Exploration at the network pharmacology level of possible targeting mechanisms of Smilacis Glabrae Rhixoma for the treatment of osteoporosis.

OBJECTIVE: The aim of this study was to evaluate the therapeutic effect of Smilacis Glabrae Rhixoma (SGR) on osteoporosis at the level of network pharmacology, and to find new targets and mechanisms of SGR in the treatment of osteoporosis, to better find new drugs and their clinical applications. MATERIALS AND METHODS: In the original network pharmacology mode, we used an improved mode, such as screening the ingredients and targets of SGR through tools such as GEO database, Autodock Vina, and GROMACS. Through molecular docking, we conducted further screening for the targets acting on the effective ingredients of SGR, and finally we performed molecular dynamics simulation and consulted a large amount of related literature for the validation of the results. RESULTS: By screening and validating the data, we finally confirmed that there were mainly 10 active ingredients in SGR, which were isoeruboside b, smilagenin, diosgenin, stigmasterol, beta-sitosterol, sodium taurocholate, sitogluside, 4,7-dihydroxy-5-methoxy-6-methyl-8-formyl-flavan, simiglaside B, and simiglaside E, and mainly acted on eleven targets. These targets mainly exert therapeutic effects on osteoporosis by regulating 20 signaling pathways including Th17 cell differentiation, HIF-1 signaling pathway, apoptosis, inflammatory bowel disease, and osteoclast differentiation. CONCLUSIONS: Our study successfully explains the effective mechanism by which SGR ameliorates osteoporosis while predicting the potential targets NFKB1 and CTSK of SGR for the treatment of osteoporosis, which provides a novel basis for investigating the mechanism of action of new Traditional Chinese medicines (TCMs) at the network pharmacology level and a great support for subsequent studies on osteoporosis.

[Downregulation of large conductance calcium-activated potassium channels in paraventricular nucleus contributes to sympathoexcitation in rats with chronic heart failure].

Objective: To elucidate the association between large conductance calcium-activated potassium channels (BKCa) in the paraventricular hypothalamic nucleus (PVN) and sympathetic outflow in rats with chronic heart failure (CHF) . Methods: Male Wistar rats (6-7 weeks old) were randomized to sham operated group and CHF group (coronary artery ligation) . Two weeks after operation, BKCa inhibitor Iberiotoxin (IBTX) was infused into PVN by osmotic minipumps, rats were divided into following groups: sham+aCSF, CHF+aCSF, sham+low dose IBTX (0.125 nmol/nl) , CHF+low dose IBTX, sham+moderate dose IBTX (1.25 nmol/nl) , CHF+moderate dose IBTX, sham+ high dose IBTX (12.5 nmol/nl) , and CHF+high dose IBTX (n=6 each) . Additional rats were grouped as follows: sham+vehicle, sham+KCNMB4 knockdown (by rAAV2-KCNMB4 shRNA virus injection in PVN) , CHF+vehicle, CHF+ KCNMB4 knockdown group (n=6 each) . The cardiac function was determined by echocardiography, left ventricular hemodynamics were measured invasively, renal sympathetic nerve activity (RSNA) was recorded at 6 weeks after coronary artery ligation or sham operation. The contents of norepinephrine (NE) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in plasma were determined by enzyme-linked immunosorbent assay. The protein and mRNA expression of KCNMB4 in PVN were measured by immunofluorescence staining, Western blot, and real-time PCR, mRNA expression of BKCa in PVN was detected by real-time PCR. Results: Compared with the sham operation group, the cardiac function of the heart failure group was significantly reduced (P<0.05) , and the plasma NE and the serum NT-proBNP were significantly elevated (P<0.05) . The protein and mRNA expression of KCNMB4 in PVN were obviously down-regulated in CHF rats (P<0.05) . After perfusion of IBTX or KCNMB4 knockdown by microinjection of rAAV2-KCNMB4 shRNA virus,right ventricular weight/body weight and lung weight/body weight ratio as well as left ventricular end-diastolic diameter were increased and left ventricular ejection fraction was decreased (all P<0.05) , the sympathetic driving indexes was increased in sham rats, changes of these parameters further aggravated in CHF rats (P<0.05) . KCNMB4 knockdown further downregulated protein expression in PVN of CHF rats. Conclusion: Downregulation and blunted function of BKCa in PVN may contribute to sympathoexcitation and deterioration of cardiac function in rats with chronic heart failure.

Goitre and urinary iodine in coastal and inland areas with low and high iodized salt coverage in Zhejiang province, China.

BACKGROUND AND OBJECTIVES: WHO recommended that iodized salt are more than 90% of households in USI programs, which may not be suitable for all regions, especially in coastal areas. This study intended to find out levels of iodine nutrition and give advice from the USI programs for areas with different iodized salt coverage. METHODS AND STUDY DESIGN: Coastal and inland areas were selected according to geographical regions in Zhejiang Province, China. The water iodine concentration (spectrophotometer analysis), salt iodine concentration (the colorimetric titration method), salt intake, urinary iodine concentration (spectrophotometer analysis), and thyroid volume examination (ultrasonography), as well as questionnaire, were measured in the two areas. RESULTS: Mean Urinary Iodine concentration (MUIs) of children in coastal areas was 149 µg/L, which was significantly lower than that in inland areas (191 µg/L). MUIs of pregnant women in coastal and inland areas were111 and 138 µg/L, respectively. Pregnant women who consumed iodine-containing supplements had higher MUIs (207 µg/L) than those did not (134 µg/L) in inland areas. Prevalence of goitre in children reached 7.0% and 6.6% in coastal and inland areas, respectively. The lowest prevalence of goitre was reached when the urinary iodine concentration was approximately 120-160 µg/L in coastal areas. CONCLUSION: Iodine levels of coastal and inland areas were in the adequate range. Advice from the USI program should be specialized for different areas to appropriately reduce the salt iodine concentrations in inland areas and to determine an appropriate proportion of households using iodized salt in coastal areas. Moreover, iodine supplement intake during pregnancy should officially be recommended.

Emissions of EC, OC, and PAHs from cottonseed oil biodiesel in a heavy-duty diesel engine.

Biodiesel fuels, made from renewable resources, have emerged as viable alternatives to conventional diesel fuel, but their impact on emissions is not fully understood. This study examines elemental carbon (EC), organic carbon (OC), and polycyclic aromatic hydrocarbons (PAHs) emissions from cottonseed oil biodiesel (CSO-B100). Relative to normal diesel fuel, CSO-B100 reduced EC emissions by 64% (±16%). The bulk of EC emitted from CSO-B100 was in the fine particle mode (<1.4 µm), which is similar to normal diesel. OC was found in all size ranges, whereas emissions of OC(1.4-2.5) were proportionately higher in OC(2.5) from CSO-B100 than from diesel. The CSO-B100 emission factors derived from this study are significantly lower, even without aftertreatment, than the China-4 emission standards established in Beijing and Euro-IV diesel engine standards. The toxic equivalency factors (TEFs) for CSO-B100 was half the TEFs of diesel, which suggests that PAHs emitted from CSO-B100 may be less toxic.

Bone mineral density and fracture among prevalent kidney stone cases in the Third National Health and Nutrition Examination Survey.

Concern that people who form kidney stones may have reduced bone mineral density (BMD) and increased fracture risk has motivated clinical and population-based studies, but findings are inconsistent. In this cross-sectional study, we use the Third National Health and Nutrition Examination Survey (NHANES III) to determine whether a history of kidney stones (n = 793) is associated with lower femoral neck BMD and whether the association is similar for men and women. We further ask whether dietary calcium modifies the association between kidney stone history and BMD and whether there is an association between kidney stone history and prevalent spine or wrist fracture. We find that men with kidney stone history have lower femoral neck BMD than men without kidney stone history after adjusting for age, body mass index (BMI), race/ethnicity, and other potential confounders. The effect of kidney stone history on BMD is weaker for women. Men with kidney stone history also are more likely to report prevalent wrist and spine fractures. Dietary calcium, represented by usual milk consumption, is associated positively with BMD for both men and women and modifies the effect of kidney stone history on BMD for men. For men who form kidney stones, milk consumption is associated more strongly with femoral neck BMD than for men without such a history. The effect modification is such that the difference in BMD between men with and without kidney stone history is observed only at lower levels of milk consumption.

Comparative mechanical property characterization of 3 all-ceramic core materials.

PURPOSE: The biaxial flexural strength and fracture toughness for 3 representative types of ceramic core materials were studied to (1) ascertain the ranking of the 3 ceramic types for strength and toughness, and (2) provide clinicians with more information to predict clinical outcomes. The former aim was deemed important in view of the importance of flaw size in the relationship between failure stress and fracture toughness of brittle materials. MATERIALS AND METHODS: The 3 representative ceramic types included a leucite-reinforced glass, a glass-infiltrated sintered alumina, and a high-purity, high-density alumina. The biaxial flexural strength was measured with the piston-on-3-ball method. The plane-strain fracture toughness was measured with the short-bar chevron-notch method. RESULTS: The biaxial flexural strengths of the high-purity, high-density alumina and glass-infiltrated sintered alumina ceramic core types were significantly higher than that of the leucite-reinforced glass ceramic type. The glass-infiltrated sintered alumina was significantly higher in fracture toughness than the high-purity, high-density alumina type, which was significantly higher than the leucite-reinforced glass. CONCLUSION: All materials surpassed the minimum strength requirement outlined by the International Standards Organization, and they also had similar strength variability according to their Weibull moduli. The glass-infiltrated sintered alumina and the high-purity, high-density alumina types were significantly stronger and tougher than currently used core materials. However, while the glass-infiltrated sintered alumina had a higher fracture toughness than the high-purity, high-density alumina, it had a lower flexural strength.

Arachidonic acid metabolism in cells transfected with sense and anti-sense cDNA to annexin I.

Thymic epithelial cell line TEA3A1 produce prostaglandin E2 (PGE2) and express high levels of annexin I. In order to study the relationship between the levels of annexin I expression and the arachidonic acid metabolism, TEA3A1 cells transfected with expression vector containing full length annexin I cDNA in either sense or anti-sense orientation was studied. In the anti-sense cells where the level of annexin I was reduced, the PGE2 production was significantly lower. On the other hand, PGE2 production was significantly higher in sense cells where the production of annexin I was also higher than in control cells. Our results show that increased PGE2 production in sense cells was accompanied by higher levels of PLA2 enzymatic activities. These results suggest that the production of annexin I is positively associated with the phospholipase A2 enzymatic activity and the prostaglandin production in thymic epithelial cells.

[A study on suitable storage conditions for Melaphis chinensis (Bell) Baker].

It is a key procedure for breeding Chinese gallnuts to put the collected Melaphis chinensis on winter host Mnium cuspidatum. The result shows that the most suitable storage condition for the collected Me. chinensis is to store it for four days in shade before putting to winter host.