Pathophysiological Mechanism of Bone Loss in Type 2 Diabetes Involves Inverse Regulation of Osteoblast Function by PGC-1α and Skeletal Muscle Atrogenes: AdipoR1 as a Potential Target for Reversing Diabetes-Induced Osteopenia.

Type 2 diabetes is associated with increased fracture risk and delayed fracture healing; the underlying mechanism, however, remains poorly understood. We systematically investigated skeletal pathology in leptin receptor-deficient diabetic mice on a C57BLKS background (db). Compared with wild type (wt), db mice displayed reduced peak bone mass and age-related trabecular and cortical bone loss.

Phytochemicals for breast cancer therapy: current status and future implications.

Breast cancer is one of the most common malignancies among women, representing nearly 30% of newly diagnosed cancers every year. Till date, various therapeutic interventions, including surgery, chemotherapy, hormonal therapy, and radiotherapy are available and are known to cause a significant decline in the overall mortality rate. However, therapeutic resistance, recurrence and lack of treatment in metastasis are the major challenges that need to be addressed.

Thioaryl naphthylmethanone oxime ether analogs as novel anticancer agents.

Employing a rational design of thioaryl naphthylmethanone oxime ether analogs containing functional properties of various anticancer drugs, a series of compounds were identified that displayed potent cytotoxicity toward various cancer cells, out of which 4-(methylthio)phenyl)(naphthalen-1-yl)methanone O-2-(diethylamino)ethyl oxime (MND) exhibited the best safety profile. MND induced apoptosis, inhibited migration and invasion, strongly inhibited cancer stem cell population on a par with salinomycin, and demonstrated orally potent tumor regression in mouse MCF-7 xenografts. Mechanistic studies revealed that MND strongly abrogated EGF-induced proliferation, migration, and tyrosine kinase (TK) signaling in breast cancer cells.

Orally active osteoanabolic agent GTDF binds to adiponectin receptors, with a preference for AdipoR1, induces adiponectin-associated signaling, and improves metabolic health in a rodent model of diabetes.

Adiponectin is an adipocytokine that signals through plasma membrane-bound adiponectin receptors 1 and 2 (AdipoR1 and -2). Plasma adiponectin depletion is associated with type 2 diabetes, obesity, and cardiovascular diseases. Adiponectin therapy, however, is yet unavailable owing to its large size, complex multimerization, and functional differences of the multimers.

Curcumin conjugates induce apoptosis via a mitochondrion dependent pathway in MCF-7 and MDA-MB-231 cell lines.

In order to enhance the bioavailability of curcumin its conjugates with piperic acid and glycine were synthesized by esterifying the 4 and 4' phenolic hydroxyls, the sites of metabolic conjugation. Antiproliferative and apoptotic efficacy of synthesized conjugates was investigated in MCF-7 and MDA-MB-231 cell lines. IC50 values of di-O-glycinoyl (CDG) and di-O-piperoyl (CDP) esters of curcumin were found to be comparable with that of curcumin.

Inhibition of N-(4-hydroxyphenyl)retinamide-induced autophagy at a lower dose enhances cell death in malignant glioma cells.

The question whether chemotherapy-induced autophagy is causative to the demise of the cells or a part of the survival mechanism activated during cellular distress is unclear. Others and we have previously demonstrated apoptosis-inducing capacity of N-(4-hydroxyphenyl)retinamide (4-HPR) in malignant glioma cells. We provide evidences of 4-HPR-induced autophagy at a lower concentration (5 microM).