Attention-based cross domain graph neural network for prediction of drug-drug interactions.

Drug-drug interactions (DDI) may lead to adverse reactions in human body and accurate prediction of DDI can mitigate the medical risk. Currently, most of computer-aided DDI prediction methods construct models based on drug-associated features or DDI network, ignoring the potential information contained in drug-related biological entities such as targets and genes. Besides, existing DDI network-based models could not make effective predictions for drugs without any known DDI records. To address the above limitations, we propose an attention-based cross domain graph neural network (ACDGNN) for DDI prediction, which considers the drug-related different entities and propagate information through cross domain operation. Different from the existing methods, ACDGNN not only considers rich information contained in drug-related biomedical entities in biological heterogeneous network, but also adopts cross-domain transformation to eliminate heterogeneity between different types of entities. ACDGNN can be used in the prediction of DDIs in both transductive and inductive setting. By conducting experiments on real-world dataset, we compare the performance of ACDGNN with several state-of-the-art methods. The experimental results show that ACDGNN can effectively predict DDIs and outperform the comparison models.

Total Flavonoids of Drynariae Rhizoma Prevent Bone Loss Induced by Hindlimb Unloading in Rats.

Drynariae Rhizoma is a kidney-tonifying herb that has a long history in clinical practice for the treatment of bone fractures and joint diseases in China. Flavonoids are considered to be its major active ingredients and are reported to ease bone loss in ovariectomized rats. However, the beneficial effects of the total flavonoids of Drynariae Rhizoma on osteoporosis caused by microgravity or mechanical inactivity remain unknown. This study assessed the effects of total Drynariae Rhizoma flavonoids (DRTF, Qihuang, Beijing, China, national medicine permit No. Z20030007, number of production: 04080081, content of DRTF ≥80%) against bone loss induced by simulated microgravity. A hindlimb unloading tail-suspended rat model was established to determine the effect of DRTF on bone mineral density (BMD), biomechanical strength and trabecular bone microarchitecture. Twenty-eight male Sprague-Dawley rats were divided into four groups: the baseline, control, hindlimb unloading with vehicle (HLU), and hindlimb unloading treated with DRTF (HLU-DRTF, 75 mg/kg/day) groups. Oral DRTF was administered for 4 weeks. The underlying mechanisms of the DRTF actions on disuse-induced osteoporosis are discussed. The results showed that DRTF treatment significantly increased the BMD and mechanical strength of tail-suspended rats. Enhanced bone turnover markers with HLU treatment were attenuated by DRTF administration. Deterioration of trabecular bone induced by HLU was prevented through elevated bone volume/tissue volume (BV/TV), trabecular number (Tb. N), trabecular thickness (Tb. Th) and decreased trabecular separation (Tb. Sp). The present study provides the first evidence that DRTF prevents bone loss induced by HLU treatment, indicating its potential application in the treatment of disuse-induced osteoporosis.

Effects of total flavonoids from Drynariae Rhizoma prevent bone loss in vivo and in vitro.

Estrogen deficiency is one of the major causes of osteoporosis in postmenopausal women. Drynariae Rhizoma is a widely used traditional Chinese medicine for the treatment of bone diseases. In this study, we investigated the therapeutic effects of the total Drynariae Rhizoma flavonoids (DRTF) on estrogen deficiency-induced bone loss using an ovariectomized rat model and osteoblast-like MC3T3-E1 cells. Our results indicated that DRTF produced osteo-protective effects on the ovariectomized rats in terms of bone loss reduction, including decreased levels of bone turnover markers, enhanced biomechanical femur strength and trabecular bone microarchitecture deterioration prevention. In vitro experiments revealed that the actions of DRTF on regulating osteoblastic activities were mediated by the estrogen receptor (ER) dependent pathway. Our data also demonstrated that DRTF inhibited osteoclastogenesis via up-regulating osteoprotegrin (OPG), as well as down-regulating receptor activator of NF-κB ligand (RANKL) expression. In conclusion, this study indicated that DRTF treatment effectively suppressed bone mass loss in an ovariectomized rat model, and in vitro evidence suggested that the effects were exerted through actions on both osteoblasts and osteoclasts.

Combination of transcriptomic and metabolomic analyses reveals a JAZ repressor in the jasmonate signaling pathway of Salvia miltiorrhiza.

Jasmonates (JAs) are plant-specific key signaling molecules that respond to various stimuli and are involved in the synthesis of secondary metabolites. However, little is known about the JA signal pathway, especially in economically significant medicinal plants. To determine the functions of novel genes that participate in the JA-mediated accumulation of secondary metabolites, we examined the metabolomic and transcriptomic signatures from Salvia miltiorrhiza. For the metabolome, 35 representative metabolites showing significant changes in rates of accumulation were extracted and identified. We also screened out 2131 differentially expressed unigenes, of which 30 were involeved in the phenolic secondary metabolic pathway, while 25 were in the JA biosynthesis and signal pathways. Among several MeJA-induced novel genes, SmJAZ8 was selected for detailed functional analysis. Transgenic plants over-expressing SmJAZ8 exhibited a JA-insensitive phenotype, suggesting that the gene is a transcriptional regulator in the JA signal pathway of S. miltiorrhiza. Furthermore, this transgenic tool revealed that JAZ genes have novel function in the constitutive accumulation of secondary metabolites. Based on these findings, we propose that the combined strategy of transcriptomic and metabolomic analyses is valuable for efficient discovery of novel genes in plants.

[Antiosteoporotic effects of naringenin on ovariectomy-induced osteoporosis in rat].

To investigate the effect of naringenin on ovariectomy-induced postmenopausal osteoporosis comprehensively and systemically, thirty-two virgin Sprague-Dawley rats about 3-month-old were used and randomly divided into 4 groups: sham control group (Sham), OVX control group (OVX), naringenin treatment group and 17ß-estradiol (E2) treatment group. After 12 weeks treatment with different drugs, 24 h urine were collected, organs were weighed and the organ indies were computed. Uterine pathological changes were observed by making paraffin section. Biochemical parameters and bone turnover markers: serum osteocalcin (BGP) and urine deoxypyridinoline (DPD) were analyzed with automatic biochemical analyzer or ELISA assay. Bone mineral density (BMD) and bone mineral content (BMC) were analyzed by DEXA, bone biomechanical properties was measured by three point bending test and the trabecular bone microarchitecture was evaluated by Micro CT. From the results, we can see that: the gaining of weight and the increasing of bone turnover markers such as serum BGP and urinary DPD could be inhibited by naringenin. The treatment could also enhance the bone strength and prevent the deterioration of trabecular microarchitecture, increase the bone volume, trabecular number and thickness, and decrease the trabecular space. The effects mentioned above were not accompanied with stimulating effects on uterus. Long-term using of naringenin had no obvious influence on other organs and the liver and kidney functions. The study suggests that naringenin had obvious antiosteoporotic effect on ovariectomized rats and it had the potential value for the treatment of postmenopausal osteoporosis.

Ergosterol reverses multidrug resistance in SGC7901/Adr cells.

Multidrug resistance (MDR) is a major obstacle in the chemotherapeutic treatment of tumors. Elevated expression of the P-glycoprotein (P-gp) transporter is associated with MDR and responsible for the resistance of tumor cells against a variety of anticancer drugs. In this study, the reversal effect of ergosterol (Erg) on SGC7901/Adr cells was investigated. At concentrations of 1 microM and 5 microM, Erg could reverse the resistance of SGC7901/Adr to adriamycin up to 4.84 and 3.92 folds, respectively. Mechanistically, Erg could increase the intracellular accumulation of adriamycin and Rh123 in SGC7901/Adr cells through inhibiting the transcription of MDR1 gene and down-regulating the expression of P-gp. In conclusion, Erg could reverse the MDR of SGC7901/Adr cells via its influence on P-gp expression and thus be a promising lead compound for future studies.

[SPME-GC-MS combined with Kovat's retention index analysis for volatile components in Pistacia chinensis].

OBJECTIVE: To analyze and compare the volatile components in fruits and leaves of Pistacia chinesis. METHODS: The volatile components were extracted from the fruits and leaves of Pistacia chinesis by solid-phrase microextration, and were analyzed and identified by gas chromatography-mass spectrometry(GC-MS) combined with Kovat's retention index. The relative content of each component was calculated by normalization method. RESULTS: 29 and 17 volatile components were identified from the fruits and leaves respectively, representing the relative content of 95. 30% and 96. 91% of the volatile components. 13 common components were identified in both the fruits and leaves. CONCLUSION: The volatile components in the fruits vary from that in the leaves in type and content, terpenoids are major components in the fruits and leaves of Pistacia chinesis in Shaanxi. Monoterpenes(76. 32%) are the major components of the fruits, while sesquiterpenes(65. 42%) are the major components of the leaves.

Rapid analysis of fatty acid profiles in raw nuts and seeds by microwave-ultrasonic synergistic in situ extraction-derivatisation and gas chromatography-mass spectrometry.

Based on microwave-ultrasonic synergistic in situ extraction-derivatisation (MUED), gas chromatography-mass spectrometry was proposed for rapid analysis of fatty acid profiles in raw nut and seed materials. Several critical experimental parameters for MUED, including reaction temperature, microwave power, amounts of catalyst and derivatisation reagent, have been optimised using response surface methodology. The results showed that the chromatographic peak areas of total fatty acids and the content of total unsaturated fatty acids obtained with MUED were markedly higher than those obtained by the conventional method (P<0.05 and P<0.01, respectively). The MUED method simplified the handling steps compared to the conventional procedure, shortened the sample preparation time whilst improving the extraction and derivatisation efficiency of lipids, and reduced oxidisation and decomposition of the unsaturated fatty acids. The simplicity, robustness and practicality of this method highlighted its significant potential for application in the rapid analysis of fatty acids in natural food resource samples.

Analysis of essential oils from different organs of Scutellaria baicalensis.

OBJECTIVE: To evaluate the differences among essential oils from the fresh flowers, stem leaves, roots and seeds of Scutellaria baicalensis. METHODS: The oils was obtained by hydrodistillation and identified by gas chromatography-mass spectrometry (GC-MS) and the Kovats retention index. The relative contents of the components were determined by the peak-area normalization method adopted in gas chromatography. RESULTS: Fifty-three compounds constituting 91.16% of flower oil, forty-eight compounds comprising 88.48% of stem-leaf oil, thirty-nine compounds representing 91. 79% of root oil and thirty-two compounds accounting 84.58% of seed oil have been identified. CONCLUSION: The results showed that the components and relative contents of the essential oils among flowers, stem leaves, roots and seeds have significant differences. Each of them had a great range of potential utilities and a prospect of development.

[Research on different processings of Scutellaria baicalensis Georgi].

OBJECTIVE: Comparing the different processings of S. baicalensis Georgi with fresh herb. METHODS: Watering, cooking and steaming method were adopted and the contents of flavonoids was determined by HPLC. RESULTS: Cooking and steaming method could not only intenerate the slices, but also destroy the activity of enzyme. So different means could be choosen according to practice. CONCLUSION: Among them, cooking method with 1 time volume of water, heating 10 min, drying at 80 degrees C and steaming method taking 20 min, drying at 80 degrees C is proper.