Lactobacillus fermentum （L. fermentum） is one of seven species in the genus Lactobacillus[1]. With a long history of safe use in fermented food production, Lactobacillus is considered as one of the most beneficial p...Lactobacillus fermentum （L. fermentum） is one of seven species in the genus Lactobacillus[1]. With a long history of safe use in fermented food production, Lactobacillus is considered as one of the most beneficial probiotics[23]. The most well-known potential health benefit is improving digestion and immune function[4.s]. Other beneficial functions of Lactobacillus strains include managing lactose intoleranceIs], lowering cholesterol and blood pressureIs], reducing inflammation[~], and prevention of cancerIs＇7]. L. fermentum is usually found during malt whisky fermentation]8]. L. fermentum CP34 was found to have the significant effect of decreasing the serum antigen-specific IgE levels compared to a control group[9].展开更多
Acrylamide is a chemical used mainly in industrial applications and the treatment of drinking and wastewater, making it easy to enter aquatic ecosystems. There are few studies known about the toxicity of acrylamide to...Acrylamide is a chemical used mainly in industrial applications and the treatment of drinking and wastewater, making it easy to enter aquatic ecosystems. There are few studies known about the toxicity of acrylamide to aquatic organisms which have shown evidence of a number of histopathological effects. To assess the effects of acrylamide to freshwater fish, Zebrafish (Danio rerio) embryos were exposed to serial concentrations of acrylamide (0, 100, 300, and 500 mg/L) to investigate the acute toxicity effects on teleost embryogenesis. Embryos less than 24 hrs old were exposed under static non-renewal conditions for ten days or until hatching. The toxic endpoints evaluated include: egg/embryo viability, hatchability, and morphological/developmental anomalies during organogenesis. The acute toxicity test resulted in a 48 h-LC50 of 585 mg/L for egg viability. Exposure of embryos significantly reduced hatchability and larval survival, in a concentration dependent manner. Dimethyl sulfoxide (DMSO) was used as a solvent carrier to permeate the uptake of acrylamide through the chorion membrane. No significant damages or complications were observed in embryos exposed to DMSO. At 500 mg/L, the highest test concentration, the survival of embryos was greatly reduced within 24 hrs of exposure. The lower test, 100 mg/L, produced a significant number of developmental anomalies to the Zebrafish that included dorsal tail flexure, severe pericardial edema, facial and cranial defects and decreased heartrate (40 bpm). Premature hatching of embryos and developmental arrest was observed in all concentrations. The severity of these anomalies was concentration-dependent and resulted in low survival rate and high frequency of malformations. These results indicate that acrylamide is teratogenic and provide support for sub-lethal toxicity testing using Zebrafish embryos.展开更多
Objective To assess the current status of the acrylamide in the Chinese food supply, the dietary acrylamide exposure in the Chinese population and to estimate the public health risks of the current consumption. Method...Objective To assess the current status of the acrylamide in the Chinese food supply, the dietary acrylamide exposure in the Chinese population and to estimate the public health risks of the current consumption. Methods The acrylamide content in the total diet study （TDS） food samples was analyzed using an LC-MS/MS method. Based on the analytical results, the dietary exposure calculations were performed using a deterministic method, combining mean acrylamide concentrations from the food group composite with their associated food consumptions. Results Acrylamide was detected in 43.7% of all samples collected and acrylamide concentration varied from ND to 526.6 I^g/kg. The estimated dietary intakes of acrylamide among Chinese general population given as the mean and the 95th percentile （P95） were 0.286 and 0.490 iJg.kg1 bw.day1, respectively. The margins of exposure （MOEs） for the population calculated using both benchmark dose lower confidence limit for a 10% extra risk of tumors in animals （BMDL10） 0.31 and 0.18 i^g.k8-1 bw-dayz, were 1069 and 621 for the mean dietary exposure, and 633 and 367 for the high dietary exposure respectively. Conclusion These MOE values might indicate a human health concern on acrylamide for Chinese population. Efforts should continue to reduce acrylamide levels in food in order to reduce the dietary risks to the human health.展开更多
Although numerous studies have examined the neurotoxicity of acrylamide in adult animals,the effects on neuronal development in the embryonic and lactational periods are largely unknown.Thus,we examined the toxicity o...Although numerous studies have examined the neurotoxicity of acrylamide in adult animals,the effects on neuronal development in the embryonic and lactational periods are largely unknown.Thus,we examined the toxicity of acrylamide on neuronal development in the hippocampus of fetal rats during pregnancy.Sprague-Dawley rats were mated with male rats at a 1：1 ratio.Rats were administered 0,5,10 or 20 mg/kg acrylamide intragastrically from embryonic days 6–21.The gait scores were examined in pregnant rats in each group to analyze maternal toxicity.Eight weaning rats from each group were also euthanized on postnatal day 21 for follow-up studies.Nissl staining was used to observe histological change in the hippocampus.Immunohistochemistry was conducted to observe the condition of neurites,including dendrites and axons.Western blot assay was used to measure the expression levels of the specific nerve axon membrane protein,growth associated protein 43,and the presynaptic vesicle membrane specific protein,synaptophysin.The gait scores of gravid rats significantly increased,suggesting that acrylamide induced maternal motor dysfunction.The number of neurons,as well as expression of growth associated protein 43 and synaptophysin,was reduced with increasing acrylamide dose in postnatal day 21 weaning rats.These data suggest that acrylamide exerts dose-dependent toxic effects on the growth and development of hippocampal neurons of weaning rats.展开更多
It is found that acetoacetanilide possesses very high promoting reactivity towards ceric ion in initiating polymerization of vinyl monomer. The kinetics of acrylamide polymerization and the activation energies were st...It is found that acetoacetanilide possesses very high promoting reactivity towards ceric ion in initiating polymerization of vinyl monomer. The kinetics of acrylamide polymerization and the activation energies were studied. The initiation mechanism of ceric/acetoacetanilide is proposed on the basis of experimental results of FT-IR and ESR.展开更多
To explore the toxicological profile of methanol extract of Chlorophytum alismifolium (MECA) tubers in Wistar rats. Methods: MECA was subjected to acute and sub-acute studies which were conducted according to Organiza...To explore the toxicological profile of methanol extract of Chlorophytum alismifolium (MECA) tubers in Wistar rats. Methods: MECA was subjected to acute and sub-acute studies which were conducted according to Organization for Economic Co-operation and Development (OECD 425 and 407 guidelines respectively). In the acute toxicity experiment, a limit test (5000 mg/kg) was administered to five rats and monitored for 2 weeks. The sub-acute studies were conducted on 4 groups of rats. The first group served as control, while the 2nd, 3rd and 4th groups received MECA (150, 300 and 600 mg/kg respectively). The treatments were given orally and daily for 4 weeks. At the end of the experiment (29th day), the animals were euthanized to obtain blood samples and organs for haematological, biochemical and histological evaluations. Results: Acute toxicity study showed that the oral median lethal dose was >5000 mg/kg. In the sub-acute studies, the results showed no significant (P>0.05) changes in the haematological, hepatic and renal indices compared to control animals. In the fourth week, a significant (P<0.01) increase in body weight of the rats was observed at 150 mg/kg and 600 mg/kg compared to week one. However, there were no major changes in the organ/body weights of the rats. Histological examination of the kidney showed slight glomerular adhesion and tubular distortion. Moderate hepatic necrosis was observed at 150 mg/kg and 300 mg/kg. Conclusions: The results of this research revealed that the MECA tubers is virtually non-toxic after acute administration and it has low sub-acute toxicity potential in rats.展开更多
Zidvovudine(AZT) is a nucleoside analogue reverse transcriptase inhibitor(NRTI), a class of anti-retroviral drug. A stability-indicating assay method for AZT was developed in line with ICH guideline. Successful separa...Zidvovudine(AZT) is a nucleoside analogue reverse transcriptase inhibitor(NRTI), a class of anti-retroviral drug. A stability-indicating assay method for AZT was developed in line with ICH guideline. Successful separation of AZT and its degradation products was achieved by gradient elution mode on reverse phase C_(18) column using 10 mM ammonium acetate: acetonitrile as the mobile phase at 0.8 mL/min flow rate, 25 μL injection volume, 30 °C column temperature and 285 nm detection wavelength. Two major acid degradation products were identified and characterized by liquid chromatography–electrospray ionization mass spectrometry(LC–ESI/MS/MS) and accurate mass measurements. The probable mechanisms for the formation of degradation products were identified based on a comparison of the fragmentation pattern of the [M + H]^+ions of AZT and its degradation products. One of the degradation products, DP-1, was isolated by semi-preparative high performance liquid chromatography(HPLC) using Waters XBridge Prep C_(18)(250 mm×10 mm, 5 μm).Degradation products showed higher toxicity compared to the drug in some models assessed by TOPKAT software. The method validation was performed with respect to robustness, specificity, linearity, precision and accuracy as per ICH guideline Q2(R1).展开更多
Introduction: Satraplatin has been given in combination therapy for lung cancer to utilize its radio-sensitizing properties. The optimal dose of satra-platin given concurrently with radiation therapy for locally advan...Introduction: Satraplatin has been given in combination therapy for lung cancer to utilize its radio-sensitizing properties. The optimal dose of satra-platin given concurrently with radiation therapy for locally advanced non-small cell lung cancer (NSC-LC) has not been defined. This phase I trial attempts to identify a maximally tolerated dose (MTD) and dose limiting toxicity (DLT) for Satraplatin given con-currently with radiation for locally advanced N-SCLC. Patients and Methods: 15 patients with histologically confirmed Stage IIIA/B NSCLC entered onto this study with four dose escalations (10 to 40 mg daily) of Satraplatin. Eligibility included patients with NSCLC and one of the following criteria: 1) previously untreated, inoperable disease and planned to receive radiation therapy to primary disease site;2) previously resected disease with mediastinal relapse;or 3) metastatic disease in no more than one distant site. Results: The most common toxicities reported were all grades of fatigue (n = 9), nausea (n = 9), constipation (n = 7), fever (n = 7), and vomiting (n = 6). No DLT at the 1st, 2nd, and 3rd dose levels was identified. At the 4th dose level, one patient developed grade III elevation of liver function tests (LFTs) and a second patient developed grade III diarrhea with fever requiring hospitalization. There were 8 partial responses out of 11 evaluable patients for response (RR 67%). Conclusion: Elevated LFTs and diarrhea appear to be the principal DLTs of concurrent daily oral Satraplatin and thoracic radiation in the outpatient setting. The MTD of concurrent Satraplatin with thoracic radiation therapy appears to be 40 mg daily.展开更多
Background:No data exist on the efficacy and safety of anlotinib plus camrelizumab doublet as second-line therapy for advanced esophageal squamous cell carcinoma(ESCC).Although anlotinib and the programmed death-1(PD1...Background:No data exist on the efficacy and safety of anlotinib plus camrelizumab doublet as second-line therapy for advanced esophageal squamous cell carcinoma(ESCC).Although anlotinib and the programmed death-1(PD1)inhibitor camrelizumab are used as treatments for ESCC,the combined use of anlotinib and camrelizumab as a second-line therapy has not been reported.Therefore,this study explored the efficacy and toxicity of anlotinib plus camrelizumab as second-line therapy for advanced ESCC.Methods:Fifty-eight patients with advanced ESCC undergoing second-line therapy,either with anlotinib plus camrelizumab or anlotinib plus S-1,were enrolled and retrospectively analyzed at Jiangsu Province Hospital of Chinese Medicine from January 2020 to December 2021.The primary endpoint was progression-free survival(PFS),with secondary endpoints including the objective response rate(ORR),disease control rate(DCR),and assessment of toxicity.Results:In patients with advanced ESCC,the anlotinib plus camrelizumab group(N=32)exhibited longer PFS(8.00 vs.4.53 months,P<0.001),higher ORR(28.1 vs.19.2%,P=0.431),and higher DCR(87.5 vs.65.4%,P=0.045)than those in the anlotinib plus S-1 group(N=26).Treatment-related adverse events(TRAEs)were predominantly grade 1/2 in both groups,with a higher incidence of grade 1/2 skin toxicity in patients treated with anlotinib plus camrelizumab(P=0.033).Two patients(6.3%)developed grade 1/2 immune-related pneumonia.The incidence of grade 3/4 TRAEs did not differ significantly between the two groups.Multivariable Cox regression analysis identified that the drug regimen(P<0.001),Eastern Cooperative Oncology Group performance status(P=0.008),and differentiation grade(P=0.008)were independent prognostic factors for PFS.Conclusions:Anlotinib plus camrelizumab exhibited promising antitumor efficacy and manageable toxicity when used as a second-line treatment for advanced ESCC.展开更多
基金supported by the National Scienceand technology support program(2012BAK01B04)
文摘Lactobacillus fermentum （L. fermentum） is one of seven species in the genus Lactobacillus[1]. With a long history of safe use in fermented food production, Lactobacillus is considered as one of the most beneficial probiotics[23]. The most well-known potential health benefit is improving digestion and immune function[4.s]. Other beneficial functions of Lactobacillus strains include managing lactose intoleranceIs], lowering cholesterol and blood pressureIs], reducing inflammation[~], and prevention of cancerIs＇7]. L. fermentum is usually found during malt whisky fermentation]8]. L. fermentum CP34 was found to have the significant effect of decreasing the serum antigen-specific IgE levels compared to a control group[9].
文摘Acrylamide is a chemical used mainly in industrial applications and the treatment of drinking and wastewater, making it easy to enter aquatic ecosystems. There are few studies known about the toxicity of acrylamide to aquatic organisms which have shown evidence of a number of histopathological effects. To assess the effects of acrylamide to freshwater fish, Zebrafish (Danio rerio) embryos were exposed to serial concentrations of acrylamide (0, 100, 300, and 500 mg/L) to investigate the acute toxicity effects on teleost embryogenesis. Embryos less than 24 hrs old were exposed under static non-renewal conditions for ten days or until hatching. The toxic endpoints evaluated include: egg/embryo viability, hatchability, and morphological/developmental anomalies during organogenesis. The acute toxicity test resulted in a 48 h-LC50 of 585 mg/L for egg viability. Exposure of embryos significantly reduced hatchability and larval survival, in a concentration dependent manner. Dimethyl sulfoxide (DMSO) was used as a solvent carrier to permeate the uptake of acrylamide through the chorion membrane. No significant damages or complications were observed in embryos exposed to DMSO. At 500 mg/L, the highest test concentration, the survival of embryos was greatly reduced within 24 hrs of exposure. The lower test, 100 mg/L, produced a significant number of developmental anomalies to the Zebrafish that included dorsal tail flexure, severe pericardial edema, facial and cranial defects and decreased heartrate (40 bpm). Premature hatching of embryos and developmental arrest was observed in all concentrations. The severity of these anomalies was concentration-dependent and resulted in low survival rate and high frequency of malformations. These results indicate that acrylamide is teratogenic and provide support for sub-lethal toxicity testing using Zebrafish embryos.
基金supported by the National Basic Resarch Program of China(2012CB20804)grant from Ministry of Health,PR China(200902009)
文摘Objective To assess the current status of the acrylamide in the Chinese food supply, the dietary acrylamide exposure in the Chinese population and to estimate the public health risks of the current consumption. Methods The acrylamide content in the total diet study （TDS） food samples was analyzed using an LC-MS/MS method. Based on the analytical results, the dietary exposure calculations were performed using a deterministic method, combining mean acrylamide concentrations from the food group composite with their associated food consumptions. Results Acrylamide was detected in 43.7% of all samples collected and acrylamide concentration varied from ND to 526.6 I^g/kg. The estimated dietary intakes of acrylamide among Chinese general population given as the mean and the 95th percentile （P95） were 0.286 and 0.490 iJg.kg1 bw.day1, respectively. The margins of exposure （MOEs） for the population calculated using both benchmark dose lower confidence limit for a 10% extra risk of tumors in animals （BMDL10） 0.31 and 0.18 i^g.k8-1 bw-dayz, were 1069 and 621 for the mean dietary exposure, and 633 and 367 for the high dietary exposure respectively. Conclusion These MOE values might indicate a human health concern on acrylamide for Chinese population. Efforts should continue to reduce acrylamide levels in food in order to reduce the dietary risks to the human health.
基金supported by the Guangdong Provincial Department of Science and Technology in China,No.2016A020225007
文摘Although numerous studies have examined the neurotoxicity of acrylamide in adult animals,the effects on neuronal development in the embryonic and lactational periods are largely unknown.Thus,we examined the toxicity of acrylamide on neuronal development in the hippocampus of fetal rats during pregnancy.Sprague-Dawley rats were mated with male rats at a 1：1 ratio.Rats were administered 0,5,10 or 20 mg/kg acrylamide intragastrically from embryonic days 6–21.The gait scores were examined in pregnant rats in each group to analyze maternal toxicity.Eight weaning rats from each group were also euthanized on postnatal day 21 for follow-up studies.Nissl staining was used to observe histological change in the hippocampus.Immunohistochemistry was conducted to observe the condition of neurites,including dendrites and axons.Western blot assay was used to measure the expression levels of the specific nerve axon membrane protein,growth associated protein 43,and the presynaptic vesicle membrane specific protein,synaptophysin.The gait scores of gravid rats significantly increased,suggesting that acrylamide induced maternal motor dysfunction.The number of neurons,as well as expression of growth associated protein 43 and synaptophysin,was reduced with increasing acrylamide dose in postnatal day 21 weaning rats.These data suggest that acrylamide exerts dose-dependent toxic effects on the growth and development of hippocampal neurons of weaning rats.
文摘It is found that acetoacetanilide possesses very high promoting reactivity towards ceric ion in initiating polymerization of vinyl monomer. The kinetics of acrylamide polymerization and the activation energies were studied. The initiation mechanism of ceric/acetoacetanilide is proposed on the basis of experimental results of FT-IR and ESR.
文摘To explore the toxicological profile of methanol extract of Chlorophytum alismifolium (MECA) tubers in Wistar rats. Methods: MECA was subjected to acute and sub-acute studies which were conducted according to Organization for Economic Co-operation and Development (OECD 425 and 407 guidelines respectively). In the acute toxicity experiment, a limit test (5000 mg/kg) was administered to five rats and monitored for 2 weeks. The sub-acute studies were conducted on 4 groups of rats. The first group served as control, while the 2nd, 3rd and 4th groups received MECA (150, 300 and 600 mg/kg respectively). The treatments were given orally and daily for 4 weeks. At the end of the experiment (29th day), the animals were euthanized to obtain blood samples and organs for haematological, biochemical and histological evaluations. Results: Acute toxicity study showed that the oral median lethal dose was >5000 mg/kg. In the sub-acute studies, the results showed no significant (P>0.05) changes in the haematological, hepatic and renal indices compared to control animals. In the fourth week, a significant (P<0.01) increase in body weight of the rats was observed at 150 mg/kg and 600 mg/kg compared to week one. However, there were no major changes in the organ/body weights of the rats. Histological examination of the kidney showed slight glomerular adhesion and tubular distortion. Moderate hepatic necrosis was observed at 150 mg/kg and 300 mg/kg. Conclusions: The results of this research revealed that the MECA tubers is virtually non-toxic after acute administration and it has low sub-acute toxicity potential in rats.
文摘Zidvovudine(AZT) is a nucleoside analogue reverse transcriptase inhibitor(NRTI), a class of anti-retroviral drug. A stability-indicating assay method for AZT was developed in line with ICH guideline. Successful separation of AZT and its degradation products was achieved by gradient elution mode on reverse phase C_(18) column using 10 mM ammonium acetate: acetonitrile as the mobile phase at 0.8 mL/min flow rate, 25 μL injection volume, 30 °C column temperature and 285 nm detection wavelength. Two major acid degradation products were identified and characterized by liquid chromatography–electrospray ionization mass spectrometry(LC–ESI/MS/MS) and accurate mass measurements. The probable mechanisms for the formation of degradation products were identified based on a comparison of the fragmentation pattern of the [M + H]^+ions of AZT and its degradation products. One of the degradation products, DP-1, was isolated by semi-preparative high performance liquid chromatography(HPLC) using Waters XBridge Prep C_(18)(250 mm×10 mm, 5 μm).Degradation products showed higher toxicity compared to the drug in some models assessed by TOPKAT software. The method validation was performed with respect to robustness, specificity, linearity, precision and accuracy as per ICH guideline Q2(R1).
文摘Introduction: Satraplatin has been given in combination therapy for lung cancer to utilize its radio-sensitizing properties. The optimal dose of satra-platin given concurrently with radiation therapy for locally advanced non-small cell lung cancer (NSC-LC) has not been defined. This phase I trial attempts to identify a maximally tolerated dose (MTD) and dose limiting toxicity (DLT) for Satraplatin given con-currently with radiation for locally advanced N-SCLC. Patients and Methods: 15 patients with histologically confirmed Stage IIIA/B NSCLC entered onto this study with four dose escalations (10 to 40 mg daily) of Satraplatin. Eligibility included patients with NSCLC and one of the following criteria: 1) previously untreated, inoperable disease and planned to receive radiation therapy to primary disease site;2) previously resected disease with mediastinal relapse;or 3) metastatic disease in no more than one distant site. Results: The most common toxicities reported were all grades of fatigue (n = 9), nausea (n = 9), constipation (n = 7), fever (n = 7), and vomiting (n = 6). No DLT at the 1st, 2nd, and 3rd dose levels was identified. At the 4th dose level, one patient developed grade III elevation of liver function tests (LFTs) and a second patient developed grade III diarrhea with fever requiring hospitalization. There were 8 partial responses out of 11 evaluable patients for response (RR 67%). Conclusion: Elevated LFTs and diarrhea appear to be the principal DLTs of concurrent daily oral Satraplatin and thoracic radiation in the outpatient setting. The MTD of concurrent Satraplatin with thoracic radiation therapy appears to be 40 mg daily.
文摘Background:No data exist on the efficacy and safety of anlotinib plus camrelizumab doublet as second-line therapy for advanced esophageal squamous cell carcinoma(ESCC).Although anlotinib and the programmed death-1(PD1)inhibitor camrelizumab are used as treatments for ESCC,the combined use of anlotinib and camrelizumab as a second-line therapy has not been reported.Therefore,this study explored the efficacy and toxicity of anlotinib plus camrelizumab as second-line therapy for advanced ESCC.Methods:Fifty-eight patients with advanced ESCC undergoing second-line therapy,either with anlotinib plus camrelizumab or anlotinib plus S-1,were enrolled and retrospectively analyzed at Jiangsu Province Hospital of Chinese Medicine from January 2020 to December 2021.The primary endpoint was progression-free survival(PFS),with secondary endpoints including the objective response rate(ORR),disease control rate(DCR),and assessment of toxicity.Results:In patients with advanced ESCC,the anlotinib plus camrelizumab group(N=32)exhibited longer PFS(8.00 vs.4.53 months,P<0.001),higher ORR(28.1 vs.19.2%,P=0.431),and higher DCR(87.5 vs.65.4%,P=0.045)than those in the anlotinib plus S-1 group(N=26).Treatment-related adverse events(TRAEs)were predominantly grade 1/2 in both groups,with a higher incidence of grade 1/2 skin toxicity in patients treated with anlotinib plus camrelizumab(P=0.033).Two patients(6.3%)developed grade 1/2 immune-related pneumonia.The incidence of grade 3/4 TRAEs did not differ significantly between the two groups.Multivariable Cox regression analysis identified that the drug regimen(P<0.001),Eastern Cooperative Oncology Group performance status(P=0.008),and differentiation grade(P=0.008)were independent prognostic factors for PFS.Conclusions:Anlotinib plus camrelizumab exhibited promising antitumor efficacy and manageable toxicity when used as a second-line treatment for advanced ESCC.
