Ginsenoside Rg1 prevents starvation-induced muscle protein degradation via regulation of AKT/mTOR/FoxO signaling in C2C12 myotubes.

Skeletal muscle atrophy is often caused by catabolic conditions including fasting, disuse, aging and chronic diseases, such as chronic obstructive pulmonary disease. Atrophy occurs when the protein degradation rate exceeds the rate of protein synthesis. Therefore, maintaining a balance between the synthesis and degradation of protein in muscle cells is a major way to prevent skeletal muscle atrophy. Ginsenoside Rg1 (Rg1) is a primary active ingredient in Panax ginseng, which is considered to be one of the most valuable herbs in traditional Chinese medicine. In the current study, Rg1 was observed to inhibit the expression of MuRF-1 and atrogin-1 in C2C12 muscle cells in a starvation model. Rg1 also activated the phosphorylation of mammalian target of rapamycin (mTOR), protein kinase B (AKT), and forkhead transcription factor O, subtypes 1 and 3a. This phosphorylation was inhibited by LY294002, a phosphatidylinositol 3-kinase inhibitor. These data suggest that Rg1 may participate in the regulation of the balance between protein synthesis and degradation, and that the function of Rg1 is associated with the AKT/mTOR/FoxO signaling pathway.

Coadministration of puerarin (low dose) and zinc attenuates bone loss and suppresses bone marrow adiposity in ovariectomized rats.

AIMS: Puerarin is a phytoestrogen that shows osteogenic effects. Meanwhile, zinc stimulates bone formation and inhibits bone resorption. The study aims to investigate the effects of coadministration of puerarin (low dose) and zinc on bone formation in ovariectomized rats. MATERIALS AND METHODS: Co-administration or use alone of puerarin (low dose) and/or zinc were gavaged in OVX rats. The estrogen-like effects were detected by the uterus weight, the histologic observation and the IGF-1 protein expression. The osteogenic effects were determined by bone histomorphometric and mechanical parameters, osteogenic and adipogenic blood markers, and so on. KEY FINDINGS: The results showed that oral administration of puerarin (low dose) plus zinc didn't significantly increase uterus weight. The glandular epithelial of endometrium had no proliferation and no protein expression of IGF-1. Moreover, co-administration attenuated bone loss and biomechanical decrease more than single use of puerarin or zinc (p<0.05). Next, combined administration of puerarin and zinc promoted the serological level of osteocalcin, bone marrow stromal cell (BMSC) proliferation, and the expression of alkaline phosphatase (ALP), and suppressed the serological level of adiponectin and adiposity in bone marrow (BM). SIGNIFICANCE: In conclusion, co-administrated puerarin (low dose) and zinc can partially reverse OVX-induced bone loss and suppress the adiposity of BM in rats, which shed light on the potential use of puerarin and zinc in the treatment of osteoporosis.

Zinc enhances bone metabolism in ovariectomized rats and exerts anabolic osteoblastic/adipocytic marrow effects ex vivo.

Investigations of bone mass and marrow adiposity are critical for defining the role of zinc (Zn) in bone metabolism. Rats used for study were grouped as follows: control (sham), ovariectomy (OVX), ovariectomy + estradiol (OVX-E), ovariectomy + Zn treatment (OVX-Zn). Bone mineral density (BMD) was quantified (microCT); serum osteocalcin, adiponectin, RANKL, and TRAP levels were assayed (ELISA); and biochemical determinations of serum alkaline phosphatase (ALP), calcium (Ca), and phosphorus (P) were done. Cells derived from bone mesenchymal stem cell (BMSC) isolates of respective test groups were compared, identifying primary osteoblasts by MTT assay and adipocytes by Oil Red O stain. Osteocalcin and adiponectin levels in culture supernatants were determined by ELISA. Zn supplementation resulted in a modest increase in BMD, but serum osteocalcin and ALP activity increased significantly (P < 0.01, both). Serum levels of RANKL and TRAP were lower in OVX-Zn (vs OVX) rats (P < 0.01), whereas serum concentrations of adiponectin, Ca, and P did not differ by group. Osteocalcin level was significantly upregulated ex vivo (P < 0.01) in the supernatant of cultured OVX-Zn (vs OVX) cells, accompanied by a slight upturn in osteoblastic differentiation. However, Oil Red O uptake and adiponectin level in supernatant were sharply diminished in cultured OVX-Zn (vs OVX) cells (P < 0.01). Overall, we concluded that Zn contributes to bone mass by marginally stimulating differentiation and proliferation of osteoblasts and by effectively inhibiting osteoclastic and adipocytic differentiation of BMSCs.

A case-cohort study of recurrent salivary adenoid cystic carcinoma after iodine 125 brachytherapy and resection treatment.

Recurrent adenoid cystic carcinoma (rAdCC) can be challenging to be treated with brachytherapy, although brachytherapy is safe and effective in treating head and neck cancers. Patients of adenoid cystic carcinoma (AdCC), who underwent resection and iodine 125 ((125)I) radioactive seed implantation, were recruited for this study. Clinical data, surgical details of resection and seed implantation, histologic characteristics, and prognosis were studied. There were 16 rAdCC cases among 140 cases of AdCC treated with brachytherapy and resection. The mean follow-up duration for the recurrent cases was 61 months. The 3-year local control rate of rAdCC was 51.6%, and the overall disease-specific survival rate was 49.4%. Eight patients showed distant metastasis (50%, 8/16). The histologic grades of 10 rAdCCs were upgraded (62.5%, 10/16).Two cases displayed sarcomatous transformation after brachytherapy (1.4%, 2/140). Although the overall local control rate and survival rate were relatively favorable, some rAdCCs with an aggressive phenotype appeared to respond poorly to (125)I seed implantation. Preventive adjuvant chemotherapy should be prescribed for these rAdCCs.