Nucleation of dendritic primaryα(Al) phase with addition of element Ce and Sr in hypoeutectic Al-7%Si-Mg cast alloy was investigated by using differential scanning calorimetry (DSC) and scanning electron microsco...Nucleation of dendritic primaryα(Al) phase with addition of element Ce and Sr in hypoeutectic Al-7%Si-Mg cast alloy was investigated by using differential scanning calorimetry (DSC) and scanning electron microscopy. DSC results were used to calculate the activation energy and nucleation work of primaryα(Al) phase. The results show that the values of activation energy and nucleation work are decreased and the nucleation frequency is increased with the additions of Ce and Sr to the alloys. Moreover, the grain size of dendriticα(Al) phase is well refined, and the nucleation temperatures of primaryα(Al) dendrites are decreased with the additions of Ce and Sr. The effects of elements Ce and Sr additions on kinetic nucleation of primary α(Al) phases were also discussed in hypoeutectic Al-7%Si-Mg cast alloy.展开更多
AIM. To investigate the influence of heme oxygenase-1 (HO-1) gene transfer on the viability and function of cultured rat islets in vitro. METHODS: Islets were isolated from the pancreata of Sprague-Dawley rats by i...AIM. To investigate the influence of heme oxygenase-1 (HO-1) gene transfer on the viability and function of cultured rat islets in vitro. METHODS: Islets were isolated from the pancreata of Sprague-Dawley rats by intraductal collagenase digestion, and purified by discontinuous Ficoll density gradient centrifugation. Purified rat islets were transfected with adenoviral vectors containing human HO-1 gene (Ad- HO-1) or enhanced green fluorescent protein gene (Ad- EGFP), and then cultured for seven days. Transfection was confirmed by fluorescence microscopy and Western blot. Islet viability was evaluated by acridine orange/ propidium iodide fluorescent staining. Glucose-stimulated insulin release was detected using insulin radioimmunoassay kits and was used to assess the function of islets. Stimulation index (SI) was calculated by dividing the insulin release upon high glucose stimulation by the insulin release upon low glucose stimulation. RESULTS: After seven days culture, the viability of cultured rat islets decreased significantly (92% ± 6% vs 52% ± 13%, P 〈 0.05), and glucose-stimulated insulin release also decreased significantly (6.47 ± 0.55 mIU/ L/30IEO vs 4.57 ± 0.40 mIU/L/3OIEO., 14.93 ± 1.17 mIU/L/30IEQ vs 9.63 ± 0.71 mIU/L/30IEQ, P 〈 0.05). Transfection of rat islets with adenoviral vectors at an 1±10 of 20 was efficient, and did not impair islet function. At 7 d post-transfection, the viability of Ad-HO-1 transfected islets was higher than that of control islets(71% ± 15% vs 52% ± 13%, P 〈 0.05). There was no significant difference in insulin release upon low glucose stimulation (2.8 mmol/L) among Ad-HO-1 transfected group, Ad-EGFP transfected group, and control group (P 〉 0.05), while when stimulated by high glucose (16.7 mmol/L) solution, insulin release in Ad-HO-1 transfected group was significantly higher than that in Ad-EGFP transfected group and control group, respectively (12.50 ±2.17 mIU/L/30IEQ vs 8.87 ± 0.65 mIU/L/30IEQ, 12.50 ± 2.17 mIU/L/30IEQ vs 9.63 ± 0.71 mIU/L/30IEQ, P 〈 0.05). The SI of Ad-HO-1 transfected group was also significantly higher than that of Ad-EGFP transfected group and control group, respectively (2.21 ± 0.02 vs 2.08 ± 0.05; 2.21 ± 0.02 vs 2.11 ± 0.03, P 〈 0.05). CONCLUSION: The viability and function of rat islets decrease over time in in vitro culture, and heine oxygenase-1 gene transfer could improve the viability and function of cultured rat islets.展开更多
AIM: To isolate and identify the soybean conglycinin peptides that selectively stimulates the growth of bifidobacteria in vitro, and to investigate the effect of soybean conglycinin peptides on intestinal ecosystem i...AIM: To isolate and identify the soybean conglycinin peptides that selectively stimulates the growth of bifidobacteria in vitro, and to investigate the effect of soybean conglycinin peptides on intestinal ecosystem in vivo. METHODS: Soybean conglycinin was purified from soybean seeds by gel filtration (Sepharose-CL-6B). These proteins were submitted to hydrolysis by pepsin. Several growth-stimulating peptides for bifidobacteria were isolated chromatographically from pepsin hydrolysis of soybean conglycinin and identified by means of matrixassisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS). Parallel to in vitro study, in vivo experiments with soybean conglycinin peptides were performed in mice. Ninety male KM mice were randomly assigned into five groups of 16 mice each, and each group was administered for 21d intragastrically with physiological saline (control), conglycinin, pepsin-treated conglycinin (PTC), the most active fraction which isolated from pepsin-treated conglycinin (P2-PTC) and HCl-full hydrolysis of conglycinin (HCl-FHC), respectively. Intestinal microflora were evaluated by standard microbiologic methods and biochemical assays of cecal content samples after treatment. RESULTS: The results showed that the peptides which were isolated from soybean conglycinin could stimulate the growth of bifidobacteria in vitro, and the molecular mass of purified peptides with MALDI-TOF-MS ranged from 693.32 to 1829.55. Compared with control group, in vivo experiments showed that P2-PTC group decreased cecal pH (7.08±0.08 vs7.21±0.09, P〈0.05) and enterococcicounts (5.38±0.26 log10CFU/g vs 5.78±0.19 log10CFU/g, P〈0.05), significantly increased sIgA level (172.08±35.40 ng/g vs 118.27±33.93 ng/g, P〈0.01) and β-galactosidase activity (1.28±0.23 U/g vs 1.82±0.58 U/g, P〈0.05) CONCLUSION: The results have shown that conglycinin is good source for enzyme-mediated production of peptides which stimulate the growth of bifidobacteria. These peptides are inactive within the sequence of the parent protein but can be released during enzymatic hydrolysis, and in vivo experiments demonstrate that conglycinin peptides may be beneficial for improving gastrointestinal health.展开更多
AIM: To investigate the relationship between gastric dysmotility,gastrointestinal hormone abnormalities, and neuroendocrine cells in gastrointestinal mucosa in patients with functional dyspepsia (FD).METHODS: Gastric ...AIM: To investigate the relationship between gastric dysmotility,gastrointestinal hormone abnormalities, and neuroendocrine cells in gastrointestinal mucosa in patients with functional dyspepsia (FD).METHODS: Gastric emptying was assessed with solid radiopaque markers in 54 FD patients, and the patients were divided into two groups according to the results, one with delayed gastric emptying and the other with normal gastric emptying. Seventeen healthy volunteers acted as normal controls. Fasting and postprandial plasma levels and gastroduodenal mucosal levels of gastrointestinal hormones gastrin, somatostatin (SS) and neurotensin (NT)were measured by radioimmunoassay in all the subjects.G cells (gastrin-producing cells) and D cells (SS-producing cells) in gastric antral mucosa were immunostained with rabbit anti-gastrin polyclonal antibody and rabbit anti-SS polyclonal antibody, respectively, and analyzed quantitatively by computerized image analysis.RESULTS: The postprandial plasma gastrin levels, the fasting and postprandial plasma levels and the gastric and duodenal mucosal levels of NT were significantly higher in the FD patients with delayed gastric emptying than in those with normal gastric emptying and normal controls. The number and gray value of G and D cells and the G cell/D cell number ratio did not differ significantly between normal controls and the FD patients with or without delayed gastric emptying.CONCLUSION: Our findings suggest that the abnormalities of gastrin and NT may play a role in the pathophysiology of gastric dysmotility in FD patients, and the abnormality of postprandial plasma gastrin levels in FD patients with delayed gastric emptying is not related to the changes both in the number and gray value of G cells and in the G cell/D cell number ratio in gastric antral mucosa.展开更多
AIM: To determine whether Lactobacillus casei strain Shirota (Yakult) can alter small intestinal bacterial overgrowth (SIBO), as tested by the lactulose breath test, and whether this is associated with changes in...AIM: To determine whether Lactobacillus casei strain Shirota (Yakult) can alter small intestinal bacterial overgrowth (SIBO), as tested by the lactulose breath test, and whether this is associated with changes in symptoms in irritable bowel syndrome (IBS). METHODS: 18 patients with IBS (Rome Ⅱ criteria), who showed an early rise in breath hydrogen with lactulose (ERBHAL), consumed 65 mL of Yakult daily for 6 wk. Lactulose breath test was repeated at the end of the treatment period. Symptoms were recorded daily using a 10 cm visual analogue scale. RESULTS: 14 patients completed the study, 9 (64%) had reversal of ERBHAL, with the median time of first rise in breath hydrogen increasing from 45 to 75 min (P = 0.03). There was no significant improvement in the symptom score with probiotic therapy, except for wind (P = 0.04). Patients commencing with at least moderate symptoms and who no longer had ERBHAL at the end of treatment, showed improvement in the overall symptoms scores [median final score 5.3 (IQR 3.9-5.9), 55% reduction; n = 6] to a greater extent than those who had had persisting ERBHAL [final score 6.9 (5.0-7.0), 12% reduction; n = 5; P = 0.18]. CONCLUSION: Yakult is effective in altering fermentation patterns in the small bowel, consistent with reducing SIBO. The loss of ERBHAL was associated with reduced symptoms. The true interpretation of these findings awaits a randornised, controlled trial.展开更多
Small GTP-binding proteins of the ADP-ribosylation fac-tor (Arf) family control various cell functional responses including protein transport and recycling between different cellular compartments, phagocytosis, prol...Small GTP-binding proteins of the ADP-ribosylation fac-tor (Arf) family control various cell functional responses including protein transport and recycling between different cellular compartments, phagocytosis, prolif-eration, cytoskeletal remodelling, and migration. The activity of Arfs is tightly regulated. GTPase-activating proteins (GAPs) inactivate Arfs by stimulating GTP hydrolysis, and guanine nucleotide exchange factors (GEFs) stimulate the conversion of inactive GDP-bound Arf to the active GTP-bound conformation. There is increasing evidence that Arf small GTPases contribute to cancer growth and invasion. Increased expression of Arf6 and of Arf-GEPs, or deregulation Arf-GAP functions have been correlated with enhanced invasive capacity of tumor cells and metastasis. The spatiotemporal spe-cifcity of Arf activation is dictated by their GEFs that integrate various signals in stimulated cells. Brefeldin A (BFA), which inactivates a subset of Arf-GEFs, has been very useful for assessing the function of Golgi-localized Arfs. However, specifc inhibitors to investigate the individual function of BFA-sensitive and insensitive Arf-GEFs are lacking. In recent years, specifc screens have been developed, and new inhibitors with improved se-lectivity and potency to study cell functional responses regulated by BFA-sensitive and BFA-insensitive Arf pathways have been identified. These inhibitors have been instrumental for our understanding of the spa-tiotemporal activation of Arf proteins in cells and dem-onstrate the feasibility of developing small molecules interfering with Arf activation to prevent tumor invasion and metastasis.展开更多
Recent studies have identified mutations in PHF8, an X-linked gene encoding a JmjC domain-containing protein, as a causal factor for X-linked mental retardation (XLMR) and cleft lip/cleft palate. However, the underl...Recent studies have identified mutations in PHF8, an X-linked gene encoding a JmjC domain-containing protein, as a causal factor for X-linked mental retardation (XLMR) and cleft lip/cleft palate. However, the underlying mechanism is unknown. Here we show that PHF8 is a histone demethylase and coactivator for retinoic acid receptor (RAR). Although activities for both H3K4me3/2/1 and H3K9me2/1 demethylation were detected in cellularbased assays, reeombinant PHF8 exhibited only H3K9me2/1 demethylase activity in vitro, suggesting that PHF8 is an H3K9me2/1 demethylase whose specificity may be modulated in vivo. Importantly, a mutant PHF8 (phenylalanine at position 279 to serine) identified in the XLMR patients is defective in enzymatie activity, indicating that the loss of histone demethylase activity is causally linked with the onset of disease. In addition, we show that PHF8 binds specifically to H3K4me3/2 peptides via an N-terminal PHD finger domain. Consistent with a role for PHF8 in neuronal differentiation, knockdown of PHF8 in mouse embryonic carcinoma P19 cells impairs RA-induced neuronal differentiation, whereas overexpression of the wild-type but not the F279S mutant PHF8 drives PI9 cells toward neuronal differentiation. Furthermore, we show that PHF8 interacts with RAR~ and functions as a coactivator for RARa. Taken together, our results suggest that histone methylation modulated by PHF8 plays a critical role in neuronal differentiation.展开更多
Structure and function of the digestive system of a bivalve mollusc, Solen grandis, were studied using light microscopy and histochemical methods. The wall of digestive tube consists of four layers: the mucosal epithe...Structure and function of the digestive system of a bivalve mollusc, Solen grandis, were studied using light microscopy and histochemical methods. The wall of digestive tube consists of four layers: the mucosal epithelium, connective tissue, muscular and fibrosa or serosa (only in the portion of rectum) from the inner to the outer. The ciliated columnar epithelial cells, dispersed by cup-shaped mucous cells, rest on a thin base membrane. There are abundant blood spaces in connective tissue layer. The digestive diverticula are composed of multi-branched duct and digestive tubules. The digestive tubules are lined with digestive and basophilic secretory cells, and surrounded by a layer of smooth muscle fibers and connective tissues. Activities of acid and alkaline phosphatases, esterase and lipase are detected in the digestive cells, and the epithelia of stomach and intestine, suggesting that these cells are capable of intracellular digesting of food materials and absorbing.Besides, acid phosphatase and esterase activities are present in the posterior portion of esophagus. Phagocytes are abundant in blood spaces and the lumens of stomach and intestine, containing brown granules derived from the engulfed food materials. The present work indicates that phagocytes play important roles in ingestion and digestion of food materials, which is supported as well by the activities of acid phosphatase, esterase and lipase detected in blood spaces.展开更多
Objective: We aimed to study the influence of neoadjuvant chemotherapy on immunity function in elderly patients with the stages of II and III esophageal cancer. Methods: Thirty-seven elderly patients (age ranged from ...Objective: We aimed to study the influence of neoadjuvant chemotherapy on immunity function in elderly patients with the stages of II and III esophageal cancer. Methods: Thirty-seven elderly patients (age ranged from 60 to 75 years) with the stages of II and III esophageal cancer underwent 2 cycles chemotherapy preoperatively with single-drug regimen (docetaxel, 35 mg/m2 once a week, on days 1, 8 and 15, at interval of 2 weeks for one cycle). Surgery were performed three weeks later. Blood samples were drawn separately on the day of admission, 1 day before operation, 7 day and 1 month after operation, and we conducted the Flow Cytometry to detect the levels of CD3+, CD4+, CD8+,CD4+/CD8+ and NK cells. Results: There were no significant differences in the levels of CD3+, CD4+, CD8+, CD4+/CD8+ and NK cells between before and after chemotherapy (P > 0.05). On day 7 after operation, the levels of CD3+, CD4+, CD4+/CD8+ and NK cells were degraded and CD8+ increased significantly (P < 0.05). One month after operation, the levels of CD3, CD4+, CD4+/CD8 and NK cells were higher than normal, and CD8 was depressed significantly (P < 0.05). Conclusion: Neoadjuvant chemotherapy has no significant impact on cellular immune function in elderly patients with the stages of II and III esophageal cancer, it is an effective and safe treatment.展开更多
Objective:Hepatocellular carcinoma (HCC) is among the most common and rapidly increasing cancers in Pakistan.There is currently no standard management for advanced HCC.The aim of the study was to assess response rate ...Objective:Hepatocellular carcinoma (HCC) is among the most common and rapidly increasing cancers in Pakistan.There is currently no standard management for advanced HCC.The aim of the study was to assess response rate and toxicity of concomitant gemcitabine and external radiation therapy (ERT) in locally advanced HCC.Methods:Sixty patients were enrolled.Gemcitabine,70 mg/m2 was given weekly during ERT.ERT was delivered with 60Co beam up to 30.6 Gy,1.8 Gy/fraction.Tumor response was assessed by computed tomography (CT) at eight weeks.Complete and partial response (CR and PR),progressive and stable disease (PD and SD) were assessed.Hematological,gastrointestinal and hepatic toxicities were assessed weekly.Results:No CR was seen.PR,SD and PD were seen in 33%,40% and 27% of patients respectively.Grade 3/4 toxicity for total leukocyte count and platelets was observed in 7% and 27% patients.Grade 3/4 toxicity for liver failure,bilirubin,aspartate aminotransferase,alanine aminotransferase and alkaline phosphatase was seen in 35%,28%,38%,24% and 43% patients respectively.Conclusion:The study showed that concomitant gemcitabine and ERT is a feasible option with moderate toxicity in advanced HCC.展开更多
基金Project (42-QP-009) support by Research Fund of the State Key Laboratory of Solidification Processing,ChinaProject (B08040) supported by the Program of Introducing Talents of Discipline to Universities ("111"Project),China
文摘Nucleation of dendritic primaryα(Al) phase with addition of element Ce and Sr in hypoeutectic Al-7%Si-Mg cast alloy was investigated by using differential scanning calorimetry (DSC) and scanning electron microscopy. DSC results were used to calculate the activation energy and nucleation work of primaryα(Al) phase. The results show that the values of activation energy and nucleation work are decreased and the nucleation frequency is increased with the additions of Ce and Sr to the alloys. Moreover, the grain size of dendriticα(Al) phase is well refined, and the nucleation temperatures of primaryα(Al) dendrites are decreased with the additions of Ce and Sr. The effects of elements Ce and Sr additions on kinetic nucleation of primary α(Al) phases were also discussed in hypoeutectic Al-7%Si-Mg cast alloy.
基金Supported by the National Natural Science Foundation of China, No. 30571759Social Development Foundation of Shanghai, No. 200253
文摘AIM. To investigate the influence of heme oxygenase-1 (HO-1) gene transfer on the viability and function of cultured rat islets in vitro. METHODS: Islets were isolated from the pancreata of Sprague-Dawley rats by intraductal collagenase digestion, and purified by discontinuous Ficoll density gradient centrifugation. Purified rat islets were transfected with adenoviral vectors containing human HO-1 gene (Ad- HO-1) or enhanced green fluorescent protein gene (Ad- EGFP), and then cultured for seven days. Transfection was confirmed by fluorescence microscopy and Western blot. Islet viability was evaluated by acridine orange/ propidium iodide fluorescent staining. Glucose-stimulated insulin release was detected using insulin radioimmunoassay kits and was used to assess the function of islets. Stimulation index (SI) was calculated by dividing the insulin release upon high glucose stimulation by the insulin release upon low glucose stimulation. RESULTS: After seven days culture, the viability of cultured rat islets decreased significantly (92% ± 6% vs 52% ± 13%, P 〈 0.05), and glucose-stimulated insulin release also decreased significantly (6.47 ± 0.55 mIU/ L/30IEO vs 4.57 ± 0.40 mIU/L/3OIEO., 14.93 ± 1.17 mIU/L/30IEQ vs 9.63 ± 0.71 mIU/L/30IEQ, P 〈 0.05). Transfection of rat islets with adenoviral vectors at an 1±10 of 20 was efficient, and did not impair islet function. At 7 d post-transfection, the viability of Ad-HO-1 transfected islets was higher than that of control islets(71% ± 15% vs 52% ± 13%, P 〈 0.05). There was no significant difference in insulin release upon low glucose stimulation (2.8 mmol/L) among Ad-HO-1 transfected group, Ad-EGFP transfected group, and control group (P 〉 0.05), while when stimulated by high glucose (16.7 mmol/L) solution, insulin release in Ad-HO-1 transfected group was significantly higher than that in Ad-EGFP transfected group and control group, respectively (12.50 ±2.17 mIU/L/30IEQ vs 8.87 ± 0.65 mIU/L/30IEQ, 12.50 ± 2.17 mIU/L/30IEQ vs 9.63 ± 0.71 mIU/L/30IEQ, P 〈 0.05). The SI of Ad-HO-1 transfected group was also significantly higher than that of Ad-EGFP transfected group and control group, respectively (2.21 ± 0.02 vs 2.08 ± 0.05; 2.21 ± 0.02 vs 2.11 ± 0.03, P 〈 0.05). CONCLUSION: The viability and function of rat islets decrease over time in in vitro culture, and heine oxygenase-1 gene transfer could improve the viability and function of cultured rat islets.
基金Supported by the National Key Basic Research Development Program of China, 973 Program, No. 2004CB117505
文摘AIM: To isolate and identify the soybean conglycinin peptides that selectively stimulates the growth of bifidobacteria in vitro, and to investigate the effect of soybean conglycinin peptides on intestinal ecosystem in vivo. METHODS: Soybean conglycinin was purified from soybean seeds by gel filtration (Sepharose-CL-6B). These proteins were submitted to hydrolysis by pepsin. Several growth-stimulating peptides for bifidobacteria were isolated chromatographically from pepsin hydrolysis of soybean conglycinin and identified by means of matrixassisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS). Parallel to in vitro study, in vivo experiments with soybean conglycinin peptides were performed in mice. Ninety male KM mice were randomly assigned into five groups of 16 mice each, and each group was administered for 21d intragastrically with physiological saline (control), conglycinin, pepsin-treated conglycinin (PTC), the most active fraction which isolated from pepsin-treated conglycinin (P2-PTC) and HCl-full hydrolysis of conglycinin (HCl-FHC), respectively. Intestinal microflora were evaluated by standard microbiologic methods and biochemical assays of cecal content samples after treatment. RESULTS: The results showed that the peptides which were isolated from soybean conglycinin could stimulate the growth of bifidobacteria in vitro, and the molecular mass of purified peptides with MALDI-TOF-MS ranged from 693.32 to 1829.55. Compared with control group, in vivo experiments showed that P2-PTC group decreased cecal pH (7.08±0.08 vs7.21±0.09, P〈0.05) and enterococcicounts (5.38±0.26 log10CFU/g vs 5.78±0.19 log10CFU/g, P〈0.05), significantly increased sIgA level (172.08±35.40 ng/g vs 118.27±33.93 ng/g, P〈0.01) and β-galactosidase activity (1.28±0.23 U/g vs 1.82±0.58 U/g, P〈0.05) CONCLUSION: The results have shown that conglycinin is good source for enzyme-mediated production of peptides which stimulate the growth of bifidobacteria. These peptides are inactive within the sequence of the parent protein but can be released during enzymatic hydrolysis, and in vivo experiments demonstrate that conglycinin peptides may be beneficial for improving gastrointestinal health.
文摘AIM: To investigate the relationship between gastric dysmotility,gastrointestinal hormone abnormalities, and neuroendocrine cells in gastrointestinal mucosa in patients with functional dyspepsia (FD).METHODS: Gastric emptying was assessed with solid radiopaque markers in 54 FD patients, and the patients were divided into two groups according to the results, one with delayed gastric emptying and the other with normal gastric emptying. Seventeen healthy volunteers acted as normal controls. Fasting and postprandial plasma levels and gastroduodenal mucosal levels of gastrointestinal hormones gastrin, somatostatin (SS) and neurotensin (NT)were measured by radioimmunoassay in all the subjects.G cells (gastrin-producing cells) and D cells (SS-producing cells) in gastric antral mucosa were immunostained with rabbit anti-gastrin polyclonal antibody and rabbit anti-SS polyclonal antibody, respectively, and analyzed quantitatively by computerized image analysis.RESULTS: The postprandial plasma gastrin levels, the fasting and postprandial plasma levels and the gastric and duodenal mucosal levels of NT were significantly higher in the FD patients with delayed gastric emptying than in those with normal gastric emptying and normal controls. The number and gray value of G and D cells and the G cell/D cell number ratio did not differ significantly between normal controls and the FD patients with or without delayed gastric emptying.CONCLUSION: Our findings suggest that the abnormalities of gastrin and NT may play a role in the pathophysiology of gastric dysmotility in FD patients, and the abnormality of postprandial plasma gastrin levels in FD patients with delayed gastric emptying is not related to the changes both in the number and gray value of G cells and in the G cell/D cell number ratio in gastric antral mucosa.
基金Yakult Ltd, Melbourne Australiain receipt of the Sir Robert Menzies Memorial Research Scholarship in Allied Health Sciences+1 种基金Pharmatel Fresenius Kabi IBD Fellowship and the New Zealand Society of Gastroenterology-Ferring Pharmaceuticals Fellowshipa Fellowship from Nycomed.
文摘AIM: To determine whether Lactobacillus casei strain Shirota (Yakult) can alter small intestinal bacterial overgrowth (SIBO), as tested by the lactulose breath test, and whether this is associated with changes in symptoms in irritable bowel syndrome (IBS). METHODS: 18 patients with IBS (Rome Ⅱ criteria), who showed an early rise in breath hydrogen with lactulose (ERBHAL), consumed 65 mL of Yakult daily for 6 wk. Lactulose breath test was repeated at the end of the treatment period. Symptoms were recorded daily using a 10 cm visual analogue scale. RESULTS: 14 patients completed the study, 9 (64%) had reversal of ERBHAL, with the median time of first rise in breath hydrogen increasing from 45 to 75 min (P = 0.03). There was no significant improvement in the symptom score with probiotic therapy, except for wind (P = 0.04). Patients commencing with at least moderate symptoms and who no longer had ERBHAL at the end of treatment, showed improvement in the overall symptoms scores [median final score 5.3 (IQR 3.9-5.9), 55% reduction; n = 6] to a greater extent than those who had had persisting ERBHAL [final score 6.9 (5.0-7.0), 12% reduction; n = 5; P = 0.18]. CONCLUSION: Yakult is effective in altering fermentation patterns in the small bowel, consistent with reducing SIBO. The loss of ERBHAL was associated with reduced symptoms. The true interpretation of these findings awaits a randornised, controlled trial.
基金Supported by A Grant from the Canadian Institutes of Health Research(MOP-14790)to Bourgoin SG
文摘Small GTP-binding proteins of the ADP-ribosylation fac-tor (Arf) family control various cell functional responses including protein transport and recycling between different cellular compartments, phagocytosis, prolif-eration, cytoskeletal remodelling, and migration. The activity of Arfs is tightly regulated. GTPase-activating proteins (GAPs) inactivate Arfs by stimulating GTP hydrolysis, and guanine nucleotide exchange factors (GEFs) stimulate the conversion of inactive GDP-bound Arf to the active GTP-bound conformation. There is increasing evidence that Arf small GTPases contribute to cancer growth and invasion. Increased expression of Arf6 and of Arf-GEPs, or deregulation Arf-GAP functions have been correlated with enhanced invasive capacity of tumor cells and metastasis. The spatiotemporal spe-cifcity of Arf activation is dictated by their GEFs that integrate various signals in stimulated cells. Brefeldin A (BFA), which inactivates a subset of Arf-GEFs, has been very useful for assessing the function of Golgi-localized Arfs. However, specifc inhibitors to investigate the individual function of BFA-sensitive and insensitive Arf-GEFs are lacking. In recent years, specifc screens have been developed, and new inhibitors with improved se-lectivity and potency to study cell functional responses regulated by BFA-sensitive and BFA-insensitive Arf pathways have been identified. These inhibitors have been instrumental for our understanding of the spa-tiotemporal activation of Arf proteins in cells and dem-onstrate the feasibility of developing small molecules interfering with Arf activation to prevent tumor invasion and metastasis.
文摘Recent studies have identified mutations in PHF8, an X-linked gene encoding a JmjC domain-containing protein, as a causal factor for X-linked mental retardation (XLMR) and cleft lip/cleft palate. However, the underlying mechanism is unknown. Here we show that PHF8 is a histone demethylase and coactivator for retinoic acid receptor (RAR). Although activities for both H3K4me3/2/1 and H3K9me2/1 demethylation were detected in cellularbased assays, reeombinant PHF8 exhibited only H3K9me2/1 demethylase activity in vitro, suggesting that PHF8 is an H3K9me2/1 demethylase whose specificity may be modulated in vivo. Importantly, a mutant PHF8 (phenylalanine at position 279 to serine) identified in the XLMR patients is defective in enzymatie activity, indicating that the loss of histone demethylase activity is causally linked with the onset of disease. In addition, we show that PHF8 binds specifically to H3K4me3/2 peptides via an N-terminal PHD finger domain. Consistent with a role for PHF8 in neuronal differentiation, knockdown of PHF8 in mouse embryonic carcinoma P19 cells impairs RA-induced neuronal differentiation, whereas overexpression of the wild-type but not the F279S mutant PHF8 drives PI9 cells toward neuronal differentiation. Furthermore, we show that PHF8 interacts with RAR~ and functions as a coactivator for RARa. Taken together, our results suggest that histone methylation modulated by PHF8 plays a critical role in neuronal differentiation.
基金supported by the Key State Basic Research and Development Program(G1999012002)the National Natural Science Foundation(30271016)+1 种基金a research grant of the Key Laboratory of Mariculture,Ministry of Education,Ocean University of China(LMMEC)(200210)the Changjiang Scholars Program of China
文摘Structure and function of the digestive system of a bivalve mollusc, Solen grandis, were studied using light microscopy and histochemical methods. The wall of digestive tube consists of four layers: the mucosal epithelium, connective tissue, muscular and fibrosa or serosa (only in the portion of rectum) from the inner to the outer. The ciliated columnar epithelial cells, dispersed by cup-shaped mucous cells, rest on a thin base membrane. There are abundant blood spaces in connective tissue layer. The digestive diverticula are composed of multi-branched duct and digestive tubules. The digestive tubules are lined with digestive and basophilic secretory cells, and surrounded by a layer of smooth muscle fibers and connective tissues. Activities of acid and alkaline phosphatases, esterase and lipase are detected in the digestive cells, and the epithelia of stomach and intestine, suggesting that these cells are capable of intracellular digesting of food materials and absorbing.Besides, acid phosphatase and esterase activities are present in the posterior portion of esophagus. Phagocytes are abundant in blood spaces and the lumens of stomach and intestine, containing brown granules derived from the engulfed food materials. The present work indicates that phagocytes play important roles in ingestion and digestion of food materials, which is supported as well by the activities of acid phosphatase, esterase and lipase detected in blood spaces.
文摘Objective: We aimed to study the influence of neoadjuvant chemotherapy on immunity function in elderly patients with the stages of II and III esophageal cancer. Methods: Thirty-seven elderly patients (age ranged from 60 to 75 years) with the stages of II and III esophageal cancer underwent 2 cycles chemotherapy preoperatively with single-drug regimen (docetaxel, 35 mg/m2 once a week, on days 1, 8 and 15, at interval of 2 weeks for one cycle). Surgery were performed three weeks later. Blood samples were drawn separately on the day of admission, 1 day before operation, 7 day and 1 month after operation, and we conducted the Flow Cytometry to detect the levels of CD3+, CD4+, CD8+,CD4+/CD8+ and NK cells. Results: There were no significant differences in the levels of CD3+, CD4+, CD8+, CD4+/CD8+ and NK cells between before and after chemotherapy (P > 0.05). On day 7 after operation, the levels of CD3+, CD4+, CD4+/CD8+ and NK cells were degraded and CD8+ increased significantly (P < 0.05). One month after operation, the levels of CD3, CD4+, CD4+/CD8 and NK cells were higher than normal, and CD8 was depressed significantly (P < 0.05). Conclusion: Neoadjuvant chemotherapy has no significant impact on cellular immune function in elderly patients with the stages of II and III esophageal cancer, it is an effective and safe treatment.
文摘Objective:Hepatocellular carcinoma (HCC) is among the most common and rapidly increasing cancers in Pakistan.There is currently no standard management for advanced HCC.The aim of the study was to assess response rate and toxicity of concomitant gemcitabine and external radiation therapy (ERT) in locally advanced HCC.Methods:Sixty patients were enrolled.Gemcitabine,70 mg/m2 was given weekly during ERT.ERT was delivered with 60Co beam up to 30.6 Gy,1.8 Gy/fraction.Tumor response was assessed by computed tomography (CT) at eight weeks.Complete and partial response (CR and PR),progressive and stable disease (PD and SD) were assessed.Hematological,gastrointestinal and hepatic toxicities were assessed weekly.Results:No CR was seen.PR,SD and PD were seen in 33%,40% and 27% of patients respectively.Grade 3/4 toxicity for total leukocyte count and platelets was observed in 7% and 27% patients.Grade 3/4 toxicity for liver failure,bilirubin,aspartate aminotransferase,alanine aminotransferase and alkaline phosphatase was seen in 35%,28%,38%,24% and 43% patients respectively.Conclusion:The study showed that concomitant gemcitabine and ERT is a feasible option with moderate toxicity in advanced HCC.