Autonomic and endocrine control of cardiovascular function

The function of the heart is to contract and pump oxygenated blood to the body and deoxygenated blood to the lungs.To achieve this goal,a normal human heart must beat regularly and continuously for one's entire life.Heartbeats originate from the rhythmic pacing discharge from the sinoatrial(SA) node within the heart itself.In the absence of extrinsic neural or hormonal influences,the SA node pacing rate would be about 100 beats per minute.Heart rate and cardiac output,however,must vary in response to the needs of the body's cells for oxygen and nutrients under varying conditions.In order to respond rapidly to the changing requirements of the body's tissues,the heart rate and contractility are regulated by the nervous system,hormones,and other factors.Here we review how the cardiovascular system is controlled and influenced by not only a unique intrinsic system,but is also heavily influenced by the autonomic nervous system as well as the endocrine system.

Effects of ECAE processing temperature on the microstructure, mechanical properties, and corrosion behavior of pure Mg

一条二拍子的圆舞平等者隧道尖挤出(ECAE ) 过程被用来处理纯 Mg。在纯 Mg 的微观结构，机械性质，和腐蚀行为上处理温度的 ECAE 的效果被学习。结果证明纯 Mg 的平均谷物尺寸与减少的挤出温度减少。在在 473 K 处理的 ECAE 以后，罚款和 equiaxed 谷物(~ 9 m ) 被获得。在 473 K 处理的样品展出优秀机械性质，而在 633 K 处理的样品让最低腐蚀评价。改进腐蚀抵抗和由 ECAE 的纯 Mg 的机械性质被归功于到谷物精炼和微结构修正。

Changes of insulin-like growth factor-Ⅱ and insulin-like growth factor binding protein-3 in cerebrospinal fluid of children with tuberculous meningitis

BACKGROUND： Recent studies have found that insulin-like growth factors （IGFs） and insulin-like growth factor binding protein-3 （IGFBP-3） have stronger neurotrophic and neuroprotective effects. But whether their levels in cerebrospinal fluid could be used as an auxiliary indicator in differentially diagnosing tuberculous meningitis and viral encephalitis is not yet clear. OBJECTIVE： To explore the changes of insulin-like growth factor-Ⅱ （IGF-Ⅱ ） and IGFBP-3 in cerebrospinal fluid （CSF） of children with tuberculous meningitis and the significance of the changes. DESIGN： A non-randomized concurrent controlled study. SETTING： Department of Pediatric Internal Medicine, the First Affiliated Hospital of Xinxiang Medical College. PARTICIPANTS： Thirty children with tuberculous meningitis （14 males and 16 females） were selected from the Department of Pediatric Internal Medicine, the First Affiliated Hospital of Xinxiang Medical College from January 2005 to December 2006. Tuberculous meningitis was diagnosed according to their clinical manifestations, the history of close contact with tuberculosis, typical cerebrospinal fluid changes of tuberculous meningitis, positive tuberculosis antibody and effective antituberculosis treatment. There were 30 children （13 males and 17 females） with viral encephalitis, and viral encephalitis was diagnosed according to epidemiological history, clinical manifestations, conventional and biochemical changes of cerebrospinal fluid, and negative bacteriology judgment. Meanwhile, 30 children （13 males and 17 females） without infectious and central nervous system disease were selected as the control group. Informed consent was obtained from the parents of all the enrolled children. METHODS： ①The lumbar puncture operation was implemented immediately to obtain cerebrospinal fluid （3 mL）. The contents of IGF-Ⅱ and IGFBP-3 were detected with immunoradiometric assay. The concentrations of glucose and protein in cerebrospinal fluid were determined with a dry-chemical method. The number of white blood cells was counted by Fushi Method. ②The Pearson correlation analysis was used to analyze the correlation of the contents of IGF-Ⅱ and IGFBP-3 in cerebrospinal fluid with the leucocyte counting and the concentrations of glucose and protein in cerebrospinal fluid. MAIN OUTCOME MEASURES： The contents of IGF- Ⅱ and IGFBP-3 in cerebrospinal fluid, and their correlation with the leucocyte counting and the concentrations of glucose and protein in cerebrospinal fluid. RESULTS： ①Contents of IGF-Ⅱ and IGFBP-3 in cerebrospinal fluid： The contents of IGF-Ⅱ and IGFBP-3 in cerebrospinal fluid in the tuberculous meningitis group were significantly higher than those in the encephalitis virus group and control group （P 〈 0.05）. There was no significant difference in the contents of IGF- Ⅱ and IGFBP-3 in cerebrospinal fluid between the viral encephalitis group and control group （P 〉 0.05）. ②Correlation： The IGF- Ⅱ and IGFBP-3 contents in cerebrospinal fluid were positively correlated with the protein concentration in cerebrospinal fluid （r =0.821, 0.855, P 〈 0.01）, but negatively with the glucose （r =0.742, - 0.605, P 〈 0.01）. CONCLUSION- ①IGFs and IGVBPs are involved in the pathophysiological process of tuberculous meningitis, as well as the glucose and protein metabolism in cerebrospinal fluid. ②The IGF-Ⅱ and IGFBP-3 contents in cerebrospinal fluid can be used as the auxiliary indicators to differentially diagnose tuberculous meningitis and viral enceohalitis.

Effect of a novel compound from <i>Lycopodium obscurum</i>L. on osteogenic activity of osteoblasts in <i>vitro</i>

We investigated the potential of an extract of Lycopodium obscurum L.;stigmastane-3-oxo- 21-oic acid (SA), to enhance osteogensis of mouse osteoblastic MC3T3-E1 cells. SA at a concentration of 16 μM was found to have no significant effect upon the viability of the cells, thus concentrations of 8 μM and 16 μM of SA were used in all further experiments. Both concentrations of SA had an inhibitory affect upon alkaline phosphatase activity (ALP) after 8 days incubation, however, after 16 days activity was restored to control levels. However Alizarin red S staining showed increased levels of mineralization for both concentrations after 16 days culture. Real time PCR showed inhibition of genes Runx2 and Osterix genes responsible for the up-regulation of ALP. However early time point (8 days) up-regulation of bone matrix mineralization genes OPN and OCN, and late time point (16 days) up-regulation of both Jun-D and Fra-2 mRNA expression was significantly enhanced. These results suggest a potential mechanism of SA in enhancing bone fracture healing is through the up-regulating bone matrix mineralization.

血管周细胞在表达PDGF-B的实体瘤中诱发造血

背景与目的肿瘤组织持续生长需要红细胞充分供氧。在各类病理生理情况下,成年哺乳动物可在主要造血器官骨髓之外发生髓外造血。然而,肿瘤组织能否造血是完全未知的。大量证据表明,在肿瘤微环境中,血管周细胞保留了祖细胞特性,可分化成其他细胞类型。在此,我们探究了肿瘤组织内周细胞是否能调节造血及其作用机制。方法使用鼠源周细胞进行全基因组表达谱分析以测试周细胞是否可向红细胞分化。使用NG2-CreERT2:R26R-tdTomato小鼠对血管周细胞进行在体遗传示踪。使用流式细胞术、单细胞测序和集落形成实验对分选细胞进行鉴定。使用定量聚合酶链反应(quantitative polymerase chain reactionq,PCR)、酶联免疫吸附实验(enzyme-linked immunosorbent assay,ELISA)、细胞磁珠分选和免疫染色检查红细胞生成素(erythropoietin,EPO)的表达。构建骨髓移植小鼠模型以研究骨髓对肿瘤红细胞生成的影响。结果表达谱显示,在PDGF-B处理后,NG2+周细胞表现出造血干祖样特征,并向红系谱系分化。同时,PDGF-B可靶向癌症相关成纤维细胞以产生促红细胞生成的关键激素EPO。通过遗传示踪及流式分析,我们定义了NG2+细胞衍生的造血亚群。进一步的单细胞测序和集落形成实验结果显示,在PDGF-B刺激下,肿瘤中的NG2+细胞形成了与典型的骨髓造血干细胞不同的红系祖细胞。结论本研究提出了肿瘤组织内造血的新概念,并阐明肿瘤周细胞分化为红细胞的分子机制。靶向肿瘤造血作为一种新的治疗理念,可能对肿瘤治疗产生深远影响。

A survey of web resources and tools for the study of TCM network pharmacology

Background: Traditional Chinese medicine (TCM) treats diseases in a holistic manner, while TCM formulae are multi-component, multi-target agents at the molecular level. Thus there are many parallels between the key ideas of TCM pharmacology and network pharmacology. These years, TCM network pharmacology has developed as an interdisciplinary of TCM science and network pharmacology, which studies the mechanism of TCM at the molecular level and in the context of biological networks. It provides a new research paradigm that can use modern biomedical science to interpret the mechanism of TCM, which is promising to accelerate the modernization and internationalization of TCM? Results: In this paper we introduce state-of-the-art free data sources, web servers and softwares that can be used in the TCM network pharmacology, including databases of TCM, drug targets and diseases, web servers for the prediction of drug targets, and tools for network and functional analysis. Conclusions: This review could help experimental pharmacologists make better use of the existing data and methods in their study of TCM.

Can amino-functionalized carbon nanotubes carry functional nerve growth factor?

Carbon nanotubes can carry protein into cells to induce biological effects. Amino-functionalized carbon nanotubes are soluble and biocompatible, have high reactivity and low toxicity, and can help promote nerve cell growth. In this study, amino-functionalized ethylenediamine-treated multi-walled carbon nanotubes were used to prepare carbon nanotubes-nerve growth factor complexes by non-covalent grafting. The physicochemical properties, cytotoxicity to PC12 and chick embryo dorsal root ganglion, and biological activity of the carbon nanotubes-nerve growth factor complexes were investigated. The results showed that amino functionalization improved carbon nanotubes-nerve growth factor complex dispersibility, reduced their toxicity to PC12 cells, and promoted PC 12 cell differentiation and chick embryo dorsal root ganglion.

A new ent-labdane diterpenoid lactone from Andrographis paniculata

A new ent-labdane diterpenoid lactone was isolated from Andrographis paniculata.Its structure was identified on the basis of spectral data including 2D NMR.

NONTRIVIAL SOLUTIONS FOR SEMILINEAR SCHRDINGER EQUATIONS

The authors prove the existence of nontrivial solutions for the SchrSdinger equation -△u ＋ V（x）u =λf（x, u） in R^N, where f is superlinear, subcritical and critical at infinity, respectively, V is periodic.

Anti-nociceptive Effect of Patchouli Alcohol: Involving Attenuation of Cyclooxygenase 2 and Modulation of Mu-Opioid Receptor

Objective: To explore the anti-nociceptive effect of patchouli alcohol(PA), the essential oil isolated from Pogostemon cablin(Blanco) Bent, and determine the mechanism in molecular levels. Methods: The acetic acid-induced writhing test and formalin-induced plantar injection test in mice were employed to con?rm the effect in vivo. Intracellular calcium ion was imaged to verify PA on mu-opioid receptor(MOR). Cyclooxygenase 2(COX2)and MOR of mouse brain were expressed for determination of PA’s target. Cellular experiments were carried out to find out COX2 and MOR expression induced by PA. Results: PA significantly reduced latency period of visceral pain and writhing induced by acetic acid saline solution(P<0.01) and allodynia after intra-plantar formalin(P<0.01) in mice. PA also up-regulated COX2 mRNA and protein(P<0.05) with a down-regulation of MOR(P<0.05) both in in vivo and in vitro experiments, which devote to the analgesic effect of PA. A decrease in the intracellular calcium level(P<0.05) induced by PA may play an important role in its anti-nociceptive effect.PA showed the characters of enhancing the MOR expression and reducing the intracellular calcium ion similar to opioid effect. Conclusions: Both COX2 and MOR are involved in the mechanism of PA’s anti-nociceptive effect,and the up-regulation of the receptor expression and the inhibition of intracellular calcium are a new perspective to PA’s effect on MOR.

Simultaneous Determination of 10 Anthraquinones in Rhubarb Based on HPLC-Q-HR/MS

Objective To develop a simple, sensitive, and precise method for simultaneous determination of 10 anthraquinones in Rhubarb. Methods HPLC-Q-HR/MS was employed for simultaneous quantification of free anthraquinones（aloe-emodin, emodin, chrysophanol, physcion, and rhein） and their glycosides. Chromatographic analysis was performed on an XBridge^（TM） C_（18） column（2.1 mm × 150 mm, 5 μm） with mobile phases consisting of 3 mmol/L ammonium acetate（A） and methanol（B） at a flow rate of 0.3 mL/min. Results All calibration curves exhibited good linear relationship（R^2 〉 0.999）. The limits of detection（LOD） and quantification（LOQ） were in the range of0.39-2.97 ng/mL and 0.56-8.90 ng/mL, respectively. The overall intra-and inter-day precisions of analytes presented as relative standard deviations（RSDs） were less than 2.79%. Relative recoveries varied between 97.83% and 104.28%. The validated method was applied to assess the quality of Rhubarb collected from different regions of China. Results showed that chrysophanol and rhein-8-O-β-D-glucoside was the largest portion of free anthraquinones and anthraquinone glycosides in Rhubarb, respectively. The total content of anthraquinones was higher in Rhubarbs from Sichuan, Qinghai, Yunnan, and Gansu provinces than that in those from Shandong and Henan provinces, while no significant variability existed in different regions of the same province.Conclusion HPLC-Q-HR/MS method is accurate and reliable for simultaneous quantification of above free anthraquinones and their glycosides in Rhubarb and can be applied to standardize the quality of Rhubarb and its quality control in different regions.

Biomechanical assessment of aortic valve stenosis:Advantages and limitations

Aortic valve stenosis(AS)is a frequent and potentially severe disease of the heart.Accurate assessment of AS is a critical factor in determining prognosis and treatment.This paper describes the advantages and limitations of AS assessment from a biomechanical engineering perspective,by contrasting the non-invasive AS diagnostic methods of echocardiography(Echo),computed tomography(CT),magnetic resonance imaging(MRI),computational analysis(CA)including the invasive technique of cardiac catheterization.The findings illustrated that current methods of AS evaluation,with assumptions of an ideal fluid,geometry and governing equations may not apply well to the aortic valve pathology and could increase the uncertainty of the degree of stenosis and valve area.This review suggests an alternative method using CA,which could potentially overcome the pitfalls of other AS assessments that incorporate geometry,pressure recovery and aorta wall compliance,based on the accurate conversion of AS imaging to the numerical modelling.Further,this review highlights the importance of CA boundary conditions,and the role of verification and validation to produce reliable computational results.

Perivascular localized cells commit erythropoiesis in PDGF-B-expressing solid tumors

Background:Tumors possess incessant growth features,and expansion of their masses demands sufficient oxygen supply by red blood cells(RBCs).In adult mammals,the bone marrow(BM)is the main organ regulating hematopoiesis with dedicated manners.Other than BM,extramedullary hematopoiesis is discovered in various pathophysiological settings.However,whether tumors can contribute to hematopoiesis is completely unknown.Accumulating evidence shows that,in the tumor microenvironment(TME),perivascular localized cells retain progenitor cell properties and can differentiate into other cells.Here,we sought to better understand whether and how perivascular localized pericytes in tumors manipulate hematopoiesis.Methods:To test if vascular cells can differentiate into RBCs,genome-wide expression profiling was performed using mouse-derived pericytes.Genetic tracing of perivascular localized cells employing NG2-CreERT2:R26R-tdTomato mouse strain was used to validate the findings in vivo.Fluorescence-activated cell sorting(FACS),single-cell sequencing,and colony formation assays were applied for biological studies.The production of erythroid differentiationspecific cytokine,erythropoietin(EPO),in TME was checked using quantitative polymerase chain reaction(qPCR),enzyme-linked immunosorbent assay(ELISA,magnetic-activated cell sorting and immunohistochemistry.To investigate BM function in tumor erythropoiesis,BM transplantation mouse models were employed.Results:Genome-wide expression profiling showed that in response to plateletderived growth factor subunit B(PDGF-B),neural/glial antigen 2(NG2)+perivascular localized cells exhibited hematopoietic stem and progenitor-like features and underwent differentiation towards the erythroid lineage.PDGF-B simultaneously targeted cancer-associated fibroblasts to produce high levels of EPO,a crucial hormone that necessitates erythropoiesis.FACS analysis using genetic tracing of NG2+cells in tumors defined the perivascular localized cell-derived subpopulation of hematopoietic cells.Single-cell sequencing and colony formation assays validated the fact that,upon PDGF-B stimulation,NG2+cells isolated from tumors acted as erythroblast progenitor cells,which were distinctive from the canonical BM hematopoietic stem cells.Conclusions:Our data provide a new concept of hematopoiesis within tumor tissues and novel mechanistic insights into perivascular localized cell-derived erythroid cells within TME.Targeting tumor hematopoiesis is a novel therapeutic concept for treating various cancers that may have profound impacts on cancer therapy.

Panax notoginseng saponins prevent colitis-associated colorectal cancer via inhibition IDO1 mediated immune regulation

Colorectal cancer(CRC)is the third most lethal cancer and leading cause of cancer mortality worldwide.A key driver of CRC development is colon inflammatory responses especially in patients with inflammatory bowl disease(IBD).It has been proved that Panax notoginseng saponins(PNS)have anti-inflammatory,anti-oxidant and anti-tumor effects.The chemopreventive and immunomodulatory functions of PNS on colitis-associated colorectal cancer(CAC)have not been evaluated.This present study was designed to study the potential protective effects of PNS on AOM/DSS-induced CAC mice to explore the possible mechanism of PNS against CAC.Our study showed that PNS significantly alleviated colitis severity and prevented the occurrence of CAC.Functional assays revealed that PNS relieved immunosuppression of Treg cells in the CAC microenvironment by inhibiting the expression of IDO 1 mediated directly by signal transducer and activator of transcription 1(STAT1)rather than phosphorylated STAT1.Ultimately,Rhl,one of the PNS metabolites,exhibited the best inhibitory effect on IDO1 enzyme activity.Our study showed that PNS exerted significant chemopreventive function and immunomodulatory properties on CAC.It could reduce macrophages accumulation and Treg cells differentiation to reshape the immune microenvironment of CAC.These findings provided a promising approach for CAC intervention.