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Interventional treatments of tricuspid regurgitation have been emerging as minimally invasive alternatives. Among those reported transcatheter tricuspid devices, the radial force between the device and native tricuspid annulus is the common principle to be employed for device immobilization. However, this immobilization mechanism may potentially lead to adverse consequences. We developed a radial force-independent stent valve device for implantation at native tricuspid annular site without inducing stress on either myocardial tissue or the bioprosthesis. We designed a radial force-independent LuX-Valve as a transcatheter bioprosthesis, comprising a stent valve and a delivery system. The device employs a combination of a right ventricle anchoring component, two leaflet-grasping clips, and an atrial disc as a mechanical integrity to immobilize the stent valve device in secure at the native tricuspid annulus. We evaluated the feasibility and safety of implantation of this device in a goat model. We successfully implanted LuX-Valves at the tricuspid position through the right atrium in 17 goats. Procedures in 16 cases were safe. Time for the operator to implant the device until immobilization in secure ranged from 3.5 to 10 min. No significant paravalvular leakage was detected by echocardiography during follow-up, up to 180 days. Histopathology showed no evidence of stent fracture and myocardial injury. The results indicated that radial force-independent LuX-Valve was safe and practicable for tricuspid valve implantation with satisfactory prosthetic function. • LuX-Valve is a new radial force-independent TTVR device. • LuX-Valve adopted an interventricular septum anchor and two graspers for fixation. • LuX-Valve adopted a valve disc to prevent perivalvular leakage. • LuX-Valve was safe and practicable for TTVR in animal. [ABSTRACT FROM AUTHOR]

Abstract: Background: Cell transplantation and gene therapy have been demonstrated to have beneficial effects after a myocardial infarction (MI). Here, we used a large animal model of MI to investigate the beneficial effects of mesenchymal stem cells (MSCs) transfected with hepatocyte growth factor (HGF) or vascular endothelial growth factor (VEGF) genes. Methods: A porcine MI model was created by balloon occlusion of the distal left anterior descending artery for 90min followed by reperfusion. At 1week after MI, the pigs were infused via the coronary vein with saline (n=8), MSCs+AdNull(n=8), MSC+VEGF(n=10), or MSC+HGF(n=10). Cardiac function and myocardial perfusion were evaluated by using echocardiography and gated cardiac perfusion imaging before and 4weeks after transplantation. Morphometric and histological analyses were performed. Results: All cell-implanted groups had better cardiac function than the saline control group. There were further functional improvements in the MSC+HGF group, accompanied by smaller infarct sizes, increased cell survival, and less collagen deposition. Blood vessel densities in the damaged area and cardiac perfusion were significantly greater in the MSC+AdNull group than in the saline control group, and further increased in the MSC+VEGF/HGF groups. Tissue fibrosis was significantly less extensive in the MSC and MSC+VEGF groups than in the saline control group and was most reduced in the MSC+HGF group. Conclusion: MSCs (alone or transfected with VEGF/HGF) delivered into the infarcted porcine heart via the coronary vein improved cardiac function and perfusion, probably by increasing angiogenesis and reducing fibrosis. MSC+HGF was superior to MSC+VEGF, possibly owing to its enhanced antifibrotic effect. [Copyright &y& Elsevier]

Background: The study aimed to evaluate the prognostic value of preoperative systemic inflammation response index (SIRI) for acute type A aortic dissection (ATAD) following open surgery. Methods and results: Totally, 410 ATAD patients underwent open surgery from 2019 to 2021 were enrolled in the study. Among the patients, the in-hospital mortality was 14.4%. Cox regression (95%CI 1.033–1.114p < 0.001) and receiver operating characteristic curve analysis (AUC = 0.718, p < 0.001) demonstrated the prognostic role of SIRI for in-hospital mortality after surgery. The optimal cut-off value of SIRI for in-hospital mortality was identified as 9.43 by maximally selected Log-Rank statistics. The patients were divided into high SIRI group (SIRI ≥ 9.43) and low SIRI group (SIRI < 9.43)) after the linear inverse relationship between SIRI and hazard ratio for in-hospital mortality was demonstrated by restricted cubic spline analysis (p = 0.0742). The Kaplan–Meier analysis illustrated that in-hospital mortality increased significantly in high SIRI group (p < 0.001). In addition, elevating SIRI was significantly associated with the incidence of coronary sinus tear (95%CI 1.020–4.475p = 0.044). Furthermore, the incidence rate of postoperative complications including renal failure (p < 0.001) and infection (p = 0.019) was higher in high SIRI group. Conclusion: The study indicated that preoperative SIRI could provide strong prognostic value for in-hospital mortality in ATAD patients following open surgery. Thus, SIRI was a promising biomarker for risk stratification and management prior to open surgery. [ABSTRACT FROM AUTHOR]

Background: Patients undergoing total knee arthroplasty (TKA) surgery are at high risk of chronic postsurgical pain (CPSP). Accumulating evidence suggests an active role of neuroinflammation in chronic pain. However, its role in the progression to CPSP following TKA surgery remains unanswered. Here, we examined the associations between preoperative neuroinflammatory states and pre‐ and postsurgical chronic pain in TKA surgery. Methods: The data of 42 patients undergoing elective TKA surgery for chronic knee arthralgia at our hospital were analyzed in this prospective study. Patients completed the following questionnaires: brief pain inventory (BPI), hospital anxiety and depression scale, painDETECT, and pain catastrophizing scale (PCS). Cerebrospinal fluid (CSF) samples were collected preoperatively and concentrations of IL‐6, IL‐8, TNF, fractalkine, and CSF‐1 were measured by electrochemiluminescence multiplex immunoassay. CPSP severity was ascertained, using the BPI, 6 months postsurgery. Results: While no significant correlation was observed between the preoperative CSF mediator levels and preoperative pain profiles, the preoperative fractalkine level in the CSF showed a significant correlation with CPSP severity (Spearman's rho = −0.525; p =.002). Furthermore, multivariate linear regression analysis revealed that the preoperative PCS score (standardized β coefficient [β]:.11; 95% confidence interval [CI]: 0.06–0.16; p <.001) and CSF fractalkine level (β: −.62; 95% CI: −1.10 to −0.15; p =.012) were independent predictors of CPSP severity 6 months after TKA surgery. Conclusions: We identified the CSF fractalkine level as a potential predictor for CPSP severity following TKA surgery. In addition, our study provided novel insights into the potential role of neuroinflammatory mediators in the pathogenesis of CPSP. [ABSTRACT FROM AUTHOR]

Patients with long-term tricuspid regurgitation (TR) are mostly accompanied by hepatic, cardiac, and venous remodeling. Transcatheter tricuspid valve replacement (TTVR) device has emerged as a promising alternative to open-heart surgery for TR patients. No study has assessed the impact of TTVR on hepatic, cardiac, and venous remodeling. Twenty-two patients with TR enrolled in this study underwent TTVR between October 2020 and January 2021. Liver, heart, and veins were reconstructed by three-dimensional computed tomography reconstruction software at baseline and 6 months follow-up. Twenty-two patients were enrolled in this study. The mean age was 64.8 ± 8.2 years, and all patients had severe or greater TR with multiple comorbidities. The left hepatic lobe volume decreased from 518.8 ± 171.9 ml to 470.4 ± 179.6 ml at 6 months during follow-up (p = 0.049). Evidence of a decrease in three hepatic veins parameters and splenic vein parameters was noted from baseline to 6 months. And a significant decrease in right atrial volume (317.5 ml [interquartile range: 216.1 to 497.3 ml] vs. 266.7 ml [interquartile range: 178.7 to 480.7 ml]; p = 0.003) were observed in the study. Six-month outcomes show that TR elimination by LuX-Valve is associated with the reverse remodeling of liver, heart, and veins. Accordingly, LuX-Valve is a promising alternative for patients presenting with severe TR. [Display omitted] • The LuX-Valve system is the first radial force-independent transcatheter tricuspid valve replacement device. • Tricuspid regurgitation elimination by LuX-Valve is associated with the reverse remodeling of liver, heart and veins. • LuX-Valve is a promising alternative for patients presenting with severe tricuspid regurgitation. [ABSTRACT FROM AUTHOR]

Aim: Redo aortic valve surgery is usually associated with a high risk of mortality and complications. The aim of this study was to investigate the perioperative and long-term outcomes of reoperation after prior mechanical prosthesis implantation at the aortic position.Method: The clinical data of 146 consecutive patients who underwent reoperation at the aortic position between 2003 and 2019 were analysed.Results: Mean age was 51.5±12.7 years and 69 (47.3%) were female. The median interval from prior surgery to redo aortic valve surgery was 6 years. The aetiologies were pannus formation with prosthetic aortic stenosis in 62 cases (42.5%), prosthetic valve endocarditis (PVE) in five (3.4%), PVE with perivalvular leakage (PVL) in 16 (11.0%), PVL in 45 (30.8%), thrombosis in seven (4.8%), and aortic disease in 11 (7.5%). As for surgical procedure, aortic valve replacement was performed in 81 cases (55.5%), Bentall in 34 (23.3%), PVL repair in six (4.1%), and pannus debridement in 25 (17.1%). Fourteen (14) (9.6%) patients expired perioperatively. Prolonged ventilation time and postoperative renal failure were proved to be significant independent predictors of mortality according to multivariate analysis. Overall survival was 87.8%±7.4% and 76.4%±15.1% at 5 and 10 years, respectively. Survival was 87.7%±13.7% and 84.2%±15.6% in the pannus group, and 84.5%±12.6% and 74.6%±19.4% in the non-pannus group at 5 and 10 years, respectively (p=0.951). Survival was 87.5%±14.2% and 75.8%±22.7% in the PVL group and 84.7%±11.9% and 81.6%±13.5% in the non-PVL group at 5 and 10 years, respectively (p=0.365).Conclusions: Pannus formation and PVL are two major indications for reoperation of mechanical prosthesis at the aortic position. Redo aortic valve surgery has a satisfactory outcome but with a high risk of complications. Long-term survival of patients seems not to be related to the aetiology. Final decision-making of redo aortic valve surgery should be based on aetiology. [ABSTRACT FROM AUTHOR]

Background: The design and fabrication of porous scaffolds are important issues for tissue engineering applications. In this study, we attempted to fabricate porous scaffolds using bovine pericardium (BP) and examined whether these scaffolds were beneficial for cell ingrowth and bioactive factors delivery. Methods: A vacuum‐freeze‐thawing‐Triton X‐100 (VFTT) protocol was used to fabricate porous BP scaffolds. The porous and mechanical properties were assessed using histology, scanning electron microscopy, and mechanical assay. The fabricated scaffolds were seeded with mesenchymal stem cells (MSCs), and cell ingrowth was evaluated. Basic fibroblast growth factor (bFGF) was subsequently incorporated into the fabricated scaffolds. The bioactive factor delivery capacity was evaluated using loading and release studies. The bioactivity of released bFGF was assessed using a rat subcutaneous model. Results: The BP scaffolds fabricated by the VFTT protocol displayed interconnected porous structures with porosity of 6.82 ± 1.36%.There were no significant differences in thickness, ultimate load, Young's modulus, and ultimate tensile strength between the fabricated porous BP scaffolds and native BPs (all P >.05). However, the water content of BPs was slightly reduced after VFTT treatment (P <.05). Cell ingrowth analysis showed that the seeded MSCs penetrated into the porous BP scaffolds with time of culture, while MSCs were limited to the surface layers of native BPs. Furthermore, bFGF was observed to be effectively loaded onto and released from the porous BP scaffolds. The released bFGF increased the phosphorylation levels of Akt, ERK 1/2, and MEK1/2, promoted host MSC recruitment, and inhibited myofibroblast differentiation in vivo. Conclusions: The porous BP scaffolds fabricated using a VFTT protocol were promising natural scaffolds for tissue engineering applications, since they had considerable mechanical properties as native BPs, supplied porous channels for cell ingrowth, and possessed bioactive factors delivery capability. [ABSTRACT FROM AUTHOR]

Background: Postoperative hypoxemia in acute type A aortic dissection (AADA) is a common complication and is associated with negative outcomes. This study aimed to analyze the efficacy of low-dose (5-10 ppm) inhaled nitric oxide (iNO) in the management of hypoxemia after AADA surgery.Methods: In this retrospective observational study, Medical records of patients who underwent AADA surgery at two institutions between January 2015 and January 2018 were collected. Patients with postoperative hypoxemia were classified as iNO and control groups. Clinical characteristics and outcomes were compared using a propensity score-matched (PSM) analysis.Results: Among 436 patients who underwent surgical repair, 187 (42.9%) had hypoxemia and 43 were treated with low-dose iNO. After PSM, patients were included in the iNO treatment (n = 40) and PSM control (n = 94) groups in a 1:3 ratio. iNO ameliorated hypoxemia at 6, 24, 48, and 72 h after initiation, and shortened the durations of ventilator support (39.0 h (31.3-47.8) vs. 69.0 h (47.8-110.3), p < 0.001) and ICU stay (122.0 h (80.8-155.0) vs 179.5 h (114.0-258.0), p < 0.001). There were no significant between-group differences in mortality, complications, or length of hospital stay.Conclusions: In this study, we found that low-dose iNO improved oxygenation in patients with hypoxemia after AADA surgery and shortened the durations of mechanical ventilation and ICU stay. No significant side effects or increase in postoperative mortality or morbidities were observed with iNO treatment. These findings warrant a randomized multicenter controlled trial to assess the exact efficiency of iNO for hypoxemia after AADA. [ABSTRACT FROM AUTHOR]

Decellularized porcine aorta (PA) is a promising biomaterial for vascular substitutes. However, decellularized PAs suffer from mechanical weakness and have less pores, which limit cellular ingrowth into the grafts and hinder the remodeling. In this study, PAs were decellularized by vacuum‐freeze‐thawing cycles and 0.3% of sodium dodecyl sulfate (SDS) buffer (VLS). Results showed that the application of vacuum‐freeze‐thawing significantly improved the decellularization efficiency of SDS while effectively preserved the mechanical function of PA tissues, decreased residual SDS, and minimized cytotoxicity. Furthermore, scanning electron microscopy (SEM) examination demonstrated that VLS generated interconnected pores with uniform distribution. In vivo subcutaneous implantation assay further demonstrated that VLS implants had less calcification and adverse inflammatory response. Moreover, VLS treatment markedly enhanced ingrowth of myofibroblasts and endothelial cells, and thereby promoted synthesis of extracellular matrix and vascularization. These results suggest that the application of vacuum‐freeze‐thawing into the decellularization process may produce a promising vascular graft candidate for tissue engineering application. [ABSTRACT FROM AUTHOR]

Purpose: To report the results of a hybrid approach to aortic arch repair using an innovative unibody double-branched stent graft in a canine model. Materials and methods: The stent-graft system consists of two parts: the main body and two branches for reconstruction of the supra-arch branches. There is a 2-cm-long suturing portion at the proximal end of the main body. Twenty adult German sheep dogs underwent a hybrid surgical treatment to place the stent-grafts into the proximal descending aorta and the supra-arch branches. Outcomes were assessed by operative mortality, complications, imaging studies, and histomorphometric analyses. Results: Placement of the stent-graft was performed successfully in all dogs without complications. One dog died of respiratory failure due to early extubation. The other dogs survived to 6 months without complications, at which time they were sacrificed. The mean cardiopulmonary bypass time was 80.3 ± 7.3 mins and hypothermic circulatory arrest time was 10.7 ± 1.9 min. The average blood loss was 373.5 mL. At 6 months, postoperative aortic imaging indicated that the main body and branches of the stent-graft were fully open and in satisfactory position. No migration, deformation, or endovascular leakage was observed. Histomorphometric results showed normal arrangement of medial and adventitial elastic fibers, moderately proliferated intima, with or without neo-microvessels, and microscopic morphological changes in internal elastic lamina. Conclusions: These results demonstrate that it is possible and safe to reconstruct the aortic arch with the novel open-branched stent-graft placement. [ABSTRACT FROM AUTHOR]

Abstract Plasmin-mediated fibrinolysis at the surface of vascular endothelial cells (SVEC) plays a key role in maintaining vascular hemostasis, in which the cAMP pathway participates. After externalization to the SVEC, annexin A2 (ANXA2) serves as a platform for conversion of plasminogen to plasmin. Here we describe a regulatory role of the e xchange p rotein directly a ctivated by c AMP (EPAC) in ANXA2 externalization and vascular fibrinolysis. Knockout of EPAC1 in mice results in a decreased ANXA2 expression on the SVEC associated with increased fibrin deposition and fibrinolytic dysfunction. Reduced levels of EPAC1 are also found in endocardial tissues beneath atrial mural thrombi in patients. Notably, administration of recombinant ANXA2 ameliorates fibrinolytic dysfunction in the EPAC1 -null mice. Mechanistically, EPAC1 regulates the SVEC plasminogen conversion depended on ANXA2. EPAC1 promotes tyrosine-23 phosphorylation of ANXA2, a prerequisite for its recruitment to the SVEC. Our data thus reveal a novel regulatory role for EPAC1 in vascular fibrinolysis. [ABSTRACT FROM AUTHOR]

Interleukin-6 (IL-6) overexpression played an important role in the pathogenesis of thoracic aortic dissection (TAD). Our previous study found enhanced autophagy accompanying with contractile proteins α smooth muscle actin (α-SMA) and smooth muscle 22α (SM22α) degradation in TAD aortic vascular smooth muscle cells (VSMCs). Autophagy is an important way for intracellular proteins degradation, while IL-6 has been found as a contributing factor of autophagy in some cancers. These indicated IL-6 might contribute to the occurrence of TAD by promoting autophagy-induced contractile proteins degradation, which has not been investigated. The aim of the present study is to verify this hypothesis and investigate the mechanism of it. We collected 10 TAD and 10 control aortic specimens from patients underwent TAD surgical repair and coronary artery bypass grafting, respectively. Quantitative real-time polymerase chain reaction was used to detect mRNA expression. Protein expression level was assessed by enzyme-linked immunosorbent assay, western blot, and immunohistochemistry. Microtubule-associated protein 1 light chain 3 beta overexpression adenovirus with green and red fluorescent protein tags and transmission electron microscopy were used to detect autophagy level in VSMCs. 3-Methyladenine (3-MA) and chloroquine were used to block autophagy in human VSMCs. Experiment results showed that the expression of IL-6 was significantly increased accompanying with up-regulated autophagy in TAD aortic wall compared with controls. In vitro results showed that IL-6 stimulation decreased the expression of VSMCs contractile proteins α-SMA and SM22α accompanying with up-regulated autophagy. Blocking autophagy with 3-MA or chloroquine inhibited IL-6 induced α-SMA and SM22α degradation. Further investigation showed that autophagy-related 4B cysteine peptidase (ATG4B) was significantly overexpressed in TAD aortic wall and played important role in IL-6 induced autophagy up-regulation. ATG4B knockdown blocked IL-6-induced autophagy and α-SMA and SM22α degradation, while ATG4B overexpression partly replaced the function of IL-6 in human VSMCs. In conclusion, our study demonstrated that IL-6 downregulated expression of VSMCs contractile proteins α-SMA and SM22α via enhancing ATG4B-mediated autophagy in TAD. [ABSTRACT FROM AUTHOR]

Oral chemotherapy is a great way to cancer treatment because it is less stressful being that the patient will have less hospital visits and can still maintain a close relationship with health care professionals. In this research, three types of nanoparticle formulation from commercial PCL and self-synthesized TPGS- b-(PCL- ran-PGA) diblock copolymer were fabricated for oral delivery of antitumor agents, including DDAB-modified PCL nanoparticles, unmodified TPGS- b-(PCL- ran-PGA) nanoparticles and DDAB-modified TPGS- b-(PCL- ran-PGA) nanoparticles. Firstly, the TPGS- b-(PCL- ran-PGA) diblock copolymer was synthesized and characterized. DDAB was adopted to increase retention time at the cell surface, thus increasing the chances of nanoparticle uptake by the gastrointestinal mucosa and improving drug absorption. The TPGS- b-(PCL- ran-PGA) nanoparticles were found by FESEM of spherical shape and around 200 nm in diameter. The surface charge of TPGS- b-(PCL- ran-PGA) nanoparticles was reversed from anionic to cationic after DDAB modification. The DDAB-modified TPGS- b-(PCL- ran-PGA) nanoparticles have significantly higher level of the cell uptake than that of DDAB-modified PCL nanoparticles and unmodified TPGS- b-(PCL- ran-PGA) nanoparticles. In vitro cell viability studies showed advantages of the DDAB-modified TPGS- b-(PCL- ran-PGA) nanoparticles over Taxotere® in terms of cytotoxicity against A549 cells. In conclusion, oral chemotherapy by DDAB-modified TPGS- b-(PCL- ran-PGA) nanoparticle formulation may provide a promising outcome for lung cancer patients. The coumarin 6-loaded nanoparticles (green) are closely around the nuclei (blue), which confirms the uptake of nanoparticles by the cells, some can even enter into the nucleus (color online). The DDAB-modified TPGS- b-(PCL- ran-PGA) nanoparticles have significant higher level of the cell uptake than that of DDAB-modified PCL nanoparticles and unmodified TPGS- b-(PCL- ran-PGA) nanoparticles. In vitro cell viability studies showed advantages of the DDAB-modified TPGS- b-(PCL- ran-PGA) nanoparticles over Taxotere® in terms of cytotoxicity against A549 cells. Oral chemotherapy by DDAB-modified TPGS- b-(PCL- ran-PGA) nanoparticle formulation may provide a promising outcome for lung cancer patients. [ABSTRACT FROM AUTHOR]

Abstract: Pericardial fibrocalcification (PF) is a prominent feature of human pericardial pathology, including constrictive pericarditis and, to a lesser extent, degenerated autologous pericardial substitutes. However, the role of pericardial interstitial cells (PICs) in the pathogenesis of PF has yet to be established. Using a combination of histology and immunohistochemistry, we showed that the critical cellular event in PF in situ was the transdifferentiation of PICs into myofibroblasts/osteoblasts and that the percentage of myofibroblasts/osteoblasts correlated positively with the severity of PF. In vitro studies demonstrated that PICs, similar to mesenchymal stem cells, had the potential to differentiate along adipogenic, osteogenic, chondrogenic or myogenic lineages. However, PICs exhibited a more limited self-renewal capacity and a lower expression of Oct4 (POU5F1) and Kruppel-like transcription factor Klf4, underwent earlier senescence and spontaneously transdifferentiated into myofibroblasts/osteoblasts. Quantitative-real-time reverse transcriptase-polymerase chain reaction (qRT-PCR) confirmed that the mRNA levels of α-smooth muscle actin (α-SMA), alkaline phosphatase (ALP), core-binding factor α1/runt-related transcription factor2 (Cbfa1/Runx2), transforming growth factor (TGF)-β1 and bone morphogenetic protein (BMP)-2 were upregulated as the passage number increased. The mRNA level of platelet-derived growth factor (PDGF)-AA was also significantly upregulated with higher levels at passage 3. Ectopic expression of Oct4 and Klf4 enhanced the colony formation of PICs and selectively impaired induction of genes involved in transdifferentiation into myofibroblasts/osteoblasts (α-SMA, ALP, Cbfa1/Runx2, PDGF-AA and BMP-2). These data, while offering new insights into the biology of PICs, reinforce the central role of these cells in cell-mediated PF and may assist in future strategies to treat fibrocalcific pericardial diseases. [Copyright &y& Elsevier]

To clarify the role of glutathione S-transferases (GSTs; GSTM1 and GSTT1) status in susceptibility to coronary heart disease (CHD), a meta-analysis of published studies was performed. A total of 19 studies including 8020 cases and 11 501 controls were included in this meta-analysis. In a combined analysis, the relative risks for CHD of the GSTM1 null and GSTT1 null polymorphisms were 1.47 [95% confidence interval (CI): 1.08–2.01] and 1.26 (95% CI: 0.90–1.75), respectively. Three potential sources of heterogeneity including ethnicity, source of control and sample size of study were also assessed. However, no significant association was found in stratified analyses. By pooling data from eight studies (2909 cases and 3745 controls) that considered combinations of GSTT1 and GSTM1 genotypes, a statistically significant increased risk for CHD [odds ratio (OR = 2.38, 95% CI: 1.03–5.48)] was detected for individuals with combined deletion mutations in both genes compared with positive genotypes. Results from the meta-analysis of five studies on GSTs stratified according to smoking status showed an increased risk for individuals with null genotype (OR = 2.21, 95% CI: 1.24–3.92 for GSTM1 and OR = 3.29, 95% CI: 1.49–7.26 for GSTT1) versus non-null genotypes. This meta-analysis suggests that the GSTM1 null genotype may slightly increase the risk of CHD and that interaction between unfavourable GSTs genotypes may exist. [ABSTRACT FROM PUBLISHER]

Objective: Therapeutic angiogenesis using basic fibroblast growth factor (bFGF) in coronary artery disease has been documented in a number of papers. However, the effectiveness is discrepant among documents. In this study, we evaluated the distribution of bFGF in the rat heart by different administration methods, and investigated the efficacy of slow-released administration of bFGF using biodegradable hydrogel microspheres (bFGF microspheres) in a pig infarction model toward an enhanced coronary bypass surgery. Methods: Heart failure due to myocardial infarction was induced in rats and pigs. In the rat study, free form of bFGF (central venous injection, intracoronary injection, and intramyocardial administration) and bFGF microspheres (intramyocardial administration) were given 4 weeks later. The remaining radioactivity of bFGF in the hearts was estimated 1, 24, and 72 h later. On the other hand, the pigs were randomized into two groups 4 weeks after myocardial infarction. While the control group (n=8) had gelatin hydrogel microspheres with saline, the FGF group (n=8) received bFGF microspheres in the left ventricular (LV) wall. Results: In the rat study, after intramyocardial administration of bFGF microspheres, more bFGF remained in the rat heart 72 h later compared with the other methods (P<0.0001). In the pig study, 4 weeks after the treatment, the FGF group had smaller LV diastolic diameter (48.7±5.3 vs. 56.7±5.2 mm, P<0.01) than the control group. LV end-systolic elastance was higher in the FGF group (2.96±1.2 vs. 1.06±0.3 mmHg/ml, P<0.01). In microscopic examinations, many neovessels were found in and around the scar tissue, and the vascular density in the FGF group was significantly higher (61.5±18.3 vs. 153.0±29.0/mm2, P<0.01). In addition, the infarcted LV walls were less expanded and more thickened in the FGF group. Conclusions: Biodegradable hydrogel microspheres with bFGF improved LV function and inhibited LV remodeling by angiogenesis in pigs with chronic myocardial infarction. bFGF microspheres into ischemic myocardium may revascularize small ungraftable vessels and may potentially increase distal run-off when applied in coronary bypass surgery. [Copyright &y& Elsevier]

Members of the family Filoviridae, including Ebola virus (EBOV) and Marburg virus (MARV), cause severe hemorrhagic fever in humans and nonhuman primates. Given their high lethality, a comprehensive understanding of filoviral pathogenesis is urgently needed. In the present studies, we revealed that the exchange protein directly activated by cAMP 1 (EPAC1) gene deletion protects vasculature in ex vivo explants from EBOV infection. Importantly, pharmacological inhibition of EPAC1 using EPAC-specific inhibitors (ESIs) mimicked the EPAC1 knockout phenotype in the ex vivo model. ESI treatment dramatically decreased EBOV infectivity in both ex vivo vasculature and in vitro vascular endothelial cells (ECs). Furthermore, postexposure protection of ECs against EBOV infection was conferred using ESIs. Protective efficacy of ESIs in ECs was observed also in MARV infection. Additional studies using a vesicular stomatitis virus pseudotype that expresses EBOV glycoprotein (EGP-VSV) confirmed that ESIs reduced infection in ECs. Ultrastructural studies suggested that ESIs blocked EGP-VSV internalization via inhibition of macropinocytosis. The inactivation of EPAC1 affects the early stage of viral entry after viral binding to the cell surface, but before early endosome formation, in a phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)-dependent manner. Our study delineated a new critical role of EPAC1 during EBOV uptake into ECs. [ABSTRACT FROM AUTHOR]

Myasthenia gravis is a neuromuscular disorder, and the severe complication of myasthenic crisis is a life-threatening condition, usually induced by stress such as fever, trauma or a surgical procedure. Simultaneous heart surgery and thymectomy in a patient with concomitant heart disease and myasthenia gravis has been previously reported. We report a female patient with rheumatic valvular disease and myasthenia gravis who received triple heart valve surgery and thymectomy simultaneously. In her early recovery, two episodes of myasthenic crisis occurred which were treated promptly with a successful surgical outcome. [ABSTRACT FROM AUTHOR]