Dynamic Alterations in Microarchitecture, Mineralization and Mechanical Property of Subchondral Bone in Rat Medial Meniscal Tear Model of Osteoarthritis.

BACKGROUND: The properties of subchondral bone influence the integrity of articular cartilage in the pathogenesis of osteoarthritis (OA). However, the characteristics of subchondral bone alterations remain unresolved. The present study aimed to observe the dynamic alterations in the microarchitecture, mineralization, and mechanical properties of subchondral bone during the progression of OA. METHODS: A medial meniscal tear (MMT) operation was performed in 128 adult Sprague Dawley rats to induce OA. At 2, 4, 8, and 12 weeks following the MMT operation, cartilage degeneration was evaluated using toluidine blue O staining, whereas changes in the microarchitecture indices and tissue mineral density (TMD), mineral-to-collagen ratio, and intrinsic mechanical properties of subchondral bone plates (BPs) and trabecular bones (Tbs) were measured using micro-computed tomography scanning, confocal Raman microspectroscopy and nanoindentation testing, respectively. RESULTS: Cartilage degeneration occurred and worsened progressively from 2 to 12 weeks after OA induction. Microarchitecture analysis revealed that the subchondral bone shifted from bone resorption early (reduced trabecular BV/TV, trabecular number, connectivity density and trabecular thickness [Tb.Th], and increased trabecular spacing (Tb.Sp) at 2 and 4 weeks) to bone accretion late (increased BV/TV, Tb.Th and thickness of subchondral bone plate, and reduced Tb.Sp at 8 and 12 weeks). The TMD of both the BP and Tb displayed no significant changes at 2 and 4 weeks but decreased at 8 and 12 weeks. The mineral-to-collagen ratio showed a significant decrease from 4 weeks for the Tb and from 8 weeks for the BP after OA induction. Both the elastic modulus and hardness of the Tb showed a significant decrease from 4 weeks after OA induction. The BP showed a significant decrease in its elastic modulus from 8 weeks and its hardness from 4 weeks. CONCLUSION: The microarchitecture, mineralization and mechanical properties of subchondral bone changed in a time-dependent manner as OA progressed.

Bactericidal properties and biocompatibility of a gentamicin-loaded Fe3O4/carbonated hydroxyapatite coating.

Postoperative implant-associated infection remains a serious complication in total joint arthroplasty (TJA) surgery. The addition of antibiotics to bone cement is used as an antimicrobial prophylaxis in cemented joint arthroplasty; however, in cementless arthroplasty, there are no comparable measures for the local delivery of antibiotics. In this study, a gentamicin-loaded Fe3O4/carbonated hydroxyapatite coating (Gent-MCHC) was fabricated according to the following steps: (i) deposition of Fe3O4/CaCO3 particles on Ti6Al4V substrates by electrophoretic deposition; (ii) conversions of MCHC from Fe3O4/CaCO3 coatings by chemical treatment; and (iii) formation of Gent-MCHC by loading gentamicin into MCHC. MCHC possessed mesoporous structure with a pore size of about 3.8 nm and magnetic property with the saturation magnetization strength of about 4.03 emu/g. Gent-MCHC had higher drug loading efficiency and drug release capacity, and superior biocompatibility and mitogenic activity than Ti6Al4V. Moreover, Gent-MCHC deterred bacterial adhesion and prevented biofilm formation. These results demonstrate that Gent-MCHC can be used as a local drug delivery system to prevent implant-associated infection in TJA surgery.

Increased peripheral proinflammatory T helper subsets contribute to cardiovascular complications in diabetic patients.

BACKGROUND: Coronary atherosclerotic heart disease (CHD) is one of the major concerns in type 2 diabetes (T2D). The systemic chronic inflammation has been postulated to bridge the increased risk of cardiovascular disease and T2D. We formulated that increased peripheral proinflammatory T helper subsets contributed to the development of cardiovascular complications in diabetic patients. METHODS: The frequencies of peripheral total CD4+ T helper cells, proinflammatory Th1, Th17, and Th22 subsets were determined by flow cytometry in diabetic patients with or without CHD (n = 42 and 67, resp.). RESULTS: Both peripheral frequencies and total numbers of Th1, Th17, and Th22 cells were further increased in diabetic patients with CHD. Logistic regression and categorical cross-table analysis further confirmed that increased proinflammatory Th subsets, especially Th22, were independent risk factors of cardiovascular complication in diabetes. Elevated Th subsets also correlated with increased CRP levels and the atherogenic index of plasma. Moreover, Th1 frequency and Th22 numbers demonstrated remarkable potential in predicting CHD in diabetes. CONCLUSIONS: Increased peripheral proinflammatory T helper subsets act in concert and contribute to the increased prevalence of diabetic cardiovasculopathy. The recently identified Th22 cells might play an independent role in CHD and represent a novel proxy for cardiovascular risks in diabetes.

Calcineurin/NFAT pathway mediates wear particle-induced TNF-α release and osteoclastogenesis from mice bone marrow macrophages in vitro.

AIM: To investigate the roles of the calcineurin/nuclear factor of activated T cells (NFAT) pathway in regulation of wear particles-induced cytokine release and osteoclastogenesis from mouse bone marrow macrophages in vitro. METHODS: Osteoclasts were induced from mouse bone marrow macrophages (BMMs) in the presence of 100 ng/mL receptor activator of NF-κB ligand (RANKL). Acridine orange staining and MTT assay were used to detect the cell viability. Osteoclastogenesis was determined using TRAP staining and RT-PCR. Bone pit resorption assay was used to examine osteoclast phenotype. The expression and cellular localization of NFATc1 were examined using RT-PCR and immunofluorescent staining. The production of TNFα was analyzed with ELISA. RESULTS: Titanium (Ti) or polymethylmethacrylate (PMMA) particles (0.1 mg/mL) did not significantly change the viability of BMMs, but twice increased the differentiation of BMMs into mature osteoclasts, and markedly increased TNF-α production. The TNF-α level in the PMMA group was significantly higher than in the Ti group (96 h). The expression of NFATc1 was found in BMMs in the presence of the wear particles and RANKL. In bone pit resorption assay, the wear particles significantly increased the resorption area and total number of resorption pits in BMMs-seeded ivory slices. Addition of 11R-VIVIT peptide (a specific inhibitor of calcineurin-mediated NFAT activation, 2.0 µmol/L) did not significantly affect the viability of BMMs, but abolished almost all the wear particle-induced alterations in BMMs. Furthermore, VIVIT reduced TNF-α production much more efficiently in the PMMA group than in the Ti group (96 h). CONCLUSION: Calcineurin/NFAT pathway mediates wear particles-induced TNF-α release and osteoclastogenesis from BMMs. Blockade of this signaling pathway with VIVIT may provide a promising therapeutic modality for the treatment of periprosthetic osteolysis.

[Double cladding ytterbium doped superfluorescence fiber source with 3 dB bandwidth reaching up to 80 nm].

The present paper reports a double pass forward superfluorescent fiber source (SFS), which uses a length of large mode area double cladding ytterbium doped fiber as gain medium. The maximum output power of this SFS is 341 mW. With the output power between 201 and 341 mW, the 3dB bandwidth of this SFS was more than 80 nm. This is the widest 3 dB bandwidth obtained from ytterbium doped SFS. The output power of the SFS linearly increased with the increment of the pump source injected current. It's output power is not very high, but under normal circumstances, it could meet the needs of the SFS. From the energy level structure of ytterbium ions and the absorption cross-section/emission cross section of ytterbium ions in quartz substrate, the physical mechanisms responsible for superfluorescence were analyzed. This double-cladding ytterbium-doped superfluorescent fiber laser benefits from the superfluorescence radiation near 1 025 and 1 075 nm, so the superfluorescence with 3 dB bandwidth reaching up to 80 nm could be obtained.

2-{(1R,2R)-2-[Bis(4-methyl-benz-yl)amino]-cyclo-hex-yl}isoindoline-1,3-dione.

In the title mol-ecule, C(30)H(32)N(2)O(2), the two tolyl rings form dihedral angles of 65.8 (1) and 6.6 (1)° with the isoindole-1,3-dione mean plane. The cyclo-hexane ring adopts a chair conformation.

[Study on correlation of insulin resistance with TCM syndrome type and activity of fibrinolytic system in patients with coronary arterial disease].

OBJECTIVE: To study the correlation of insulin resistance (IR) with TCM syndrome type and activity of fibrinolytic system in patients with coronary arterial disease (CAD). METHODS: One hundred and twelve CAD patients were classified according to TCM Syndrome into 4 types, the Xin-blood stasis (XBS) type, the phelgm blocking Xin-channel (PBXC) type, the Qi-insufficiency with blood stasis (QIBS) type and the both Qi-Yin deficiency (QYD) type. Patients' fasting blood glucose (FBG), fasting blood insulin (FIns) were measured, the insulin sensitive index (ISI) calculated. Data were compared between various types, also with those obtained from 30 healthy persons in the control group respectively. Moreover, activity of tissue plasminogen activator (t-PA) and content of plasminogen activator inhibitor-1 (PAI-1) were determined in 90 patients selected from the 112 to conduct linear correlation analysis of IR with t-PA activity and PAI-1 content. RESULTS: FBG and FIns levels in the CAD patients were higher than those in the healthy control significantly (P < 0.01); ISI in the 4 syndrome type of CAD patients were all lower than that in the control (P < 0.01). IR existed in all the 4 types, but the level in the XBS type and the PBXC type was more severe than in the other two types. Correlation analysis showed that IR was correlated with t-PA activity and PAI-1 content (P < 0.01). CONCLUSION: IR often exists in CAD patients, the severity of IR varies in patients of different TCM syndrome types, and IR is correlated with the abnormality of fibrinolytic system activity.