Molecular docking technology and network pharmacology based on Rhapontici Radix-Cremastrae Pseudobulbus drug pair in treating breast cancer.

OBJECTIVE: Network pharmacology is a bioinformatics-based research strategy for identifying the mechanisms of drugs and promoting drug development. This study used network pharmacology to investigate the mechanism of the Loulu-Cremastrae Pseudobulbus drug pair treating breast cancer (BC). MATERIALS AND METHODS: The ingredients and potential targets of the drug pair were searched with Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCSMP). National Center for Biotechnology Information (NCBI) and gene cards were used to search the targets of BC. Networks of "drugs-components-targets" and protein-protein interaction were constructed through Cytoscape. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were carried out through common targets. Using AutoDock tool, molecular docking was performed to verify the binding between key targets and compounds. RESULTS: Finally, we selected 6 active compounds from the drug pair. A total of 61 targets were associated with the drug pair, and 15,295 targets were related to BC. 55 common targets were obtained after the intersection. The key targets included Transcription factor Jun (JUN), Heat shock protein HSP 90-alpha (HSP90AA1), and Caspase-3(CASP3). 327 terms were obtained by GO analysis. 78 pathways (p < 0.05) were identified through KEGG analysis. Molecular docking indicated that important compounds combined well with key targets. CONCLUSIONS: Various active compounds, including beta-sitosterol, 2-methoxy-9,10-dihydrophenanthrene-4,5-diol, and stigmasterol, can regulate multiple signaling pathways related to BC, such as the estrogen and prolactin signaling pathways, playing therapeutic roles in BC.

[Estradiol regulates the expression of plasma membrane Ca2+-ATPase isoform 2 in inner ear of rats].

Objective: To observe the effects of estradiol on expression of plasma membrane Ca2+-ATPase isoform 2 in inner ear of rats. Methods: Twenty-five Three-months-old female Sprague-Dawley rats were randomly and equally divided into five groups by random number table mathod,with five rats in each group. Animals in Sham group were sham-operated while others were bilateral ovariactmized. One month after modeling, the OVX groups were supplemented with estradiol (E2 group), progesterone (P group), estradiol and progesterone (E2+P group)and vehicle sesame oil (Veh group), while the Sham operation group (Sham group) was supplemented with vehicle sesame oil.All rats were sacrificed and otocysts were obtained immediately. Enzyme-linked immunosorbent assay was used to detect the changes in serum estradiol and progesterone levels of each group of rats before operation, before treatment and before sacrifice. Western blot and quantitative real-time polymerase chain reaction were used to detect the expression of total PMCA2 protein and mRNA in the inner ear of each group. Results: There was no significant difference in serum estradiol and progesterone levels among the five groups before operated(P>0.05). Before treatment, the serum estradiol and progesterone levels of rats in each group were significantly lower than those in Sham group (P<0.05). The serum estradiol level in E2 group and E2+P group was not significantly different from that in Sham group (P>0.05), while the serum estradiol level in P group and Veh group was significantly different from that in Sham group (P<0.05). The level of progesterone in P group and E2+P group was higher than that in Sham group (P<0.05), while the level of progesterone in Veh group and E2 group was lower than that in Sham group (P<0.05). Protein and mRNA expression of PMCA2 in P and Veh groups were significantly decreased compared with that of Sham group (P<0.05) while the expression levels underwent no significantly change in E2 and E2+P groups (P<0.05). Conclusion: The decrease of serum estradiol level can reduce the expression of otolith regulatory protein PMCA2 in rats, and then affect otolith metabolism, which may be an important link of estrogen affecting otolith metabolism.

[Preliminary results of Chinese magnetic sphincter augmentation in treating gastroesophageal reflux disease].

Objective: To examine the preliminary clinical efficacy of Chinese magnetic sphincter augmentation (MSA) in the treatment of gastroesophageal reflux disease (GERD). Methods: According to the enrollment criteria for the MSA developed by ShengJieKang Co. and Shanghai Chest Hospital (SS-MSA) clinical trial, a total of 19 GERD patients were treated with SS-MSA from August 2018 to January 2020 at Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University. The majority of registered cases were male patients with age of (32.2±7.3) years (range: 22 to 50 years), height of (170.7±6.2) cm (range: 160 to 179 cm) and weight of (65.2±10.3) kg (range: 47.5 to 90.0 kg). SS-MSA was implanted via laparoscopy. The major evaluation indexs of postoperative efficacy were the total time of acid exposure within 24 hours and the total number of reflux. Secondary efficacy indicators included: (1) evaluation of the average daily dose of proton pump inhibitor medications; (2) the score of GERD health related quality of life questionnaire (GERD-Q) before and after MSA implantation. Paired design t-test was used to evaluate the efficacy of the SS-MSA. Results: A total of 19 patients underwent SS-MSA surgery successfully. The history of the GERD were 19 (54) months (M(Q(R))). The operation time was 63 (22) minutes and the in-hospital stay was 3 (2) days. No obvious surgical complications occurred. Postoperative adverse events included 14 cases with mild to moderate dysphagia exited after surgery, gradually eased within 1 to 3 months, 1 case with the removal of the device after 1 month of severe swallowing difficulties, 1 case of diarrhea. No corrosion, perforation, displacement occurred. The GERD-Q score (11.0(4.5) vs. 6(1.0), t=4.274, P=0.013), 24-hour acid exposure time (6.2(4.8)% vs. 0.1(0.9)%, t=5.814, P=0.004), and Demeester score (23.72(16.20) vs. 0.96(3.10), t=6.678, P=0.003) were significantly decreased 1 year after surgery(n=5). Proton pump inhibitor reuse rates were 6/18, 5/15, 3/10, and 1/5 in 1, 3, 6 and 12 months after the operation, respectively. Conclusions: SS-MSA implantation is feasible and safe with short hospital stay and rare perioperative complications. The preliminary results is good after 1 year follow-up. It could be expected to be an ideal substitutive for future GERD treatment.

[Correlation of liver stiffness measured by FibroTouch and FibroScan with Ishak fibrosis score in patients with chronic hepatitis B].

Objective: To investigate the correlation of liver stiffness measured by FibroTouch (FT) and FibroScan (FS) with Ishak fibrosis score in patients with chronic hepatitis B. Methods: A total of 313 patients with chronic hepatitis B who visited Department of Liver Cirrhosis in Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from November 2014 to May 2016 were enrolled. All the patients underwent liver biopsy, and FT and FS were used to determine liver stiffness measurement (LSM). Serum biochemical parameters were measured, and the aspartate aminotransferase-to-platelet ratio index (APRI) in a multi-parameter model of liver fibrosis and fibrosis-4 (FIB-4) index were calculated. The consistency between the results of four noninvasive examinations and Ishak fibrosis score was compared. The t-test was used for comparison of LSM determined by FT and FS. Pearson correlation analysis was used investigate the correlation between LSM determined by FT and FS; Spearman correlation analysis was used to investigate the correlation of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and Knodell score with LSM determined by FT and FS; the correlation between LSM determined by FT and FS and fibrosis stage was analyzed by partial correlation analysis adjusted by Knodell score for liver inflammatory activity; Spearman correlation analysis was used for APRI, FIB-4, and fibrosis stage. Based on the Ishak fibrosis score, the receiver operating characteristic (ROC) curve was used to analyze the values of four noninvasive methods in the diagnosis of liver fibrosis. Results: There was no significant difference in LSM measured by FT and FS in all patients (15.75±9.42 kPa vs 15.42±10.52 kPa, P > 0.05) and Pearson correlation analysis indicated a significant positive correlation between them (r = 0.858, P < 0.01); serum ALT and AST levels and liver inflammatory activity were correlated with LSM determined by FT and FS. There was a significant positive correlation between LSM determined by FT and FS and fibrosis stage (r = 0.501 and 0.526, both P < 0.001), and APRI and FIB-4 were also positively correlated with fibrosis stage (r = 0.236 and 0.218, both P < 0.001). Based on the Ishak fibrosis score, in the diagnosis of fibrosis stages F3, F4, F5, and F6, the areas under the ROC curve were 0.915/0.856/0.839/0.816 for FT, 0.933/0.883/0.849/0.856 for FS, 0.618/0.630/0.608/0.638 for APRI, and 0.614/0.624/0.595/0.649 for FIB-4, and FT and FS had a significantly larger areas under the ROC curve than APRI and FIB-4. Conclusion: LSM determined by FT or FS has a good correlation with the Ishak fibrosis score, so FT and FS have a significantly better diagnostic performance for liver fibrosis than APRI and FIB-4.

[Current status of Chinese herbal preparations included in LiverTox database].

Objective: To investigate the contents and features of drug-induced liver injury (DILI) database called LiverTox, as well as 37 herbal preparations included in this database. Methods: Firstly, the source and contents of LiverTox were briefly introduced, including the clinical features, types, severity, and causality assessment scale of DILI. Secondly, detailed information of 37 herbal preparations included in the class of "Herbals and Dietary Supplements" were extracted, including drug name, origin, efficacy, constituents, type of liver injury, and manifestations, to perform a preliminary statistical analysis. Finally, a comparative analysis was performed between such information and current knowledge of Chinese herbal medicine-induced liver injury in China. Results: LiverTox was a DILI database with open access and rich information and provided practical information on treatment, typing, causality assessment, and treatment. Among the 37 herbal preparations, 28 had the risk of liver injury. The most common indication was weight loss, followed by arthritis and constipation. The latency of hepatotoxicity ranged from 4 weeks to 6 months. Compared with the current knowledge in China, there were differences in the varieties and indications for herbal preparations with hepatotoxicity included in LiverTox, and many herbals with acknowledged hepatotoxicity in China were not included. Conclusion: LiverTox database is concise and practical, but there are certain differences between the herbal preparations included in this database and current knowledge in China.

Safety evaluation of daidzein in laying hens: part I. Effects on laying performance, clinical blood parameters, and organs development.

Daidzein, an estrogen-like product, becomes increasingly popular as a dietary supplement, particularly for postpeak-estrus animals seeking a safe natural alternative to play a role of estrogen. However, there is little available safety data of it for raisers and consumers. A subchronic laying hen safety study was conducted to examine if the high-dose daidzein could affect the safety of hens selves, including laying performance, clinical blood parameters and organs development. Seven hundred and sixty-eight 56-week-old Hyline Brown were randomly assigned to 4 groups with 8 replicates of 24 birds each and 3weeks later fed diets supplemented with 0, 10, 50 and 100mg of daidzein/kg for 12weeks. The mortality was significantly decreased (P<0.05). No treatment related adverse clinical signs were observed. Mean egg production, egg mass and feed conversion of whole experiment period was significantly influenced by dietary daidzein supplement (P<0.05), showing significant quadratic response to increasing dietary daidzein supplement (P=0.029, P=0.003 and P=0.019, respectively). There was no statistically significant changes in haematology (P>0.05). In clinical chemistry parameters, total protein, total cholesterol, calcium and phosphorus were significantly affected by dietary daidzein supplement (P<0.05). The no observed adverse effect level (NOAEL) is considered to be 50mg/kg.

Safety evaluation of daidzein in laying hens: part II. Effects on calcium-related metabolism.

Daidzein, an estrogen-like product, has become increasingly popular as a dietary supplement, particularly for postpeak-estrus animals seeking a safe natural alternative to play a role of estrogen. However, there is little available safety data of it for raisers and consumers. A subchronic laying hensafety study has been conducted to examine if the high-dose daidzein could affect calcium-related metabolism (eggshell quality and bone mineralization). Seven hundred and sixty-eight 56-week-old Hyline Brown were randomly assigned to 4 groups with 8 replicates of 24 birds each (192 laying hensper group) and 3weeks later fed diets supplemented with 0(control), 10, 50 and 100mg of daidzein/kg for 12week. Eggshell thickness, eggshell percentage, eggshell strength, eggshell Ca concentration was increased linearly with increasing dietary daidzein supplementation (P=0.001, P=0.007, P=0.002 and P=0.000, respectively). Serum Ca increased linearly with increasing dietarydaidzein supplementation (P=0.042), and serum P showed a significant quadratic response to dietarydaidzein supplementation (P=0.036). Bone ash and bone Ca were significantly influenced by dietarydaidzein supplementation (P<0.05). These findings indicate that daidzein hold no observed adverse effect on calcium metabolism, but also a safe and effective food additive for calcium metabolism in animals and humans.

Beneficial metabolic effects of the Malaysian herb Labisia pumila var. alata in a rat model of polycystic ovary syndrome.

AIM OF THE STUDY: New options are needed to prevent and treat metabolic disorders associated with polycystic ovary syndrome (PCOS). Labisia pumila var. alata (LPva)-a Malaysian herb thought to have phytoestrogenic effects-has shown promise in reducing body weight gain in ovariectomized rats. In this study, we investigated the effect of LPva on body composition and metabolic features in female rats treated continuously with dihydrotestosterone, starting before puberty, to induce PCOS. MATERIAL AND METHODS: At 9 weeks of age, the PCOS rats were randomly subdivided into two groups; PCOS LPva and PCOS control. PCOS LPva rats received a daily oral dose of LPva (50mg/kg body weight), dissolved in 1 ml of deionised water, for 4-5 weeks. PCOS controls received 1 ml of deionised water on the same schedule. RESULTS: LPva increased uterine weight (27%) and insulin sensitivity (36%) measured by euglycemic hyperinsulinemic clamp. Plasma resistin levels were increased and lipid profile was improved in LPva rats. In adipose tissue, LPva decreased leptin mRNA expression but did not affect expression of resistin and adiponectin. No effects on body composition, adipocyte size, or plasma leptin levels were observed. CONCLUSION: LPva increases uterine weight, indicating estrogenic effects, and improves insulin sensitivity and lipid profile in PCOS rats without affecting body composition.

Divergent roles of SHP-2 in ERK activation by leptin receptors.

The protein tyrosine phosphatase SHP-2 has been proposed to serve as a regulator of leptin signaling, but its specific roles are not fully examined. To directly investigate the role of SHP-2, we employed dominant negative strategies in transfected cells. We show that a catalytically inactive mutant of SHP-2 blocks leptin-stimulated ERK phosphorylation by the long leptin receptor, ObRb. SHP-2, lacking two C-terminal tyrosine residues, partially inhibits ERK phosphorylation. We find similar effects of the SHP-2 mutants after examining stimulation of an ERK-dependent egr-1 promoter-construct by leptin. We also demonstrate ERK phosphorylation and egr-1 mRNA expression in the hypothalamus by leptin. Analysis of signaling by ObRb lacking intracellular tyrosine residues or by the short leptin receptor, ObRa, enabled us to conclude that two pathways are critical for ERK activation. One pathway does not require the intracellular domain of ObRb, whereas the other pathway requires tyrosine residue 985 of ObRb. The phosphatase activity of SHP-2 is required for both pathways, whereas activation of ERK via Tyr-985 of ObRb also requires tyrosine phosphorylation of SHP-2. SHP-2 is thus a positive regulator of ERK by leptin receptors, and both the adaptor function and the phosphatase activity of SHP-2 are critical for this regulation.

[Study on improving the dissolution rate of tanshinone in vitro by solvent deposition method].

OBJECTIVE: To improve the dissolution rate of a poorly watersoluble drug, tanshinone. METHOD: Using pregeletinged starch as carrier, to prepare solvent deposition systems of tanshinone solvent method. The dissolution rate of tanshinone, solvent deposition systems and physical mixture were detected, and the physico-chemical properties of these study forms were investigated with scanning electron microscopy and infrared spectroscopy. RESULT: The dissolution rate of tanshinone from the solvent deposition systems in vitro was significantly higher than that from physical mixtures and tanshinone powered alone. Tanshinone deposited on the surface of the carrier in crystal form, and the size was obviously reduced. A lot of acerose crystals of tanshinone on the surface of the carrier occurred. No chemical reaction acted between tanshinone and carrier. CONCLUSION: The dissolution rate of tanshinone in vitro can be improved with solvent deposition method.

[The regulation of Lycium barbarum on apoptosis of rat spleen in vitro].

The regulation of Lycium barbarum (LB) on apoptosis of rat spleen induced by hydrocortisone (HYD) was studied in this paper. The results indicated LB could inhibit the apoptosis induced by HYD and the inhibition is dose dependent.

Identification of a candidate human spectrin Src homology 3 domain-binding protein suggests a general mechanism of association of tyrosine kinases with the spectrin-based membrane skeleton.

Spectrin is a widely expressed protein with specific isoforms found in erythroid and nonerythroid cells. Spectrin contains an Src homology 3 (SH3) domain of unknown function. A cDNA encoding a candidate spectrin SH3 domain-binding protein was identified by interaction screening of a human brain expression library using the human erythroid spectrin (alphaI) SH3 domain as a bait. Five isoforms of the alphaI SH3 domain-binding protein mRNA were identified in human brain. Mapping of SH3 binding regions revealed the presence of two alphaI SH3 domain binding regions and one Abl-SH3 domain binding region. The gene encoding the candidate spectrin SH3 domain-binding protein has been located to human chromosome 10p11.2 --> p12. The gene belongs to a recently identified family of tyrosine kinase-binding proteins, and one of its isoforms is identical to e3B1, an eps8-binding protein (Biesova, Z., Piccoli, C., and Wong, W. T. (1997)Oncogene 14, 233-241). Overexpression of the green fluorescent protein fusion of the SH3 domain-binding protein in NIH3T3 cells resulted in cytoplasmic punctate fluorescence characteristic of the reticulovesicular system. This fluorescence pattern was similar to that obtained with the anti-human erythroid spectrin alphaI SigmaI/betaI SigmaI antibody in untransfected NIH3T3 cells; in addition, the anti-alphaI SigmaI/betaI SigmaI antibody also stained Golgi apparatus. Immunofluorescence obtained using antibodies against alphaI SigmaI/++betaI SigmaI spectrin and Abl tyrosine kinase but not against alphaII/betaII spectrin colocalized with the overexpressed green fluorescent protein-SH3-binding protein. Based on the conservation of the spectrin SH3 binding site within members of this protein family and published interactions, a general mechanism of interactions of tyrosine kinases with the spectrin-based membrane skeleton is proposed.

Synthetic osteochondral replacement of the femoral articular surface.

We have studied damage to the tibial articular surface after replacement of the femoral surface in dogs. We inserted pairs of implants made of alumina, titanium and polyvinyl alcohol (PVA) hydrogel on titanium fibre mesh into the femoral condyles. The two hard materials caused marked pathological changes in the articular cartilage and menisci, but the hydrogel composite replacement caused minimal damage. The composite osteochondral device became rapidly attached to host bone by ingrowth into the supporting mesh. We discuss the clinical implications of the possible use of this material in articular resurfacing and joint replacement.

A clinical study on severe hydroa vacciniforme.

OBJECTIVE: To describe a severe type of hydroa vacciniforme (HV) in order to provide basis for treatment and prevention of this disease. METHODS: Nine cases of HV were collected in our outpatient department, and clinical and laboratory examinations were performed. RESULTS: All the cases had erythemas, papules, bullae, erosions or ulcers on exposed sites, with recurrences, gradually resulting in deformation. Five patients suffered from hand deformation manifesting rigidity, flexor tetanus, or malposition of the first, second and third interphalangeal joints of hands. Two of the above mentioned patients manifested partial bone absorption of fingers. Five patients showed partial defect of auricle. Two patients showed saddle nose, and partial absorption of nasal cartilage. One patient displayed cicatricial contracture of lower lip, with incisor extrusion. Four patients showed opacity of cornea. Through laboratory examinations, porphyrinopathies were excluded. Phototests showed increased sensitivity to ultraviolet-A radiation (UVA). CONCLUSIONS: Based on the clinical features and laboratory examinations, these patients were diagnosed as having severe HV. It is believed that this condition belongs to a disease spectrum induced by ultraviolet light. Our analysis suggests that for children with severe type of HV, preventive measures and therapeutic agents should be taken as soon as possible in order to avoid deterioration of the disease and malformations.

Bone remodeling around implanted ceramics.

Bone formation and remodeling around implanted materials is influenced by the kind of material, its surface properties, and the anatomical site of implantation. In this study, differences in bone formation around three kinds of ceramics and the importance of the implant location in the tibia were investigated. In the first experiment, we placed three kinds of ceramics--alumina, zirconia and hydroxyapatite (HA)--into the medullary cavity of rabbit tibiae and examined histologically the time-dependent formation of bone around the materials for up to 24 weeks postoperatively. We found that bone formation depends on whether or not the materials are in direct contact with the endosteum. In the second experiment, the same three ceramic materials were implanted transcortically into rabbit tibiae. The bone formed around the implants was most abundant in regions adjacent to the periosteum, followed by the endosteum and the marrow cavity in the approximate ratios of 70%, 40%, and 10%, respectively. In these two experiments, the difference between bioactive and bioinert ceramics could be seen in the interface between the implanted material and the bone. It can be concluded that bone formation around these materials is related to the osteoconductivity of the materials and to the osteogenic capacity of the tissues.

[Effect of xiao chaihu decoction on experimental alkaline reflux gastritis in rats].

UNLABELLED: The effects of Xiao Chaihu Decoction (XCHD) on alkaline reflux gastritis and gastric secretion in rats was observed. RESULTS: (1) 5g/kg, 20 g/kg of XCHD might markedly inhibit the gastric lesion induced by gastric feeding of sodium taurocholate; (2) 5g/kg, 20g/kg of XCHD might significantly prevent the gastric lesion induced by gastric feeding of intestinal juice; (3) On chronic reflux gastritis model induced by spring-expanded pylorus after 4 or 8 weeks, 4g/kg-20g/kg of XCHD might lower the incidence of gastritis, and reduce the intragastric bile acid; (4) 5g/kg and 20g/kg of XCHD might significantly inhibit the secretion of gastric juice and acid as well as the activity of pepsin. The results suggested that XCHD had anti-reflux gastritis effect.

[Effects of 3 Chinese medical prescriptions on alkaline reflux gastritis in rats].

The experimental alkaline reflux gastritis in rats was established after 9 weeks of anastomosis between stomach and jejunum. The experiment shows that xiangsha liujunzi decoction, xiaochaihu decoction and dahuang gancao decoction all help to inhibit edema, hyperamia and extravasted blood, as well as depress inflammatory infiltration and hyperplasia. The number of intestinal metaplasia in the group treated with xiangsha liujunzi decoction is decreased. All the three prescriptions are not able to lower the contents of bile acid in the stomach.

Dialyzed fetal bovine serum increases cytogenetic fragile X expression.

UNLABELLED: Short-term whole blood cultures from 9 unrelated male individuals with the fragile X [fra(X)] syndrome were exposed to 5-fluorodeoxyuridine (FUdR). The fra(X) frequency was higher in 8 of 9 cases where the complete medium contained dialyzed fetal bovine serum (DFBS). In 3 of the cases, the fra(X) frequency nearly tripled (e.g., 12/100 to 33/100) while in 2 others, it nearly doubled (e.g., 15/100 to 29/100). When DFBS cultures from 2 other fra(X) individuals were exposed to increasing folic acid concentrations ranging from 2 to 4,000 x 10(-6) M, there was virtually no change in fra(X) expression. In 6 of 9 DFBS cultures, the mitotic index decreased, and it increased in 3. Therefore, although the fra(X) frequency increased, in most DFBS cultures the mitotic index decreased. Whether the reduction in mitotic index indicates an inverse correlation between reduced mitotic index and increased fra(X) expression, at least in cultures from some individuals, will be determined by additional studies. IN CONCLUSION: (1) medium supplementation with dialyzed fetal bovine serum should be considered when using FUdR for fra(X) identification in order to avoid potentially false negative results; (2) there appears to be no direct correlation between increased mitotic index and increased fra(X) expression in whole blood cultures; (3) increased folic acid concentrations do not affect fra(X) expression when FUdR fra(X) induction is employed; therefore requesting people to refrain from taking vitamins, including folic acid, before fra(X) testing (a practice that still persists in some places) appears unnecessary.