Bone Morphogenetic Protein 7 (BMP7) Gene Polymorphisms Are Associated With Inverse Relationships Between Vascular Calcification and BMD: The Diabetes Heart Study

Inverse relationships have been observed between BMD and vascular calcification (VC), suggesting an underlying metabolic pathway linking these processes. Bone morphogenetic proteins (BMPs) are potential candidate genes that may mediate this relationship. Four single nucleotide polymorphisms (SNPs) in the BMP2 gene, 2 SNPs in BMP4, and 16 SNPs in BMP7 were tested for association with measures of VC using CT (coronary and carotid arteries, abdominal aorta), and BMD was measured using DXA (lumbar spine, hip, and distal radius) and quantitative CT (QCT; thoracic and lumbar spine) in 920 European Americans from 374 Diabetes Heart Study families: 762 with type 2 diabetes. Variance components quantitative trait locus association analysis was computed using SOLAR software, and a bivariate principal component analysis (PCA) assessed for genetic relationships between BMD and VC. Association was observed between several measures of BMD and BMP7 rs17404303 (thoracic spine QCT p = 0.03; lumbar spine QCT p = 0.02; hip DXA p = 0.06, dominant models). In addition, 6 of 16 BMP7 SNPs showed significant and opposing effects on the bivariate PCA for VC and BMD (two‐sided exact test, p = 0.0143). Polymorphisms in BMP7 are associated with inverse relationships between bone mineralization and VC in the coronary, carotid, and abdominal aorta in a diabetes‐enriched cohort of European Americans.     

Soy isoflavonoid effects on endogenous estrogen metabolism in postmenopausal female monkeys

Endogenous estrogens are important determinants of breast cancer risk in postmenopausal women. In this study we evaluated the effects of dietary soy isoflavonoids on endogenous estrogen metabolism in a postmenopausal primate model. Ovariectomized female cynomolgus monkeys were randomized to receive one of three diets for 36 months: (i) isoflavonoid-depleted soy protein isolate (SPI-) (n = 29); (ii) soy protein isolate with 129 mg isoflavonoids/1800 kcal diet (8.6 mg isoflavonoids/kg body weight (BW), expressed in aglycone units) (SPI+) (n = 29) or (iii) isoflavonoid-depleted soy protein isolate with conjugated equine estrogens (CEE) at a dose of 0.625 mg/1800 kcal diet (0.042 mg CEE/kg BW) (n = 30). Mean plasma isoflavonoid concentrations in the SPI+ group were 946.9 +/- 135.9 nmol/l, and equol was the primary circulating isoflavonoid (549.7 +/- 61.6 nmol/l). The SPI+ diet resulted in lower serum estrone (E(1)) after 29 (-26%, P = 0.03) and 34 months (-21%, P = 0.04) compared to the SPI- diet, while urinary 2-hydroxyestrone (P = 0.005) and the 2 to 16alpha-hydroxyestrone ratio (P < 0.0001) were markedly higher in the SPI+ group compared to SPI-. Isoflavonoid treatment did not significantly alter gene markers of estrogen metabolism or estrogen receptor agonist activity in breast tissue. Within the SPI+ group, higher concentrations of serum equol (but not daidzein or genistein) corresponded to significantly lower serum E(1), mammary gland epithelial area and uterine weight (P < 0.01 for all). These findings suggest that long-term exposure to soy isoflavonoids, equol in particular, may facilitate endogenous estrogen clearance and catabolism to more benign 2-hydroxylated metabolites.     

Effects of estradiol with micronized progesterone or medroxyprogesterone acetate on risk markers for breast cancer in postmenopausal monkeys

The addition of the synthetic progestin medroxyprogesterone acetate (MPA) to postmenopausal estrogen therapy significantly increases breast cancer risk. Whether this adverse effect is specific to MPA or characteristic of all progestogens is not known. The goal of this study was to compare the effects of oral estradiol (E2) given with either MPA or micronized progesterone (P4) on risk biomarkers for breast cancer in a postmenopausal primate model. For this randomized crossover trial, twenty-six ovariectomized adult female cynomolgus macaques were divided into social groups and rotated randomly through the following treatments (expressed as equivalent doses for women): (1) placebo; (2) E2 (1 mg/day); (3) E2 + P4 (200 mg/day); and (4) E2 + MPA (2.5 mg/day). Hormones were administered orally, and all animals were individually dosed. Treatments lasted two months and were separated by a one-month washout period. The main outcome measure was breast epithelial proliferation, as measured by Ki67 expression. Compared to placebo, E2 + MPA resulted in significantly greater breast proliferation in lobular (P < 0.01) and ductal (P < 0.01) epithelium, while E2 + P4 did not. Intramammary gene expression of the proliferation markers Ki67 and cyclin B1 was also higher after treatment with E2 + MPA (P < 0.01) but not E2 + P4. Both progestogens significantly attenuated E2 effects on body weight, endometrium, and the TFF1 marker of estrogen receptor activity in the breast. These findings suggest that oral micronized progesterone has a more favorable effect on risk biomarkers for postmenopausal breast cancer than medroxyprogesterone acetate.     

Design and synergistic effect of nano-sized epoxy-NiCo2O4 nanocomposites for anticorrosion applications

In the present work, we evaluated the corrosion inhibition properties of a ligand and mixed metal oxide nanocomposite. The ligand and mixed nickel–cobalt complex were synthesized using 1-naphthoic acid and aminoguanidine with the formulae [C₁₁H₇O₂(CN₄H₅)(CN₄H₆)]·H₂O and {Ni–Co[(CH₅N₄)₂(C₁₁H₇O₂)₂]}·H₂O, respectively. After their synthesis, physicochemical techniques such as CHNS analysis, infrared and UV-visible spectroscopy, thermal analysis, and X-ray diffraction (XRD) were employed to characterize both the synthesized ligand and nickel–cobalt complex. The metal oxide prepared from the decomposition of the metal complex was also characterized using several techniques to confirm its bonding and structure. In addition, the corrosion inhibition efficiency of the epoxy-ligand and epoxy-NiCo₂O₄ nanocomposite on mild steel (MS) in 3 M hydrochloric acid (HCl), 1.5 M sulfuric acid (H₂SO₄), and 0.5 M phosphoric acid (H₃PO₄) solution was examined and compared using weight loss measurements, Tafel plots, isotherms and electrochemical impedance spectroscopy (EIS). The results from the electrochemical studies disclosed that the epoxy coating of mixed metal oxides with 0.8 ppm concentration yielded excellent corrosion protection. The SEM images of mild steel and mild steel coated with epoxy-ligand/epoxy-NiCo₂O₄ in HCl confirmed the anti-corrosive behavior of the synthesized compounds. Hence, the as-prepared material can be a next-generation tool for sustainable anti-corrosive coatings.

This study reports the synthesis of nano-sized epoxy-NiCo₂O₄ nanocomposites and their anti-corrosive efficiency to attain sustainable development.     

Mediterranean Diet Reduces Social Isolation and Anxiety in Adult Female Nonhuman Primates

Dietary composition is associated with the differential prevalence of psychiatric disorders; the Western diet confers increased risk, while the Mediterranean diet appears to reduce risk. In nonhuman primates, anxiety-like behaviors and social isolation have been linked to both Western diet consumption and increased inflammatory disease risk, and recent evidence suggests that diet composition may affect immune system function in part through its effects on behavior. This is particularly important in the context of the global COVID-19 pandemic in which social isolation has been associated with disease. Here, we examined the effects of Western- and Mediterranean-like diets on social behavior in a randomized, 34-month preclinical trial in middle-aged female cynomolgus macaques (Macaca fascicularis). Diet induced rapid and persistent changes in a suite of behaviors. After just three months of experimental diet consumption, a composite measure of diet-altered behavior (DAB) significantly differed between the two diets (p = 0.014) and remained different throughout the 24-month experimental observation period (p = 2.2 × 10⁻⁸). Monkeys fed the Western diet spent more time alone (FDR = 4.4 × 10⁻⁵) and displayed more anxiety behavior (FDR = 0.048), whereas monkeys fed the Mediterranean diet spent more time resting (FDR = 0.0013), attentive (FDR = 0.017), and in body contact with groupmates (FDR = 4.1 × 10⁻⁸). These differences were largely due to changes in behavior of animals fed the Mediterranean diet, while Western-diet-fed-animals exhibited similar behaviors compared to the eight-month baseline period, during which all monkeys consumed a common laboratory diet. These observations provide experimental support in a nonhuman primate model, demonstrating a potential therapeutic benefit of the Mediterranean diet consumption to reduce social isolation and anxiety and thus mitigate social isolation-associated disorders that often accompany illness and disability.