Toxic effects of Tripterygium glycoside tablets on the reproductive system of male rats by metabolomics, cytotoxicity, and molecular docking.

BACKGROUND: Tripterygium glycoside tablets (TGT) is the most common preparation from Tripterygium wilfordii Hook F, which is widely used in clinical for treating rheumatoid arthritis (RA) and other autoimmune diseases. However, its serious reproductive toxicity limits its application. PURPOSE: This study aimed to elucidate the toxic effects of TGT on the reproductive system of male RA rats and its potential toxic components and mechanism. METHODS: Collagen-induced arthritis (CIA) rat model was established, and TGT suspension was given at low, medium, and high doses. Gonadal index, pathological changes, and the number of spermatogenic cells were used to evaluate the toxic effects of TGT on the reproductive system. Non-targeted metabolomics of testicular tissue was conducted by UHPLC-QTOF/MS. Combined with network toxicology, the key targets of TGT-induced reproductive toxicity were screened and RT-qPCR was used to validation. In vitro toxicity of 19 components of TGT was evaluated using TM3 and TM4 cell lines. Molecular docking was used to predict the interaction between toxic components and key targets. RESULTS: TGT reduced testicular and epididymis weight. Pathology analysis showed a lot of deformed and atrophic spermatogenic tubules. The number of spermatogenic cells decreased significantly (P<0.0001). A total of 58 different metabolites including platelet-activating factor (PAF), lysophosphatidylcholine (Lyso PC), phosphatidylinositol (PI), glutathione (GSH), and adenosine monophosphate (AMP) were identified by testicular metabolomics. Glycerophospholipid metabolism, ether lipid metabolism, and glutathione metabolism were key pathways responsible for the reproductive toxicity of TGT. Ten key reproductive toxicity targets were screened by network toxicology. The cytotoxicity test showed that triptolide, triptonide, celastrol, and demethylzeylasteral could significantly reduce the viability of TM3 and TM4 cells. Alkaloids had no apparent toxic effects. Molecular docking showed that the four toxic components had a good affinity with 10 key targets. All binding energies were less than -7 kcal/mol. The RT-qPCR results showed the Cyp19a1 level was significantly up-regulated. Pik3ca and Pik3cg levels were significantly down-regulated. CONCLUSION: Through testicular metabolomics, we found that TGT may cause reproductive toxicity through CYP19A1, PIK3CA, and PIK3CG three target, which was preliminarily revealed. This study laid the foundation for elucidating the toxicity mechanism of TGT and evaluating its safety and quality.

Biochemical characterization, and anti-inflammatory and antitumor activities of glycoprotein from lamb abomasum.

ETHNOPHARMACOLOGICAL RELEVANCE: Lamb abomasum is used as an edible medicinal source in traditional Chinese medicine for the treatment of gastrointestinal disorders. Lamb abomasum sourced biochemical drug Lamb's trip extract and Vitamin B12 capsule used for the clinical treatment of chronic gastritis, gastric ulcer, and reversal of intestinal metaplasia. Therefore, claimed to have prevention of gastric cancer activity. AIM OF THE STUDY: In this study, we aim to assess whether the glycoprotein has biological activity in the cure of gastric disorder and conduct a structure-activity relationship. MATERIALS AND METHODS: Glycoproteins' extraction conditions were optimized by the response surface method and purified with DEAE-cellulose and Sephadex G-50 chromatography. Two homogenous glycoproteins' physiochemical structures were studied with electrophoresis, HPLC analysis, peroxide oxidation, and ß-elimination, FT-IR, CD, LC-MS/MS, and EDS analysis. The antiinflammation activity of the glycoprotein was determined against COX-2 and LOX-15 enzyme inhibitory ability in vitro, and antitumor activity against HT-29 and HGC-25, and cytotoxicity on L-02 cells was determined in vivo with the MTT method. RESULTS: The abomasum was abundant in glycoprotein and the extraction yield of glycoprotein was up to 24.6 ± 2.1% under optimized conditions. Two homogeneous glycoproteins SAGP-I and SAGP-II determined to be ribose-conjugated and sulfated glycoproteins with a molecular weight of 15.6 kDa and 6.4 kDa. And according to the structural analysis, SAGP-I was a mucin-type ribose-conjugated glycoprotein with 14 O-glycosylation and one N- glycosylation site. SAGP-I and SAGP-II have remarkable anti-inflammatory activity against COX-2 enzyme with the IC50 of 17.64 ± 1.25 µg/mL and 16.14 ± 1.11 µg/mL, respectively. Meanwhile, the two glycoproteins showed strong antitumor activity against HT-29 with the EC50 of 19.19 ± 1.46 µg/mL and 184.9 ± 5.6 µg/mL, respectively. CONCLUSION: The Highly purified glycoprotein SAGP-1 and SAGP-II showed anti-inflammatory activity against the COX-2 enzyme, and antitumor activity against HT-29 human colon cancer cells and noun-inhibitory activity against LOX-15 enzyme and HGC-25. Both glycoproteins are ribose conjugated and sulfated whose characters are related to their anti-inflammatory and anti-tumor activity. Such results suggest the possibility of anti-inflammatory and pre-cancer activity. And in some degree explains the pharmacy of abomasum's traditional use in gastric disorder and clinical use of lamb abomasum APIs drugs' in gastric disorders and gastric cancer development. This study provides a preliminary basis for the further study of the per-cancer mechanism of lamb abomasum glycoprotein. And, would be the material basis of the clinical use of Lamb's trip extract and Vitamin B12 capsule.

Revealment study on the regulation of lipid metabolism by Lingguizhugan Decoction in heart failure treatment based on integrated lipidomics and proteomics.

Lingguizhugan Decoction (LGZGD) is a classical traditional Chinese medicine prescription. Our previous studies found that disorders of lipid metabolism were reversed by LGZGD in heart failure (HF) mice. This study aimed to reveal the regulation of lipid metabolism of LGZGD. A mice model of HF was established by intraperitoneal injection of doxorubicin. The components of LGZGD were identified with the UHPLC-QTOF-MS method. The regulation of lipid metabolism by LGZGD was detected by serum lipidomics and heart tissue proteomics. Molecular docking was further performed to screen active components. A total of 78 compounds in LGZGD were identified. Results of lipidomics showed that 37 lipids illustrated a significant recovery trend to normal after the treatment of LGZGD. Results of proteomics demonstrated that 55 proteins were altered by the administration of LGZGD in HF mice. After enrichment analysis, the Prakg2/Ucp2/Plin1 axis on the Apelin pathway plays a vital role in HF treatment by LGZGD. Nine active components exhibited the outstanding ability of binding to the apelin receptor with MM-GBSA value lower than -60 Kcal/mol. In conclusion, all results combined together revealed that multi-component in the LGZGD had beneficial effects on the HF through ameliorating lipid disorders, which provides a novel insight into the cardioprotective effects of LGZGD and its clinical application.

Synchronous Investigation of the Mechanism and Substance Basis of Tripterygium Glycosides Tablets on Anti-rheumatoid Arthritis and Hepatotoxicity.

Tripterygium Glycosides Tablets (TGT) has shown obvious anti-rheumatoid arthritis (RA) effects accompanied by hepatotoxicity. Despite that many studies looked at TGT's anti-RA or hepatotoxic mechanism and substance basis, the results were still insufficient. Furthermore, the anti-RA and hepatotoxicity investigations of TGT were undertaken separately, neglecting the relationship between efficacy and toxicity. Herein, an integrated approach combining metabolomics, network pharmacology, serum pharmacochemistry, and molecular docking was adopted to elucidate the mechanism and substance basis of Tripterygium Glycosides Tablets (TGT) on anti-rheumatoid arthritis and hepatotoxicity simultaneously. The results showed that 33 components in TGT were absorbed into rat serum. Two toxic targets (PRKCA, FASN), three effective targets (PLA2G10, PTGES, PLA2G1B), and four effective and toxic targets (PTGS1, PTGS2, PLA2G2A, ALOX5) were obtained by metabolomics combined with network analysis and network pharmacology. A component-target-RA-hepatotoxicity network was constructed and five hepatotoxic components (1-desacetylwilforgine, wilfordconine, wilforgine, wilformine, wilfornine D), eight effective-toxic components (14-oxo-19-(4 → 3) abeo-abieta-3,8,12-tetraen-19,18-olide, 7-oxo-18(4 → 3) abeo-abieta-3,8,11,13-tetraen-18-oic acid, hypoglaulide, triptotriterpenic acid A, wilforol F, wilforlide B, triptoquinone B, wilforlide A); and 23 non-effective and non-toxic components were acquired and validated by molecular docking. In addition, our research revealed that glycerophospholipid metabolism and ether lipid metabolism were correlated to both hepatotoxicity and anti-RA of TGT. While in sphingolipid metabolism, ceramidases regulated ceramide-sphingosine and phytoceramide-phytosphingosine reaction were found to be correlated to hepatotoxicity, sphinganine-1-phosphate lyase (SPL) regulated sphingosine 1-phosphate (S1P)-phosphoethanolamine and sphinganine 1-phosphate-phosphoethanolamine were found to be attributed to anti-RA effects.

An integrated approach for investigating pharmacodynamic material basis of Lingguizhugan Decoction in the treatment of heart failure.

ETHNOPHARMACOLOGICAL RELEVANCE: As a classical formula of traditional Chinese medicine (TCM), Lingguizhugan Decoction (LGZGD) has been used for treating heart failure (HF) because it has an efficiency of yang-warming and fluid-dispersing. However, the pharmacodynamic material basis of LGZGD responsible for the therapeutic benefits is not well understood. AIM OF THE STUDY: The aim of this study was to elucidate the pharmacodynamic material basis of LGZGD by an integrated approach. MATERIALS AND METHODS: Following oral administration of LGZGD in mice, ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS/MS) was used to identify prototype substances. A heart failure (HF) model was established, followed by an untargeted metabolomics study to determine potential targets of LGZGD. The network pharmacology method was performed to screen substances that interacted with potential targets of LGZGD treating HF. Molecular docking technology was applied to further screen substances based on binding energy. Cell viability assays were conducted to verify pharmacodynamic effects of selected substances. RESULTS: In all, forty-two prototype substances were identified in the blood, urine, and fecal samples of mice. A total of fifty-five differential metabolites were identified using heart tissue untargeted metabolomics. Twenty-five substances of LGZGD were screened relating to thirty-three targets treating HF. Twenty-two substances were filtered according to their binding energy using molecular docking technology. Cell experiments revealed cinnamaldehyde, glycyrrhetinic acid, kaempferol, daidzein, caffeic acid, and catechin could significantly improve the survival rate of H9c2 cells, which might be the pharmacodynamic material basis of LGZGD. CONCLUSIONS: A scientific approach that integrated in vivo substances identification, metabolomics, network pharmacology, molecular docking, and cell pharmacodynamic assay has been developed to study the pharmacodynamic material basis of LGZGD in the treatment of HF.

Identification and comparison of compounds in commercial Tripterygium wilfordii genus preparations with HPLC-QTOF/MS based on molecular networking and multivariate statistical analysis.

Tripterygium wilfordii genus preparations (TWGP) are widely used in traditional Chinese medicines for the treatment of autoimmune diseases and immune diseases with definite therapeutic effects but high toxicity. The aim of this study is to identify and compare chemical compounds in three types of commercial TWGP using UHPLC-QTOF-MS/MS and molecular networking (MN) technology. First, the mass fragmentation pathways of 10 compounds were investigated, which included two sesquiterpene alkaloids, four diterpenoids, and four triterpenoids. The chemical compounds were then identified using UHPLC-QTOF-MS/MS and a conventional database. Following that, molecular network technology was used to further identify the GNPS platform. Finally, metabonomic data analysis was used to compare 92 commercial TWGP samples from 13 manufacturers. A total of 103 compounds were identified, with the molecular network detecting 40 of them. Moreover, the quality of commercial Tripterygium glycoside tablets varies greatly and 26 compounds, including triptolide, wilforine, wilforgine, and demethylzeylasteral, were discovered to be the main differential compounds in tripterygium glycosides tablets. This was the first time MN technology was used for compound analysis in TWGP, laying the foundation for classifying effective and toxic substances and TWGP quality control.

Dynamic profiles of fermentation characteristics and bacterial community composition of Broussonetia papyrifera ensiled with perennial ryegrass.

Broussonetia papyrifera (B. papyrifera) has been proposed to improve silage fermentation due to its high content of protein and abundant active plant extracts. Thus, dynamic profiles of fermentation quality and bacterial community of B. papyrifera mixing with perennial ryegrass in different ratios: 100:0, 90:10, 80:20, 70:30, 60:40, and 50:50 were examined during 60-d fermentation. Results showed that adding perennial ryegrass increased soluble carbohydrate content and lactic acid production in silage and decreased pH and population of epiphytic microorganisms. Adding ryegrass exerted a remarkable effect on the silage bacterial community with a dramatic decrease in the abundance of Enterobacter. Spearman's rank correlation showed that silage lactic acid concentration was positively correlated with Lactobacillus and Stenotrophomonas abundance, while ammonia nitrogen concentration was positively correlated with the abundance of Enterobacter. In conclusion, B. papyrifera ensiled with perennial ryegrass could improve B. papyrifera silage quality and provide high-quality forage resources for sustainable ruminant livestock production.

Biological Activity of Endophytic Fungi from the Roots of the Medicinal Plant Vernonia anthelmintica.

Endophytic fungi were first isolated from the fresh root of the Chinese medicinal plant Vernonia anthelmintica collected from the Hotan Prefecture within the Xinjiang Autonomous region of the People's Republic of China. This plant has been used in Uyghur traditional medicine to treat vitiligo, a skin condition characterized by patches of the skin losing their pigment. In total, fifteen fungal strains were isolated. Among these, four endophytic fungi were identified by their DNA sequences and registered to GenBank with accession numbers. The isolates were identified as Schizophyllum commune XJA1, Talaromyces sp. XJA4, Aspergillus sp. XJA6, Aspergillus terreus XJA8. Ethyl acetate extracts of all fungal strains were used to quantify melanin content and to identify in vitro biological activity assays including antimicrobial, antioxidant, cytotoxic, antidiabetic and tyrosinase activity on B16 cells. Among the extracts of all four identified strains, the ethyl acetate extract of the Aspergillus sp. XJA6 was chosen for further characterization because it presented the highest biological activity against these tests. In addition, twenty four volatile compounds from the petroleum ether fraction were characterized by GC-MS.

Endophytic Bacteria Associated with Medicinal Plant Vernonia anthelmintica: Diversity and Characterization.

Increasing evidence shows that endophytic bacteria living inside plant tissue may possess similar biological activity and produce similar metabolites to their hosts. This study aimed to determine the diversity of endophytic bacteria associated with Vernonia anthelmintica and to evaluate their biological activity. The bacteria were isolated from the plant tissue using culture-dependent techniques. Comparison of the 16S rRNA gene sequences of endophytic bacteria isolated from V. anthelmintica showed that isolates belong to the species Micrococcus endophyticus VERA1, Bacillus megaterium VERA2, Pseudomonas chlororaphis VERA3, P. kilonensis VERA4, Stenotrophomonas pavanii VERA5, B. endophyticus VERA6, S. maltophilia VERA7, Pantoea ananatis VERA8, B. atrophaeus VERA9 and M. flavus VERA10. Activity studies showed that the endophytic bacteria share several similar biological properties with their host plant including antimicrobial, anti-vitiligo and antidiabetic activities. These findings indicate that plant phytochemical compounds and activity play an important role in the physiological properties of their endophytes.

Integrative serum metabolomics and network analysis on mechanisms exploration of Ling-Gui-Zhu-Gan Decoction on doxorubicin-induced heart failure mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Ling-Gui-Zhu-Gan Decoction (LGZGD) formula, derived from traditional Chinese medicine (TCM), has definitive clinical efficacy in the treatment of heart failure (HF) in China. However, little is known of the underlying mechanism of LGZGD. AIM OF THE STUDY: The aim of this work was to investigate the therapeutic mechanism of LGZGD on HF treatment based on an integration of the serum metabolomics and network analysis. MATERIALS AND METHODS: HF model mice were established by intraperitoneal injecting of doxorubicin. Body weight, echocardiography, biochemical assay and hematoxylin and eosin staining experiments were used to evaluate the efficacy of LGZGD. A metabolomics approach based on ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) was performed to analyze the serum biomarkers from model group, control group and LGZGD-treatment group. Principle component analysis (PCA) and orthogonal projection to latent structures-discriminant analysis (OPLS-DA) were utilized to identify differences of metabolic profiles in mice among the three groups. The network of "gene-enzyme-metabolite" was built to investigate the possible mechanism of LGZGD from the systematic perspective. RESULTS: 54 metabolites, which showed a significantly restoring trend from HF to normal condition, were regarded as potential biomarkers of LGZGD treatment. The most critical pathway was glycerophospholipid metabolism and arachidonic acid metabolism. According to the results of network analysis, 8 biomarkers were regarded as hub metabolites, which meant these metabolites may have a major relationship with the LGZGD therapeutic effects for the HF. 8 enzymes and 29 genes in the network were considered as potential targets of LGZGD treatment. CONCLUSIONS: By integrated serum metabolomic and network analysis, we found that LGZGD might retard the pathological process of HF by regulating the disturbed metabolic pathways and the relative enzymes, which may be potential mechanism for LGZGD in the treatment of HF.

Optimization of Scorpion Protein Extraction and Characterization of the Proteins' Functional Properties.

Scorpion has long been used in traditional Chinese medicine, because whole scorpion body extract has anti-cancer, analgesic, anti-thrombotic blood anti-coagulation, immune modulating, anti-epileptic, and other functions. The purpose of this study was to find an efficient extraction method and investigate some of physical and chemical parameters, like water solubility, emulsification, foaming properties, and oil-holding capacity of obtained scorpion proteins. Response surface methodology (RSM) was used for the determination of optimal parameters of ultrasonic extraction (UE). Based on single factor experiments, three factors (ultrasonic power (w), liquid/solid (mL/g) ratio, and extraction time (min)) were used for the determination of scorpion proteins (SPs). The order of the effects of the three factors on the protein content and yield were ultrasonic power > extraction time > liquid/solid ratio, and the optimum conditions of extraction proteins were as follows: extraction time = 50.00 min, ultrasonic power = 400.00 w, and liquid/solid ratio = 18.00 mL/g. For the optimal conditions, the protein content of the ultrasonic extraction and yield were 78.94% and 24.80%, respectively. The solubility, emulsification and foaming properties, and water and oil holding capacity of scorpion proteins were investigated. The results of this study suggest that scorpion proteins can be considered as an important ingredient and raw material for the creation of water-soluble supramolecular complexes for drugs.

Pea polyphenolics and hydrolysis processing alter microbial community structure and early pathogen colonization in mice.

Health benefits associated with pea consumption have been attributed to the fiber and polyphenolic content concentrated within the pea seed coat. However, the amount of pea polyphenols can vary between cultivars, and it has yet to be studied whether pea polyphenols impact the intestinal microbiota. We hypothesized that pea polyphenols promote a healthy microbiome that supports intestinal integrity and pathogen colonization resistance. To investigate the effects of pea polyphenols, pea cultivars rich and poor in proanthocyanidins were supplemented in raw or acid hydrolyzed form to an isocaloric diet in mice. Acid hydrolysis increases the absorption of pea polyphenols by cleaving polymeric proanthocyanidins to their readily absorbable anthocyanidin monomers. After 3 weeks of diet, mice were challenged with Citrobacter rodentium and pathogen colonization and inflammation were assessed. Counter to our hypothesis, pea seed coat fraction supplementation, especially the non-hydrolyzed proanthocyanidin-rich fraction diet adversely increased C. rodentium pathogen load and inflammation. Ileal, cecal and colon microbial communities were notably distinct between pea seed cultivar and hydrolysis processing. The consumption of intact proanthocyanidins decreased microbial diversity indicating that proanthocyanidins have antimicrobial properties. Together our results indicate supplementation of raw pea seed coat rich in proanthocyanidins adversely affect intestinal integrity. However, acid hydrolysis processing restored community structure and colonization resistance, and the anthocyanidin-rich fractions reduced weight gain on a high fat diet. Establishing a clear understanding of the effects of pea fiber and polyphenolic form on health will help to develop research-based pea products and dietary recommendations.

Lipid Emulsion Formulation of Parenteral Nutrition Affects Intestinal Microbiota and Host Responses in Neonatal Piglets.

BACKGROUND: Total parenteral nutrition (TPN) is a cause of intestinal microbial dysbiosis and impaired gut barrier function. This may contribute to life-threatening parenteral nutrition-associated liver disease and sepsis in infants. We compared the effects of a lipid emulsion containing long-chain ω-3 polyunsaturated fatty acids (PUFAs; SMOFlipid) and a predominantly ω-6 PUFA emulsion (Intralipid) on microbial composition and host response at the mucosal surface. MATERIALS AND METHODS: Neonatal piglets were provided isocaloric, isonitrogenous TPN for 14 days versus sow-fed (SF) controls. Equivalent lipid doses (10 g/kg/d) were given of either SMOFlipid (ML; n = 10) or Intralipid (SO; n = 9). Ileal segments and mucosal scrapings were used to characterize microbial composition by 16S rRNA gene sequencing and quantitative gene expression of tight junction proteins, mucins, antimicrobial peptides, and inflammatory cytokines. RESULTS: The microbial composition of TPN piglets differed from SF, while ML and SO differed from each other (analysis of molecular variance; P < .05); ML piglets were more similar to SF, as indicated by UniFrac distance ( P < .05). SO piglets showed a specific and dramatic increase in Parabacteroides ( P < .05), while ML showed an increase in Enterobacteriaceae ( P < .05). Gene expression of mucin, claudin 1, ß-defensin 2, and interleukin 8 were higher in TPN; overall increases were significantly less in ML versus SO ( P < .05). CONCLUSION: The formulation of parenteral lipid is associated with differences in the gut microbiota and host response of TPN-fed neonatal piglets. Inclusion of ω-3 long-chain PUFAs appears to improve host-microbial interactions at the mucosal surface, although mechanisms are yet to be defined.

Isoflavones extracted from chickpea Cicer arietinum L. sprouts induce mitochondria-dependent apoptosis in human breast cancer cells.

Isoflavones are important chemical components of the seeds and sprouts of chickpeas. We systematically investigated the effects of isoflavones extracted from chickpea sprouts (ICS) on the human breast cancer cell lines SKBr3 and Michigan Cancer Foundation-7 (MCF-7). 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays showed that ICS (10-60 µg/mL) significantly inhibited the proliferation of both cell lines in a time-dependent and dose-dependent fashion. Wright-Giemsa staining as well as annexin V-fluorescein isothiocyanate and propidium iodide (Annexin V/PI) staining showed that ICS significantly increased cytoclasis and apoptotic body formation. Quantitative Annexin V/PI assays further showed that the number of apoptotic cells increased in a dose-dependent manner following ICS treatment. Semiquantitative reverse transcription PCR showed that ICS increased the expression of the apoptosis-promoting gene Bcl-2-associated X protein and decreased the expression of the antiapoptotic gene Bcl-2. Western blot analysis showed that treatment of SKBr3 and MCF-7 cells with ICS increased the expression of caspase 7, caspase 9, P53, and P21 in a dose-dependent manner. Flow cytometry assays using the fluorescent probe 3,3'-dihexyloxacarbocyanine iodide showed a dose-dependent decrease in mitochondrial membrane potential following ICS treatment. Treatment using ICS also induced a dose-dependent increase in reactive oxygen species production. This is the first study to demonstrate that ICS may be a chemopreventive or therapeutic agent against breast cancer.

Assessment of the estrogenic activities of chickpea (Cicer arietinum L) sprout isoflavone extract in ovariectomized rats.

AIM: Chickpea (Cicer arietinum L) is a traditional Uighur herb. In this study we investigated the estrogenic activities of the isoflavones extracted from chickpea sprouts (ICS) in ovariectomized rats. METHODS: Ten-week-old virgin Sprague-Dawley female rats were ovariectomized (OVX). The rats were administered via intragastric gavage 3 different doses of ICS (20, 50, or 100 mg·kg(-1)·d(-1)) for 5 weeks. Their uterine weight and serum levels of 17ß-estradiol (E2), follicle stimulating hormone (FSH) and luteinizing hormone (LH) were measured. The epithelial height, number of glands in the uterus, and number of osteoclasts in the femur were histologically quantified, and the expression of proliferating cell nuclear antigen (PCNA) was assessed immunohistochemically. Bone structural parameters, including bone mineral density (BMD), bone volume/tissue volume (BV/TV), trabecular thickness (Tb.Th) and trabecular separation (Tb.Sp) were measured using Micro-CT scanning. RESULTS: Treatments of OVX rats with ICS (50 or 100 mg·kg(-1)·d(-1)) produced significant estrogenic effects on the uteruses, including the increases in uterine weight, epithelial height and gland number, as well as in the expression of the cell proliferation marker PCNA. The treatments changed the secretory profile of ovarian hormones and pituitary gonadotropins: serum E2 level was significantly increased, while serum LH and FSH levels were decreased compared with the vehicle-treated OVX rats. Furthermore, the treatments significantly attenuated the bone loss, increased BMD, BV/TV and Tb.Th and decreased Tb.Sp and the number of osteoclasts. Treatment of OVX rats with the positive control drug E2 (0.25 mg·kg(-1)·d(-1)) produced similar, but more prominent effects. CONCLUSION: ICS exhibits moderate estrogenic activities as compared to E2 in ovariectomized rats, suggesting the potential use of ICS for the treatment of menopausal symptoms and osteoporosis caused by estrogen deficiency.

Meta-analysis of randomized controlled trials on magnesium in addition to beta-blocker for prevention of postoperative atrial arrhythmias after coronary artery bypass grafting.

BACKGROUND: Atrial arrhythmia (AA) is the most common complication after coronary artery bypass grafting (CABG). Only beta-blockers and amiodarone have been convincingly shown to decrease its incidence. The effectiveness of magnesium on this complication is still controversial. This meta-analysis was performed to evaluate the effect of magnesium as a sole or adjuvant agent in addition to beta-blocker on suppressing postoperative AA after CABG. METHODS: We searched the PubMed, Medline, ISI Web of Knowledge, Cochrane library databases and online clinical trial database up to May 2012. We used random effects model when there was significant heterogeneity between trials and fixed effects model when heterogeneity was negligible. RESULTS: Five randomized controlled trials were identified, enrolling a total of 1251 patients. The combination of magnesium and beta-blocker did not significantly decrease the incidence of postoperative AA after CABG versus beta-blocker alone (odds ratio (OR) 1.12, 95% confidence interval (CI) 0.86-1.47, P = 0.40). Magnesium in addition to beta-blocker did not significantly affect LOS (weighted mean difference -0.14 days of stay, 95% CI -0.58 to 0.29, P = 0.24) or the overall mortality (OR 0.59, 95% CI 0.08-4.56, P = 0.62). However the risk of postoperative adverse events was higher in the combination of magnesium and beta-blocker group than beta-blocker alone (OR 2.80, 95% CI 1.66-4.71, P = 0.0001). CONCLUSIONS: This meta-analysis offers the more definitive evidence against the prophylactic administration of intravenous magnesium for prevention of AA after CABG when beta-blockers are routinely administered, and shows an association with more adverse events in those people who received magnesium.

[Study of the effect of super painkiller on the sexual function of male rats with type I diabetes].

OBJECTIVE: To study the effects of super painkiller on the sexual function of male Wistar rats with diabetes. METHODS: Thirty-two Wistar rats at 3-5 months of age were divided into two groups at random: 22 in the diabetes group, and 10 in the control group. After 72 hours, the former was further divided into 2 subgroups: non-treatment and super painkiller treatment. In 5 weeks, blood glucose was determined. After the apomorphines experiment, the rats were killed, blood taken from the vein, homogenate prepared from the isolated testis tissue and the level of NO and NOS in the serum and tissue homogenate surveyed, separately. RESULTS: Compared with the control group, serum NO and NOS of the diabetic rats dropped sharply. Compared with the non-treatment group, the serum NO and NOS of the super painkiller treatment group were very high and the difference was significant (P < 0.01). Apomorphine injection showed that the times of penis erection of the treated rats were more than those of the non-treatment group (P < 0.01) , but the difference was not significant compared with the control (P > 0.05). CONCLUSION: Super painkiller has sure effect of reducing blood glucose, with a certain curative value for sexual and reproductive malfunction of diabetic rats.