Effect of electroacupuncture on liver Akt/FoxO1 signaling pathway in rats with diabetic fatty / 中国针灸

OBJECTIVE@#To observe the effect of electroacupuncture (EA) on liver protein kinase B (Akt)/forkhead box transcription factor 1 (FoxO1) signaling pathway in Zucker diabetic fatty (ZDF) rats, and to explore the possible mechanism of EA on improving liver insulin resistance of type 2 diabetes mellitus.@*METHODS@#Twelve male 2-month-old ZDF rats were fed with high-fat diet for 4 weeks to establish diabetes model. After modeling, the rats were randomly divided into a model group and an EA group, with 6 rats in each group. In addition, six male Zucker lean (ZL) rats were used as the blank group. The rats in the EA group were treated with EA at bilateral "Zusanli" (ST 36), "Sanyinjiao" (SP 6), "Weiwanxiashu" (EX-B 3), and "Pishu" (BL 20). The ipsilateral "Zusanli" (ST 36) and "Weiwanxiashu" (EX-B 3) were connected to EA device, continuous wave, frequency of 15 Hz, 20 min each time, once a day, six times a week, for a total of 4 weeks. The fasting blood glucose (FBG) in each group was compared before modeling, before intervention and after intervention; the serum levels of insulin (INS) and C-peptide were measured by radioimmunoassay method, and the insulin resistance index (HOMA-IR) was calculated; HE staining method was used to observe the liver tissue morphology; Western blot method was used to detect the protein expression of Akt, FoxO1 and phosphoenolpyruvate carboxykinase (PEPCK) in the liver.@*RESULTS@#Before intervention, compared with the blank group, FBG was increased in the model group and the EA group (P<0.01); after intervention, compared with the model group, FBG in the EA group was decreased (P<0.01). Compared with the blank group, the serum levels of INS and C-peptide, HOMA-IR, and the protein expression of hepatic FoxO1 and PEPCK were increased (P<0.01), while the protein expression of hepatic Akt was decreased (P<0.01) in the model group. Compared with the model group, the serum levels of INS and C-peptide, HOMA-IR, and the protein expression of hepatic FoxO1 and PEPCK were decreased (P<0.01), while the protein expression of hepatic Akt was increased (P<0.01) in the EA group. In the model group, the hepatocytes were structurally disordered and randomly arranged, with a large number of lipid vacuoles in the cytoplasm. In the EA group, the morphology of hepatocytes tended to be normal and lipid vacuoles were decreased.@*CONCLUSION@#EA could reduce FBG and HOMA-IR in ZDF rats, improve liver insulin resistance, which may be related to regulating Akt/FoxO1 signaling pathway.

Effects of electroacupuncture on the glucose-lipid metabolism and the expression of ZAG and GLUT4 in the femoral quadriceps and adipose tissue in the rats with type 2 diabetes mellitus / 中国针灸

OBJECTIVES@#To observe the effects on the glucose-lipid metabolism and the expression of zinc-α2-glycoprotein (ZAG) and glucose transporter 4 (GLUT4) in the femoral quadriceps and adipose tissue after electroacupuncture (EA) at "Pishu" (BL 20), "Weiwanxiashu" (EX-B 3), "Zusanli" (ST 36) and "Sanyinjiao" (SP 6) in the rats with diabetes mellitus type 2 (T2DM), so as to explore the effect mechanism of EA in treatment of T2DM.@*METHODS@#Twelve ZDF male rats were fed with high-sugar and high-fat fodder, Purina #5008 for 4 weeks to induce T2DM model. After successfully modeled, the rats were randomly divided into a model group and an EA group, with 6 rats in each one. Additionally, 6 ZL male rats of the same months age were collected as the blank group. The rats in the EA group were treated with EA at bilateral "Pishu" (BL 20), "Weiwanxiashu" (EX-B 3), "Zusanli" (ST 36) and "Sanyinjiao" (SP 6), with continuous wave, 15 Hz in frequency, and 2 mA in intensity. The electric stimulation lasted 20 min each time. EA was delivered once daily, 6 times a week for 4 weeks. Separately, the levels of fasting blood glucose (FBG) was measured before modeling, before and after intervention, and the body mass of each rat was weighted before and after intervention. After intervention, the levels of the total cholesterol (TC), triacylglycerol (TG) and free fatty acid (FFA) in serum were detected using enzyme colorimetric method; and the levels of the serum insulin (INS) and ZAG were detected by ELISA. Besides, the insulin sensitivity index (HOMA-ISI) was calculated. With Western blot technique adopted, the protein expressions of ZAG and GLUT4 in the femoral quadriceps and adipose tissue were determined.@*RESULTS@#After intervention, compared with the blank group, the levels of FBG and body mass, and the levels of serum TC, TG, FFA and INS increased (P<0.01), while HOMA-ISI decreased (P<0.01); the level of ZAG in the serum and the protein expressions of ZAG and GLUT4 in the femoral quadriceps and adipose tissue dropped (P<0.01) in the model group. In the EA group, compared with the model group, the levels of FBG and body mass, and the levels of serum TC, TG, FFA and INS were reduced (P<0.01), and HOMA-ISI increased (P<0.01); the level of ZAG in the serum and the protein expressions of ZAG and GLUT4 in the femoral quadriceps and adipose tissue increased (P<0.01, P<0.05).@*CONCLUSIONS@#Electroacupuncture can effectively regulate glucose-lipid metabolism, improve insulin resistance and sensitivity in the rats with T2DM, which is associated with the modulation of ZAG and GLUT4 expression in the skeletal muscle and adipose tissue.

Synthesis, evaluation and proteomic analysis of PROTAC based on parthenolide / 药学学报

As a natural product with a long history of medicinal use, parthenolide has aroused great interest of chemists and biologists. Existing studies have shown that it has anti-inflammatory, antitumor and other pharmacological activities, and also revealed its action on NF-κB signaling pathway, DNMT1 enzyme and Wnt/β-catenin signaling pathway. But its biological targets remain to be elucidated systematically. Proteolysis Targeting Chimeras (PROTAC) provides a new strategy for target discovery of natural products, which can be used to explore the panorama of protein changes in cells through proteomic investigation, so as to analyze their potential targets. Based on this idea, current study designed and synthesized 20 parthenolide-derived degraders. After measured their antitumor activity in vitro, selected compounds were carried out the proteomic experiment. Finally, 139 down-regulated differentially expressed proteins were identified and the discovery of parthenolide interacting protein was preliminarily explored.

Anti-depressant Mechanism of Qing' ewan in CUMS Rats Based on Estrogen Receptor Pathway / 中国实验方剂学杂志

Objective::To study the anti-depressive effect of Qing' ewan in treating chronic unpredictable mild stress (CUMS) in rats, and the regulatory effect on estrogen receptor and estrogen receptor-related signaling pathways, in order to explore its anti-depressive mechanism. Method::The CUMS model was established. The experiment was divided into normal control group, model group, escitalopram oxalate group (positive control) and Qing' ewan groups (1.71, 5.13, 15.39 g·kg-1). After 4 weeks of modeling, rats were treated with corresponding drugs for 2 weeks. Behavioral evaluation [sucrose preference test (SPT), forced swimming test (FST), open field test (OFT)] was conducted to assess if the CUMS model was successful. Western blot was used to analyze the protein expression levels of estrogen receptor α (ERα), estrogen receptor β (ERβ), brain-derived neurotrophic factor (BDNF) and tyrosine kinase receptor B (TrkB). Result::Compared with the normal group, the sucrose consumption rate and the score of OFT in the model group decreased(P<0.05, P<0.01), the immobility time of FST prolonged significantly(P<0.01), and the protein expression levels of ERα, ERβ, BDNF and TrkB decreased(P<0.05, P<0.01). Compared with the model group, the behavioral performance of the treated group was improved, the sucrose consumption rate and the score of OFT increased(P<0.05, P<0.01), and the immobility time decreased(P<0.05). The protein expressions of ERα, ERβ, BDNF and TrkB in the treated group were significantly up-regulated(P<0.05, P<0.01), especially the middle-dose Qing' ewan group (5.13 g·kg-1). Conclusion::Qing' ewan can improve depression-like behavior in CUMS rats. Its mechanism may be related to the neuroprotective effect by up-regulating the expressions of ERα and ERβ and activating estrogen receptor-mediated ERβ/BDNF/TrkB pathways.

The expression and clinical importance of Reg IV in different molecular subtypes of breast cancer / 医学研究生学报

Objective RegIV, which is the latest member of the regenerative gene family, has been found to be closely related to the development of various tumors, but rarely reported in invasive breast cancer. This article is intended to explore the expression levels of regenerative factor 4(regeneration islet-derived family, member 4, RegIV), and the correlation with clinicopathological features and prognosis in 4 molecular subtypes of breast cancer(LA, LB,HER-2+, TNBC). Methods Pathological data of 284 breast cancer patients from March 2011 to October 2017 in the department of pathology, Lianyungang first people’s hospital were collected. To analyze the expression of RegIV in different molecular subtypes (LA, LB, HER-2+, TNBC) and its relationship with clinicopathological features, we analyzed the expression level of RegIVmRNA in breast cancer and its prognosis of patients. Results The positive rates of Reg IV in Luminal A group, Luminal B group, HER-2 positive group and triple negative breast cancer were 52.11%（37/71）, 50.00%（42/84）, 65.22%（45/69）and 20.00%（12/60）,which was statistically significant when comparing them in pairs(P<0.01). The expression of RegIV was associated with tumor diameter, lymph node metastasis, TNM stage(P<0.01). The recurrence risk of breast cancer patients with high RegIV expression was lower than those with low RegIV expression (HR=0.59,95%CI:0.50-0.69). Further analysis found that the recurrence risk of LA breast cancer patients with high RegIV expression (HR=0.63,95%CI:0.48-0.82), and so it was with LB(HR=0.56,95%CI:0.40-0.76) and TNBC(HR=0.51,95%CI:0.36-0.71). Conclusion RegIV can provide reference for molecular subtypes diagnosis and it may be one of the indicators to evaluate the prognosis of breast cancer patients.

Studies on chemical constituents of Valeriana plants and their biological activities / 中国中药杂志

The recent progresses on chemical components and pharmacological activities of the genus Valerianawere summarized.Besides-essential oil, the chemical composition of Valerianais mainly focused on monoterpenoids,sesquiterpenoids,lignans, flavonoids, alkaloids, etc. Iridoids are the main chemical components ofmonoterpenoids. There are two types ofiridoidson the basis of the cyclopentane open or not. The Valerianahas been drawmuch attention for their significant sedation,spasmolysis,antidepression,antitumor, against adenosine A1 receptors and cytotoxicityactivity,and had certain function for cardiovascular disease treatment. Given to the fact of the lack of systematic review and summary of studies on the Valeriana, we summarized and analyze the study literatures on the pharmacological activity of Valerianain recent years, and providedsome basisfor further study.

Eye-movement study during visual search in Chinese children with developmental dyslexia / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Developmental dyslexia (DD) is a disorder in which children with normal intelligence and sensory abilities show learning deficits in reading. Abnormal eye movements have been found in DD. However, eye-movement abnormalities during visual search among Chinese children with DD remain unknown. We aimed to identify the eyemovement characteristics and search efficiency of Chinese children with DD during visual search for targets of different conceptual categories, under same-category conditions.</p><p><b>METHODS</b>We compared 32 Chinese dyslexic children and 39 non-dyslexic children in visual search tasks, which were assessed using EyeLink II High-Speed Eye Tracker (SR Research Ltd., Canada). Letters, single Chinese characters, digits, Chinese phrases, figures and facial expressions were used as stimuli. Targets were similar to distractors in meaning, phonology and/or shape.</p><p><b>RESULTS</b>A main effect of task on visual search scores and all eye-movement parameters were found. Search scores, average saccade amplitude and saccade distance were significantly smaller in the DD group than in the controls. An interaction between group and task was found for pupil diameter.</p><p><b>CONCLUSIONS</b>Unlike normal readers, children with DD had a reduction in the visual attention span and search accuracy. Besides, children with DD could not increase their mental workload with increase in task difficulty. The conceptual category of the stimulus materials significantly impacts search speed, accuracy and eye-movement parameters.</p>