Hybrid heart valves with VEGF-loaded zwitterionic hydrogel coating for improved anti-calcification and re-endothelialization.

With the aging of the population in worldwide, valvular heart disease has become one of the most prominent life-threatening diseases in human health, and heart valve replacement surgery is one of the therapeutic methods for valvular heart disease. Currently, commercial bioprosthetic heart valves (BHVs) for clinical application are prepared with xenograft heart valves or pericardium crosslinked by glutaraldehyde. Due to the residual cell toxicity from glutaraldehyde, heterologous antigens, and immune response, there are still some drawbacks related to the limited lifespan of bioprosthetic heart valves, such as thrombosis, calcification, degeneration, and defectiveness of re-endothelialization. Therefore, the problems of calcification, defectiveness of re-endothelialization, and poor biocompatibility from the use of bioprosthetic heart valve need to be solved. In this study, hydrogel hybrid heart valves with improved anti-calcification and re-endothelialization were prepared by taking decellularized porcine heart valves as scaffolds following grafting with double bonds. Then, the anti-biofouling zwitterionic monomers 2-methacryloyloxyethyl phosphorylcholine (MPC) and vascular endothelial growth factor (VEGF) were utilized to obtain a hydrogel-coated hybrid heart valve (PEGDA-MPC-DHVs@VEGF). The results showed that fewer platelets and thrombi were observed on the surface of the PEGDA-MPC-DHVs@VEGF. Additionally, the PEGDA-MPC-DHVs@VEGF exhibited excellent collagen stability, biocompatibility and re-endothelialization potential. Moreover, less calcification deposition and a lower immune response were observed in the PEGDA-MPC-DHVs@VEGF compared to the glutaraldehyde-crosslinked DHVs (Glu-DHVs) after subcutaneous implantation in rats for 30 days. These studies demonstrated that the strategy of zwitterionic hydrogels loaded with VEGF may be an effective approach to improving the biocompatibility, anti-calcification and re-endothelialization of bioprosthetic heart valves.

The Determinant of DNA Repair Pathway Choices in Ionising Radiation-Induced DNA Double-Strand Breaks.

Ionising radiation- (IR-) induced DNA double-strand breaks (DSBs) are considered to be the deleterious DNA lesions that pose a serious threat to genomic stability. The major DNA repair pathways, including classical nonhomologous end joining, homologous recombination, single-strand annealing, and alternative end joining, play critical roles in countering and eliciting IR-induced DSBs to ensure genome integrity. If the IR-induced DNA DSBs are not repaired correctly, the residual or incorrectly repaired DSBs can result in genomic instability that is associated with certain human diseases. Although many efforts have been made in investigating the major mechanisms of IR-induced DNA DSB repair, it is still unclear what determines the choices of IR-induced DNA DSB repair pathways. In this review, we discuss how the mechanisms of IR-induced DSB repair pathway choices can operate in irradiated cells. We first briefly describe the main mechanisms of the major DNA DSB repair pathways and the related key repair proteins. Based on our understanding of the characteristics of IR-induced DNA DSBs and the regulatory mechanisms of DSB repair pathways in irradiated cells and recent advances in this field, We then highlight the main factors and associated challenges to determine the IR-induced DSB repair pathway choices. We conclude that the type and distribution of IR-induced DSBs, chromatin state, DNA-end structure, and DNA-end resection are the main determinants of the choice of the IR-induced DNA DSB repair pathway.

Identification of potential radiation-responsive biomarkers based on human orthologous genes with possible roles in DNA repair pathways by comparison between Arabidopsis thaliana and homo sapiens.

Rapid and reliable ionization radiation (IR) exposure estimation has become increasingly important in environment due to the urgent requirement of medical evaluation and treatment in the event of nuclear accident emergency. Human DNA repair genes can be identified as important candidate biomarkers to assess IR exposure, while how to find the enough sensitive and specific biomarkers in the DNA repair networks is still challenged and not fully determined. The conserved features of DNA repair pathways may facilitate interdisciplinary studies that cross the traditional boundaries between animal and plant biology, with the aim of identifying undiscovered human DNA repair genes for potential radiation-responsive biomarkers. In this work, an in silico method of homologous comparison was performed to identify the human orthologues of A. thaliana DNA repair genes, and thereby to explore the sensitive and specific human radiation-responsive genes to evaluate the IR exposure levels. The results showed that a total of 16 putative candidate genes were involved in the human DNA repair pathways of homologous recombination (HR) and non-homologous end joining (NHEJ), and most of them were confirmed by previous experiments. Additionally, we analyzed the gene expression patterns of these 16 candidate genes in several human transcript microarray datasets with different IR treatments. The results indicated that most of the gene expression levels for these candidate genes were significantly changed under different radiation treatments. Based on these results, we integrated these putative human DNA repair genes into the DNA repair pathways to propose new insights of the HR and NHEJ pathways, which can also provide the potential targets for the development of radiation biomarkers. Notably, two putative DNA repair genes, named ERCC1 and ESCO2, were identified and were considered to be the sensitive and specific biomarkers in response to γ-ray exposures.

Fitting the Generalized Target Model to Cell Survival Data of Proton Radiation Reveals Dose-Dependent RBE and Inspires an Alternative Method to Estimate RBE in High-Dose Regions.

The imprecise estimation of the relative biological effectiveness (RBE) of proton radiation has been one of the main challenges for further calculating the biologically effective dose in proton therapy. Since dose levels can greatly influence the proton RBE, the relationship between the two should be clarified first. In addition, since the dose-response curves are usually too complex to readily assess RBE in high-dose regions, a reliable and simple method is needed to predict the RBE of proton radiation accurately in clinically relevant doses. The standard linear-quadratic (LQ) model is widely used to determine the RBE of particles for clinical applications. However, there has been some debate over its use when modeling the cell survival curves in high-dose regions, since those survival curves usually show linear behavior in the semilogarithmic plot. By considering both cellular repair effects and indirect effects of radiation, we have proposed a generalized target model with linear-quadratic linear (LQL) characteristics. For the more accurate evaluation of proton RBE in radiotherapy, here we used this generalized target model to fit the cell survival data in V79 and C3H 10T1/2 cells exposed to proton radiation with different LETs. The fitting results show that the generalized target model works as well as the LQ model in general. Based on the fitting parameters of the generalized target model, the RBE of six given doses DT (RBET) could be calculated in the corresponding cell lines with different LETs. The results show that the RBET gradually decreases with increased dose in both cell types. In addition, inspired by the calculation method of the maximum values of RBE (RBEM) in the low-dose region, a novel method was proposed for estimating the RBE in the high-dose region (RBEH) based on the slope ratio of the dose-response curves in this region. Linear regression analysis indicated a significant linear correlation between the proposed RBEH and the RBET in high-dose regions, which suggests that the current method can be used as an alternative tool, which is both simple and robust, to estimate RBE in high-dose regions.

Preparation of Bone Marrow Mesenchymal Stem Cells Combined with Hydroxyapatite/Poly(d,l-lactide) Porous Microspheres for Bone Regeneration in Calvarial Defects.

A novel three-dimensional biomimetic porous microsphere was successfully designed in this study, which was composed of PDLLA, bone marrow mesenchymal stem cells (MSCs), and nanohydroxyapatite (nHAp). nHAp/PDLLA/MSC porous microspheres that are supposed to be a significant constituent of bone in vertebrate were prepared to act as biodegradable support materials. In addition, bone MSCs act as seeding cells in bone defect repair. The microstructure of the obtained nHAp/PDLLA/MSC porous microspheres was characterized. Scanning electronic microscopy showed that the composite materials exhibited a cross-linked porous structure. In vivo biocompatibility was studied by the way of implanting the nHAp/PDLLA porous microspheres subcutaneously in rats for 4 and 8 weeks. In addition, the osteogenic capacity of the nHAp/PDLLA/MSC porous microspheres was assessed by implanting the 10 mm × 10 mm × 3 mm cranial defect of New Zealand white rabbits. In vivo studies confirmed that nHAp/PDLLA/MSC porous microspheres had a good biocompatibility and were better in inducing bone regeneration than nHAp/PDLLA porous microspheres and the self-healing process. All of the results suggested that the nHAp/PDLLA/MSC porous microspheres present a remarkable potential in calvarial defect repair and bone tissue engineering.

A novel botryoidal aramid fiber reinforcement of a PMMA resin for a restorative biomaterial.

Poly(methyl methacrylate) (PMMA) resin is widely used as a prosthetic and restorative biomaterial, such as in bone cement, denture base resin, etc. The flexural and compressive strength of a PMMA resin is of great concern and many approaches have been made to improve the flexural resistance and compressive strength of PMMA. To strengthen PMMA via high-performance (HP) fibers is a feasible way; however, the HP fibers are not very satisfactory in practice, with a complex handling process and esthetic concerns. The aim of this study is to investigate the preparation of a novel botryoidal PMMA microsphere-grafted aramid fiber system, which has never been reported before, and the flexural and compression behavior of the PMMA/aramid composite, and evaluate the cytotoxic effects of the PMMA/aramid composite. As a result, the addition of a microsphere-grafted aramid fiber to an acrylic resin, with the esthetic problem of the aramid fiber minimized, simultaneously improves the mechanical properties and the safety of the PMMA/aramid composite in vitro is proven acceptable, suggesting that the novel composite has great potential in the field of restorative materials in clinical applications where high mechanical properties are required such as hard tissue repairing.

Hypertension prevalence, awareness, treatment, and control in 115 rural and urban communities involving 47 000 people from China.

BACKGROUND: Identification and treatment of hypertension in China remain suboptimal despite high prevalence of hypertension and increasing incidence of stroke and myocardial infarction. OBJECTIVE: This study reported blood pressure levels, prevalence, awareness, treatment, and control rates of hypertension, in addition to drug treatments in China. METHODS: This is a country-specific analysis of 45 108 individuals, average age 51.4 (standard deviation 9.6) (35-70) years, enrolled between 2005 and 2009, from 70 rural and 45 urban communities in 12 provinces. RESULTS: Among 18 915 (41.9% overall population) hypertensive participants, 7866 (41.6%) were aware, 6503 (34.4%) treated but only 1545 (8.2%) controlled. Prevalence of hypertension was higher, but awareness, treatment, and control were lower in rural than urban residents. Prevalence of hypertension was highest in eastern (44.3%), intermediate in central (39.3%), and lowest in western regions (37.0%). Awareness was higher in central (44.3%) and eastern (42.4%) but lower in western regions (37.0%). Similar patterns were observed in treatment rates, 37.7% central, 35.2% eastern, and 26.7% in western regions with control rates of 8.3% in eastern, 7.6% central, and 5.3% west regions. Of 4744 participants receiving documented treatments, 37.5% received traditional combination drugs alone, 55.4% western drugs alone and 7.1% combination of traditional combination drug in addition to western drugs. CONCLUSION: In China, hypertension is common, and while recent studies suggest some improvements, more than half of affected individuals were unaware that they had hypertension. Rates of control remain low. National programs effective in preventing and controlling hypertension in China are urgently needed.

Superior effect of an angiotensin-converting enzyme inhibitor over a diuretic for reducing aortic systolic pressure.

BACKGROUND: In recent studies, benefit has been shown for angiotensin-converting enzyme (ACE) inhibitors and calcium antagonists over a beta-blocker in hypertension, through a greater reduction in aortic than brachial systolic and pulse pressure. No data are available on diuretics, even though these are the preferred initial treatment of patients with mild hypertension. METHODS: In this study, 101 patients with mild essential hypertension were randomly assigned to an 8-week period of monotherapy with enalapril 10 mg a day or indapamide 2.5 mg a day. Central as well as brachial systolic, augmented, and pulse pressure were determined using SphygmoCor, as in the REASON and CAFE trials. RESULTS: Enalapril and indapamide reduced brachial systolic, diastolic, mean and pulse pressure to the same extent, and the heart rate was unchanged. Although there was no difference in brachial pressure with enalapril and indapamide, enalapril caused a greater fall in estimated aortic systolic, and pulse pressures. The augmentation index, an index of wave reflection, fell from 33.7 to 28.3% with enalapril but was unchanged with indapamide. CONCLUSION: Results infer a reduction in wave reflection with enalapril, causing a fall in aortic pressure augmentation, and a corresponding fall in aortic systolic and pulse pressure. These were not apparent from brachial cuff measurements. Results show that a diuretic, like a beta-blocker agent, is not as effective a therapy as an ACE inhibitor in reducing aortic systolic and pulse pressure, and that the difference is not attributable to a change in heart rate.

Hypertension and health-related quality of life: an epidemiological study in patients attending hospital clinics in China.

OBJECTIVE: To examine the relationship between hypertension and health-related quality of life in patients attending hospital clinics in China. DESIGN AND METHODS: A cross-sectional survey. Patients over the age of 35 years attending outpatient clinics in 18 hospitals of eight major cities of northern and southern China were interviewed between June and July, 1999. Trained fieldworkers completed questionnaires regarding demographics, hypertension knowledge and awareness, treatment history and quality of life issues. Qualified physicians performed blood pressure assessments. RESULTS: A total of 9703 volunteers were enrolled; 4510 (46.5%) had hypertension. The results showed that hypertensive subjects scored lower in the multiple linear regression analyses in most questions on the quality of life questionnaire than those without hypertension after controlling for age, sex, sociodemographic factors, and co-morbidity. There was a strikingly high prevalence of physical complaints or symptoms. Among the variables considered, age, sex, hypertension, body mass index, educational level, smoking, history of cholesterol, family history of cardiovascular diseases and history of diabetes were statistically significantly correlated with health-related quality of life. Subjects aware of having high blood pressure had a lower health-related quality of life score than subjects with high blood pressure but unaware of the diagnosis. Among treated subjects, those with controlled hypertension had higher health-related quality of life scores than those with poorly controlled hypertension. CONCLUSIONS: Hypertensive individuals represent a vulnerable population that merits special attention from healthcare providers and systems. This is especially important given that low health-related quality of life can be a risk factor for subsequent cardiovascular events or complications.

Awareness, treatment and control of hypertension in patients attending hospital clinics in China.

OBJECTIVES: To determine awareness, treatment and control of hypertension in patients attending hospital clinics in China. DESIGN: A cross-sectional survey. PATIENTS AND SETTING: Patients over the age of 35 years, who were attending outpatient clinics in 18 hospitals of eight major cities of Northern and Southern China, were interviewed face-to-face between June and July 1999. METHODS: Trained fieldworkers completed questionnaires regarding demographics, hypertension knowledge and awareness, treatment history and quality of life issues. Qualified physicians performed blood pressure assessment. RESULTS: A total of 9703 volunteers enrolled, of which 4510 (46.5%) were hypertensives. Among hypertensives, 23% were unaware of their high blood pressure. Although 89% of those aware reported receiving therapy, only 56% of them were taking medication regularly, and 33% were thus controlled. Although 69% of all hypertensives measuring at examination reported taking antihypertensive therapy, only 44% of them were actually taking medication regularly. Furthermore, 73% of hypertensives believed hypertension was not a serious problem, and required no regular medication. CONCLUSIONS: The results showed that a substantial number of outpatients have a hypertensive range of blood pressure. Although most of these patients are already being treated with drug regimen, the patient's misconceptions and lack of knowledge about the disease appear to be the major cause of treatment failure. The low rate of high blood pressure control for both sexes calls for further improvements.