Sika deer velvet antler protein extract modulater bone metabolism and the structure of gut microbiota in ovariectomized mice.

Osteoporosis is a systemic osteopathy characterized by bone metabolism disorders that become more serious with age increases in postmenopausal women. Recent studies have found that antler protein is the main bioactive component of cervus pantotrichum, and it has a positive regulatory effect on bone metabolism and can improve estrogen level. This study aimed to investigate the effect of velvet antler extract (VAE) on the prevention of osteoporosis and the modulation of gut microbiota in ovariectomized (OVX) mice. OVX mice treated with 12 weeks of VAE exhibited higher levels of serum BGP, Ca2+, CT, and HyP (p < .05). Micro-CT scans showed that VAE significantly elevated bone volume fraction (BV/TV), trabecular bone number (Tb.N), trabecular bone thickness (Tb.Th), trabecular bone connection density (Conn.D), decreased trabecular separation (Tb.Sp), and structural modality index (SMI) than untreated OVX mice. The right tibial retinaculum in the VAE group was clearer, with a clearer reticular structure, smaller gaps, a tighter distribution, and a more orderly arrangement. The gut microbiota of the cecal contents was analyzed by 16 s rDNA amplicon sequencing. The data indicated that VAE modulated the species, numbers, and diversity of the gut microbiota in OVX mice. Ovariectomy caused dysbiosis of the intestinal microbiota by increasing the ratio of Firmicutes to Bacteroidetes in mice, but the ratio decreased after treatment with VAE. These results suggest that VAE has a therapeutic effect on OVX mice via modulate bone-related biochemical markers in serum and structure of gut microbiota.

Mechanistic insights into the effect of drug content on adhesive properties of transdermal patch containing lidocaine.

This study aims to shed light on the relationship between drug content and adhesive properties in drug-in-adhesive transdermal patch, and to elucidate molecular mechanisms from the perspective of polymer chain mobility. Lidocaine was selected as model drug. Two acrylate pressure sensitive adhesives (PSAs) with different polymer chain mobility were synthesized. Tack adhesion, shear adhesion and peel adhesion of PSAs with 0, 5%, 10%, 15% and 20% w/w lidocaine contents were tested. Polymer chain mobility was determined by rheology and modulated differential scanning calorimetry experiments. Drug-PSA interaction was analyzed by FT-IR. The effect of drug content on free volume of PSA were determined by positron annihilation lifetime spectroscopy and molecular dynamics simulation. It was found that the polymer chain mobility of PSA was increased with increasing drug content. Due to the variation of polymer chain mobility, tack adhesion increased, and shear adhesion decreased. It was proved that interactions between polymer chains were destroyed by drug-PSA interactions, free volume between polymer chains was expanded, resulting in the increase of polymer chain mobility. We can conclude that the effect of drug content on polymer chain mobility should be considered, when designing a transdermal drug delivery system with controlled and satisfactory adhesion.

Effects of compound deer bone extract on osteoporosis model mice and intestinal microflora.

The preventive and therapeutic mechanisms of CDBE on osteoporosis were studied by observing the serum bone-related biochemical indicators, bone trabecular micro-structure and intestinal flora in ovariectomized osteoporosis model mice, in order to provide a scientific theoretical basis for the further study on the effect of CDBE on osteoporosis, and the prevention and treatment of osteoporosis with clinical traditional Chinese medicines. The components in CDBE were detected by UHPLC-MS. A mouse osteoporosis model was established by the bilateral ovariectomy in female ICR mice. The biochemical indicators related to osteoporosis were detected, the right proximal tibia was scanned by Micro-CT, the intestinal microflora in the colon contents were examined, and the changes of microflora were taken as the main target to evaluate the effect of CDBE on the intestinal microflora in the model mice. A total of 16 compounds were obtained by the combined application of UHPLC-MS. CDBE could significantly increase the contents of E2, Ca2+ , CT, HyP, OCN, FOXP3, P1NP and CTX-II, in the model mice. CDBE could significantly improve the trabecular micro-structure, Tb.N, Tb.Sp, SMI and Conn.D. CDBE could make the intestinal flora of osteoporosis model mice tend to healthy mice in species and quantity. CDBE can improve the symptoms of postmenopausal osteoporosis in mice, with a positive effect on the intestinal flora of postmenopausal mice. Its mechanism of regulating the symptoms of osteoporosis may be related to the regulation of bone-related biochemical indicators in the serum of mice. PRACTICAL APPLICATIONS: This research has a positive impact on the development of functional food with anti-osteoporosis in the future.

Erratum: Combined antitumor effects of P-5m octapeptide and 5- fluorouracil on a murine model of H22 hepatoma ascites.

[This corrects the article DOI: 10.3892/etm.2018.6422.].

Combined antitumor effects of P-5m octapeptide and 5-fluorouracil on a murine model of H22 hepatoma ascites.

The present study has demonstrated that P-5m octapeptide (P-5m) has therapeutic potential in metastatic human hepatocarcinoma, possibly through the modulation of matrix metalloproteinase-2 expression. The purpose of the present study was to evaluate the antitumor effect of P-5m combined with 5-fluorouracil (5-Fu) on the treatment of hepatoma 22 (H22) hepatocarcinoma malignant ascites in a mouse model. The inhibitory effect on the growth of mouse ascites tumors was monitored by measuring body weight gain, survival time, ascites volume, numbers of tumor cells, DNA synthesis and peritoneal capillary permeability analysis. The present data revealed a significant reduction in ascites volume and cell count in mice that were treated with P-5m plus 5-Fu. Furthermore, the median survival time in mice in the combination group was prolonged compared with the disease control group. Moreover, a significant reduction in the total H22 ascites cell count in mice from the combination group was observed when compared with the disease control group. P-5m plus 5-Fu was able to induce the cell cycle arrest and inhibit the peritoneal capillary permeability of the mice. To conclude, the present study indicated that P-5m may have therapeutic potential in ascites caused by hepatocellular carcinoma.

[A survey on the contents of nutrient and nutrition in the orderings of customers when eating at three restaurants in Beijing].

OBJECTIVE: To study the median nutrient content of customers' ordering in the restaurants in Beijing. METHODS: The median contents of nutrients regarding ordering/per person from the customers were estimated, via combining the nutrient content of menu offering. Data, based on all weights of ingredients and Chinese food composition with all the ordered records from customers, was collected within a set period of time, from 2011 to 2013. Nutrition status was then estimated, under the Nutrient-Rich Foods (NRF). RESULTS: The median energy intake reached 4 973.9 (P25-P75: 3 575.6-6 971.0) kJ and 88.2% of the tables were exceeding the recommended energy limits, respectively, with 3 347.2 kJ for lunch and 2 510.4 kJ for dinner. Data was gathered from three restaurants in Beijing. In all the three restaurants, the median nutrient contents appeared 70% outnumbered the daily value of fat and cholesterol. The median sodium contents (87.9%) were also over the standard set for sodium adequate intake. In addition, the median nutrition on fibers, calcium, vitamin A, vitamin C and vitamin E were far below the recommended nutritional intakes (RNI), in the ordering. For NRF9.3, the Wenzhou restaurant showed the highest score (5.50) but the restaurant in Yunnan appeared the lowest (2.26), with difference statistically significant (P<0.001). CONCLUSION: Eating-out habit ended in taking low nutrition with higher limited nutrients, but with low recommended nutrients, when compared to the recommended Chinese Dietary Reference Intake.

[A survey on the sodium content of customers' orderings at three restaurants in Beijing].

OBJECTIVE: To survey the mean sodium content of menu offering and customers' orderings on sodium when eating out. METHODS: All weights of ingredients of menu offerings at three Chinese restaurants with Wenzhou, Shandong, and Yunnan cuisine, in Beijing, were collected and their sodium values were estimated based on data from the Chinese Food Composition. All records from customers' orders were collected in a certain period of time from year 2011 to 2013. The mean sodium content of ordering per person and the proportion of all orders exceeding the recommended daily sodium limit that applicable to most native Chinese, were estimated. RESULTS: Of all the menu offerings, hot dishes (1 728.6 mg; P25, P75: 1 198.7, 2 482.8) and soup dishes (2 101.5 mg; P25, P75: 1 467.8, 2 291.2) had the highest sodium contents, followed by cold dressed dishes (790.7 mg; P25, P75: 128.1, 1 472.9) staple foods (802.9 mg; P25, P75: 115.1, 1 563.2) while the beverages having the lowest sodium contents (17.0 mg; P25, P 75: 2.0, 19.5) (P < 0.05). Meat dishes (1 796.3 mg; P25, P75: 1 303.9, 2 670.3) contained more sodium than vegetable dishes (1 105.5 mg; P25, P75: 423.6, 1 628.6) (P < 0.001). The median sodium contents in per person orderings were 2 325.6 mg (P25, P75:1 700.7, 3 213.8) for lunch and 2 542.5 mg (P25, P75: 1 857.5, 3 498.1) for dinner. Current dietary guideline recommended for Chinese adults was: in general, the amount of consumption should not exceed 2 400 mg of sodium per day. Based on the recommended optimal daily calories intake ratio as 3:4:3 for breakfast, lunch, and dinner, we would suggest that the sodium intake should follow the amount as 960 mg for lunch and 720 mg for dinner. Our data indicated that 97.5% of the ordered meals appeared that they were over the recommended sodium limit and 76.5% of the tables showed two times more than the limit of recommendation. CONCLUSION: Soup and hot dishes provided at these three restaurants contained more sodium contents. People ordered dishes at restaurants would contain more sodium than the recommended Chinese daily sodium intake.

In vitro percutaneous absorption enhancement of granisetron by chemical penetration enhancers.

UNLABELLED: Granisetron (GRN), a potent antiemetic agent, is frequently used to prevent nausea and vomiting induced by cancer cytotoxic chemotherapy and radiation therapy. OBJECTIVE: As part of our efforts to further modify the physicochemical properties of this market drug, with the ultimate goal to formulate a better dosage form for GRN, this work was carried out to improve its permeability in vitro. METHODS: The permeation behavior of GRN in isopropyl myristate (IPM) was investigated across excised rabbit abdominal skin and the enhancing activities of three novel O-acylmenthol derivatives synthesized in our laboratory as well as five well-known chemical enhancers were evaluated. RESULTS: It was found that the steady-state flux of granisetron free base (GRN-B) was about 26-fold higher than that of granisetron hydrochloride (GRN-H). The novel enhancer, 2-isopropyl-5-methylcyclohexyl heptanoate (M-HEP), was observed to provide the most significant enhancement for the absorption of GRN-B. When incorporated in the donor solution with the optimal enhancer M-HEP, the steady-state flux of GRN-B increased from (196.44 ± 12.03) µg·cm⁻²·h⁻¹ to (1044.95 ± 71.99) µg·cm⁻²·h⁻¹ (P < 0.01). CONCLUSION: These findings indicated that the application of chemical enhancers was an effective approach to increase the percutaneous absorption of GRN in vitro.

The transdermal patches for site-specific delivery of letrozole: a new option for breast cancer therapy.

The aim of this work was to evaluate capability of site-specific delivery of a transdermal patch through determination of letrozole in local tissues disposition in female mice. After transdermal administration, the letrozole levels in skin, muscle, and plasma were 10.4-49.3 µg/g, 1.64-6.89 µg/g, and 0.35-1.64 µg/mL, respectively. However, after the mice received letrozole suspension, the drug concentration of plasma and muscle were 0.20-4.80 µg/mL and 0.15-2.38 µg/g. There was even no drug determined in skin through all experiments. Compared with oral administration, the transdermal patch for site-specific delivery of letrozole could produce high drug concentrations in skin and muscle and meanwhile obtain low drug level in plasma. These findings show that letrozole transdermal patch is an appropriate delivery system for application to the breast tumor region for site-specific drug delivery to obtain a high local drug concentration and low circulating drug concentrations avoiding the risk of systemic side effects.

Transdermal patches for site-specific delivery of anastrozole: In vitro and local tissue disposition evaluation.

Anastrozole is a potent aromatase inhibitor and there is a need for an alternative to the oral method of administration to target cancer tissues. The purpose of the current study was to prepare a drug-in-adhesive transdermal patch for anastrozole and evaluate this for the site-specific delivery of anastrozole. Different adhesive matrixes, permeation enhancers and amounts of anastrozole were investigated for promoting the passage of anastrozole through the skin of rats in vitro. The best in vitro skin permeation profile was obtained with the formulation containing DURO-TAK 87-4098, IPM 8% and anastrozole 8%. For local tissue disposition studies, the anastrozole patch was applied to mouse abdominal skin, and blood, skin, and muscle samples were taken at different times after removing the residual adhesive from the skin. High accumulation of the drug in the skin and muscle tissue beneath the patch application site was observed in mice compared with that after oral administration. These findings show that anastrozole transdermal patches are an appropriate delivery system for application to the breast tumor region for site-specific drug delivery to obtain a high local drug concentration.

Effect of counter-ions and penetration enhancers on the skin permeation of flurbiprofen.

The aim of this work was to investigate the percutaneous absorption of flurbiprofen (FP) using counter-ions as enhancers as well as to compare their enhancing activity with penetration enhancers in vitro. The in vitro permeation studies of FP were performed in isopropyl myristate (IPM) solution by two-chamber diffusion cells, using rat abdominal skin as a model. Among the penetration enhancers examined, including the cosolvents of propylene glycol and ethanol (EtOH), oleic acid, menthol, laurocapram, sorbitan monooleate, and N-methyl-2-pyrrolidone (NMP), 10% (w/w) EtOH and NMP exhibited the most potent solubilization and enhancing effects of FP from IPM, with a flux of (372.60 +/- 45.12) microg/cm(2)/h and (474.21 +/- 46.64) microg/cm(2)/h, respectively. Ten percent (w/w) EtOH/IPM binary system was used to investigate the effect of the counter-ions, namely diethylamine (DEA), triethylamine (TEA), ethanolamine (EtA), diethanolamine (DEtA), triethanolamine (TEtA), and N-(2'-hydroxyethanol)-piperdine (HEPP). The cumulative amounts were markedly increased in the presence of the counter-ions, and the highest flux of (1297.53 +/- 121.81) microg/cm(2)/h was obtained by DEA. This was related to the decreased lipophilicity and different physicochemical properties of the ion-pairs. In particular, we proved the formation of an FP/amine ion-pair in solution by (1)H-NMR. The results suggest that the counter-ions are more efficient than penetration enhancers.