In order to analyze and explain the mechanism of the two small inhibitors (ADS-JI and ADS-J2) binding to HIV-1 gp41, a computational study is carried out to help identifying possible binding modes by docking these c...In order to analyze and explain the mechanism of the two small inhibitors (ADS-JI and ADS-J2) binding to HIV-1 gp41, a computational study is carried out to help identifying possible binding modes by docking these compounds onto the hydrophobic pocket on gp41 and characterize structures of binding complexes. The binding interactions of gp41-molecule and free energies of binding are obtained through molecular dynamics simulation and molecular mechanic/Poisson- Boitzmann surface area ( MM/PBSA ) calculation. Specific molecular interactions in the gp41-inhibitor complexes are identified. The present computational study complements the corresponding experimental investigation and helps establish a good starting point tbr further refinement of small molecular gp41 inhibitors.展开更多
AIM: To investigate the inhibitory effect of gefitinib combined with cytotoxic agent cisplatin (CDDP) on hepatocellular carcinoma (HCC). METHODS: Female Kunming mice and H22 hepatocarcinoma cells were used. Gefitinib ...AIM: To investigate the inhibitory effect of gefitinib combined with cytotoxic agent cisplatin (CDDP) on hepatocellular carcinoma (HCC). METHODS: Female Kunming mice and H22 hepatocarcinoma cells were used. Gefitinib at daily dose of 100 mg/kg body weight (BW) or lecithin liquid was given by gastrogavage once a day for 5 or 10 successive days. CDDP or normal saline (NS) was administered intraperitoneally (i.p.) once a day for 5 successive days. Mice were randomly divided into control group (lecithin, or NS, i.p.), CDDP group (daily dose, 1.2 mg/kg BW; d1-5, or d6-10), Gefitinib (d1-5, or d6-10, or d1-10), and Gefitinib combined with CDDP groups. The inhibitory rate (IR) of tumor, net BW, spleen index (SI), thymus index (TI) and the amount of peripheral blood cells of mice were detected on the 12th experiment day. RESULTS: The growth of HCC in mice was inhibited by Gefitinib alone (IR: 41% in d1-10 group and 30% in d1-5 group, respectively) or CDDP alone (IR: 32-54% in d1-5 group or d6-10 group). The highest inhibitory effect (IR: 56%) on HCC growth was observed in Gefitinib (d1-10) combined with CDDP (d1-5) group. Higher inhibition was also observed in CDDP (d1-5) followed by Gefitinib (d6-10) group than that in Gefitinib (d1-5) followed by CDDP (d6-10) group (IR: 61% vs 36%, P<0.01) in the independent study. Net BW, SI, TI and the amount of blood cells of mice in Gefitinib alone group were not significantly different from those in control groups. CONCLUSION: Gefitinib can significantly inhibit the growth of murine H22 hepatocellular carcinoma. If Gefitinib is used after CDDP treatment in animal experiments, the inhibitory effect could be enhanced.展开更多
Anti-tumor necrosis factor alpha (TNF-α) inhibitors are effective in the treatment of various inflammatory rheumatic conditions. Increased risks of serious infections are the major issues concerning the long-term saf...Anti-tumor necrosis factor alpha (TNF-α) inhibitors are effective in the treatment of various inflammatory rheumatic conditions. Increased risks of serious infections are the major issues concerning the long-term safety of these agents. We present a case of a young male Behcet’s patient whose disease was complicated by cytomegalovirus (CMV) colitis. Colitis started 10 d after the third Infliximab dose and responded to the cessation of TNF blocking treatment and administration of ganciclovir. Tumor necrosis factor alpha and interferon gamma act at several levels in combating viral infections.CMV infections should be kept in mind and included in the differential diagnosis of severe gastrointestinal symptoms in patients receiving anti-TNF agents.展开更多
In the past,there has been considerable focus on a host of drugs and chemicals that may produce colonic toxicity.Now,a variety of new biological monoclonal antibody agents,usually administered by infusion,have appeare...In the past,there has been considerable focus on a host of drugs and chemicals that may produce colonic toxicity.Now,a variety of new biological monoclonal antibody agents,usually administered by infusion,have appeared in the clinical realm over the last decade or so to treat different chronic inflammatory or malignant disorders.For some of these agents,adverse effects have been documented,including apparently new forms of immune-mediated inflammatory bowel disease.In some,only limited symptoms have been recorded,but in others,severe colitis with serious complications,such as bowel perforation has been recorded.In others,adverse effects may have a direct vascular or ischemic basis,while other intestinal effects may be related to a superimposed infection.Some new onset cases of ulcerative colitis or Crohn's disease may also be attributed to the same agents used to treat these diseases,or be responsible for disease exacerbation.Dramatic and well documented side effects have been observed with ipilimumab,a humanized monoclonal antibody developed to reduce and overcome cytotoxic T-lymphocyte antigen 4,a key negative feedback regulator of the T-cell anti-tumor response.This agent has frequently been used in the treatment of different malignancies,notably,malignant melanoma.Side effects with this agent occur in up to 40% and these are believed to be largely immune-mediated.One of these is a form of enterocolitis that may be severe,and occa-sionally,fatal.Other agents include rituximab(an antiCD20 monoclonal antibody),bevacizumab(a monoclonal antibody against the vascular endothelial growth factor) and anti-tumor necrosis factor agents,including infliximab,adalimumab and etanercept.展开更多
The cytotoxicity of abamectin to the Gill Cell Line of Flounder (FG cell line) was examined in this study. It was found that the exposure of FG cells to abamectin caused the decreases of both cell growth rate and an...The cytotoxicity of abamectin to the Gill Cell Line of Flounder (FG cell line) was examined in this study. It was found that the exposure of FG cells to abamectin caused the decreases of both cell growth rate and antioxidant enzyme activities, and the increase of intracellular 02 content. It was proposed that the reduction of antioxidant enzyme activities in FG cells caused the accumulation of 02 content in FG cells, leading to the change of cell morphology and even the death of cells. The results showed that FG cell line is suitable for the evaluation of the acute toxicity of abamectin.展开更多
Antioxidants play an important role in inhibiting and scavenging free radicals in human, providing protection against cellular damage in relation to cancer initiation. Seaweeds have been proved to have high antioxidan...Antioxidants play an important role in inhibiting and scavenging free radicals in human, providing protection against cellular damage in relation to cancer initiation. Seaweeds have been proved to have high antioxidant activity. Thus, this research was carried out to determine the antioxidant and anticancer properties of edible red seaweed, Gracilaria manilaensis (Gracilariales, Rhodophyta). The extracts were prepared by Soxhlet extraction using organic solvents with different polarities. The antioxidant activities of extracts were determined in terms of their flee radical scavenging activity (RSA IC50) and total phenolic content (TPC). The cytotoxic activity of extracts were tested against human ovarian cancer cell line (Caov-3), human breast cancer cell line (MDA-MB-231 and MCF-7), human cervical cell line (HeLa), mouse fibroblast cell line (L929) and Madin-Darby canine kidney (MDCK) and the cell viability after 72 h incubation was determined by methylene blue assay. The findings showed that acetone extract has the lowest DPPH IC50 value followed by ethyl acetate extract. Both extracts also showed high values of TPC. Dichloromethane extract had the strongest cytotoxic on MDA-MB-231 (53.90 μg/mL ± 5.59 μg/mL) and HeLa (95.50 μg/mL). While, acetone and ethyl acetate extracts were cytotoxic on MCF-7 (66.07 μg/mL) and Caov-3 (69.67 μg/mL ± 13.94 μg/mL). It could be concluded that the antioxidant and cytotoxic activities of G. manilaensis were influenced by the types of solvents used and thus had a potential to develop as a cancer chemoprevention or anticancer agent against selected cancer.展开更多
基金The National Basic Research Program of China (973 Program) (No. 2007CB936300)
文摘In order to analyze and explain the mechanism of the two small inhibitors (ADS-JI and ADS-J2) binding to HIV-1 gp41, a computational study is carried out to help identifying possible binding modes by docking these compounds onto the hydrophobic pocket on gp41 and characterize structures of binding complexes. The binding interactions of gp41-molecule and free energies of binding are obtained through molecular dynamics simulation and molecular mechanic/Poisson- Boitzmann surface area ( MM/PBSA ) calculation. Specific molecular interactions in the gp41-inhibitor complexes are identified. The present computational study complements the corresponding experimental investigation and helps establish a good starting point tbr further refinement of small molecular gp41 inhibitors.
文摘AIM: To investigate the inhibitory effect of gefitinib combined with cytotoxic agent cisplatin (CDDP) on hepatocellular carcinoma (HCC). METHODS: Female Kunming mice and H22 hepatocarcinoma cells were used. Gefitinib at daily dose of 100 mg/kg body weight (BW) or lecithin liquid was given by gastrogavage once a day for 5 or 10 successive days. CDDP or normal saline (NS) was administered intraperitoneally (i.p.) once a day for 5 successive days. Mice were randomly divided into control group (lecithin, or NS, i.p.), CDDP group (daily dose, 1.2 mg/kg BW; d1-5, or d6-10), Gefitinib (d1-5, or d6-10, or d1-10), and Gefitinib combined with CDDP groups. The inhibitory rate (IR) of tumor, net BW, spleen index (SI), thymus index (TI) and the amount of peripheral blood cells of mice were detected on the 12th experiment day. RESULTS: The growth of HCC in mice was inhibited by Gefitinib alone (IR: 41% in d1-10 group and 30% in d1-5 group, respectively) or CDDP alone (IR: 32-54% in d1-5 group or d6-10 group). The highest inhibitory effect (IR: 56%) on HCC growth was observed in Gefitinib (d1-10) combined with CDDP (d1-5) group. Higher inhibition was also observed in CDDP (d1-5) followed by Gefitinib (d6-10) group than that in Gefitinib (d1-5) followed by CDDP (d6-10) group (IR: 61% vs 36%, P<0.01) in the independent study. Net BW, SI, TI and the amount of blood cells of mice in Gefitinib alone group were not significantly different from those in control groups. CONCLUSION: Gefitinib can significantly inhibit the growth of murine H22 hepatocellular carcinoma. If Gefitinib is used after CDDP treatment in animal experiments, the inhibitory effect could be enhanced.
文摘Anti-tumor necrosis factor alpha (TNF-α) inhibitors are effective in the treatment of various inflammatory rheumatic conditions. Increased risks of serious infections are the major issues concerning the long-term safety of these agents. We present a case of a young male Behcet’s patient whose disease was complicated by cytomegalovirus (CMV) colitis. Colitis started 10 d after the third Infliximab dose and responded to the cessation of TNF blocking treatment and administration of ganciclovir. Tumor necrosis factor alpha and interferon gamma act at several levels in combating viral infections.CMV infections should be kept in mind and included in the differential diagnosis of severe gastrointestinal symptoms in patients receiving anti-TNF agents.
文摘In the past,there has been considerable focus on a host of drugs and chemicals that may produce colonic toxicity.Now,a variety of new biological monoclonal antibody agents,usually administered by infusion,have appeared in the clinical realm over the last decade or so to treat different chronic inflammatory or malignant disorders.For some of these agents,adverse effects have been documented,including apparently new forms of immune-mediated inflammatory bowel disease.In some,only limited symptoms have been recorded,but in others,severe colitis with serious complications,such as bowel perforation has been recorded.In others,adverse effects may have a direct vascular or ischemic basis,while other intestinal effects may be related to a superimposed infection.Some new onset cases of ulcerative colitis or Crohn's disease may also be attributed to the same agents used to treat these diseases,or be responsible for disease exacerbation.Dramatic and well documented side effects have been observed with ipilimumab,a humanized monoclonal antibody developed to reduce and overcome cytotoxic T-lymphocyte antigen 4,a key negative feedback regulator of the T-cell anti-tumor response.This agent has frequently been used in the treatment of different malignancies,notably,malignant melanoma.Side effects with this agent occur in up to 40% and these are believed to be largely immune-mediated.One of these is a form of enterocolitis that may be severe,and occa-sionally,fatal.Other agents include rituximab(an antiCD20 monoclonal antibody),bevacizumab(a monoclonal antibody against the vascular endothelial growth factor) and anti-tumor necrosis factor agents,including infliximab,adalimumab and etanercept.
文摘The cytotoxicity of abamectin to the Gill Cell Line of Flounder (FG cell line) was examined in this study. It was found that the exposure of FG cells to abamectin caused the decreases of both cell growth rate and antioxidant enzyme activities, and the increase of intracellular 02 content. It was proposed that the reduction of antioxidant enzyme activities in FG cells caused the accumulation of 02 content in FG cells, leading to the change of cell morphology and even the death of cells. The results showed that FG cell line is suitable for the evaluation of the acute toxicity of abamectin.
文摘Antioxidants play an important role in inhibiting and scavenging free radicals in human, providing protection against cellular damage in relation to cancer initiation. Seaweeds have been proved to have high antioxidant activity. Thus, this research was carried out to determine the antioxidant and anticancer properties of edible red seaweed, Gracilaria manilaensis (Gracilariales, Rhodophyta). The extracts were prepared by Soxhlet extraction using organic solvents with different polarities. The antioxidant activities of extracts were determined in terms of their flee radical scavenging activity (RSA IC50) and total phenolic content (TPC). The cytotoxic activity of extracts were tested against human ovarian cancer cell line (Caov-3), human breast cancer cell line (MDA-MB-231 and MCF-7), human cervical cell line (HeLa), mouse fibroblast cell line (L929) and Madin-Darby canine kidney (MDCK) and the cell viability after 72 h incubation was determined by methylene blue assay. The findings showed that acetone extract has the lowest DPPH IC50 value followed by ethyl acetate extract. Both extracts also showed high values of TPC. Dichloromethane extract had the strongest cytotoxic on MDA-MB-231 (53.90 μg/mL ± 5.59 μg/mL) and HeLa (95.50 μg/mL). While, acetone and ethyl acetate extracts were cytotoxic on MCF-7 (66.07 μg/mL) and Caov-3 (69.67 μg/mL ± 13.94 μg/mL). It could be concluded that the antioxidant and cytotoxic activities of G. manilaensis were influenced by the types of solvents used and thus had a potential to develop as a cancer chemoprevention or anticancer agent against selected cancer.