Investigation of Mechanism of Premature Ovarian Failure Regulation by Kidney-tonifying Herbs and Liver-clearing Herbs in Dingjing Decoction / 中草药·英文版

Objective: To investigate the mechanisms through which kidney-tonifying herbs (KTHs) and liver-clearing herbs (LCHs) in Dingjing Decoction (DJD) regulate premature ovarian failure (POF). Methods: One hundred and fifty Sprague-Dawley rats were randomly divided into five groups such as control, model, KTHs, LCHs, and DJD groups. POF-related biological molecules were examined. Factor analysis was performed to investigate the regulatory networks and key biomolecules involved in mediating POF after treatment with KTHs and LCHs. Results: The master regulatory factors in the reproductive endocrine network associated with KTHs intervention included four molecules in the pituitary-ovarian axis, cortisol (CORT) in the target gland of pituitary-adrenal axis, and some molecules in the hypothalamus. In contrast, the master regulatory factors associated with LCHs intervention included four molecules in the pituitary-ovarian axis and some molecules in the hypothalamus; No biomolecules in the pituitary-adrenal axis were involved in the LCH-mediated mechanisms. Gonadotropin-releasing hormone (GnRH), which was identified as a common biological molecule in the hypothalamus, was involved in regulating the reproductive endocrine network in association with KTHs intervention. Conclusion: KTHs directly regulates biological molecules in the pituitary-adrenal axis and indirectly regulates those in the pituitary-adrenal axis through the hypothalamus, while the LCHs only exert its effects indirectly. GnRH is the key biological molecule associated with KTHs intervention.

Challenges of Ionizing Radiation in Tumor Treatment and Role of Angiogenesis.

Ionizing radiation is a non-specific, but most widely used therapeutic method for cancer treatment. However, a minor fraction of tumor cell population manages to survive after radiation. Radiation efficacy depends on adequate oxygen supply. Rapid growing tumors cause hypoxia that upregulates many pro-survival pathways. At clinical doses, radiation activates inflammatory pathways and causes oxidative stress that plays a positive role during angiogenesis. Selective targeting of signaling mechanisms may radiosensitize tumors.

Signaling mechanisms in endothelial monocyte-activating polypeptide-Ⅱ-enhanced permeability of the blood-tumor barrier / 中国药理学通报

Aim To investigate the signaling mecha-nisms in endothelial monocyte-activating polypeptide-Ⅱ( EMAP-Ⅱ)-induced increase in blood-tumor barri-er ( BTB ) permeability. Methods Relatively pure cerebral microvessel fragments were obtained from the cortex of 3-5 days old Wistar rats by using careful dis-section, enzyme digestion, and dextran centrifugation. Then, these fragments were seeded on dishes and cul-tured primarily. In vitro BTB models were constructed by co-cultivation of rat brain microvascular endothelial cells ( BMECs) with C6 glioma cells. Confluent mono-layers of co-cultured BMECs were divided randomly in-to 5 groups ( each n=6 ): control, EMAP-Ⅱ, H7 +EMAP-Ⅱ, C3 exoenzyme + EMAP-Ⅱ, and C3 ex-oenzyme + H7 + EMAP-Ⅱ groups. Transendothelial electric resistance values and horseradish peroxidase flux were measured to evaluate changes in the BTB permeability . The expression levels of tight junction-re-lated protein occludin and ZO-1 in BMECs were meas-ured by Western blot. Immunofluorescence was used to identify the expression and distribution of occludin and ZO-1 in BMECs. Also, Western blot were used to de-tect the expression levels of myosin light chain ( MLC) and phosphomyosin light chain ( pMLC ) in BMECs. Results Compared with control group, the BTB per-meability of EMAP-Ⅱ group was increased significant-ly. The expression levels of occludin and ZO-1 in BMECs were significantly decreased, accompanied with marked increase in the expression level of pMLC. These above-mentioned effects of EMAP-Ⅱ were sig-nificantly inhibited by pretreatment with H7 ( an inhib-itor of PKC ) or/and C3 exoenzyme ( an inhibitor of RhoA ) . Conclusion Signaling molecules PKC and RhoA play important roles in EMAP-Ⅱ-induced in-crease in BTB permeability; signaling pathways PKC-pMLC and RhoA-pMLC are involved in this process.

VSMCs Proliferation and Mechanism of Signal Transduction by Angiotensin Ⅱ Type 1 Receptor Autoantibodies Mediated from Hypertensive Patients / 中华高血压杂志

Objective The autoantibodies against angiotensin Ⅱ type 1 receptor(AT_1 RAb)have been dis- covered in the patients with malignant hypertensive and preeclampsia,this autoantiboies(AT_1-AA)have an ago- nist-like activity effect similar to angiotensin Ⅱ(Ang Ⅱ).This study aimed at investigation the effect of Ang Ⅱ agonist-like activity by AT_1-AA on VSMCs proliferation was obtained from essential hypertensive patients. Methods VSMCs were cultured from aorta of WKY rats.The hypertensive patients" serum was purified by am- monium sulfate precipitation and affinity chromatography.The effect on VSMC proliferation this autoantilody was determined by BrdU incorporation.Total protein and the expression of phosphorylation JAK-STAT were assessed by Western blotting.Results AT_1RAb caused a significant increase in BrdU incorporation similar to Ang Ⅱ during 0-24 h reaching peak value at 12 h.The A value of in 450 nm was higher in AT_1RAb group (0.236?0.012)than AG490+AT_1RAb group(0.176?0.009),Losartan+AT_1RAb groups(0.119?0.006) and Serum Free group(0.127?0.006)(P