Long-term results of the metaphyseal-loading anterolaterally flared anatomic femoral stem for total hip arthroplasty.

Background: Patients with secondary hip osteoarthritis due to developmental dysplasia of the hip (DDH) often have abnormal femoral morphology, making stem design critical for long-term outcomes. The FMS-anatomic stem previously demonstrated favourable mid-term results. Its successor, the Anatomic Fit stem, was developed with a reduced hydroxyapatite-coated area to enhance proximal load transfer and a narrower lateral flare to facilitate insertion.

Evaluation of -[C]PK11195 PET/MRI for Spinal Cord-Related Neuropathic Pain in Patients with Cervical Spinal Disorders.

Activated microglia are involved in secondary injury after acute spinal cord injury (SCI) and in development of spinal cord-related neuropathic pain (NeP). The aim of the study was to assess expression of translocator protein 18 kDa (TSPO) as an indicator of microglial activation and to investigate visualization of the dynamics of activated microglia in the injured spinal cord using PET imaging with -[C]PK11195, a specific ligand for TSPO. In SCI chimeric animal models, TSPO was expressed mainly in activated microglia.

Thermodynamic Dissection of Potency and Selectivity of Cytosolic Hsp90 Inhibitors.

The cytosolic Hsp90-selective inhibitor TAS-116 has an acceptable safety profile and promising antitumor activity in clinical trials. We examined the binding characteristics of TAS-116 and its analogs to determine the impact of the ligand binding mode on selectivity for cytosolic Hsp90. Analyses of the co-crystal structure of Hsp90 and inhibitor TAS-116 suggest that TAS-116 interacts with the ATP-binding pocket, the ATP lid region, and the hydrophobic pocket.

Discovery of 3-Ethyl-4-(3-isopropyl-4-(4-(1-methyl-1 H-pyrazol-4-yl)-1 H-imidazol-1-yl)-1 H-pyrazolo[3,4- b]pyridin-1-yl)benzamide (TAS-116) as a Potent, Selective, and Orally Available HSP90 Inhibitor.

The molecular chaperone heat shock protein 90 (HSP90) is a promising target for cancer therapy, as it assists in the stabilization of cancer-related proteins, promoting cancer cell growth, and survival. A novel series of HSP90 inhibitors were discovered by structure-activity relationship (SAR)-based optimization of an initial hit compound 11a having a 4-(4-(quinolin-3-yl)-1 H-indol-1-yl)benzamide structure. The pyrazolo[3,4- b]pyridine derivative, 16e (TAS-116), is a selective inhibitor of HSP90α and HSP90β among the HSP90 family proteins and exhibits oral availability in mice.

Comparison of Mesenchymal Stromal Cells Isolated from Murine Adipose Tissue and Bone Marrow in the Treatment of Spinal Cord Injury.

The use of mesenchymal stromal cell (MSC) transplantation to repair the injured spinal cord has shown consistent benefits in preclinical models. However, the low survival rate of grafted MSC is one of the most important problems. In the injured spinal cord, transplanted cells are exposed to hypoxic conditions and exposed to nutritional deficiency caused by poor vascular supply.

Surgical treatment of low lumbar osteoporotic vertebral collapse: a single-institution experience.

Objective: Low lumbar osteoporotic vertebral collapse (OVC) has not been well documented compared with OVC of the thoracolumbar spine. The differences between low lumbar and thoracolumbar lesions should be studied to provide better treatment. The aim of this study was to clarify the clinical and imaging features as well as outcomes of low lumbar OVC and to discuss the appropriate surgical treatment.

Extensive Loss of Tibialis Anterior Tendon: Surgical Repair With Split Tendon Transfer of Tibialis Posterior Tendon: A Case Report.

Extensive damage of the tibialis anterior tendon is rare and mainly caused by trauma. Surgical treatment of these injuries can become challenging owing to the limited availability of autogenous graft resources for reconstruction of the defect. In the present case report, we describe a large defect in the midfoot soft tissue after a traffic injury, which included complete loss of the tibialis anterior tendon.

TAS-116, a highly selective inhibitor of heat shock protein 90α and β, demonstrates potent antitumor activity and minimal ocular toxicity in preclinical models.

The molecular chaperone HSP90 plays a crucial role in cancer cell growth and survival by stabilizing cancer-related proteins. A number of HSP90 inhibitors have been developed clinically for cancer therapy; however, potential off-target and/or HSP90-related toxicities have proved problematic. The 4-(1H-pyrazolo[3,4-b]pyridine-1-yl)benzamide TAS-116 is a selective inhibitor of cytosolic HSP90α and β that does not inhibit HSP90 paralogs such as endoplasmic reticulum GRP94 or mitochondrial TRAP1.

Solid-phase synthesis and biological activity of a combinatorial cross-conjugated dienone library.

The solid-phase synthesis of a combinatorial cross-conjugated dienone library based on the structure of clavulones and their biological activity are reported. Clavulones are a family of marine prostanoids, and are composed of a cross-conjugated dienone system bearing two alkyl side-chains. The cross-conjugated dienone system irreversibly reacted with two nucleophiles.

A novel cinnamic acid derivative that inhibits Cdc25 dual-specificity phosphatase activity.

The Cdc25 dual-specificity phosphatases are key regulators of cell cycle progression through activation of cyclin-dependent kinases (Cdk). Three homologs exist in humans: Cdc25A, Cdc25B, and Cdc25C. Cdc25A and Cdc25B have oncogenic properties and are overexpressed in some types of tumors.

Effective irreversible alkylating reagents based on the structure of clavulones.

We describe the design and synthesis of alkylating reagents based on the structure of clavulones. They are composed of cross-conjugated dienone system and irreversibly reacted with two nucleophiles under mildly basic conditions via beta-elimination. Hydroxyl derivative 7b showed the highest reactivity toward thiols and showed the strongest cytotoxicity in Hela S3 cells among the three derivatives having a different protecting group at the tert-hydroxyl group.