Cyclodextrin-based metal-organic framework materials: Classifications, synthesis strategies and applications in variegated delivery systems.

Metal-organic frameworks (MOFs) are coordination compounds that possess an adjustable structure and controllable function. Despite their wide applications in various industries, the use of MOFs in the fields of food and biomedicine is limited mainly due to their potential biological toxicity. Researchers have thus focused on developing biocompatible MOFs to address this issue. Among them, cyclodextrin-based metal-organic frameworks (CD-MOFs) have emerged as a promising alternative. CD-MOFs are novel MOFs synthesized using naturally carbohydrate cyclodextrin and alkali metal cations, and possess renewable, non-toxic, and edible characteristics. Due to their high specific surface area, controllable porosity, great biocompatibility, CD-MOFs have been widely used in various delivery systems, such as encapsulation of nutraceuticals, flavors, and antibacterial agents. Although the field of CD-MOF materials is still in its early stages, they provide a promising direction for the development of MOF materials in the delivery field. This review describes classification and structural characteristics, followed by an introduction to formation mechanism and commonly used synthetic methods for CD-MOFs. Additionally, we discuss the status of the application of various delivery systems based on CD-MOFs. Finally, we address the challenges and prospects of CD-MOF materials, with the aim of providing new insights and ideas for their future development.

Predictive value of left ventricular dyssynchrony for short-term outcomes in three-vessel disease patients undergoing coronary artery bypass grafting with preserved or mildly reduced left ventricular ejection fraction.

Background and objective: Coronary artery bypass grafting (CABG) is the reference standard intervention in coronary artery disease (CAD) patients with three-vessel disease (3VD). We aimed to evaluate the predictive value of left ventricular (LV) dyssynchrony for short-term adverse outcomes in patients with 3VD undergoing CABG with preserved or mildly reduced LV ejection fraction (LVEF). Materials and methods: This study involved ninety-five 3VD patients with preserved or mildly reduced LVEF undergoing scheduled on-pump CABG. The pre-operative diameters and volumes of LV and LVEF were obtained by two-dimensional echocardiography. LV dyssynchrony parameters were acquired by real-time three-dimensional echocardiography (RT-3DE) and analyzed by HeartModel quantification software. And the perfusion index of LV was obtained by contrast echocardiography. The clinical endpoints of short-term adverse outcomes comprised 30-day mortality and/or composite outcomes of postoperative complications. Univariate and multivariate logistic regression analyses were used to identify risk factors for the occurrence of post-CABG short-term adverse outcomes. Results: Short-term adverse outcomes occurred in 12 (12.6%) patients. These patients had higher LV dyssynchrony parameters obtained through RT-3DE. The standard deviation (SD) of the time to minimum systolic volume (Tmsv) corrected by heart rate over 16 segments (Tmsv16-SD%) [odds ratio (OR), 1.362; 95% confidence interval (CI) (1.090-1.702); P = 0.006], one of the LV dyssynchrony parameters, was independently associated with short-term adverse outcomes. Patients with poor synchronization tended to spend more time in the intensive care unit (ICU) and hospital after surgery. Conclusion: Pre-operative LV dyssynchrony parameter Tmsv16-SD% obtained through RT-3DE could be a useful additional predictor of postoperative short-term adverse outcomes in 3VD patients with preserved or mildly reduced LVEF undergoing CABG.

Lesion outline and thermal field distribution of ablative in vitro experiments in myocardia: comparison of radiofrequency and laser ablation.

OBJECTIVES: To explore the lesion outline and thermal field distribution of radiofrequency ablation (RFA) and laser ablation (LA) in myocardial ablation in vitro. MATERIALS AND METHODS: Twenty-four fresh porcine hearts were ablated with RFA or LA in vitro. The radiofrequency electrode or laser fiber and two parallel thermocouple probes were inserted into the myocardium under ultrasound guidance. The output power for RFA was 20 W/s and for LA was 5 W/s, and the total thermal energies were 1200 J, 2400 J, 3600 J, and 4800 J. The range of ablation lesions was measured, and temperature data were recorded simultaneously. RESULTS: All coagulation zones were ellipsoidal with clear boundaries. The center of LA was carbonized more obviously than that of RFA. With the accumulation of thermal energy and the extended time, all the ablation lesions induced by both RFA and LA were enlarged. By comparing the increase in thermal energy between the two groups, both the short-axis diameter and the volume change showed significant differences between the 1200 J and 3600 J groups and between the 2400 J and 4800 J groups (all P < 0.05). Both the short-axis diameter and the volume of the coagulation necrosis zone formed by LA were always larger than those of RFA at the same accumulated thermal energy. The temperatures of the two thermocouple probes increased with each energy increment. At the same accumulated energy, the temperature of LA was much higher than that of RFA at the same point. The initial temperature increase at 0.5 cm of LA was rapid. The temperature reached 43 °C and the accumulated energy reached 1200 J after approximately 4 min. After that the temperature increased at a slower rate to 70  C. For the RFA at the point of 0.5 cm, the initial temperature increased rapidly to 30 °C with the same accumulated energy of 1200 J after only 1 min. In the range of 4800 J of accumulated thermal energy, only the temperature of LA at the point of 0.5 cm exceeded 60 °C when the energy reached approximately 3000 J. CONCLUSIONS: Both RFA and LA were shown to be reliable methods for myocardial ablation. The lesion outline and thermal field distribution of RFA and LA should be considered when performing thermal ablation in the intramyocardial septum during hypertrophic obstructive cardiomyopathy.

Circulating extracellular vesicles from patients with valvular heart disease induce neutrophil chemotaxis via FOXO3a and the inhibiting role of dexmedetomidine.

We previously demonstrated that circulating extracellular vesicles (EVs) from patients with valvular heart disease (VHD; vEVs) contain inflammatory components and inhibit endothelium-dependent vasodilation. Neutrophil chemotaxis plays a key role in renal dysfunction, and dexmedetomidine (DEX) can reduce renal dysfunction in cardiac surgery. However, the roles of vEVs in neutrophil chemotaxis and effects of DEX on vEVs are unknown. Here, we investigated the impact of vEVs on neutrophil chemotaxis in kidneys and the influence of DEX on vEVs. Circulating EVs were isolated from healthy subjects and patients with VHD. The effects of EVs on chemokine generation, forkhead box protein O3a (FOXO3a) pathway activation and neutrophil chemotaxis on cultured human umbilical vein endothelial cells (HUVECs) and kidneys in mice and the influence of DEX on EVs were detected. vEVs increased FOXO3a expression, decreased phosphorylation of Akt and FOXO3a, promoted FOXO3a nuclear translocation, and activated the FOXO3a signaling pathway in vitro. DEX pretreatment reduced vEV-induced CXCL4 and CCL5 expression and neutrophil chemotaxis in cultured HUVECs via the FOXO3a signaling pathway. vEVs were also found to suppress Akt phosphorylation and activate FOXO3a signaling to increase plasma levels of CXCL4 and CCL5 and neutrophil accumulation in kidney. The overall mechanism was inhibited in vivo with DEX pretreatment. Our data demonstrated that vEVs induced CXCL4-CCL5 to stimulate neutrophil infiltration in kidney, which can be inhibited by DEX via the FOXO3a signaling. Our findings reveal a unique mechanism involving vEVs in inducing neutrophils chemotaxis and may provide a novel basis for using DEX in reducing renal dysfunction in valvular heart surgery.

High pressure-assisted vacuum-freeze drying: A novel, efficient way to accelerate moisture migration in shrimp processing.

High pressure processing (HPP), as nonthermal processing technology, has the potential to increase the drying rate due to its improvement of heat and mass exchange in different processes. In this study, the moisture migration in shrimps during HPP-vacuum-freeze drying (HPP-VFD) processes has been monitored by using low-field nuclear magnetic resonance and magnetic resonance image (MRI) in comparison with hot air-drying and VFD. Based on the T2 relaxation spectra, three water fractions corresponding to bound water (hydrogen-bonded water), immobile water (water trapped by organization structure or cell member), and free water were observed. For group B, with increasing drying time (4 to 22 hr), the transverse relaxation times of T21 , T22 , and T23 were significantly decreased (76.79%, 57.78%, and 40.9%) (P < 0.05). The content of immobile water (A22 ) and free water (A23 ) decreased (81.55% and 89.07%), whereas the bound water (A21 ) increased (7.26%). In comparison with group B, the T21 , T22 , and T23 of group C showed greater decrease (83.12%, 87.12%, and 89.57% for group C) so that HPP pretreatment could shorten the relaxation time. MRI analysis further proved that HPP-VFD drying has improved drying efficiency, and moisture migration was from the exterior to the interior part with increasing drying time. SEM analysis demonstrated that no significant damage of muscle fibers with narrower gaps was observed for groups B and C. Overall, HPP, as a pretreatment technology, could accelerate the moisture migration and improve the drying efficiency of VFD process for shrimp. PRACTICAL APPLICATION: High pressure processing (HPP) is now well known as a nonthermal processing technology and becoming increasingly acknowledged. However, there is limited information about its application in shrimp-drying process and the moisture dynamic of shrimp subjected to high pressure processing-assisted vacuum-freeze drying. This study could provide valuable information regarding the moisture status and migration in HPP-VFD shrimp monitored by LF-NMR and MRI methods. The results showed that HPP processing at 550 MPa for 10 min can be used as an interesting method for drying pretreatment, increasing its drying rate and consequently reducing its process time, and it demonstrated that the methods used in this study had good correlation coefficient with physicochemical properties of shrimp, which may be real-time and nondestructive monitoring methods for shrimp-drying process.

Myocardial contrast echocardiography in the diagnosis of postoperative takotsubo myocardiopathy: case report and literature review.

BACKGROUND: Takotsubo cardiomyopathy (TCM) is a brief ventricular dysfunction that usually occurs after emotional or physical stress. Here, we report a patient who underwent cardiac surgery and then developed TCM during the postoperative period. CASE PRESENTATION: A 51-year-old woman was admitted to our hospital complaining of chest tightness, palpitations and dyspnoea after activity. An echocardiogram performed by our hospital showed rheumatic heart disease (severe mitral stenosis and regurgitation) with normal cardiac function and wall motion. After mitral valve replacement, this patient developed heart failure with low blood pressure and tachycardia. Urgent bedside echocardiography demonstrated akinesis in the middle and apical segments of the left ventricle and a depressed ejection fraction (EF) of 36%. Myocardial contrast echocardiography (MCE) showed similar enhancement intensity in the basal, middle and apical segments. Quantitative analysis showed approximately equivalent maximum intensity in these regions. The diagnosis was considered TCM instead of myocardial infarction. Then, an intra-aortic balloon pump was inserted to maintain effective circulation and reduce the postcardiac load. Given ventilation therapy, postoperative anticoagulation therapy and anti-infection treatment, the patient recovered quickly. In the follow-up examination, the patient remained asymptomatic and showed normalization of ventricular wall motion in the apical segment. CONCLUSION: This report presents a case of TCM in which MCE was used to demonstrate intact microvascular perfusion despite apical akinesis. This report might support the use of MCE as a substitute for invasive coronary angiography.

[Association of Ureaplasma urealyticum with the types of antisperm antibody in infertile men].

OBJECTIVE: To investigate the prevalence of Ureaplasma urealyticum (UU) infection in infertile men, its influence on routine semen parameters and the distribution of antisperm antibody (AsAb) and its types in infertile patients with UU infection. METHODS: We detected the positive rate of UU infection, semen parameters, and the distribution of AsAb and its types in 662 infertile men and 25 normal fertile male controls followed by comparison of the obtained data between the two groups of subjects. RESULTS: The positive rate of UU infection was significantly higher in the infertile men than in the normal controls (52.87% ï¼»350/662ï¼½ vs 16.00% ï¼»4/25ï¼½, χ2 = 11.68, P <0.05). The semen volume, sperm count, sperm concentration and percentage of progressively motile sperm were remarkably lower in the UU-positive infertile males than in the control group (P <0.05). No statistically significant difference was observed between the UU-positive and UU-negative groups in the positive rates of total AsAb (43.4% vs 36.5%, χ2 = 3.25, P >0.05) and AsAb IgA, IgM and IgG in the seminal plasma, or in the percentages of serum AsAb IgM (16.9% vs 20.5%, χ2 = 1.22, P >0.05) and IgG (32.7% vs 28.9%, χ2 = 0.99, P >0.05) except in that of serum AsAb IgA (23.6% vs 17.0%, χ2 = 4.03, P <0.05). CONCLUSIONS: The UU infection rate is high in infertile males, which decreases the semen volume, total sperm count, motile sperm concentration and percentage of progressively motile sperm and increases the positive rate of serum AsAb IgA.

Predictive modeling of microbial single cells: A review.

In practice, food products tend to be contaminated with food-borne pathogens at a low inoculum level. However, the huge potential risk cannot be ignored because microbes may initiate high-speed growth suitable conditions during the food chain, such as transportation or storage. Thus, it is important to perform predictive modeling of microbial single cells. Several key aspects of microbial single-cell modeling are covered in this review. First, based on previous studies, the techniques of microbial single-cell data acquisition and growth data collection are presented in detail. In addition, the sources of microbial single-cell variability are also summarized. Due to model microbial growth, traditional deterministic mathematical models have been developed. However, most models fail to make accurate predictions at low cell numbers or at the single-cell level due to high cell-to-cell heterogeneity. Stochastic models have been a subject of great interest; and these models take into consideration the variability in microbial single-cell behavior.

[Habitat areas extracting of Poria cocos in Anhui based on "3S" technologies].

"Adversity" is one primary element that impacts the pharmacology components of authentic Chinese herbal medicine. Knowledge about "adversity" is a precondition of yield estimation, quality monitoring, location selection and the geo-herbalism protection. Used 3S(GIS, RS and GPS) technology to combine multi-source key ecological factors of "Anling", and used parasitic relationships between organisms to extracting its suitable region for the first time. Results showed that the "Anling" were mainly distributed in Dabie coteau. Suitable area amount to 36.8 km², Yuexi, Shucheng, Jinzhai and Qianshan which account for about 93.55% of whole congenial region. The first three accounts for about 80.82%. It was Yuexi that account for 1/3 above especially. Field investigation verify accuracy of extraction about 91.67%, which has confirmed it is feasible that using the relationship between parasitic host and parasitic to extract native environment of parasitic traditional medicine based on 3S technology.

In vitro fermentation behaviors of fucosylated chondroitin sulfate from Pearsonothuria graeffei by human gut microflora.

A fucosylated chondroitin sulfate (FCS-pg) with highly repeated structure from Pearsonothuria graeffei was subjected to a in vitro fermentation model to investigate its fermentability and effects on human gut microflora. High performance liquid chromatography (HPLC) measurement found FCS-pg can be fermented to short chain fatty acids (SCFAs) by gut microflora from partial human fecal samples. 16S rRNA gene-based polymerase chain reaction-based denaturing gradient gel electrophoresis (PCR-DGGE) profiling and real-time quantitative PCR analysis showed that FCS-pg mainly increased the proportions of Clostridium cluster XI, Bacteriodes prevotella group, Bifidobacterium genus, Clostridium cluster I and Clostridium cluster XIVab, whereas the numbers of the Enterobacteriaceae and Lactobacillus decreased. These results indicated that FCS-pg was mainly fermented by Bacteroides, Bifidobacterium and Clostridium. It increased the content of probiotics bacteria in achieving health-enhancing effect, was slightly different than most sulfated polysaccharides from marine animals. The current study provides useful new information on the mechanism of absorption and functional activity on FCS-pg within the gastrointestinal tract of the human body.

Endothelial microparticles are increased in congenital heart diseases and contribute to endothelial dysfunction.

BACKGROUND: We previously demonstrated that endothelial microparticles (EMPs) are increased in mitral valve diseases and impair valvular endothelial cell function. Perioperative systemic inflammation is an important risk factor and complication of cardiac surgery. In this study, we investigate whether EMPs increase in congenital heart diseases to promote inflammation and endothelial dysfunction. METHODS: The level of plasma EMPs in 20 patients with atrial septal defect (ASD), 23 patients with ventricular septal defect (VSD), and 30 healthy subjects were analyzed by flow cytometry. EMPs generated from human umbilical vascular endothelial cells (HUVECs) were injected into C57BL6 mice, or cultured with HUVECs without or with siRNAs targeting P38 MAPK. The expression and/or phosphorylation of endothelial nitric oxide synthase (eNOS), P38 MAPK, and caveolin-1 in mouse heart and/or in cultured HUVECs were determined. We evaluated generation of nitric oxide (NO) in mouse hearts, and levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in cultured HUVECs and in mice. RESULTS: EMPs were significantly elevated in patients with ASD and VSD, especially in those with pulmonary hypertension when compared with controls. EMPs increased caveolin-1 expression and P38 MAPK phosphorylation and decreased eNOS phosphorylation and NO production in mouse hearts. EMPs stimulated P38 MAPK expression, TNF-α and IL-6 production, which were all inhibited by siRNAs targeting P38 MAPK in cultured HUVECs. CONCLUSIONS: EMPs were increased in adult patients with congenital heart diseases and may contribute to increased inflammation leading to endothelial dysfunction via P38 MAPK-dependent pathways. This novel data provides a potential therapeutic target to address important complications of surgery of congenial heart disease.

Burn wound healing properties of asiaticoside and madecassoside.

The healing of burn wounds has been widely characterized to be highly intricate, involving processes such as neo-vascularization, granulation, re-epithelialization, inflammation and wound contraction. Various therapies are available for the management of burn wounds; however, a truly effective therapeutic strategy has yet to be identified due to safety issues. The aim of the present study was to assess and confirm the burn wound healing properties of the compounds asiaticoside (AE) and madecassoside (MA), which are found in the herb Centella asiatica. The cytotoxic nature of the AE and MA were inspected and were confirmed to be non-toxic up to 500 ppm. The compounds AE and MA increased monocyte chemoattractant protein-1 production, but caused no significant effect on vascular endothelial growth factor production. In addition, an in vivo animal burn model was employed to represent the features of burn wound healing. Hence, the present results warrant the further investigation of C. asiatica extracts for use in burn healing.

Storage Stability of Slightly Acidic Electrolyzed Water and Circulating Electrolyzed Water and Their Property Changes after Application.

Slightly acidic electrolyzed water (SAEW) has been recognized as an effective bactericidal agent with free chlorine, but its limitations include its instability and its great dependence on equipment. Newly developed circulating electrolyzed water (CEW) with a higher available chlorine concentration (ACC) could successfully overcome these limitations. In this study, SAEW (ACC of 20 mg/L), CEW1 (ACC of 200 mg/L), and CEW2 (ACC of 20 mg/L) were evaluated for changes in properties (pH, oxidization reduction potential [ORP], and ACC) during storage in open or closed glass bottles under light or dark conditions at room temperature (approximately 20 °C) and after washing pork and lettuce. Additionally, the washed pork and lettuce were evaluated for total viable counts, pH and general appearance. The results showed that CEW1 with a higher ACC has better stability than SAEW with a lower ACC for the storage and washing experiments, and CEW still remained stable after dilution with distilled water. The property indices of EW were greatly affected for the pork-washing experiments compared with the lettuce-washing experiments, probably due to the existence of alkaline and organic materials on the surface of pork. Furthermore, EWs were more effective for inactivating microbes in lettuce than in pork, while there was no significant difference in tissue pH and the general appearance of pork and lettuce. These findings indicated that CEW with a higher ACC shows potential for reducing foodborne pathogens on pork and lettuce without effects on their physicochemical characteristics, and it can be applied in a diluted form.

Modeling the Effect of Water Activity, pH, and Temperature on the Probability of Enterotoxin A Production by Staphylococcus aureus.

The objectives of this study were to develop a probability model of Staphylococcus aureus enterotoxin A (SEA) production as affected by water activity (a(w)), pH, and temperature in broth and assess its applicability for milk. The probability of SEA production was assessed in tryptic soy broth using 24 combinations of a(w) (0.86 to 0.99), pH (5.0 to 7.0), and storage temperature (10 to 30°C). The observed probabilities were fitted with a logistic regression to develop a probability model. The model had a concordant value of 97.5% and concordant index of 0.98, indicating that the model satisfactorily describes the probability of SEA production. The model showed that a(w), pH, and temperature were significant factors affecting the probability of toxin production. The model predictions were in good agreement with the observed values obtained from milk. The model may help manufacturers in selecting product pH and a(w) and storage temperatures to prevent SEA production.

Liquid chromatographic method for toxic biogenic amines in foods using a chaotropic salt.

Direct separation of biogenic amines by reversed-phase liquid chromatography (RPLC) is not an easy task because their basic and hydrophilic characteristics can lead to poor retention, column overloading, peak tailing, and hence low efficiency. Rather than routinely resorting to derivatization or using classical hydrophobic ion-pair reagents (IPR), this work proposes a new RPLC method making use of the chaotropic salt KPF6 as inorganic additive to an acidic acetonitrilic eluent to remedy the difficulties. Amine retention, overload behavior, peak shape, and column efficiency were significantly improved. The use of excess KPF6 led to a very slight decrease of amine retention. Depending on amine, the dependence of the logarithmic retention factor on the volume percent of acetonitrile could be reasonably linear or quite convex. Coupled with UV detection, the method was applied to trace analysis for six biogenic, aromatic or heterocyclic amines in three types of food after a sample cleanup, as necessary, by ion-pair extraction. The reliability of the whole analysis was demonstrated to be satisfactory. The proposed method outperforms existing methods in that it eliminates the need for long and cumbersome derivatization procedures without losing sensitivity; it also represents a good surrogate for classical ion-pair chromatography (IPC) because of the desirable hydrophilicity of chaotropic salts.

Exogenous hydrogen sulfide alleviates high glucose-induced cardiotoxicity via inhibition of leptin signaling in H9c2 cells.

Hydrogen sulfide (H2S) protects cardiomyoblasts against high glucose (HG)-induced injury by inhibiting the activation of p38 mitogen-activated protein kinase (MAPK). This study aims to determine whether the leptin-p38 MAPK pathway is involved in HG-induced injury and whether exogenous H2S prevents the HG-induced insult through inhibition of the leptin-p38 MAPK pathway in H9c2 cells. H9c2 cells were treated with 35 mM glucose (HG) for 24 h to establish a HG-induced cardiomyocyte injury model. Cell viability; mitochondrial membrane potential (ΔΨ m); apoptosis; reactive oxygen species (ROS) level; and leptin, leptin receptor, and p38 MAPK expression level were measured by the methods indicated. The results showed pretreatment of H9c2 cells with NaHS before exposure to HG led to an increase in cell viability, decrease in apoptotic cells, ROS generation, and a loss of ΔΨ m. Exposure of H9c2 cells to 35 mM glucose for 24 h significantly upregulated the expression levels of leptin and leptin receptors. The increased expression levels of leptin and leptin receptors were markedly attenuated by pretreatment with 400 µM NaHS. In addition, the HG-induced increase in phosphorylated (p) p38 MAPK expression was ameliorated by pretreatment with 50 ng/ml leptin antagonist. In conclusion, the present study has demonstrated for the first time that the leptin-p38 MAPK pathway contributes to the HG-induced injury in H9c2 cells and that exogenous H2S protects H9c2 cells against HG-induced injury at least in part by inhibiting the activation of leptin-p38 MAPK pathway.

Enhanced external counterpulsation inhibits endothelial apoptosis via modulation of BIRC2 and Apaf-1 genes in porcine hypercholesterolemia.

OBJECTIVES: Enhanced external counterpulsation (EECP) could improve endothelium-dependent vasodilatation of carotid artery and restore imbalance of nitric oxide and endothein-1 in patients with coronary artery disease. Our study was designed to test the hypothesis that long-term EECP may protect vascular endothelial cells from apoptosis by modifying apoptosis-related gene expression. METHODS: Eighteen male Yorkshire pigs were randomly assigned to three groups: usual diet (Normal), high cholesterol diet (HC) and high cholesterol diet plus EECP (HC+EECP). Vascular endothelial cells were isolated from the aortic endothelium and identified by CD31 staining and DiI-Ac-LDL reaction. Morphological changes were observed by both scanning and transmission electronic microscopes. TUNEL technique was applied to detect the apoptotic index of vascular endothelial cells. Two genes, Apaf-1 and BIRC2, were chosen for exploring the potential mechanisms of action at the molecular level. RESULTS: EECP brought a certain degree of alleviation from ultrastructural changes such as shrinking and blebbing of cytomembrane, marginalization, degeneration, and fragmentation of the nucleus. EECP also significantly reduced apoptotic indices while compared with that of control (177±12‰ vs. 237±23‰, P<0.05). The Apaf-1 expression at both protein and mRNA level in pigs of HC+EECP group was significantly decreased than those of the HC group (P<0.05), whereas the BIRC2 expression was significantly enhanced after EECP treatment, documented by immunostaining and semi-quantitative RT-PCR analysis, respectively (P<0.05). CONCLUSIONS: EECP could protect vascular endothelial cells from apoptosis, thereby delaying the progression of early atherosclerotic lesions possibly through transcriptional down-regulation of pro-apoptotic gene Apaf-1, and up-regulation of anti-apoptotic gene BIRC2.

Matrix metalloproteinase-9 expression in carotid atherosclerotic plaque and contrast-enhanced MRI in a swine model.

BACKGROUND: A swine model of carotid atherosclerosis may greatly facilitate the identification of imaging characteristics of vulnerable plaques and the preclinical evaluation of endovascular intervention. In this study we assess the association of matrix metalloproteinase (MMP)-9 expression and neovascularity in carotid atherosclerotic plaques with MRI patterns in a swine model. METHODS: Carotid atherosclerosis models were created in miniswine using a combination of partial ligation and a high cholesterol diet. The animals were imaged in a 1.5 T MR scanner at 3 months and carotid arteries were obtained for histopathological and immunohistochemical examination. Contrast-enhanced T1-weighted imaging (T1WI) was used to match the histology findings. The contrast-to-noise ratio (CNR) of the plaques on T1WI and contrast-enhanced T1WI were measured and the association of MMP-9 expression and neovascularity in the carotid plaque with CNR on MRI was analyzed. RESULT: Forty carotid artery segments were matched between MRI and histology. All segments were advanced carotid atherosclerotic plaques. The matched contrast-enhanced T1WI and histology slices showed good correlation for ratio of plaque size to lumen diameter (r=0.94, p<0.001). Plaque CNR on contrast-enhanced T1WI was higher in plaques with strong MMP-9 expression than in those with weak MMP-9 expression (p=0.05). Plaque CNR on contrast-enhanced T1WI was also higher in plaques with marked neovascularization than in those without (p=0.02). CONCLUSIONS: Increased plaque CNR on contrast-enhanced T1WI is associated with MMP-9 expression and neovascularization in carotid atherosclerotic plaques and may be used to identify vulnerable plaques.

Increased carotid intima media thickness is associated with prolactin levels in subjects with untreated prolactinoma: a pilot study.

Hyperprolactinemia is associated with endothelial dysfunction and atherogenic risk factors, but carotid intima media thickness (IMT) has not been studied in hyperprolactinemic patients. To determine whether untreated hyperprolactinemia contributes to increased carotid IMT. Thirty-one prolactinoma patients and 60 healthy controls were respectively studied. Participants underwent hormone evaluation. Anthropometric parameters (body mass index and blood pressure), inflammatory markers (high-sensitivity C-reactive protein and fibrinogen), serum glucose, insulin, lipid and apolipoprotein profiles were also determined. Endothelial function measured as the flow-mediated dilation (FMD) of a brachial artery and carotid IMT were evaluated using high-resolution ultrasonography. Multivariate linear regression analysis was applied to identify independent determinants of FMD and carotid IMT. Triglycerides, homeostasis model assessment of insulin resistance, apolipoprotein (apo)B/apoA-I ratio, high-sensitivity C-reactive protein (hsCRP) and fibrinogen were significantly higher, while apoA-I was significantly lower in patients with prolactinomas than in the controls. Meanwhile, decreased FMD and increased carotid IMT were observed in hyperprolactinemic group. Serum prolactin was positively correlated with triglycerides, apoB/apoA-I ratio, hypogonadal, hsCRP and fibrinogen (P < 0.05), but inversely associated with apoA-I and HDL-C (P ≤ 0.001). Moreover, prolactin was found negatively correlated with FMD (r = -0.576, P < 0.0001), and positively correlated with mean carotid IMT (r = 0.652, P < 0.0001). Multivariate regression analysis revealed that prolactin determined, independent of traditional risk factors, FMD (B = -0.589, 95% confidence interval (CI) -2.525 to -0.804, P = 0.001) and mean carotid IMT (B = 0.527, 95% CI 0.027-0.069, P < 0.0001). Hyperprolactinemia may be involved in the preclinical increase in carotid IMT, directly or by promoting atherogenic factors, including insulin resistance, low-grade inflammation and endothelial dysfunction. Additional studies are warranted to confirm our findings and explore the mechanisms underlying prolactin-associated early atherosclerosis.

Endothelial microparticles increase in mitral valve disease and impair mitral valve endothelial function.

Mitral valve endothelial cells are important for maintaining lifelong mitral valve integrity and function. Plasma endothelial microparticles (EMPs) increased in various pathological conditions related to activation of endothelial cells. However, whether EMPs will increase in mitral valve disease and their relationship remains unclear. Here, 81 patients with mitral valve disease and 45 healthy subjects were analyzed for the generation of EMPs by flow cytometry. Human mitral valve endothelial cells (HMVECs) were treated with EMPs. The phosphorylation of Akt and endothelial nitric oxide synthase (eNOS), the association of eNOS and heat shock protein 90 (HSP90), and the generation of nitric oxide (NO) and superoxide anion (O(2)(∙-)) were measured. EMPs were increased significantly in patients with mitral valve disease compared with those in healthy subjects. EMPs were negatively correlated with mitral valve area in patients with isolated mitral stenosis. EMPs were significantly higher in the group with severe mitral regurgitation than those in the group with mild and moderate mitral regurgitation. Furthermore, EMPs were decreased dramatically in both Akt and eNOS phosphorylation and the association of HSP90 with eNOS in HMVECs. EMPs decreased NO production but increased O(2)(∙-) generation in HMVECs. Our data demonstrated that EMPs were significantly increased in patients with mitral valve disease. The increase of EMPs can in turn impair HMVEC function by inhibiting the Akt/eNOS-HSP90 signaling pathway. These findings suggest that EMPs may be a therapeutic target for mitral valve disease.