Huoxue Jiedu Recipe represses mitochondrial fission to alleviate submandibular gland inflammation in Sjögren's syndrome.

Sjögren's syndrome (SS) is the second most common autoimmune rheumatism. Huoxue Jiedu Recipe (HXJDR) is a kind of traditional Chinese medicine with a variety of pharmacological functions; however, its biological function in SS has not been studied yet. Peripheral blood mononuclear cells (PBMCs) and serum samples were isolated from healthy controls and patients with SS. NOD/Ltj mice were used for developing the SS mouse model. The levels of inflammatory cytokines and NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome-related markers as well as dynamin-related protein 1 (Drp1) were determined by ELISA, quantitative real-time PCR, and western blot analysis, respectively. Hematoxylin and eosin and TUNEL staining detected the pathological damage. A transmission electron microscope was used to observe the mitochondrial microstructure. Inflammatory cytokines IL-18, IL-1ß, B-cell activating factor (BAFF), BAFF-receptor (BAFF-R), IL-6, and TNF-α in serum samples and NLRP3 inflammasome-related makers (NLRP3, cysteinyl aspartate-specific proteinase 1 [caspase-1], apoptosis-associated speck-like protein containing a caspase-1 recruitment domain [ASC], IL-1ß) in PBMCs were greatly upregulated in patients with SS. Furthermore, cytoplasmic phosphorylation of Drp1 and mitochondrial Drp1 level were significantly increased in PBMCs, while mitochondrial swelling and fuzzy inner ridge were observed in PBMCs of patients with SS, suggesting increased mitochondrial fission. Compared with control mice, SS mice showed decreased salivary flow rate, increased submandibular gland index, and more severe inflammatory infiltration and damage as well as mitochondrial fission in submandibular gland tissues. After HXJDR administration, these effects were significantly reversed. HXJDR treatment could alleviate the inflammatory infiltration and pathological damage in submandibular glands of SS mice by inhibiting Drp-1-dependent mitochondrial fission.

IGF-1 induces cellular senescence in rat articular chondrocytes via Akt pathway activation.

Cellular senescence decreases cell proliferation over time and is characterized by typical markers, including larger cell volume, a flattened morphology, irreversible cell cycle arrest, augmentation of senescence-associated ß-galactosidase (SA-ß-gal) activity and senescence-associated secretory phenotype. A variety of factors are implicated in the process of cellular aging, which mediates an organisms' lifespan. Insulin-like growth factor-1 (IGF-1) serves an essential role in regulating cell growth, division, proliferation and senescence. In the present study, the role of IGF-1 and the downstream Akt signaling pathway in rat articular chondrocyte senescence was assessed. The results of the current study demonstrated that IGF-1 promoted cellular senescence in rat articular chondrocytes via activation of SA-ß-gal and the upregulation of p53 and p21 mRNA and protein levels. IGF-1 enhanced Akt phosphorylation and treatment with Akt inhibitor, MK-2206, significantly suppressed the induction of these markers. Overall, the results indicated the involvement of IGF-1 and Akt in senescence exhibited by rat articular chondrocytes.

Comparison of the effects of exercise with chondroitin sulfate on knee osteoarthritis in rabbits.

BACKGROUND: The aim of the study is to compare the effects of exercise therapy with chondroitin sulfate (CS) therapy in an experimental model of osteoarthritis (OA). METHODS: Twenty-one New Zealand rabbits were randomly divided into four groups: normal group (N group, n = 3); OA control group (C group, n = 6); OA plus medication group (CS group, n = 6); and OA plus exercise group (E group, n = 6). Four weeks after modeling, the rabbits were subjected to exercise (artificial, 30 min/time, 4 times/week) or medicated with CS (2% CS, 0.3 ml/time, once/week) for 4 weeks. Histopathological changes in treated joints were examined after staining. X-ray and scanning electron microscopy was used to evaluate the different therapies by examining the surfaces and joint spaces of the articular cartilage. RT-qPCR was used to assess chondrogenic gene expression including Col2, Col10, mmp-13, il-1ß, adamats-5, and acan in the experimental groups. RESULTS: Histology showed both treatment groups resulted in cartilage that was in good condition, with increased numbers of chondrocytes, and the results of X-ray and scanning electron microscopy showed the therapeutic effect of exercise therapy is equivalent to CS therapy, surface articular cartilage was flat, and the of cartilage layer was thinning. All treated groups induced the expression of Col10 and Col2 and decreased expression of mmp-13, il-1ß, and adamats-5 compared with the control groups. The expression of acan was upregulated in the E group and downregulated in the CS group. Furthermore, expression of Col10 was higher and il-1ß was lower in the exercise group compared to that of the CS group. CONCLUSION: These results indicate that exercise has a positive effect on OA compare with CS, and it also supplies reference for the movement mode to improve function.

[Comparison between external fixator and DVR system for the treatment of AO type C distal radial fractures].

OBJECTIVE: To compare the clinical effects of external fixator versus DVR system for the treatment of AO type C distal radius fractures. METHODS: The clinical data of 52 patients with type C distal radial fractures treated with external fixator or DVR system respectively from January 2009 to December 2013 were analyzed retrospectively. In DVR system group, 31 patients were treated by open reduction and internal fixation with DVR system, involved 11 males and 20 females, with an average age of(47.3±10.9) years ranging from 24 to 65 years;according to AO/ASIF classification, 12 cases were type C1, 15 cases were type C2, 4 cases were type C3. In external fixator group, 21 patients were treated by closed reduction and cross wrist external fixation, involved 8 males and 13 females, with an average age of (48.1±12.1) years ranging from 26 to 69 years; according to AO/ASIF classification, 7 cases were type C1, 11 cases were type C2, 3 cases were type C3. The postoperative images, wrist joint functions and Gartland-Wetley scores were evaluated and compared. RESULTS: Thirty-one patients in DVR system group were followed up for 20.4 months(ranged from 13 to 36 months) and in external fixator group 21 patients were followed up for 17.1 months (ranged from 11 to 33 months) respectively. X-rays showed all fractures healed. The palm dip and radial inclination in the DVR system group were significantly better than in the external fixator group(P<0.05), while there was no significant difference in radial height and Gartland-Werley score(P>0.05). There was 1 case of wrist stiffness in the DVR system group; 2 cases of pin tract infection, 1 case of fixator loosening and 2 cases of wrist stiffness in the external fixator group. CONCLUSIONS: Clinical outcomes of DVR system fixation for type C distal radial fractures are better than that of external fixator fixation. However, DVR system fixation costs more and requires a secondary surgery to remove the internal fixation. The choices of surgical method depend on the clinical conditions of the patients.

Adhesion of osteoblast-like cell on silicon-doped TiO2 film prepared by cathodic arc deposition.

Silicon-doped TiO2 (Si-TiO2) and pure TiO2 films were deposited on titanium substrates by cathodic arc deposition technique. The surface characteristics of the films, such as surface topography, elemental composition and wettability, were studied. About 4.6 % Si was incorporated into the Si-TiO2 films with a water contact angle of about 83°. The adhesive behaviors of osteoblast-like MG63 cells on both films were investigated through cell counting assay, immunocytochemistry, real-time PCR and western blotting analysis. Cells cultured on the Si-TiO2 films had a greater cellular viability, stronger cytoskeleton and focal adhesion, and more cellular spreading than those on the pure TiO2 films. Moreover, the expression levels of integrin ß1 and focal adhesion kinase (FAK) genes, FAK and the phosphorylation of FAK proteins were up-regulated in cells cultured on the Si-TiO2 films. These results indicated that the Si-TiO2 films possess significantly enhanced cytocompatibility and provide potential solutions for the surface modification of implants in the future.

Predictive potential of glutathione S-transferase polymorphisms for prognosis of osteosarcoma patients on chemotherapy.

OBJECTIVE: To evaluate the predictive value of glutathione S-transferase (GST) gene polymorphisms for the prognosis of osteosarcoma patients receiving chemotherapy. METHODS: A total of 159 patients were included in our study between January 2005 and December 2007., with follow-up until January 2012. Genotyping was based upon the duplex polymerase-chain-reaction with the PCR-CTPP method. RESULTS: At the time of diagnosis, 15.4% of the patients presented with metastasis, while 22.3% developed metastasis during follow-up. At the time of final analysis on January 2012, the median follow-up was 45.5 months. Patients with null GSTM1 and GSTT1 had a higher event free survival rate than non-null genotype, but no significant association was found between the two genotypes and prognosis of osteosarcoma. Individuals with GSTP1 Val/Val genotype tended to live shorter than with the IIe/IIe genotype, and we found a significantly higher risk of death from osteosarcoma (adjusted HR=2.35, 95% CI=1.13-4.85). CONCLUSION: The GSTP1 gene polymorphism may have an important role in the prognosis of osteosarcoma patients with chemotherapy. Further analyses with larger samples and more genes encoding metabolizing and DNA repair enzymes are warranted.