Traditional Chinese medicine health literacy among rural older adults: a cross-sectional study.

Background: The purpose of this study was to understand the current status of traditional Chinese medicine (TCM) health literacy among rural older adults people and its influencing factors. Methods: This study used a random number table method to select one prefecture from Henan Province, China and used a convenience sampling method to select 200 rural older adults who met the inclusion criteria in a township in northern Henan from March to April 2023. A cross-sectional survey was conducted using a general information questionnaire and a traditional Chinese medicine health literacy questionnaire, and the influencing factors of rural older adults were analyzed using univariate analysis of variance (ANOVA) and multiple linear regression. Results: The total TCM health literacy score of 200 rural older adults people was 84.14 ± 6.709. One-way ANOVA revealed that six factors, including education level, marital status, type of occupation, presence of family members engaged in medical-related work, main economic sources, and monthly income, influenced the TCM health literacy score of rural older adults people (p < 0.05). Multiple linear regression analysis revealed that education level, occupation type, and the presence of family members engaged in medical-related work were the factors influencing the TCM health literacy of rural older adults. Conclusion: The TCM health literacy level of rural older adults people is at the lower to middle level, and health educators should strengthen the publicity and education of TCM healthcare knowledge for rural older adults people to improve their TCM health literacy level and thus enhance their quality of life.

Accelerated corrosion of 316L stainless steel in a simulated oral environment via extracellular electron transfer and acid metabolites of subgingival microbiota.

316L stainless steel (SS) is widely applied as microimplant anchorage (MIA) due to its excellent mechanical properties. However, the risk that the oral microorganisms can corrode 316L SS is fully neglected. Microbiologically influenced corrosion (MIC) of 316L SS is essential to the health and safety of all patients because the accelerated corrosion caused by the oral microbiota can trigger the release of Cr and Ni ions. This study investigated the corrosion behavior and mechanism of subgingival microbiota on 316L SS by 16S rRNA and metagenome sequencing, electrochemical measurements, and surface characterization techniques. Multispecies biofilms were formed by the oral subgingival microbiota in the simulated oral anaerobic environment on 316L SS surfaces, significantly accelerating the corrosion in the form of pitting. The microbiota samples collected from the subjects differed in biofilm compositions, corrosion behaviors, and mechanisms. The oral subgingival microbiota contributed to the accelerated corrosion of 316L SS via acidic metabolites and extracellular electron transfer. Our findings provide a new insight into the underlying mechanisms of oral microbial corrosion and guide the design of oral microbial corrosion-resistant materials.

Delivery of Small-Molecule Drugs and Protein Drugs by Injectable Acid-Responsive Self-Assembled COF Hydrogels for Combinatorial Lung Cancer Treatment.

Covalent organic frameworks (COFs) have revealed enormous application prospects for cancer therapeutics recently, but their assembly systems face considerable challenges, such as the codelivery of hydrophobic and hydrophilic protein drugs with different physicochemical properties for in vivo delivery and release, as well as endosomal/lysosomal escape of protein drugs. To address these issues, we leveraged the high specific surface area, lipotropism, and structural tunability of boronate ester-linked COFs (COF-1) for the construction of advanced drug delivery systems. We first encapsulated the small-molecule drug doxorubicin (DOX) into a lipophilic COF (COF-1@DOX) and immobilized the functional protein drug ribonuclease A (RNase A) on the surface of the COF (RNase A-COF-1@DOX). We then created a novel composite delivery system (RNase A-COF-1@DOX gel) by cross-linking an albumin-oxygenated hydrogel (gel) network into the pores of COFs, allowing targeted codelivery of protein and small-molecule drugs in vivo. Using in-living body and multichannel fluorescence imaging, we analyzed the in vivo codelivery of protein and small-molecule drugs in a Lewis lung carcinoma (LLC) model. Finally, we applied the RNase A-COF-1@DOX gel to treat lung cancer in mice. This study paves an avenue for constructing COF-based drug delivery systems for lung cancer treatment and holds the potential to be extended to other types of cancer for more effective and targeted therapeutic treatments.

The active aging level of the rural older adults with disability in China: a cross-sectional study.

Background: Active aging has been listed as an important indicator to measure the quality of life of the older adults and the construction of the senior care system. There is an imbalance between the supply and demand of senior care services for the disabled older adults in rural areas, and the quality of life needs to be improved. Objectives: We aimed to analyze the current situation of active aging and the influencing factors of the rural disabled older adults, in order to provide a reference basis for improving the quality of life of the rural disabled older adults. Methods: We conducted a multicenter and cross-sectional study, using the Barthel Index Scale and Chinese version of the Active Aging Scale, to facilitate the selection of 304 rural older adults with disability in 26 villages under Henan Province for a questionnaire survey. Results: The mean score for the level of active aging of rural older adults with disability was 1.87 (SD 0.36), with the highest score for the dimension of being self-reliant (Mean2.29, SD 0.61) and lower scores for the dimension of active contribution to society (Mean 1.37, SD 0.55) and building up financial security (Mean 1.37, SD 0.57). The results of the multiple regression analysis showed higher levels of active aging among the disabled older adults with retirement pay, mild disability, and longer time per activity/rehabilitation exercise (p < 0.05). Conclusion: Active aging of the rural disabled older adults is at a low level, with insufficient economic security and social participation. The national government should help improve the quality of primary health care in rural areas, build a friendly environment for senior communities, and improve policies to protect the welfare of the older adults, so as to collaboratively empower the disabled older adults in rural areas at three levels: health, participation, and protection.

Analysis of the information ability of nurses in county hospitals in northern Henan province: a survey.

OBJECTIVE: To investigate the status quo of nursing information ability of nurses in county-level hospitals and analyze its influencing factors. METHODS: In June 2022, a total of 303 on-the-job clinical nurses from 3 county-level hospitals in Hebi City, Henan Province were selected as subjects by convenience sampling method. General data questionnaire and self-rating nursing information ability scale were used to investigate them. RESULTS: The total score of nursing information ability of 303 nurses in county hospitals of Hebi City, Henan Province was (77.72 ± 18.76). There were statistically significant differences in the scores of nursing information ability among different ages, working years, positions, education, marriage, monthly income, whether they had learned computer-related knowledge and skills, and whether they had participated in the learning or training of nursing information system (all p < 0.05).Multiple linear regression analysis showed that age, years, position, monthly income and whether they had learned computer-related knowledge and skills were the main influencing factors of nursing information ability of county-level nurses (all p < 0.05). CONCLUSIONS: The nursing information ability of nurses in county-level hospitals in northern Henan is at a medium level. The government or society should provide training and guidance on nursing information ability, so as to provide more opportunities for nurses in county-level hospitals to participate in and learn nursing information technology to improve their ability.

Structural and optical characterization of banknotes using spectral-domain optical coherence tomography.

Counterfeiting of banknotes remains a severe threat to economic security and social stability. The characterization of banknote has mainly relied on the assessment of various security features applied to the surface of the note. However, the surface features are easy to forge and contain insufficient information to discover the source. In this paper, a novel approach for banknote characterization has been proposed by employing spectral-domain optical coherence tomography (SD-OCT) that can provide structural and optical features. Three groups of counterfeit Chinese 100 Yuan banknotes produced by different printing manners and one group of authentic banknotes were examined by SD-OCT without any sample preparation and four distinct areas were selected for imaging. High-resolution tomographic and three-dimensional (3D) volumetric OCT images were obtained and a set of features were first revealed to characterize the banknotes qualitatively and quantitatively. The results demonstrated that SD-OCT was effective to detect and classify different types of counterfeit banknotes and could potentially be used to link counterfeit banknotes to their sources in a fast, simple and nondestructive manner.

Initial Study for the Determination of the Sequence of Intersecting Lines between Gel Pens and Seals by Optical Coherence Tomography.

Determining the sequence of intersecting lines is a significant issue in the forensic document examination that can reveal the fraud or distinguish between different allegations. Optical coherence tomography (OCT) is a high-resolution cross-sectional imaging technique that has been introduced into forensic science field recently. The potential of OCT as a novel method to determine the sequence of intersecting lines was examined for the first time. In this study, a spectral-domain OCT system with a center wavelength of 900 nm was employed to perform nondestructive examination on determining the sequence of 18 heterogeneous intersecting line samples produced using three types of gel pens and three brands of stamp pad ink seals. Two-dimensional (2D) cross-sectional, and three-dimensional (3D) volumetric images of the intersecting lines were obtained by the OCT system. Several features were noted and analyzed to successfully determine the sequence of all the 18 samples. Blind tests were also conducted to demonstrate the effectiveness of OCT technique. The results illustrate that OCT technology can provide an effective and accurate method for sequencing intersecting lines of gel pen ink and seal ink, which may complement the conventional methods used in the examination of questioned documents.

LncRNA DANCR promotes the proliferation, migration, and invasion of tongue squamous cell carcinoma cells through miR-135a-5p/KLF8 axis.

BACKGROUND: Tongue squamous cell carcinoma (TSCC) is a most invasive cancer with high mortality and poor prognosis. It is reported that lncRNA DANCR has implications in multiple types of cancers. However, its biological role and underlying mechanism in TSCC progress are not well elucidated. METHODS: Our present study first investigated the function of DANCR on the proliferation, migration and invasion of TSCC cells by silencing or overexpressing DANCR. Further, the miR-135a-5p-Kruppel-like Factor 8 (KLF8) axis was focused on to explore the regulatory mechanism of DANCR on TSCC cell malignant phenotypes. Xenografted tumor growth using nude mice was performed to examine the role of DANCR in vivo. RESULTS: DANCR knockdown reduced the viability and inhibited the migration and invasion of TSCC cells in vitro, while ectopic expression of DANCR induced opposite effects. In vivo, the tumor growth and the expression of matrix metalloproteinase (MMP)-2/9 and KLF8 were also blocked by DANCR inhibition. In addition, we found that miR-135-5p directly targeted DANCR, which was negatively correlated with DANCR on TSCC progression. Its inhibition reversed the beneficial effects of DANCR silence on TSCC malignancies. Furthermore, the expression of KLF8 evidently altered by both DANCR and miR-135a-5p. Silencing KLF8 using its specific siRNA showed that KLF8 was responsible for the induction of miR-135a-5p inhibitor on TSCC cell malignancies and MMP-2/9 expression. CONCLUSIONS: These findings, for the first time, suggest that DANCR plays an oncogenic role in TSCC progression via targeting miR-135a-5p/KLF8 axis, which provides a promising biomarker and treatment approach for preventing TSCC.

S100B is required for maintaining an intermediate state with double-positive Sca-1+ progenitor and vascular smooth muscle cells during neointimal formation.

INTRODUCTION: Accumulation of vascular smooth muscle cells (VSMCs) within the neointimal region is a hallmark of atherosclerosis and vessel injury. Evidence has shown that Sca-1-positive (Sca-1+) progenitor cells residing in the vascular adventitia play a crucial role in VSMC assemblages and intimal lesions. However, the underlying mechanisms, especially in the circumstances of vascular injury, remain unknown. METHODS AND RESULTS: The neointimal formation model in rats was established by carotid artery balloon injury using a 2F-Forgaty catheter. Most Sca-1+ cells first appeared at the adventitia of the vascular wall. S100B expressions were highest within the adventitia on the first day after vessel injury. Along with the sequentially increasing trend of S100B expression in the intima, media, and adventitia, respectively, the numbers of Sca-1+ cells were prominently increased at the media or neointima during the time course of neointimal formation. Furthermore, the Sca-1+ cells were markedly increased in the tunica media on the third day of vessel injury, SDF-1α expressions were obviously increased, and SDF-1α levels and Sca-1+ cells were almost synchronously increased within the neointima on the seventh day of vessel injury. These effects could effectually be reversed by knockdown of S100B by shRNA, RAGE inhibitor (SPF-ZM1), or CXCR4 blocker (AMD3100), indicating that migration of Sca-1+ cells from the adventitia into the neointima was associated with S100B/RAGE and SDF-1α/CXCR4. More importantly, the intermediate state of double-positive Sca-1+ and α-SMA cells was first found in the neointima of injured arteries, which could be substantially abrogated by using shRNA for S100B or blockade of CXCR4. S100B dose-dependently regulated SDF-1α expressions in VSMCs by activating PI3K/AKT and NF-κB, which were markedly abolished by PI3K/AKT inhibitor wortmannin and enhanced by p65 blocker PDTC. Furthermore, S100B was involved in human umbilical cord-derived Sca-1+ progenitor cells' differentiation into VSMCs, especially in maintaining the intermediate state of double-positive Sca-1+ and α-SMA. CONCLUSIONS: S100B triggered neointimal formation in rat injured arteries by maintaining the intermediate state of double-positive Sca-1+ progenitor and VSMCs, which were associated with direct activation of RAGE by S100B and indirect induction of SDF-1α by activating PI3K/AKT and NF-κB.

KPC1 alleviates hypoxia/reoxygenation-induced apoptosis in rat cardiomyocyte cells though BAX degradation.

Bax triggers cell apoptosis by permeabilizing the outer mitochondrial membrane, leading to membrane potential loss and cytochrome c release. However, it is unclear if proteasomal degradation of Bax is involved in the apoptotic process, especially in heart ischemia-reperfusion (I/R)-induced injury. In the present study, KPC1 expression was heightened in left ventricular cardiomyocytes of patients with coronary heart disease (CHD), in I/R-myocardium in vivo and in hypoxia and reoxygenation (H/R)-induced cardiomyocytes in vitro. Overexpression of KPC1 reduced infarction size and cell apoptosis in I/R rat hearts. Similarly, the forced expression of KPC1 restored mitochondrial membrane potential (MMP) and cytochrome c release driven by H/R in H9c2 cells, whereas reducing cell apoptosis, and knockdown of KPC1 by short-hairpin RNA (shRNA) deteriorated cell apoptosis induced by H/R. Mechanistically, forced expression of KPC1 promoted Bax protein degradation, which was abolished by proteasome inhibitor MG132, suggesting that KPC1 promoted proteasomal degradation of Bax. Furthermore, KPC1 prevented basal and apoptotic stress-induced Bax translocation to mitochondria. Bax can be a novel target for the antiapoptotic effects of KPC1 on I/R-induced cardiomyocyte apoptosis and render mechanistic penetration into at least a subset of the mitochondrial effects of KPC1.

Continuous exposure of isoprenaline inhibits myoblast differentiation and fusion through PKA/ERK1/2-FOXO1 signaling pathway.

AIM: The objective of this study is to determine if exuberant sympathetic nerve activity is involved in muscle satellite cell differentiation and myoblast fusion. METHODS AND RESULTS: By using immunoassaying and western blot analyses, we found that ß1 and ß2-adrenergic receptors (AdR) were expressed in C2C12 cells. The differentiated satellite cells exhibited an increased expression of ß2-AdR, as compared with the proliferating cells. Continuous exposure of isoprenaline (ISO), a ß-AdR agonist, delayed C2C12 cell differentiation, and myoblast fusion in time- and dose-dependent manner. ISO also increased short myotube numbers while decreasing long myotube numbers, consistent with the greater reduction in MyHC1, MyHC2a, and MyHC2x expression. Moreover, continuous exposure of ISO gradually decreased the ratio of PKA RI/RII, and PKA RI activator efficiently reversed the ISO effect on C2C12 cell differentiation and myoblast fusion while PKA inhibitor H-89 deteriorated the effects. Continuous single-dose ISO increased ß1-AdR expression in C2C12 cells. More importantly, the cells showed enhanced phospho-ERK1/2 levels, resulting in increasing phospho-ß2-AdR levels while decreasing ß2-AdR levels, and the specific effects could be abolished by ERK1/2 inhibitor. Furthermore, continuous exposure of ISO induced FOXO1 nuclear translocation and increased the levels of FOXO1 in nuclear extracts while reducing pAKT, p-p38MAPK, and pFOXO1 levels. Conversely, blockade of ERK1/2 signaling partially abrogated ISO effects on AKT, p38MAPK, and FOXO1signaling, which partially restored C2C12 cell differentiation and myoblast fusion, leading to an increase in the numbers of medium myotube along with the increased expression of MyHC1 and MyHC2a. CONCLUSION: Continuous exposure of ISO impedes satellite cell differentiation and myoblast fusion, at least in part, through PKA-ERK1/2-FOXO1 signaling pathways, which were associated with the reduced ß2-AdR and increased ß1-AdR levels.

VEGF-A and VEGF-B Coordinate the Arteriogenesis to Repair the Infarcted Heart with Vagus Nerve Stimulation.

BACKGROUND/AIMS: Vagus nerve stimulation (VNS) suppresses arrhythmic activity and minimizes cardiomyocyte injury. However, how VNS affects angiogenesis/arteriogenesis in infarcted hearts, is poorly understood. METHODS: Myocardial infarction (MI) was achieved by ligation of the left anterior descending coronary artery (LAD) in rats. 7 days after LAD, stainless-steel wires were looped around the left and right vagal nerve in the neck for vagus nerve stimulation (VNS). The vagal nerve was stimulated with regular pulses of 0.2ms duration at 20 Hz for 10 seconds every minute for 4 hours, and then ACh levels by ELISA in cardiac tissue and serum were evaluated for its release after VNS. Three and 14 days after VNS, Real-time PCR, immunostaining and western blot were respectively used to determine VEGF-A/B expressions and α-SMA- and CD31-postive vessels in VNS-hearts with pretreatment of α7-nAChR blocker mecamylamine (10 mg/kg, ip) or mACh-R blocker atropine (10 mg/kg, ip) for 1 hour. The coronary function and left ventricular performance were analyzed by Langendorff system and hemodynamic parameters in VNS-hearts with pretreatment of VEGF-A/B-knockdown or VEGFR blocker AMG706. Coronary arterial endothelial cells proliferation, migration and tube formation were evaluated for angiogenesis following the stimulation of VNS in coronary arterial smooth muscle cells (VSMCs). RESULTS: VNS has been shown to stimulate VEGF-A and VEGF-B expressions in coronary arterial smooth muscle cells (VSMCs) and endothelial cells (ECs) with an increase of α-SMA- and CD31-postive vessel number in infarcted hearts. The VNS-induced VEGF-A/B expressions and angiogenesis were abolished by m-AChR inhibitor atropine and α7-nAChR blocker mecamylamine in vivo. Interestingly, knockdown of VEGF-A by shRNA mainly reduced VNS-mediated formation of CD31+ microvessels. In contrast, knockdown of VEGF-B powerfully abrogated VNS-induced formation of α-SMA+ vessels. Consistently, VNS-induced VEGF-A showed a greater effect on EC tube formation as compared to VNS-induced VEGF-B. Moreover, VEGF-A promoted EC proliferation and VSMC migration while VEGF-B induced VSMC proliferation and EC migration in vitro. Mechanistically, vagal neurotransmitter acetylcholine stimulated VEGF-A/B expressions through m/nACh-R/PI3K/Akt/Sp1 pathway in EC. Functionally, VNS improved the coronary function and left ventricular performance. However, blockade of VEGF receptor by antagonist AMG706 or knockdown of VEGF-A or VEGF-B by shRNA significantly diminished the beneficial effects of VNS on ventricular performance. CONCLUSION: VNS promoted angiogenesis/arteriogenesis to repair the infracted heart through the synergistic effects of VEGF-A and VEGF-B.

Detection of latent fingerprint hidden beneath adhesive tape by optical coherence tomography.

Adhesive tape is one type of common item which can be encountered in criminal cases involving rape, murder, kidnapping and explosives. It is often the case that a suspect deposits latent fingerprints on the sticky side of adhesive tape material when tying up victims, manufacturing improvised explosive devices or packaging illegal goods. However, the adhesive tapes found at crime scenes are usually stuck together or attached to a certain substrate, and thus the latent fingerprints may be hidden beneath the tapes. Current methods to detect latent fingerprint hidden beneath adhesive tape need to peel it off first and then apply physical or chemical methods to develop the fingerprint, which undergo complicated procedures and would affect the original condition of latent print. Optical coherence tomography (OCT) is a novel applied techniques in forensics which enables obtaining cross-sectional structure with the advantages of non-invasive, in-situ, high resolution and high speed. In this paper, a custom-built spectral-domain OCT (SD-OCT) system with a hand-held probe was employed to detect fingerprints hidden beneath different types of adhesive tapes. Three-dimensional (3D) OCT reconstructions were performed and the en face images were presented to reveal the hidden fingerprints. The results demonstrate that OCT is a promising tool for rapidly detecting and recovering high quality image of latent fingerprint hidden beneath adhesive tape without any changes to the original state and preserve the integrity of the evidence.

Reducing the stigma associated with anorexia nervosa: An evaluation of a social consensus intervention among Australian and Chinese young women.

OBJECTIVE: This study examined the effectiveness of a social consensus intervention in reducing stigma toward individuals with anorexia nervosa (AN) among women from Australia and mainland China. Moreover, the different predictions of informational/normative social influence theory and the social identity approach in terms of the effectiveness of the social consensus intervention were investigated. METHOD: Participants were female students from the Australian National University (n = 97) and Central China Normal University (n = 76) who reported their levels of stigma toward a fictional character with AN before and after receiving normative information regarding the attitudes of others toward people with AN. Three experimental conditions of normative information were utilized: in-group, out-group, and neutral. RESULTS: Chinese participants reported higher levels of baseline stigma across all measures than Australian participants. Social consensus was effective in reducing most types of AN stigma, and supported the social identity approach in that improvements in attitudinal, affective, and behavioral aspects of stigma were significantly greater for participants in the in-group (but not the out-group) versus the neutral condition. The effectiveness of the social consensus approach was not moderated by nationality. DISCUSSION: A social consensus approach holds potential as an additional strategy for reducing AN stigma, with its benefits extending across diverse cultural settings. Such an approach would entail ensuring that positive messages regarding people with AN are delivered by members of a valued in-group.

S100B promotes injury-induced vascular remodeling through modulating smooth muscle phenotype.

S100B is a biomarker of nervous system injury, but it is unknown if it is also involved in vascular injury. In the present study, we investigated S100B function in vascular remodeling following injury. Balloon injury in rat carotid artery progressively induced neointima formation while increasing S100B expression in both neointimal vascular smooth muscle (VSMC) and serum along with an induction of proliferating cell nuclear antigen (PCNA). Knockdown of S100B by its shRNA delivered by adenoviral transduction attenuated the PCNA expression and neointimal hyperplasia in vivo and suppressed PDGF-BB-induced VSMC proliferation and migration in vitro. Conversely, overexpression of S100B promoted VSMC proliferation and migration. Mechanistically, S100B altered VSMC phenotype by decreasing the contractile protein expression, which appeared to be mediated by NF-κB activity. S100B induced NF-κB-p65 gene transcription, protein expression and nuclear translocation. Blockade of NF-κB activity by its inhibitor reversed S100B-mediated downregulation of VSMC contractile protein and increase in VSMC proliferation and migration. It appeared that S100B regulated NF-κB expression through, at least partially, the Receptor for Advanced Glycation End products (RAGE) because RAGE inhibitor attenuated S100B-mediated NF-κB promoter activity as well as VSMC proliferation. Most importantly, S100B secreted from VSMC impaired endothelial tube formation in vitro, and knockdown of S100B promoted re-endothelialization of injury-denuded arteries in vivo. These data indicated that S100B is a novel regulator for vascular remodeling following injury and may serve as a potential biomarker for vascular damage or drug target for treating proliferative vascular diseases.

Characterization of automotive paint by optical coherence tomography.

Automotive paint is common trace evidence that plays a significant role in many vehicle-related criminal cases. However, the conventional methods of obtaining tomographic images tend to damage the samples. Optical coherence tomography (OCT) is a novel method to obtain high-resolution and cross-sectional images of the automotive paints in a non-destructive, and high-speed manner. In this study, OCT was applied to image and analyze the automotive paint, using scanning electron microscope (SEM) as reference. Eight automotive paint samples of different brands were examined. The images of multi-layer structures provided by OCT system with 5µm depth resolution were consistent with those by SEM. To distinguish different paints with similar visual appearance, we extracted internal structural features from the images using peak analysis and optical attenuation fit. Six characterized parameters were found to distinguish the samples including the optical path length (OPL) of base coat, the optical attenuation coefficient (OAC) of base coat, the OPL of clear coat, the back-scattering ratio (BSR) of clear coat and base coat, the OPL of primer surfacer, and the BSR of base coat and primer. Statistical differences were evaluated by an independent t-test with p<0.05. OCT was applied to analyze repainted paint as well. Three-dimensional OCT reconstruction of the paints was also implemented to create en face (transverse section) images for morphology examination and comparison. These results suggest that OCT imaging can provide additional new features for analyzing the automotive paints and thereby may be a promising supplement to traditional methods. Meanwhile, the OCT system is favorable for achieving in-situ and real-time examination at the scene of crime.

Vascular endothelial growth factor-C protects heart from ischemia/reperfusion injury by inhibiting cardiomyocyte apoptosis.

VEGF-C is a newly identified proangiogenic protein playing an important role in vascular disease and angiogenesis. However, its role in myocardial ischemia/reperfusion (I/R) injury remains unknown. The objective of this study was to determine the role and mechanism of VEGF-C in myocardial ischemia-reperfusion injury. Rat left ventricle myocardium was injected with recombinant human VEGF-C protein (0.1 or 1.0 µg/kg b.w.) 1 h prior to myocardial ischemia-reperfusion (I/R) injury. 24 h later, the myocardial infarction size, the number of TUNEL-positive cardiomyocytes, the levels of creatine kinase (CK), CK-MB, cardiac troponin, malondialdehyde (MDA) content, and apoptosis protein Bax expression were decreased, while Bcl2 and pAkt expression were increased in VEGF-C-treated myocardium as compared to the saline-treated I/R hearts. VEGF-C also improved the function of I/R-injured hearts. In the H2O2-induced H9c2 cardiomyocytes, which mimicked the I/R injury in vivo, VEGF-C pre-treatment decreased the LDH release and MDA content, blocked H2O2-induced apoptosis by inhibiting the pro-apoptotic protein Bax expression and its translocation to the mitochondrial membrane, and consequently attenuated H2O2-induced decrease of mitochondrial membrane potential and increase of cytochrome c release from mitochondria. Mechanistically, VEGF-C activated Akt signaling pathway via VEGF receptor 2, leading to a blockade of Bax expression and mitochondrial membrane translocation and thus protected cardiomyocyte from H2O2-induced activation of intrinsic apoptotic pathway. VEGF-C exerts its cardiac protection following I/R injury via its anti-apoptotic effect.

VEGF-A promotes cardiac stem cell engraftment and myocardial repair in the infarcted heart.

BACKGROUND: The objective of this study was to determine whether vascular endothelial growth factor (VEGF)-A subtypes improve cardiac stem cell (CSC) engraftment and promote CSC-mediated myocardial repair in the infarcted heart. METHODS: CSCs were treated with VEGF receptor (VEGFR) inhibitors, VCAM-1 antibody (VCAM-1-Ab), or PKC-α inhibitor followed by the treatment with VEGF-A. CSC adhesion assays were performed in vitro. In vivo, the PKH26-labeled and VCAM-1-Ab or PKC-α inhibitor pre-treated CSCs were treated with VEGF-A followed by implantation into infarcted rat hearts. The hearts were then collected for measuring CSC engraftment and evaluating cardiac fibrosis and function 3 or 28days after the CSC transplantation. RESULTS: All three VEGF-A subtypes promoted CSC adhesion to extracellular matrix and endothelial cells. VEGF-A-mediated CSC adhesion required VEGFR and PKCα signaling. Importantly, VEGF-A induced VCAM-1, but not ICAM-1 expression in CSCs through PKCα signaling. In vivo, VEGF-A promoted the engraftment of CSCs in infarcted hearts, which was attenuated by PKCα inhibitor or VCAM-1-Ab. Moreover, VEGF-A-mediated CSC engraftment resulted in a reduction in infarct size and fibrosis. Functional studies showed that the transplantation of the VEGF-A-treated CSCs stimulated extensive angiomyogenesis in infarcted hearts as indicated by the expression of cardiac troponin T and von Willebrand factor, leading to an improved performance of left ventricle. Blockade of PKCα signaling or VCAM-1 significantly diminished the beneficial effects of CSCs treated with VEGF-A. CONCLUSION: VEGF-A promotes myocardial repair through, at least in part, enhancing the engraftment of CSCs mediated by PKCα/VCAM-1 pathway.