Objective To characterize the effects of parathyroid hormone (PTH) and alendronate (Alend) on the osteochondral tissue of temporomandibular joint (TMJ). Materials and Methods Ninety-six male and female transgenic reporter mice, 4 to 5 weeks old were divided into 6 groups: (1) Control group: Saline was injected daily for 14 days; (2) PTH: PTH was injected daily for 14 days; (3) Alend: Alend was injected every alternate days for 14 days; (4) Combined PTH and Alend: PTH was injected daily and Alend injected every alternate days for 14 days; (5) PTH then Alend: PTH was injected daily for 14 days followed by Alend injections in alternate days for 14 days; and (6) PTH wait Alend: PTH was injected daily for 14 days. There was a waiting period of 1 week before administration of Alend in alternate days for 14 days. Mice were injected with 5-ethnyl-2′-deoxyuridine (EdU), 48 and 24 hours prior to euthanization. Results There was significant increase in bone volume and decrease in osteoclastic activity in groups in which Alend was administered after PTH in both gender. There was significant increase in cartilage thickness with PTH or Alend alone in females, whereas in males, PTH alone led to increase in cartilage thickness. Chondrocyte apoptosis was significantly decreased with PTH or Alend alone in both male and female. Matrix metallopeptidase 13, and aggreganase-2 (ADAMTS5) expression were significantly decreased with PTH and Alend alone in both gender. Conclusion PTH and Alend administration causes anabolic effects in the osteochondral tissue of TMJ.
AbstractThe spatial information of soil organic matter (SOM) is crucial for precision agriculture and environmental modeling. It is, however, difficult to obtain the regional details of SOM by dense sampling due to the high cost. Although a variety of interpolation methods are available for mapping SOM at regional scales, accurate prediction usually needs densely distributed samples and requires the interpolated variable to meet some constraints such as spatial stationarity. This paper introduces the Geographically Weighted Regression (GWR) technique as an alternative approach for SOM mapping. We interpolated the spatial distribution of SOM based on a limited number of samples with the incorporation of multiple independent variables. We also compared GWR with the ordinary least squares regression approach in mapping SOM. Results indicated that GWR could capture more local details and improve the prediction accuracy. However, more attention should be paid to the selection of independent variables.Keywords:: soil organic mattermappinggeographically weighted regressionordinary least squaresenvironmental modeling AcknowledgementsSupport for this work was provided by the National Natural Science Foundation of China (No. 41271232), the Natural Science Foundation of Fujian Province, China (No. 2012J01179), and the Science and Technological Project of the Educational Commission of Fujian Province, China (No. JA11202). We thank the two anonymous reviewers for their constructive comments.
The epidermal growth factor receptor (EGFR) and its ligands function in diverse cellular functions including cell proliferation, differentiation, motility, and survival. EGFR signaling is important for the development of many tissues, including skin, lungs, intestines, and the craniofacial skeleton. We have now determined the role of EGFR signaling in endochondral ossification. We analyzed long bone development in EGFR-deficient mice. EGFR deficiency caused delayed primary ossification of the cartilage anlage and delayed osteoclast and osteoblast recruitment. Ossification of the growth plates was also abnormal resulting in an expanded area of growth plate hypertrophic cartilage and few bony trabeculae. The delayed osteoclast recruitment was not because of inadequate expression of matrix metalloproteinases, including matrix metalloproteinase-9, which have previously been shown to be important for osteoclast recruitment. EGFR was expressed by osteoclasts, suggesting that EGFR ligands may act directly to affect the formation and/or function of these cells. EGFR signaling regulated osteoclast formation. Inhibition of EGFR tyrosine kinase activity decreased the generation of osteoclasts from cultured bone marrow cells.
The Warburg effect, glycolytic production of ATP under aerobic conditions, is found to be a universal feature of most cancer cells. Our study was aimed to determine whether rosmarinic acid (RA) had the anti-Warburg effect activity against colorectal carcinoma. Furthermore, the mechanism for the anti-Warburg effect by RA would be investigated. In our study, we found that RA suppressed glucose consumption and lactate generation in colorectal carcinoma cells; meanwhile, RA inhibited the expression of transcription factor hypoxia-inducible factor-1α (HIF-1α) that affects the glycolytic pathway. Chronic inflammation is a key promoting factor of the Warburg effect. As we supposed, the present study also showed that RA could not only repress proinflammatory cytokines using enzyme-linked immunosorbent assay but it could also suppress microRNAs related to inflammation by real-time PCR. Therefore, we proposed that RA may inhibit the Warburg effect by suppressing the inflammatory response of colorectal carcinoma cells. Recent studies have provided evidence that miR-155 was an important mediator between inflammation and carcinogenesis. We further showed that miR-155 acted to repress the Warburg effect through the mechanism of inactivating the IL-6/STAT3 pathway. Above all, RA might be a potential therapeutic agent against colorectal carcinoma.
Background and Aims: In obesity, depletion of KCs expressing CRIg (complement receptor of the Ig superfamily) leads to microbial DNA accumulation, which subsequently triggers tissue inflammation and insulin resistance. However, the mechanism underlying obesity-mediated changes in KC complement immune functions is largely unknown. Approach and Results: Using KC-specific deactivated Cas9 transgenic mice treated with guide RNA, we assessed the effects of restoring CRIg or the serine/arginine-rich splicing factor 3 (SRSF3) abundance on KC functions and metabolic phenotypes in obese mice. The impacts of weight loss on KC responses were evaluated in a diet switch mouse model. The role of SRSF3 in regulating KC functions was also evaluated using KC-specific SRSF3 knockout mice. Here, we report that overexpression of CRIg in KCs of obese mice protects against bacterial DNA accumulation in metabolic tissues. Mechanistically, SRSF3 regulates CRIg expression, which is essential for maintaining the CRIg+ KC population. During obesity, SRSF3 expression decreases, but it is restored with weight loss through a diet switch, normalizing CRIg+ KCs. KC SRSF3 is also repressed in obese human livers. Lack of SRSF3 in KCs in lean and obese mice decreases their CRIg+ population, impairing metabolic parameters. During the diet switch, the benefits of weight loss are compromised due to SRSF3 deficiency. Conversely, SRSF3 overexpression in obese mice preserves CRIg+ KCs and improves metabolic responses. Conclusions: Restoring SRSF3 abundance in KCs offers a strategy against obesity-associated tissue inflammation and insulin resistance by preventing bacterial DNA accumulation.
Background Osteoporosis is a progressive bone disease, which is characterized by high bone resorption, and low bone density and mass. Osteoporosis elevates the risk of bone fragility and fracture, which leads to significant morbidity and poor life quality. Objectives The current study focuses to explore the anti-osteoporosis activity of cynaropicrin against the ovariectomized (OVX)-induced osteoporosis in rats. Materials and Methods The OVX method was performed on the female rats to induce osteoporosis and then treated with 10 and 20 mg/kg of cynaropicrin, respectively, for 16 weeks. The uterus and femur tissues were excised from rats after the sacrification. The biomechanical properties of femur bones were analyzed to detect the stiffness, maximum load, young modulus, and energy absorption. The levels of acid phosphatase (ACP), bone-gla-protein (BGP), and estradiol (E2) in the serum were analyzed. The status of TNF-α, IL-6, IL-1β, osteoprotegerin (OPG), and receptor activator of nuclear factor-κB ligand (RANKL) was analyzed in the serum samples of experimental rats. The femur tissues were examined by histopathological analysis. Results The cynaropicrin treatment effectively increased the uterine and femoral weight in the OVX rats. The stiffness, maximum load, young modulus, energy, and femoral length were effectively increased by the cynaropicrin treatment. Cynaropicrin decreased the levels of BGP and ACP and increased the E2 level. The Cr, Ca, and P levels were appreciably increased and TNF-α, IL-6 and IL-1β levels were decreased by cynaropicrin on the OVX rats. The cynaropicrin treatment also increased the OPG and reduced the RANKL in the OVX rats. The histological findings revealed that cynaropicrin improved the femur trabecular bone microarchitecture in the OVX rats. Conclusion Our findings revealed that cynaropicrin increased the femoral weight and length, restored bone turnover markers and mineral profiles, and decreased inflammatory markers.
Objective The goal of this study was to report on the expression of Brachyury and Galectin-3 protein in chordoma and their correlation with the patients' clinical characteristics.Methods The author retrospectively studied data from 28 patients with skull-base chordoma who had undergone surgeries in the Department of Skullbase and Brain Stem of Beijing Tiantan Hospital between 2005 and 2012,and follow up was performed through recheck in out-patient department,telephone and letter.Paraffin-embedded chordoma specimens of these patients was made after their surgeries,the pathological type can be confirmed by hematoxylin-eosin (HE) staining,Brachyury and Galectin-3 expression was investigated by immunohistochemistry.Spss 13.0 was used to analysis the related data.Results In these 28 specimens,23 are typical type,1 is chondroid type and 4 are atypical type,all specimens contain chordoma tumor cells whichexpressbrachyury and Galectin-3 strongly.Brachyury protein level is lower in atypical chordomas than that in typical chordomas (P =0.011) and chondroid chordoma (P =0.004),while the atypical ones express higher level Galectin-3 than typical chordomas (P =0.018).Conclusions All specimens expressed Brachyury and Galectin-3 strongly,and the expression level of these two proteins have no correlation with patients' age,sex,history of treatment and size of tumor while correlate obviously with their pathologies.The atypical chordoma is comparatively more malignant than typical chordoma and chondroid chordoma.Brachyury level is lower in atypical chordomas than that in the other two types; Gal-3 protein level is higher in atypical chordomas than that in the typical ones.Brachyury and Gal-3 protein level of the tumor are important factors in forecasting patients' prognosis.
Key words:
Chordoma; Brachyury ; Galectin-3 ; Immunohistochemistry
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