01). Following recent APM, people may adapt their gait to protect the operated knee from excessive loads, as evidenced by a lower maximum loading rate in the APM leg compared to controls, and a reduced peak F-z in the APM leg compared to the non-APM leg. No differences at follow-up may suggest an eventual return to more typical gait. However, the increase in peak F-z in the APM leg may be of concern for long-term joint health given the compromised function of the meniscus. (C) 2014 Elsevier Ltd. All rights reserved.”
“Background: This study investigated the potential involvement of
Axl signaling in polarization of tumor-associated macrophages (TAMs) in oral squamous cell carcinoma (OSCC). Methods: Condition medium (CM) from OSCC cells (OEC-M1 and YD38) were collected and their effects
on macrophage Pevonedistat nmr (THP-1) polarization were examined. Modulation of Axl, PI3/Akt, and NF-kappa B were performed PCI-32765 inhibitor to investigate their potential involvement in TAM polarization. Expression of pAxl and CD206 were analyzed by immunohistochemistry in OSCC tissues. Results: THP-1 polarized to M2 phenotype with increasing expression of interleukins, vascular endothelial growth factor, matrix metalloproteinase and CD206 upon treatment with CM of OSCC. Activated Axl signaling in OSCC enhanced M2 induction ability. Suppression of Axl signaling and inhibition of PI3/Akt and NF-kappa B diminished M2 induction. pAxl expression was significantly associated with distribution of CD206
positive cells in OSCC tissues. Conclusion: Axl signaling of OSCC involved in polarizing TAMs toward M2 phenotype. Induction of M2 phenotype macrophage polarization by OSCC cells might involve the Axl/PI3/Akt/NF-kappa B pathway. (C) 2015 Elsevier Ltd. All rights reserved.”
“The glucagonlike peptide 1 receptor (GLP-1R) is mainly expressed on beta-cells in the Wets of Langerhans and is therefore an attractive target for imaging of the beta-cell mass. In the present study, Ga-68-labeled exendin-4 was evaluated for PET imaging and quantification of GLP-1R in the pancreas. Methods: Dose drug discovery escalation studies of Ga-68-labeled 1,4,7-tris(carboxymethylaza)cyclododecane-10-azaacetyl (DO3A)-exendin-4 were performed in rats (organ distribution) and cynomolgus monkeys (PET/CT imaging) to determine the GLP-1R-specific tissue uptake in vivo. Pancreatic uptake (as determined by organ distribution) in healthy rats was compared with that in diabetic rats. GLP-1R occupancy in the cynomolgus pancreas was quantified with a 1-tissue-compartment model. Results: In rodents, uptake in the pancreas was decreased from the baseline by up to 90% (P < 0.0001) by coadministration of DO3A-exendin-4 at 100 mu g/kg. Pancreatic uptake in diabetic animals was decreased by more than 80% (P < 0.001) compared with that in healthy controls, as measured by organ distribution. GLP-1R occupancy in the cynomolgus pancreas after coinjection of DO3A-exendin-4 at 0.