HHT和HMM在血细胞信号识别中的应用

针对血细胞信号具有多形态、非线性、非平稳的特点,提出将希尔伯特黄变换(HHT)和隐马尔可夫模型(HMM)相结合的血细胞信号识别方法。该方法采用HHT对血细胞信号进行分析,选取经过经验模态分解得到的各本质模态函数中相关性较大的分量,以这些分量的能量矩作为信号的特征量,由HMM训练得到正常人和病患者的模型参数并用做分类识别。实验结果表明,该方法可以较好地识别正常人和病患者的血细胞信号,综合准确率达89.13%。

基于Nios Ⅱ的血细胞信号识别算法研究

本文研究一种基于SOPC的智能血细胞信号识别处理的算法，并在Altera公司的DE2开发平台上实现。脉冲信号的识别与统计作为系统的核心部分利用Mos Ⅱ CPU实现。经过实际测试表明，本系统能有效地识别出单细胞信号以及双细胞信号造成的M信号，有效地避免了干扰脉冲信号的误计数。

化痰通络颗粒对脑梗死患者外周血细胞因子信号转导抑制因子-3及肿瘤坏死因子-α的影响

目的观察化痰通络颗粒对风痰瘀阻型急性脑梗死(ACI)患者外周血细胞因子信号转导抑制因子-3(SOCS-3)及肿瘤坏死因子-α(TNF-α)表达的影响。方法 66例发病72 h内的风痰瘀阻型ACI患者随机分为两组,治疗组34例口服化痰通络颗粒加基础治疗,对照组32例仅基础治疗;用酶联免疫分析法(ELISA)测定两组ACI患者治疗前及治疗后第3、7天血清SOCS-3水平,用化学发光法检测两组治疗前及治疗后第7天血清TNF-α水平,并与20名健康人作比较,同时用Barthel指数、NIHSS评分法评价两组治疗前及治疗后第7、14、21天神经功能缺损程度的变化。结果两组患者治疗前及治疗后第3、7天血清SOCS-3、治疗前及治疗后第7天TNF-α水平均显著高于健康人组(P<0.05)。治疗第7天时治疗组SOCS-3水平(ng/L,360.98±123.31)高于对照组(281.87±133.66,P<0.05),TNF-α水平(ng/L,35.72±19.94)低于对照组(49.86±34.79,P<0.05);治疗第7、14天时治疗组NIHSS评分低于对照组(P<0.05),Barthel指数评分治疗组治疗后第14、21天高于对照组(P<0.05)。结论化痰通络颗粒促进风痰瘀阻型ACI患者神经功能恢复的作用可能与上调炎症抑制因子SOCS-3与下调促炎因子TNF-α水平,减轻脑缺血继发的炎症损伤等机制密切相关。

免疫相关基因HCST对肾透明细胞癌预后的影响及其机制

目的:分析造血细胞信号转导因子(hematopoietic cell signal transducer, HCST)在肾透明细胞癌(clear cell renal cell carcinoma, ccRCC)中的表达及与ccRCC预后、免疫浸润的关系,探讨HCST对ccRCC细胞生长侵袭的影响及其作用机制。方法:利用TCGA数据库分析HCST基因在ccRCC组织中的表达水平。Cox比例风险模型分析HCST表达水平及临床特征与ccRCC患者预后的关系。肿瘤免疫评分数据库(tumor immune estimation resource, TIMER)分析ccRCC组织中HCST表达水平与免疫细胞浸润程度的相关性。体外培养ACHN细胞,分为对照组、siRNA阴性对照组和HCST siRNA组。MTT法、流式细胞实验和Transwell实验分别检测各组ACHN细胞增殖、凋亡和侵袭活性。蛋白质印迹法检测caspase-3、Bax、Bcl-2、E-cadherin、N-cadherin和Vimentin蛋白的表达。结果:与正常肾脏组织比较,HCST mRNA在ccRCC组织中的表达显著上调,且与肿瘤的分期、淋巴转移及远处转移正相关(P<0.01)。HCST高表达、肿瘤T分期及M分期是影响ccRCC患者预后的独立危险因素(P<0.05)。ccRCC中HCST表达与CD8^(+)T细胞、树突状细胞、NK细胞及Treg细胞的浸润程度正相关(P<0.001)。与对照组比较,HCST siRNA组ACHN细胞的增殖活性、侵袭能力、Bcl-2、N-cadherin和Vimentin蛋白表达水平显著降低(P<0.05),ACHN细胞凋亡活性、caspase-3、Bax和E-cadherin蛋白表达水平显著升高(P<0.05)。siRNA阴性对照组与对照组比较上述各指标,差异无统计学意义(P<0.05)。结论:HCST在ccRCC中表达上调,且与ccRCC患者的免疫浸润和预后相关。沉默HCST的表达可抑制ccRCC细胞的增殖与侵袭、促进其凋亡。

HHT在血细胞特征提取中的应用

提出一种基于Hilbert-Huang变换(HHT)的特征分析方法,该方法将血细胞信号进行经验模态分解和Hilbert变换,提取信号的平均强度、频谱质心和能量贡献率作为频域特征,与信号的时域特征结合,最终完成血细胞特征向量对脉冲信号的统计和识别。仿真实验中,使用HHT的识别算法正确率由模拟电路法的72.33%提高至94.33%;而使用该算法的血细胞分析仪与奥菲MYTHIC 18的可比性合格率达到98.5%,分类相关性系数都在94%以上。实验结果表明,该方法能提高仪器的计数正确度和分类准确性。

N-methyl-D-aspartate receptors mediate diphosphorylation of extracellular signal-regulated kinases through Src family tyrosine kinases and Ca^2＋/calmodulin-dependent protein kinase Ⅱ in rat hippocampus after cerebral ischemia

Objective： Extracellular signal-regulated kinases （ERKs） can be activated by calcium signals. In this study, we investigated whether calcium-dependent kinases were involved in ERKs cascade activation after global cerebral ischemia. Methods Cerebral ischemia was induced by four-vessel occlusion, and the calcium-dependent proteins were detected by immunoblot. Results Lethal-simulated ischemia significantly resulted in ERKs activation in N-methyl-D-aspartate （NMDA） receptor-dependent manner, accompanying with differential upregulation of Src kinase and Ca^2＋/calmodulin-dependent protein kinase Ⅱ （CaMKⅡ） activities. With the inhibition of Src family tyrosine kinases or CaMKⅡ by administration of PP2 or KN62, the phosphorylation of ERKs was impaired dramatically during post-ischemia recovery. However, ischemic challenge also repressed ERKs activity when Src kinase was excessively activated. Conclusions Src family tyrosine kinases and CaMKⅡ might be involved in the activation of ERKs mediated by NMDA receptor in response to acute ischemic stimuli in vivo, but the intense activation of Src kinase resulted from ischemia may play a reverse role in the ERKs cascade.

外周血SOCS-1的表达及与慢性丙型肝炎自身免疫现象的关系

目的探讨慢性丙型肝炎病毒(HCV)感染者体内外周血细胞因子信号转导抑制因子-1(SOCS-1)和自身免疫现象的关系。方法选取78例HCV感染者及40例健康对照者,分为健康对照组、慢性丙肝有自身免疫现象组和慢性丙肝无自身免疫现象组,以及肝硬化组及非肝硬化组,检测肝功能、HCV RNA、自身抗体、免疫球蛋白、肝纤维化4项及SOCS-1 mRNA水平。结果 HCV感染者有自身免疫现象组血清SOCS-1 mRNA水平较其他两组显著降低(P<0.05);SOCS-1 mRNA水平与谷丙转氨酶(ALT)、HCV RNA、IgG、IgA、IgM无相关性,与肝纤维化4项中透明质酸(HA)、Ⅲ型前胶原(PcⅢ)、屈黏蛋白(LN)有相关性。结论 SOCS-1表达降低可能是刺激机体产生自身免疫现象的原因。

Molecular signal transduction in vascular cell apoptosis

Apoptosis is a form of genetically programmed cell death, which plays a key role in regulation of cellularity in a variety of tissue and cell types including the cardiovascular tissues. Under both physiological and pathophysiological conditions, various biophysiological and biochemical factors, including mechanical forces, reactive oxygen and nitrogen species, cytokines, growth factors, oxidized lipoproteins, etc., may influence apoptosis of vascular cells. The Fas/Fas ligand/caspase death-signaling pathway, Bcl-2 protein family/mitochondria, the tumor suppressive gene p53, and the proto-oncogene c-myc may be activated in atherosclerotic lesions, and mediates vascular apoptosis during the development of atherosclerosis. Abnormal expression and dysfunction of these apoptosis-regulating genes may attenuate or accelerate vascular cell apoptosis and affect the integrity and stability of atherosclerotic plaques. Clarification of the molecular mechanism that regulates apoptosis may help design a new strategy for treatment of atherosclerosis and its major complication, the acute vascular syndromes.

Inhibition of methionine adenosyltransferase II induces FasL expression, Fas-DISC formation and caspase-8-dependent apoptotic death in T leukemic cells

Methionine adenosyltransferase Ⅱ（MAT Ⅱ） is a key enzyme in cellular metabolism and catalyzes the formation of S-adenosylmethionine （SAMe） from L-methionine and ATE Normal resting T lymphocytes have minimal MAT Ⅱ activity, whereas activated proliferating T lymphocytes and transformed T leukemic cells show significantly enhanced MAT Ⅱ activity. This work was carried out to examine the role of MAT Ⅱ activity and SAMe biosynthesis in the survival of leukemic T cells. Inhibition of MAT Ⅱ and the resultant decrease in SAMe levels enhanced expression of FasL mRNA and protein, and induced DISC （Death Inducing Signaling Complex） formation with FADD （Fasassociated Death Domain） and procaspase-8 recruitment, as well as concomitant increase in caspase-8 activation and decrease in c-FLIPs levels. Fas-initiated signaling induced by MAT Ⅱ inhibition was observed to link to the mitochondrial pathway via Bid cleavage and to ultimately lead to increased caspase-3 activation and DNA fragmentation in these cells. Furthermore, blocking MAT 2A mRNA expression, which encodes the catalytic subunits of MAT Ⅱ, using a small-interfering RNA approach enhanced FasL expression and cell death, validating the essential nature of MAT Ⅱ activity in the survival of T leukemic cells.

Switching-on of serotonergic calcium signaling in activated hepatic stellate cells

AIM:To investigate serotonergic Ca 2+ signaling and the expression of 5-hydroxytryptamine(5-HT) receptors,as well as Ca 2+ transporting proteins,in hepatic stellate cells(HSCs) . METHODS:The intracellular Ca 2+ concentration([Ca 2+ ]i) of isolated rat HSCs was measured with a fluorescence microscopic imaging system.Quantitative PCR was per-formed to determine the transcriptional levels of 5-HT receptors and endoplasmic reticulum(ER) proteins involved in Ca 2+ storage and release in cultured rat HSCs. RESULTS:Distinct from quiescent cells,activated HSCs exhibited[Ca 2+ ]i transients following treatment with 5-HT,which was abolished by U-73122,a phospholipase C inhibitor.Upregulation of 5-HT2A and 5-HT2B receptors,but not 5-HT3,was prominent during trans-differentiation of HSCs.Pretreatment with ritanserin,a 5-HT2 antagonist,inhibited[Ca 2+ ]i changes upon application of 5-HT.Expression of type 1 inositol-5'-triphosphate receptor and type 2 sarcoplasmic/endoplasmic reticulum Ca 2+ ATPase were also increased during activation of HSCs and serve as the major isotypes for ER Ca 2+ storage and release in activated HSCs.Ca 2+ binding chaperone proteins of the ER,including calreticulin,calnexin and calsequestrin,were up-regulated following activation of HSCs. CONCLUSION:The appearance of 5-HT-induced[Ca 2+ ]i response accompanied by upregulation of metabotropic 5-HT2 receptors and Ca 2+ transporting/chaperone ER proteins may participate in the activating process of HSCs.

Baicalin inhibits PDGF-BB-stimulated vascular smooth muscle cell proliferation through suppressing PDGFRβ-ERK signaling and increase in p27 accumulation and prevents injury-induced neointimal hyperplasia

The increased proliferation and migration of vascular smooth muscle cells （VSMCs） are key events in the development of atherosclerotic lesions. Baicalin, an herb-derived flavonoid compound, has been previously shown to induce apoptosis and growth inhibition in cancer cells through multiple pathways. However, the potential role of baicalin in regulation of VSMC proliferation and prevention of cardiovascular diseases remains unexplored. In this study, we show that pretreatment with baicalin has a dose-dependent inhibitory effect on PDGF-BB-stimulated VSMC pro- liferation, accompanied with the reduction of proliferating cell nuclear antigen （PCNA） expression. We also show that baicalin-induced growth inhibition is associated with a decrease in cyclin E-CDK2 activation and increase in p27 level in PDGF-stimulated VSMCs, which appears to be at least partly mediated by blockade of PDGF recep- tor [~ （PDGFR~）-extracellular signal-regulated kinase 1/2 （ERK1/2） signaling. In addition, baicalin was also found to inhibit adhesion molecule expression and cell migration induced by PDGF-BB in VSMCs. Furthermore, using an animal carotid arterial balloon-injury model, we found that baicalin significantly inhibited neointimal hyperplasia. Taken together, our results reveal a novel function of baicalin in inducing growth arrest of PDGF-stimulated VSMCs and suppressing neointimal hyperplasia after balloon injury, and suggest that the underlying mechanism involves the inhibition of cyclin E-CDK2 activation and the increase in p27 accumulation via blockade of the PDGFR^-ERK1/2 signaling cascade.

Glycer-AGEs-RAGE signaling enhances the angiogenic potential of hepatocellular carcinoma by upregulating VEGF expression

AIM:To investigate the effect of glyceraldehyde-derived advanced glycation end-products(Glycer-AGEs) on hepatocellular carcinoma(HCC)cells.METHODS:Two HCC cell lines(Hep3B and HepG2 cells)and human umbilical vein endothelial cells(HUVEC)were used.Cell viability was determined using the WST-8 assay.Western blotting,enzyme linked immunosorbent assay,and real-time reverse transcriptionpolymerase chain reactions were used to detect protein and mRNA.Angiogenesis was evaluated by assessing the proliferation,migration,and tube formation of HUVEC.RESULTS:The receptor for AGEs(RAGE)protein was detected in Hep3B and HepG2 cells.HepG2 cells werenot affected by the addition of Glycer-AGEs.GlycerAGEs markedly increased vascular endothelial growth factor(VEGF)mRNA and protein expression,which is one of the most potent angiogenic factors.Compared with the control unglycated bovine serum albumin(BSA) treatment,VEGF mRNA expression levels induced by the Glycer-AGEs treatment were 1.00±0.10 vs 1.92 ±0.09(P<0.01).Similarly,protein expression levels induced by the Glycer-AGEs treatment were 1.63±0.04 ng/mL vs 2.28±0.17 ng/mL for the 24 h treatment and 3.36±0.10 ng/mL vs 4.79±0.31 ng/mL for the 48 h treatment,respectively(P<0.01).Furthermore,compared with the effect of the control unglycated BSA-treated conditioned medium,the Glycer-AGEstreated conditioned medium significantly increased the proliferation,migration,and tube formation of HUVEC,with values of 122.4%±9.0%vs 144.5%±11.3%for cell viability,4.29±1.53 vs 6.78±1.84 for migration indices,and 71.0±7.5 vs 112.4±8.0 for the number of branching points,respectively(P<0.01).CONCLUSION:These results suggest that Glycer-AGEs-RAGE signaling enhances the angiogenic potential of HCC cells by upregulating VEGF expression.

Recombinant adeno-associated virus serotype 9 with p65 ribozyme protects H9c2 cells from oxidative stress through inhibiting NF-κB signaling pathway

Background Oxidative stress is a major mechanism underlying the pathogenesis of cardiovascular disease. It can trigger inflammatory cascades which are primarily mediated via nuclear factor-κB （NF-κB）. The NF-κB transcription factor family includes several subunits （p50, p52, p65, c-Rel, and Rel B） that respond to myocardial ischemia. It has been proved that persistent myocyte NF-κB p65 activation in heart failure exacerbates cardiac remodeling. Mechods A recombinant adeno-associated virus serotype 9 carrying enhanced green fluorescent protein and anti-NF-κB p65 ribozyme （AAV9-R65-CMV-eGFP） was constructed. The cells were assessed by MTT assay, Annexin V–propidium iodide dual staining to study apoptosis. The expression of P65 and P50 were assessed by Western blot to investigate the under-lying molecular mechanisms. Results After stimulation with H2O2 for 6 h, H9c2 cells viability decreased significantly, a large fraction of cells underwent apoptosis. We observed a rescue of H9c2 cells from H2O2-induced apoptosis in pretreatment with AAV9-R65-CMV-eGFP. Moreover, AAV9-R65-CMV-eGFP decreased H2O2-induced P65 expression. Conclusions AAV9-R65-CMV-eGFP protects H9c2 cells from oxidative stress induced apoptosis through down-regulation of P65 expression. These observations indicate that AAV9-R65-CMV-eGFP has the potential to exert cardioprotective effects against oxidative stress, which might be of great importance to clinical efficacy for cardiovascular disease.

STAT1 is involved in signal transduction in the EPOinduced HEL cells

Erythropoietin (EPO) is the ma jor regulator of mammalian erythropoisis, which stimulates the growth and differentiation of hematopoietic cells through interaction with its receptor (EPO-R). Here we use HEL cells (a human erythro-leukemia cell line) as a model to elucidate the pathway of signal transduction in the EPO-induced HEL cells. our data show that the EPOR (EPO receptor) on the surface of HEL cells interacts with the Janus tyrosine protein kinase (Jak2) to transduce intracellular signals through phosphorylation of cytoplasmic proteins in EPO-treated HEL cells. Both STAT1 and STAT5 in this cell line are tyrosine-phosphorylated and translocated to nucleus following the binding of EPO to HEL cells.Furthermore, the binding of both STAT1 and STAT5 proteins to specific DNA elements (SIE and PIE elements) is revealed in an EPO-dependent manner. Our data demonstrate that the pathway of signal transduction following the binding of EPO to HEL cells is similar to immature erythroid cell from the spleen of mice infected with anemia strain of Friend virus.

hVEGF165 Expression in Escherichia coli Conserves Its Biological Function

The paper describes the expression of human protein VEGF165 in Escherichia coli and its purification. This growth factor isoform contains exon 7, which is essential for binding to extracellular domain of VEGF receptor 2, located on endothelial cells lining the surface of blood vessels. This binding stimulates the cascade of downstream signalling events leading to process known as angiogenesis, hVEGF165 overexpressed with His-tag in BL21 E. coli cells forms inclusion bodies （insoluble protein）, so the research found the procedure for its solubilization and purification on a Nickel based affinity chromatography. Although this eukaryotic signal protein needs posttranslational processing for its full function as a homodimer, author verified the biological activity of our hVEGF165 protein, obtained as monomer, by wound healing test.

Monocyte-secreted Wnt5a interacts with FZD5 in microvascular endothelial cells and induces angiogenesis through tissue factor signaling

Angiogenesis during reactive and pathologic processes is characteristically associated with inflammation. Inflammatory cells partici- pate in angiogenesis by secreting different molecules that affect endothelial celt functions. We had previously shown that induced tissue factor （TF） expression in activated rnicrovascular endothelial celts （rn EC） is able to induce angiogenesis via autocrine regulation. However, the signals that induce TF expression in mEC are not fully known. Here, we demonstrate that rnonocyte paracrine cross-talk with mECs triggers rnEC-TF expression. We have identified that rnonocyte-secreted Wnt5a induces TF expression in rnEC and function-ally induces celt rnonolayer repair and angiotube formation in vitro as well as rnicrovesset formation in vivo. Monocyte-secreted Wnt5a activates FZD5 in mECs, which signals to induce the release of intraceUular Ca2＋ and increase NFKB transcription activity and TF gene expression. In sum, WntSa secreted by monocytes signals through the noncanonical Wnt-FZD5 pathway in mECs to induce TF expression that induces angiogenesis by autocrine regulation.

On signaling pathways: hematopoietic stem cell specification from hemogenic endothelium

Hematopoietic stem cells(HSCs) are specified and generated during the embryonic development and have remarkable potential to replenish the full set of blood cell lineages. Researchers have long been interested in clarifying the molecular events involved in HSC specification. Many studies have reported the development of methods for generating functional hematopoietic cells from pluripotent stem cells(PSCs-embryonic stem cells(ESCs) and induced pluripotent stem cells(i PSCs)) for decades. However, the generation of HSCs with robust long-term repopulation potential remains a swingeing challenge, of which a major factor contributing to this failure is the difficulty to define the intraembryonic signals related to the specification of HSCs. Since HSCs directly derive from hemogenic endothelium, in this review, we summarize both in vivo and in vitro studies on conserved signaling pathways that control the specification of HSCs from hemogenic endothelial cells.

IP3R-mediated Ca2＋ signals govern hematopoietic and cardiac divergence of Flk1＋ cells via the calcineurin-N FATc3-Etv2 pathway

Ca2＋ signals participate in various cellular processes with spatial and temporal dynamics, among which, inositol 1,4,5-trisphosphate receptors （IP3Rs）-mediated Ca2＋ signals are essential for early development. However, the underlying mechanisms of IP3R- regulated cell fate decision remain largely unknown. Here we report that IP3Rs are required for the hematopoietic and cardiac fate divergence of mouse embryonic stem cells （mESCs）. Deletion of IP3Rs （IP3R-tKO） reduced FIkl＋/PDGFRα- hematopoietic mesoderm, c-Kit＋/CD41＋ hematopoietic progenitor ceil population, and the colony-forming unit activity, but increased cardiac progenitor markers as well as cardiomyocytes. Concomitantly, the expression of a key regulator of hematopoiesis, Ely2, was reduced in IP3R-tKO cells, which could be rescued by the activation of Ca2＋ signals and calcineurin or overexpression of constitutively active form of NFATc3. Furthermore, IP3R-tKO impaired specific targeting of Ely2 by NFATc3 via its evolutionarily conserved cis-element in differentiating ESCs. Importantly, the activation of Ca2＋-calcineurin-NFAT pathway reversed the phenotype of IP3R-tKO cells. These findings reveal an unrecognized governing role of IP3Rs in hematopoietic and cardiac fate commitment via IP3Rs-Ca2＋-calcineurin-NFATc3- Etv2 pathway.

Effect of penehyclidine hydrochloride on patients with acute lung injury and its mechanisms

Objective： To assess the effects of penehyclidine hydrochloride on patients with acute lung injury （ALI）, to observe the expression of Toll-like receptor 4 （TLR4） on the peripheral monocytes of ALI patients and changes of inflammatory ＆ anti-inflammatory cytokines and to investigate the mechanism of TLR4 in ALI.Methods： Forty-five patients with ALI were randomly divided into penehyclidine hydrochloride treatment group （P group, n=21） and conventional treatment group （control group, C group, n=24）. Patients in both groups received conventional treatment, including active treatment of the primary disease, respiratory support, nutritional support and fluid management therapy, while those in P group were given penehyclidine hydrochloride （1 mg, im, q. 12 h） in addition.The TLR4 expression of 20 healthy volunteers were detected.The clinical effect, average length of stay in ICU and hospital,values of PaO2 and PaO2/FiO2, expression of TLR4 on the surface of peripheral blood mononuclear cells and some serum cytokines were evaluated for 48 h.Results： The general conditions of the two groups were improved gradually and PaO2 increased progressively.Compared with 0 h, PaO2 and PaO2/FiO2 at 6, 12, 24 and 48 h after treatment were significantly increased （P＜0.05）. The improvement in P group was obviously greater than that in C group （P＜0.05）. The average length of hospitalization showed no difference between the two groups, but penehyclidine hydrochloride significantly decreased the average length of stay in ICU （t=3.485, P＜0.01）. The expression of TLR4 in two groups were both obviously higher than that of healthy volunteers （P＜0.01）. It decreased significantly at 24 h （t=2.032, P＜0.05） and 48 h （t=3.620, P＜0.01）and was lower in P group than in C group. The patients who showed a higher level of TLR4 expression in early stage had a worse prognosis and most of them developed acute respiratory distress syndrome （ARDS）. The incidence of ARDS was 23.8% in P group and 29.17% in C group at 24 h.Until148 h, there were other two patients developing ARDS in control group. Serum IL-l, IL-8 and TNF-α expressions reduced after 24 h in both groups. The reduction in P group was more obvious than that in C group （P＜0.05）. IL-13 increased gradually from 0 h to 24 h, and decreased slightly at 48 h, which showed no difference between two groups （t=1.028, P＞0.05）.Conclusions： Penehyclidine hydrochloride improves the arterial oxygen pressure, down-regulates the expression of TLR4 and restrains the inflammatory cytokines in the downstream of TLR4 signaling pathway. It prevents the development of ALI and can be considered as an important drug in ALI treatment.

Transportation of dynamic biochemical signals in non-reversing oscillatory flows in blood vessels

Biological processes and behaviors of endothelial cells on the inner surfaces of blood vessels are regulated by the stimulation from biochemical signals contained in the blood.In this paper,the transportation of dynamic biochemical signals in non-reversing oscillatory flows in blood vessels is analyzed by numerically solving a nonlinear governing equation for the time-dependent Taylor-Aris dispersion.Results show that the nonlinear frequency-amplitude modulation of the transportation of biochemical signals is more(less) significant when the frequency of an oscillatory flow is close to(higher than) that of an oscillatory signal.Under steady flow,the transfer function for the signal transmission system is obtained,showing that the system is a low-pass filter.Lower inner radius or higher center-line velocity of a blood vessel increases the cutoff frequency of the transportation system.These results suggest the possibility and condition for the 'remote' transmission of low-frequency dynamic biochemical signals in pulsatile blood flows.