Identification and Functional Characterization of Metabolites for Bone Mass in Peri- and Postmenopausal Chinese Women.

CONTEXT: Although metabolic profiles appear to play an important role in menopausal bone loss, the functional mechanisms by which metabolites influence bone mineral density (BMD) during menopause are largely unknown. OBJECTIVE: We aimed to systematically identify metabolites associated with BMD variation and their potential functional mechanisms in peri- and postmenopausal women. DESIGN AND METHODS: We performed serum metabolomic profiling and whole-genome sequencing for 517 perimenopausal (16%) and early postmenopausal (84%) women aged 41 to 64 years in this cross-sectional study. Partial least squares regression and general linear regression analysis were applied to identify BMD-associated metabolites, and weighted gene co-expression network analysis was performed to construct co-functional metabolite modules. Furthermore, we performed Mendelian randomization analysis to identify causal relationships between BMD-associated metabolites and BMD variation. Finally, we explored the effects of a novel prominent BMD-associated metabolite on bone metabolism through both in vivo/in vitro experiments. RESULTS: Twenty metabolites and a co-functional metabolite module (consisting of fatty acids) were significantly associated with BMD variation. We found dodecanoic acid (DA), within the identified module causally decreased total hip BMD. Subsequently, the in vivo experiments might support that dietary supplementation with DA could promote bone loss, as well as increase the osteoblast and osteoclast numbers in normal/ovariectomized mice. Dodecanoic acid treatment differentially promoted osteoblast and osteoclast differentiation, especially for osteoclast differentiation at higher concentrations in vitro (eg,10, 100 µM). CONCLUSIONS: This study sheds light on metabolomic profiles associated with postmenopausal osteoporosis risk, highlighting the potential importance of fatty acids, as exemplified by DA, in regulating BMD.

[Musk and carterii birdw enhance the effect of polygonum extract on chronic non-bacterial prostatitis: an animal experimental study].

OBJECTIVE: To observe the effects of musk and carterii birdw on the pathology and the expressions of inflammatory cytokines in chronic non-bacterial prostatitis (CNBP) rats treated with polygonum extract. METHODS: Five male Wistar rats were used for the preparation of SC purified prostate protein solution, and another 48 randomly divided into four groups: polygonum extract, polygonum extract + musk and carterii birdw, CNBP model control and normal control. CNBP models were established by injecting SC purified prostate protein solution and Freund's complete adjuvant. At 60 days after modeling, the CNBP model control and normal control rats were treated with normal saline, and the other two groups with polygonum extract and polygonum extract + musk and carterii birdw, respectively (polygonum 1.575 g per kg per d, musk 0.021 g per kg per d, and carterii birdw 1.05 g per kg per d). After 14 days of continuous intragastric medication, all the rats were sacrificed for pathological examination, determination of the levels of TNF-alpha, IL-1beta, IL-6 and IL-8 in the prostate tissue homogenate by ELISA, and detection of the mRNA and protein expressions of inflammatory cytokines MCP-1 (CCL2) and CCR2 by RT-PCR and Western blot. RESULTS: The polygonum extract + musk and carterii birdw group showed apparent improvement in the structure of the prostate tissue but no inflammatory infiltration, as was quite obvious in the polygonum extract group. Polygonum extract + musk and carterii birdw significantly decreased the inflammatory cytokines TNF-alpha ( [11.04 +/- 4.07] pg/ml), IL-1beta ([16.94 +/- 4.26] pg/ml), IL-6 ([110.08 +/- 28.42] pg/ml) and IL-8 ([26.28 +/- 7.36] pg/ml) in the prostate tissue, as compared with polygonum extract alone ([63.21 +/- 21.37] pg/ml, [41.32 +/- 14.62] pg/ml, [177.64 +/- 42.65] pg/ml and [96.37 +/- 37.61] pg/ml) (P < 0.05, P < 0.01). The former also exhibited significantly lower expressions of MCP-1 mRNA (0.32 +/- 0.17), MCP-1 protein (0.28 +/- 0.15), CCR2 mRNA (0.28 +/- 0.11) and CCR2 protein (0.11 +/- 0.04) than either the model control group (1.15 +/- 0.39, 0.93 +/- 0.34, 0.83 +/- 0.26 and 0.93 +/- 0.34) (P < 0.01), or the polygonum extract group (0.65 +/- 0.27, 0.56 +/- 0.22, 0.78 +/- 0.24 and 0.25 +/- 0.09) (P < 0.05, P < 0.01). CONCLUSION: Musk and carterii birdw can enhance the effect of polygonum extract on chronic prostatitis, reduce inflammatory response and improve tissue repair of the prostate in rats.