4-Acetylantroquinonol B Inhibits Osteoclastogenesis by Inhibiting the Autophagy Pathway in a Simulated Microgravity Model.

Astronauts suffer from 1-2% bone loss per month during space missions. Targeting osteoclast differentiation has been regarded as a promising strategy to prevent osteoporosis in microgravity (µXg). 4-acetylantroquinonol B (4-AAQB), a ubiquinone from Antrodia cinnamomea, has shown anti-inflammatory and anti-hepatoma activities. However, the effect of 4-AAQB on µXg-induced osteoclastogenesis remains unclear. In this study, we aimed to explore the mechanistic impact of 4-AAQB on osteoclast formation under µXg conditions. The monocyte/macrophage-like cell line RAW264.7 was exposed to simulated µXg (Rotary Cell Culture System; Synthecon, Houston, TX, USA) for 24 h and then treated with 4-AAQB or alendronate (ALN) and osteoclast differentiation factor receptor activator of nuclear factor kappa-B ligand (RANKL). Osteoclastogenesis, bone resorption activity, and osteoclast differentiation-related signaling pathways were analyzed using tartrate-resistant acid phosphatase (TRAP) staining, actin ring fluorescent staining, bone resorption, and western blotting assays. Based on the results of TRAP staining, actin ring staining, and bone resorption assays, we found that 4-AAQB significantly inhibited µXg-induced osteoclast differentiation. The critical regulators of osteoclast differentiation, including nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), c-Fos, and dendritic cell-specific transmembrane protein (DC-STAMP), were consistently decreased. Meanwhile, osteoclast apoptosis and cell cycle arrest were also observed along with autophagy suppression. Interestingly, the autophagy inhibitors 3-methyladenine (3-MA) and chloroquine (CQ) showed similar effects to 4-AAQB. In conclusion, we suggest that 4-AAQB may serve as a potential agent against µXg-induced osteoclast formation.

Astragaloside VI and cycloastragenol-6-O-beta-D-glucoside promote wound healing in vitro and in vivo.

BACKGROUND: Astragalus genus includes most of the common, historical herbal medicines that have various applications in Asian countries. However, clinical data and mechanistic insights into their actions are still lacking. PURPOSE: In this study, we aimed to examine the effects of astragalosides on wound healing in vitro and in vivo, as well as the underlying mechanisms of these actions. METHODS: The wound healing activity of astragalosides was investigated in human HaCaT keratinocytes, human dermal fibroblast (HDF) cells, and murine models of wound healing. RESULTS: All eight astragalosides studied enhanced epidermal growth factor receptor (EGFR) activity in HaCaT cells. Among them, astragaloside VI (AS-VI) showed the strongest EGFR activation. Consistently, AS-VI and cycloastragenol-6-O-beta-D-glucoside (CMG), which is the major metabolite of astragalosides, enhanced extracellular signal-regulated kinase (ERK) activity in a concentration-dependent manner. In agreement, both compounds induced EGFR-dependent cell proliferation and migration in HaCaT and HDF cells. In addition, we showed that AS-VI and CMG accelerated the healing of both sterile and infected wounds in vivo. These effects were associated with increased angiogenesis in the scar tissue. CONCLUSION: AS-VI and CMG increased the proliferation and migration of skin cells via activation of the EGFR/ERK signalling pathway, resulting in the improvement of wound healing in vitro and in vivo. These findings indicate the therapeutic potential of AS-VI and CMG to accelerate wound healing; additionally, they suggest the mechanistic basis of this activity.

Melaleuca alternifolia Induces Heme Oxygenase-1 Expression in Murine RAW264.7 Cells through Activation of the Nrf2-ARE Pathway.

Melaleuca alternifolia concentrate (MAC) is the refined essential oil of the Australian native plant Melaleuca alternifolia. MAC has been reported to suppress the production of pro-inflammatory cytokines in both murine RAW264.7 macrophages and human monocytes stimulated with lipopolysaccharide (LPS). However, the mechanisms involved in this effect remain unclear. This study aims to delineate the molecular mechanisms that drive the anti-inflammatory activity of MAC and its active component, terpinen-4-ol, in macrophages. The effects of MAC on RAW264.7 cells were studied using western blotting, real-time PCR, an electrophoretic mobility shift assay (EMSA), and NF-[Formula: see text]B luciferase reporter assays. Our results showed that MAC significantly increased both the mRNA and protein levels of heme oxygenase-1 (HO-1) via p38 and JNK MAPK activation. In addition, we showed that MAC significantly increased the activation and nuclear translocation of NF-E2-related factor 2 (Nrf2), a key transcription factor regulating HO-1 induction. MAC was also associated with significant inhibition of iNOS expression, NO production, and NF-[Formula: see text]B activation. HO-1 was required for these anti-inflammatory effects as tin protoporphyrin IX (SnPPIX), an HO-1 inhibitor, abolished the effects of MAC on LPS-induced iNOS, NO, and NF-[Formula: see text]B activation. Our results indicate that MAC induces HO-1 expression in murine macrophages via the p38 MAPK and JNK pathways and that this induction is required for its anti-inflammatory activity.

Transesophageal echocardiography for incremental value of Amplatezer cribriform septal occluder for percutaneous transcatheter closure of complex septal defects: Case series.

BACKGROUND: The anatomy of septal defects can be complex and morphologically unpredictable. Balloon sizing of such defects may not be feasible, and an appropriately sized commercial occluder may not be available. Therefore, percutaneous transcatheter closure of such defects can be challenging because of an increased risk of complications. In this study, we have described the efficacy and safety of transcatheter closure of complex septal defects using Amplatzer cribriform occluder devices, assessed by real time three-dimensional (RT 3D) color Doppler transesophageal echocardiography (TEE). METHODS AND RESULTS: Four complex septal defects were involved in this investigation: (1) reimplanted multiple atrial septal defects (ASD) with one device embolization; (2) postinfarction ventricular septal defect; (3) long tunnel patent foramen ovale; and (4) postoperative residual ASD. All patients underwent percutaneous transcatheter interventions due to the high risk of surgical complications, and one of the three available cribriform ASD device sizes (18 mm, 25 mm, or 35 mm) was implanted. Perioperative RT 3D TEE combined with fluoroscopy was used for monitoring during the procedure. All defects were successfully occluded by cribriform septal occluder devices using the transcatheter technique. CONCLUSION: Our patients with complex septal defects were successfully treated by transcatheter closure using an Amplazter cribriform septal occluder device with careful planning based on patient presentation and close interdisciplinary collaboration. RT 3D color Doppler TEE provided precise information for the selection of the appropriate occluder device and facilitated the procedure by guiding the catheter through the often challenging patient anatomy.

Intraoperative three-dimensional transesophageal echocardiography for assessing the defect geometries of mitral prosthetic paravalvular leak during transcatheter closure.

BACKGROUND: Paravalvular leaks (PVLs) are a common complication of prosthetic valve replacement. Use of the transcatheter intervention technique is a suitable alternative in high-risk patients who may not tolerate repeat surgery. Common reasons for failure of this demanding intervention include poor imaging quality and unsuitable anatomy. The purpose of this study was to assess the usefulness and the incremental value of real-time three-dimensional (RT 3D) transesophageal echocardiography (TEE) over two-dimensional (2D) TEE findings in the evaluation of the geometry and track of mitral PVLs during transcatheter closure. METHODS: Five patients with six mitral PVLs at high risk for repeat surgery underwent transcatheter leak closure. Intraoperative RT 3DTEE was used to assess the location, shape, number, and size of the defects. Transapical approaches were used in all cases with fluoroscopic and RT 3D TEE guidance of the wire and catheter, device positioning, and assessment of residual leak after the procedure. RESULTS: In all of the cases, defects with irregular crescent shapes and distorted tracks were clearly delineated by RT 3D TEE. This was compared to those results obtained through 2D TEE, which was unable to characterize the defects. Three cases showed small leaks, which were completely occluded with a patent ductus arteriosus (PDA) device in two cases, and a muscular ventricular septal defect (mVSD) occluder combined with coil devices in one case. One case involved a large leak and early device embolization of the muscular VSD occluder, which was removed surgically, and demonstrated a crescent-shaped defect. One patient had two releaks 2 months subsequent to the procedure due to two new extended leaks at the tails of the crescent-shaped defect. CONCLUSION: RT 3D TEE can clearly delineate the geometries of defects in their entirety, including shape, size, and location of the defect and track canal. It would also appear that RT 3D TEE is superior to 2D TEE in the process of guiding the wire through the difficult canal anatomy, facilitating the overall procedure. The small mitral PVLs can be completely occluded, but subsequent complications occurred with large defect closures because of embolization or releak. Therefore, transcatheter closure of PVLs seems to be an attractive alternative for these patients, but newer occluder designs that better conform to leak geometry will be required to improve outcomes.

Transcatheter intervention for complex ascending aortic pseudoaneurysm after cardiac surgery.

BACKGROUND: Ascending aortic pseudoaneurysm (PsA) is an uncommon but surgically challenging problem with high morbidity and mortality. Herein we describe the efficacy and safety of the different approaches to transcatheter intervention for repair of ascending PsA and assess the selection of occluder devices using real-time 3-dimensional (RT 3D) color Doppler transesophageal echocardiography (TEE).METHODS AND RESULTS: Three patients with complex ascending PsA after cardiac or aortic root surgery were treated with transcatheter intervention due to high risk for redo surgery. Perioperative RT 3D-TEE combined with fluoroscopy was used for monitoring. All ascending PsA were successfully occluded with different devices using the transcatheter technique either with the transapical, transarterial approach, or transvenous combined with hybrid process depending on lesion anatomy. CONCLUSIONS: Treatment of complex ascending PsA with transcatheter or combined hybrid intervention with cautious planning based on patient presentation and well-coordinated teamwork was successful. RT 3D color Doppler TEE provided precise information for the selection of appropriate occluder device, and also facilitated the procedure by guiding the catheter through difficult anatomy.

The additional value of live/real-time three-dimensional transesophageal echocardiography over two-dimensional transesophageal echocardiography for assessing mitral regurgitation with eccentric jets.

BACKGROUND: Two-dimensional transesophageal echocardiography (2D TEE) Doppler color flow imaging is the gold standard for assessing the severity of mitral regurgitation (MR). Severe MR with very eccentric jet may involve more than one mitral leaflet lesion and can be missed by 2D TEE. The purpose of this study was to assess the usefulness and the incremental value of real-time three-dimensional (RT 3D) TEE over 2D TEE findings in the evaluation of patients suffering eccentric MR with more than one mitral leaflet lesion. METHODS: Intraoperative 2D TEE and RT 3D TEE examinations were performed on 168 patients with Carpenter II MR who underwent surgery. MR was defined as either central, free-standing eccentric jet or very eccentric jet. 2D TEE and RT 3D TEE finding were compared with surgical findings. RESULTS: Of these 168 MR patients, 25 patients (14.9%) had central jets and 143 patients (85.1%) had eccentric jets. Among 143 patients with eccentric jets, 47 patients (32.9%) had free-standing eccentric MR jets, and 96 (67.1%) patients had very eccentric jets. 3D TEE diagnosed the severity and location of MR lesions correctly in all patients; this was not the case with 2D TEE, which had significant diagnostic misses in nine patients (9.4%, p < 0.001) having MR with very eccentric jets. These nine patients had lesions on both mitral leaflets, which were missed during 2D TEE examination owing to the highly turbulent flows produced by very eccentric jets from one mitral leaflet lesion and impinging the opposite mitral leaflet lesion. CONCLUSION: The severity of MR with very eccentric jet was more accurately and comprehensively assessed by 3D TEE than by 2D TEE. Therefore, intraoperative RT 3D TEE provides incremental information that is generally superior to 2D TEE in patients with complex MR due to very eccentric jets.

Atrial septal occluder device embolization to an iliac artery: a case highlighting the utility of three-dimensional transesophageal echocardiography during percutaneous closure.

Percutaneous closure of secundum atrial defects has become an accepted treatment in part because it is minimally invasive and relatively low risk. Despite recent advances in implantation technique and device improvements, complications occur. Here, we report a case of device embolization during percutaneous repair of an atrial septal defect (ASD) with multiple fenestrations. We highlight the value of using live/real time three-dimensional transesophageal echocardiography to help plan the percutaneous procedure and detect complications.

Successful intraoperative identification of an anomalous origin of the left coronary artery from the pulmonary artery using real time three-dimensional transesophageal echocardiography.

Anomalous origin of the left coronary artery (LCA) from the pulmonary artery (ALCAPA) is a rare congenital defect that presents only infrequently in adults. An adult diagnosed with ALCAPA, heart failure, and mitral regurgitation underwent surgical ligation of the anomalous origin of the LCA from the pulmonary artery (PA) and coronary artery bypass grafting (CABG). The anomalous origin in the PA and proximal segment of the left anterior descending artery (LAD) was successfully delineated via real time, three-dimensional transesophageal echocardiography during surgery. This modality allows for fast assessment and novel views of complex cardiac abnormalities and can aid in perioperative monitoring.

Successful transcatheter closure of a residual patent ductus arteriosus with complex anatomy after surgical ligation using an amplatzer ductal occluder guided by live three-dimensional transesophageal echocardiography.

Residual patent ductus arteriosus (PDA) after surgical ligation is not common, but the anatomy of the residual duct may be distorted by the surgical ligation resulting in a difficult transcatheter closure. Such distorted anatomy of the duct may not be demonstrated by the two-dimensional transesophageal echocardiography (2D TEE). Fortunately, live 3D TEE provided the precise anatomy of the elongated distorted residual duct, and as in the case presented herein, guided the Amplatzer ductal occluder (ADO). We concluded that live 3D TEE provided novel images of complex residual ducts and successful guidance of a ductal occluder.

Emergent bedside real-time three-dimensional transesophageal echocardiography in a patient with cardiac arrest following a caesarean section.

Post-caesarean pulmonary embolism (PE) is associated with significant peri-operative morbidity and mortality. This report describes a case of sudden cardiac arrest 2 days post-caesarean due to massive PE diagnosed via bedside transesophageal echocardiography (TEE). Recognition of the PE at the bifurcation of the right and left pulmonary arteries was achieved by real-time three-dimensional TEE, but not two-dimensional TEE. Extracorporeal membrane oxygenation was immediately established and emergent pulmonary thromboembolectomy was performed. The patient was discharged without residual deficits on Day 22 of hospitalization.

Live three-dimensional transesophageal echocardiography in an unusual case of aorto-left ventricular tunnel with a large interventricular septal aneurysm.

Aorto-left ventricular tunnel (ALVT) is a rare congenital malformation. We report an unusual case of ALVT with a large interventricular septal aneurysm causing severe aortic regurgitation and left ventricular outflow obstruction diagnosed with real time three-dimensional transesophageal echocardiography (3D TEE). Real time 3D TEE allows for assessment and novel views of complex cardiac abnormalities and can aid in perioperative monitoring.

Embolization of the stent to the right heart after a motor vehicle accident.

Endovascular stent grafts have become increasingly used in the management of arterial trauma, chronic vascular occlusive diseases, and deep vein thrombosis (DVT). Here, we describe a case of stent migration to the right heart due to a motor vehicle accident in a patient with iliac venous stent implanted for venous stenosis. Computed tomography (CT) scan imaging identification of a metallic stent was superior to the standard two-dimensional transesophageal echocardiography (TEE) techniques without imaging artifact from reverberation. However, real time three-dimensional (3D) TEE can precisely defined a metallic stent in right heart oriented with shape and direction without consuming time compared to that of CT scanning. The use of 3DTEE can facilitate identification of intracardiac metallic foreign bodies perioperatively in a patient with accident and emergent unstable condition. (Echocardiography 2010;27:587-589).

The routine use of live three-dimensional transesophageal echocardiography in mitral valve surgery: clinical experience.

BACKGROUND: Perioperative monitoring of mitral valve (MV) anatomy, function, and pathology is essential for surgical management of different MV disease. AIMS: To overcome the several potential pitfalls of two-dimensional transesophageal echocardiography (2D TEE) and offline 3D TEE. METHODS: Live 3D TEE was used to assess 73 patients (44 men and 29 women) with Carpentier type II MV regurgitation undergoing MV surgery perioperatively. RESULTS: The isolated segment most frequently involved was A2/P2, but A1or P1 rarely was involved in an isolated lesion or combined lesions. The agreement between 3D TEE finding and surgery was 88% (64/73). In nine patients, the live 3D TEE images revealed more segments or scallops with prolapse than the surgeon noted intraoperatively. CONCLUSIONS: Live 3D TEE allows more sensitivity and was feasible identification of prolapse or flail of individual segments of MV leaflets during surgery. We conclude that live 3D TEE should be regarded as an important adjunct to the standard 2D TEE examination in making decisions about MV surgery.

The utility of live three-dimensional echocardiography in the surgical treatment of bilateral coronary fistulas.

In patients with coronary and pulmonary arterial fistulas, the drainage sites may be difficult to identify if there are multiple connections by standard 2D echocardiography techniques. However, real time 3D TEE was used intraoperatively in our case to facilitate site identification, the number of fistulous connections, and documentation of the fistula ligation.

Occurrence of the Bezold-Jarisch reflex during Cesarean section under spinal anesthesia--a case report.

We report a 35-year-old parturient with gestational diabetes mellitus (GDM) history who sustained a nearly fatal Bezold-Jarisch reflex during Cesarean section under spinal anesthesia. A high spinal block combined with acute massive hemorrhage may produce life-threatening Bezold-Jarisch reflex which should be treated prophylactically and aggressively during surgery. Additionally, the autonomic disturbance associated with GDM might exaggerate the reflex in this episode. The patient survived after successful resuscitation and was discharged without any sequela.

Carbon dioxide embolism diagnosed by transesophageal echocardiography during endoscopic vein harvesting for coronary artery bypass grafting.

IMPLICATIONS: We describe a case of massive carbon dioxide embolism with an abrupt decrease in arterial blood pressure and continuous mixed venous oxygen saturation during endoscopic vein harvesting that was immediately diagnosed by intraoperative transesophageal echocardiography.