GPR4 signaling is essential for the promotion of acid-mediated angiogenic capacity of endothelial progenitor cells by activating STAT3/VEGFA pathway in patients with coronary artery disease.

BACKGROUND: Patients with coronary artery disease (CAD) are characterized by a decline in vascular regeneration, which is related to the dysfunction of endothelial progenitor cells (EPCs). G-protein-coupled receptor 4 (GPR4) is a proton-sensing G-protein-coupled receptor (GPCR) that contributes to neovascularization in acidic microenvironments. However, the role of GPR4 in regulating the angiogenic capacity of EPCs from CAD patients in response to acidity generated in ischemic tissue remains completely unclear. METHODS: The angiogenic capacity of EPCs collected from CAD patients and healthy subjects was evaluated in different pH environments. The GPR4 function of regulating EPC-mediated angiogenesis was analyzed both in vitro and in vivo. The downstream mechanisms were further investigated by genetic overexpression and inhibition. RESULTS: Acidic environment prestimulation significantly enhanced the angiogenic capacity of EPCs from the non-CAD group both in vivo and in vitro, while the same treatment yielded the opposite result in the CAD group. Among the four canonical proton-sensing GPCRs, GPR4 displays the highest expression in EPCs. The expression of GRP4 was markedly lower in EPCs from CAD patients than in EPCs from non-CAD individuals independent of acid stimulation. The siRNA-mediated knockdown of GPR4 with subsequent decreased phosphorylation of STAT3 mimicked the impaired function of EPCs from CAD patients at pH 6.4 but not at pH 7.4. Elevating GPR4 expression restored the neovessel formation mediated by EPCs from CAD patients in an acidic environment by activating STAT3/VEGFA signaling. Moreover, the beneficial impact of GPR4 upregulation on EPC-mediated angiogenic capacity was abrogated by blockade of the STAT3/VEGFA signaling pathway. CONCLUSIONS: Our present study demonstrated for the first time that loss of GPR4 is responsible for the decline in proton sensing and angiogenic capacity of EPCs from CAD patients. Augmentation of GPR4 expression promotes the neovessel formation of EPCs by activating STAT3/VEGF signaling. This finding implicates GPR4 as a potential therapeutic target for CAD characterized by impaired neovascularization in ischemic tissues.

Declined circulating Elabela levels in patients with essential hypertension and its association with impaired vascular function: A preliminary study.

Background: Elabela (ELA) is a newly identified endogenous ligand of apelin receptor (APJ) which has been confirmed to be implicated in the pathogenesis of hypertension. Previous experiments have revealed the critical role of ELA in eliciting vasodilation and lowering blood pressure. However, the role of plasma ELA levels in hypertensive patients and its relationship with vascular function have not been investigated.Method: Thirty-one patients with essential hypertension (EH) and 31 age-matched healthy subjects as controls were recruited in the study. Plasma ELA concentration and vascular function parameters including brachial artery flow-mediated dilation (FMD) and brachial-ankle pulse wave velocity (baPWV) were measured.Results: We observed remarkably lower plasma ELA concentration in hypertensive patients as compared with controls (1.29 ± 0.56 ng/ml vs. 1.79 ± 0.55 ng/ml; P = 0.001). Linear correlation analysis showed that ELA was negatively correlated with systolic blood pressure (r = -0.388, P = 0.002) and diastolic blood pressure (r = -0.321, P = 0.011) and positively correlated with FMD (r = 0.319, P = 0.011). There was no statistically significant relationship between ELA and baPWV (r = 0.234, P = 0.067). Stepwise multiple linear analysis also identified a close association of plasma ELA levels with endothelial function.Conclusion: The present study demonstrates for the first time that circulating ELA levels are reduced in patients with EH. The fall in endogenous ELA levels may be involved in the pathogenesis of hypertension-related vascular damage.

[Spectroscopic Research on Slag Nanocrystal Glass Ceramics Containing Rare Earth Elements].

The research group prepared the high-performance slag nanocrystal glass ceramics by utilizing the valuable elements of the wastes in the Chinese Bayan Obo which are characterized by their symbiotic or associated existence. In this paper, inductively coupled plasma emission spectroscopy (ICP), X-ray diffraction (XRD), Raman spectroscopy (Raman) and scanning electron microscopy (SEM) are all used in the depth analysis for the composition and structure of the samples. The experiment results of ICP, XRD and SEM showed that the principal crystalline phase of the slag nanocrystal glass ceramics containing rare earth elements is diopside, its grain size ranges from 45 to 100 nm, the elements showed in the SEM scan are basically in consistent with the component analysis of ICP. Raman analysis indicated that its amorphous phase is a three-dimensional network structure composed by the structural unit of silicon-oxy tetrahedron with different non-bridging oxygen bonds. According to the further analysis, we found that the rare earth microelement has significant effect on the network structure. Compared the nanocrystal slag glass ceramic with the glass ceramics of similar ingredients, we found that generally, the Raman band wavenumber for the former is lower than the later. The composition difference between the glass ceramics and the slag nanocrystal with the similar ingredients mainly lies on the rare earth elements and other trace elements. Therefore, we think that the rare earth elements and other trace elements remains in the slag nanocrystal glass ceramics have a significant effect on the network structure of amorphous phase. The research method of this study provides an approach for the relationship among the composition, structure and performance of the glass ceramics.

[Effect of temperature on the structure of CaO-MgO-Al2O3-SiO2 nanocrystalline glass-ceramics studied by Raman spectroscopy].

In the present paper, nanocrystalline glass-ceramic of CaO-MgO-Al2O3-SiO2 system was produced by melting method. The CaO-MgO-Al2O3-SiO2 nanocrystalline glass-ceramic was measured by Raman spectroscopy in the temperature range from -190 to 310 degrees C in order to study the effect of temperature on the structure of this system nanocrystalline glass-ceramics. The results showed that different non-bridge oxygen bond silicon-oxygen tetrahedron structural unit changes are not consistent with rising temperature. Further analyses indicated that: the SiO4 tetrahedron with 2 non-bridged oxygen (Q2), the SiO4 tetrahedron with 3 non-bridged oxygen (Q(1)), which are situated at the edge of the 3-D SiO4 tetrahedrons network, and the SiO4 tetrahedron with 4 non-bridged oxygen (Q(0)), which is situated outside the 3-D network all suffered a significant influence by the temperature change, which has been expressed as: shifts towards the high wave-number, increased bond force constants, and shortened bond lengths. This paper studied the influence of temperature on CMAS system nanocrystalline glass-ceramics using variable temperature Raman technology. It provides experiment basis to the research on external environment influence on CMAS system nanocrystalline glass-ceramics materials in terms of structure and performance. In addition, the research provides experimental basis for controlling the expansion coefficient of nanocrystalline glass-ceramic of CaO-MgO-Al2O3-SiO2 system.

[Temperature effect on the hydrogen bonding behavior between DMSO and water in aqueous DMSO solutions studied by raman spectroscopy].

In the present paper, DMSO/H2O mixture with the ratio of volume 1:1 was measured in the cooling process by Raman spectroscopy, and the Raman assignments was made to the DMSO molecular and water molecular. The results showed that the behavior between intra-molecular hydrogen bonds and inter-molecular hydrogen bonds of DMSO and water leads to the change in the Raman spectra of the S==O stretching vibration of DMSO and the O--H stretching vibration of water. Further analysis showed that the hydrogen bond between DMSO and water was enhanced in the course of temperature decreasing process (27 to -30 degrees C), and the intramolecular hydrogen bonds between water and water replaced the intermolecular hydrogen bonds of DMSO and water in the course of temperature decreasing process (-30 to -60 degrees C). The research provides experimental basis for hydrogen bonding theory in aqueous solution.

[Study on the effect of pressure on the molecular structure and pi-electron delocalization of beta-carotene by raman spectroscopy].

In the present paper, studies on in-situ Raman spectra at high pressure up to 12.85 Gpa were performed on beta-carotene using a diamond anvil cell (DAC), and the effects of pressure on the characteristic peaks and pi-electron delocalization of beta-carotene were discussed. The results showed that Raman frequencies of the main characteristic peaks of beta-carotene shifted to high wavenumber with the increase in pressure. The relation between pressure and the three main characteristic peaks of beta-carotene was given as follows: nu1, (C==C) = 4. 74P + 1511.4, w (C-C) = 2.55P + 157.6 and nu3 (CH3) = 2.25P + 1011.3. Under the pressure of 5.38 GPa, Raman spectrum of nu1 + nu2 sum frequency of beta-carotene was subjected to cleavage. Fuethermore, the degree of relectron decolization was reduced with the increase in pressure, leading to C==C double bond more compressible than C-C bond on the main chain of beta-carotene.

[Effect of hydrogen bond on line width of Raman spectra in three aqueous solutions].

In the present paper, the frequency shift and line widths of acetonitrile/H2O, DMSO/H2O and acetone/H2O aqueous binary solutions at different concentration were measured by Raman spectroscopy. The experimental results were analyzed by mixture model and empirical formula of line widths. The results show that the stronger the hydrogen bond interaction, the greater the line widths of Raman spectra in the three aqueous binary solutions; the line width of Raman spectra not only is affected by concentration fluctuation, but also is affected by hydrogen bond. In addition, the experimental data points are again nicely fitted using the empirical formula.

[Lycopene and beta-carotene content in tomato analyzed by the second harmonic].

Lycopene and beta-carotene are two important nutritional components in tomato. The main Raman spectrum group of lycopene and beta-carotene abundant in tomato is identical and difficult to be distinguished through fundamental frequency. With excitation wavelength of 514.5 nm, the excited light was just present in the half width range of the main absorption bands of Lycopene and beta-carotene, so the resonance Raman effect can occur. Based on resonance Raman spectra, by on-body measuring the second harmonic of stretching vibration of carbon-carbon conjugated double bond in lycopene and beta-carotene, the content of lycopene and beta-carotene can be obtained according to the integrated intensity of each component calculated by software. And this provides a method for on-body determining the content of the components with the homologous group.

[Detection of hearing threshold and polymorphic molecular marker analysis of guinea pigs of mimetic aging].

OBJECTIVE: To explore the establishment of the mimetic aging effect in guinea pigs induced by D-galactose, and to detect the biological indicatrix associated with hearing loss and provide a new tool for molecular pathogenesis of hearing loss. METHODS: Total of 51 guinea pigs were randomly divided into three groups: group A (model aging group, n = 25), which were injected with D-galactose (200 mgxkg(-1)xd(-1)) by intra peritoneum for 6 weeks, group B (model control group, n = 18), which were given the same amount of saline only, and group C (vacant group, n = 15) were not treated. Then, The guinea pigs in group A and B were exposed in noise for 8 days, 8 hours once a day. Auditory brainstem response (ABR) was used to test the hearing threshold of guinea pigs thrice, first before the drug administered, then after 6 weeks the drug used, third after noise exposure. And colorimetry was used to analyze the activity of superoxide dismutase (SOD) and malon dialdehyde (MDA) in brain and liver tissue. The DNA of inner ear tissue was harvested and amplified fragment length polymorphism (AFLP) was used to detect the differential polymorphic markers. RESULTS: After injection, there was no significant difference in elevation of ABR threshold between the group A and group B (t = 1.14, P > 0.05). However, exposure of noise later, elevation in ABR threshold of (22.97 +/- 10.56) dB peSPL was observed in group A, and (14.16 +/- 7.36) dB peSPL in group B. The was significant difference in variation of hearing threshold between group A and group B (t = 2.78, P < 0.05). The activity of SOD in brain and liver tissue in group A was lower than that in group B. the level of MDA was opposite between group A and group B. The difference between group A and group B was significant (P < 0.01). A differential polymorphic marker was observed by AFLP. CONCLUSIONS: The mimetic aging effect of the guinea pigs can be induced by D-galactose, and this model can not directly induce the hearing loss. The differential polymorphic marker possibly act as a predisposing factor which can greatly enhance the sensitivity of the ear to the noise.