Search

An emerging body of evidence indicates that transient receptor potential TRP channels act as important mediators for a wide variety of physiological functions and are potential targets for drug discovery. Our previous study has identified transient receptor potential channel 3 (TRPC3) and TRPC6 as cation channels through which most of the damaging calcium enters, aggravates pathological changes in vivo and increases ischemia/reperfusion (I/R) injury in mice. This study aimed to verify the effects of TRPC3 inhibitor Pyr3 on myocardial I/R injury in mice. C57BL/6J wild-type male mice (8 to 12 weeks old) were anesthetized with 3.3% chloral hydrate. A murine I (30 min)/R (24 h) injury model was established by temporary occlusion of the left anterior descending (LAD) coronary artery. Pyr3 was administered at concentrations of 0, 2.5, 5, or 10 mg/kg via the right jugular vein 5 min before reperfusion. We observed that the selective TRPC3 inhibitor, 10 mg/kg Pyr3, significantly decreased the infarct size of left ventricle, and reduced the myocardial cell apoptosis rate and inflammatory response in mice. In a conclusion, TRPC3 can function as a candidate target for I/R injury prevention, and Pyr3 may directly bind to TRPC3 channel protein, inhibit TRPC3 channel activity, and improve TRPC3-related myocardial I/R injury. Pyr3 may be used for clarification of TRPC3 functions and for treatments of TRPC3-mediated diseases.

The infrared spectrum (IR) characteristic peaks of amide I, amide II, and amide III bands are marked as amide or peptide characteristic peaks. Through the nuclear magnetic resonance study, N-methylacetamide has been determined to have six fine components, which include protonation, hydration, and hydroxy structures. Then the independent IR spectrum of every component in N-methylacetamide is calculated by using the density functional theory quantum chemistry method, and the contribution of each component to amide I, II, and III bands is analyzed. The results of this research can help to explain the formation of the amide infrared spectrum, which has positive significance in organic chemistry, analytical chemistry, and chemical biology.

Cancer multidrug resistance (MDR) is existence in stem cell-like cancer cells characterized by stemness including high-proliferation and self-renewal. Programmed cell death 4 (PDCD4), as a proapoptotic gene, whether it engaged in cancer stemness and cisplatin resistance is still unknown. Here we showed that PDCD4 expressions in Hela/DDP (cisplatin resistance) cells were lower than in parental Hela cells. Moreover, the levels of drug resistance genes and typical stemness markers were markedly elevated in Hela/DDP cells. In vivo, xenograft tumor assay confirmed that knockdown of PDCD4 accelerated the grafted tumor growth. In vitro, colony formation and MTT assay demonstrated that PDCD4 overexpression inhibited cells proliferation in conditions with or without cisplatin. By contrast, PDCD4 deficiency provoked cell proliferation and cisplatin resistance. On mechanism, PDCD4 decreased the protein levels of pAKT and pYB1, accompanied by reduced MDR1 expression. Correspondingly, luciferase reporter assay showed PDCD4 regulated MDR1 promoter activity entirely relied on YB1. Furthermore, Ch-IP, GST-pulldown, and Co-IP assays provided novel evidence that PDCD4 could directly bind with YB1 by the nucleolar localization signal (NOLS) segment, causing the reduced YB1 binding into the MDR1 promoter region through blocking YB1 nucleus translocation, triggering the decreased MDR1 transcription. Taken together, PDCD4-pAKT-pYB1 forms the integrated molecular network to regulate MDR1 transcription during the process of stemness-associated cisplatin resistance.

Background An emerging body of evidence indicates that puerarin (PUE) plays an important role in the treatment of angina pectoris, myocardial ischemia-reperfusion injury, hypertension and other cardiovascular diseases, but how PUE affects the vascular remodeling of hypertensive rats has not been reported yet. This study aimed to investigate the effect and mechanism of PUE on carotid arteries of spontaneously hypertensive rats (SHR) to provide the basis for the clinical application of PUE. Methods Thirty male SHR and six male Wistar Kyoto rats (WKY) aged 3 months were used in this study, SHR rats were randomly divided into 5 groups, PUE(40 or 80 mg/kg/d, ip) and telmisartan (TELMI) (30 mg/kg/d, ig) were administrated for 3 months. We use DMT myography pressure-diameter system to investigate biomechanical properties of carotid arteries, 10 μM pan-classical transient receptor potential channels (TRPCs) inhibitor SKF96365, 200 nM specific TRPC6 inhibitor SAR7334 and 100 μM Orai1 inhibitor ANCOA4 were used in the mechanical test. Results PUE can significantly decrease systolic and diastolic blood pressure, long-term administration of PUE resulted in a mild reduction of thickness and inner diameter of carotid artery. PUE ameliorate NE-response and vascular remodeling mainly through inhibiting TRPCs channel activities of VSMC. Conclusion PUE can ameliorate biomechanical remodeling of carotid arteries through inhibiting TRPCs channel activities of VSMC in spontaneously hypertensive rats.

C11H16Br2N4O2Zn, monoclinic, Cc (no. 9), a = 15.534(7) Å, b = 7.956(4) Å, c = 14.589(7) Å, β = 119.094(8)°, V = 1575.5(13) Å3, Z = 4, R gt (F) = 0.0296, wR ref (F 2) = 0.0703, T = 296 K.

C2H6O⋅C6H6N2O⋅C7H6O4, triclinic, P1̄ (no. 2), a = 7.4217(18) Å, b = 7.7021(18) Å, c = 15.362(4) Å, α = 79.223(2)°, β = 82.086(3)°, γ = 65.182(2)°, V = 781.2(3) Å3, Z = 2, R gt(F) = 0.0444, wR ref(F 2) = 0.1341, T = 296(2) K.

The genetic variations and dysbiosis of gut microbiota are associated with ASD. However, the role of the microbiota in the etiology of ASD in terms of host genetic susceptibility remains unclear. This study aims to systematically explore the interplay between host genetic variation and gut microbiota in ASD children. Whole-exon sequencing was applied to 26 ASD children and 26 matched controls to identify the single nucleotide variations (SNVs) in ASD. Our previous study revealed alteration in gut microbiota and disorder of metabolism activity in ASD for this cohort. Systematic bioinformatic analyses were further performed to identify associations between SNVs and gut microbiota, as well as their metabolites. The ASD SNVs were significantly enriched in genes associated with innate immune response, protein glycosylation process, and retrograde axonal transport. These SNVs were also correlated with the microbiome composition and a broad aspect of microbial functions, especially metabolism. Additionally, the abundance of metabolites involved in the metabolic network of neurotransmitters was inferred to be causally related to specific SNVs and microbes. Furthermore, our data suggested that the interaction of host genetics and gut microbes may play a crucial role in the immune and metabolism homeostasis of ASD. This study may provide valuable clues to investigate the interaction of host genetic variations and gut microbiota in the pathogenesis of ASD.

Background Qiliqiangxin (QLQX) is a preparation refined from a traditional Chinese medicine compound. It plays an important role in protecting cardiac function after myocardial infarction (MI). However, the underline mechanism of QLQX action is not clear. The purpose of this study was to detect the effects of QLQX on mitophagy after MI. Methods Male FVB/NJ mice aged 8–10 weeks were underwent left coronary artery ligation and were orally administered either QLQX (0.25 g/kg/d) or saline. Twenty-eight days after surgical operation, the cardiac function of mice was detected by echocardiography. Electron Microscopy was used to observe the microstructure of cardiomyocytes. Myocardial apoptosis was examined by TdT-mediated dUTP Nick-End Labeling (TUNEL) and western blot. H9c2 cells were cultured in a hypoxic incubator chamber (5% CO2, 1% O2, 94% N2) for 12 h and pretreated with or without QLQX (0.5 mg/mL). The cell apoptosis, reactive oxygen species (ROS), mitochondrial membrane potential and mitophagy were detected. Results When compared to sham group, the cardiac function of MI mice decreased significantly, and their cardiomyocyte apoptosis and mitochondrial damage were more serious. These MI-induced cardiac changes could be reversed by QLQX treatment. In vitro experiments also confirmed that QLQX could protect cardiomyocytes from hypoxia-induced apoptosis and mitochondrial damage. Further study indicated that QLQX could increase the expression of Pink1 and Parkin in cardiomyocytes. Conclusion Qiliqiangxin could reduce cardiomyocytes apotosis and improved heart function in infarcted heart through Pink1-mediated mitochondrial autophagy.

Additional file 2.

Additional file 3.

Additional file 1.

Rationale: Hypertension prevalence is much higher among children and adolescents with low birth weight and greater postnatal weight gain than in individuals with normal birth weight. However, the cause and molecular mechanisms underlying this complication remain largely unknown. Our previous studies have shown that RGC-32 (response gene to complement 32)–deficient (RGC-32 −/− ) mice are born significantly smaller but grow faster than their WT (wild type) controls, which allows adult RGC-32 −/− mice to attain body weights similar to those of control mice. Objective: The objective of this study is to determine whether RGC-32 −/− mice develop hypertension, and if so, to elucidate the underlying mechanisms. Methods and Results: By using a radiotelemetry system, we found that RGC-32 −/− mice exhibit higher mean arterial pressure than WT mice (101±4 versus 119±5 mm Hg), which enabled us to use RGC-32 −/− mice to study the mechanisms underlying low birth weight–related hypertension. The increased blood pressure in RGC-32 −/− mice was associated with increased vascular tone and decreased distensibility of small resistance arteries. The increased vascular tone was because of an increase in the relative contribution of sympathetic versus parasympathetic activity and was linked to increased expression of AT1R (angiotensin II type I receptor) and α1-AdR (α1-adrenergic receptor) in arterial smooth muscles. Mechanistically, RGC-32 regulated AT1R gene transcription by interacting with Sp1 (specificity protein 1) transcription factor and further blocking its binding to the AT1R promoter, leading to suppression of AT1R expression. The attenuation of AT1R leads to reduction in α1-AdR expression, which was critical for the balance of sympathetic versus parasympathetic control of vascular tone. Of importance, downregulation of RGC-32 in arterial smooth muscles was also associated with low birth weight and hypertension in humans. Conclusions: Our results indicate that RGC-32 is a novel protein factor vital for maintaining blood pressure homeostasis, especially in individuals with low birth weight.

BACKGROUND An animal study reported that TGF-β1 maturation was linked to the homeostasis of blood pressure and elastogenesis of essential hypertension (EH). Recent advances require further research of TGF-β1 receptor in EH. METHODS A case-control study comprised of 2,012 adult hypertension case patients and 2,210 adult control subjects was conducted, and the association with blood pressure was further tested in children. Logistic regression and calculated genetic risk score were used to evaluate the effects of one single nucleotide polymorphism (SNP) and multiple SNPs on EH, respectively. RESULTS The genetic risk score of 10 SNPs showed a significant association with hypertension; the odds ratio of the upper quartile vs. the lower quartile was 1.282 (P = 4.67 × 10(-3)). rs7256241 in miR-518 was significantly associated with diastolic blood pressure (DBP) change in control subjects (P = 0.002), and this association was also observed in children (P = 0.04). The systolic blood pressure (SBP) and DBP of female patients taking reserpine were higher with the C and G alleles of rs3773661 (P = 0.004) and rs7256241 (P = 0.002), respectively. In patients taking Zhen Ju Jiang Ya tablets, SBP and DBP decreased linearly with rs749794 (P = 0.004 and P = 0.048, respectively). SBP decreased linearly with rs1155705 (P = 0.007) and rs11709624 (P = 0.04), but increased with rs1036096 (P = 0.03) in male patients. In male patients taking Jiang Ya tablets, SBP increased linearly with rs11709624 (P = 0.007), DBP increased linearly with rs1155705 (P = 0.03) whereas decreased with rs7256241 (P = 0.04). CONCLUSIONS Our results suggest that TGFBR2 and miR-518 harbor variants that increase the risk of EH and affect blood pressure homeostasis as well as efficacy of antihypertensive agents.

Fibrillin-1 (FBN1) was reported to have impact on the physiological arterial stiffness and vascular remodeling with hypertension of recent years. In the previous study we reported the association of four functional single nucleotide polymorphisms (SNPs) of FBN1 gene and hypertension. Here, we further investigate the association of four tagging SNPs (tagSNPs) which covered remain genetic variation blocks of FBN1 gene with hypertension, blood pressure and efficacy of antihypertensive in a South Han Chinese population. A case–control study including 2,012 hypertension cases and 2,116 controls age- and sex-matched controls was conducted from a community-based population and four candidate tagSNPs of the FBN1 gene were genotyped. Association analysis by multiple logistic regression was conducted for allele, genotype and haplotype and hypertension, blood pressure trait and control status with antihypertensive. General linear model was applied to compare blood pressure levels between genotypes. The association of rs17361868 and hypertension was statistically significant and that was further observed in female, ≥55 years, non-smoking and non-drinking populations (P

Most HIV-1-infected patients experience hematopoiesis suppression complications. Bone marrow mesenchymal stem cells (BMSCs) are involved in regulation of hematopoietic homeostasis, so we investigated the role of Tat, a protein released by infected cells in bone marrow and impacted differentiation potential of mesenchymal stem cells, in the BMSC hematopoietic support function. BMSCs were treated with HIV-1 Tat protein (BMSCTat-p), transfected with HIV-1 Tat mRNA (BMSCTat-m) or treated with solvent (PBS) (BMSCcon) for 20 days. Then, the hematopoietic support function of BMSCTat-p, BMSCTat-m and BMSCcon was analyzed via ex vivo expansion of hematopoietic stem cells (HSCs) grown on the BMSCs and via in vivo cotransplantation of HSCs and BMSCs. In addition, the hematopoiesis-supporting gene expression patterns of BMSCTat-p, BMSCTat-m and BMSCcon were compared. The results showed that BMSCTat-p and BMSCTat-m displayed reduced expansion, a decline in the number of colony forming units (CFUs) and a decreased proportion of the primitive subpopulation of hematopoietic stem cells under coculture conditions compared with BMSCcon. The ability of BMSCTat-p to support hematopoietic recovery was also impaired, which was further confirmed by the patterns in gene expression analysis. In conclusion, Tat treatment reduced the function of BMSCs in hematopoietic support, likely by downregulating the expression of a series of hematopoietic cytokines.

Owing to the increasingly serious problems caused by multidrug resistance in community-acquired infection pathogens, it has become an urgent need to develop new classes of antibiotics for overcoming the resistance. In this paper, we describe the design and synthesis of novel pleuromutilin derivatives containing the (2-aminothiazol-4-yl)-4-methyl group, as well as their in vitro antibacterial activities against Gram-positive clinical bacteria. Most of the tested compounds displayed strong antibacterial activities against these methicillin-susceptible and methicillin-resistant bacteria. Particularly noteworthy compound 15 and its derivative 16e , both showed potent antibacterial properties (0.0625–0.5 μg/mL) that are superior to amoxicillin and tiamulin. Molecular docking studies suggested that the amino thiazole ring on the side chains of the pleuromutilin derivatives can in general be accommodated near the mutilin core in the binding pocket, and thus play an important role in the activity of the whole molecule. The findings reported herein may provide a new insight into the design of novel pleuromutilin derivatives for human clinical use.

Viscosity B-coefficients for sodium halides (NaX, X- = Cl-, Br-, and I-) in aqueous monosaccharides (d-glucose, d-galactose, d-xylose, and d-arabinose) were determined from density and viscosity (eta) measurements at 298.15 K. The contributions of solvent property (B1) and the electrolyte-solvent interaction (B2) to the B-coefficient were also obtained together with molar activation energies (Delta(mu)E0(not equal)) of the electrolytes for viscous flow of the aqueous saccharide-electrolyte solution. In addition, 1H spin-lattice relaxation times (T1) were measured for two glycosides in D2O with and without sodium halides. The results show the interactions between X- and the saccharides are in the following order: Cl-Br-I-. A linear relationship is observed between the relaxation rate (1/T1) and electrolyte concentration.

13C spin-lattice relaxation times of room temperature ionic liquids [C4mim][PF6], [C6mim][PF6], [C8mim][PF6],[C6mim][BF4] and [C6mim]Br in acetone-d6 have been determined at various acetone-d6 mole fractions. It was shown that the spin-lattice relaxation time increased with increasing acetone-d6 mole fractions, and was influenced not only by the type of the anions but also by the length of alkyl chain on the imidazolium cations. The results suggested that interactions between the cation and the anion of ionic liquids were weakened and the ionic motion of ionic liquids was enhanced with the addition of acetone-d6.

Apparent molar volumes V 2,ϕ and standard partial molar volumes V 2,ϕ 0 of LiBF 4 have been determined at 298.15 K from precise density measurements in propylene carbonate (PC) or ethylene carbonate (EC) based mixed solvents. The chosen cosolvents were dimethylformamide (DMF), tetrahydrofuran (THF), acetonitrile (AN), 1,2-dimethoxyethane (DME) and ethyl acetate (EA). The results have been interpreted from solvation of LiBF 4 in carbonate based mixed solvents. It is shown that nature of the cosolvents plays an important role for the concentration dependence of V 2,ϕ 0 values. Compared with the previous studies, the differences between ClO 4 − and BF 4 − have been embodied in the concentration dependence of V 2,ϕ 0 values and also interpreted by the interaction of the anion with solvents.

Summary 1H and 13C NMR chemical shifts have been determined to investigate the interactions of acetone with room temperature ionic liquids ([C4mim][PF6], [C6mim][PF6], [C8mim][PF6] and [C6mim][BF4]) at various acetone mole fractions. Changes in the chemical shifts of hydrogen and carbon atoms of the above systems indicated that hydrogen bonds were formed between the ring protons, the methyl and methylene next to the nitrogen of the ionic liquids and the carbonyl oxygen of the acetone molecules. The strength of hydrogen bond was found to be influenced not only by the type of the anion but also by the length of alkyl chain on the imidazolium ring of cations. At the same time, ab initio calculations have been performed to support the NMR results.

Previous studies have indicated that macrophage phenotype diversity is involved in the progression of renal fibrosis. However, the factors facilitating M1 or M2 phenotypes and the function of these polarized macrophages in kidney injury and fibrosis remain largely unknown. In the present study, we found that macrophages accumulated in the kidney interstitium exhibited mainly as the M1 phenotype at the early stage of unilateral ureter obstruction (UUO). High-mobility group box 1 (HMGB1) protein expressed and released from tubular epithelial cells and interstitial macrophages was essential for the M1 macrophage transition. HMGB1 significantly induced the expression of the M1 marker inducible nitric oxide synthase while decreasing the M2 marker IL-10 in macrophages. Moreover, a glycyrrhizic acid derivative, a blocker of HMGB1 release, reduced UUO-mediated kidney injury and ameliorated UUO-induced renal fibrosis. Interestingly and importantly, UUO caused a low pH value in the urine accumulated in the obstructed ureter, and the acidified urine induced HMGB1 release from tubular epithelial cells and macrophages in vitro. Our data demonstrate that HMGB1 is an essential contributor in facilitating M1 polarization at the early stage of UUO. Inhibition of HMGB1 release may alter macrophage phenotype and contribute to the protection of kidney tissue from injury and fibrosis.

The infrared (IR) and Raman spectra of propylene carbonate (PC) containing various concentrations of LiClO4 have been measured and analyzed. The difference in spectra of PC with and without LiClO4 was attributed to the interaction of the PC molecules and lithium ions. This interaction occurs mainly on the carbonyl oxygen atom of the PC molecule. The ring deformation, symmetric ring deformation, carbonyl stretching and stretching of ring oxygens for PC are sensitive to this interaction. The solvation number of Li+ is also calculated. On the other hand, the structure of the ClO− 4 is also affected by PC molecule, forming the solvent separated ion pairs.

The infrared (IR) and Raman spectra are reported for solutions of lithium perchlorate in propylene carbonate (PC), N,N-dimethylformamide (DMF) and PC + DMF mixtures. The band splittings of symmetric ring deformation for PC and O=CN deformation for DMF suggest that there is a strong interaction between lithium cations and solvent molecules. The solvent molecules have been assigned to two types, the free and complexed molecules. By a comparison of the intensity for the corresponding bands, it has been concluded that Li+ cations are preferentially solvated by DMF molecules in the LiClO4/PC-DMF solutions. This has been explained by the difference in values of donor number.

Rationale: Vascular smooth muscle cell (VSMC) differentiation from neural crest cells (NCCs) is critical for cardiovascular development, but the mechanisms remain largely unknown. Objective: Transforming growth factor-β (TGF-β) function in VSMC differentiation from NCCs is controversial. Therefore, we determined the role and mechanism of a TGF-β downstream signaling intermediate Smad2 in NCC differentiation to VSMCs. Methods and Results: By using Cre/loxP system, we generated a NCC tissue–specific Smad2 knockout mouse model and found that Smad2 deletion resulted in defective NCC differentiation to VSMCs in aortic arch arteries during embryonic development and caused vessel wall abnormality in adult carotid arteries where the VSMCs are derived from NCCs. The abnormalities included 1 layer of VSMCs missing in the media of the arteries with distorted and thinner elastic lamina, leading to a thinner vessel wall compared with wild-type vessel. Mechanistically, Smad2 interacted with myocardin-related transcription factor B (MRTFB) to regulate VSMC marker gene expression. Smad2 was required for TGF-β–induced MRTFB nuclear translocation, whereas MRTFB enhanced Smad2 binding to VSMC marker promoter. Furthermore, we found that Smad2, but not Smad3, was a progenitor-specific transcription factor mediating TGF-β–induced VSMC differentiation from NCCs. Smad2 also seemed to be involved in determining the physiological differences between NCC-derived and mesoderm-derived VSMCs. Conclusions: Smad2 is an important factor in regulating progenitor-specific VSMC development and physiological differences between NCC-derived and mesoderm-derived VSMCs.

Serum C-reactive protein (CRP) and genetic variation of CRP gene have been reported as a strong, independent predictor of myocardial infarction and stroke. But there is rare association evidence of CRP genetic variation and hypertension (HT).A community-based case-control study including 1331 cases with HT and 1400 controls was used to evaluate the association of tagSNPs covered CRP gene, CRPP1 gene and 40kb upstream with HT in a Chinese Han population. Haplotypes and stratification analysis were applied to further evaluate relationships between the screened SNPs and HT and general linear model (GLM) was applied to compare blood pressure levels between genotypes.In stage 1, five SNPs had positive association with HT (P0.05) and entered stage 2 and two SNPs rs876537 and rs10737175 polymorphisms showed significant association with HT in joint sample. Haplotype analysis showed that comparing with common haplotype T-C which was constructed by rs6677719 and rs10737175, haplotype T-T significantly associated with HT after adjusted covariates. Stratification analysis found significant associations of HT for rs876537, rs2808630, rs6677719 and rs10737175 in ≥50years group, rs876537, rs10737175 in female, rs876537 and rs10737175 in non-smoking and non-drinking populations as well as rs2808630 in non-drinking population. Furthermore, quantitative trait analysis indicated significant differences of SBP and DBP between the genotypes of rs10737175, rs876537 and rs2808630 in non-treatment hypertensive cases and control population.The findings of this study support that CRP gene polymorphisms have significant association with genetic susceptibility of HT and quantitative traits of blood pressure.

There is growing evidence suggesting that glomerular endothelial cell proliferation and angiogenesis may be responsible for the pathophysiological events in the early stage of diabetic nephropathy. This study was designed to investigate the factors related to glomerular endothelial cell proliferation and glomerular angiogenesis and assess the effect of propyl gallate on preventing these disorders in diabetic rats. We found that glomerular hypertrophy, glomerular mesangial matrix expansion, and albuminuria were significantly increased in DN rats. CD31+ endothelial cells significantly increased in glomerulus of diabetic rats. Double immunofluorescence staining showed some structurally defective vasculus tubes in glomerulus. Real-time PCR and western blot demonstrated the glomerular eNOS expression remained at the same level, while remarkable decreased NO productions and suppressed eNOS activities were observed in diabetic rats. Treatment with propyl gallate improved glomerular pathological changes, reduced endothelial cell proliferation, decreased albuminuria, and restored eNOS activity, but did not alter eNOS expression. These data suggest that endothelial cell proliferation and immature angiogenesis may be the contributors to progression of DN. Propyl gallate is a potential novel therapeutic agent on prevention of diabetic nephropathy.

Background: In addition to its multipotent capability, the mesenchymal stem cell (MSC) can secrete and supply a large amount of vascular endothelial growth factor (VEGF). The stromal-derived factor-1 alpha (SDF-1a) plays an important role in the homing of stem cells to the injured tissues of the heart. Therefore, the MSCs over-expressing SDF-1a could augment the angiogenesis pathway. Methods: In vitro, the differentiation of theMSCsinto endothelial-likecells wasinducedbycultivation of cellsin 10%foetalcalfserumand50 ng ml � 1 SDF-1aorin specificinhibitorsfor endothelial nitrous oxide synthase (eNOS). In vivo, the rat model of myocardial infarction was established by occlusion of the left anterior descending coronary artery. Seven days following surgery, 5.0 � 10 9 pfu Ad-SDF-1a (adenoviral vector containing human SDF-1a gene under the controlof theroussarcomavirus(RSV)promoter),5.0 � 10 6 Ad-LacZ-MSCor 5.0 � 10 6 Ad-SDF-MSCsuspension in a0.2-ml serum-freemediumwas injected into four sites in infarcted areas (0.05 ml per site). The rats receiving Ad-SDF-MSCalso receivedthe nitrousoxide (NO) synthesis inhibitor N G -nitro-L-arginine methyl ester (L-NAME) in drinking water (1 mg kg � 1 ). The rats in the control group received the same volume of cell-free medium. Four weeks following transplantation, the heart function was assessed, and histological and molecular analyses were conducted. Results: The MSCs could differentiate into endothelial cells in the presence of SDF-1a, and the effect could be inhibited by L-NAME in vitro and in vivo. Western Blotting revealed an increased expression of VEGF, Akt and eNOS. Four weeks following transplantation, a reduced infarct size and fibrosis, greater vascular density and thicker left ventricular wall were observed in the Ad-SDF-MSC group. The measurement of haemodynamic parameters showed an improvement in the left ventricular performance in the Ad-SDF-MSC group as compared with other groups. Conclusion: The MSCs over-expressing the SDF-1a can produce effective angiogenesis, resulting in the prevention of progressive heart dysfunction after a myocardial infarction. # 2009 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Aqueous solutions of five ionic liquids (ILs) of the 1-n-alkyl-3-methylimidazolium bromide family, [C(n)mim]Br (n = 4, 6, 8, 10, 12), were investigated by NMR measurements at 298.2 K as a function of IL concentrations. Critical aggregation concentrations and aggregation numbers of these ILs were determined by 1H NMR except for [C4mim]Br in D2O. The effects of the alkyl chain length of the cations were examined on the aggregation behavior of the ILs. 1H NMR data of the solvent D2O were used to investigate the hydration of the ILs in D2O, and it was found that the ionic hydration and the cation-anion association or aggregation of the ILs offset each other. The microenvironment of different protons of cations of the ILs in the aggregates was probed by determining the spin-lattice relaxation rate (1/T1). It is suggested that the imidazolium rings in the aggregates are exposed to water and that the molecular motion of the aggregates is more restricted than that of the monomers of the ILs. Furthermore, a stair-like microscopic aggregation structure is suggested for the [C(n)mim]Br/D2O (n = 6, 8, 10) systems from 2-D 1H-1H NOESY measurements.

Dendritic cells (DCs), which are the most efficient antigen-presenting cells (APCs) currently known, can be derived from CD14+ monocytes (DC predecessor cells) in vitro. Immature DCs actively take up antigens and pathogens, generate major histocompatability complex-peptide complexes, and migrate from the sites of antigen acquisition to secondary lymphoid organs to become mature dendritic cells that interact with and stimulate T-lymphocytes. During this process, the cells must undergo deformation to translocate through several barriers, including the basement membrane and interstitial connective tissue in the blood vessel wall. To further understand the mechanisms of the activation of immunological responses and the migration from peripheral tissue to secondary lymphoid organs, we have applied biophysical and microrheological methods to study the development processes of DCs in vitro. The results showed that membrane fluidity, osmotic fragility, membrane viscoelastic properties, infrared spectroscopy, and cytoskeleton organization of DCs exhibit significant differences in different developmental stages.