Discovery of Novel Azaphenothiazine Derivatives to Suppress Endometrial Cancer by Targeting GRP75 to Impair Its Interaction with IP3R and Mitochondrial Ca Homeostasis.

Endometrial cancer (EC) is the most common cancer of the female reproductive tract, and there is an urgent need to develop new candidate drugs with good efficacy and safety to improve the survival rate and life quality of EC patients. Herein, a series of new azaphenothiazine derivatives were designed and synthesized and their anti-EC activities were evaluated. Among them, compound showed excellent antiproliferative activities against both progesterone-sensitive ISK cells and progesterone-resistant KLE cells.

Targeting GRP75 with a Chlorpromazine Derivative Inhibits Endometrial Cancer Progression Through GRP75-IP3R-Ca-AMPK Axis.

Tumors often overexpress glucose-regulated proteins, and agents that interfere with the production or activity of these proteins may represent novel cancer treatments. The chlorpromazine derivative JX57 exhibits promising effects against endometrial cancer with minimal extrapyramidal side effects; however, its mechanisms of action are currently unknown. Here, glucose-regulated protein 75 kD (GRP75) is identified as a direct target of JX57 using activity-based protein profiling and loss-of-function experiments.

Dietary acid-base balance, bone resorption, and calcium excretion.

Objective: Metabolic studies reveal that acidogenic diets increase bone resorption acutely. This study was conducted to examine associations between diet-induced changes in net acid excretion (NAE) and changes in serum parathyroid hormone (PTH), bone resorption, and calcium excretion over a longer period of 60 days.

Methods: Forty healthy older men and women were given 0.

Lack of effect of calcium intake on the 25-hydroxyvitamin d response to oral vitamin D3.

This study was conducted to examine the effect of calcium intake on the rise in serum 25-hydroxyvitamin D [25(OH)D] levels in response to supplemental vitamin D(3). Fifty-two healthy older men and women were randomly assigned to take calcium (500 mg twice daily with meals) or placebo tablets for 90 d between October 1 and the end of March. All participants were placed on 800 IU/d (20 microg/d) vitamin D(3).

Calcium supplement and osteoporosis medication use in women and men with recent fractures.

Patients with low-trauma fractures are at risk of future fractures and so should be evaluated and treated for osteoporosis. This study was conducted to assess and compare bone medication use and calcium and vitamin D intake at the time of and after an acute fracture. One hundred and six patients, mean age 66.

Effect of dietary protein supplements on calcium excretion in healthy older men and women.

Currently there is no consensus on the impact of dietary protein on calcium and bone metabolism. This study was conducted to examine the effect of increasing protein intake on urinary calcium excretion and to compare circulating levels of IGF-I and biochemical markers of bone turnover in healthy older men and women who consumed either a high or a low protein food supplement for 9 wk. Thirty-two subjects with usual protein intakes of less than 0.