Free fatty acids receptor 3 (FFA3, GPR41) and 2 (FFA2, GPR43), for which the short-chain fatty acids (SCFAs) acetate and propionate are agonist, have emerged as important G-protein-coupled receptors influenced by diet and gut flora composition. A recent study (Kimura et al., 2011) demonstrated functional expression of FFA3 in the rodent sympathetic nervous system (SNS) providing a potential link between nutritional status and autonomic function. However, little is known of the source of endogenous ligands, signaling pathways, or effectors in sympathetic neurons. In this study, we found that FFA3 and FFA2 are unevenly expressed in the rat SNS with higher transcript levels in prevertebral (e.g., celiac-superior mesenteric and major pelvic) versus paravertebral (e.g., superior cervical and stellate) ganglia. FFA3, whether heterologously or natively expressed, coupled via PTX-sensitive G-proteins to produce voltage-dependent inhibition of N-type Ca 2ϩ channels (Ca v 2.2) in sympathetic neurons. In addition to acetate and propionate, we show that ␤-hydroxybutyrate (BHB), a metabolite produced during ketogenic conditions, is also an FFA3 agonist. This contrasts with previous interpretations of BHB as an antagonist at FFA3. Together, these results indicate that endogenous BHB levels, especially when elevated under certain conditions, such as starvation, diabetic ketoacidosis, and ketogenic diets, play a potentially important role in regulating the activity of the SNS through FFA3.

Surface properties of scaffolds play an important role in cell adhesion and growth. Biodegradable poly(alpha-hydroxy acids) have been widely used as scaffolding materials for tissue engineering; however, the lack of functional groups is a limitation. In this work, gelatin was successfully immobilized onto the surface of poly(alpha-hydroxy acids) films and porous scaffolds by a new entrapment process. The surface composition and properties were examined using attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR), X-ray photoelectron spectra (XPS), and contact angle measurements. Control over the amount of entrapped gelatin was achieved by varying the solvent composition, the duration of soaking, the concentration of gelatin in solution, and chemical crosslinking. The amount of entrapped gelatin increased with the ratio of dioxane/water in the solvent mixture used. Chemical crosslinking after physical entrapment considerably increased the amount of retained gelatin on the surface of poly(alpha-hydroxy acids). Osteoblasts were cultured on these films and scaffolds. The surface modification significantly improved cell attachment and proliferation. Cell numbers on the surface-modified films and scaffolds were significantly higher than those on controls 4 h and 1 day after cell seeding. The osteoblasts showed higher proliferation on surface-modified scaffolds than on the control during 4 weeks of in vitro cultivation. More collagen fibers and other cell secretions were deposited on the surface-modified scaffolds than on the control scaffolds. This novel surface treatment strategy provides a convenient and universal way to modify the surface properties of three-dimensional scaffolds and thus promote cell adhesion and proliferation for tissue engineering.

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The risk of complications of nonsurgical hypoparathyroidism in Asia is unclear. We estimated the prevalence and risk of complications in patients with nonsurgical hypoparathyroidism. Methods We performed a retrospective cohort study using a nationwide claims database from 2005 to 2016. Among the entire Korean population, we identified 897 patients diagnosed with nonsurgical hypoparathyroidism during 2005-2015. We selected 210 patients with nonsurgical hypoparathyroidism during 2005-2008 who had no complications at baseline and followed them to 2016. Control subjects (n = 2075) were matched using propensity scores based on age, sex, and comorbid disease with a 1:10 ratio and monitored until 2016. Results The age-standardized prevalence of nonsurgical hypoparathyroidism was 0.2 cases per 100,000 persons in 2005. During a mean follow-up period of 9.5 years, patients with nonsurgical hypoparathyroidism had a higher risk of cardiovascular disease, especially arrhythmia (hazard ratio [HR], 2.03; 95% confidence interval [CI], 1.11-3.70) and heart failure (HR, 2.43; 95% CI, 1.22-4.83). The risk of vertebral fracture was higher in patients than in controls (HR, 2.27; 95% CI, 1.09-4.72). Patients had a significantly increased risk of renal disease (

To study the relative abundance and the changes of both estrogen receptor alpha (ER␣) and ER␤ mRNA before and after ovariectomy in major organs important to the regulation of calcium homeostasis, we compared the degree of mRNA expression of ER␣ to that of ER␤ in rat tissues by performing competitive reverse transcription polymerase chain reaction (RT-PCR) with internal standards. Both ER␣ and ER␤ were highly expressed in the ovary {ER␣ 2 copies/µg of total RNA], but the parathyroid gland was negative for both ER␣ and ER␤ mRNA. In cultured stromal cells, ER␣ and ER␤ mRNAs were not detected after a 24-h culture; however, the rates of mRNA expression of ER␣ and ER␤ reached ∼10 5 copies/µg of total RNA and ∼10 2 copies/µg of total RNA, respectively, after 9-, 11-, and 13-day cultures. After ovariectomy, the expression of ER␣ mRNA decreased abruptly in the bone marrow and renal cortex, and both ER␣ and ER␤ were barely detected in the trabecular bone. In conclusion, ER␣ might be the main ER in organs important for calcium homeostasis, except in the jejunum. The mRNA expression of ER␣ in the bone marrow and renal cortex decreased abruptly after ovariectomy, which may partially explain why the effect of estrogen deficiency can be amplified and why trabecular bone loss is more predominant than cortical bone loss shortly after surgical or natural

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