SIRT1-mediated deacetylation of NF-κB inhibits the MLCK/MLC2 pathway and the expression of ET-1, thus alleviating the development of coronary artery spasm.

Coronary artery spasm (CAS) is an intense vasoconstriction of coronary arteries that causes total or subtotal vessel occlusion. The cardioprotective effect of sirtuin-1 (SIRT1) has been extensively highlighted in coronary artery diseases. The aims within this study include the investigation of the molecular mechanism by which SIRT1 alleviates CAS. SIRT1 expression was first determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis in an endothelin-1 (ET-1)-induced rat CAS model. Interaction among SIRT1, nuclear factor-kappaB (NF-κB), myosin light chain kinase/myosin light chain-2 (MLCK/MLC2), and ET-1 was analyzed using luciferase reporter assay, RT-qPCR, and Western blot analysis. After ectopic expression and depletion experiments in vascular smooth muscle cells (VSMCs), contraction and proliferation of VSMCs and expression of contraction-related proteins (α-SMA, calponin, and SM22α) were measured by collagen gel contraction, 5-ethynyl-2'-deoxyuridine (EdU) assay, RT-qPCR, and Western blot analysis. The obtained results showed that SIRT1 expression was reduced in rat CAS models. However, overexpression of SIRT1 inhibited the contraction and proliferation of VSMCs in vitro. Mechanistic investigation indicated that SIRT1 inhibited NF-κB expression through deacetylation. Moreover, NF-κB could activate the MLCK/MLC2 pathway and upregulate ET-1 expression by binding to their promoter regions, thus inducing VSMC contraction and proliferation in vitro. In vivo experimental results also revealed that SIRT1 alleviated CAS through regulation of the NF-κB/MLCK/MLC2/ET-1 signaling axis. Collectively, our data suggested that SIRT1 could mediate the deacetylation of NF-κB, disrupt the MLCK/MLC2 pathway, and inhibit the expression of ET-1 to relieve CAS, providing a theoretical basis for the prospect of CAS treatment and prevention.NEW & NOTEWORTHY Rat coronary artery spasm models exhibit reduced expression of SIRT1. Overexpression of SIRT1 inhibits contraction and proliferation of VSMCs. SIRT1 inhibits NF-κB through deacetylation to modulate VSMC contraction and proliferation. NF-κB activates the MLCK/MLC2 pathway. NF-κB upregulates ET-1 to modulate VSMC contraction and proliferation.

[Research on regularity of traditional Chinese medicine in treatment of Alzheimer's disease based on data mining].

To explore prescription medication regularity in the treatment of Alzheimer's disease with traditional Chinese medicine(TCM). With Alzheimer's disease or senile dementia as the subject, collecting and sorting out the journal papers in CNKI were collected as the data source to establish the literature research database of Alzheimer's disease prescriptions, and then the association rule analysis, factor analysis and systematic cluster analysis on the included TCM were conducted. Among the 113 prescriptions included in the standard, the single herb Acori Tatarinowii Rhizoma was the most common. The herbs were mainly warm and flat among four pro-perties, mainly sweet, bitter and spicy among five flavors. The drugs were mainly distributed in five internal organs, and the most commonly used drugs were deficiency tonifying drugs as well as blood activating and stasis removing drugs. In the association rule analysis, it was found that there were 6 drug pairs with the highest association strength. Eight common factors were extracted from the factor analysis, and they were classified into 6 categories in the systematic cluster analysis. The results have shown that the overall principles in treating Alzheimer's disease with modern Chinese medicine are tonifying deficiency, invigorating circulation, activating blood and dispelling phlegm.

Downregulation of microRNA-135b promotes atherosclerotic plaque stabilization in atherosclerotic mice by upregulating erythropoietin receptor.

Atherosclerotic plaque rupture is an important pathophysiologic mechanism of acute coronary syndrome. Emerging microRNAs (miRNAs) have been implicated in the atherosclerotic plaque formation and macrophage autophagy during the development of atherosclerosis (AS). Hence, this study was conducted to explore the role microRNA-135b (miR-135b) in macrophages and atherosclerotic plaque in mouse models of AS. The expression of miR-135b and erythropoietin receptor (EPOR) was altered in atherosclerotic mice to clarify their effect on inflammation, cell activities of aortic tissues, and macrophage autophagy. The obtained findings unraveled that miR-135b was upregulated and EPOR was downregulated in atherosclerotic mice. Upregulated miR-135b expression promoted cell apoptosis and inflammation, along with inhibited cell proliferation and decreased macrophage autophagy. Notably, miR-135 was validated to target EPOR and activate the PI3K/Akt signaling pathway. Moreover, miR-135b inhibition attenuated inflammation, atherosclerotic plaque development, and promoted macrophage autophagy. Besides, the effect of miR-135b inhibition was reversed in response to EPOR silencing. Taken conjointly, the study revealed that inhibition of miR-135b promoted macrophage autophagy and atherosclerotic plaque stabilization in atherosclerotic mice by inactivating the PI3K/Akt signaling pathway and upregulating EPOR.

Effects of microRNA-10a on synapse remodeling in hippocampal neurons and neuronal cell proliferation and apoptosis through the BDNF-TrkB signaling pathway in a rat model of Alzheimer's disease.

The aim of this study was to research the effects of microRNA-10a (miR-10a) on synapse remodeling and neuronal cells in rats with Alzheimer's disease (AD) through BDNF-TrkB signaling pathway. Rat models of AD were established. The neuronal cells were allocated into blank, negative control (NC), miR-10a mimics, miR-10a inhibitors, K252a, and miR-10a inhibitors + K252a groups. Expressions of miR-10a, p38, PSD95, BDNF, cAMP-response element-binding protein (CREB), and tropomyosin receptor kinase B (TrκB) were tested using RT-qPCR and Western blotting. Neuron cell proliferation, cycle, and apoptosis were observed using Cell counting kit-8 (CCK8) assay and flow cytometry. The ultrastructure was observed under a scanning electron microscope. The miR-10a expression of AD rats increased while p38, PSD95, BDNF, CREB, and TrκB expression decreased compared with the normal rats. Dual luciferase reporter gene assay testified miR-10a targeted BDNF. The expressions of p38, PSD95, BDNF, CREB, and TrκB decreased in the miR-10a mimics and K252a groups. Compared with the blank and NC group, the miR-10a mimics and K252a groups showed inhibited cell growth rate with cells mainly rest in the G1 satge, and increased spoptosis. The miR-10a inhibitors group presented an opposite trend to the miR-10a mimics and K252a groups. The synapse was complete and abundant in the miR-10a inhibitors group while disappeared in the miR-10a mimics and K252a groups. The results indicated that miR-10a restrains synapse remodeling and neuronal cell proliferation while promoting apoptosis in AD rats via inhibiting BDNF-TrkB signaling pathway.

[Experimental study on effect of anhydroicaritin phytosomes in preventing and treating bone loss and enhancing bone quality in ovariectomized osteoporosis rats].

OBJECTIVE: To explore the effect of anhydroicaritin phytosomes (AIP) in preventing and treating bone loss and enhancing bone quality in ovariectomized osteoporosis rats. METHOD: Seventy-two SD female rats were randomly divided into 6 groups: the sham group, the model group, the estrogen group and AIP groups (low, middle, high). The sham group was only sham operated, and the remaining five groups were ovariectomized. One week after the ovariectomy, the rats were given 17 beta-estrogen and AIP (15, 30, 60 mg x kg(-1)) for consecutively three months, during which period their serum calcium (s-Ca), serum phosphorus(s-P), alkaline phosphate (ALP), urine calcium (u-Ca), urine phosphorus(u-P), urinary deoxypyridinoline (D-Pyr) and creatinine (Cr) were detected. Subsequently, rats were sacrificed, and their thighbone, second lumbar vertebrate and forth lumbar vertebrate were collected to detect bone mineral density (BMD), bone calcium (b-Ca) and phosphorus (b-P), biomechanical properties and bone histomorphometric parameters. RESULT: Compared with the sham group, the model group showed a significant increase in serum ALP, u-Ca and D-Pyr /Cr, and reduction in BMD of femur, b-Ca and b-P, biomechanical properties (elastic load, maximum load, break load, stiffness), static parameters (total tissue area, trabecular area, trabecular perimeter) and dynamic parameters (% L Pm, BFR/BV and BFR/ TV), with metratrophia. Compared with the model group, ALP high and middle-dose groups and the estrogen group showed a decrease in serum ALP, u-Ca and D-Pyr/Cr, and growth in BMD of femur, b-Ca and b-P, biomechanical properties of the forth lumbar vertebrae (elastic load, maximum load, break load, stiffness), static parameters (total tissue area, trabecular area, trabecular perimeter) and dynamic parameters (% L Pm, BFR/BV and BFR/TV). The beta-estrogen group showed endometrial hyperplasia, whereas AIP groups showed no hyperplastic change. CONCLUSION: AIP could inhibit enhanced bone turnover induced by ovariectomy, improve BMD the biomechanical properties of vertebrae, without any stimulation on uterus.

Osteoblast-derived lipocalin-2 regulated by miRNA-96-5p/Foxo1 advances the progression of Alzheimer's disease.

Aim: Alzheimer's disease (AD) is the most frequent cause of dementia and characterized by the accumulation of ß-amyloid peptides in plaques and vessel walls. This study proposed a hypothesis of an inhibitory role of miR-96-5p in AD via regulating Foxo1. Methods & methods: AD mouse models were established by injecting with 1% pentobarbital. Results: Knockdown of miR-96-5p in the presence of naringin was shown to reduce the expression of Foxo1 and contents of superoxide dismutase, catalase and glutathione peroxidase, yet increase lipocalin-2 expression as well as hydroxyproline and malondialdehyde contents. Also, Foxo1-mediated lipocalin-2 inhibition attenuated AD. Conclusion: Our study shows downregulating miR-96-5p limited AD progression, highlighting miR-96-5p a potential therapeutic target in treating AD.

Medicine in Future and Advantages of Integrated Chinese and Western Medicine.

The history of medical development shows that oriental medicine, or traditional medicine, was born through medical practice during the times when science and technology were immature and underdeveloped, whereas with the development of science and technology, Western medicine, or modern medicine, was born through experimental analysis and research. With the development of medicine, the pros and cons of both medical systems become increasingly evident. How to integrate them and learn from each other will be the direction of future development of medicine. The formation and development of integrated medicine will, inevitably, usher in a new era for medicine.

[The influence of the different components of nourishing kidney herbs on osteoporosis rats].

OBJECTIVE: To observe the influent of the different components of nourishing kidney herbs on the main items of bone metabolism in osteoporosis rats induced with Dexamethasona(DXM). METHOD: Models of three-month old SD female rats with osteoporosis here made by being fed with low calcium diet (containing calcium 0.2%) and distilled water, and injected with DXM 0.1 mg/100 g weight intramuscularly, twice a week. Then the osteoporosis rats were treated with different components of nourishing kidney herbs, and the change of calcium, phosphate, alkaline phosphatase(ALP), calcitonin(CT), PTH, CT/PTH, estrogen(E2), testosterone(T), T/E2 and bone section and bone quantitative morphology in these osteoporosis rats were observed. RESULT: The total components of nourishing kidney herbs could improve the general condition of osteoporosis rats, decrease PTH, increase CT, estrogen, testosterone, CT/PTH and T/E2. The total components of nourishing kidney herbs could improve osteoporotic state, promote bone formation, and inhibite bone resorption. But no effect of the A, B, C, D components of nourishing kidney herbs on the main items of bone metabolism in osteoporosis rats induced with DXM was found. CONCLUSION: It is possible that the purification and separation of these herbs weaken or destroy the integrative effect of nourishing kidney herbs or destroy effective components of nourishing kidney herbs during the process of purification and separation.