The use of non-steroidal anti-inflammatory drugs(NSAIDs) is widespread worldwide thanks to their analgesic, anti-inflammatory and antipyretic effects. However, even more attention is placed upon the recurrence of dige...The use of non-steroidal anti-inflammatory drugs(NSAIDs) is widespread worldwide thanks to their analgesic, anti-inflammatory and antipyretic effects. However, even more attention is placed upon the recurrence of digestive system complications in the course of their use. Recent data suggests that the complications of the lower gastro-intestinal tract may be as frequent and severe as those of the upper tract. NSAIDs enteropathy is due to enterohepatic recycling of the drugs resulting in a prolonged and repeated exposure of the intestinal mucosa to the compound and its metabolites. Thus leading to so-called topical effects, which, in turn, lead to an impairment of the intestinal barrier. This process determines bacterial translocation and toxic substances of intestinal origin in the portal circulation, leading to an endotoxaemia. This condition could determine a liver inflammatory response and might promote the development of nonalcoholic steatohepatitis, mostly in patients with risk factors such as obesity, metabolic syndrome and a high fat diet, which may induce a small intestinal bacterial overgrowth and dysbiosis. This alteration of gut microbiota may contribute to nonalcoholic fatty liver disease and its related disorders in two ways: firstly causing a malfunction of the tight junctions that play a critical role in the increase of intestinal permeability, and then secondly leading to the development of insulin resistance, body weight gain, lipogenesis, fibrogenesis and hepatic oxidative stress.展开更多
This paper has two aims. The first one is to investigate the existence of chaotic structures in the oil prices, expectations of investors and stock returns by combining the Lyapunov exponent and Kolmogorov entropy, an...This paper has two aims. The first one is to investigate the existence of chaotic structures in the oil prices, expectations of investors and stock returns by combining the Lyapunov exponent and Kolmogorov entropy, and the second one is to analyze the dependence behavior of oil prices, expectations of investors and stock returns from January 02, 1990, to June06, 2017. Lyapunov exponents and Kolmogorov entropy determined that the oil price and the stock return series exhibited chaotic behavior. TAR-TR-GARCH and TAR-TR-TGARCH copula methods were applied to study the co-movement among the selected variables. The results showed significant evidence of nonlinear tail dependence between the volatility of the oil prices, the expectations of investors and the stock returns. Further, upper and lower tail dependence and comovement between the analyzed series could not be rejected. Moreover, the TAR-TR-GARCH and TAR-TR-TGARCH copula methods revealed that the volatility of oil price had crucial effects on the stock returns and on the expectations of investors in the long run.展开更多
Proceeding from natural amino acid L-asparagine and commercially available aldehydes a stereoselective synthesis was developed of (2S,4S)-2-alkyl(aryl)-3-(3-sulfanylpropanoyl)-6-oxohexahy- dropyrimidine-4-carboxylic a...Proceeding from natural amino acid L-asparagine and commercially available aldehydes a stereoselective synthesis was developed of (2S,4S)-2-alkyl(aryl)-3-(3-sulfanylpropanoyl)-6-oxohexahy- dropyrimidine-4-carboxylic acids, potential antihypertensive drugs, inhibitors of the angiotensin converting enzyme.展开更多
Aim: To reveal the exonic and 3’UTR sequences of KRAS, TP53, APC, BRAF, PIK3CA genes in sporadic colorectal tumors and to investigate the clinical relevance of 3’UTR variations in miRNA profiles. Methods: In the stu...Aim: To reveal the exonic and 3’UTR sequences of KRAS, TP53, APC, BRAF, PIK3CA genes in sporadic colorectal tumors and to investigate the clinical relevance of 3’UTR variations in miRNA profiles. Methods: In the study, the exonic and 3’UTR sequences of five genes in 12 sporadic colorectal tumors were extracted by next generation sequencing. In tumors with variation in the 3’UTR region, the changes caused by the variation in the miRNA binding profile were detected. The expression profile of these miRNAs in colorectal and other solid tumors compared to normal tissue was determined. Pathway analysis was performed to determine which signaling pathways miRNAs affect. Results: Case-10 in our study was wild type KRAS and received cetuximab treatment and developed drug resistance. In this case, it was concluded that the expression of KRAS increased and tumorigenesis progressed due to miRNAs that do not bind to this region due to variations in the 3’UTR region. Among these miRNAs, hsa-miR-124-3p was found to have decreased expression in colorectal tumors and to be associated with the ECM-receptor interaction pathway. Conclusion: Variations in the 3’UTR regions of genes critical in the process of carsinogenesis are associated with drug resistance and the process of tumorigenesis.展开更多
The different investigation has been carried out on the biological activities of titanium dioxide nanoparticle but the effect of this nano product on the antibacterial activity of different antibiotics has not been ye...The different investigation has been carried out on the biological activities of titanium dioxide nanoparticle but the effect of this nano product on the antibacterial activity of different antibiotics has not been yet demonstrated. In this study the nano size TiO2 is synthesized using citric acid and alpha dextrose and the enhancement effect of TiO2 nanoparticle on the antibacterial activity of different antibiotics was evaluated against Methicillin-resistant Staphylococcus aureus (MRSA). During the present study, different concentrations of nano-scale TiO2 were tested to find out the best concentration that can have the most effective antibacterial property against the MRSA culture. Disk diffusion method was used to determine the antibacterial activity of these antibiotics in the absence and presence of sub inhibitory concentration of TiO2 nano particle. A clinical isolate of MRSA, isolated from Intensive Care Unit (ICU) was used as test strain. In the presence of sub-inhibitory concentration of TiO2 nanoparticle (20 μg/disc) the antibacterial activities of all antibiotics have been increased against test strain with minimum 2 mm to maximum 10mm. The highest increase in inhibitory zone for MRSA was observed against pencillin G and amikacin (each 10 mm). Conversely, in case of nalidixic acid, TiO2 nanoparticle showed a Synergic effect on the antibacterial activity of this antibiotic against test strain. These results signify that the TiO2 nanoparticle potentate the antimicrobial action of beta lactums, cephalosporins, aminoglycosides, glycopeptides, macrolids and lincosamides, tetracycline a possible utilization of nano compound in combination effect against MRSA.展开更多
As a result of advances in horizontal comple- tions and multi-stage hydraulic fracturing, the U.S. has been able to economically develop several decades of worth of natural gas. However, a considerable concern has ris...As a result of advances in horizontal comple- tions and multi-stage hydraulic fracturing, the U.S. has been able to economically develop several decades of worth of natural gas. However, a considerable concern has risen on the economic viability of shale gas development for reasons associated with the fast production declines as well as recent down-turns of natural gas prices besides rises in the costs of new technologies. Therefore, an economic analysis is required to investigate the profitability of the re- fracturing treatment of unconventional gas resources. Net present value of cash flows and internal rate of return are calculated for a range of gas prices considering 20 years of natural gas production from a typical unconventional shale gas reservoir. A systematic comparison is then accom- plished for three scenarios： （1） re-fracturing versus no re- fracturing, （2） combination of re-fracturing and drilling new wells, and （3） time-dependent re-fracturing treatment. Further, this paper incorporates the cost of re-fracturing treatment, the cost of drilling a new horizontal well, the water treatment cost, as well as the current and future price of natural gas in the model. The findings of this work would help the future re-stimulation development plans of the emerging unconventional shale gas plays.展开更多
AIM： To investigate EP4-selective agonist effect on indomethacin-induced gastric lesions and on the spontaneous healing of chronic gastric ulcers. METHODS： In a mouse model of gastric bleeding with high dose of indo...AIM： To investigate EP4-selective agonist effect on indomethacin-induced gastric lesions and on the spontaneous healing of chronic gastric ulcers. METHODS： In a mouse model of gastric bleeding with high dose of indomethacin （20 mg/kg）, an EP4-selective agonist was administered orally. Stomach lesions and gastric mucous regeneration were monitored. In a mouse model of chronic gastric ulcer induced by acetic acid, EP4 agonist effect on the healing of chronic gastric ulcer was evaluated in the presence or absence of low dose indomethadn （3 mg/kg）. In cultured human gastric mucous cells, EP4 agonist effect on indomethacin- induced apoptosis was assessed by flow cytometry. RESULTS： The EP4-selective agonist reduced high dose indomethacin-induced acute hemorrhagic damage and promoted mucous epithelial regeneration. Low-dose indomethacin aggravated ulcer bleeding and inflammation, and delayed the healing of the established chronic gastric ulcer. The EP4 agonist, when applied locally, not only offset indomethacin-induced gastric bleeding and inflammation, but also accelerated ulcer healing. In the absence of indomethacin, the EP4 agonist even accelerated chronic gastric ulcer healing and suppressed inflammatory cell infiltration in the granulation tissue. In vitro, the EP4 agonist protected human gastric mucous cells from indomethacin-induced apoptosis.CONCLUSION： EP4-selective agonist may prevent indomethacin-induced gastric lesions and promote healing of existing and i ulcers, via promoting mucous epithelial cells. proliferation and survival of mucous epithelial cells.展开更多
Objective:"Epimedium - Cistanche deserticola" is a kind of kidney tonifying drug commonly used in the treatment of breast cancer bone metastasis, which has good clinical effect, but the pharmacological mecha...Objective:"Epimedium - Cistanche deserticola" is a kind of kidney tonifying drug commonly used in the treatment of breast cancer bone metastasis, which has good clinical effect, but the pharmacological mechanism has not been fully clarified. Methods: In this study, the network pharmacology and bioinformatics technology were used to explore the mechanism of "Epimedium - Cistanche deserticola" in the treatment of breast cancer bone metastasis. TCMSP, TCM database@Taiwan and TCMID databases were used to screen the main effective components of the drug. Swiss Target Prediction and STITCH databases were used to search the potential target of action of Epimedium and Cistanche deserticola. Genecards, OMIN and Drugbank databases were used to search the cause of bone metastasis of breast cancer. The target of action of the drug and the disease gene were mapped for GO and KEGG signal pathway analysis, A visualized network of "drug - component - target - signaling pathway" was constructed by using the software of Cytoscape 3.6.0, and the core genes were screened out. Results: The study found that there are 30 main effective components of Epimedium and Cistanche deserticola, and 544 genes are involved in the potential therapeutic targets, among which 101 genes are potential targets of Epimedium and Cistanche deserticola in the treatment of breast cancer bone metastasis. Through the analysis of GO and KEGG pathways, we found that the mechanisms involved in antitumor, osteoblast differentiation, osteoclast apoptosis and regulation of bone microenvironment, such as apoptosis, osteoclast differentiation, PI3K-Akt, HIF-1 signaling pathway, T cell receptor signaling pathway, etc. TP53, VEGFA, AKT1, EGFR, SRC, CCND1, MAPK3, ESR1 may be the key genes in the treatment of breast cancer bone metastasis. Conclusion: In this study, the network of "drug - component - target- signaling pathway" was constructed through network pharmacology, and it was found that the mechanism of "Epimedium - Cistanche deserticola" in the treatment of breast cancer bone metastasis involves multiple targets and pathways, which is conducive to guiding clinical medication.展开更多
文摘The use of non-steroidal anti-inflammatory drugs(NSAIDs) is widespread worldwide thanks to their analgesic, anti-inflammatory and antipyretic effects. However, even more attention is placed upon the recurrence of digestive system complications in the course of their use. Recent data suggests that the complications of the lower gastro-intestinal tract may be as frequent and severe as those of the upper tract. NSAIDs enteropathy is due to enterohepatic recycling of the drugs resulting in a prolonged and repeated exposure of the intestinal mucosa to the compound and its metabolites. Thus leading to so-called topical effects, which, in turn, lead to an impairment of the intestinal barrier. This process determines bacterial translocation and toxic substances of intestinal origin in the portal circulation, leading to an endotoxaemia. This condition could determine a liver inflammatory response and might promote the development of nonalcoholic steatohepatitis, mostly in patients with risk factors such as obesity, metabolic syndrome and a high fat diet, which may induce a small intestinal bacterial overgrowth and dysbiosis. This alteration of gut microbiota may contribute to nonalcoholic fatty liver disease and its related disorders in two ways: firstly causing a malfunction of the tight junctions that play a critical role in the increase of intestinal permeability, and then secondly leading to the development of insulin resistance, body weight gain, lipogenesis, fibrogenesis and hepatic oxidative stress.
文摘This paper has two aims. The first one is to investigate the existence of chaotic structures in the oil prices, expectations of investors and stock returns by combining the Lyapunov exponent and Kolmogorov entropy, and the second one is to analyze the dependence behavior of oil prices, expectations of investors and stock returns from January 02, 1990, to June06, 2017. Lyapunov exponents and Kolmogorov entropy determined that the oil price and the stock return series exhibited chaotic behavior. TAR-TR-GARCH and TAR-TR-TGARCH copula methods were applied to study the co-movement among the selected variables. The results showed significant evidence of nonlinear tail dependence between the volatility of the oil prices, the expectations of investors and the stock returns. Further, upper and lower tail dependence and comovement between the analyzed series could not be rejected. Moreover, the TAR-TR-GARCH and TAR-TR-TGARCH copula methods revealed that the volatility of oil price had crucial effects on the stock returns and on the expectations of investors in the long run.
文摘Proceeding from natural amino acid L-asparagine and commercially available aldehydes a stereoselective synthesis was developed of (2S,4S)-2-alkyl(aryl)-3-(3-sulfanylpropanoyl)-6-oxohexahy- dropyrimidine-4-carboxylic acids, potential antihypertensive drugs, inhibitors of the angiotensin converting enzyme.
文摘Aim: To reveal the exonic and 3’UTR sequences of KRAS, TP53, APC, BRAF, PIK3CA genes in sporadic colorectal tumors and to investigate the clinical relevance of 3’UTR variations in miRNA profiles. Methods: In the study, the exonic and 3’UTR sequences of five genes in 12 sporadic colorectal tumors were extracted by next generation sequencing. In tumors with variation in the 3’UTR region, the changes caused by the variation in the miRNA binding profile were detected. The expression profile of these miRNAs in colorectal and other solid tumors compared to normal tissue was determined. Pathway analysis was performed to determine which signaling pathways miRNAs affect. Results: Case-10 in our study was wild type KRAS and received cetuximab treatment and developed drug resistance. In this case, it was concluded that the expression of KRAS increased and tumorigenesis progressed due to miRNAs that do not bind to this region due to variations in the 3’UTR region. Among these miRNAs, hsa-miR-124-3p was found to have decreased expression in colorectal tumors and to be associated with the ECM-receptor interaction pathway. Conclusion: Variations in the 3’UTR regions of genes critical in the process of carsinogenesis are associated with drug resistance and the process of tumorigenesis.
文摘The different investigation has been carried out on the biological activities of titanium dioxide nanoparticle but the effect of this nano product on the antibacterial activity of different antibiotics has not been yet demonstrated. In this study the nano size TiO2 is synthesized using citric acid and alpha dextrose and the enhancement effect of TiO2 nanoparticle on the antibacterial activity of different antibiotics was evaluated against Methicillin-resistant Staphylococcus aureus (MRSA). During the present study, different concentrations of nano-scale TiO2 were tested to find out the best concentration that can have the most effective antibacterial property against the MRSA culture. Disk diffusion method was used to determine the antibacterial activity of these antibiotics in the absence and presence of sub inhibitory concentration of TiO2 nano particle. A clinical isolate of MRSA, isolated from Intensive Care Unit (ICU) was used as test strain. In the presence of sub-inhibitory concentration of TiO2 nanoparticle (20 μg/disc) the antibacterial activities of all antibiotics have been increased against test strain with minimum 2 mm to maximum 10mm. The highest increase in inhibitory zone for MRSA was observed against pencillin G and amikacin (each 10 mm). Conversely, in case of nalidixic acid, TiO2 nanoparticle showed a Synergic effect on the antibacterial activity of this antibiotic against test strain. These results signify that the TiO2 nanoparticle potentate the antimicrobial action of beta lactums, cephalosporins, aminoglycosides, glycopeptides, macrolids and lincosamides, tetracycline a possible utilization of nano compound in combination effect against MRSA.
文摘As a result of advances in horizontal comple- tions and multi-stage hydraulic fracturing, the U.S. has been able to economically develop several decades of worth of natural gas. However, a considerable concern has risen on the economic viability of shale gas development for reasons associated with the fast production declines as well as recent down-turns of natural gas prices besides rises in the costs of new technologies. Therefore, an economic analysis is required to investigate the profitability of the re- fracturing treatment of unconventional gas resources. Net present value of cash flows and internal rate of return are calculated for a range of gas prices considering 20 years of natural gas production from a typical unconventional shale gas reservoir. A systematic comparison is then accom- plished for three scenarios： （1） re-fracturing versus no re- fracturing, （2） combination of re-fracturing and drilling new wells, and （3） time-dependent re-fracturing treatment. Further, this paper incorporates the cost of re-fracturing treatment, the cost of drilling a new horizontal well, the water treatment cost, as well as the current and future price of natural gas in the model. The findings of this work would help the future re-stimulation development plans of the emerging unconventional shale gas plays.
文摘AIM： To investigate EP4-selective agonist effect on indomethacin-induced gastric lesions and on the spontaneous healing of chronic gastric ulcers. METHODS： In a mouse model of gastric bleeding with high dose of indomethacin （20 mg/kg）, an EP4-selective agonist was administered orally. Stomach lesions and gastric mucous regeneration were monitored. In a mouse model of chronic gastric ulcer induced by acetic acid, EP4 agonist effect on the healing of chronic gastric ulcer was evaluated in the presence or absence of low dose indomethadn （3 mg/kg）. In cultured human gastric mucous cells, EP4 agonist effect on indomethacin- induced apoptosis was assessed by flow cytometry. RESULTS： The EP4-selective agonist reduced high dose indomethacin-induced acute hemorrhagic damage and promoted mucous epithelial regeneration. Low-dose indomethacin aggravated ulcer bleeding and inflammation, and delayed the healing of the established chronic gastric ulcer. The EP4 agonist, when applied locally, not only offset indomethacin-induced gastric bleeding and inflammation, but also accelerated ulcer healing. In the absence of indomethacin, the EP4 agonist even accelerated chronic gastric ulcer healing and suppressed inflammatory cell infiltration in the granulation tissue. In vitro, the EP4 agonist protected human gastric mucous cells from indomethacin-induced apoptosis.CONCLUSION： EP4-selective agonist may prevent indomethacin-induced gastric lesions and promote healing of existing and i ulcers, via promoting mucous epithelial cells. proliferation and survival of mucous epithelial cells.
基金supported by the National Natural Science Foundation of China(No.81973640).
文摘Objective:"Epimedium - Cistanche deserticola" is a kind of kidney tonifying drug commonly used in the treatment of breast cancer bone metastasis, which has good clinical effect, but the pharmacological mechanism has not been fully clarified. Methods: In this study, the network pharmacology and bioinformatics technology were used to explore the mechanism of "Epimedium - Cistanche deserticola" in the treatment of breast cancer bone metastasis. TCMSP, TCM database@Taiwan and TCMID databases were used to screen the main effective components of the drug. Swiss Target Prediction and STITCH databases were used to search the potential target of action of Epimedium and Cistanche deserticola. Genecards, OMIN and Drugbank databases were used to search the cause of bone metastasis of breast cancer. The target of action of the drug and the disease gene were mapped for GO and KEGG signal pathway analysis, A visualized network of "drug - component - target - signaling pathway" was constructed by using the software of Cytoscape 3.6.0, and the core genes were screened out. Results: The study found that there are 30 main effective components of Epimedium and Cistanche deserticola, and 544 genes are involved in the potential therapeutic targets, among which 101 genes are potential targets of Epimedium and Cistanche deserticola in the treatment of breast cancer bone metastasis. Through the analysis of GO and KEGG pathways, we found that the mechanisms involved in antitumor, osteoblast differentiation, osteoclast apoptosis and regulation of bone microenvironment, such as apoptosis, osteoclast differentiation, PI3K-Akt, HIF-1 signaling pathway, T cell receptor signaling pathway, etc. TP53, VEGFA, AKT1, EGFR, SRC, CCND1, MAPK3, ESR1 may be the key genes in the treatment of breast cancer bone metastasis. Conclusion: In this study, the network of "drug - component - target- signaling pathway" was constructed through network pharmacology, and it was found that the mechanism of "Epimedium - Cistanche deserticola" in the treatment of breast cancer bone metastasis involves multiple targets and pathways, which is conducive to guiding clinical medication.
