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Aim To investigate the effects of daidzeinDD on the proliferation and apoptosis of non-small cell lung cancer cells,with a focus on the possible role of the p53 signaling pathway in this regard. Methods CCK-8 method and flow cytometry were used to detect the effects of soy isoflavone crude extract and DD on the viability and apoptosis of HELF and H1299 cells. Gene microarray was used to detect the changes in gene expression after treatment of H1299 cells with DD. GSEA and differential analysis were used to screen the major pathways and key genes. RT-qPCR and Western blot were performed to verify the differences in mRNA and protein expression of key genesp53 and CASP9 in the major pathways. After p53 inhibitor Pifithrin-α inhibited the expression of p53,the effect of DD on p53 mRNA and protein expression levels was examined,and the proliferative effect on H1299 cells was observed. Results Soy isoflavone crude extract and DD promoted proliferation and inhibited apoptosis of normal lung cells and inhibited proliferation and promoted apoptosis of lung cancer cells. p53 signaling pathway was significantly enriched in the DD-treated groupNES=1.78,P=0.000,and the expressions of p53 and CASP9 genes were found to be significantly up-regulated in the treated group. Compared with the control group,mRNA expression of CASP9 and p53 significantly increased in both HELF and H1299 cells treated with DDP<0.05,and p53 protein expression also increased in HELF cellsP<0.05. After inhibition of p53 expression,DD significantly increased the mRNA expression of p53 in H1299 and HELF cellsP<0.05 and also markedly increased the expression of p53 protein in H1299 cellsP<0.05,and it was observed that DD inhibited the proliferation of lung cancer cells. Conclusions DD inhibits the proliferation and promotes the apoptosis of lung cancer H1299 cells,and the mechanism mainly involves the p53 signaling pathway.
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Inflammatory cytokines are known to be involved in acute ischemic stroke (AIS), while the relationship of multiple inflammatory cytokines with mental disorders in AIS is less reported. This research intended to explore the longitudinal variation of common inflammatory cytokines and their correlation with anxiety, depression, and cognitive impairment in AIS patients. Six inflammatory cytokines were detected by enzyme-linked immunosorbent assay among 175 AIS patients at admission (baseline) and on the day (D)1, D3, and D7 after admission. Anxiety, depression, and cognition were evaluated using the Hospital Anxiety and Depression Scale and Mini-Mental State Examination at discharge, respectively. Anxiety, depression, and cognitive impairment rates were 32.6, 39.4, and 19.4%, respectively. Tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-8, and IL-17A increased from baseline to D1, then decreased from D1 to D7 (all P<0.001), while IL-10 presented an opposite trend (P<0.001). Interestingly, TNF-α on D1 and D3, IL-6 on D3, IL-8 on D3 and D7, and IL-17A on D1, D3, and D7 correlated with higher anxiety rate (all P<0.05). TNF-α on D1, D3, and D7, IL-8 at baseline, D1, D3, and D7, IL-17A on D1 and D7 correlated with increased depression rate (all P<0.05). In addition, IL-1β on D1 and IL-17 at baseline, D1, D3, and D7 correlated with elevated cognitive-impairment rate (all P<0.05). Inflammatory cytokines were dysregulated after disease onset, and their longitudinal change correlated with psychological issues in AIS patients.
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Objective To study the expression of adhesion molecules CD44 and ICAM-1 in BALB/c mice infected with Mycoplasma pneumoniae (MP) and elucidate the relationship between MP and infection.Methods BALB/c mouse MP model was established by MP nasal instillation,and the pathological changes of lung in MP mice were observed.The expression levels of adhesion molecules CD44 and ICAM-1 in serum and bronchoalveolar lavage fluid of mice infected with 5,8,15,20 and 30d MP were determined by ELISA.Results Compared with the model group,MP infected BALB/c mice after lung inflammation was significantly up-regulated MP,the expression in BALB/c mice infected with the serum and bronchoalveolar layage fluid in CD44 and adhesion molecule ICAM 1 (t5 d serum CD44 =53.64 ng/L,t5 d BALF CD44 =144.3 ng/L;t5 d serum ICAM-1 =73.72 ng/L,t5 d BALF ICAM-1 =165.06 ng/L,all P＜ 0.000;t8 d serum CD44 =40.86 ng/L,t8 d BALF CD44 =21.31 ng/L;t8 d serum ICAM-1 =30.57 ng/L,t8 d BALF ICAM-1 =19.61 ng/L,all P＜0.000).The Mycoplasma pneumoniae infection increased the expression levels of adhesion molecules CD44 and ICAM-1 in mice.Conclusion After MP mice were cured,the expression of CD44 and ICAM-1 was down regulated,and the up regulation of CD44 and ICAM-1 expression might be related to the severity of MP pneumonia.
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Objective To investigate the expression of non receptor protein tyrosine phosphatase 12 (PTPN12) in hepatocellular carcinoma (HCC) and its adjacent tissues and investigate the relationship between the expression of non receptor protein and prognosis of hepatocellular carcinoma (HCC).Methods The expresson of PTPN12 protein in HCC tissues and adjacent liver tissues was detected by immunohistochemistry.The relationship between the expression of PTPN12 protein and prognosis of primary hepatocellular carcinoma was evaluated by rank correlation and Cox proportional hazards regression model.Results Compared with the adjacent liver tissues,the expression of PTPN12 protein in HCC tissues was significantly lower (55.83％ vs 43.12％,P＜0.005).Further analysis showed that the decreased expression of PTPN12 was closely related with tumor recurrence (x2 =4.346,P=0.015).Single factor analysis showed that the decreased expression of PTPN12 in hepatocellular carcinoma and liver cancer specific survival and recurrence of hepatocellular carcinoma related (x2=5.687,P＜0.001),and multivariate Cox proportional hazards regression model analysis showed that the expression of PTPN12 in patients with liver cancer were independent prognostic factors (x2 =6.687,P＜0.05).Conclusion The expression of PTPN12 protein was down or absent in human hepatocellular carcinoma,and the expression of PTPN12 may be a biomarker for the recurrence and prognosis of HCC patients.
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The innovation of Chinese materia medica (CMM) is the central driver of CMM modernization. The application of modern theories and techniques in life sciences to innovating CMM research remains to be an urgent issue to be solved. Currently, the international R&D for drug is stepping into a new trend, in which these transformations are going through a signal target to multiple drug combination and active constituents selection by pharmacodynamics to optimize the design with pharmacokinetics. In the face of changes, the pace of CMM R&D is slow. Based on the R&D content of system biology and Huangqin Decoction extract (PHY906), the "preceded pharmacokinetics" concept is introduced. Taking pharmacokinetics as the tool to rapidly screen the potential constituents with the aims at CMM R&D. Furthermore, why the "preceded pharmacokinetics" is needed and how to start the innovation model are preliminarily discussed in this paper.
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<p><b>OBJECTIVE</b>To explore the influence of water fluoride exposure on reproductive hormones in female.</p><p><b>METHODS</b>Cross-sectional study was conducted in seven villages of a county in Henan province by using simple random sampling including high fluoride area, defluoridation project area and control area on April, 2011 based on the preliminary study results of fluoride concentration in drinking water. Women who were born and growth or lived in the village at least 5 years and aged 18-48 years old were recruited using cluster sampling. They were divided into high fluoride group (HFG, 116 subjects), defluoridation project group (DFPG, 132 subjects) and control group (CG, 227 subjects) in accordance with the above areas. All subjects accepted questionnaire and physical checkup. Fasting blood and morning urine samples were collected. The concentration of fluoride in urine was determined by fluoride ion selective electrode method. The serum level of GnRH was detected using enzyme linked immunosorbent assay (ELISA). The serum level of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T), estradiol (E2) were determined by chemiluminesence immunoassay (CLIA).</p><p><b>RESULTS</b>The average age was (39.44 ± 7.34), (38.84 ± 8.03), (37.45 ± 7.70) years old in female from DFPG, HFG and CG respectively, there were no significant differences among the three groups (F = 3.02, P = 0.05). The urine fluoride levels were (1.34 ± 1.07), (2.59 ± 1.57), (0.92 ± 0.46) mg/ml in female from DFPG, HFG and CG respectively, there was a significant difference among three groups (F = 105.38, P < 0.01). No significant differences were observed of serum GnRH, LH, T, FSH and E2 among three groups in follicular phase (P > 0.05). The serum levels of E2 in Ovulatory period were 67.73, 58.09, 84.96 pg/ml in female from DFPG, HFG and CG respectively. It was lower in HFG than that in CG (H = 4.00, P < 0.05). The serum levels of T in Ovulatory period were 0.55, 0.45, 0.55 ng/ml in female from DFPG, HFG and CG respectively. It was lower in HFG than that in DFPG (H = 6.47, P < 0.05), but no significant difference was observed between HFG and CG (H = 2.41, P > 0.05). The serum levels of GnRH in Luteal phase were 24.09, 20.16, 23.50 ng/ml in female from DFPG, HFG and CG respectively. It was lower in HFG than that in DFPG (H = 14.14, P < 0.05) and CG (H = 12.53, P < 0.05). The serum level of E2 in luteal phase were 81.47, 64.60, 74.55 pg/ml in female from DFPG, HFG and CG respectively. It was lower in HFG than that in DFPG (H = 5.69, P < 0.05). As for LH, FSH and T, no significant differences were observed among the three groups (P > 0.05 respectively). The abnormal rates of E2 level were 22.73 (30/102), 37.93 (44/72), 20.26 (46/181) in female from DFPG, HFG and CG respectively. The E2 abnormal rate in female from HFG was higher that from DFPG (χ(2) = 6.82, P < 0.05) and CG (χ(2) = 12.38, P < 0.05).</p><p><b>CONCLUSION</b>Fluoride exposure may influence reproductive hormones in female, especially in ovulatory and luteal phase of menstrual cycle.</p>
Subject(s)
Adult , Female , Humans , Middle Aged , Cross-Sectional Studies , Drinking Water , Chemistry , Environmental Exposure , Estradiol , Blood , Fluorides , Urine , Follicle Stimulating Hormone , Blood , Gonadotropin-Releasing Hormone , Blood , Luteinizing Hormone , Blood , Menstrual Cycle , Progesterone , Blood , Testosterone , BloodABSTRACT
<p><b>OBJECTIVE</b>To investigate the influence of the polluted SY River on children's growth and sex hormones, and provide scientific data for assessment of the polluted status of the SY River.</p><p><b>METHODS</b>The study areas were selected randomly from the SY River Basin. Lead (Pb), mercury (Hg), arsenic (As), phthalates (DEP, DBP, DMP, DEHP), and bisphenol A (BPA) were measured both in the river water and in the drinking water. School children were selected by cluster sampling (n=154). Physical development indexes (height, weight, bust-circumference, and skinfold thickness) and sex hormones [testosterone (T) and estradiol (E2)] were measured for all the children.</p><p><b>RESULTS</b>The contents of Pb and Hg exceeded Class V standards of surface water quality in each section of the river and other indicators exceeded Class III. Compared to the control area, the concentrations of Pb, Hg, As, BPA, DEP, and DBP in the drinking water were significantly higher than in the polluted area (P<0.05). Children from the control area had significantly lower E2 and T than children from the polluted area (P<0.05). Among anthropometric results, only skinfold thickness had statistically significant difference between the two groups (P<0.05), while the other indexes showed no significant differences between the two groups (P>0.05).</p><p><b>CONCLUSION</b>The drinking water has been polluted by the SY River and affected serum sex hormone levels of children living in the polluted area.</p>