1451: Positive Efect of Prostaglandin on Regulation of Prostate Blood Flow-Investigation of the Key Factor in the Signaling Pathway of The Prostate Blood Flow-

2005 ◽  
Vol 173 (4S) ◽  
pp. 393-393
Author(s):  
Bunzo Kashiwagi ◽  
Yasuhiro Shibata ◽  
Kazunari Ohki ◽  
Seiji Arai ◽  
Seijiro Honma ◽  
...  
Keyword(s):  
Blood Flow ◽  
Signaling Pathway ◽  
Flow Investigation ◽  
Key Factor

scholarly journals Advanced Constitutive Modeling of the Thixotropic Elasto-Visco-Plastic Behavior of Blood: Steady-State Blood Flow in Microtubes

Materials ◽  
2021 ◽  
Vol 14 (2) ◽  
pp. 367
Author(s):  
Konstantinos Giannokostas ◽  
Yannis Dimakopoulos ◽  
Andreas Anayiotos ◽  
John Tsamopoulos
Keyword(s):  
Blood Flow ◽  
Steady State ◽  
Constitutive Model ◽  
Blood Plasma ◽  
Constitutive Modeling ◽  
Flow Direction ◽  
Momentum Balance ◽  
Plastic Behavior ◽  
Flow Investigation ◽  
The Impact

The present work focuses on the in-silico investigation of the steady-state blood flow in straight microtubes, incorporating advanced constitutive modeling for human blood and blood plasma. The blood constitutive model accounts for the interplay between thixotropy and elasto-visco-plasticity via a scalar variable that describes the level of the local blood structure at any instance. The constitutive model is enhanced by the non-Newtonian modeling of the plasma phase, which features bulk viscoelasticity. Incorporating microcirculation phenomena such as the cell-free layer (CFL) formation or the Fåhraeus and the Fåhraeus-Lindqvist effects is an indispensable part of the blood flow investigation. The coupling between them and the momentum balance is achieved through correlations based on experimental observations. Notably, we propose a new simplified form for the dependence of the apparent viscosity on the hematocrit that predicts the CFL thickness correctly. Our investigation focuses on the impact of the microtube diameter and the pressure-gradient on velocity profiles, normal and shear viscoelastic stresses, and thixotropic properties. We demonstrate the microstructural configuration of blood in steady-state conditions, revealing that blood is highly aggregated in narrow tubes, promoting a flat velocity profile. Additionally, the proper accounting of the CFL thickness shows that for narrow microtubes, the reduction of discharged hematocrit is significant, which in some cases is up to 70%. At high pressure-gradients, the plasmatic proteins in both regions are extended in the flow direction, developing large axial normal stresses, which are more significant in the core region. We also provide normal stress predictions at both the blood/plasma interface (INS) and the tube wall (WNS), which are difficult to measure experimentally. Both decrease with the tube radius; however, they exhibit significant differences in magnitude and type of variation. INS varies linearly from 4.5 to 2 Pa, while WNS exhibits an exponential decrease taking values from 50 mPa to zero.

scholarly journals Increased tissue oxygenation explains the attenuation of hyperemia upon repetitive pneumatic compression of the lower leg

2017 ◽  
Vol 123 (6) ◽  
pp. 1451-1460 ◽  
Author(s):  
Alessandro Messere ◽  
Gianluca Ceravolo ◽  
Walter Franco ◽  
Daniela Maffiodo ◽  
Carlo Ferraresi ◽  
...  
Keyword(s):  
Blood Flow ◽  
Blood Volume ◽  
Near Infrared ◽  
Tissue Oxygenation ◽  
Femoral Vein ◽  
Lower Leg ◽  
Local Circulation ◽  
Doppler Measurement ◽  
Key Factor ◽  
Interstimulus Intervals

The rapid hyperemia evoked by muscle compression is short lived and was recently shown to undergo a rapid decrease even in spite of continuing mechanical stimulation. The present study aims at investigating the mechanisms underlying this attenuation, which include local metabolic mechanisms, desensitization of mechanosensitive pathways, and reduced efficacy of the muscle pump. In 10 healthy subjects, short sequences of mechanical compressions ( n = 3–6; 150 mmHg) of the lower leg were delivered at different interstimulus intervals (ranging from 20 to 160 s) through a customized pneumatic device. Hemodynamic monitoring included near-infrared spectroscopy, detecting tissue oxygenation and blood volume in calf muscles, and simultaneous echo-Doppler measurement of arterial (superficial femoral artery) and venous (femoral vein) blood flow. The results indicate that 1) a long-lasting (>100 s) increase in local tissue oxygenation follows compression-induced hyperemia, 2) compression-induced hyperemia exhibits different patterns of attenuation depending on the interstimulus interval, 3) the amplitude of the hyperemia is not correlated with the amount of blood volume displaced by the compression, and 4) the extent of attenuation negatively correlates with tissue oxygenation ( r = −0,78, P < 0.05). Increased tissue oxygenation appears to be the key factor for the attenuation of hyperemia upon repetitive compressive stimulation. Tissue oxygenation monitoring is suggested as a useful integration in medical treatments aimed at improving local circulation by repetitive tissue compression. NEW & NOTEWORTHY This study shows that 1) the hyperemia induced by muscle compression produces a long-lasting increase in tissue oxygenation, 2) the hyperemia produced by subsequent muscle compressions exhibits different patterns of attenuation at different interstimulus intervals, and 3) the extent of attenuation of the compression-induced hyperemia is proportional to the level of oxygenation achieved in the tissue. The results support the concept that tissue oxygenation is a key variable in blood flow regulation.

scholarly journals Expression Profile and Prognostic Value of Wnt Signaling Pathway Molecules in Colorectal Cancer

Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1331
Author(s):  
Yung-Fu Wu ◽  
Chih-Yang Wang ◽  
Wan-Chun Tang ◽  
Yu-Cheng Lee ◽  
Hoang Dang Khoa Ta ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Messenger Rna ◽  
Wnt Signaling Pathway ◽  
Interaction Network ◽  
Mrna Levels ◽  
Key Factor ◽  
Canonical Wnt ◽  
Upregulated Genes

Colorectal cancer (CRC) is a heterogeneous disease with changes in the genetic and epigenetic levels of various genes. The molecular assessment of CRC is gaining increasing attention, and furthermore, there is an increase in biomarker use for disease prognostication. Therefore, the identification of different gene biomarkers through messenger RNA (mRNA) abundance levels may be useful for capturing the complex effects of CRC. In this study, we demonstrate that the high mRNA levels of 10 upregulated genes (DPEP1, KRT80, FABP6, NKD2, FOXQ1, CEMIP, ETV4, TESC, FUT1, and GAS2) are observed in CRC cell lines and public CRC datasets. Moreover, we find that a high mRNA expression of DPEP1, NKD2, CEMIP, ETV4, TESC, or FUT1 is significantly correlated with a worse prognosis in CRC patients. Further investigation reveals that CTNNB1 is the key factor in the interaction of the canonical Wnt signaling pathway with 10 upregulated CRC-associated genes. In particular, we identify NKD2, FOXQ1, and CEMIP as three CTNNB1-regulated genes. Moreover, individual inhibition of the expression of three CTNNB1-regulated genes can cause the growth inhibition of CRC cells. This study reveals efficient biomarkers for the prognosis of CRC and provides a new molecular interaction network for CRC.

scholarly journals Gentiopicroside Ameliorates Diabetic Peripheral Neuropathy by Modulating PPAR- Γ/AMPK/ACC Signaling Pathway

2018 ◽  
Vol 50 (2) ◽  
pp. 585-596 ◽  
Author(s):  
Yi Lu ◽  
Jiayin Yao ◽  
Chulian Gong ◽  
Bao Wang ◽  
Piao Zhou ◽  
...  
Keyword(s):  
Blood Flow ◽  
Peripheral Neuropathy ◽  
Signaling Pathway ◽  
Conduction Velocity ◽  
Nerve Conduction ◽  
Diabetic Peripheral Neuropathy ◽  
Nerve Conduction Velocity ◽  
Nerve Blood Flow ◽  
Ppar Γ ◽  
Compound C

Background/Aims: Gentiopicroside is promising as an important secoiridoid compound against pain. The present study aimed to investigate the analgesic effect and the probable mechanism of Gentiopicroside on Diabetic Peripheral Neuropathy (DPN), and to figure out the association among Gentiopicroside, dyslipidemia and PPAR- γ/AMPK/ACC signaling pathway. Methods: DPN rat models were established by streptozotocin and RSC96 cells were cultured. Hot, cold and mechanical tactile allodynia were conducted. Blood lipids, nerve blood flow, Motor Nerve Conduction Velocity (MNCV) and Sensory Nerve Conduction Velocity (SNCV) were detected. Gene and protein expression of PPAR- γ/AMPK/ACC pathway was analyzed by reverse transcription-quan titative polymerase chain reaction (RT-qPCR) and Westernblot. Besides, PPAR-γ antagonist GW9662 and agonist rosiglitazone, AMPK antagonist compound C and activator AICAR as well as ACC inhibitor TOFA were used to further confirm the relationship between PPAR-γ and AMPK. Results: The results demonstrated that Gentiopicroside markedly ameliorated hyperalgesia with prolonged paw withdrawal latency to heat and cold stimuli and fewer responses to mechanical allodynia compared with DPN model group. Gentiopicroside regulated dyslipidemia, enhanced nerve blood flow and improved MNCV as well as SNCV. Gentiopicroside suppressed ACC expression through the activation of AMPK and PPAR-γ mediated the activation of AMPK and subsequent inhibition of ACC expression. Conclusion: In conclusion, the present study demon strated that Gentiopicroside exerted nerve-protective effect and attenuated experimental DPN by restoring dyslipidmia and improved nerve blood flow through regulating PPAR-γ/AMPK/ACC signal pathway. These results provided a promising potential treatment of DPN.

PEDF Induces Native Coronary Collateral Microcirculation Remodeling in a Manner Similar to That of FSS Through Activing Canonical and Non-canonical Notch1 Signaling Pathway Simultaneously

2020 ◽  
Author(s):  
Jiali Chen ◽  
Xiucheng Liu ◽  
Xichun Qin ◽  
Hao Zhang ◽  
Zhiwei Liu ◽  
...  
Keyword(s):  
Blood Flow ◽  
Signaling Pathway ◽  
Fluid Shear Stress ◽  
Adherens Junctions ◽  
Pigment Epithelium ◽  
Butyl Ester ◽  
Specific Mechanism ◽  
Notch1 Signaling ◽  
Coronary Collateral ◽  
Notch1 Signaling Pathway

Abstract Background Our previous studies showed that the coronary collateral microcirculation reserve (CCMR) in rat hearts is abundant, but the structure is naturally flawed, which preventing it from continuously providing alternative blood flow to the ischemic myocardium. Further research indicated that pigment epithelium-derived factor (PEDF) can induce CCMR vessels remodeling in a manner similar to that of fluid shear stress (FSS), thus improving compensatory blood flow. However, the specific mechanism remained unclear. Methods We established the rat model of PEDF overexpression in the myocardium and the cardiac explant angiogenesis model in matrigel to identify the role of the canonical and non-canonical Notch1 signaling pathway in the process of PEDF-induced CCMR remodeling. Results: We found that pharmaceutical blockage of Notch1 pathway via γ-secretase inhibitor N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT) would effectively abrogate the remodeling process, including the diameter expansion and adherens junctions reorganization of CCMR induced by PEDF. In vitro, western blot and enzyme activity assay analysis indicated that PEDF treatment simultaneously active the canonical Notch1 pathway (NICD/AKT/eNOS/NO) and non-canonical Notch1 pathway (TMD/VE-cadherin-LAR-Trio complex). To our amusement, using L-Nitromonomethylarginine (L-NMMA) acetate to inhibit endothelial nitric oxide synthase (eNOS) activity could significantly block PEDF-induced the diameter expansion of the nascent blood vessels, but it had little effect on the reassembly of adherens junctions. While activation of non-canonical Notch1 pathway seems to be the cause of adherens junctions remodeling. Blocking of the non-canonical Notch1 pathway canceled PEDF-driven adherens junctions assembly. Conclusions We demonstrate the specific mechanism of PEDF-induced native collateral microcirculation remodeling. PEDF can active the canonical Notch1 pathway signaling pathway to promote lumenal remodeling and, Simultaneously, active non-canonical Notch1 signaling pathway responsible for adherens junctions assembly.

RAF1 as Downstream Molecule Mediates the FSH Signaling Pathway to Stimulate E2 Synthesis and Secretion in Mouse Ovarian Granulosa Cells

2020 ◽  
Author(s):  
Xuan Luo ◽  
Hui Liu ◽  
Hongzhou Guo ◽  
Longjie Sun ◽  
Kemian Gou ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Granulosa Cells ◽  
Regulatory Function ◽  
Hormone Synthesis ◽  
Ovarian Granulosa Cells ◽  
Erk Phosphorylation ◽  
Extracellular Signal ◽  
Key Factor ◽  
Cytochrome P450 Family ◽  
Estradiol Synthesis

Abstract Background: V-raf-leukemia viral oncogene 1 (RAF1) kinase is the key factor in extracellular signal regulated pathway, which transmits signals to the downstream extracellular regulated protein kinases (ERK). Regulatory function of RAF1 has been proved to mediate steroid hormone synthesis, which played an essential physiological function in reproduction and development. Whether RAF1 takes part in the signaling events of gonadotropic hormones follicle-stimulating hormone (FSH) in ovarian is unknown.Results: We found that RAF1 as downstream molecule mediates the FSH signaling pathway to stimulate estradiol (E2) synthesis and secretion in mouse ovarian granulosa cells (GCs). The expression of RAF1 is induced by FSH and the production of E2 is increased in the serum and primary ovarian GCs supernatant, the process of which is blocked by treating with RAF1 inhibitor (N-(2-Methyl-5'-morpholino-6'-((tetrahydro-2H-pyran-4-yl)oxy)-[3,3'-bipyridin]-5-yl)-3(trifluoromethyl) benzamide, RAF709). Inhibition of RAF1 activity by RAF709 decreased ERK phosphorylation, and suppressed the expression of cytochrome P450 family 19 subfamily a member 1 (CYP19A1) which is a major rate-limiting enzyme to participate in the last step of E2 biosynthesis. Conclusion: Our results suggest that RAF1 play a pivotal mediating roles toward E2 production in FSH signaling pathway by inducing the phosphorylation of ERK and promoting the process of estradiol synthesis. RAF1 may be a potential and effective factor to regulate the function of the female mouse reproductive system.

Evaluation of Intra-Aneurysmal Blood Flow: Investigation of the Flow in Experimental Aneurysms

1998 ◽  
Vol 4 (1_suppl) ◽  
pp. 77-80 ◽  
Author(s):  
F. Asakura ◽  
H. Tenjin ◽  
K. Matsumoto ◽  
S. Ueda
Keyword(s):  
Blood Flow ◽  
Flow Velocity ◽  
Coil Embolization ◽  
High Speed ◽  
Mean Transit Time ◽  
Digital Subtraction ◽  
High Speed Video ◽  
Tracer Particles ◽  
Flow Investigation ◽  
Platinum Coil

We evaluated the flow in experimental pig aneurysms using a high speed video system with tracer particles and digital subtraction angiography (DSA). We found that flow velocity in experimental aneurysms was fast on the inflow of aneurysms. There was a certain correlation between mean transit time (MTT) and velocity in experimental aneurysms. Therefore, the differences of flow velocity in aneurysms will be detected using DSA. The flow in aneurysms was much changed by platinum coil embolization.

scholarly journals miR-375 mediates CRH signaling pathway in inhibiting E2 synthesis in porcine ovary

Reproduction ◽  
2017 ◽  
Vol 153 (1) ◽  
pp. 63-73 ◽  
Author(s):  
Chulin Yu ◽  
Meiling Li ◽  
Yue Wang ◽  
Ying Liu ◽  
Chengzhi Yan ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Granulosa Cells ◽  
Reproductive System ◽  
Follicular Development ◽  
Cell Types ◽  
Signaling System ◽  
Key Factor ◽  
The Relationship

The corticotropin-releasing hormone (CRH) signaling system is involved in numbers of stress-related physiological and pathological responses, including its inhibiting effects on estradiol (E2) synthesis and follicular development in the ovary. In addition, there are reports that microRNAs (miRNAs) can control the function of animal reproductive system. The aim of present study was to investigate the functions of miR-375 and the relationship between miR-375 and CRH signaling molecules in the porcine ovary. First, our common PCR results show that miR-375 and the CRH receptor 1 (CRHR1) are expressed in porcine ovary, whereas CRH receptor 2 (CRHR2) is not detected. We further have located the cell types of miR-375 and CRHR1 by in situ hybridization (ISH), and the results show that miR-375 is located only in the granulosa cells, whereas CRHR1 is positive in all of granulosa cells and oocytes, inferring that miR-375 and CRHR1 are co-localized in granulosa cells. Second, we show that overexpression of miR-375 in cultured granulosa cells suppresses the E2 production, whereas miR-375 knockdown demonstrates the opposite result. Besides, our in vitro results demonstrate that miR-375 mediates the signaling pathway of CRH inhibiting E2 synthesis. Finally, our data show that the action of miR-375 is accomplished by directly binding to the 3′UTR of specificity protein1 (SP1) mRNA to decrease the SP1 protein level. Thus, we conclude that miR-375 is a key factor in regulating E2 synthesis by mediating the CRH signaling pathway.

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