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1.
J Pharm Biomed Anal ; 195: 113839, 2021 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-33388645

RESUMO

The root and rhizome of Polygonum cuspidatum (Hu-Zhang) has been used for treatment of various inflammatory disorders in China. In our pervious study, we found that three fractions (HZE-30, HZE-60 and HZE-95) from the ethanol extract of Hu-Zhang (HZE) all could inhibit NO production, and HZE-60 shows the most potent anti-inflammatory activity. In order to understand the major contribution constituents of Hu-Zhang responsible for its anti-inflammatory effect, quantitative composition-activity relationship method was performed. Firstly, the constituents in HZE-60 were characterized using an ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) approach. Second, quantitative analyzed five major constituents identified in HZE-60 and compare the difference of five major constituents in HZE and three anti-inflammatory activity fractions. Finally, evaluated the anti-inflammatory effects of major constituents in lipopolysaccharide (LPS)-activated RAW264.7 macrophages. The results showed that a total of 31 compounds were identified from HZE-60, including 12 anthraquinones, 7 diphenylethenes, 9 phenols and 3 others. The contents of five major constituents (polydatin (6), resveratrol (7), emodin-1-O-ß-d-glucoside (15), emodin-8-O-ß-d-glucoside (21) and emodin (31)) were simultaneously determined by UPLC-PDA with good linearity (correlation coefficients > 0.9990) and satisfactory repeatability (RSD < 0.99 %), precision (RSD < 0.01 %), stability (RSD < 0.67 %) and recoveries (99.52 %-101.23 %, RSD < 0.91 %). All five major constituents could be detected in HZE and HZE-60 fraction, but only 6 was detected in HZE-30, and 31 in HZE-95. Moreover, 7, 15 and 21 exhibited significant anti-inflammatory activity via suppressing supernatant pro-inflammatory mediators, such as NO, tumor Necrosis Factor-α (TNF-α), interleukin-6 (IL-6) and monocyte chemotactic protein-1 (MCP-1). Therefore, we conclude that the bioactivity of HZE is the syngeneic effect of its constituents, and 7, 15 and 21 should make great contributions for the anti-inflammatory effect of Hu-Zhang. The findings define the anti-inflammatory chemical constituents of Hu-Zhang, which will benefit further investigation on its quality control and the mechanism of action.

2.
Molecules ; 26(3)2021 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-33498966

RESUMO

Mesenchymalstem cell (MSC)-based therapy is being increasingly explored in preclinical and clinical studies as a regenerative method for treating osteoarthritis (OA). However, the use of primary MSCs is hampered by a number of limitations, including donor heterogeneity and inconsistent cell quality. Here, we tested the therapeutic potential of embryonic stem cell-derived MSCs (ES-MSCs) in anOA rat model. ES-MSCs were generated and identified by morphology, trilineage differentiation and flow cytometry. Sprague Dawley rats were treated with either a single dose (106 cells/rat) of ES-MSCs or with three doses spaced one week apart for each dose, starting at four weeks after anterior cruciate ligament transectionto induce OA. Cartilage quality was evaluated at 6 and 10 weeks after treatment with behavioral analysis, macroscopic examination, and histology. At sixweeks after treatment, the groups treated with both single and repeated doses of ES-MSCs had significantly better modified Mankin scores and International Cartilage Repair Society (ICRS) macroscopic scores in the femoral condyle compared to the control group. At 10 weeks after treatment, the repeated doses group had a significantly better ICRS macroscopic scores in the femoral condyle compared to the single dose and control groups. Histological analysis also showed more proteoglycan and less cartilage loss, along with lower Mankin scores in the repeated doses group. In conclusion, treatment with multiple injections of ES-MSCs can ameliorate OA in a rat model. TheES-MSCs have potential to be considered as a regenerative therapy for OA, and can provide an infinite cellular source.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33267667

RESUMO

OBJECTIVE: To provide an up-to-date review of studies that used preclinical animal models for the evaluation of tissue engineering treatments for spinal cord injury (SCI), which involved the use of biomaterials with or without the addition of cells or biomolecules. METHODS: Electronic search of the PubMed, Web of Science and Embase databases was performed for relevant studies published between January 2009 and December 2019. RESULTS: 1579 articles were retrieved, of which 58 studies were included for analysis. Among the included studies, rats were the most common species used for animal models of SCI, while complete transection was the most commonly used injury pattern. Immediate intervention after injury was conducted in the majority of studies, and 8 weeks was the most common final time point of outcome assessment. A wide range of natural and synthetic biomaterials with different morphologies were used as a part of tissue engineering treatments for SCI, including scaffolds, hydrogels and particles. CONCLUSION: Experimental parameters in studies using SCI animal models to evaluate tissue engineering treatments should be carefully considered to match the purpose of the study. Biomaterials that have functional modifications or are applied in combination with cells and biomolecules can be effective in creating a permissive environment for SCI repair in preclinical animal models.

4.
Biomed Res Int ; 2020: 1758071, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33299860

RESUMO

This study was performed to assess the efficacy and safety of a topical diclofenac solution in patients with knee osteoarthritis (OA). PubMed, Embase, Cochrane Library, Web of Science, and Scopus databases were searched for randomized controlled trials until June 2020. The WOMAC pain, stiffness, physical function subscales, pain on walking, and the occurrence of adverse events were pooled to comprehensively analyse the efficacy and safety of topical diclofenac solution. All statistical analyses were conducted using Review Manager 5.3 software. Five RCTs were included, which provided high-quality evidence. In comparison to the vehicle control, the mean differences for WOMAC pain, stiffness, and physical function subscales, as well as pain on walking, were all statistically significant in favor of topical diclofenac solution. The safety of topical diclofenac solution was similar to the vehicle control, apart from adverse events involving application-site skin reactions. Topical diclofenac solution is effective and safe for use in patients with knee OA, but may cause minor skin reactions.

5.
Zhonghua Nan Ke Xue ; 26(9): 826-831, 2020 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-33377708

RESUMO

Objective: To investigate the effect of Bushen Huoxue Recipe (BHR) on cyclophosphamide-induced apoptosis of testicular spermatogenic cells in mice and its possible action mechanisms. METHODS: Fifty male Babl/c mice aged 8-9 weeks were randomly divided into five groups of an equal number: blank control, model control, low-dose BHR, medium-dose BHR and high-dose BHR. The animals in the blank control group were intraperitoneally injected with normal saline, while those in the other four groups with cyclophosphamide at 50 mg/kg/d, all for 7 days. After modeling, the mice in the blank and model control groups were given distilled water via gavage once a day, and those in the low-, medium- and high-dose BHR groups treated intragastrically with BHR at 7.5, 15 and 30 g/kg/d qd for 30 successive days. Then, the apoptosis index of the testicular spermatogenic cells was obtained by TUNEL and the expressions of Bax and Bcl-2 mRNA and proteins determined by RT-PCR and Western blot, respectively. RESULTS: Compared with the mice in the blank control group, the BHR model controls showed dramatically increased apoptosis of testicular spermatogenic cells and up-regulated mRNA and protein expressions of Bax and Bcl-2 in the testis tissue (P < 0.01). In comparison with the model controls, the mice in the BHR treatment groups exhibited significantly reduced apoptosis of testicular spermatogenic cells and down-regulated mRNA and protein expressions of Bax and Bcl-2 in the testis tissue (P < 0.01). CONCLUSIONS: Bushen Huoxue Recipe can reduce cyclophosphamide-induced apoptosis of testicular spermatogenic cells in mice, which may be associated with its ability of regulating the expressions of Bax and Bcl-2 mRNA and proteins in the testis tissue.


Assuntos
Apoptose , Medicamentos de Ervas Chinesas/farmacologia , Testículo/efeitos dos fármacos , Animais , Ciclofosfamida/toxicidade , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Distribuição Aleatória , Testículo/patologia
6.
Artigo em Inglês | MEDLINE | ID: mdl-33336534

RESUMO

The synthesis and isolation of alkynyl/chloride-protected gold nanoclusters is described. Silica gel column chromatography is effective in isolating gold nanoclusters from the as-synthesized cluster mixture to give the clusters Na[Au25 L18 ] (Au25 ), [HNEt3 ]3 [Au67 L32 Cl4 ] (Au67 ), [HNEt3 ]4 [Au106 L40 Cl12 ] (Au106 ), L=3,5-bis(trifluoromethyl)-phenylacetylide. Au67 and Au106 are new clusters; the structures were determined by X-ray single-crystal diffraction. Au67 contains a distorted Au18 Marks decahedron shelled by an irregular Au32 and further protected with two V-shaped Au2 L3 , 13 linear AuL2 staples and 4 chlorides. Au67 is the first structurally determined 34e superatomic gold nanocluster. Au106 is composed of 106 Au atoms co-protected by alkynyls and chlorides. It has a Au79 kernel, like in Au102 (p-MBA)44 . The surface structure of Au106 includes 20 linear Au-alkynyl staples, 5 Cl-Au-Cl and 2 Cl-Au motifs. These three gold nanoclusters show size-dependent electrochemical properties.

7.
Ying Yong Sheng Tai Xue Bao ; 31(9): 3216-3226, 2020 Sep 15.
Artigo em Chinês | MEDLINE | ID: mdl-33345523

RESUMO

In recent years, Chinese scientists have made remarkable achievements in on mycorrhizal molecular biology, nutrition, taxonomy, and ecology, with arbuscular mycorrhizal fungus (AMF) having been mostly studied. AMF can form symbiotic relationship with roots of most terrestrial plants, promote plant growth and development, improve plant stress resistance, maintain ecological balance, and protect ecological environment. This review mainly introduced the ecological function and mechanism of AMF in plant rhizosphere stress from the aspects of abiotic (drought stress, heavy metal pollution, saline-alkali stress) and biotic stresses (pathogenic bacteria and nematode infection). We proposed the remaining deficiencies and research prospects in this field to provide refe-rence for future research of AMF.


Assuntos
Micorrizas , Raízes de Plantas , Plantas , Rizosfera , Simbiose
8.
Cartilage ; : 1947603520973255, 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33215510

RESUMO

OBJECTIVE: Osteoarthritis (OA) is an incurable joint disease characterized by pronounced pain. MicroRNAs constitute epigenetic mechanisms that may affect OA progression by contributing to changes in chondrocyte phenotype. This study investigates for the first time whether there is a link between miRNA-1 (miR-1) and OA pathogenesis, and the molecular mechanisms involved. DESIGN: OA-associated gene expression, including MMP-13, ADAMTS5, and COL2A1 was compared in chondrocytes from non-OA and OA cartilage, and in SW1353 cells over- and underexpressing miR-1. Bioinformatics and luciferase reporter assay were conducted to confirm whether FZD7 was a target of miR-1. The effects of miR-1 on FZD7 expression and downstream Wnt/ß-catenin signalling were investigated. RESULTS: Non-OA and OA chondrocytes differed significantly in the expression of miR-1 and OA-associated genes. MiR-1 over- and underexpression in SW1353 cells, respectively, reduced and enhanced gene expression associated with cartilage catabolism. FZD7, which has an important role in the Wnt/ß-catenin signaling pathway, was shown to be a potential target of miR-1. MiR-1 binding to FZD7 increased the levels of phosphorylated (inactivated) ß-catenin, thereby preventing downstream ß-catenin signaling. CONCLUSIONS: Inhibition of Wnt/ß-catenin signaling by miR-1 in chondrocytes may attenuate the expression of genes that regulate the activity of catabolic enzymes. This finding may be useful for future investigations of molecular targets for OA treatment.

9.
Indian J Orthop ; 54(6): 795-804, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33133402

RESUMO

Background: Hip hemiarthroplasty (HA) is a standard surgical procedure for elderly patients with displaced fracture of the femoral neck, where dislocation is a possible complication. This study is a systematic review on the risk factors of implant dislocation in patients with femoral neck fracture following hip hemiarthroplasty (HA), and evaluates the methodological quality of the included studies. Methods: Studies on risk factor assessment of dislocation following hip HA were sourced from EMBASE, Ovid, PubMed and ScienceDirect databases. The quality of included studies was evaluated using an improved quality evaluation method combined with a best-evidence synthesis method. Results: A total of 130,127 patients were involved in 17 observational studies included in this systematic review, with a dislocation rate that ranged between 0.76 and 12.2% (overall incidence was 4-5% by meta-analysis). According to the applied quality evaluation criteria, eight studies were considered to be of high quality, six to be of medium quality, and three to be of low quality. The posterolateral surgical approach was identified as the only risk factor supported by strong evidence, while patients with small acetabular coverage and low postoperative offset were identified as risk factors supported by moderate evidence, and 11 other risk factors were supported by limited evidence. Conclusion: This systematic review provides some evidence in helping surgeons develop optimal prevention strategies for dislocation following hip HA during the perioperative period based on common risk factors identified in the literature. However, conclusive evidence supporting most of these risk factors is lacking and more methodologically rigorous studies are required to increase the confidence of recommendations.

10.
Int J Med Robot ; : e2189, 2020 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-33108058

RESUMO

BACKGROUND: The radiological and clinical efficiency among robot-assisted surgery (RAS), computer-assisted navigation system (CAS) and conventional (CON) total knee arthroplasty (TKA) remains controversial. METHODS: Bayesian network meta-analysis (NMA) and systematic review were performed to investigate radiological and clinical efficiency respectively. The certainty of the evidence was evaluated using GRADE and CERQual tool. RESULTS: Thirty-four RCTs (7289 patients and 7424 knees) were included. The NMA showed that RAS-TKA had the highest probability for mechanical axis restoration (odds ratio for RAS vs. CAS 3.79, CrI 1.14 to 20.54, very low certainty), followed by CAS-TKA (odds ratio for CAS vs. CON 2.55, CrI 1.67 to 4.01, very low certainty) and then CON-TKA, without significant differences in other radiological parameters. No differences were found in clinical outcomes after qualitative systematic review (overall low certainty). CONCLUSIONS: Technology-based assistive techniques (CAS and RAS) may surpass the CON-TKA, when considering higher radiological accuracy and comparable clinical outcomes. This article is protected by copyright. All rights reserved.

11.
Cell Regen ; 9(1): 15, 2020 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-32880028

RESUMO

BACKGROUND: Apparent Young's modulus (AYM), which reflects the fundamental mechanical property of live cells measured by atomic force microscopy and is determined by substrate stiffness regulated cytoskeletal organization, has been investigated as potential indicators of cell fate in specific cell types. However, applying biophysical cues, such as modulating the substrate stiffness, to regulate AYM and thereby reflect and/or control stem cell lineage specificity for downstream applications, remains a primary challenge during in vitro stem cell expansion. Moreover, substrate stiffness could modulate cell heterogeneity in the single-cell stage and contribute to cell fate regulation, yet the indicative link between AYM and cell fate determination during in vitro dynamic cell expansion (from single-cell stage to multi-cell stage) has not been established. RESULTS: Here, we show that the AYM of cells changed dynamically during passaging and proliferation on substrates with different stiffness. Moreover, the same change in substrate stiffness caused different patterns of AYM change in epithelial and mesenchymal cell types. Embryonic stem cells and their derived progenitor cells exhibited distinguishing AYM changes in response to different substrate stiffness that had significant effects on their maintenance of pluripotency and/or lineage-specific characteristics. On substrates that were too rigid or too soft, fluctuations in AYM occurred during cell passaging and proliferation that led to a loss in lineage specificity. On a substrate with 'optimal' stiffness (i.e., 3.5 kPa), the AYM was maintained at a constant level that was consistent with the parental cells during passaging and proliferation and led to preservation of lineage specificity. The effects of substrate stiffness on AYM and downstream cell fate were correlated with intracellular cytoskeletal organization and nuclear/cytoplasmic localization of YAP. CONCLUSIONS: In summary, this study suggests that optimal substrate stiffness regulated consistent AYM during passaging and proliferation reflects and contributes to hESCs and their derived progenitor cells lineage specificity maintenance, through the underlying mechanistic pathways of stiffness-induced cytoskeletal organization and the downstream YAP signaling. These findings highlighted the potential of AYM as an indicator to select suitable substrate stiffness for stem cell specificity maintenance during in vitro expansion for regenerative applications.

12.
BMC Musculoskelet Disord ; 21(1): 632, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32977786

RESUMO

BACKGROUND: Management of Rüedi-Allgöwer III or AO/OTA type C3 pilon fracture presents numerous challenges to the orthopaedic surgeon. A joint preservation technique using a large autologous ilium with periosteum in combination with internal implant fixation was reported to improve the outcome of reconstruction. METHODS: Twenty-five patients according to Tscherne/Oestern FxCO-I closed fracture and FxOI open fractures classification after Rüedi-Allgöwer III or AO/OTA type C3 pilon fracture received a large autologous ilium with periosteum for tibiotalar joint reconstruction and open reduction and internal fixation (ORIF), between March 2015 and September 2018. The visual analog scale (VAS), American Orthopaedic Foot & Ankle Society (AOFAS) score, and Burwell and Charnley criteria were used for outcome analysis. RESULTS: Twenty patients with an average age of 45.2 years were followed for an average of 18.3 months. The VAS and AOFAS scores, and Burwell and Charnley ratings were recorded at the last follow-up after reconstructive surgery. Two patients developed redness and swelling at the wound site, but recovered after local care and dressing changes. No patient displayed deep surgical site infection, donor site complication, non-union or local complication during the final follow-up. The average bone union time was 18.3 months (range 3-36). CONCLUSIONS: Large autologous ilium with periosteum in combination with ORIF can be performed for tibiotalar joint reconstruction. This experimental procedure reduces the risk of post-operative complications following articular reconstruction for Rüedi-Allgöwer III or AO/OTA type C3 pilon fractures in short follow-up. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

13.
Acta Biomater ; 114: 170-182, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32771588

RESUMO

Tissue engineering using traditional size fixed scaffolds and injectable biomaterials are faced with many limitations due to the difficulties of producing macroscopic functional tissues. In this study, 3D functional tissue constructs were developed by inducing self-assembly of microniches, which were cell-laden gelatin microcryogels. During self-assembly, the accumulation of extracellular matrix (ECM) components was found to strengthen cell-cell and cell-ECM interactions, leading to the construction of a 'native' microenvironment that better preserved cell viability and functions. MSCs grown in self-assembled constructs showed increased maintenance of stemness, reduced senescence and improved paracrine activity compared with cells grown in individual microniches without self-assembly. As an example of applying the self-assembled constructs in tissue regeneration, the constructs were used to induce in vivo articular cartilage repair and successfully regenerated hyaline-like cartilage tissue in the absence of other extrinsic factors. This unique approach of developing self-assembled 3D functional constructs holds great promise for the generation of tissue engineered organoids and repair of challenging tissue defects. STATEMENT OF SIGNIFICANCE: We developed 3D functional tissue constructs using a unique gelatin-based microscopic hydrogel (microcryogels). Mesenchymal stem cells (MSCs) were loaded into gelatin microcryogels to form microscopic cell-laden units (microniches), which were induced to undergo self-assembly using a specially designed 3D printed frame. Extracellular matrix accumulation among the microniches resulted in self-assembled macroscopic constructs with superior ability to maintain the phenotypic characteristics and stemness of MSCs, together with the suppression of senescence and enhanced paracrine function. As an example of application in tissue regeneration, the self-assembled constructs were shown to successfully repair articular cartilage defects without any other supplements. This unique strategy for developing 3D functional tissue constructs allows the optimisation of stem cell functions and construction of biomimetic tissue organoids.

14.
Artigo em Inglês | MEDLINE | ID: mdl-32813044

RESUMO

PURPOSE: Anterior cruciate ligament (ACL) reconstruction is widely accepted as the first choice of treatment for ACL injury, but there is disagreement in the literature regarding the optimal femoral fixation method. This meta-analysis assesses the evidence surrounding three common femoral fixation methods: cortical button (CB), cross-pin (CP) and interference screws (IS). METHODS: A systematic search was conducted in Medline, EMBASE and the Cochrane Library to identify studies with evidence level I or II that compared at least two femoral fixation methods with hamstring autograft for ACL reconstruction. Ten primary outcomes were collected. Risk of bias was assessed following the Cochrane Handbook for Systematic Reviews of Interventions. Standardized mean differences (SMD) were estimated using random-effects network meta-analysis in a Bayesian framework. Probability of ranking best (ProBest) and surface under the cumulative ranking curve (SUCRA) were used to rank all treatments. Funnel plots were used to identify publication bias and small-study effects. RESULTS: Sixteen clinical trials were included for analysis out of 2536 retrieved studies. Bayesian network meta-analysis showed no significant differences among the three fixation methods for the ten primary outcome measures. Based on the 10 outcome measures, the IS, CB and CP had the highest ProBest in 5, 5 and 0 outcomes, and the highest SUCRA values in 5, 4 and 1 outcomes, respectively. No substantial inconsistency between direct and indirect evidence, or publication bias was detected in the outcomes. CONCLUSION: There were no statistical differences in performance among the CP, CB and IS femoral fixation methods with hamstring autograft in ACL reconstruction, although the IS was more likely to perform better than CB and CP based on the analysis of outcome measures from the included studies. LEVEL OF EVIDENCE: 1.

15.
BMC Mol Cell Biol ; 21(1): 53, 2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32650720

RESUMO

BACKGROUND: Long noncoding RNAs (lncRNAs) are recently found to be critical regulators of the epigenome. However, our knowledge of their role in osteoarthritis (OA) development is limited. This study investigates the mechanism by which HOTAIR, a key lncRNA with elevated expression in OA, affects OA disease progression. RESULTS: HOTAIR expression was greatly elevated in osteoarthritic compared to normal chondrocytes. Silencing and over-expression of HOTAIR in SW1353 cells respectively reduced and increased the expression of genes associated with cartilage degradation in OA. Investigation of molecular pathways revealed that HOTAIR acted directly on Wnt inhibitory factor 1 (WIF-1) by increasing histone H3K27 trimethylation in the WIF-1 promoter, leading to WIF-1 repression that favours activation of the Wnt/ß-catenin pathway. CONCLUSIONS: Activation of Wnt/ß-catenin signalling by HOTAIR through WIF-1 repression in osteoarthritic chondrocytes increases catabolic gene expression and promotes cartilage degradation. This is the first study to demonstrate a direct link between HOTAIR, WIF-1 and OA progression, which may be useful for future investigations into disease biomarkers or therapeutic targets.

16.
Cell Transplant ; 29: 963689720932142, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32608995

RESUMO

Intra-articular injection of mesenchymal stem cells (MSCs) in an osteoarthritic joint can help slow down cartilage destruction. However, cell survival and the efficiency of repair are generally low due to mechanical damage during injection and a high rate of cell loss. We, thus, investigated an improved strategy for cell delivery to an osteoarthritic joint through the use of three-dimensional (3D) microcryogels. MSCs were seeded into 3D microcryogels. The viability and proliferation of MSCs in microcryogels were determined over 5 d, and the phenotype of MSCs was confirmed through trilineage differentiation tests and flow cytometry. In Sprague Dawley rats with induced osteoarthritis (OA) of the knee joint, a single injection was made with the following groups: saline control, low-dose free MSCs (1 × 105 cells), high-dose free MSCs (1 × 106 cells), and microcryogels + MSCs (1 × 105 cells). Cartilage degeneration was evaluated by macroscopic examination, micro-computed tomographic analysis, and histology. MSCs grown in microcryogels exhibited optimal viability and proliferation at 3 d with stable maintenance of phenotype in vitro. Microcryogels seeded with MSCs were, therefore, primed for 3 d before being used for in vivo experiments. At 4 and 8 wk, the microcryogels + MSCs and high-dose free MSC groups had significantly higher International Cartilage Repair Society macroscopic scores, histological evidence of more proteoglycan deposition and less cartilage loss accompanied by a lower Mankin score, and minimal radiographic evidence of osteoarthritic changes in the joint compared to the other two groups. In conclusion, intra-articular injection of cell-laden 3D microcryogels containing a low dose of MSCs can achieve similar effects as a high dose of free MSCs for OA in a rat model. Primed MSCs in 3D microcryogels can be considered as an improved delivery strategy for cell therapy in treating OA that minimizes cell dose while retaining therapeutic efficacy.

17.
Tissue Eng Part A ; 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-32539550

RESUMO

In knee osteoarthritis (OA), there is more pronounced cartilage damage in the medial compartment ("lesion zone") than the lateral compartment ("remote zone"). This study fills a gap in the literature by conducting a systematic comparison of cartilage and chondrocyte characteristics from these two zones. It also investigates whether chondrocytes from the different zones respond distinctly to changes in the physical and mechanical microenvironment using three-dimensional porous scaffolds by changing stiffness and pore size. Cartilage was harvested from patients with end-stage varus knee OA. Cartilage from the lesion and remote zones were compared through histological and biomechanical assessments, and through proteomic and gene transcription analyses of chondrocytes. Gelatin scaffolds with varied pore sizes and stiffness were used to investigate in vitro microenvironmental regulation of chondrocytes from the two zones. Cartilage from the lesion and remote zones differed significantly (p < 0.05) in histological and biomechanical characteristics, as well as phenotype, protein, and gene expression of chondrocytes. Chondrocytes from both zones were sensitive to changes in the structural and mechanical properties of gelatin scaffolds. Of interest, although all chondrocytes better retained chondrocyte phenotype in stiffer scaffolds, those from the lesion and remote zones, respectively, preferred scaffolds with larger and smaller pores. Distinct variations exist in cartilage and chondrocyte characteristics in the lesion and remote zones of knee OA. Cells in these two zones respond differently to variations in the physical and mechanical microenvironment. Understanding and manipulating these differences will facilitate the development of more efficient and precise diagnostic and therapeutic approaches for knee OA. Impact statement This study performs a novel systematic analysis of cartilage properties in the lesion (medial) and remote (lateral) zones of knee osteoarthritis (OA), from the tissue level right down to the cell and molecular levels. It also demonstrates for the first time the effects of manipulating the physical and mechanical microenvironment on the behavior of chondrocytes from the lesion and remote zones. This study improves our understanding of the properties and responses of tissues and cells in different zones of knee OA, providing novel insights into OA pathophysiology and also demonstrating a new application of biomaterial scaffolds in studying cell-matrix interactions.

18.
Nanoscale ; 12(25): 13346-13350, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32573630

RESUMO

We report two novel homoleptic alkynyl-protected gold nanoclusters, which were synthesized by direct reduction of AuC[triple bond, length as m-dash]CR. Single-crystal X-ray structural analysis reveals that they have compositions of Au42(C[triple bond, length as m-dash]CC6H4-2-CF3)22 (1) and Au50(C[triple bond, length as m-dash]C6H4-3-F)26 (2), respectively. Cluster 2 is the first Au50 nanocluster, and the metal-to-ligand ratios of 1 and 2 are different from those of known Aun(SR)m or Aux(C[triple bond, length as m-dash]CR)y nanoclusters. In addition, the metal kernels of these two clusters are built up unprecedented units. This work offers further insights into the synthesis of all-alkynyl-protected gold nanoclusters via a direct reduction method.

19.
Chem Commun (Camb) ; 56(51): 7037-7040, 2020 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-32453310

RESUMO

The identification of hydride(s) in gold nanoclusters is a challenging task, due to the instability of gold nanoclusters containing hydrides. Herein, we report two ultrastable hydrido gold nanoclusters protected by phosphine ligands: [Au20(PPh3)12H3](SbF6)3 (1H) and [Au20(PPh3)12H2(2-COOH-PhS)](PF6)3 (2H). The presence of hydrides in gold(0)-gold(i) nanoclusters is clearly demonstrated by ESI mass spectrometry and NMR spectroscopy. Single crystal structural determination reveals that both nanoclusters have an unprecedented Au20 core consisting of a Au9 unit and a Au11 unit. Such cores derived from the connection of different basic units are important for understanding the evolution and stability of metal nanoclusters. The hydride (H-) was also verified by a charge distribution calculation.

20.
Int J Rheum Dis ; 23(6): 778-787, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32319197

RESUMO

AIM: Mesenchymal stem cell (MSC)-based therapy is being explored in treating osteoarthritis (OA). Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) are least reported. In this study, we investigated the effects of single intra-articular injections of hUC-MSCs on a rat OA model. METHOD: hUC-MSCs were isolated from the Wharton's jelly of the human umbilical cord and identified. Eighteen Sprague-Dawley rats were used for the OA model. All rats were divided into 3 groups: hyaluronic acid (HA)+MSCs (n = 6), HA (n = 6), and control group (n = 6). One by 106 hUC-MSCs in 100 µL HA, 100 µL HA or 100 µL saline were injected into the knee joint 4 weeks post-surgery as a single dose. Cartilage degeneration was evaluated at 6 and 12 weeks after treatment with macroscopic examination, micro-computed tomography analysis, behavioral analysis, and histology. RESULTS: At 6 weeks, the HA + MSCs group had a significantly better International Cartilage Repair Society score in the femoral condyle compared to the HA and control groups. Histological analysis also showed more proteoglycan and less cartilage loss, with lower modified Mankin score in the HA + MSCs group. However, at 12 weeks there were no significant differences between groups from macroscopic examination and histological analysis. Subchondral bone sclerosis of the medial femoral condyle and behavioral tests showed no significant differences between groups at 6 and 12 weeks. CONCLUSION: These findings indicate that single injection of hUC-MSCs can have temporary effects on decelerating the progression of cartilage degeneration in OA rats, but may not inhibit OA progression in the long-term.

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