Screening and characterization estrogen receptor ligands from Arnebia euchroma (Royle) Johnst. via affinity ultrafiltration LC-MS and molecular docking.

Arnebiae Radix (dried root of Arnebia euchroma (Royle) Johnst.) is a traditional Chinese medicine (TCM) used to treat macular eruptions, measles, sore throat, carbuncles, burns, skin ulcers, and inflammations. The Arnebiae Radix extract can exert anti-breast cancer effects through various mechanisms of action. This study aimed to rapidly screen potential estrogen receptor (estrogen receptor α and estrogen receptor ß) ligands from the Arnebiae Radix extract. In this study, an analytical method based on affinity ultrafiltration coupled with UHPLC-Q-Exactive Orbitrap mass spectrometry was established for rapidly screening and identifying estrogen receptor ligands. Then, bindings of the components to the active site of estrogen receptor (estrogen receptor α and estrogen receptor ß) were investigated via molecular docking. Moreover, surface plasmon resonance (SPR) experiments with six compounds were performed to verify the affinity. As a result, a total of 21 ligands were screened from Arnebiae Radix using affinity ultrafiltration. Among them, 14 and 10 compounds from Arnebiae Radix showed affinity with estrogen receptor α and estrogen receptor ß, respectively. All of those ligands could have a good affinity for the multiple amino acid residues of the estrogen receptor based on molecular docking. In addition, six compounds display the great affinity by SPR. The method established in the study could be used to rapidly screen estrogen receptor ligands in Traditional Chinese medicine. The results demonstrated that the affinity ultrafiltration-UHPLC-Q-Exactive Orbitrap mass spectrometry method not only aids in the interpretation of the potential bioactive components and possible mechanisms of action of Arnebiae Radix but also provides a further effective basis for the quality control of this valuable herb medicine.

Environmentally benign cinchonain IIa from Uncaria laevigata for corrosion inhibition of Q235 steel in HCl corrosive medium: Experimental and theoretical investigation.

Traditional corrosion inhibitors make great contribution to metal protection, but also cause environmental pollution. To solve the problem, plant extracts as green corrosion inhibitors have attracted much attention in recent years. Plants are good raw materials for corrosion inhibitors and also meet the requirements of industry. However, they have not been successfully applied in industry due to the unknown composition of the effective corrosion inhibitors and large dosage thereof. Therefore, cinchonain IIa was separated from Uncaria laevigata with abundant sources and low cost from nature in this work. Here we hypothesized that cinchonain IIa could show good corrosion inhibition performance for Q235 steel in the acidic medium. Through experiments and theoretical calculation, we studied the corrosion inhibition effect of cinchonain IIa on Q235 in 1 M HCl solution at 298 K for 48 h. Electrochemical experiments revealed that the inhibition efficiency of 200 mg/L cinchonain IIa in 1 M HCl for Q235 steel was 94.08% for 48 h. It even showed over 93% corrosion inhibition efficiency and durable protection performance to 28 d. Surface observations indicated that cinchonain IIa were firmly attached to the steel surface by forming a protective film. Moreover, quantum chemical calculation and molecular dynamics simulation revealed the inhibition mechanism at molecular and atomic level. Compared with some plant extracts, here we demonstrate that the outstanding advantages of cinchonain IIa include sustained protective effect, small dosage, and low toxicity. Accordingly, it may be used as a green industrial corrosion inhibitor with great potential in oilfield acidification and acid pickling.

The effects of acarbose therapy on reductions of myocardial infarction and all-cause death in T2DM during 10-year multifactorial interventions (The Beijing Community Diabetes Study 24).

To investigate the potential benefits of acarbose therapy on cardiovascular events (CVD) in Type 2 diabetes (T2DM) in an urban community over 10-year follow-up. The study population of Beijing Community Diabetes Study (BCDS) were type 2 diabetes (T2DM) living in 21 communities in Beijing. All patients received comprehensive intervention in accordance with the Chinese guidelines for the prevention and treatment of diabetes. Professors in endocrinology from top tier hospitals regularly visited the communities for consultations, which was a feature of this study. A total of 1797 T2DM in BCDS study had complete screening data, including blood glucose, blood pressure, lipid profiles and acarbose continuous therapy. After 10-year follow-up, the risks of CVD outcomes were assessed according to whether patients had received acarbose therapy or not. All patients were followed-up to assess the long-term effects of the multifactorial interventions. At baseline, compared with the acarbose therapy free in T2DM, there was no significant difference in achieving the joint target control in patients with acarbose therapy. From the beginning of 8th year follow-up, the joint target control rate in patients with acarbose therapy was significantly higher than that of acarbose therapy free. During the 10-year follow-up, a total of 446 endpoint events occurred, including all-cause death, cardiovascular events, cerebrovascular events. The incidences of myocardial infarction (from the 4th year of follow-up) and all-cause death (from the 2nd year of follow-up) in patients who received acarbose therapy were significantly lower than that of acarbose therapy free respectively. In Cox multivariate analyses, there were significant differences in incidences of myocardial infarction and all-cause death between afore two groups during the 10-year follow-up, and the adjusted HRs were 0.50 and 0.52, respectively. After multifactorial interventions, T2DM with acarbose therapy revealed significant reductions of myocardial infarction and all-cause death. The long-term effects of with acarbose therapy on improving joint target control might be one of the main reasons of myocardial infarction and all-cause death reduction.Trial Registration: ChiCTR-TRC-13003978, ChiCTR-OOC-15006090.

Phenolic constituents with neuroprotective activities from Hypericum wightianum.

Five undescribed phenolic compounds, inclusing a depsidone derivative, hyperwightin A, a flavone derivative, hyperwightin B, and three benzophenone glycosides, hyperwightins C-E, along with four known ones were isolated from the 95% EtOH extract of the whole plants of Hypericum wightianum. Structures of the obtained compounds were elucidated by spectroscopic analyses. The protective effects of the isolates against corticosterone-induced PC12 cell injury were assessed. Hyperwightin E, petiolin G and hyperxanthone exhibited noticeable neuroprotection at 10 µM.

Epigallocatechin gallate from green tea exhibits potent anticancer effects in A-549 non-small lung cancer cells by inducing apoptosis, cell cycle arrest and inhibition of cell migration.

PURPOSE: Green tea (Camellia sinensis) is considered as a rich source of epigallocatechin gallate (EGCG) which has been shown to exert impressive pharmacological properties. The anticancer properties of EGCG have been extensively studied however, its anticancer activity has not been explored in lung cancer. The present study was therefore designed to evaluate the anticancer effects of EGCG against non-small cell lung cancer (NSCLC) cell line A-549 and normal human fibroblast FR-2 cells. METHODS: Cell viability was assessed by CCK8 assay, apoptosis by DAPI, annexin V/propidium iodide (PI) and flowcytometery and cell cycle analysis by flow cytometry. Cell migration capacity was investigated by wound-healing assay and protein expression was examined by Western blotting. RESULTS: The results revealed that EGCC could inhibit the proliferation of A-549 cells in a concentration-dependent manner and exhibited an IC50 of 25 µM against the IC50 of 100 µM against the normal human fibroblasts. Further evaluation revealed that EGCG exerts its anticancer effects via induction of apoptosis, modulation of Bax/blc-2 ratio and by triggering G2/M cell cycle arrest. Furthermore, EGCG could also inhibit the migration of A5-49 cells in a concentration-dependent manner. CONCLUSION: In conclusion, based on our results, we believe that EGCG could prove to be an important lead molecule for the treatment of lung cancer.

Isoflavones and Prostate Cancer: A Review of Some Critical Issues.

OBJECTIVE: The purpose of this review is to discuss some critical issues of isoflavones protective against the development of prostate cancer (PCa). DATA SOURCES: Data cited in this review were obtained primarily from PubMed and Embase from 1975 to 2015. STUDY SELECTION: Articles were selected with the search terms "isoflavone", "Phytoestrogen", "soy", "genistin", and "PCa ". RESULTS: Isoflavones do not play an important role on prostate-specific antigen levels reduction in PCa patients or healthy men. The effect of isoflavones on sex hormone levels and PCa risk may be determined by equol converting bacteria in the intestine, specific polymorphic variation and concentrations of isoflavones. The intake of various types of phytoestrogens with lower concentrations in the daily diet may produce synergistic effects against PCa. Moreover, prostate tissue may concentrate isoflavones to potentially anti-carcinogenic levels. In addition, it is noteworthy that isoflavones may act as an agonist in PCa. CONCLUSIONS: Isoflavones play a protective role against the development of PCa. However, careful consideration should be given when isoflavones are used in the prevention and treatment of PCa.

Disruption of reproductive development in male rat offspring following gestational and lactational exposure to di-(2-ethylhexyl) phthalate and genistein.

Studies of developmental effects of mixtures of endocrine disrupters on the male reproductive system are of great concern. In this study, the reproductive effects of the co-administration of di-2-(ethylhexyl) phthalate (DEHP) and genistein (GEN) during pregnancy and lactation were studied in male rat offspring. Pregnant Sprague-Dawley rats were gavaged from gestation day 3 to postnatal day 21 with vehicle control, DEHP 250 mg/kg body weight (bwyday, GEN 50 mg/kg bwday, GEN 400 mg/kg bwday, and two combinations of the two compounds (DEHP 250 mg/kg bwday + GEN 50 mg/kg bwday, DEHP 250 mg/kg bwday + GEN 400 mg/kg bwday). The outcomes studied were general morphometry (weight, AGD), testicular histology, testosterone levels, and expression at the mRNA level of genes involved in steroidogenesis. Organ coefficient, AGD / body weight1/3 י, serum testosterone concentration and genes involved in steroidogenic pathway expression when exposed to DEHP (250mg/kg bwday), GEN(50mg/kg bwday) or GEN(400mg/kg bwday) alone were not significantly different from the control group. When exposed to (DEHP 250mg/kg bwday +GEN 50mg/kg bwday) together during pregnancy and lactation, serum testosterone concentration, epididymis coefficient and Cypal17a1,Scarb1 m RNA expression significantly decreased compared to the control and GEN(50mg/kg bwday). When exposed to (DEHP 250mg/kg bwday +GEN 400mg/kg bwday) together during pregnancy and lactation, AGD / body weight1/3 י, serum testosterone concentration, testis and epididymis coefficient and Star, Cypal17a1 mRNA expression appeared significantly decreased compared to the control and DEHP/GEN single exposure, together with developmental impairment of seminiferous tubules and seminiferous epithelium. Overall, co-administration of DEHP and GEN during gestation and lactation seem to acts in a cumulative manner to induce the most significant alterations in the neonate, especially with GEN at high dose, although the effect of the DEHP-GEN mixture on adult offspring should be observed further.

Baicalein induces apoptosis via a mitochondrial-dependent caspase activation pathway in T24 bladder cancer cells.

Recurrence of bladder cancer following transurethral resection of bladder tumor (TURBt) is an obstacle in clinical management. In the current study, we investigated the antitumor activity of baicalein, a Chinese herbal medicine, against T24 bladder cancer cells in vitro. Baicalein inhibited growth and caused G1/S arrest of the cell cycle in the T24 cells. Moreover, baicalein induced apoptosis via loss of mitochondrial transmembrane potential (ΔΨm), release of cytochrome c and activation of caspase-9 and caspase-3. Baicalein inhibited Akt phosphorylation, downregulated Bcl-2 expression and upregulated Bax expression, which in turn increased the ratio of Bax/Bcl-2. Our results demonstrate that baicalein repressed growth inhibition and induced apoptosis via loss of ΔΨm and activation of caspase-9 and caspase-3 in T24 bladder cancer cells, which indicates that baicalein may be an effective agent in the clinical management of bladder cancer.

Disruption of reproductive development in male rat offspring following gestational and lactational exposure to di-(2-ethylhexyl) phthalate and genistein

Studies of developmental effects of mixtures of endocrine disrupters on the male reproductive system are of great concern. In this study, the reproductive effects of the co-administration of di-2-(ethylhexyl) phthalate (DEHP) and genistein (GEN) during pregnancy and lactation were studied in male rat offspring. Pregnant Sprague-Dawley rats were gavaged from gestation day 3 to postnatal day 21 with vehicle control, DEHP 250 mg/kg body weight (bwyday, GEN 50 mg/kg bwday, GEN 400 mg/kg bwday, and two combinations of the two compounds (DEHP 250 mg/kg bwday + GEN 50 mg/kg bwday, DEHP 250 mg/kg bwday + GEN 400 mg/kg bwday). The outcomes studied were general morphometry (weight, AGD), testicular histology, testosterone levels, and expression at the mRNA level of genes involved in steroidogenesis. Organ coefficient, AGD / body weight1/3 י, serum testosterone concentration and genes involved in steroidogenic pathway expression when exposed to DEHP (250mg/kg bwday), GEN(50mg/kg bwday) or GEN(400mg/kg bwday) alone were not significantly different from the control group. When exposed to (DEHP 250mg/kg bwday +GEN 50mg/kg bwday) together during pregnancy and lactation, serum testosterone concentration, epididymis coefficient and Cypal17a1,Scarb1 m RNA expression significantly decreased compared to the control and GEN(50mg/kg bwday). When exposed to (DEHP 250mg/kg bwday +GEN 400mg/kg bwday) together during pregnancy and lactation, AGD / body weight1/3 י, serum testosterone concentration, testis and epididymis coefficient and Star, Cypal17a1 mRNA expression appeared significantly decreased compared to the control and DEHP/GEN single exposure, together with developmental impairment of seminiferous tubules and seminiferous epithelium. Overall, co-administration of DEHP and GEN during gestation and lactation seem to acts in a cumulative manner to induce the most significant alterations in the neonate, especially with GEN at high dose, although the effect of the DEHP-GEN mixture on adult offspring should be observed further.

[Research of beta-elemene interventional treatment on VX2 carcinoma transplanted on kidney in rabbits].

OBJECTIVE: To investigate the curative effect and mechanism of beta-elemene interventional treatment on VX2 carcinoma transplanted on kidney in rabbits. METHODS: The rabbits were all transplanted with VX2 carcinoma on kidney. Fifty-five rabbits were randomly divided into 11 groups. Rabbits in these groups were administered interventional treatment of normal saline, iodinated oil, mitomycin, 5-fluorouracil, beta-elemene, cisplatin, carboplatin, adriamycin, thiotepa, cyclophopsphamide, and vincristine, respectively. After corresponding intervention, the tumor volume in each group was measured by ultrasonography and spiral computed tomography, and the tumor growth rate (TGR) was calculated. Nenal and hepatic functions of the rabbits in each group were compared 1 day, 7 and 14 days after the interventional treatment. Morphologic change of the tumor was observed by a light microscopy and a transmission electron microscopy 14 days after interventional treatment. The expressions of Bax and Bcl-2 were measured by immunohistochemical straining. RESULTS: There was statistical significance in the effects of different medicines intervened on VX2 kidney transplanted carcinoma. The VX2 carcinoma of rabbits had high-sensitivity to iodized oil embolism, mitomycin, cisplatin and carboplatin, which showed serious damage to the kidney function, medium-sensitivity to beta-elemene, adriamycin and 5-fluorouracil, in which beta-elemene showed slight damage to the kidney function, and resistance to thiotepa, cyclohosphamide and vincristine. Most tumor cells displayed apoptosis in the beta-elemene interventional treatment group under light microscopy and transmission electron microscopy, and only few tumor cells displayed necrosis. The Bax expression was up-regulated (P<0.05) and the Bcl-2 expression had no significant difference (P>0.05) in the beta-elemene interventional treatment group. CONCLUSION: Intervention treatment of beta-elemene has significant effect on VX2 kidney transplanted carcinoma and little side effect on the kidney function. Its mechanism is related to enhancing the apoptosis of tumor cells, and Bax gene participates in this action.

[Simultaneous treatment for benign prostate hyperplasia and its concomitant diseases].

OBJECTIVE: To investigate the surgical treatment of benign prostate hyperplasia (BPH) and its concomitant diseases at the same time. METHODS: One hundred and fourteen operations were performed for BPH patients, including transurethral resection/vapor of the prostate (TURP/TUVP), inguinal herniorrhaphy, internal urethrotomy, transurethral resection of bladder tumor (TURBt) or vesical litholapaxy, and the data were reviewed. RESULTS: The procedures were successful in all cases. A follow-up of 3 to 60 months found a good outcome of TURP. There was no recurrence in 30 cases of inguinal hernia and 39 cases of vesical calculus. Of the 25 cases of urethral stricture, 1 had an obvious hypotension during the operation and 4 needed urethral dilatation after operation. Six of the 20 cases of bladder tumor underwent a second TURBt due to the recurring tumor which was far from prostatic urethra. CONCLUSION: Inguinal hernia, urethral stricture, bladder tumor or vesical calculus can be treated simultaneously during TURP.

[Effects of matrine on proliferation and apoptosis of human renal cell carcinoma cell line GRC-1].

OBJECTIVE: To observe the effects of matrine on proliferation and apoptosis of human renal cell carcinoma cell line GRC-1 in vitro, and to explore its mechanism. METHODS: The human renal cell carcinoma cell line GRC-1 was treated with matrine of different concentrations for 24, 48, 72 and 96 h respectively. The MTT assay was used to evaluate the cytotoxic effects of matrine on GRC-1 cells. The transmission electron microscope and flow cytometry were utilized to observe and detect the apoptosis of GRC-1 cells induced by matrine. The expression levels of Bcl-2 and Bax proteins were evaluated by streptavidin-biotin-peroxidase method. RESULTS: The matrine of different concentrations all have cytotoxic effects on GRC-1 cells, with obvious dose- and time-dependent effects. The apoptosis induced by matrine was confirmed in GRC-1 cells. With intervention of matrine (1.5 g/L) for 12 h, the expression level of Bcl-2 in GRC-1 cells was decreased while the expression level of Bax was increased as compared with those in the untreated group. CONCLUSION: The proliferation-inhibiting effects of matrine on human renal cell carcinoma cell line GRC-1 may be related to down-regulating the ratio of Bcl-2/Bax protein expression and promoting the apoptosis.

[Radiosensitization of beta-elemene on VX2 carcinoma transplanted on kidney in rabbits in vivo].

OBJECTIVE: To investigate the radiosensitization of beta-elemene on VX2 carcinoma transplanted on kidney in rabbits in vivo. METHODS: The rabbits were all transplanted with VX2 carcinoma on kidney. The appropriate dose of beta-elemene infusion via renal artery for further study on radiosensitization was determined. Then fifty-five rabbits were divided into three groups: untreated group, radiation group and radiation plus beta-elemene-treated group. After corresponding intervention for each group, the tumor volume was measured by ultrasonography and spiral computed tomography. The sensitization enhancement ratio (SER) of beta-elemene was calculated. The pathological change of tumor tissue in kidney was observed by light microscopy and electron transmission microscopy. The apoptotic index was also examined by TdT-mediated dUTP-biotin nick end labeling method. RESULTS: The most significant radiosensitivity was observed in the radiation plus beta-elemene-treated group with 6 Mev X-ray radiation dose of 3 Gy.Fx(-1).d(-1) x 5 d and beta-elemene dose of 10 mg.kg(-1).d(-1). The average time delayed for tumor growth was obviously longer in the radiation plus beta-elemene-treated group than those in the untreated group and radiation group. The SER of beta-elemene was 1.89. The apoptotic index of tumor cells in the radiation plus beta-elemene-treated group was also significantly higher than those in the untreated group and radiation group. CONCLUSION: The beta-elemene can enhance the effects of irradiation on VX2 carcinoma transplanted to kidney in rabbits in vivo by inducing apoptosis of tumor cells.