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Background As emerging environmental contaminants with ecological risks, flame retardants (FRs) exhibit obvious toxicity and persistence. In recent years, as FRs have been widely detected in indoor environments and human samples, the human health risks after FRs exposure are of great concern. Objective To systematically understand the topic evolution, research status, progress, and development trends on the toxicity and health effects of FRs on humans worldwide. Methods We retrieved the literature regarding toxicity of FRs and their effects on human health through the Web of Science database from 2000 to 2020, screened and processed the literature using Endnote software, and analyzed annual publications, important citations, and authors. CiteSpace and VOSviewer were employed to draw co-citation network, keyword co-occurrence network, and keyword clustering map for bibliometric visualization analysis. Results From 2000 to 2020, 472 international papers on toxic effects and human health impacts of FRs were published. In terms of publication years, FRs-related research was mainly divided into three stages: the infancy and exploration stage (2001—2006), when the research on the toxic effects of FRs was just starting; the growth stage (2007—2015), when the risk assessments of FRs on human health were conducted; and the acceleration stage (2016—), when the studies have shifted to the mechanism of FRs damage to human health. In this field, China published the largest number of published articles in the world (177 papers), but the intermediary centrality (reflecting academic influence) was only 0.19, far lower than that of European and American countries such as the Netherlands (0.78), Britain (0.51), and Germany (0.44). Among the top 10 research institutions in terms of the number of articles published, the Chinese Academy of Sciences topped the list with 49 articles. Van der Veen and other researchers had a strong influence on the research of the toxic effects of phosphorous FRs since their papers published in 2012 were cited 1319 times and in the most prominent node in the literature co-citation network. The high-frequency keywords in the literature on the human health effects of FRs were polybrominated diphenyl ethers (217 times), brominated FRs (166 times), toxicity (147 times), FRs (102 times), exposure, polychlorinated biphenyls, in vitro experiment, plasticizer, etc. Through keyword clustering and co-occurrence analyses, it was found that current research is systematically exploring the toxic mechanism of FRs from a perspective integrating pollution source-exposure route-final receptor of pollutants, and is evaluating the environmental health risks via different exposure routes. The visualized bibliometric analysis findings suggested that future studies understand the underlying mechanisms of various cell damage caused by FRs toxicity, identify the key factors of change and their relationships, aiming to provide a scientific basis for targeted prevention of health effects of FRs. Conclusion The research hotspots on the toxic effects of FRs and their effects on human health have changed over time, and the breadth and depth have been increasing. The toxic effects of brominated/phosphorus FRs have always been the mainstream direction in this field. Further studies will focus on the molecular mechanisms of human toxicity after FRs exposure.
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Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease caused by the combined effect of genetic and environmental factors and characterized by the apoptotic necrosis of biliary epithelial cells (BEC) in the small intrahepatic bile ducts. This article describes the effect of B cells, macrophages, natural killer cells, NKT, and T cells on the immune injury of BEC during PBC, so as to provide some guidance for the targeted immune therapy for PBC.
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Primary biliary cholangitis (PBC) has the pathological feature of progressive intrahepatic cholestasis caused by immune-mediated apoptotic necrosis of small biliary epithelial cells, with a risk of progression to bile duct fibrosis, liver cirrhosis, and hepatocellular carcinoma. PBC has immunogenetic characteristics, and the abnormal genetic regulation of immune response in patients with PBC includes abnormal immune response of T and B lymphocytes involving human leukocyte antigen (HLA) and non-HLA genes and taking pyruvate dehydrogenase complex-E2 in mitochondria of intrahepatic small biliary epithelial cells as the antigen. More than 30% of PBC patients have poor response to ursodeoxycholic acid treatment, and therefore, clarifying the mechanism of abnormal immune regulation in PBC has great clinical significance in guiding the immunotherapy for PBC.
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Objective:To compare the clinical outcomes of one and two blastocysts in the freeze-thaw transplantation cycle.Methods:Totally 3 675 cycles of frozen thawed blastocyst transplantation in Reproductive Medical Center of the Second Nanning People′s Hospital from January 2012 to December 2016 were analyzed retrospectively. According to the quantity and quality of transferred blastocysts, all the patient were divided into two groups: (1) one embryo group, including the single excellent group (one high quality blastocyst) and the single non excellent group (one non high quality blastocyst); (2) two embryo groups, including the double excellent group (two high quality blastocysts), the one excellent and one non excellent group (one high quality blastocyst+one non high quality blastocyst), and the two non excellent group (two non high quality blastocysts were transplanted). Then the patients were divided into subgroups according to their ages: less than 35 years old, 35-40 years old and over 40 years old. On this basis, the implantation rate, clinical pregnancy rate, multiple birth rate and live birth rate were compared.Results:(1) The implantation rate, clinical pregnancy rate, multiple birth rate, preterm birth rate and live birth rate were all significantly increased, while the abortion rate was significantly reduced in the double blastocyst group (all P<0.05). (2) In the group of<35 years old, the rates of multiple birth and preterm birth in the double blastocyst group were significantly higher than those in the single optimal group ( P<0.01). (3) In the 35-40 years old group, the clinical pregnancy rate, multiple birth rate and live birth rate of the double excellent group were significantly higher than those of the single excellent group ( P<0.01); while the clinical pregnancy rate and live birth rate of the one excellent and one non excellent group and the double non excellent group were not significantly different from those of the single excellent group ( P>0.05), but the multiple birth rate and preterm birth rate were significantly increased ( P<0.01). The clinical pregnancy rate, live birth rate and multiple birth rate of double non optimal group were significantly higher than those of single non optimal group ( P<0.01). (4) In the group>40 years old, there were no significant differences in clinical pregnancy rate and live birth rate between the two groups ( P>0.05). There were no significant differences in implantation rate, clinical pregnancy rate and live birth rate between double non optimal group and single non optimal group ( P>0.05). Conclusion:No matter the age of the patients, if the couple have high quality blastocysts, we should give priority to single high quality blastocyst transplantation; even if they have no high quality blastocysts, we should also consider single blastocyst transplantation, in order to reduce the risk of multiple pregnancy and improve the cumulative live birth rate, so as to improve the pregnancy outcome.
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Primary biliary cholangitis (PBC) is a chronic, non-suppurative, autoimmune cholestatic group of liver disorder, which more frequently affects middle-aged women and eventually leads to liver failure. Its pathogenesis is not completely clear, yet the study has confirmed that the occurrence and development of PBC is closely associated to the individual's genetic background, with obvious genetic heterogeneity. Currently, PBC has been divided into five types based on their related genes dissimilarities, aside from PBC-1, which is an autosomal dominant inheritance, while the other four types of inheritance are unidentified. The ratio of middle-aged women to male cases with PBC goes overs 9:1, and it mostly occurs in perimenopausal period. It is speculated that the occurrence of PBC may be related to estrogen and estrogen receptors. This article reviews the advances in the study of genetic theory of PBC and the role of estrogen and its receptor in this disease.
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Objective To investigate the clinical value of serum follicle stimulating hormone(FSH) and testicular volume in the etiology diagnosis of azoospermia.Methods The clinical data of 373 patients with azoospermia were analyzed retrospectively.The patients were divided into the group A,B and C according to their FSH detected level.The FSH level was normal in the group A,slightly increase in the group B and severe increase in the group C.The testicular volume and the spern retrieval success rate of each group were analyzed statistically.Results The testicular sperm retrieval success rates in the group A,B and C were 70.81％,22.22％ and 0 respectively;the average testicular volumes in the three groups were(11.39±5.06),(8.79±4.18),(6.96±4.12)mL respectively,the differences among the three groups were statistically significant(P＜0.05).Conclusion In the patients with azoospermia,the FSH level and testicular volume help to judge the testicular spermatogenic functional status and identify the type of azoospermia.
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Autoimmune hepatitis (AIH) is liver parenchymal inflammation mediated by the autoimmune response of hepatocytes. Its clinical features include elevation of aminotransferases in serum, presence of various autoantibodies in circulation, hypergammaglobulinemia, and interface hepatitis in liver tissue. Although the etiology and pathogenesis of AIH have not been fully elucidated, a consensus has been reached on the theories of "genetic susceptibility" and "molecular simulation" , and "immunoregulatory disorder" remains a hot research topic for many scholars. This article reviews the research advances in the theories of "genetic susceptibility" , "molecular simulation" , and "immunoregulatory disorder" .
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As a T cell subsets growth factor,interleukin-2 (IL-2) can inhibit cancer cell proliferation,reduce tumorigenicity and transitivity,improve local tumor microenvironment,enhance the immunogenicity of hepatocellular carcinoma cells,reduce the load of hepatitis virus and greatly enhance the ability of anti-tumor.On the other hand,it can enhance tumor hypercoagulable state.The effect of IL-2 on primary hepatic carcinoma and its potential clinical value have a bright future.
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Objective To observe the effect of human telomerase reverse transcriptase-thymidine kinase/ganciclovir (phTERT-TK/GCV) system combined human telomerase reverse transcriptase-tumstatin (phTERT-tumstatin) system on apoptosis of human HepG2 and mRNA expression and protein content of AFP,RhoC related with cancer.Methods Fluorescence microscopy was used to observe expression of EGFP and MCHERRY in transfected HepG2 and L-02.Real-time PCR and Western blot were used to detect AFP and RhoC mRNA and protein content.Flow cytometry was used to detect the apoptosis of transfected HepG2.Results phTERT-tumstatin and phTERT-TK/GCV genes expressed in transfected HepG2.Real-time PCR showed that AFP and RhoC mRNA expression in different group were 0.76±0.09 and 0.80±0.04 (TK/GCV group),0.62±0.09 and 0.40±0.02 (TM group),0.49±0.07 and 0.54±0.03 (MK group).The differences were significant (P ＜ 0.01) except TK/GCV group compared with empty plasmid group.Western blot test results showed that protein content of AFP and RhoC were higher in TK/GCV group (0.97±0.02/1.17± 0.01),TM group (0.83±0.02/0.99±0.02),MK group (0.69±0.01/0.77±0.02) than in empty plasmid group (1.19±0.03/1.32±0.05) and non-transfected group (1.15±0.05/1.29±0.30) (P ＜ 0.01).Additionally,protein content of AFP and RhoC in MK group were significant difference with TK/GCV group and TM group (P ＜ 0.01).Flow cytometry showed that phTERT-tumstatin,phTERT-TK/GCV co-transfected HepG2 cells apoptosis rate was significantly higher than both individually transected group.Cells apoptosis rate of alone and co-transfected groups was significant difference compared with empty vector group and untransfected group.Conclusions The effect of phTERT-TK/GCV and phTERT-tumstatin on pro-apoptotic of HepG2 cells is significant.phTERT-TK/GCV combined with phTERT-tumstatin has strong therapeutic function.
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Objective To observe if IL-2 gene can express in hepatic carcinoma cells by double targeting of hepatitis B virus envelope (HBVE) and alpha fetoprotein (AFP) promoter.Methods HepG2 cells,L02 cells,and HepG2.2.15 cells were cultured in vitro.HBVE was obtained by PEG8000 concentration assay,and the acquired HBVE was used to pack recombintional gene.Human AFP promoter-IL-2 recombinational gene was obtained by PCR.Then HepG2 cells and L02 cells were transfected by transient transfection and the expression of IL-2 was detected by RT-PCR and Western blot.Results IL-2 was detected in HepG2 cells by RT-PCR and Western blot but not in L02 cells.Conclusion By using HBVE as a gene transporter,human AFP promoter-IL-2 recombinational gene can express in hepatic carcinoma cells,thereby it can increase the safety of exogenous gene transfection of hepatic carcinoma cells.
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Lentiviral vectors (LV),a special member of retroviral vectors,has become hot in gene therapy research.Studies have shown that LV can make exogenous gene expressed stably in tumor cells.As a tool for transportation,LV plays a significant role in the gene therapy of digestive system,hematologic system and gynecological tumor,which provides a promising new way for neoplasms gene therapy.
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The process of apoptosis runs through a variety of signal transduction, and is regulated by many apoptosis-related genes. Inhibitors of apoptosis protein (IAPs) are closely related to the infinite proliferation of tumor cells. IAPs including the recently discovered survivin, livin, are closely related to tumors. The anti-apoptotic mechanism is to be further studied.
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Objective To compare the transfection efficiency of galactosylated chitosan nanoparticle vehicle with chitosan nanoparticles vehicle,and observe the therapeutic effect of pGL3-hTERTp-TK on HCC cell line HepG2. Methods Preparing the chitosan and galaetosylated chitosan. Constructing the pGL3-hTERTp-TK plasmid and the Ch/DNA and GC/DNA complexes.Transfecting the HepG2 and the normal hepatic cell L-02 with chitosan/DNA and galactosylated chitosan/DNA complexs.Detecting the fluorescence and the expression of luciferase gene using the fluorescent microscope and the scintillation counter.Detecting the cell growth and apoptosis through the Caspase-3 and the flow cytometry. Results Two clear straps appeared in the agarose gel.The locations were 300 bp and 1100 bp.The relative lueiferase activity of pGL3-hTERTp-Luc+mediated by galactosylated chitosan was powerful than which of pGL3-hTERTp-Luc+mediated by chitosan in HepG2 by the scintillation counter.However,the relative luciferase activity was very weak in L-02.The same results were observed by fluorescent microscope.When the concertration of the GCV was 10 μg/ml(t=51.40,P=0.000),the HepG2 cell inhibition which was transfected by GC-pGL3-hTERTp-TK was obviously different from the L-02 cell inhibition which was transfected by GC-pGL3-hTERTp-TK in the statistics.The significant apoptotic rate was 65.28%in HepG2 which was transfected with GC/DNA,whereas it was only 10.80% in L-02. The significant apoptotic rate in HepG2 which was transfected with GC/DNA was very higher than the other groups (LSD, P ＜0.05). The significant apoptotic rate (10.80%) in L-02 which was transfected with GC/DNA was very higher than the group which was Ch-pGL3-control (LSD, P =0.000). The average fluorescence intensity of the HepG2 which is transfected by the Ch-pGL3-hTERTp-TK was 168.02± 3.68. The average fluorescence intensity of the HepG2 which is transfected by the GC-pGL3-hTERTp-TK was 204.45 ±3.45. The two groups had a significant difference in the statistics (t=-12.504, P＜0.05). Conclusion Galactosylated chitosan has higher transfection efficiency than chitosan. GC-pGL3-hTERTp-TK could specially attack HCC cell line and almost has no influence on normal hepatic cells.
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The hTERT gene promoter is a tumor-specific promoter, regulated by a number of factors.Modulation of the chromatin structure via DNA methylation or histone acetylation plays an important role in regulating the hTERT promoter. Recent study also found that glycogen synthase kinase -3 cytokines, macrophage colony-stimulating factor receptor 1, bone inducing factor -7, transcription factors c-myc inhibitor, transforming growth factor β, cyclopentenone prostaglandin regulate the activity of hTERT through various pathways. Telomelysin, the telomerase-specific replication competent oncolytic adenovirus, has been used in clinical settings.Various gene therapies based on hTERT are current under-way.
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Objective To evaluate the lethal effect of adenovirus-mediated Ad-hTERTp-HSV-TK/GCV suicide gene system in combination with oxaliplatin (L-OHP) on human hepato carcinoma cell line HepG2 in vitro.Methods It was used that the replication-defective adenovirus carring the HSV-TK gene under control of the hTERT promoter to transfer the HepG2 cells in vitro. Human hepato carcinoma cell line HepG2 was transfected with MOI=100. It was studied that the grow inhibitory effct with Ad-hTERTp-HSV-TK/GCV therapy, oxaliplatin, Ad-hTERTp-HSV-TK/GCV therapy in combination with oxaliplatin through different drug concentration on human hepato carcinoma cell line HepG2. The growth inhibition rate of HepG2 cells was determined by trypan blue exclusion assay and MTT.Results The growth of HepG2 cells Ad-hTERTp-HSV-TK/GCV, oxaliplatin, and combination of Ad-hTERTp-HSV-TK/GCV and oxaliplatin was significantly slower.The more concentration the greater inhibition of cell growth. The growth inhibition rate of combined Ad-hTERTp-HSV-TK/GCV with oxaliplatin was 86.63 %.The growth inhibition rate of Ad-hTERTp-HSV-TK/GCV was 72.12 % compared to the combined therapy (P =0.023). The growth inhibition rate of oxaliplatin was 59.41% compared to the combined therapy (P =0.019). Combination of Ad-hTERTp-HSV-TK/GCV and oxaliplatin resulted in greater inhibition of cell growth compared with TK gene and L-OHP (P ＜0.05).Conclusion HSV-TK/GCV in combination with L-OHP can enhance thelethal effect of suicide gene therapy against HepG2 cells.It is more targetable than the function of single drug therapy.Also, it could reduce drug level and plays an important role on the future's clinical medication.
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Objective To observe the effect of Ad-bTERTp-HSV-TK/GCV system on malignant ascites of mice and probe into its mechanism of action.Methods The SX1 inbred strain mice were injected with H22 cell line of liver cancer and were divided into 4 groups at random.The mice in each group were given corresponding treatment after 48 hours.The production of ascites and survival period were evaluated. The apoptosis rates of tumor cells were detected by FCM.Morphological changes of tumor cells were studied by electromicroscope.Results Compared with other groups.Ad-hTERTp-HSV-TK/GCV Can obviously inhibit the production of ascites(P<0.01),prolong the survival period (P<0.01),and apoptosis rate in this group (27.12±2.12)% was significantly higher than that in other groups.No obvious side effect Was found during the treatment.Conclusion Ad-hTERTp-HSV-TK/GCV system Can inhibit production of ascites and prolong the survical period of mice by inducing apoptosis of hepatoma cells,which is a safe and feasible treatment for hepatoma therapy.
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Objective To construct the recombinant adenovirus vector with hTERT-HSV-TK and observe the killing effect of Ad-hTERTp-HSV-TK/GCV system on hepatocellular carcinoma cells. Methods A recombinant replication defective adenoviral vector of Ad-hTERTp-HSV-TK was constructed via homologous recombination which both shuttle plasmid pSU-Tp-TK and adenovirus backbone plasmid pBHGE3 transfected into the HEK293 packaging cells. Then the Ad-hTERTp-HSV-TK was amplified and purified through PCR. The activity of the HepG2 cells and the L-02 cells were tested by methyl thiazolyl terazolium (MTT) after they were transfected by the recombinant adenovirus of different multiplicities of infection (MOI) and then were added GCV of different conc.entration. Results The recombinant replication defective adenoviral vector of Ad-hTERTp-HSV-TK were identified by PCR successfully. The viral titer was 1.5×1010 pfu/ml after amplification and purification. The HepG2 cells were targetedly suppressed by Ad-hTERTp-HSV-TK/GCV system. The survival rate of cells decreased gradually along with the increase of the MOI and the GCV' s concentration. Conclusion The recombinant replication defective adenoviral vector of Ad-hTERTp-HSV-TK can inhibit the HepG2 cells significantly, but has not influence on the L-02 cells.
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Telomerase, as a factor of tumour's happening and development, is a kind of cell element not existing or with low activity in normal cells. Moreover, the activity of telomerase is a common channel for cell's immortalization and deterioration, and is also the main factor in cloning tumour and developing malignant turnour. Therefore, the tumour gene therapy focusing on telomerase has become the new target of present study of tumor.This therapy has greater prospects on clinical application than the past tumour gene therapy simply directing at one cancer gene.
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Objective: To observe the effect of telomerase-antisense DNA on apoptosis of hepatoma cells induced by arsenic trioxide, in an effort to look for a new anti-hepatic cancer agent with high efficiency, low cytotoxicity. Methods: We designed and synthesized a 20nt telomerase-antisense DNA targeting telomerase template and observed its influence on the telomerase activity of hepatoma cells. H-E staining, flow cytometry, and DNA agarose electrophoresis were used to study the preventive effect of telomerase-antisense DNA on hepatoma cells apoptosis induced by arsenic trioxide. Flow cytometry was used to detect the expression of Fas, Fas-L, and bcl-2. Results: Telomerase-antisense DNA (5 ?mol/L) effectively inhibited the telomerase activity of hepatoma cells after 24 hours (P
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<p><b>BACKGROUND</b>The interaction between tumor cells and stroma cells plays an important role in the invasion and metastasis of tumor. The purpose of this study is to evaluate the proliferative activity of fibroblasts in lung cancer, and to explore its correlation with tumor biologic behavior.</p><p><b>METHODS</b>Ninety-four cases of surgically resected specimens of lung cancer were collected. The proliferative activity of fibroblasts was immunohistochemically evaluated with the mouse monoclonal antibody against proliferating cell nuclear antigen (PCNA).</p><p><b>RESULTS</b>The tumor cells in the outer area had significantly higher PCNA label index (LI) than those in the inner area, however, the PCNA LI of fibroblasts in the inner area was significantly higher than those in the outer area regardless of tumor size. The PCNA LI of fibroblasts in the paracancerous tissues was significantly lower than that of fibroblasts in the inner or outer area of tumor. There was a significant correlation between the PCNA LI of fibroblasts and that of tumor cells in the inner or outer area of tumor. The PCNA LI of fibroblasts in either inner or outer area showed a significant correlation with lymph node metastasis of lung cancer.</p><p><b>CONCLUSIONS</b>The results demonstrate that there is a discrepancy in the distribution of highly proliferative tumor cells and highly proliferative fibroblasts in lung cancer. The proliferative activity of tumor cells should be assessed in tumor cells in the outer area, and proliferative activity of fibroblasts should be assessed in fibroblasts in the inner area.</p>