoblastic formation in the absent of pro-osteogenic agents. Therefore, injectable CaPs, especially biphasic calcium phosphate (BCP), could be developed as novel agents for the therapy of osteolysis-related diseases caused by inflammation.

3.
J Cell Physiol ; 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32026468

RESUMO

Osteoporosis is a devastating disease that features reduced bone quantity and microstructure, which causes fragility fracture and increases mortality, especially in the aged population. Due to the long-term side-effects of current drugs for osteoporosis, it is of importance to find other safe and effective medications. Ellagic acid (EA) is a phenolic compound found in nut galls, plant extracts, and fruits, and exhibits antioxidant and antineoplastic effects. Here, we showed that EA attenuated the formation and function of osteoclast dose-dependently. The underlying mechanism was further discovered by western blot, immunofluorescence assay, and luciferase assay, which elucidated that EA suppressed osteoclastogenesis and bone resorption mainly through attenuating receptor activator of nuclear factor-κB (NF-κB) ligand-induced NF-κB activation and extracellular signal-regulated kinase signaling pathways, accompanied by decreased protein expression of nuclear factor of activated T-cells calcineurin-dependent 1 and c-Fos. Moreover, EA inhibits osteoclast marker genes expression including Dc-stamp, Ctsk, Atp6v0d2, and Acp5. Intriguingly, we also found that EA treatment could significantly protect ovariectomy-induced bone loss in vivo. Conclusively, this study suggested that EA might have the therapeutic potentiality for preventing or treating osteoporosis.

4.
J Cell Physiol ; 235(5): 4983, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32048735
7.
Exp Mol Med ; 52(1): 181-182, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31988332

RESUMO

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

8.
Biomed Pharmacother ; 122: 109388, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31919041

RESUMO

Autologous chondrocyte implantation (ACI) is commonly used for the treatment of cartilage defects. Since the cell number for transplantation is limited, the expand culture of chondrocytes in vitro is needed. However, the phenotype of chondrocytes is easy to lose in monolayer cultured in vitro. Traditional growth factors such as transformation growth factor -ß1 (TGF-ß1) have been used for promoting the proliferation and maintained the phenotype of chondrocytes, but the high cost and functional heterogeneity limit their clinical application. It is of significant to develop substitutes that can accelerate proliferation and prevent dedifferentiation of chondrocytes for further study. In our present study, the effect of salidroside on proliferation and phenotype maintenance of chondrocytes and cartilage repair was investigated by performing the cell viability, morphology, glycosaminoglycan (GAG) synthesis, cartilage relative genes expression, macroscopic and histological analyzsis. The TGF-ß/smad3 signal which may involve in the protective effect of salidroside on chondrocytes was also detected by ELISA and qRT-PCR assays. The results indicated that salidroside could promote chondrocytes proliferation and enhance synthesis of cartilage extracellular matrix (ECM). Expression of collagen type I was significantly down-regulated which suggesting that salidroside could prevent chondrocytes from dedifferentiation. The in vivo experiments for cartilage repair also indicated that in the treatment of salidroside, chondrocytes used for ACI significantly accelerated the hyaline cartilage repair. While in the absence of salidroside, the repaired cartilage is mainly the fibrous cartilage. Additional experiments demonstrated that salidroside promotes the proliferation and maintain the phenotype of chondrocytes by activate the TGF-ß/smad3 signal. Salidroside may be a potential agent for ACI to promote the proliferation and maintain the phenotype of chondrocytes expansion in vitro.

9.
Int J Biol Sci ; 16(2): 309-319, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31929758

RESUMO

Osteoporosis is a disease characterized by abnormally increased formation and function of osteoclasts. Anti-RANKL treatment using natural medicine is a potential therapy for osteoporosis. Here, we studied the effect of fangchinoline, which is extracted from the root of Stephania tetrandra S. Moore, on osteoclast formation and function. We found that fangchinoline inhibited osteoclastogenesis at doses of 0.5 and 1 µM. In addition, we also examined the mechanism of the inhibitory effect of fangchinoline on osteoclasts. We found that fangchinoline down regulated NFATc1 activity and expression. However, fangchinoline did not affect IκBα degradation and MAPK pathways. In addition, we also found that fangchinoline could protect against bone loss in OVX mice. Taken together, fangchinoline may be a potential compound for osteoporosis.

10.
Carbohydr Polym ; 231: 115727, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31888849

RESUMO

Carbazate groups were grafted on the commercial cellulose membrane (CM) to specifically scavenge the carbonylated proteins for hemodialysis. It confirmed that carbazate groups were successfully covalently attached on the CMs by XPS and EDS, and the modified CMs still saved their original morphology and crystalline structures by SEM and XRD. Furthermore, the modified CMs presented favorable physicochemical stability at wide pH range from 2.5 to 7.4. It was also found that the carbazate modified CMs could selectively remove carbonylated proteins from acrolein treated bovine serum albumin (BSA) or ESRD patient's blood serum in PBS buffer. The modified CMs showed the potential to be utilized as the substitute of dialysis membranes in hemodialysis.

11.
J Inorg Biochem ; 205: 110983, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31954343

RESUMO

Six N-phenylcarbazole/triphenylamine-appended half-sandwich iridium(III) 2-phenylpyridine complexes ([(η5-Cp*)Ir(C^N)Cl]) were prepared and characterized. Compared with cisplatin, these complexes exhibited potential antitumor activity against A549 and HeLa tumor cells, with IC50 values (half-maximum inhibitory concentration) that changed from 2.8 ± 0.8 µM to 39.5 ± 2.7 µM, and could block the migration of tumor cells. These complexes also effectively bound to protein (binding constant: ~104 M-1) and were transported through serum proteins, catalyzed the oxidation of coenzyme nicotinamide-adenine dinucleotide. Additionally, laser confocal microscopy and flow cytometry confirmed that these complexes possessed a non-energy-dependent cellular uptake mechanism, effectively accumulated in lysosomes (Pearson colocalization coefficient: ~0.74), damaged the integrity of acidic lysosomes, led to a change in the mitochondrial membrane potential, disrupted the cell cycle (G0/G1 phase), and eventually induced apoptosis. Above all, these complexes are potential antitumor agents with dual functions: metastasis inhibition and lysosomal damage.

12.
Life Sci ; 244: 117336, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31972206

RESUMO

AIMS: Postmenopausal osteoporosis and other osteolytic bone diseases are often caused by the elevation in osteoclastogenesis and/or increased osteoclastic bone resorption, leading to excessive bone loss. Hederagenin (Hed) is a pentacyclic triterpenoid saponin extracted from various natural medicinal plants and exhibits numerous biological activities and may offer benefits against bone-related conditions. We evaluated the effects of Hed on osteoclast formation and bone resorption in vitro and the in vivo therapeutic benefits in the mouse model of ovariectomy (OVX)-induced bone loss. MAIN METHODS: In vitro, osteoclast formation were determined by TRAcp staining; bone resorption were examined using Hydroxyapatite resorption assay and Podosomal actin belt formation assay; Related molecular mechanisms were determined by western blot assay. Construction of OVX mice by bilateral oophorectomy to simulate bone loss in vivo. KEY FINDINGS: In vitro cellular assays showed that Hed inhibited RANKL-induced osteoclast formation and osteoclast bone (hydroxyapatite) resorption as well as marker gene expression from BMM culture. Mechanistically, Hed attenuated RANKL-induced intracellular reactive oxygen species (ROS) production, and MAPK signaling pathway (ERK and p38) activation which curbed the downstream induction of c-Fos and NFATc1. Consistent with the in vitro findings, Hed administration effectively protected OVX mice from bone loss by reducing osteoclast number and activity on bone surface. SIGNIFICANCE: Our data provided promising evidence for the potential use of Hederagenin in the treatment of osteoclast-mediated osteolytic bone diseases such as postmenopausal osteoporosis.


Assuntos
Reabsorção Óssea/prevenção & controle , Ácido Oleanólico/análogos & derivados , Osteogênese/efeitos dos fármacos , Ovariectomia/efeitos adversos , Substâncias Protetoras/farmacologia , Ligante RANK/metabolismo , Animais , Reabsorção Óssea/etiologia , Reabsorção Óssea/metabolismo , Reabsorção Óssea/patologia , Feminino , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Ácido Oleanólico/farmacologia , Ligante RANK/genética , Transdução de Sinais
13.
Biomaterials ; 230: 119601, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31711715

RESUMO

Osteoarthritis (OA) is one of the most common musculoskeletal disorders worldwide. Oxidative stress initiated by excessive free radicals such as reactive oxygen species (ROS) is a leading cause of cartilage degradation and OA. However, conventional injection or oral intake of antioxidants usually cannot provide effective treatment due to rapid clearance and degradation or low bioavailability. Here, a new strategy is proposed based on nanofibers made of poly (ε-caprolactone) (PCL) and PCL-grafted lignin (PCL-g-lignin) copolymer. Lignin offers intrinsic antioxidant activity while PCL tailors the mechanical properties. Electrospun PCL-lignin nanofibers show excellent antioxidant activity, low cytotoxicity and excellent anti-inflammatory effects as demonstrated using both H2O2-stimulated human chondrocytes and an OA rabbit model. PCL-lignin nanofibers inhibit ROS generation and activate antioxidant enzymes through autophagic mechanism. Arthroscopic implantation of nanofibrous membrane of PCL-lignin is effective to OA therapy because it is biocompatible, biodegradable and able to provide sustained antioxidant activity.

14.
J Cell Biochem ; 121(3): 2643-2654, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31692043

RESUMO

Immune infiltration is reported to be highly associated with tumor progress. Since butyrophilin subfamily 3 member A2 (BTN3A2) serves as a crucial mediator in immune activation, we aimed to investigate the correlation of BTN3A2 in immune infiltration and tumor prognosis via extensive-cancer analysis. The levels of BTN3A2 expression in extensive cancers were analyzed with Oncomine and TIMER databases. Univariate cox and multivariate cox regression analyses were conducted to assess the associations of BTN3A2 to prognosis of various cancers. The correlations of BTN3A2 with immune infiltration were assessed by TIMER database. It suggested that BTN3A2 was a potential prognosis signature for breast cancer (BRCA) and ovarian cancer (OV). However, immune infiltrations were highly correlated with BTN3A2 in triple-negative breast cancer (TNBC), compared with OV and other subtypes of BRCA. Multivariate cox regression analysis revealed that BTN3A2 was an independently prognostic signature of TNBC, as well as weighted correlation network analysis suggested BTN3A2 was only correlated with TNBC, rather than other subtypes of BRCA. Immune cell subtypes correlation analysis showed that BTN3A2 was highly correlated with general T, CD8+ T, T helper type 1, exhausted T cells, and dendritic cells in TNBC. And the coexpression geneset of BTN3A2 was mainly involved in T-cell receptor interaction and the nuclear factor-κB (NF-κB) signaling pathway. Collectively, BTN3A2 that was positively associated with better prognosis could be served as a special diagnostic and independently prognostic marker for TNBC by regulating the T-cell receptor interaction and NF-κB signaling pathways.

15.
J Cell Physiol ; 235(2): 1746-1758, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31309562

RESUMO

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease, and the pathogenesis of RA is still unknown. Rheumatoid arthritis fibroblast-like synoviocytes (RA-FLSs) are of significance in the pathogenesis of RA. In this study, three microarray profiles (GSE55457, GSE55584, and GSE55235) of human joint FLSs from 33 RA patients and 20 normal controls were extracted from the Gene Expression Omnibus Dataset and analyzed to investigate the underlying pathogenesis of RA. As analyzed by the differently expressed genes, gene ontology, Kyoto Encyclopedia of Genes and Genomes pathway enrichment, and protein-protein interaction network analysis, syndecan-4 (SDC4), a receptor of multiple cytokines and chemokines, which played a key role in the regulation of inflammatory response, was found to be an essential regulator in RA. To further validate these results, the levels of SDC4, reactive oxygen species (ROS), nitric oxide (NO), inflammation, and apoptosis in RA-FLSs were examined. SDC4-silenced RA-FLSs were also used. The results demonstrated that SDC4 and the level of ROS, NO, and inflammation were highly expressed while the apoptosis was decreased in RA-FLSs compared with normal FLSs. SDC4 silencing significantly suppressed the levels of ROS, NO, and inflammation; elevated the expression of nuclear factor erythroid 2-related factor 2; and promoted the apoptosis of RA-FLSs. Collectively, our results demonstrated a new mechanism of SDC4 in initiating the inflammation and inhibiting the apoptosis of RA-FLSs and that a potential target for the diagnosis and treatment of RA in the clinic might be developed.

17.
Nanoscale ; 11(48): 23504-23505, 2019 12 28.
Artigo em Inglês | MEDLINE | ID: mdl-31799537

RESUMO

Correction for 'Dopamine-melanin nanoparticles scavenge reactive oxygen and nitrogen species and activate autophagy for osteoarthritis therapy' by Gang Zhong et al., Nanoscale, 2019, 11, 11605-11616.

18.
Artigo em Inglês | MEDLINE | ID: mdl-31794478

RESUMO

BACKGROUND: The management of severe and recalcitrant diabetic foot ulcers is challenging. Distraction osteogenesis is accompanied by vascularization and regeneration of the surrounding tissues. Longitudinal distraction of the proximal tibia stimulates increased and prolonged blood flow to the distal tibia. However, the effects of transverse distraction of the proximal tibia cortex on severe and recalcitrant diabetic foot ulcers are largely unknown. QUESTIONS/PURPOSES: (1) Does tibial cortex transverse distraction increase healing and decrease major amputation and recurrence of severe and recalcitrant diabetic foot ulcers compared with routine management (which generally included débridement, revascularization, negative pressure wound therapy, local or free flaps, or skin grafts as indicated)? (2) Does neovascularization and perfusion increase at the foot after the procedure? (3) What are the complications of tibial cortex transverse distraction in patients with severe and recalcitrant diabetic foot ulcers? METHODS: Between July 2014 and March 2017, we treated 136 patients with diabetes mellitus and University of Texas Grade 2B to 3D ulcers (wound penetrating to the tendon, capsule, bone, or joint with infection and/or ischemia). The patients had failed to respond to treatment for at least 6 months, and their ulcers had a mean ± SD area of 44 cm ± 10 cm. All 136 patients underwent tibial cortex transverse distraction (partial corticotomy of the upper tibia, which was in normal condition, followed by 4 weeks of transverse distraction medially then laterally). We compared these patients with the last 137 consecutive patients we treated with standard surgical treatment, consisting of débridement, revascularization, local or free flap or skin equivalent, or graft reconstruction along with negative-pressure wound therapy between May 2011 and June 2013; there was a 1-year period during which both treatments were in use, and we did not include patients whose procedures were performed during this time in either group. Patients in both groups received standard off-loading and wound care. The patients lost to follow-up by 2 years (0.7% of the treatment group [one of 137] and 1.4% of the control group [two of 139]; p = 0.57) were excluded. The patients in the treatment and control groups had a mean age of 61 years and 60 years, respectively, and they were predominantly men in both groups (70% [95 of 136] versus 64% [88 of 137]; p = 0.32). There were no differences with respect to parameters associated with the likelihood of ulcer healing, such as diabetes and ulcer duration, ulcer grades and area, smoking, and arterial status. We compared the groups with respect to ulcer healing (complete epithelialization without discharge, maintained for at least 2 weeks, which was determined by an assessor not involved with clinical care) in a 2-year follow-up, the proportion of ulcers that healed by 6 months, major amputation, recurrence, and complications in the 2-year follow-up. Foot arterial status and perfusion were assessed in the tibial cortex transverse distraction group using CT angiography and perfusion imaging. RESULTS: The tibial cortex transverse distraction group had a higher proportion of ulcers that healed in the 2-year follow-up than the control group (96% [131 of 136] versus 68% [98 of 137]; odds ratio 10.40 [95% CI 3.96 to 27.43]; p < 0.001). By 6 months, a higher proportion of ulcers healed in the tibia cortex transverse distraction group than the control group (93% [126 of 136] versus 41% [56 of 137]; OR 18.2 [95% CI 8.80 to 37.76]; p < 0.001). Lower proportions of patients in the tibia cortex transverse distraction group underwent major amputation (2.9% [four of 136] versus 23% [31 of 137], OR 0.10 [95% CI 0.04 to 0.30]; p < 0.001) or had recurrences 2.9% (4 of 136) versus 17% (23 of 137), OR 0.20 [95% CI 0.05 to 0.45]; p < 0.001) than the control group in 2-year follow-up. In the feet of the patients in the tibial cortex transverse distraction group, there was a higher density of small vessels (19 ± 2.1/mm versus 9 ± 1.9/mm; mean difference 10/mm; p = 0.010), higher blood flow (24 ± 5 mL/100 g/min versus 8 ± 2.4 mL/100 g/min, mean difference 16 mL/100 g/min; p = 0.004) and blood volume (2.5 ± 0.29 mL/100 g versus 1.3 ± 0.33 mL/100 g, mean difference 1.2 mL/100 g; p = 0.03) 12 weeks postoperatively than preoperatively. Complications included closed fractures at the corticotomy site (in 1.5% of patients; two of 136), which were treated with closed reduction and healed, as well as pin-site infections (in 2.2% of patients; three of 136), which were treated with dressing changes and they resolved without osteomyelitis. CONCLUSIONS: Proximal tibial cortex transverse distraction substantially facilitated healing and limb salvage and decreased the recurrence of severe and recalcitrant diabetic foot ulcers. The surgical techniques were relatively straightforward although the treatment was unorthodox, and the complications were few and minor. These findings suggest that tibial cortex transverse distraction is an effective procedure to treat severe and recalcitrant diabetic foot ulcers compared with standard surgical therapy. Randomized controlled trials are required to confirm these findings. LEVEL OF EVIDENCE: Level II, therapeutic study.

19.
Mol Ther Nucleic Acids ; 18: 696-707, 2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31726387

RESUMO

Ankylosing spondylitis (AS) is a chronic inflammatory disease characterized with heterotopic ossification of the axis joints ligaments, resulting in joint disability. MicroRNAs (miRNAs) are regulators of mRNAs that play a crucial role in the AS pathological process. Here, we showed that the level of miR-17-5p was significantly higher in fibroblasts and ligament tissues from AS patients as compared to the non-AS individuals. Knockdown of the miR-17-5p from the fibroblasts derived from AS patients exhibited decreased osteogenic differentiation and ossification. On the other hand, AS patient-derived fibroblasts overexpressing miR-17-5p displayed the increased osteogenesis. Furthermore, inhibition of miR-17-5p ameliorated osteophyte formation, and the sacroiliitis phenotype in AS rats received emulsified collagen. Mechanistically, miR-17-5p regulated osteogenic differentiation by targeting the 3' UTR of ankylosis protein homolog (ANKH). Also, downregulation of miR-17-5p slowed AS progression through regulation of cytokines, such as dickkopf-1 (DKK1) and vascular endothelial growth factor (VEGF). In conclusion, our findings reveal a role of the miR-17-5p-ANKH axis in the regulation of heterotopic ossification, which is essential for therapeutic intervention in heterotopic ossification in AS.

20.
Biomaterials ; 225: 119520, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31586865

RESUMO

Osteoarthritis (OA) microenvironment is marked by matrix metalloproteinases-13 (MMP-13) overexpression and weak acidity, making it possible to develop dual-stimuli responsive theranostic nanoprobes for OA diagnosis and therapy. However, current MMP/pH-responsive systems are not suitable for OA because of their poor biocompatibility, poor degradation and non-cartilage-targeting of the responsive probes. Here we designed a novel biocompatible cartilage-targeting and MMP-13/pH-responsive ferritin nanocages (CMFn) loaded with an anti-inflammatory drug (Hydroxychloroquine, HCQ), termed CMFn@HCQ, for OA imaging and therapy. We found that CMFn could be smartly "turned on" to emit light for OA imaging in response to the level of overexpressed MMP-13 in OA microenvironment, corresponding to the degree of OA severity. Thus the light intensity detected reflected the degree of OA severity, enabling the precise disease classification by our CMFn. CMFn could be "turned off" to stop emitting light in the normal joint. CMFn@HCQ nanocages could target the cartilage and release HCQ in the OA joint specifically under acidic pH conditions in a sustained manner, prolonging the drug retention time to 14 days to remarkably reduce synovial inflammation in the OA joints. The CMFn@HCQ nanocages represent a smart dual-stimuli responsive and cartilage-targeting nanoprobes, and hold promise for imaging-guided precision therapy for OA.

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