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Diabetes osteoporosis is a chronic complication of diabetes mellitus (DM) and is associated with osteoclast formation and enhanced bone resorption. Specnuezhenide (SPN) is an active compound with anti-inflammatory and immunomodulatory properties. However, the roles of SPN in diabetic osteoporosis remain unknown. In this study, primary bone marrow macrophages (BMMs) were pretreated with SPN and were stimulated with receptor activator of nuclear factor kappa B ligand (RANKL; 50 ng/mL) to induce osteoclastogenesis. The number of osteoclasts was detected by tartrate-resistant acid phosphatase (TRAP) staining. The protein levels of cellular oncogene fos/nuclear factor of activated T cells c1 (c-Fos/NFATc1), nuclear factor kappa-B (NF-κB), and mitogen-activated protein kinases (MAPKs) were evaluated by western blot analysis. NF-κB luciferase assays were used to examine the role of SPN in NF-κB activation. The DM model group received a high-glucose, high-fat diet and was then intraperitoneally injected with streptozotocin (STZ). Micro-CT scanning, serum biochemical analysis, histological analysis were used to assess bone loss. We found that SPN suppressed RANKL-induced osteoclast formation and that SPN inhibited the expression of osteoclast-related genes and c-Fos/NFATc1. SPN inhibited RANKL-induced activation of NF-κB and MAPKs. In vivo experiments revealed that SPN suppressed diabetes-induced bone loss and the number of osteoclasts. Furthermore, SPN decreased the levels of bone turnover markers and increased the levels of runt-related transcription factor 2 (RUNX2), osteoprotegerin (OPG), calcium (Ca) and phosphorus (P). SPN also regulated diabetes-related markers. This study suggests that SPN suppresses diabetes-induced bone loss by inhibiting RANKL-induced osteoclastogenesis, and provides an experimental basis for the treatment of diabetic osteoporosis.

Background: No conventional creatinine- or cystatin C-based glomerular filtration rate (GFR) estimation equation performed consistently outstandingly in elderly Chinese in our previous studies. This research aimed to further evaluate the performance of some recently proposed estimation equations based on creatinine and cystatin C, alone or combined, in this specific population., Materials and Methods: The equations were validated in a population totaling 419 participants (median age 68 [range 60-94] years). The estimated GFR (eGFR) calculated separately by ten equations was compared with the reference GFR (rGFR) measured by the (99m)Tc-DTPA renal dynamic imaging method., Results: Median serum creatinine, cystatin C, and rGFR levels were 0.93 mg/L, 1.13 mg/L, and 74.20 mL/min/1.73 m(2), respectively. The Chinese population-developed creatinine- and cystatin C-based (Cscr-cys) equation yielded the least median absolute difference (8.81 vs range 9.53-16.32, P<0.05, vs the Chronic Kidney Disease Epidemiology Collaboration serum creatinine equation), the highest proportion of eGFR within 15% and 30% of rGFR (P15 and P30, 55.13 and 85.44, P<0.05 and P<0.01, vs the Chronic Kidney Disease Epidemiology Collaboration serum creatinine equation), and the lowest root mean square error (14.87 vs range 15.30-22.45) in the whole cohort. A substantial agreement of diagnostic consistency between eGFR and rGFR (with a kappa 0.61-0.80) was also observed with the Cscr-cys equation. Moreover, measures of performance in the Cscr-cys equation were consistent across normal to mildly injured GFR strata and individuals aged ≤ 80 years. Among all the Cscr-cys equations, the elderly Chinese-developed creatinine-based (CEscr) equation performed best in this specific population. Nevertheless, none of the equations achieved ideal manifestation in the moderately to severely GFR-injured group or in individuals aged ≥ 80 years., Conclusion: The Cscr-cys equation appeared to be optimal in elderly Chinese among the investigated equations. If cystatin C is not available, the CEscr equation is an acceptable alternative. A multicenter study with abundant subjects to develop an apposite formula for elderly Chinese is assumed to be essential.