Synthetic Studies on Amphirionin-5: Stereochemical Assignment/Reassignment of the C1–C9 Portion through Stereodivergent Synthesis

Synthesis of four diastereomers of the C1–C12 fragment of amphirionin-5 has been achieved in a convergent and stereodivergent manner. Detailed comparison of the ¹H and ¹³C NMR data of each compound with those reported for the natural product led to not only the stereochemical assignment of the relative configuration of the C4/C5 stereogenic centers but also reassignment of the proposed relative configuration at C9 of amphirionin-5

Three dimensional CT analysis of the change in rotational alignment in double level osteotomy after double level osteotomy performed for varus osteoarthritic knees

Purpose: To analyze the change in rotational alignment caused by double level osteotomy (DLO) based on comparative three-dimensional image analysis of pre- and postoperative CT images. Methods: Pre- and postoperative CT examination of the lower extremities were performed with informed consent for 39 consecutive knees undergoing DLO for varus knee deformity. The DLO procedure consisted of closed wedge distal femoral osteotomy (CWDFO) and open wedge high tibial osteotomy (OWHTO). Among those cases, 20 knees complicated with hinge fracture at the osteotomy site were excluded from the analysis to eliminate a confounding factor affecting the results. Consequently, data obtained from 19 knees were subjected to the study analysis while osteotomies with hinge fractures complications were excluded from the study. In the three-dimensional CT image analysis of axial plane images, femoral torsion (the angle between midline along the femoral neck axis and the tangent of the posterior edges of the medial/lateral femoral condyles) and tibial torsion (the angle between the tangent of the posterior edges of the medial/lateral tibial condyles and the transmalleolar axis) were measured. The torsion angle was measured in each of the femurs and the tibias on both pre- and postoperative CT axial images, and the change induced by the osteotomy was calculated and statistically(using Wilcoxon signed-rank test) compared. Results: The mean pre- and postoperative femoral torsion (anteversion) angles were 29.3° and 31.4° with a significant postoperative increase in internal rotation of the bony segment distal to the osteotomy(P = 0.002). On the tibial side, the mean pre- and postoperative torsion angles were 26.5° and 25.7°, indicating no significant postoperative change(P = 0.199)（NS）. Conclusions: This study showed that the DLO procedure (combining CWDFO and OWHTO) increased torsion (anteversion) of the femur by 2.1° on average while inducing no significant rotational change on the tibial side

Stereodivergent Synthesis and Configurational Assignment of the C1–C15 Segment of Amphirionin‑5

The relative configuration of the C3–C12 portion of amphirionin-5, a novel marine polyketide with potent cell proliferation-promoting activity, was established by the stereodivergent synthesis of six diastereomeric model compounds and comparison of their NMR spectroscopic data with those reported for the natural product. This study led to the elucidation of the relative configuration between C4/C5 and C9/C12 and to the reassignment of the proposed configuration of the C9 position of amphirionin-5

Characteristic Poses in Ballet in the Case of a Retired Classical Ballerina after Bilateral THA: A Case Report and Review of Literature

Background. Ballet dance involves extreme range of motion (ROM) in the hip joint. This ROM can cause injuries including labral strain, tears, and subluxation episodes. Case Presentation. A 69-year-old female classical ballet dance instructor presented bilateral hip pain. The plain radiograph showed end-stage osteoarthritic change in the bilateral hip. She could neither dance nor perform daily activities. Bilateral hybrid total hip arthroplasty (THA) was performed. After surgery, she was able to demonstrate the split position on the floor as an active classical ballerina. The plain radiograph was taken in the split position, and the radiograph did not show any characteristics of impingement or subluxation of the femoral head. Conclusion. She was able to continue working as a classical ballet instructor after bilateral THA. Additionally, any characteristics of impingement or subluxation of the femoral head were not revealed in the postoperative radiograph in the split position

Repression of the PRELP gene is relieved by histone deacetylase inhibitors through acetylation of histone H2B lysine 5 in bladder cancer.

BACKGROUND: Proline/arginine-rich end leucine-rich repeat protein (PRELP) is a member of the small leucine-rich proteoglycan family of extracellular matrix proteins, which is markedly suppressed in the majority of early-stage epithelial cancers and plays a role in regulating the epithelial-mesenchymal transition by altering cell-cell adhesion. Although PRELP is an important factor in the development and progression of bladder cancer, the mechanism of PRELP gene repression remains unclear. RESULTS: Here, we show that repression of PRELP mRNA expression in bladder cancer cells is alleviated by HDAC inhibitors (HDACi) through histone acetylation. Using ChIP-qPCR analysis, we found that acetylation of lysine residue 5 of histone H2B in the PRELP gene promoter region is a marker for the de-repression of PRELP expression. CONCLUSIONS: These results suggest a mechanism through which HDACi may partially regulate the function of PRELP to suppress the development and progression of bladder cancer. Some HDACi are already in clinical use, and the findings of this study provide a mechanistic basis for further investigation of HDACi-based therapeutic strategies

Infection with flaviviruses requires BCLXL for cell survival.

BCL2 family proteins including pro-survival proteins, BH3-only proteins and BAX/BAK proteins control mitochondria-mediated apoptosis to maintain cell homeostasis via the removal of damaged cells and pathogen-infected cells. In this study, we examined the roles of BCL2 proteins in the induction of apoptosis in cells upon infection with flaviviruses, such as Japanese encephalitis virus, Dengue virus and Zika virus. We showed that survival of the infected cells depends on BCLXL, a pro-survival BCL2 protein due to suppression of the expression of another pro-survival protein, MCL1. Treatment with BCLXL inhibitors, as well as deficient BCLXL gene expression, induced BAX/BAK-dependent apoptosis upon infection with flaviviruses. Flavivirus infection attenuates cellular protein synthesis, which confers reduction of short-half-life proteins like MCL1. Inhibition of BCLXL increased phagocytosis of virus-infected cells by macrophages, thereby suppressing viral dissemination and chemokine production. Furthermore, we examined the roles of BCLXL in the death of JEV-infected cells during in vivo infection. Haploinsufficiency of the BCLXL gene, as well as administration of BH3 mimetic compounds, increased survival rate after challenge of JEV infection and suppressed inflammation. These results suggest that BCLXL plays a crucial role in the survival of cells infected with flaviviruses, and that BCLXL may provide a novel antiviral target to suppress propagation of the family of Flaviviridae viruses