Immune-related adverse events(irAEs)represent an increasingly concerning challenge in the assessment of biopharmaceutical products.In contrast to historically rare allergic reactions associated with small chemical dru...Immune-related adverse events(irAEs)represent an increasingly concerning challenge in the assessment of biopharmaceutical products.In contrast to historically rare allergic reactions associated with small chemical drugs,contemporary biotherapeutics exhibit a significantly higher morbidity of irAEs,because of their complex structure and comprehensive mechanisms of action.While the immunogenicity of protein-based compounds is associated with the induction of anti-drug antibodies,the pathogenesis of irAEs in advanced biologics,such as cell and gene therapy,remains to be further delineated.In the current study,I present an updated profile regarding the untoward immune effects of medications,covering various material categories systematically,with the underlying mechanisms to inspire risk mitigation in biopharmaceutical development and application.展开更多
Bisphenol A （BPA） is the monomer component of polycarbonate plastics and classified as an endocrine disrupting chemical （EDC）. The reproductive toxicity of BPA has been extensively studied in mammals; however, rel...Bisphenol A （BPA） is the monomer component of polycarbonate plastics and classified as an endocrine disrupting chemical （EDC）. The reproductive toxicity of BPA has been extensively studied in mammals; however, relatively little information is available on the immunotoxic responses of fish to BPA. In this study, we investigated the effects of BPA on the immune functions of lymphocytes and macrophages in Carassius auratus. The effects of BPA were compared with those of two natural steroid hormones, estradiol and hydrocortisone. Proliferation of the two types of cells in response to PHA was measured using colorimetric MTT assay. Macrophage respiratory burst stimulated by Con A was measured using chemiluminescence assay. Results showed that BPA （0.054-5.4 mg/L）, estradiol （0.0002-2.0 mg/L） and hydrocortisone （5-50 mg/L） significantly induced Carassius auratus lymphocyte proliferation while higher doses of hydrocortisone （500-5000 mg/L） appeared to be inhibitory. BPA （0.005-50 mg/L）, estradiol （0.005-800 mg/L） and hydrocortisone （0.005-500 mg/L） markedly enhanced macrophage proliferation, whereas higher doses of BPA （500-1000 mg/L） appeared to inhibit cell proliferation. Furthermore, higher dosage of BPA （50 mg/L） and hydrocortisone （50 and 500 mg/L） suppressed the macrophages respiratory burst while estradiol is stimulative all the doses tested （0.05-500 mg/L）. In conclusion, BPA could have immunotoxicity to Carassius auratus and functional changes of lymphocyte and macrophage in Carassius auratus may be different between low and high dosages.展开更多
Objective To evaluate the immunotoxicological effects of genetically modified wheat with TaDREB4 gene in female BALB/c mice. Methods Female mice weighing 18-22 g were divided into five groups （10 mice/group）, which ...Objective To evaluate the immunotoxicological effects of genetically modified wheat with TaDREB4 gene in female BALB/c mice. Methods Female mice weighing 18-22 g were divided into five groups （10 mice/group）, which were set as negative control group, common wheat group, parental wheat group, genetically modified wheat group and cyclophosphamide positive control group, respectively. Mice in negative control group and positive control group were fed with AIN93G diet, mice in common wheat group, non-genetically modified parental wheat group and genetically modified wheat group were fed with feedstuffs added corresponding wheat （the proportion is 76%} for 30 days, then body weight, absolute and relative weight of spleen and thymus, white blood cell count, histological examination of immune organ, peripheral blood lymphocytes phenotyping, serum cytokine, serum immunoglobulin, antibody plaque-forming cell, serum half hemolysis value, mitogen-induced splenocyte proliferation, delayed-type hypersensitivity reaction and phagocytic activities of phagocytes were detected. Results No immunotoxicological effects related to the consumption of the genetically modified wheat were observed in BALB/c mice when compared with parental wheat group, common wheat group and negative control group. Conclusion From the immunotoxicological point of view, results from this study demonstrate that genetically modified wheat with TaDREB4 gene is as safe as the parental wheat.展开更多
Toxicological pathology plays a key role in drug safety assessment. To enhance the research level of toxicological pathology, the following stud-ies should be carried out urgently: setting up a standard operation proc...Toxicological pathology plays a key role in drug safety assessment. To enhance the research level of toxicological pathology, the following stud-ies should be carried out urgently: setting up a standard operation procedure (SOP) for toxico-logical pathology assessment; emphasizing on immunotoxicology evaluation; adopting a new ex-periment model of replacement, featuring high speed and reliability; introducing new techniques and new models in toxicological mechanism re-search; and establishing a new appraisal system to screen innovative drug and rapid and high pre-cision methods for early security assessment, de-tection and measurement.展开更多
文摘Immune-related adverse events(irAEs)represent an increasingly concerning challenge in the assessment of biopharmaceutical products.In contrast to historically rare allergic reactions associated with small chemical drugs,contemporary biotherapeutics exhibit a significantly higher morbidity of irAEs,because of their complex structure and comprehensive mechanisms of action.While the immunogenicity of protein-based compounds is associated with the induction of anti-drug antibodies,the pathogenesis of irAEs in advanced biologics,such as cell and gene therapy,remains to be further delineated.In the current study,I present an updated profile regarding the untoward immune effects of medications,covering various material categories systematically,with the underlying mechanisms to inspire risk mitigation in biopharmaceutical development and application.
基金Project supported by the National Natural Science Foundation of China (No. 20377022, 20237010)the National Basic Research Program (973) of China (No. 2002CB412307).
文摘Bisphenol A （BPA） is the monomer component of polycarbonate plastics and classified as an endocrine disrupting chemical （EDC）. The reproductive toxicity of BPA has been extensively studied in mammals; however, relatively little information is available on the immunotoxic responses of fish to BPA. In this study, we investigated the effects of BPA on the immune functions of lymphocytes and macrophages in Carassius auratus. The effects of BPA were compared with those of two natural steroid hormones, estradiol and hydrocortisone. Proliferation of the two types of cells in response to PHA was measured using colorimetric MTT assay. Macrophage respiratory burst stimulated by Con A was measured using chemiluminescence assay. Results showed that BPA （0.054-5.4 mg/L）, estradiol （0.0002-2.0 mg/L） and hydrocortisone （5-50 mg/L） significantly induced Carassius auratus lymphocyte proliferation while higher doses of hydrocortisone （500-5000 mg/L） appeared to be inhibitory. BPA （0.005-50 mg/L）, estradiol （0.005-800 mg/L） and hydrocortisone （0.005-500 mg/L） markedly enhanced macrophage proliferation, whereas higher doses of BPA （500-1000 mg/L） appeared to inhibit cell proliferation. Furthermore, higher dosage of BPA （50 mg/L） and hydrocortisone （50 and 500 mg/L） suppressed the macrophages respiratory burst while estradiol is stimulative all the doses tested （0.05-500 mg/L）. In conclusion, BPA could have immunotoxicity to Carassius auratus and functional changes of lymphocyte and macrophage in Carassius auratus may be different between low and high dosages.
基金supported by the National GMO Cultivation Major Project of New Varieties (2008ZX08011-005,2011ZX08011-005)
文摘Objective To evaluate the immunotoxicological effects of genetically modified wheat with TaDREB4 gene in female BALB/c mice. Methods Female mice weighing 18-22 g were divided into five groups （10 mice/group）, which were set as negative control group, common wheat group, parental wheat group, genetically modified wheat group and cyclophosphamide positive control group, respectively. Mice in negative control group and positive control group were fed with AIN93G diet, mice in common wheat group, non-genetically modified parental wheat group and genetically modified wheat group were fed with feedstuffs added corresponding wheat （the proportion is 76%} for 30 days, then body weight, absolute and relative weight of spleen and thymus, white blood cell count, histological examination of immune organ, peripheral blood lymphocytes phenotyping, serum cytokine, serum immunoglobulin, antibody plaque-forming cell, serum half hemolysis value, mitogen-induced splenocyte proliferation, delayed-type hypersensitivity reaction and phagocytic activities of phagocytes were detected. Results No immunotoxicological effects related to the consumption of the genetically modified wheat were observed in BALB/c mice when compared with parental wheat group, common wheat group and negative control group. Conclusion From the immunotoxicological point of view, results from this study demonstrate that genetically modified wheat with TaDREB4 gene is as safe as the parental wheat.
文摘Toxicological pathology plays a key role in drug safety assessment. To enhance the research level of toxicological pathology, the following stud-ies should be carried out urgently: setting up a standard operation procedure (SOP) for toxico-logical pathology assessment; emphasizing on immunotoxicology evaluation; adopting a new ex-periment model of replacement, featuring high speed and reliability; introducing new techniques and new models in toxicological mechanism re-search; and establishing a new appraisal system to screen innovative drug and rapid and high pre-cision methods for early security assessment, de-tection and measurement.
