Association between Maternal Drug Use and Cytochrome P450 Genetic Polymorphisms and the Risk of Congenital Heart Defects in Offspring / 生物医学与环境科学（英文）

OBJECTIVE@#This study aimed to assess the associations between maternal drug use, cytochrome P450 ( CYP450) genetic polymorphisms, and their interactions with the risk of congenital heart defects (CHDs) in offspring.@*METHODS@#A case-control study involving 569 mothers of CHD cases and 652 controls was conducted from November 2017 to January 2020.@*RESULTS@#After adjusting for potential confounding factors, the results show that mothers who used ovulatory drugs (adjusted odds ratio [a OR] = 2.12; 95% confidence interval [ CI]: 1.08-4.16), antidepressants (a OR = 2.56; 95% CI: 1.36-4.82), antiabortifacients (a OR = 1.55; 95% CI: 1.00-2.40), or traditional Chinese drugs (a OR = 1.97; 95% CI: 1.26-3.09) during pregnancy were at a significantly higher risk of CHDs in offspring. Maternal CYP450 genetic polymorphisms at rs1065852 (A/T vs. A/A: OR = 1.53, 95% CI: 1.10-2.14; T/T vs. A/A: OR = 1.57, 95% CI: 1.07-2.31) and rs16947 (G/G vs. C/C: OR = 3.41, 95% CI: 1.82-6.39) were also significantly associated with the risk of CHDs in offspring. Additionally, significant interactions were observed between the CYP450genetic variants and drug use on the development of CHDs.@*CONCLUSIONS@#In those of Chinese descent, ovulatory drugs, antidepressants, antiabortifacients, and traditional Chinese medicines may be associated with the risk of CHDs in offspring. Maternal CYP450 genes may regulate the effects of maternal drug exposure on fetal heart development.

[Immune Modulatory Effect of Outer Membrane Vesicles Derived from Salmonella on Mouse Bone Marrow-Derived Dendritic Cells].

OBJECTIVE: To study the effect of outer membrane vesicles (OMVs) derived from Salmonella typhimurium (ST) on the ultrastructural features and immune function of dendritic cells (DC). METHODS: Mice bone marrow cells were collected aseptically, and myeloid DC were generated by the combined induction and amplification with recombinant mouse granulocyte-macrophage colony-stimulating factor (GM-CSF) and recombinant mouse interleukin-4 (rm IL-4). Cell morphology was observed under inverted phase contrast microscope and the phenotype was identified with flow cytometry. ST-OMVs were isolated through ultracentrifugation. The survival rate of DC was assessed with CCK-8 assay, and the stimulus concentration of OMVs was henceforth determined. The ultrastructural characteristics of DC loaded with OMVs were observed with transmission electron microscopy. The cytokine secretion, surface molecule expression and phagocytic capacity of DC were examined with flow cytometry. RESULTS: The DC induced and amplified in vitro displayed typical DC phenotype in morphological analysis and the purity of DC exceeded 85%. Transmission electron microscopy showed that there were large numbers of protrusions on the cell surface. After stimulation with ST-OMVs, it was observed that the dendritic structures on the surface of DC were reduced and a large number of phagolysosomes were found in the cytoplasm. In addition, increased numbers of mitochondria, swelling and typical apoptosis were observed. After treatment with ST-OMVs at 5 µg/mL and 10 µg/mL, the secretion of tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) of DC increased significantly ( P<0.05). Furthermore, the immature DC could differentiate into mature DCs after stimulation with ST-OMVs, which were characterized by a decrease in phagocytic capacity ( P<0.05) and an upregulation of phenotypic markers ( P<0.05). CONCLUSION: ST-OMVs can stimulate DC to produce TNF-α and IL-1ß and promote DC maturation and antigen presentation.

[Research on Immunomodulatory Effects of Listeria monocytogenes L-form on Mouse Splenic Dendritic Cells].

OBJECTIVE: To study the effect of Listeria monocytogenes (LM) infection on dendritic cell (DC) immune function, and to compare the difference of immune activation ability on DC cell between bacterial form (WT) and L-form. METHODS: C57BL/6 mice were randomly divided into 3 groups and infected intravenously with LM WT, LM L-form or PBS respectively. The ultrastructural characteristics of splenic DC were observed by transmission electron microscopy (TEM). The number of splenic DC, the expression of costimulatory molecules, the secretion of cytokine and the activation of splenic T lymphocyte were detected by flow cytometry. RESULTS: TEM observation found that there were a large number of filamentous pseudopodia on the surface of splenic DC cells. The cytoplasm of DC was homogeneous and its nucleus was large. After phagocytosis of bacteria, the number of pseudopodia on the surface decreased and vacuoles in the cytoplasm increased. The number of splenic DC did not show significant changes at 1 d post infection (P>0.05). However, the expression of mature phenotypic molecules were significantly up-regulated (P < 0.05), in L-form infection group, both CD80 and CD86 molecules expressed on DC surface were higher than WT group (P < 0.05). Compared with control group, the proportion of TNF-α+DC were elevated after LM infection, and the average percentage of TNF-α+DC of L-form infection group was significantly higher than that of WT group (P < 0.05). At 7 d after infection, the average percentage of CD69+ T cells of L-form group was significantly higher than that of WT group (P < 0.05). CONCLUSION: LM L-form can induce relatively high levels of TNF-α and promote DC maturation so that to enhance their antigen presenting ability.

Analysis of development trend of Chinese medicine health products based on history of western health products development / 中国药理学与毒理学杂志

Because of the rapidly rhythm of modern society, fast food and take-out become the main dining methods for most of young people,while the outside foods always have few types of foods and nutrition is not complete. Nutrient imbalances may cause many diseases such as gastrointestinal diseases,cardiovascular diseases,diabetes,obesity,and cancer.In this environment,health products have emerged.At present,there are a wide variety of health care products at home and abroad,which are broadly divided into three categories:traditional vitamins,emerging nutrient products,and extracts of natural plant active ingredients.In the early 1970s,the sales of health products in the United States had reached 170 million dollars.At present,it has nearly 100 billion dollars,which is almost 1/3 of the total food sales, people's demand for health products is increasing rapidly. In recent years, Chinese medicine health products become more popular in western,in fact, Chinese medicine health products have a long history of application in China and have a good reputation in the folk. Obviously, Chinese medicine health products have great potential for development.So this article mainly compared the de-velopment and state of health products between China and west countries.Based on the development of health products in western countries, this article analyzes the development trend and prospects for the development of Chinese medicine health products. It is roughly divided into three parts. The first part introduces the development reasons and history of western health products development.The sec-ond part introduces the history of Chinese health products and the current situation of Chinese medi-cine health products. The third part guesses the development trend of Chinese medicine health prod-ucts and provides some development ideas. The purpose of this airticle is to provide reference and ideas for the future research and development of traditional Chinese medicine health products.

Research method of psoriasis based on HaCaT cells / 中国药理学与毒理学杂志

Psoriasis is a chronic,refractory,inflammatory skin disease that occurs in young adults.The traditional animal model cannot simulate the skin characteristics of patients with psoriasis effectively, so it is difficult to be used for in-depth study of psoriasis mechanism. Immortalized human epidermal cells (HaCaT)is a non-tumor,immortalized human epidermal cell which is widely used in the study of dermatosis.HaCaT cells are the best choice for the study of psoriasis mechanism because their immu-nological characteristics and reproductive ability are coincide with the pathological features of psoriasis. This article reviews the specific methods such as establishment of cell method, cytokine and chemo-kine analysisin the pathogenesis study of psoriasis based on HaCaT cells, hoping to provide some thoughts for drug′s pharmacological activity research.

[The Enhanceing effect of IL-12 on phagocytosis and killing of Mycobacterium tuberculosis by neutrophils in tuberculosis patients].

AIM: To explore the effects of IL-12 on phagocytosis and killing of Mycobacterium tuberculosis by neutrophils or polymorphonuclear cells (PMNs) in tuberculosis patients. METHODS: The fresh peripheral blood samples from TB patients and healthy adults were incubated with M.tb labeled with FITC, and the percentages of phagocytosis of M.tb by PMNs was measured by flow cytometry (FCM). The fresh peripheral blood samples were incubated with DCFH-DA, and with or without M.tb for different times, the percentage of activation and the ROS production of PMNs were measured by FCM. Whole blood samples were pretreated with IL-12, the changes of phagocytosis, activation and ROS production of PMNs were measured by FCM. RESULTS: The percentages of phagocytosis by PMNs, activation and ROS production of PMNs in both TB patients and healthy adults increased dependent on the time of incubation with M.tb. Only the phagocytosis of M.tb by PMNs at 5 min in TB patients of tuberculosis patients (51.82±6.93)% was obviously higher than that in healthy adults (47.20±4.26)%, (P<0.05). Pretreatment of whole blood with IL-12 before incubation with M.tb, the percentages of phagocytosis, activation and ROS production of PMNs in both TB patients and healthy adults increased in dose dependent manner, but no significant difference was found between both groups. CONCLUSION: The results indicated that the phagocytosis of M.tb and ROS production by PMNs in TB patients were almost the same as that in healthy controls, except for phagocytosis is higher at early stage. Furthermore, IL-12 can enhance the responsiveness to the phagocytosis and ROS production of PMNs.

Interleukin 17-producing gamma delta T cells increased in patients with active pulmonary tuberculosis.

Although it has been known that gammadelta T cells may play an important role in the immune response to infection of Mycobacterium tuberculosis (M. tb), the mechanisms by which the gammadelta T cells participate in the innate and/or acquired immunity to tuberculosis (TB) have not been full elucidated. In the present study, 27 patients with active pulmonary TB and 16 healthy donors (HD) were performed. We found that proportion of IL-17-producing cells among lymphocyte was similar between TB patients and HD, whereas the proportions of gammadelta T cells in IL-17-producing cells (59.2%) and IL-17-producing cells in gammadelta T cells (19.4%) in peripheral blood were markedly increased in TB patients when compared to those in HD (43.9% and 7.7%, respectively). In addition, the proportions of IFN-gamma-producing gammadelta T cells in TB patients were obviously lower than that in HD. Upon re-stimulated with M. tb heat-treated antigen (M. tb-HAg) in vitro, fewer IL-17-producing gammadelta T cells were generated from HD and TB patients, whereas IFN-gamma-producing gammadelta T cells were increased in TB patients compared to that in HD. Our findings in TB patients and healthy human were consistent with other murine investigation that the IL-17-producing gammadelta T cells were main source of IL-17 in mouse model of BCG infection, suggesting that gammadelta T cells might be involved in the formation of tubercular granuloma in pulmonary TB patients, but need further identification.