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@#Arsenic is a toxic metalloid, which may enter the human body through a variety of routes, including drinking water, food, and air. Previous studies have shown that arsenic exposure during pregnancy may cause pregnancy complications and adverse pregnancy outcomes, and maternal arsenic levels correlate with neonatal neurodevelopment and adult health. However, the negative impact of arsenic exposure during pregnancy on maternal and child health has not been widely accepted because of inconsistent study conclusions and unclear mechanisms. Based on international and national studies pertaining to the effect of arsenic exposure during pregnancy on maternal and child health during the period between 2007 and 2022, this review describes the influencing factors and biomarkers of arsenic exposure during pregnancy, associations of arsenic exposure during pregnancy with pregnancy complications and adverse pregnancy outcomes and impact of arsenic exposure during pregnancy on neonatal neurodevelopment, and discusses the mechanisms underlying negative health effects caused by arsenic exposure during pregnancy, so as to provide the evidence for assessing the hazards of arsenic exposure during pregnancy and formulating the control strategy.
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ObjectiveTo explore the effect of Xiao Xianxiongtang （XXXT） on the transforming growth factor （TGF）-β1-induced invasion， metastasis， and epithelial-mesenchymal transition （EMT） of gastric cancer MGC-803 cells and the underlying mechanism. MethodThe molecular docking between XXXT and nuclear factor of activated T cells （NFAT） was performed by CB-DOCK （http：//clab.labshare.cn/cb-dock/）. The invasion and metastasis model of MGC-803 cells was established with 10 μg·L-1 TGF-β1. MGC-803 cells were classified into blank group， model group， 0.1 g·L-1 XXXT group， 0.2 g·L-1 XXXT group， and 0.4 g·L-1 XXXT group. For further clarifying the key role of Wnt5a/Ca2+/NFAT signaling pathway in the inhibition of XXXT on gastric cancer， MGC-803 cells were transfected with Wnt5a overexpression plasmid， and then the cells were classified into blank plasmid group， Wnt5a-OE group， blank plasmid + XXXT （0.4 g·L-1） group， and Wnt5a-OE + XXXT （0.4 g·L-1） group. Cell viability was determined by cell counting kit-8 （CCK-8） assay， cell invasion and migration ability by Transwell invasion assay and wound healing assay， expression of EMT-related proteins （E-cadherin， N-cadherin， Vimentin， Snail） and Wnt5a/Ca2+/NFAT signaling pathway-related key proteins ［Wnt5a， calcineurin （CaN）， NFAT1， and p-NFAT1］ by Western blot， and changes in intracellular Ca2+ concentration by immunofluorescence assay. ResultMolecular docking suggested that XXXT acted on Wnt5a/Ca2+/NFAT signaling pathway. XXXT （0.1， 0.2， 0.4 g·L-1） significantly promoted the loss of MGC-803 cell viability （P<0.05，P<0.01）. It inhibited cells from invading the transwell lower chamber and slowed down the healing of cell wounds in a dose-dependent manner （P<0.05， P<0.01）. Moreover， it promoted the expression of E-cadherin while suppressed the expression of N-cadherin， Vimentin， and Snail （P<0.05， P<0.01）. Further experiments showed that XXXT could inhibit the expression of Wnt5a， CaN， NFAT1， and p-NFAT1， and reduce the nuclear expression of NFAT1 and the transcription activity mediated by NFAT1， so as to reduce the cellular Ca2+ concentration （P<0.05， P<0.01）. XXXT can reverse the effect of Wnt5a （P<0.05， P<0.01）. ConclusionXXXT can attenuate the invasion， metastasis， and EMT of MGC-803 cells via the Wnt5a/Ca2+/NFAT pathway， thereby weakening the tumor-promoting effect of TGF-β1. In summary， XXXT may exert therapeutic effect on gastric cancer by regulating the invasion， metastasis， and EMT of gastric cancer cells.
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ObjectiveTo observe the inhibitory effect of modified Xiao Xianxiongtang on epithelial-mesenchymal transition （EMT） of human gastric cancer MGC803 cells and its relationship with secretory glycoprotein Wnt/β-catenin pathway. MethodThe BALB/c nude mice were implanted with human gastric cancer MGC803 cell suspension in the heterotopic subcutaneous position for inducing tumor. After successful modeling， they were randomly divided into the model group， low-， medium-， and high-dose （16.0，32.0，and 64.0 g·kg-1） groups of modified Xiao Xianxiongtang， and capecitabine （400 mg·kg-1） group， with eight mice in each group， and gavaged with the corresponding drugs， once per day， for 28 consecutive days. Those in the capecitabine group received one-week discontinuation after every two weeks of treatment. The general state and body weight of the nude mice were observed， and the transplanted tumor volume was measured. After being killed， they were weighed and the tumor inhibition rate was calculated. Hematoxylin-eosin （HE） staining was carried out for observing the pathological changes in transplanted tumor tissues. The gene and protein expression levels of Wnt1 and β-catenin were detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot， followed by the determination of matrix metalloproteinase-9 （MMP-9）， vascular endothelial growth factor （VEGF）， N-cadherin， E-cadherin， Vimentin， and Snail protein expression by Western blot. The expression levels of cyclooxygenase 2 （COX2） and prostaglandin E2 （PGE2） were detected by enzyme-linked immunosorbent assay （ELISA）. ResultIt was found that the transplanted tumor in each group showed different growth trends with time， with the most obvious growth observed in the model group. Compared with the model group， the low-， medium-， and high-dose modified Xiao Xianxiongtang groups exhibited reduced tumor volume and slowed growth to varying degrees over time. After medication for days 7，14，21，and 28， the tumor volumes in the low- and high-dose modified Xiao Xianxiongtang groups and capecitabine group declined （P<0.05， P<0.01）， and that in the medium-dose Xiao Xianxiongtang group was also remarkably reduced after medication for days 14，21，and 28 （P<0.01）. Compared with the model group， the high-dose modified Xiao Xianxiongtang group and capecitabine group showed a significant reduction in the relative tumor volume after treatment for days 7，14，21，28 （P<0.01）， and the low- and medium-dose modified Xiao Xianxiongtang groups also presented with decreased relative tumor volume after treatment for days 14，21，28 （P<0.05， P<0.01）. Compared with the model group， the modified Xiao Xianxiongtang at low， medium， and high doses and capecitabine all increased the tumor inhibition rate to varying degrees （P<0.01）， down-regulated the mRNA and protein expression levels of Wnt1 and β-catenin in tumor tissue （P<0.05， P<0.01） and protein expression levels of MMP-9， VEGF， N-cadherin， Vimentin， and Snail （P<0.05， P<0.01）， up-regulated E-cadherin protein expression （P<0.05， P<0.01）， and reduced COX2 and PGE2 contents （P<0.05， P<0.01）. ConclusionModified Xiao Xianxiongtang inhibits the EMT of human gastric cancer MGC803 cell-transplanted tumor， which may be related to Wnt/β-catenin pathway.
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Tumor is one of the diseases that seriously endanger human health， and how to treat tumor effectively is still one of the important problems in the field of medicine. At present， most of the radiotherapies and chemical drugs for cancer have serious side effect despite of an obvious efficacy. With a unique syndrome differentiation treatment system and overall concept， traditional Chinese medicine has become the key research and development object of antitumor drugs due to many advantages， such as multiple channels， multiple levels， multiple links， multiple targets and less toxicity， and could can fully mobilize the immune and epidemic prevention mechanism of the body. A large number of studies have shown that Xiao Xianxiongtang and its effective ingredients have obvious antitumor effect. Many doctors have applied Xiao Xianxiongtang and modified formulas in clinical treatment of tumors， and relevant pharmacological studies have also confirmed the effectiveness of this formula， but with a lack of systematic summary of its effective ingredients and its mechanism of action. Now， with alkaloids， ketones， sterols and phenols in Xiao Xianxiongtang as the starting point， this study mainly focuses on inhibition of tumor cell proliferation， invasion and migration， induction of tumor cell apoptosis and autophagy， inhibition of tumor cell cycle， enhancement of tumor cell sensitivity， inhibition of tumor angiogenesis and regulation of immunosuppressive tumor microenvironment from two ways to sort out composition， function and mechanism of drugs. In this paper， effective components， main targets and mechanism of intervention in the tumor development of Xiao Xianxiongtang were reviewed， in order to provide a new idea for subsequent antitumor research and development of this prescription.
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This study was purpose to analyze the frequency and of isocitrate dehydrogenase 2 (IDH2) gene mutation in acute myeloid leukemia (AML) and its clinic significance. The multiplex polymerase chain reaction (PCR) and sequencing were performed to screen 192 AML patients for exon 4 of the IDH2 gene. FLT3, NPM1, CEBPA, c-kit and WT1 mutations were also included in analysis. The results showed that IDH2 mutation was found in 14 (7.29%) of 192 patients. There were 9 AML patients with R140Q mutation, 1 patient with R140W mutation, and 1 patient with R172K mutation. IDH2 aberrations significantly more were detected in French-American-British (FAB) M5 (P < 0.005) than other types. There was no statistical difference in age, sex, WBC, platelet count, bone marrow blasts count, hemoglobin as compared with IDH2 wild-type. For immunotype analysis, IDH2 mutation patients were more likely to express CD34 and CD13, less CD36. IDH2 mutation combined with FLT3/ITD mutation was found in 7 cases, with CEBPA mutation in 4 cases, with NPM1 mutation in 4 cases, with Dnmt3a mutation in 5 cases, neither with c-kit, IDH1 or WT1 mutation for no one, which revealed a significant interaction between IDH2 mutation and the FLT3/ITD positive genotype, Dnmt3a mutated, and IDH1 wild-type. IDH2 mutation was detected in 5 (8.47%) of 59 CN-AML. There was no significant difference of IDH2 mutation incidence between the normal and abnormal karyotype. The CR rate was higher in IDH2 R140 mutated patients than wild-type ones, but there was no significant in the two group. It is concluded that the rate of IDH2 mutation is 7.29% in Chinese AML patients and 7.81% in CN-AML. IDH2 mutation is significantly associated with AML-M5, FLT3/ITD, Dnmt3a, IDH1 wild-type and fusion gene wild-type, but not with age, leucocyte and platelet counts in peripheral blood, karyotype, NPM1, CEBPA, c-kit or WT1 mutation. And IDH2 R140 mutation has no impact on CR rate.
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Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Povo Asiático , Genética , DNA (Citosina-5-)-Metiltransferases , Genética , Genótipo , Isocitrato Desidrogenase , Genética , Cariotipagem , Leucemia Mieloide Aguda , Epidemiologia , Genética , Mutação , Proteínas Nucleares , Genética , Prognóstico , Indução de Remissão , Proteínas WT1 , Genética , Tirosina Quinase 3 Semelhante a fms , GenéticaRESUMO
Patients with FLT3-ITD (mut) /NPM1 (-) cytogenetically normal acute myeloid leukemia (CN-AML), as high-risk molecular group in CN-AML, are associated with a worse prognosis than other CN-AML patients. It is beneficial to generate xenotransplantation model of FLT3-ITD (mut) /NPM1 (-) CN-AML to better understand the pathogenesis and therapeutic strategies of such AML subtype. The purpose of present study was to establish the xenotransplantation model in NOD/SCID mice with FLT3-ITD (mut) /NPM1 (-) CN-AML primary cells. The FLT3-ITD (mut) /NPM1 (-) CN-AML primary cells from 3 of 7 cases were successfully transplanted into NOD/SCID mice, and human CD45 positive cells were detected in the peripheral blood, spleen and bone marrow of mice by using flow cytometry. Infiltration of human leukemia cells in various organs of mice was observed by using immunohistochemistry. Gene analysis confirmed sustained FLT3/ITD mutation without NPM1 mutation in mice. By performing serial transplantation, it was found that characteristics of the leukemia cells in secondary and tertiary generation models remained unchanged. Moreover, in vivo cytarabine administration could extend survival of NOD/SCID mice, which was consistent with clinical observation. In conclusion, we successfully established xenotransplantation model of human FLT3-ITD (mut) /NPM1 (-) CN-AML in NOD/SCID mice. The model was able to present primary disease and suitable to evaluate the curative effects of new drugs or therapy strategies.
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Patients with FLT3-ITD (mut) /NPM1 (-) cytogenetically normal acute myeloid leukemia (CN-AML), as high-risk molecular group in CN-AML, are associated with a worse prognosis than other CN-AML patients. It is beneficial to generate xenotransplantation model of FLT3-ITD (mut) /NPM1 (-) CN-AML to better understand the pathogenesis and therapeutic strategies of such AML subtype. The purpose of present study was to establish the xenotransplantation model in NOD/SCID mice with FLT3-ITD (mut) /NPM1 (-) CN-AML primary cells. The FLT3-ITD (mut) /NPM1 (-) CN-AML primary cells from 3 of 7 cases were successfully transplanted into NOD/SCID mice, and human CD45 positive cells were detected in the peripheral blood, spleen and bone marrow of mice by using flow cytometry. Infiltration of human leukemia cells in various organs of mice was observed by using immunohistochemistry. Gene analysis confirmed sustained FLT3/ITD mutation without NPM1 mutation in mice. By performing serial transplantation, it was found that characteristics of the leukemia cells in secondary and tertiary generation models remained unchanged. Moreover, in vivo cytarabine administration could extend survival of NOD/SCID mice, which was consistent with clinical observation. In conclusion, we successfully established xenotransplantation model of human FLT3-ITD (mut) /NPM1 (-) CN-AML in NOD/SCID mice. The model was able to present primary disease and suitable to evaluate the curative effects of new drugs or therapy strategies.
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Adolescente , Adulto , Idoso , Animais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Linhagem Celular Tumoral , Modelos Animais de Doenças , Leucemia Mieloide Aguda , Patologia , Cirurgia Geral , Camundongos Endogâmicos NOD , Camundongos Knockout , Camundongos SCID , Transplante de Neoplasias , Métodos , Proteínas Nucleares , Genética , Transplante Heterólogo , Métodos , Tirosina Quinase 3 Semelhante a fms , GenéticaRESUMO
This study was purposed to detect the mutation of isocitrate dehydrogenase 1 (IDH-1) gene in patients with acute myeloid leukemia (AML) and to explore its clinical significance. The genomic DNA was extracted from mononuclear cells (MNC) of bone marrow or peripheral blood in 205 adult AML patients, the exon 4 of IDH1 gene was amplified by PCR, then the sequencing and comparison were performed. The results showed that IDH1 mutation was detected in 9 (4.39%) of 205 AML patients. There were 6 cases of R132H mutation, 1 of R132L mutation, 1 of R132G mutation and 1 of R132S mutation. Significantly more IDH1 aberrations were detected in AML-M2 (P = 0.002) than other types. And the 9 patients with IDH1 mutation were characterized by low platelet count which was lower than patients with wild type IDH1 (P = 0.003). IDH1 mutation combined with FLT3/ITD mutation was found in 5 cases, c-kit mutation in 1, NPM1 mutation in 2, and IDH1 mutation with CEBPA or WT1 mutation was not found, which revealed a significant interaction between IDH1 mutation and the FLT3/ITD positive genotype or the CEBPA wild-type. IDH1 mutation were detected in 4 of 71 (5.63%) CN-AML. There was no significant difference of IDH1 mutation incidence between the normal and abnormal karyotypes. It is concluded that the rate of IDH1 mutation was 4.39% in Chinese AML patients. IDH1 mutation is significantly associated with AML-M2, lower platelet counts in peripheral blood, FLT3/ITD mutation and CEBPA wild-type, but not with age, white blood cell count in peripheral blood, karyotype, NPM1, c-kit or WT1 mutation.
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Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Análise Mutacional de DNA , Isocitrato Desidrogenase , Genética , Cariotipagem , Leucemia Mieloide Aguda , Genética , MutaçãoRESUMO
<p><b>OBJECTIVE</b>To study the expression of nm23-H(1) gene in children with acute lymphoblastic leukemia (ALL) and the relationship between nm23-H(1) expression and immunophenotype.</p><p><b>METHODS</b>nm23-H(1) expression was measured by semiquantitative RT-PCR in children with ALL (newly diagnosed, n = 40; remission, n = 32; relapse, n = 16; refractory, n = 3). Twenty normal children served as the control group. The relationship between nm23-H(1) expression and immunophenotype was evaluated.</p><p><b>RESULTS</b>The expression of nm23-H(1) in the newly diagnosed ALL group was significantly higher than that in the control (p<0.01) and the remission groups (p<0.01). There was no difference in the nm23-H(1) expression between the remission and the control groups. The expression of nm23-H(1) in the relapse group was significantly higher than that in the control (p<0.01) and the remission groups (p<0.01), and similar to that in the newly diagnosed ALL group. The three children with refractory ALL had higher nm23-H(1) expression. Both the positive rate and expression of nm23-H(1) in children with T-lineage ALL were higher than in children with B-lineage ALL (p<0.05).</p><p><b>CONCLUSIONS</b>The expression level of nm23-H(1) varies with the stages of ALL. Newly diagnosed, relapsed and refractory ALL children have higher nm23-H(1) expression. High nm23-H(1) expression may be associated with a poor prognosis and relapse. A higher expression of nm23-H(1) in children with T-ALL may be contributed to a low remission rate and a poor prognosis.</p>
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Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Imunofenotipagem , Nucleosídeo NM23 Difosfato Quinases , Genética , Leucemia-Linfoma Linfoblástico de Células Precursoras , Genética , Alergia e Imunologia , PrognósticoRESUMO
<p><b>OBJECTIVE</b>To probe into the method for effectively increasing complete abortion rate of medicine-induced abortion and observe pathological changes.</p><p><b>METHODS</b>Two hundred cases were randomly divided into an observation group and a control group, 100 cases in each group. The observation group were treated by acupuncture at Hegu (LI 4), Sanyinjiao (SP 6), Neiguan (PC 6) and Kunlun (BL 60), and the control group were not treated by acupuncture. The abortion rate, bleeding condition, adverse reaction and pathological changes were observed in the two groups.</p><p><b>RESULTS</b>The complete abortion rate was 96.0% in the observation group, better than 88.0% in the control group (P < 0.05). There were significant differences between the two groups in bleeding time and pathological changes (P < 0.05).</p><p><b>CONCLUSION</b>Acupuncture can increase complete abortion rate of medicine-induced abortion, with shorter bleeding time and less residual villus.</p>
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Feminino , Humanos , Gravidez , Aborto Induzido , Terapia por AcupunturaRESUMO
Objective To study the incidence of vitamin K deficiency in low-birth weight premature infants and its relationship with intraventricular hemorrhage.Methods We use emzymoimmunoelectrophoresis to detect prophrombin protein precursors(PIVKA-Ⅱ) in vein blood in premature infants