Lactic acid induces lactate transport and glycolysis/OXPHOS interconversion in glioblastoma.

The Warburg effect is a dominant phenotype of most tumor cells. Recent reports have shown that the Warburg effect can be reprogrammed by the tumor microenvironment. Lactic acidosis and glucose deprivation are the common adverse microenvironments in solid tumor. The metabolic reprogramming induced by lactic acid and glucose deprivation remains to be elucidated in glioblastoma. Here, we show that, under glucose deprivation, lactic acid can preserve high ATP levels and resist cell death in U251 cells. At the same time, we find that MCT1 and MCT4 are significantly highly expressed. The metabolic regulation factor HIF-1α decreased and C-MYC increased. Nuclear respiratory factor 1 (NRF1) and oxidative phosphorylation (OXPHOS)-related proteins (NDUFB8, ND1) are all distinctly increased. Therefore, lactic acid can induce lactate transport and convert the dominant Warburg effect to OXPHOS. Through bioinformatics analysis, the high expression of HIF-1α, MCT1 or MCT4 indicate a poor prognosis in glioblastoma. In addition, in glioblastoma tissue, HIF-1α, MCT4 and LDH are highly expressed in the interior region, and their expression is decreased in the lateral region. MCT1 can not be detected in the interior region and is highly expressed in the lateral region. Hence, different regions of glioblastoma have diverse energy metabolic pathways. Glycolysis occurs mainly in the interior region and OXPHOS in the lateral region. In general, lactic acid can induce regional energy metabolic reprogramming and assist tumor cells to adapt and resist adverse microenvironments. This study provides new ideas for furthering understanding of the metabolic features of glioblastoma. It may promote the development of new therapeutic strategies in GBM.

Functional bundles of the medial patellofemoral ligament.

The purpose of this study was to explore the anatomy and evaluate the function of the medial patellofemoral ligament (MPFL). Anatomical dissection was performed on 12 fresh-frozen knee specimens. The MPFL is a condensation of capsular fibers, which originates at the medial femoral condyle. It runs transversely and inserts to the medial edge of the patella. With the landmark of the medial femur epicondyle (MFE), the femoral origination was located: just 8.90 ± 3.27 mm proximally and 13.47 ± 3.68 mm posteriorly to the MFE. The most interesting finding in present study was functional bundles of its patellar insertion. Approximately from the femoral origination point, fibers of the MPFL form two relatively concentrated fiber bundles: the inferior-straight bundle and the superior-oblique bundle. The whole length of each was 71.78 ± 5.51 and 73.67 ± 5.40 mm, respectively. The included angle between bundles was 15.1° ± 2.1°. Although the superior-oblique bundle and the inferior-straight bundle run on the patellar MPFL inferiorly and superiorly, respectively, as their name indicates, the two bundles are not entirely separated, which make MPFL one intact structure. The inferior-straight bundle is the main static soft tissue restraints where the superior-oblique bundle associated with vastus medialis obliquus (VMO) is to serve as the main dynamic soft tissue restraints. So this finding may provide the theoretical foundation for the anatomical reconstruction of the MPFL and shed lights on the future researchers.

[The clinical value of cartilaginous surface and corresponding osseous contour of patellofemoral joint].

OBJECTIVE: to investigate if the cartilaginous surface and corresponding osseous contour of the patellofemoral joint match in the axial plane for providing theoretical basis with evaluating alignment of patellofemoral joint and designing the part of patellofemoral joint in knee prosthesis. METHODS: from January 2009 to March 2010, 9 human cadaver knees were prepared, which chandra of patellofemoral joint didn't degenerate. Each specimen was sectioned in the axial plane at 20° to 30° knee flax. The cross-sections revealed characteristics in the bony anatomy and corresponding articular surface geometry of the patellofemoral joint in the axial plane. Evaluating parameters included osseous patella congruence angle (OPCA), chondral patella congruence angle (CPCA), patella chondral convex point parameter (PCCPP), patella subchondral osseous convex point parameter (PSOCPP), the parameters of the deepest (chondral or osseous) point of the intercondylar sulcus. After that, the osseous and cartilaginous contours and subchondral osseous contours of the patella in the axial plane were analyzed through MRI data of 11 patients who didn't degenerate in patellofemoral joint cartilage. Parameters as same as cadaver knees were compared. RESULTS: data from specimens of OPCA was (-4.5 ± 1.1)°, CPCA was (0.5 ± 0.8)°, PCCPP was 1.13 ± 0.11, PSOCPP was 1.67 ± 0.14, PCDPIS was 1.35 ± 0.28, PODPIS was 1.38 ± 0.33. Date from MRI of OPCA was (-3.8 ± 1.4)°, CPCA was (0.7 ± 1.0)°, PCCPP was 1.05 ± 0.21, PSOCPP was 1.73 ± 0.18, PCDPIS was 1.41 ± 0.21, PODPIS was 1.37 ± 0.27. The patella exhibited significant differences in the bony vs. chondral anatomy (P < 0.05), but the intercondylar sulcus nearly match in the bony vs. chondral anatomy. CONCLUSIONS: the cartilaginous surface and corresponding osseous contour of the patella don't match in the patellofemoral joint axial plane, but that of the trochlea nearly matches. This is very important for accurately evaluating alignment of patellofemoral joint because the normal osseous alignment of patellofemoral joint don't represent the normal alignment and helpful for designing the part of patellofemoral joint in knee prosthesis.