Plumbagin is a NF-κB-inducing kinase inhibitor with dual anabolic and antiresorptive effects that prevents menopausal-related osteoporosis in mice

Hydroxychloroquine and a low activity bisphosphonate conjugate prevent and reverse ovariectomy-induced bone loss in mice through dual antiresorptive and anabolic effects

“…Bone histomorphometric analysis: After micro-CT scanning, L3-L5 vertebrae were decalci ed for 3 wk using 10% EDTA at 4°C, processed, and embedded in para n. 3-µm-thick sections at the center of the vertebrae with fewest trabeculae, selected from a series of continuously cut sections to ensure the measurement of all the sections was comparable, were blindly quanti ed for histomorphometric parameters, including the structural trabecular bone parameters, BV/TV (%), Tb.Th (µm), Tb.N (#/mm), Tb.Sp (µm), and OB surfaces on H&E-stained sections, and OC parameters on TRAP-stained sections using an OsteoMeasure Image Analysis System (Osteometrics, Decatur, GA) 50,51 following the recommendations of the ASBMR Histomorphometry Nomenclature Committee 53 . T12 to L2 vertebrae were processed as LR white plastic-embedded blocks, as we reported previously 50,51 . 3 µm-thick plastic sections were cut using a carbide steel knife on a Shandon Microtome.…”

“…To determine if a low dose of HABP-HCQ can treat established OVX-induced bone loss, 3-mon-old female C57Bl6 mice were ovariectomized and subsequently given different doses of HABP-HCQ, HCQ, HABP or PTH for 4 wk from the 5 th wk post-surgery when bone loss in the vertebrae of OVX mice was confirmed by micro-CT. The mice were given injections of calcein (5 mg/kg) on the 5 th and last day before sacrifice, following our standard protocol to assess bone formation parameters 50 , 51 . After the mice were euthanized, the spinal bones were collected for micro-CT scanning, followed by histologic analysis of OBs and OCs in paraffin-embedded sections or dynamic bone formation parameters in plastic-embedded sections.…”

“…3 μm-thick plastic sections were cut using a carbide steel knife on a Shandon Microtome. Sections at the center of the vertebrae were collected to evaluate the dynamic parameters of bone formation using an OsteoMeasure Image Analysis System, as we reported previously 50 , 51 , following the recommendations of the ASBMR Histomorphometry Nomenclature Committee 53 .…”

Lipopolysaccharide sensitizes the therapeutic response of breast cancer to IAP antagonist

“…The cultured MDA-MB-231 cells at sub-confluence in 100-mm dishes were treated with vehicle, SM-164, LPS, or SM-164/LPS −/+ TLR4 inhibitor or MyD88 inhibitor 4210 ( 42 ) for 8 h. The cells were lysed with M-PER mammalian protein extraction reagent (Thermo Scientific, Waltham, MA, USA) containing a protease inhibitor cocktail. As we reported recently ( 43 ), 20 μg of whole-cell lysate protein was loaded in 10% sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS-PAGE) gels and transferred onto polyvinylidene difluoride membranes. Membranes were incubated overnight with primary antibody for MyD88, h/m cIAP pan, or β-actin or GAPDH followed by incubation with horseradish peroxidase-linked secondary antibody (Bio-Rad, Hercules, CA, USA) for 2 h. The membranes were exposed to enhanced chemiluminescence (ECL) substrate, and signals were detected by a Bio-Rad imaging system.…”

The Therapeutic Potential of Targeting NIK in B Cell Malignancies

“…Some in vitro studies have shown promising results with NIK inhibition in Hodgkin lymphoma (66) and mantle cell lymphoma (MCL) (49), yet these studies did apply inhibitors designed before publication of the crystal structure of NIK in 2012 (12,13). Furthermore, some studies report NIK inhibition after application of pan-kinase inhibitors or naturally occurring compounds that inhibit a wide spectrum of kinases (67)(68)(69). Virtually all inhibitors designed to specifically target NIK are small molecule inhibitors aimed at binding the catalytic ATPbinding site, and this type we will discuss here.…”