Research progress on cell signal transduction pathway mediating age-related cataract / 国际眼科杂志(Guoji Yanke Zazhi)

@#Age-related cataract is a blinding eye disease that affects vision due to opacity of intraocular lens, ranking first in the world. Under oxidative stress, the activation of apoptosis related signal transduction pathways in lens epithelial cells is the main mechanism mediating age-related cataract. There are many related signaling pathways for apoptosis, and it is a complex network system. The purpose of this literature review is to summarize different apoptotic cell signal transduction pathways that mediate age-related cataract, laying the foundation for further researching.

The action and mechanism of ethanol extract of Cichorium glandulosum on type 2 diabetes mellitus accompanied with nonalcoholic fatty liver disease based on systems pharmacology / 药学学报

italic>Cichorium glandulosum has been used to treat non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) in Uyghur folk medicine. The mechanism of Cichorium glandulosum (CG)on type 2 diabetes mellitus accompanied with non-alcoholic fatty liver disease (T2DM-NAFLD) remains unclear. The effect of CGextraction on T2DM-NAFLD was determined in animal experiments here (all the experiments here were approved by the Animal Care Committee of the First Affiliated Hospital of the Medical College, Shihezi University). The mechanism of CG for treatment of T2DM-NAFLD was predicted and verified based on systems pharmacology. Based on the active compounds of CGon T2DM-NAFLD, T2DM and NAFLD-related targets, pathways and diseases were screened and predicted. Active compounds-targets, compounds-targets-pathways and compounds-targets-diseases were constructed and analyzed. The results of animal experiments showed that CGextractioncan reduce the levels of blood glucose and blood lipid in T2DM-NAFLD rats. In addition, it can improve the glucose tolerance and relieve liver injury. Total 29 active compounds and 198 targets were screened by systems pharmacology, of which 106 targets were involved in T2DM, 88 were involved in NAFLD, and 56 targets were common between T2DM and NAFLD, mainly related to insulin resistance and inflammation. These 198 targets include those in metabolic pathways, calcium pathway, PI3K/Akt pathway, cAMP pathway, and MAPK pathway. Our study confirmed that CG can be potential phytomedicine for treatment of T2DM-NAFLD. This work provides a reference for studying the treatment of multiple diseases using multiple-targets phytomedicine in systems pharmacology.

Relationship of Serum D-dimer, Fibrinogen, C Reactive Protein and Interleukin 6 with Thrombus Dissolution Volume in Acute Iliac Femoral Vein Thrombosis Model Rats / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To explore the relationship among the serum D- two polymer, fibrinogen, C reactive protein and interleukin 6 and thrombus dissolution volume in acute iliac femoral venous thrombosis model rats.</p><p><b>METHODS</b>A total of 60 rats were randomly divided into 3 groups: deep venous thrombosis group (DVT group), sham operation group and normal control group. In DVT group the single side of the iliofemoral vein incomplete with micro vessel was cliped under chloral hydrate anesthesia; in sham operation group the single side of the iliofemoral vein should be explored without using micro vessel clip under chloral hydrate anesthesia; the and normal control group only experienced chloral hydrate anesthesia. A positive correlation was showed between the 2 time points of D-dimer and the corresponding thrombolytic volume, and the Pearson coefficient was 0.307, and Rwas 0.412 (P<0.05).</p><p><b>RESULTS</b>The D-dimer, fibrinogen, C reactive protein and interleukin-6 levels before and after treatment of 60 rats were shown to be significantly different (P<0.05) between DVT group, sham operation group and normal control group. The D-dimer and fibrinogen level was first rised and then decreased in DVT group, sham operation group. There was a positive correlation between C reactive protein/interleukin-6 and the level of D-dimer /fibrinogen from T1 to T3 time point (P<0.05). There was a negative correlation between C reactive protein/interleukin-6 and the level of D-dimer /fibrinogen from T4 to T6 time point (P<0.05).</p><p><b>CONCLUSION</b>The changes of serum D-dimer, fibrinogen, C reactive protein and interleukin 6 in the acute iliac femoral vein thrombosis model firstly increase and then decrease. These changes can reflect the process of blood coagulation and fibrin dissolution in the course of venous thrombosis of iliac vein.</p>

Invasive ductal carcinomas of breast showing partial reversed cell polarity are associated with lymphatic tumor spread / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the relationship between partial reversed cell polarity (PRCP) and lymphatic tumor spread in invasive ductal carcinoma (IDC), not othervise specified (NOS).</p><p><b>METHODS</b>Immunohistochemistry (EnVision method) was used to examine the expression of epithelial membrane antigen (EMA) and the reversed cell polarity in 199 cases of IDC.</p><p><b>RESULTS</b>Of the 199 cases, including five cases with micropapillary differentiation,30 cases with PRCP and 164 cases of IDC-NOS (without micropapillary differentiation and/or PRCP), lymphovascular invasion was seen in four (4/5), 13(43.3%) and 30 cases (18.3%) respectively; nodal metastasis was seen in four (4/5), 19 (63.3%) and 56 cases (34.1%) respectively. The rates of lymphovascular invasion and nodal metastasis were significantly higher in IDC with PRCP or IMPC than IDC-NOS (P = 0.00); there was however no significant difference between IDC with PRCP and IMPC for lymphovascular invasion and nodal metastasis (P = 0.18, P = 0.64).</p><p><b>CONCLUSIONS</b>IDC with PRCP, similar to IMPC, is more likely to show lymphovascular invasion and nodal metastasis. Complete or partial reversal of cell polarity may play a significant role in lymphatic tumor spread.</p>

The role of Src kinase inhibitor ZD6474 on multi-drug resistant K562/A02 cells / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the role of Src kinase inhibitor ZD6474 on the growth of multidrug-resistant K562/A02 cells and its regulatory mechanisms.</p><p><b>METHODS</b>The possible mechanisms of drug-resistance were tested by Western blot. Proliferation assays and cell cycle distribution were analyzed by WST metric analysis. Western blot were used to investigate the mechanisms of antiproliferative activity induced by tyrosine kinase inhibitor ZD6474. The in vivo anti-tumor activity was evaluated in K562, K562/A02 xenografted nude mice by administration of ZD6474 (25 - 100 mg×kg(-1)×d(-1), PO).</p><p><b>RESULTS</b>Compared with parental K562 cells, marked high levels of p-Src and Src expression were detected in K562/A02 cells. WST results showed that the IC(50) values of ZD6474 on K562 and K562/A02 after 48 hours incubation were (1.61 ± 0.07) µmol/L and (3.22 ± 0.21)µmol/L, respectively. ZD6474 caused an accumulation of cells in the G(0)/G(1) fraction and apoptosis by inhibiting the expressions of p-Src and Src kinase. Administration of ZD6474 produced a dose-dependent inhibition of tumor growth. 50 mg/kg ZD6474 produced the growth inhibition rates of 43.7% and 56.3%, respectively in K562 and K562/A02.</p><p><b>CONCLUSION</b>Our results indicated that inhibiting Src kinase could induce K562/A02 cells apoptosis in vitro and in vivo.</p>

Nasal airway changes after maxillary advancement following Le Fort I osteotomy / 中华整形外科杂志

<p><b>OBJECTIVE</b>To assess the nasal airway changes after maxillary advancement following Le Fort I osteotomy.</p><p><b>METHODS</b>13 cases with class III malocclusion, aged 18-35 years old, were studied prospectively. All the patients underwent Le Fort I osteotomy and maxillary advancement. Rhinological inspectrum, acoustic rhinometry (AR) were performed before operation, 3 and 6 months after operation. The Nasal Obstruction Symptom Evaluation (NOSE) scale was also completed by 13 patients before and after operation. SPSS was used for statistical assay.</p><p><b>RESULTS</b>AR assessment showed that NAR was (1.189 +/- 0.38) cm H2O/L/mi, (1.081 +/- 0.43) cm H2O/L/mi and (1.111 +/- 0.40) cm H2O/L/mi before operation, 3 and 6 months after operation; NV was (14.920 +/- 1.95) ml, (16.380 +/- 4.32) ml and (15.660 +/- 4.25) ml; and MCA was (0.500 +/- 0.09) cm2, (0.570 +/- 0.15) cm2 and (0.560 +/- 0.14) cm2, respectively. However, no significant improvement was showed. For the whole cohort, significant improvement in nasal breathing was documented (by NOSE scores) at 6 months after surgery.</p><p><b>CONCLUSIONS</b>Le Fort I osteotomy with maxillary advancement doesn't cause bad effect on nasal airways in patients with maxillary dysplasia. And the combination of objective (AR) and subjective (NOSE scale) assessment can better evaluate of the structure and function of the nose.</p>

Effect of sphingosine 1-phosphate/sphingosine 1-phosphate receptor signal pathway on function of neutrophils / 中国实验血液学杂志

The aim of this study was to examine the priming effect of sphingosine 1-phosphate (S1P) on fMLP-activated neutrophils, mainly to detect the neutrophil respiratory burst products, and to investigate the signaling pathway involved in S1P activity. Flow cytometry was used to evaluate the new isolated neutrophil; the superoxide anion output was detected indirectly by cytochrome C reduction in respiratory burst; the dihydro-rhodamine 123 was used to detect the intensity of respiratory burst; the signal transduction pathways of neutrophil respiratory burst were explored by Western blot. The results showed that after pretreated with S1P, the level of superoxide anion released by fMLP-activated neutrophils significantly increased; the Rhodamine 123 mean fluorescence intensity in S1P primed fMLP-activated neutrophils group was significantly higher than that in fMLP treatment group; PI3K and Akt proteins involved in the signal pathway of neutrophil respiratory burst. It is concluded that S1P is a new priming reagent, which primes respiratory burst of fMLP-activated neutrophils; this signal pathway may be that S1P interacts with its receptor, activates PI3K, then activates Akt-transmitting signals through NADPH oxidase, finally results in the respiratory burst.

Effect of ZD6474 on the proliferation of imatinib-resistant K562 cells / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the effect of tyrosine kinase inhibitor ZD6474 (Vandetanib) on the proliferative inhibition of K562 cells and its derived imatinib-resistant K562/G cells and its mechanism.</p><p><b>METHODS</b>Imatinib-resistant K562/G cells were obtained by culturing cells in gradually increasing concentrations of imatinib. The changed factors related to drug-resistance were tested by Western blot. ZD6474 and imatinib affected K562/G and parental K562 cells proliferation were analyzed by WST assay. Flow cytometry was used to analyze cell cycle. Direct inhibition of Src activity by ZD6474 was measured by a colorimetric ELISA assay with recombinant human Src kinase.</p><p><b>RESULTS</b>10 µmol/L imatinib failed to inhibit K562/G cells proliferation or induce cell cycle arrest. Compared with that in parental K562 cells, there were marked high levels of p-Src and Src protein in K562/G cells. The expression of Bcl-2 and p-STAT3 also increased in K562/G cells. After 48 hours incubation, the IC(50) values of ZD6474 in K562 and K562/G cells were 1.61 µmol/L and 3.18 µmol/L, respectively. ZD6474 treatment caused accumulation of cells in the G(0)/G(1) fraction and cell apoptosis in K562 and K562/G cells. ZD6474 decreased the expression of p-Src and Src at post-transcriptional level. Moreover, ZD6474 increased the ratio of Bax/Bcl-2 and decreased the expression of p-STAT3 at the same concentration for inducing apoptosis.</p><p><b>CONCLUSIONS</b>ZD6474 is effective in inhibiting the proliferation of imatinib-resistant K562/G cells and parental K562 cells, and induces their apoptasis by significant inhibition of Src kinase activity. Our study provides a reliable experimental basis for chronic myeloid leukemia treatment with ZD6474.</p>