Apolipoprotein E enhances migration of endometrial cancer cells byactivating the ERK/MMP9 signaling pathway / 南方医科大学学报

OBJECTIVE@#To study the role of apolipoprotein E (APOE) in regulating endometrial cancer metastasis and explore the signaling pathway in the regulatory mechanism.@*METHODS@#Human endometrial cancer cell line HEC-1B was transfected with a control siRNA (siCtrl) or a specific siRNA targeting APOE (siAPOE) or with either pEGFP-N1 plasmid or an APOEoverexpressing plasmid. The changes in migration, proliferation, apoptosis and cell cycle of the transfected cells were examined using wound healing assay, Transwell migration assay, MTT assay, flow cytometry, and Hoechst staining. The activity of the ERK/MMP9 signaling pathway in the transfected cells was assessed using RT-qPCR and Western blotting. The expression level of APOE in clinical specimens of endometrial cancer tissues were detected using immunohistochemistry and its correlation with differentiation of endometrial cancer tissues was analyzed.@*RESULTS@#Wound healing assay and Transwell migration assay showed that compared with those in siCtrl group, HEC-1B cells transfected with siAPOE showed significantly reduced migration ability (P < 0.05), whereas APOE overexpression significantly promoted the migration of the cells (P < 0.05). Neither APOE knockdown nor overexpression produced significant effects on HEC-1B cell proliferation as shown by MTT assay and flow cytometry. Hoechst staining revealed that transfection with siAPOE did not significantly affect apoptosis of HEC-1B cells. APOE knockdown obviously reduced and APOE overexpression enhanced ERK phosphorylation and MMP9 expression in HEC-1B cells (P < 0.05). Treatment with U0126 partially reversed the effects of APOE overexpression on ERK phosphorylation, migration and MMP9 expression in HEC-1B cells (P < 0.05). APOE is highly expressed in clinical samples of endometrial cancer tissues as compared with the adjacent tissues.@*CONCLUSION@#APOE is highly expressed in endometrial cancer tissues to promote cancer cell migration by enhancing ERK phosphorylation and MMP9 expression.

Effects of Sedimentary Type Limonitum on 6-keto-PGF1α，TXB2 and Other Related Indexes and Metal Ions in Blood of Warfarin Hemorrhage Model Rats / 中国实验方剂学杂志

Objective:To study the effect of sedimentary type Limonitum on hemostatic indexes in blood and metal ions in serum of rats with hemorrhage. Method:The hemorrhagic rat models were established by warfarin sodium. The experimental animals were divided into control group，model group，powder group and water decoction group. On day 15 from drug administration， the contents of 6-keto prostaglandin F₁<italic>_α</italic>（6-keto-PGF₁<italic>_α</italic>），thromboxane B₂（TXB₂），arachidonic acid（AA），endothelin 1（ET-1），platelet activating factor（PAF），P-selectin（PS），and Ca²⁺ in the whole blood of rats in each group were determined by enzyme-linked immunosorbent assay（ELISA）. The contents of Na，Mg，K，Ca，Fe，Al，Li，Be，Ti，V，Cr，Mn，Co，Ni，Cu，Zn，As，Sr，Cd，Sn，Sb，Ba，and Pb in serum samples were determined by inductively coupled plasma optical emission spectrometer（ICP-OES） and inductively coupled plasma mass spectrometry（ICP-MS）. Result:Compared with the model group，the content of 6-keto-PGF₁<italic>_α</italic> was reduced in the powder group and water decoction group （<italic>P</italic><0.05），and the contents of TXB₂，AA，ET-1，PAF，PS，Ca²⁺weresignificantly increased（<italic>P</italic><0.01），with a positive and beneficial regulatory effect. In the powder group， 10 kinds of metal elements in serum of rats were significantly and positively regulated： Na，K，Ca，Fe，Li，Ti，V，Co，Cu，and Zn（<italic>P</italic><0.05，<italic>P</italic><0.01）. In the water decoction group， 10 metal elements with significant positive regulation were as follows： Na，K，Ca，Fe，Li，V，Ni，Cu，Zn，and Sr（<italic>P</italic><0.05，<italic>P</italic><0.01）. In addition，the content of Cr（<italic>P</italic><0.01） in the powder group and Cr（<italic>P</italic><0.01），Pb（<italic>P</italic><0.05） in the water decoction group were significantly reduced. Conclusion:The powder and water decoction of sedimentary type Limonitum had definite and positive intervention effect on warfarin hemorrhage model rats，which could play a coagulation role by enhancing the vasoconstriction ability，promoting the activation of platelets，and increasing the platelet aggregation rate and blood viscosity. The metal elements such as Na，K，Ca，Fe，Li，Ti，V，Co，Cu，Zn，Ni and Sr may be the material basis for sedimentary type Limonitum to exert hemostatic effect. According to the above indicators，the intervention effect of powder group and decoction group was basically the same.

Research Progress on Hemostatic Pharmacological Effects and Clinical Application of Mineral Chinese Medicine / 中国实验方剂学杂志

Mineral Chinese medicine is an indispensable part in traditional Chinese medicine, with a history of several thousand years in research and utilization of medicinal mineral resources. It is a summary of the medical experience accumulated in numerous trials,observations and practices during the survival process of people of all nationalities, showing distinctive characteristics. At present,the scope of mineral medicine treatment involves internal medicine,surgery,gynecology,pediatrics,facial features and so on. The mineral Chinese medicine has broad clinical application in many kinds of hemorrhagic diseases,with rich experience in medication and remarkable curative effects. However, there are few papers in modern research, mainly concentrated in the 1970s-1990s. In this paper, the pharmacology and clinical application of mineral Chinese medicine with hemostatic effects in the last 40 years were reviewed, aiming to provide references for its clinical rational use in bleeding diseases,further development and utilization of mineral Chinese medicine resources of traditional Chinese medicine,in-depth study of material basis and action mechanism,and further exploration of mineral Chinese medicine resources. According to the statistics of the major Chinese medicine works,27 kinds of mineral drugs have hemostatic effects. The researches on hemostatic pharmacology of mineral Chinese medicine mainly focus on the analysis of mineral medicine elements and the effect of related elements on hemostasis,as well as the pharmacological experimental study on hemostasis, but the research is not deep-going and comprehensive. The clinical application of mineral Chinese medicine for hemostasis mainly includes digestive tract hemorrhage,hemoptysis,epistaxis,gingival hemorrhage,cerebral hemorrhage,post-abortion hemorrhage,metrorrhagia,uterine bleeding,hematochezia and external hemostasis.

Antidiarrheal Effect of Limonitum with Different Mineral Genesis / 中国实验方剂学杂志

Objective: To investigate the antidiarrheal effect and the gastrointestinal motility of two kinds of Limonitum with different mineral genesis, so as to select the optimal mineral genesis, and provide a theoretical basis for clinical use. Method: The selected research samples were leaching type and sedimentary type Limonitum with different mineral genesis, including powder, water decoction and dregs. In the experiment, castor oil (0.2 mL/10 g) was used to induce diarrhea, loperamide (4 mg·kg-1) was used for positive control, and then the antidiarrheal activity and the gastrointestinal motility were observed. Result: In the castor oil-induced diarrhea experiment, the diarrhea index of the water decoction (2.5,5,10 g·kg-1) and the dregs (2.5 g·kg-1) of leaching type Limonitum significantly reduced (P-1) of leaching type limonitum and the dregs (2.5,5,10 g·kg-1) of the leaching type Limonitum were significant different at the first defecation (P-1) and the water decoction (2.5 g·kg-1) of leaching type Limonitum, and the total feces weight of the mice were significantly decreased (P-1), the dregs (2.5,5,10 g·kg-1) of the sedimentary, the powder (2.5,5 g·kg-1), the water decoction (2.5,5,10 g·kg-1) and the dregs (10 g·kg-1) of leaching type Limonitum were significantly lower than those of the model group on the intestinal motility, with charcoal as a marker (P-1) of leaching type Limonitum was significantly higher than that of the model group on the content of small intestine contents (P-1) of sedimentary type limonitum, and the water decoction (2.5,5 g·kg-1) of leaching type Limonitum were significantly lower than those of the model group on gastric residual rate (P-1), the dregs (5 g·kg-1) of sedimentary type Limonitum were significantly reduced on the water content of large intestine compared with the model group (P-1 of Limonitum can inhibit the contraction of isolated ileum induced by acetylcholine in rabbits except 0.003 3 g·mL-1 water decoction of leaching type. Conclusion: Mineral medicine Limonitum has a certain therapeutic effect in castor oil-induced diarrhea. Leaching type limonitum has the best antidiarrheal effect.

Quality Evaluation and Selection of High Quality Mineral Resources of Limonitum from Different Mineral Genesis / 中国实验方剂学杂志

Objective: To evaluate the quality of Limonitum from different mineral genesis and select its high quality mineral resources by analyzing its mineral compositions and content. Method: The mineral compositions and content of different samples were analyzed by polarizing microscope and X-ray diffraction,and goethite content was taken as the evaluation index. SPSS 16.0 statistical software was used for hierarchical cluster analysis of the mineral compositions in different samples. Result: Limonite,quartz,illite and mica kaolinite were the main components of Limonitum from leaching disseminated type. Sedimentary type limonite was mainly composed of limonite,quartz and albite. Residual-alteration type limonite was mainly composed of limonite,quartz,diopside and carnallite. The content of goethite in limonite was highest (46.4%) in sedimentary type limonite from Jiangxi province,followed by that in leaching-disseminated type from Jiangsu province (17.9%) and leaching-disseminated type from Shandong province (0.5%). The content of sedimentary goethite was higher than 12.0%and the content of leaching-disseminated type goethite was between 0.5%and 18.0%, with significant difference; and the content of residual-alteration type was below 3.0%. Cluster analysis of mineral components in different samples showed that 6 samples of leaching-dissemination type were clustered into one group,3 samples of sedimentation type were clustered into one group,and 2 samples of residual-alteration type were clustered into one group. Conclusion: The quality of sedimentary type Limonitum in Jiangxi is the best. Generally,the quality of sedimentary type is better than that of leaching-disseminated type, and the quality of leaching disseminated type is better than that of residual-alteration type.

Clinical Effect of Jinlida and Tongxinluo on Type 2 Diabetic Kidney Disease Under Vessel Collateral Theory / 中国实验方剂学杂志

Objective: To observe the clinical efficacy of Jinlida (JLD) granules and Tongxinluo (TXL) capsules on type 2 diabetic kidney disease (DKD) under the guidance of vessel collateral theory. Method: A total of 120 patients with type 2 DKD, were randomly divided into 2 groups:the normal control group (60 cases) and the treatment group (60 cases). The patients in normal control group were treated with dietary control and hyperglycemia control. Based on treatment in control group, patients in treatment group were additionally treated with JLD granules (1 bag, tid), and TXL capsules (4 capsules, tid). The treatment was lasted for 12 weeks. The clinical efficacy, traditional Chinese medicine(TCM) syndrome scores were observed and compared before and after treatment. At the same time, the levels of glucose metabolism indexes including fasting blood glucose (FBG),postprandial 2 h plasma glucose (2 hPG), glycosylated hemoglobin (HbA1c) and the insulin resistance (IR); the levels of lipid metabolism indexes including total cholesterol(TC),triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and the high-density lipoprotein cholesterol (HDL-C); the levels of renal function indexes including urinary albumin excretion rate (UAER) and serum creatinine (SCr); as well as nailfold microcirculation were detected and compared. Result: ①The total effective rate was 80.0% in treatment group, significantly higher than 61.67% in the normal control group (PPPPPβ2-MG in treatment group was significantly obvious than that in the control group (PPConclusion: Tongxinluo combined with Jinlida can improve the clinical symptoms of patients with type 2 diabetic nephropathy and reduce urinary trace albumin, and its mechanism may be related to lowering glucose, regulating lipid metabolism and improving microcirculation.

Mineral composition analysis and hemostatic effect of limonitum with different mineral genesis / 中国中药杂志

Models were established in mice with warfarin sodium method, and their bleeding time and hemostasis time were measured by tail cutting method and slide method respectively. Rats were administered for 15 consecutive days to measure their recalcification time, plasma viscosity, platelet adhesion rate, platelet aggregation rate and other blood indexes. As compared with the blank group, the bleeding time was prolonged in model groupn(P<0.05). As compared with the model group, the results showed that the positive vitamin K, the leaching type water decoction and the sediment type decoction could significantly shorten the bleeding time (P<0.01); positive vitamin K significantly (P<0.01) shortened clotting time, and the leaching type water decoction, the sediment type water decoction and the sediment type powder could also shorten the clotting time (P<0.05). As compared with blank group, low dose, medium dose of leaching type water decoction, medium dose of powder, high dose of sediment type decoction and low dose of drug residues could reduce plasma viscosity (P<0.05), and high dose of leaching powder and low dose of water decoction could significantly reduce (P<0.01) plasma viscosity. As compared with blank group, Limonitum leaching type decoction high dose group could significantly reduce the platelet adhesion rate (P<0.05), while sediment type water decoction could significantly increase the platelet adhesion rate (P<0.05); the high dose of leaching type water decoction, high dose of drug residues, low dose of leaching type powder and low dose of drug residues could decrease the platelet aggregation rate (P<0.05), while high dose of leaching type water decoction and high dose of the powder could increase the platelet aggregation rate (P<0.05). Analysis of mineral compositions was conducted by polarized light microscopy and X-ray diffraction (XRD). The results of the both methods showed that Limonitum mineral compositions contained goethite, quartz, and kaolinite, and sedimentary type also contained illite and albite. Sediment type of Limonitum showed better hemostatic effect, which may be related to the high content of goethite and illite.

Role of progesterone in TLR4-MyD88-dependent signaling pathway in pre-eclampsia / 华中科技大学学报（医学）（英德文版）

The role of progesterone in the Toll-like receptor 4 (TLR4)-MyD88-dependent signaling pathway in pre-eclampsia was studied. Peripheral blood mononuclear cells (PBMCs) from pre-eclampsia (PE) patients were subjected to primary culture, and stimulated with different concentrations of progesterone (0, 10(-8), 10(-6), and 10(-4) mol/L). The mRNA expression of TLR4, MyD88 and nuclear factor-kappaB (NF-κB) was detected by using real-time PCR. The Ikappa-B protein expression was detected by using Western blotting. The expression of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the supernatant was determined by using ELISA. With the concentrations of progesterone increasing, the mRNA expression levels of TLR4, MyD88 and NF-κB in 2(-ΔΔCT) value were significantly decreased, and the IkappaB protein expression levels were significantly increased. The TNF-α and IL-6 expression showed a downward trend when the progesterone concentration increased, and there were significant differences among all of the groups (P<0.05). It was suggested that progesterone can inhibit the TLR4-MyD88-dependent signaling pathway in PE significantly and benefit for the pregnancy.

Role of progesterone in TLR4-MyD88-dependent signaling pathway in pre-eclampsia / 华中科技大学学报（医学）（英德文版）

The role of progesterone in the Toll-like receptor 4 (TLR4)-MyD88-dependent signaling pathway in pre-eclampsia was studied. Peripheral blood mononuclear cells (PBMCs) from pre-eclampsia (PE) patients were subjected to primary culture, and stimulated with different concentrations of progesterone (0, 10(-8), 10(-6), and 10(-4) mol/L). The mRNA expression of TLR4, MyD88 and nuclear factor-kappaB (NF-κB) was detected by using real-time PCR. The Ikappa-B protein expression was detected by using Western blotting. The expression of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the supernatant was determined by using ELISA. With the concentrations of progesterone increasing, the mRNA expression levels of TLR4, MyD88 and NF-κB in 2(-ΔΔCT) value were significantly decreased, and the IkappaB protein expression levels were significantly increased. The TNF-α and IL-6 expression showed a downward trend when the progesterone concentration increased, and there were significant differences among all of the groups (P<0.05). It was suggested that progesterone can inhibit the TLR4-MyD88-dependent signaling pathway in PE significantly and benefit for the pregnancy.