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In order to explore the improvement of radar radial velocity data assimilation on the initial and forecast fields of typhoons, this study assimilates the quality-controlled radial velocity data in the case of Typhoon Linfa (2015) using the three-dimensional variational data assimilation system of the weather research and forecasting model (WRF-3DVAR), and then conducts several sensitivity experiments with different horizontal length scale factors. The results show that reducing the horizontal length scale factor of the background error covariance can effectively assimilate the micro- and meso-scale information from radar data and improve the forecasting effect of Linfa. Following the optimization of the horizontal length scale factor, the radial velocity data assimilation can improve the typhoon wind field structure, produce reasonable cyclonic wind field increments, and further improve the dynamic and thermal structure of the inner core area of the typhoon. Then, we can obtain a better initial field of model forecasting, and thus typhoon track and intensity forecasting are improved. [ABSTRACT FROM AUTHOR]

Berberine exerts neuroprotective and modulates hypoxia inducible factor-1-alpha (HIF-1. Based on the role of HIF-1 in hypoxia preconditioning and association between HIF-1 and sphingosine-1-phosphate (S1P), we hypothesized that berberine preconditioning (BP) would ameliorate the cerebral injury induced by ischemia through activating the system of HIF-1 and S1P. Adult male rats with middle cerebral artery occlusion (MCAO) and rat primary cortical neurons treated with oxygen and glucose deprivation (OGD) with BP at 24h (40mg/kg) and 2h (10mol/L), respectively, were used to determine the neuroprotective effects. The HIF-1 accumulation, and S1P metabolism were assayed in the berberine-preconditioned neurons, and the HIF-1-mediated transcriptional modulation of sphingosine kinases (Sphk) 1 and 2 was analyzed using chromatin immunoprecipitation and real-time polymerase chain reaction. BP significantly prevented cerebral ischemic injury in the MCAO rats at 24h and 72h following ischemia/reperfusion. In OGD-treated neurons, BP enhanced HIF-1 accumulation with activation of PI3K/Akt, and induced S1P production by activating Sphk2 via the promotion of HIF-1-mediated Sphk2 transcription. In conclusion, BP activated endogenous neuroprotective mechanisms associated with the S1P/HIF-1 pathway and helped protect neuronal cells against hypoxia/ischemia. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Huang-Lian-Jie-Du-Tang (HLJDT) is a classical heat-clearing and detoxicating formula of traditional Chinese medicine that is widely used to treat stroke. The present study was designed to investigate the effects of HLJDT preconditioning on neurons under oxygen and glucose deprivation (OGD) and rats subjected to middle cerebral artery occlusion (MCAO). Materials and methods: A stroke model of rats was obtained through MCAO. Following HLJDT preconditioning, the cerebral infarction volume, cerebral water content, and neurological deficient score were determined. Cerebral cortical neurons cultured in vitro were preconditioned with HLJDT and then subjected to OGD treatment. The release of lactate dehydrogenase (LDH) from neurons was detected. The levels of hypoxia-inducible factor-1α (HIF-1α) and PI3K/Akt signaling were analyzed by western blotting, and the levels of erythropoietin (EPO) and vascular endothelial growth factor (VEGF) in the supernatant of the neurons and the plasma of MCAO rats were measured through a radioimmunological assay. The apoptosis and proliferation of neurons were analyzed by immunohistochemistry. Results: HLJDT preconditioning significantly reduced the cerebral infarction volume and cerebral water content and ameliorated the neurological deficient score of MCAO rats. In addition, HLJDT preconditioning protected neurons against OGD. Increased HIF-1α, EPO, and VEGF levels and the activation of PI3K/Akt signaling were observed as a result of HLJDT preconditioning. Furthermore, HLJDT preconditioning was found to inhibit ischemia-induced neuron apoptosis and to promote neuron proliferation under conditions of ischemia/reperfusion. Conclusion: Both rats and neurons subjected to HLJDT preconditioning were able to resist ischemia/reperfusion or hypoxia injury through the inhibition of apoptosis and the enhancement of proliferation, and these effects were primarily dependent on the activation of the PI3K/Akt signaling pathway and HIF-1α. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Huang-Lian-Jie-Du-Tang (HLJDT) is a classical heat-clearing and detoxicating formula of traditional Chinese medicine that is widely used to treat stroke. The present study was designed to investigate the effects of HLJDT preconditioning on neurons under oxygen and glucose deprivation (OGD) and rats subjected to middle cerebral artery occlusion (MCAO). Materials and methods: A stroke model of rats was obtained through MCAO. Following HLJDT preconditioning, the cerebral infarction volume, cerebral water content, and neurological deficient score were determined. Cerebral cortical neurons cultured in vitro were preconditioned with HLJDT and then subjected to OGD treatment. The release of lactate dehydrogenase (LDH) from neurons was detected. The levels of hypoxia-inducible factor-1α (HIF-1α) and PI3K/Akt signaling were analyzed by western blotting, and the levels of erythropoietin (EPO) and vascular endothelial growth factor (VEGF) in the supernatant of the neurons and the plasma of MCAO rats were measured through a radioimmunological assay. The apoptosis and proliferation of neurons were analyzed by immunohistochemistry. Results: HLJDT preconditioning significantly reduced the cerebral infarction volume and cerebral water content and ameliorated the neurological deficient score of MCAO rats. In addition, HLJDT preconditioning protected neurons against OGD. Increased HIF-1α, EPO, and VEGF levels and the activation of PI3K/Akt signaling were observed as a result of HLJDT preconditioning. Furthermore, HLJDT preconditioning was found to inhibit ischemia-induced neuron apoptosis and to promote neuron proliferation under conditions of ischemia/reperfusion. Conclusion: Both rats and neurons subjected to HLJDT preconditioning were able to resist ischemia/reperfusion or hypoxia injury through the inhibition of apoptosis and the enhancement of proliferation, and these effects were primarily dependent on the activation of the PI3K/Akt signaling pathway and HIF-1α. [Copyright &y& Elsevier]

Objective: Mobilization of hematopoietic stem and progenitor cells (HSPC) by stromal cell-derived factor-1 (SDF-1) has been described; however, sustained adenoviral delivery or N-terminal modification was required for effect and could not be demonstrated with native protein. The aim of this study was to further investigate the SDF-1α/CXCR4 axis in HSPC mobilization using CTCE-0021, a cyclized CXCR4 agonist peptide, with comparable bioactivity and improved stability relative to SDF-1α. Methods: Peripheral blood cells and hematopoietic progenitor cells (HPC) were quantitated in mice administered single or multiple doses of CTCE-0021 or SDF-1α, or mobilized by granulocyte colony-stimulating factor (G-CSF) in combination with CTCE-0021. Proteases, cytokines, and receptors implicated in HSPC mobilization were evaluated to determine mechanism of action. Results: CTCE-0021 dose-dependently elevated blood neutrophils polymorphonuclear neutrophil [PMN] within 5 minutes that peaked after 1 hour and persisted for 24 hours. PMN mobilization could be maintained by daily dosing. CTCE-0021 mobilized colony-forming unit granulocyte macrophage (CFU-GM), burst-forming unit erythroid (BFU-E), and CFU-granulocyte-erythrocyte-monocyte-megakaryocyte (CFU-GEMM) that peaked within 1 hour after administration, and synergistically enhanced both PMN and HSPC mobilization when combined with G-CSF. Mobilization induced by CTCE-0021 was associated with rapid downregulation of CXCR4 expression on HPC. No appreciable changes in proteases implicated in HPC mobilization were observed. Significantly elevated plasma SDF-1 was detected in mobilized mice, which likely represents CTCE-0021. Conclusion: These studies indicate that CTCE-0021 is an efficient and rapid mobilizer of PMN and HPC when used alone and shows synergistic activity when used in combination with G-CSF. The mobilizing effect of this peptide appears to be mediated by downregulation of the CXCR4 receptor on HPC and altered chemokine gradient. [Copyright &y& Elsevier]

Many antimicrobial peptides (AMPs) have been identified from the skin secretion of the frog Hylarana guentheri (H.guentheri), including Temporin, Brevinin-1, and Brevinin-2. In this study, an antimicrobial peptide named Brevinin-1GHa was identified for the first time by using 'shotgun' cloning. The primary structure was also confirmed through mass spectral analysis of the skin secretion purified by reversed-phase high-performance liquid chromatography (RP-HPLC). There was a Rana-box (CKISKKC) in the C-terminal of Brevinin-1GHa, which formed an intra-disulfide bridge. To detect the significance of Rana-box and reduce the hemolytic activity, we chemically synthesized Brevinin-1GHb (without Rana-box) and Brevinin-1GHc (Rana-box in central position). Brevinin-1GHa exhibited a strong and broad-spectrum antimicrobial activity against seven microorganisms, while Brevinin-1GHb only inhibited the growth of Staphylococcus aureus (S. aureus), which indicates Rana-box was necessary for the antimicrobial activity of Brevinin-1GHa. The results of Brevinin-1GHc suggested transferring Rana-box to the central position could reduce the hemolytic activity, but the antimicrobial activity also declined. Additionally, Brevinin-1GHa demonstrated the capability of permeating cell membrane and eliminating biofilm of S. aureus, Escherichia coli (E. coli), and Candida albicans (C. albicans). The discovery of this research may provide some novel insights into natural antimicrobial drug design. [ABSTRACT FROM AUTHOR]

Background: Myocardial ischemia (MI) can cause angina, myocardial infarction, and even death. Angiogenesis is beneficial for ensuring oxygen and blood supply to ischemic tissue, promoting tissue repair, and reducing cell damage. In this study, we evaluated the effects of Salvianolic acid B (Sal B) against myocardial ischemia and explored its underlying mechanism on autophagy. Methods: The anti-apoptosis effect of Sal B was conducted by staining Annexin V-FITC/PI and Hoechst as well as evaluating apoptosis bio-markers at protein level in H9c2 cells at glucose deprivation condition. HUVECs were co-cultured with H9c2, and the tube formation assay was used to monitor Sal B's impact on angiogenesis. The MI model of mice was induced by intraperitoneal injection of isoproterenol (ISO). The effect of Sal B on MI mice was evaluated by HE, Masson, immunohistochemistry, WB and kits. In addition, Atg5 siRNA was applied to verify whether the protective effect of Sal B was regulated to autophagy. Results: In H9c2, Sal B reduced the levels of lactate dehydrogenase (LDH), malondialdehyde (MDA) and reactive oxygen species (ROS), improved the levels of superoxide dismutase (SOD) and mitochondrial membrane potential, downregulated the expressions of Bax and cleaved-Caspase3, upregulated the expression of Bcl-2. Therefore, Sal B could significantly inhibit the damage of H9c2 caused by glucose deprivation. In the co-culture system of H9c2 and HUVECs, vascular endothelial growth factor (VEGF) level in the supernatant was dramatically raised by Sal B. Sal B upregulated the expressions of VEGF, platelet derived growth factor (PDGF) and endothelial marker CD31. It implied that Sal B exerted a significant pro-angiogenic effect. Moreover, Sal B increased the expression of LC3, Atg5, and Beclin1, while reducing the level of P62. When the expression of Atg5 was inhibited, the protective effects of Sal B on apoptosis and angiogenesis was reversed. Conclusions: Sal B inhibited cardiomyocyte apoptosis and promoted angiogenesis by regulating autophagy, thereby improving MI. [ABSTRACT FROM AUTHOR]

Cognitive dysfunction increases as menopause progresses. We previously found that estrogen receptors (ERs) contribute to dyslipidemia, but the specific relationship between ERs, dyslipidemia and cognitive dysfunction remains poorly understood. In the present study, we analyzed sequencing data from female hippocampus and normal breast aspirate samples from normal and Alzheimer's disease (AD) women, and the results suggest that abnormal ERs signaling is associated with dyslipidemia and cognitive dysfunction. We replicated a mouse model of dyslipidemia and postmenopausal status in LDLR−/− mice and treated them with β-estradiol or simvastatin, and found that ovariectomy in LDLR−/− mice led to an exacerbation of dyslipidemia and increased hippocampal apoptosis and cognitive impairment, which were associated with reduced estradiol levels and ERα, ERβ and GPER expression. In vitro, a lipid overload model of SH-SY-5Y cells was established and treated with inhibitors of ERs. β-estradiol or simvastatin effectively attenuated dyslipidemia-induced neuronal apoptosis via upregulation of ERs, whereas ERα, ERβ and GPER inhibitors together abolished the protective effect of simvastatin on lipid-induced neuronal apoptosis. We conclude that decreased estrogen and its receptor function in the postmenopausal stage promote neuronal damage and cognitive impairment by exacerbating dyslipidemia, and that estrogen supplementation or lipid lowering is an effective way to ameliorate hippocampal damage and cognitive dysfunction via upregulation of ERs. [ABSTRACT FROM AUTHOR]

Background: The long-term excessive intake of exogenous cholesterol can lead to abnormally elevated blood lipid levels and induce cardiovascular and cerebrovascular diseases. However, the influence and relevance of exogenous cholesterol on plasma cholesterol components were still unclear, and the influence on intestinal lipid metabolism targets needs to be further explored. Methods: In vivo, the C57BL/6 + NF group and ApoE−/− + NF group mice were fed a normal specific pathogen-free (SPF) diet; the ApoE−/− + HF group mice were fed a high-cholesterol SPF diet. The plasma and jejunum tissue homogenate were obtained for non-targeted lipid metabolomics. The lipid droplets in tissues were observed by transmission electron microscope and oil red O staining. Jejunum tissue morphology was observed by HE staining. The kits were used to detect lipid content in plasma, tissues, intestinal contents, and cells. Western blot, RT-PCR, immunohistochemistry (IHC), and immunofluorescence (IF) were used to observe the key target of lipid metabolism. In vitro, the final concentration of cholesterol was 100 μmol/L in Caco-cells. Oil red O staining, western blot, RT-PCR and immunofluorescence (IF) were used to observe the changes of lipid metabolism. Finally, the influence of liver X receptor alpha (LXRα) on intestinal cholesterol metabolism was clarified by applying the LXRα inhibitor GSK2033 and siRNA targeting LXRα. Results: The aortic arch and intestinal villi of the two groups of ApoE−/− mice showed apparent lesions and lipid accumulation, and there were significant changes in a variety of lipids in the plasma and jejunum. Additionally, jejunum LXRα was markedly activated. High cholesterol can significantly activate LXRα in Caco-2 cells. After LXRα was inhibited, the protein level of ATP-binding cassette transporter A1/G5/G8 (ABCA1/G5/G8) decreased, and the quantity and volume of intracellular lipids soared. Conclusion: In a high-cholesterol environment, the intestine promotes the excretion of cholesterol from the cell through the LXRα-ABCA1/G5/G8 pathway, reduces the intestinal intake of a variety of exogenous cholesterol, and reduces the risk of AS. [ABSTRACT FROM AUTHOR]

The boundaries of talent management (TM) are shifting. However, there remains insufficient understanding of the impact of context and stakeholders within the conceptualisation of TM. Considerable confusion remains about how TM is conceived and defined in the Chinese context. Even less is known about how to reconceptualise Chinese TM in a changing new context. This review adopts a new theoretical lens of talent value to reconsider the current definitions of Chinese TM and presents a framework for re‐examining the relationships between the components of Chinese TM. Integrating the findings of the academic and practical literature, this article proposes a model to identify key contextual factors of the new context to observe and analyse the impacts of contextual changes on the concept of Chinese TM. By reviewing the English and Chinese literature on TM in the Chinese context, we bridge the knowledge gap and provide non‐Chinese readers with insights into the Chinese TM phenomenon and ways of conceptualisation that will be relevant to multinational firms operating in China and cross‐country comparative studies. [ABSTRACT FROM AUTHOR]

Atherosclerosis can be regarded as a chronic disease derived from the interaction between disordered lipoproteins and an unsuitable immune response. The evolution of foam cells is not only a significant pathological change in the early stage of atherosclerosis but also a key stage in the occurrence and development of atherosclerosis. The formation of foam cells is mainly caused by the imbalance among lipids uptake, lipids treatment, and reverse cholesterol transport. Although a large number of studies have summarized the source of foam cells and the mechanism of foam cells formation, we propose a new idea about foam cells in atherosclerosis. Rather than an isolated microenvironment, the macrophage multiple lipid uptake pathways, lipid internalization, lysosome, mitochondria, endoplasmic reticulum, neutral cholesterol ester hydrolase (NCEH), acyl‐coenzyme A–cholesterol acyltransferase (ACAT), and reverse cholesterol transport are mutually influential, and form a dynamic process under multi‐factor regulation. The macrophage takes on different uptake lipid statuses depending on multiple uptake pathways and intracellular lipids, lipid metabolites versus pro‐inflammatory factors. Except for NCEH and ACAT, the lipid internalization of macrophages also depends on multicellular organelles including the lysosome, mitochondria, and endoplasmic reticulum, which are associated with each other. A dynamic balance between esterification and hydrolysis of cholesterol for macrophages is essential for physiology and pathology. Therefore, we propose that the foam cell in the process of atherosclerosis may be dynamic under multi‐factor regulation, and collate this study to provide a holistic and dynamic idea of the foam cell. [ABSTRACT FROM AUTHOR]

Excessive inflammation and the pyroptosis of vascular endothelial cells caused by estrogen deficiency is one cause of atherosclerosis in post-menopausal women. The autophagy is highly regulated by estrogen, however whether estrogen can reduce vascular endothelial cell pyroptosis through estrogen receptor-mediated activation of autophagy to improve atherosclerosis in post-menopausal stage is still unknown. To explore whether estrogen can prevent atherosclerosis by regulating estrogen receptor and subsequently activating autophagy to reduce inflammation and pyroptosis. Aortic samples from pro-menopausal and post-menopausal women with ascending aortic arteriosclerosis were analyzed, and bilateral ovariectomized (OVX) female ApoE-/- mice and homocysteine (Hcy)-treated HUVECs were used to analyze the effect of estrogen supplementation therapy. The aortic endothelium showed a decrease in ERα expression and autophagy, but presented an increase in inflammation and pyroptosis in female post-menopausal patients. Estrogen treatment accelerated autophagy and ameliorated cell pyroptosis in the cardiac aortas of OVX ApoE-/- mice and Hcy-treated HUVECs. Estrogen had therapeutic effect on atherosclerosis and improved the symptoms associated with lipid metabolism disorders in OVX ApoE-/- mice. Inhibition and silencing of ERα led to a reduction in the autophagy promoting ability of estrogen and aggravated pyroptosis. Moreover, the inhibition of autophagy promoted pyroptosis and abolished the protective effect of estrogen, but had no influence on ERα expression. The results of the present study demonstrated that post-menopausal women present decreased autophagy and ERα expression and excessive damage to the ascending aorta. In addition, in vitro and in vivo assay results demonstrated that estrogen prevents atherosclerosis by upregulating ERα expression and subsequently induces autophagy to reduce inflammation and pyroptosis. [ABSTRACT FROM AUTHOR]

In the present work, mesoporous silica films with hexagonally packed perpendicular nanochannels treated as a 2D photonic crystal in extreme ultraviolet (EUV) range are explored by combining theories and experiments. The simulation results show that this film structure exhibits high reflectivities in a wide band range from 5 nm to 11 nm and at broad incidences angle range. The better reflective properties can be ascribed to its excellent photonic crystal structure corresponding to short spectral region. Experimentally, highly ordered mesoporous silica films with vertical mesochannels were fabricated by electrochemically assisted self-assembly method. Moreover, the reflectances of the fabricated film at 5–11 nm region were also tested using synchrotron radiation, which can reach up to 80.4% at 2°from grazing incidence direction. Meanwhile, a relative high reflectance can be maintained at 5–11 nm at incidence angles of 2–7°. This research results offer a new strategy to developing a promising extreme ultraviolet optical film with high reflectance and broad band range. • The oriented mesoporous silica films are treated as 2D photonic crystals. • An ordered and oriented mesoporous silica film was prepared by EASA method. • The oriented mesoporous silica films show high reflectance in a broad band range. [ABSTRACT FROM AUTHOR]

Background: Heart failure (HF) is one of the most common causes of cardiovascular diseases in the world. Currently, the drugs used to treat HF in the clinic may cause serious side effects. Liguzinediol, 2, 5-dimethyl-3, 6-dimethyl-pyrazine, is a compound synthesized after the structural modification of ligustrazine (one active ingredient of Szechwan Lovage Rhizome). We aimed to observe the effects of liguzinediol on preventing HF and explore the related mechanisms. Methods: The ligation of left anterior descending coronary artery was operated to established the myocardial infarction (MI) model in Sprague–Dawley rats. Cardiac functions were recorded by echocardiography and hemodynamics. The changes in the Renin–Angiotensin–Aldosterone System (RAAS), inflammation, and oxidative stress were detected by radioimmunoassay and Elisa kits. Western blot and real-time PCR were applied to determine the expressions of the TGF-β1/Smads pathway. Results: Firstly, liguzinediol enhanced the systolic and diastolic functions of the heart in MI rats. Liguzinediol improved ventricular remodeling by reducing myocardial cell necrosis, as well as reducing collagen deposition and myocardial fibrosis. Then, liguzinediol suppressed the activation of RAAS, inhibited the synthesis of pro-inflammation factors, and reduced oxidative stress. In the end, liguzinediol also down-regulated the expressions of the TGF-β1/Smads pathway. Conclusions: Liguzinediol could alleviate HF caused by MI in rats, and the protective effect was associated with the regulation of the TGF-β1/Smads pathway. [ABSTRACT FROM AUTHOR]

Background: Mulberry (Morus alba L.) leaf tea benefits the control of diabetes in Asian nations. This study was aim to investigate if the flavonoids, which extracts from mulberry leaves, could regulate the metabolism of glycolipid, and to investigate if flavonoids could regulate IRS1/PI3K/AKT pathway signal to affect the expression of FAS and membrane transfer capacity GLUT4 in 3T3-L1 adipocytes. Results: Results revealed that flavonoids decreased the levels of free fatty acid and increased the glucose consumption and the levels of adiponectin and leptin in a dose-dependent manner, and remarkably increased the protein expression levels of p-IRS1, p-PI3K, p-Akt, total GLUT4, and membrane GLUT4, and decreased the protein expression levels of PTEN and FAS in 3T3-L1 adipocytes IR model. On the other hand, wortmannin (2 nM), a selective and irreversible PI3K inhibitor, significantly decreased the glucose consumption and the adiponectin and leptin levels, and increased the free fatty acid level in flavonoids treated 3T3-L1 adipocytes IR model. Furthermore, wortmannin (2 nM) partly eliminated the activation of PI3K/AKT signaling, the suppression of FAS, and the up-regulated membrane transfer capacity of GLUT4 in flavonoids treated 3T3-L1 adipocytes IR model. Conclusion: In conclusion, our results illustrated that mulberry leaf extracts flavonoids alleviated the glycolipid metabolic abnormalities in 3T3-L1 adipocytes IR model, and the effect was associated with the activation of IRS1/PI3K/AKT pathway, the suppression of FAS, and the up-regulation of membrane transfer capacity of GLUT4. [ABSTRACT FROM AUTHOR]

[Display omitted] • A label-free electrochemical aptasensor for LDL detection was constructed. • MoS 2 -Au-Fc NSs are used as a high-performance redox indicator. • MoS 2 -Au-Fc NSs are used as a biocompatible substrate for LDLapt stabilization. • LDL aptasensor responses logarithm LDL linearly from 0.001 μg/mL to 100 μg/mL. • LDL aptasensor shows low-cost, high-sensitivity and good actual errors. Low-density lipoprotein (LDL) is a key biomarker involved in cardiovascular disease (CVD) risk assessment. Early-stage diagnosis of CVD complications by monitoring LDL levels could be a significant clinical tool and the first step toward adopting efficient therapy. Herein, a novel label-free electrochemical aptasensor for LDL detection was developed via the molybdenum disulfide-gold nanoparticle- ferrocene-carboxylic acid nanosheets (MoS 2 -Au-Fc NSs) enhanced signal amplification strategy. The MoS 2 -Au-Fc NSs were used not only as the biocompatible substrate for LDL aptamer (LDLapt) stabilization due to the increasing electrical conductivity and effective surface area, but also as a redox probe for monitoring the changes of the electrochemical signal because of good electroactive properties of Fc. The aptasensor fabrication steps were investigated by cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), and scanning electron microscopy (SEM). When LDL was captured onto the sensor via the specific affinity of the LDLapt, the formed LDLapt-LDL complexes shed from the electrode and enhanced the electron transfer rate on the electrode surface, resulting in an increase of the peak current. Thus, LDL can be easily detected by measuring the changes of peak current. Under ideal circumstances, the aptasensor was linearly correlated with logarithm LDL concentration from 0.001 to 100.0 μg/mL with R2 of 0.9914, and a low detection limit of 0.42 ng/mL. Furthermore, the LDL detected by aptasensor in actual serum samples with good actual errors (0.73%–5.00%) and satisfactory relative standard deviations (RSDs) (0.04%–0.84%). This study provides a new analytical method for measuring the level of LDL which is specifically up-regulated in CVD patients at an early stage. [ABSTRACT FROM AUTHOR]

Abstract SSZ-13 zeolite with a SiO 2 /Al 2 O 3 ratio in the range of 26–183 was synthesized by adding zeolite L in the synthesis gel absent from additional aluminum source, and the effects of SiO 2 /Al 2 O 3 and N,N,N-trimethyladamantammonium hydroxide (TMAdaOH)/SiO 2 ratios on the crystallization were investigated. The crystallization mechanism was studied with X-ray diffraction, Scanning electron microscopy, Fourier transform infrared spectroscopy and 29Si and 27Al MAS NMR spectroscopy techniques. It is shown that the SiO 2 /Al 2 O 3 and TMAdaOH/SiO 2 ratios have a significant effect on the acidity, and thus, the methanol-to-olefins (MTO) performance of SSZ-13. The co-presence of TMAdaOH, NaOH and extra silica source (SiO 2) is necessary for formation of SSZ-13. The crystallization of SSZ-13 occurs by decomposing structure of zeolite L into double six- and four-membered rings that subsequently restructure into CHA topology under the direction of TMAdaOH, and further induce the nucleation and crystal growth. It is noteworthy that the Al species in zeolite L directly transform into those of SSZ-13 without forming monomeric species. The prepared SSZ-13 shows higher catalytic stability and selectivity to ethylene and proplyene than the conventionally synthesized sample from amorphous aluminosilicate gel in MTO reaction. Graphical abstract Image 1 Highlights • LTL hydrothermal conversion into high silica CHA was performed with the TMAdaOH. • The product SSZ-13 zeolite was strongly affected by starting Si/Al and SDA/Si ratio. • The crystallization rate of SSZ-13 from L-added starting gel was distinctly enhanced. • The crystallization mechanism of SSZ-13 from L-added starting gel was discussed. • The obtained SSZ-13 from L-added gel showed enhanced catalysis for MTO reaction. [ABSTRACT FROM AUTHOR]

The education sector is an important pillar of a nation's economic and social development. Yet, limited research has been conducted on the performance management of those in managerial positions in the Chinese higher education sector context. Given the Chinese government's recent espoused ambition, and resource commitment, to build world‐class universities and world‐class disciplines, this is a significant gap. Drawing on data collected from 18 semi‐structured interviews and 693 survey responses, we examine the relationship between the extent to which performance evaluation is used for monitoring and decision‐making purposes, and role conflict, organizational citizenship behavior and performance. Our study contributes to existing knowledge on the performance management system in the Chinese higher education sector by revealing its unique characteristics underpinned by competing rationalities and demands on academic leaders. It highlights the need for improvement in human resource management if China is serious in building first‐class universities. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Liuwei Dihuang (LWDH), a classical traditional Chinese medicine prescription, has been widely used to prevent and to treat various diseases with symptoms of ‘Kidney-Yin’ deficiency syndrome for over 1000 years in China. It is commonly used to treat functional decline associated with senile disease and menopausal syndrome, especially memory decline, insomnia, diabetes and osteoporosis. Modern experimental pharmacological studies indicated that the mechanism of LWDH treatment of menopausal syndrome may be associated with enhanced estrogenic effects. However, little attention has been paid to the potential impact of LWDH on atherosclerosis (AS) associated with female menopause. The aim of this study was to evaluate the preventive effects of LWDH intake on an animal model of female menopause AS and to explore the underlying molecular mechanism. Materials and methods ApoE −/− mice were randomly divided into 4 groups, with C57BN/L6 mice as the control group. All ApoE −/− mice were ovariectomized (Ovx) one week prior to oral administration and initiation of high-fat diet. C57BL/6 mice were given sham operation and maintained on normal diet. The three administered groups were given simvastatin (4 mg/kg via i.g.) and LWDH (4.5, 9.0 g/kg via i.g.) every day for 14 weeks. Atherosclerotic lesions in the aortic root were determined by oil red O staining and hematoxylin-eosin staining. α-Actin and CD68 in atherosclerotic lesions were detected by immunohistological assay. Serum lipids and homocysteine (Hcy) levels were measured in the 14th week. The cleaved caspase-3, C/EBP homologous protein (CHOP) and G protein coupled estrogen receptor 30 (GPR30) expressions in the aortic arch endothelium were determined by immunohistochemistry and Western blot. The inhibitory effect of LWDH-medicated (20%, 12 h) on Hcy (20%, 24 h)-induced apoptosis of human umbilical vein endothelial cells (HUVECs) was examined by flow cytometry and Hoechst 33258 staining. Intracellular ROS production, nitric oxide release, and endothelial NO synthase (eNOS) activity were measured with or without LWDH-medicated serum pretreatment. In addition, CHOP, glucose-regulated protein GPR30, 78 (Grp78), Bcl-2, Bax and cleaved caspase-3 were analyzed by Western blot. Finally, the influence of G15, a specific antagonist of GPR30, on the protective effect of LWDH on endothelial cells was investigated. Results In vivo administration of LWDH prevented plaque formation and reduced plasma lipid and Hcy levels. LWDH inhibited CHOP and cleaved caspase-3 expression in vivo and in vitro while maintaining GPR30 expression. In vitro study showed that Hcy-induced HUVECs apoptosis was weakened by LWDH-medicated serum pretreatment. Treatment with LWDH-medicated serum significantly upregulated NO release and eNOS activity in HUVECs. In addition, LWDH-medicated serum treatment optimized the balance between Bax and Bcl-2, and attenuated intracellular ROS production. G15 reversed the protective effect of LWDH on endothelial cells and the changes of apoptosis-related proteins. Conclusions LWDH treatment can significantly reduce plaque formation in an animal model of menopausal AS. The mechanism may be inhibition of Hcy-induced endothelial cell apoptosis by modulating GPR30. Hence, LWDH can potentially be used to prevent AS-related vascular disease in menopausal women. [ABSTRACT FROM AUTHOR]

Pinellia ternata , a widely used traditional Chinese medicine, contains a strong mucosal irritant that is connected with Pinellia ternata lectin (PTL) in its tubers. The purpose of this study was to explore the mechanisms by which PTL induces inflammation. We found that in RAW264.7 cells, PTL activated the PI3K/Akt/mTOR and NF-κB pathways, which resulted in the release of proinflammatory cytokines. Flow cytometry and laser confocal microscopy analysis showed that FITC-labeled PTL bound to the macrophages' surface. Based on kinetic analyses and protein-protein docking simulations, PTL was shown to bind toll-like receptor 4 (TLR4).it was demonstrated that PTL binds highly to Toll-like receptor 4 (TLR4). TLR4 knock-down or knockout resulted in a decrease in both cytokine release and PI3K/Akt/mTOR and NF-κB pathway activation in PTL-stimulated macrophages or mice. RNA-seq analysis showed that genes involved in the PI3K/Akt/mTOR signaling pathway were strongly upregulated in response to PTL stimulation, confirming that the PI3K/Akt/mTOR pathway is linked to the inflammatory effect of PTL in RAW264.7 cells. These findings reveal that PTL can mediate inflammation through TLR4 and activating the PI3K/Akt/mTOR to regulate NF-κB signaling pathways. • PTL induces inflammation through PI3K/Akt/mTOR regulation of NF-KB pathway. • PTL can bind to TLR4 receptor. • PTL mediates inflammatory responses through activation of the PI3K/Akt/mTOR pathway by TLR4 receptor. [ABSTRACT FROM AUTHOR]

[Display omitted] • • ERα decline in the postmenopausal stage increases TLR4 activation in macrophages to promote plaque instability. • • Estrogen or phytoestrogen therapy reduces macrophage-associated inflammation and matrix degradation to improve plaque instability. • • ERα mediated the regulation of estrogen and phytoestrogens on macrophages by inhibiting TLR4 signal activation. Acute cardiovascular events increase significantly in postmenopausal women. The relationship between estrogen receptor (ER) and plaque stability in the postmenopausal stage remains to be elucidated. We aimed to explore whether ERα activation improves plaque instability in the postmenopausal stage. Here, we report that postmenopausal women showed increased macrophage activation and plaque instability with increased MCP-1, MMP9, TLR4, MYD88 and NF-κB p65 and decreased ERα and TIMP1 expression in the vascular endothelium. Moreover, ovariectomy in LDLR-/- mice resulted in a significant increase in plaque area and necrotic core area, as well as a significant decrease in collagen content and an increase in macrophage accumulation in the artery. Ovariectomy also reduced serum estrogen levels and ERα expression and upregulated TLR4 and MMP9 expression in arteries in LDLR-/- mice. Estrogen or phytoestrogen therapy upregulated the expression level of ERα in ovariectomized mice and increased plaque stability by inhibiting macrophage accumulation and TLR4 signaling. In vitro, LPS incubation of RAW264.7 cells resulted in a significant decrease in ERα and TIMP1 expression and an increase in TLR4 activation, and estrogen or phytoestrogen treatment increased ERα and TIMP1 expression and inhibited TLR4 activation and MMP9 expression in LPS-treated RAW264.7 cells. Compared to control siRNA transfected RAW264.7 cells, TLR4 siRNA promoted TIMP1 expression in RAW264.7 cells with LPS incubation, but did not affect ERα expression in RAW264.7 cells with or without LPS treatment. The ERα inhibitor MPP abolished the regulatory effect of estrogen or phytoestrogen on LPS-induced RAW264.7 cells. In conclusion, the present study demonstrates that decreased ERα expression promotes macrophage infiltration and plaque instability in the postmenopausal stage, and activation of ERα in the postmenopausal stage alleviates atherosclerotic plaque instability by inhibiting TLR4 signaling and macrophage-related inflammation. [ABSTRACT FROM AUTHOR]

Catalpol, a bioactive component from Rehmannia glutinosa (Di Huang), has been widely used to protect cardiomyocytes against myocardial ischemia. The aim of the present study was to investigate the anti-apoptotic and anti-oxidative effects of Catalpol on glucose-starved H9c2 cells for cardio-protection and to elucidate the underlying mechanisms. Here, we showed that Catalpol protected the glucose-starved H9c2 cells through reducing apoptosis and attenuating oxidative damage. Moreover, the increases of autophagic lysosomes, LC3, autophagic flux and autophagic vacuole were observed in Catalpol-treated cells using flow cytometer and fluorescence microscope. Western blotting analyses showed that the autophagy-related proteins (LC3, Beclin1 and ULK) were markedly increased in Catalpol-treated cells, suggesting that Catalpol up-regulated autophagy in glucose starved H9c2 cells. Mechanistic investigations revealed that the autophagy inhibitor 3-MA markedly abrogated Catalpol’s anti-apoptotic and anti-oxidative effects and prevented Catalpol-induced mitophagy. Furthermore, the estrogen receptor inhibitor tamoxifen significantly abolished Catalpol up-regulation of mitophagic related proteins (LC3, Beclin 1, p62, ATG5). Collectively, these data revealed that Catalpol inhibited apoptosis and oxidative stress in glucose-deprived H9c2 cell through promoting cell mitophagy and modulating estrogen receptor, supporting the notion that Catalpol could be a novel drug candidate against myocardial ischemia for the treatment of cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Aims Sang-Tong-Jian (STJ), a novel formula composed of flavonoids and alkaloids derived from mulberry leaf, has been found to reduce blood glucose levels in rats with type 2 diabetes mellitus (T2DM) in our previous studies. However, the precise mechanisms remain unknown. Insulin resistance is the main characteristic of T2DM, which may be due to impairment of the PI3K/AKT signaling pathway. In this study, we investigated the effects of STJ on glycometabolism and insulin resistance in KKAy mice. Methods A total of 50 KKAy male mice were randomly divided into five groups: model, metformin at 260 mg/kg, and STJ at 105, 210 and 420 mg/kg. C57BL/6J mice were used as the control group. Random blood glucose levels in KKAy mice were determined every 10 days after treatments. At the 10th and 13th week, oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) were conducted after a 12 h overnight fast, respectively. After 13-week treatments, glycosylated hemoglobin (GHb) and serum insulin were measured using a colorimetric method and ELISA kits. Liver glycogen and muscle glycogen levels were analyzed using a colorimetric method. The morphology of pancreas, liver, skeletal muscle and epididymal fat were visualized by haematoxylin and eosin staining. The gene level of GLUT2 (liver) and GLUT4 (skeletal muscle, epididymal fat) were detected by real-time PCR. The proteins of GLUT2, GLUT4, IRS1, PI3K, AKT and their phosphorylation were assayed by Western blot analyses. Results STJ significantly decreased the random blood glucose and GHb levels, and increased liver and muscle glycogen levels. The results of OGTT and ITT and measurement of serum insulin indicated that STJ ameliorated insulin resistance in KKAy mice. STJ treatments also ameliorated the histopathological alterations in pancreas, liver, skeletal muscle and epididymal fat in KKAy mice. Furthermore, STJ upregulated the gene and protein expression of GLUT2 (liver) and GLUT4 (skeletal muscle, epididymal fat). Meanwhile, GLUT4 translocation and phosphorylation of IRS1, p85-PI3K and AKT were significantly increased by STJ treatments. Conclusions Our results indicated that STJ ameliorated glycometabolism and insulin resistance in KKAy mice, which might be due to activation of PI3K/AKT pathway. [ABSTRACT FROM AUTHOR]

Objectives The aim of this study was to investigate the cardioprotective effect of salvianolic acid B (Sal B) on acute myocardial infarction ( AMI) in rats and its potential mechanisms. Methods The AMI model was established in rats to study the effect of Sal B on AMI. Haematoxylin-eosin ( HE) staining was used to evaluate the pathological change in AMI rats. Immunofluorescence and TUNEL staining were used to detect autophagy and apoptosis of myocardial cells in hearts of AMI rats, respectively. Protein expression of apoptosis-related, autophagy-related and angiogenesis-related proteins were examined by Western blot. Key findings Sal B attenuated myocardial infarction significantly compared with that of the model group. Rats administered with Sal B showed higher inhibition rate of infarction and lower infarct size than those of the model group. Moreover, Sal B decreased the serum levels of creatine kinase, lactate dehydrogenase and malondialdehyde, while increased such level of superoxide dismutase significantly compared with those of the model group. Sal B inhibited the expression of Bax, cleaved caspase-9 and cleaved PARP, while promoted the expression of Bcl-2, LC3- II, Beclin1 and VEGF. Conclusions Sal B has cardioprotective effect on AMI and Sal B may be a promising candidate for AMI treatment. [ABSTRACT FROM AUTHOR]

Cardiac fibrosis plays a causal role in the development of heart failure, and anti-fibrotic therapy represents a promising strategy to mitigate heart failure. The purpose of this study was to investigate the effect of a new drug-liguzinediol on cardiac fibrosis of heart failure Male Sprague-Dawley rats (SD) rats and the underlying mechanisms. Liguzinediol was administered to rats that were injected with doxorubicin (Dox) for four weeks. Two weeks later, its effects on cardiac fibrosis were assessed by haematoxylin and eosin (HE) staining and Masson staining. The collagen content was determined by Elisa, and protein expression was detected by western blot in vitro and in vivo . Liguzinediol decreased cardiac muscle fiber break evidenced by HE staining and it significantly reduced cardiac fibrosis evidenced by Masson staining in DOX-treated rats. In addition, the hydroxyproline level and the ratio of type I/III collagens were also significantly decreased, and western blot assays showed that liguzinediol regulated the balance between matrix matalloproteinases (MMPs) and tissue inhibitor of metalloproteinase (TIMPs) to protect cardiac remodeling in vivo and in vitro . These data collectively indicated that liguzinediol could protect against cardiac fibrosis in rats. Liguzinediol could be exploited to be a promising candidate for cardiac fibrosis. [ABSTRACT FROM AUTHOR]

Examines the role of transcription factors in the stimulation of cyclooxygenase-2 gene transcription by Interleukin-1 Beta in articular chondrocytes. Induction of gene expression; Role of proximal site in the stimulation of COX-2 gene transcription; Determination of basal promoter activity in the pancreatic islet cell line.

The risk of atherosclerosis (AS) ascends among post-menopausal women, while current hormone replacement therapy exerts several adverse effects. Alisol B 23-acetate (AB23A), a tetracyclic triterpenoid isolated from the rhizome of Alisma orientale , was reported to show multiple physiological activities, including regulating lipid metabolism. According to molecular docking analysis, it was predicted to bind with estrogen receptor α (ERα). In this study, we aimed to observe the effect of AB23A on preventing post-menopausal AS and explore whether the mechanism was mediated by ERα. In vitro, free fatty acid (FFA) was applied to induce the abnormal lipid metabolism of L02 cells. In vivo, the ApoE−/− mice were ovariectomized to mimic the cessation of estrogen. The high-fat diet was also given to induce post-menopausal AS. We demonstrated AB23A attenuated the accumulation of total cholesterol and triglyceride induced by free fatty acids in hepatocytes. In high-fat diet-ovariectomy-treated ApoE−/− mice, AB23A eliminated lipids in blood and liver. AB23A not only reduced the synthesis of proprotein convertase subtilisin/kexin type 9 (PCSK9) through sterol-regulatory element binding proteins (SREBPs) but also suppressed the secretion of PCSK9 through silent information regulator 1 (SIRT1). Notably, AB23A promoted the expression of ERα in vivo and in vitro. The both ERα inhibitor and ERα siRNA were also applied in confirming whether the hepatic protective effect of AB23A was mediated by ERα. We found that AB23A significantly promoted the expression of ERα. AB23A could inhibit the synthesis and secretion of PCSK9 through ERα, lower the accumulation of triglyceride and cholesterol, and prevent post-menopausal AS. Unlabelled Image [ABSTRACT FROM AUTHOR]

Decreases in estrogen secretion and estrogen receptor function lead to an increase in the incidence of dyslipidemia and cardiovascular disease (CVD) in postmenopausal women. We previously reported that β-estradiol has a significant regulatory effect on lipids in ApoE−/− mice with bilateral ovariectomy. In the present study, we investigated how β-estradiol regulates intestinal function via estrogen receptors to alleviate postmenopausal dyslipidemia. Ovariectomized ApoE−/− mice were treated with β-estradiol for 90 days, and we found that β-estradiol reduced TC, TG, LDL-c, IL-1β and IL-18 levels in serum and decreased lipid accumulation in the liver. β-estradiol reduced injury and inflammation in the jejunum in ovariectomized mice, and promoted the expression of tight junction-related proteins. Moreover, β-estradiol increased ERα, ERβ, GPR30 and ABCG5 protein expression, and decreased the levels of NPC1L1 and SR-B1 in the jejunum of ovariectomized mice. In Caco-2 cells incubated with cholesterol, β-estradiol up-regulated PI3K/AKT signaling, reduced cholesterol accumulation, suppressed inflammatory signaling, and increased the expression of tight junction-related proteins. ERβ or GPR30 inhibition decreased the protective effect of β-estradiol on cholesterol accumulation, tight junctions, and inflammation in cholesterol incubated Caco-2 cells, while silencing both ERβ and GPR30 completely eliminated the protective effect of β-estradiol. PI3K/AKT inhibition abolished the protective effect of β-estradiol on cholesterol accumulation, tight junction-related protein expression, and inflammation, but had no influence on ERα, ERβ or GPR30 expression in cholesterol incubated Caco-2 cells. Our results provide evidence that β-estradiol regulates intestinal function via ERβ and GPR30 mediated PI3K/AKT signaling activation to alleviate postmenopausal dyslipidemia. [ABSTRACT FROM AUTHOR]

The classical and traditional Chinese medicine prescription, Liuwei Dihuang (LWDH), has been commonly used to treat the menopausal syndrome. It has been reported that LWDH could improve estrogen receptor α (ERα) expression to prevent atherosclerosis (AS), while the mechanism of LWDH on regulating ERα expression was still unknown. To reveal the mechanism of LWDH on regulating the ERα expression. The protective effect of LWDH on Hcy-induced apoptosis of human umbilical vein endothelial cells (HUVECs) was examined. The expression of ERα and DNA methyltransferases 1 (DNMT1) were detected by Western blot and real-time polymerase chain reaction (RT-PCR). The methylation rate of the ERα gene was assayed by the bisulfite sequencing PCR (BSP). High-performance liquid chromatography-tandem mass spectrometry (HPLC-MS) was applied to determine the level of S-Adenosyl methionine (SAM) and S-Adenosyl homocysteine (SAH). In vivo, the ApoE−/- mice were ovariectomized to establish postmenopausal atherosclerosis (AS) model. In vitro study showed that LWDH protects HUVECs from Hcy-induced apoptosis. Treatment with LWDH significantly increased the ERα expression and reduced the methylation rate of the ERα gene by inhibiting the DNMT1 expression. The level of main methyl donor SAM and the ration of SAM/SAH were reduced by LWDH. In vivo, LWDH prevented the formation of plaque and reduced the concentration of Hcy. In addition, LWDH upregulated the ERα expression, as well as inhibiting the expression of DNMT1 in atherosclerotic mice. LWDH exerted protective effects on postmenopausal AS mice, and HUVECs treated with Hcy. LWDH increased of ERα expression via inhibiting DNMT1-dependent ERα methylation. Image 1 [ABSTRACT FROM AUTHOR]

Mulberry (Morus alba L.) leaves have been widely applied to controlling blood glucose as a efficacious traditional Chinese medicine or salutary medical supplement. The extracts of mulberry leaf suppress inflammatory mediators and oxidative stress, protect the pancreatic β-cells and modulate glucose metabolism in diabetic rats. Our previous studies and others have shown that mulberry leaf extract has excellent therapeutic effects on type 2 diabetes mellitus (T2DM), however, the underlying mechanism remains to be studied. Skeletal muscle insulin resistance (IR) plays an important role in the pathogenesis of T2DM. The aim of this study was to investigate the effects and mechanisms of Mulberry leaf flavonoids (MLF) in L6 skeletal muscle cells and db/db mice. L6 skeletal muscle cells were cultured and treated with/without MLF for in vitro studies. For in vivo studies, the db/db mice with/without MLF therapy were used. Coomassie brilliant blue staining and α-SMA immunofluorescence staining were used to identify the differentiated L6 cells. Glucose level and ATP level of L6 myotubes were performed by optical density detection and cell viability was performed by MTT method. Mitochondrial membrane potential of L6 myotubes was detected by JC-1 fluorescent staining. ROS level of L6 myotubes was detected by DCFH-DA fluorescent staining. The body weight, food intake, and blood glucose of the mice were measured in different treatment days. Oral glucose tolerance test (OGTT), starch glucose tolerance test (STT) and insulin tolerance test (ITT) were performed in mice. Glycated hemoglobin, glycated serum protein, insulin, liver and muscle glycogen, total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-c) and low-density lipoprotein cholesterol (LDL-c) of the mice were detected by corresponding kit. The pathologic change of pancreas and skeletal muscle of mice were performed by H & E staining. Immunohistochemistry staining was used to detect the GLUT4 and p-AMPK expressions in skeletal muscle in mice. GLUT4, CPT-1, NRF1, COXIV, PGC-1α, and p-AMPK expression levels in L6 cells and mice were detected by western bolt assay. MLF and metformin significantly ameliorated muscle glucose uptake and mitochondrial function in L6 muscle cells. MLF also increased the phosphorylation of AMPK and the expression of PGC-1α, and up-regulated the protein levels of m-GLUT4 and T-GLUT4. These effects were reversed by the AMPK inhibitor compound C. In db/db mice, MLF improve diabetes symptoms and insulin resistance. Moreover, MLF elevated the levels of p-AMPK and PGC-1α, raised m-GLUT4 and T-GLUT4 protein expression, and ameliorated mitochondrial function in skeletal muscle of db/db mice. MLF significantly improved skeletal muscle insulin resistance and mitochondrial function in db/db mice and L6 myocytes through AMPK-PGC-1α signaling pathway, and our findings support the therapeutic effects of MLF on type 2 diabetes. Image 1 [ABSTRACT FROM AUTHOR]

Liuwei Dihuang (LWDH) is a classic prescription that has been used as a traditional medicinal formula for more than 1000 years in China. In clinical, LWDF is used for treating functional decline associated with senile disease and menopausal syndrome. Studies have demonstrated that LWDH could significantly improve estrogen level and ER expression, and suspend the process of atherosclerosis. However, the under mechanism of how LWDH suppressing VSMCs phenotypic conversion and proliferation through ER is still unknown. This study was to reveal the under mechanism of how LWDH inhibits the phenotypic conversion of VSMCs. 24 ApoE−/− mice were divided into 4 groups: sham group, model group, E 2 group, and LWDH group, and 6 C57BN/L6 mice were used as control group. The primary VSMCs were divided into control group, model group, E 2 group, LWDH group, LWDH + MPP group, and LWDH + PHTPP group with or without control siRNA, ERα siRNA, ERβ siRNA, and myocardin siRNA. Oil red staining was used to evaluate the lipid deposition in the cardiac aorta. Serum chemistry analysis to test serum TG, TC, LDL, and HDL. Immunofluorescence staining was used to test α-SMA, osteopontin and F-actin. Immunohistochemical staining was performed to check out the myocardin in the cardiac aorta. The mRNA levels of α-SMA, osteopontin, ERα, ERβ, SRC3 and myocardin were detected by Real Time-PCR, and the protein expression levels of them were detected by Western blotting. Co-immunoprecipitation was proceed to test the interaction between ERα and SRC3 and SRC3 and myocardin. Flow cytometry was used to check out the cell cycle. Wound healing assay and Transwell were managed to evaluate the migration capacity of VSMCs. In vivo administration of LWDH suppressed AS symptoms, decreases phenotypic marker of vascular endothelial cell, and increases phenotypic marker of VSMC in ovariectomized ApoE−/− female mice. Moreover, LWDH significantly increased the mRNA and protein expression levels of ERα, ERβ, SRC3 and myocardin in the cardiac aorta of ovariectomized ApoE−/− female mice. In vitro, LWDH altered cell cycle and reduced the elevated cyclinD protein expression migration capacity and in the model VSMCs. In addition, LWDH inhibited phenotypic conversion and promoted the expression of ER, SRC3, and myocardin of the primary VSMC phenotypic conversion model. Inhibition of ERα almost completely eliminated the impacts of LWDH on α- SMA and osteopontin. Furthermore, LWDH promoted the interaction between ERα and SRC3 and up-regulated the co-activation of SRC3 and myocardin. LWDH could inhibit the phenotypic conversion of VSMCs in vitro and in vivo by increasing the activity of myocardin through up-regulating the expression of ERα and promoting the interaction between ERα and SRC3. Our research reveals the under mechanism of how LWDH inhibits the phenotypic conversion of VSMCs. Image 1 [ABSTRACT FROM AUTHOR]

Treating ventricular remodeling continues to be a clinical challenge. Studies have shown that hypertension is one of the most common causes of ventricular remodeling, and is a major cause of cardiovascular risk in adults. Here, we report that Tongsaimai (TSM), a Chinese traditional medicine, could inhibit arterial pressure and left ventricular pressure to improve hemodynamic abnormalities in rats impaired by abdominal aortic constriction (AAC). Administration of TSM significantly reduced the heart mass index and the left ventricular mass index significantly in AAC rats. TSM could also markedly ameliorate cardiac collagen deposition and reduce the concentration of hydroxyproline in the heart of AAC rats. Moreover, TSM alleviated cardiac histomorphology injury resulting from AAC, including reducing cardiomyocyte hypertrophy, fibrous connective tissue hyperplasia, cardiomyocyte apoptosis, replacement fibrosis and the disorders of myocardial myofibrils, intercalated discs, mitochondria and mitochondrial crista. In addition, the levels of transforming growth factor (TGF) - β and inflammation-related molecules including tumor necrosis factor-α (TNF-α), which were over-expressed with AAC, were decreased by STM. In conclusion, STM could reverse the hypertension and left ventricular remolding caused by abdominal aortic constriction in rats. Image 1 [ABSTRACT FROM AUTHOR]