Anomalous origin of the left coronary artery from the pulmonary artery as a rare cause of mitral valve prolapse: a case report.

BACKGROUND: Mitral valve prolapse (MVP) is an etiologically heterogeneous disorder. Early diagnosis and prompt treatment of the underlying disease are of great significance. Herein, we present a rare case of MVP caused by anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA). CASE PRESENTATION: A 22-year-old female presented with a 16-year history of anterior mitral leaflet prolapse. However, she had never experienced any discomfort before. At a routine follow-up, a transthoracic echocardiogram showed anterior mitral leaflet prolapse (A2) with moderate mitral regurgitation, and a retrograde blood flow from an extremely dilated left coronary artery (LCA). Further coronary angiography and coronary computed tomography angiography confirmed the diagnosis of ALCAPA. She subsequently underwent successful LCA reimplantation and concomitant mitral valve replacement. Intraoperatively, her mitral annulus was mildly dilated, anterior mitral valve leaflet appeared markedly thickened with rolled edges, and a chordae tendineae connecting the anterior leaflet (A2) was ruptured and markedly shortened. CONCLUSIONS: ALCAPA is a rare and potentially life-threatening congenital coronary artery anomaly that may cause mitral valve prolapse. Echocardiogram is an important screening tool for this disorder.

Protective Effect of Se-Methylselenocysteine on Elaidic Acid-Induced Inflammation in Human Arterial Endothelial Cells.

This study was designed to investigate the anti-inflammatory effect of Se-methylselenocysteine (MSC) on elaidic acid (9t18:1, EA) induced human arterial endothelial cells (HAECs). MTT and flow cytometry were used to determine cell viability and cell apoptosis respectively. Western blotting was used to assess protein expression of intercellular adhesion molecular 1 (ICAM-1), E-selectin, interleukin-8 (IL-8), endothelial nitric oxide synthase (e-NOS) and phospholipases A2 (PLA2), while enzyme-linked immunosorbent assay (ELISA) was performed to examine the secretion level of nitric oxide (NO). In the cell viability assay, EA significantly decreased cell viability when compared with negative control (NC) group, and MSC effectively reversed this adverse effect, especially at the concentration of 200 µmol/L with 24 h incubation. Also, the same concentration of MSC prevented HAECs cell apoptosis induced by EA. In addition, we found that the expression of ICAM-1, E-selectin, IL-8 and PLA2 were significantly increased and e-NOS decreased in EA group compared with NC group. Inhibition of PLA2 promoted ICAM-1, E-slectin and IL-8 expression in HAECs induced by EA. And MSC down-regulated the secretion of NO level in EA-induced HAECs. Based on these results, we concluded that MSC activated PLA2 which regulated the expression of ICAM-1, E-selectin and IL-8 to protect inflammation induced by EA in HEACs.

Theranostic Lysosomal Targeting Anticancer and Antimetastatic Agents: Half-Sandwich Iridium(III) Rhodamine Complexes.

Two rhodamine-modified half-sandwich Ir(III) complexes with the general formula [(Cpx)Ir(CN) Cl] were synthesized and characterized, where Cpx is 1-biphenyl-2,3,4,5-tetramethylcyclopentadienyl (Cpxbiph). Both complexes showed potent anticancer activity against A549, HeLa, and HepG2 cancer cells and normal cells, and altered ligands had an effect on proliferation resistance. The complex enters cells through energy dependence, and because of the different ligands, not only could it affect the anticancer ability of the complex but also could affect the degree of complex lysosome targeting, lysosomal damage, and further prove the antiproliferative mechanism of the complex. Excitingly, antimetastatic experiments demonstrated that complex 1 has the ability to block the migration of cancer cells. Furthermore, although the complex did not show a stronger ability to interfere with the coenzyme NAD+/NADH pair by transfer hydrogenation, the intracellular reactive oxygen species (ROS) content has shown a marked increase. NF-κB activity is increased by ROS regulation, and the role of ROS-NF-κB signaling pathway further induces apoptosis. Moreover, cell flow experiments also demonstrated that complex 1 blocked the cell cycle in S phase, but the complex did not cause significant changes in the mitochondrial membrane potential.

Melanin-loaded biocompatible photosensitive nanoparticles for controlled drug release in combined photothermal-chemotherapy guided by photoacoustic/ultrasound dual-modality imaging.

Combined photothermal-chemotherapy guided by multimodal imaging is a promising strategy for cancer diagnosis and treatment. Multifunctional nanoparticles, such as those comprising organic and inorganic compounds, have been extensively investigated for combined photothermal-chemotherapy; however, their application is still limited by their potential long-term toxicity and lack of contrast properties. To solve these problems, in this study, a new type of multifunctional nanoparticle for combined photothermal-chemotherapy guided by dual-modality imaging was prepared with endogenous melanin by multistep emulsification to enhance tumor ablation. The nanoparticles were coated with poly(lactide-co-glycolic acid) (PLGA) and loaded with paclitaxel (PTX), encapsulated melanin and perfluoropentane (PFP). The materials in the nanoparticles were endogenous, ensuring high stability, biocompatibility, and biosafety. Nanoparticles irradiated with a laser, which induced their phase transformation into microbubbles, exhibited high photothermal conversion efficiency, thereby achieving photoacoustic (PA)/ultrasound (US) dual-modality imaging to determine tumor location, boundary, and size and to monitor drug distribution. Furthermore, optical droplet vaporization (ODV) of the nanoparticles could trigger the release of PTX; thus, these nanoparticles are a useful drug carrier. In vivo and in vitro experiments revealed that a strong synergistic antitumor effect was achieved by combining the photothermal properties of the nanoparticles with a chemotherapy drug. Importantly, the cavitation, thermoelastic expansion, and sonoporation caused by the phase transformation of the nanoparticles could directly damage the tumors. These processes also promoted the release, penetration and absorption of the drug, further enhancing the effect of combined photothermal-chemotherapy on tumor suppression. Therefore, the multifunctional nanoparticles prepared in this study provide a new strategy of using endogenous materials for controlled near-infrared (NIR)-responsive drug release and combined photothermal-chemotherapy guided by multimodal imaging.

Potential anticancer agent for selective damage to mitochondria or lysosomes: Naphthalimide-modified fluorescent biomarker half-sandwich iridium (III) and ruthenium (II) complexes.

In this work, five naphthalimide-modified half-sandwich iridium and ruthenium complexes ([(η5-Cpx)Ir(NˆN)Cl]PF6, [(η6-p-cym)Ru(NˆN)Cl]PF6) have been presented. The anticancer activities of the complexes against various cancer cell lines were investigated, among them, complexes 2 and 4 showed better anticancer activity than cisplatin, and their anticancer activity is better than complex 5 without fluorophore. In addition, a series of biological tests of complex 2 were performed using flow cytometry, the results indicated that the complex could induce cell death in a variety of ways. By changing of the ligands, the complexes exhibited different photophysical properties, and the mechanism of action of the complexes entering the cell and inducing apoptosis are different. Moreover, complex 2 successfully targeted mitochondria, while complex 4 targeted lysosomes, causing mitochondrial damage and lysosomal damage to induce apoptosis. Excitingly, complex 2 has good antimetastatic ability to cancer cells. Furthermore, complexes 2 and 4 did not have a significant effect on the NADH binding reaction, but they had a moderate binding ability to BSA.

NH4HCO3 gas-generating liposomal nanoparticle for photoacoustic imaging in breast cancer.

In this study, we have developed a biodegradable nanomaterial for photoacoustic imaging (PAI). Its biodegradation products can be fully eliminated from a living organism. It is a gas-generating nanoparticle of liposome-encapsulating ammonium bicarbonate (NH4HCO3) solution, which is safe, effective, inexpensive, and free of side effects. When lasers irradiate these nanoparticles, NH4HCO3 decomposes to produce CO2, which can absorb much of the light energy under laser irradiation with a specific wavelength, and then expand under heat to generate a thermal acoustic wave. An acoustic detector can detect this wave and show it as a photoacoustic signal on a display screen. The intensity of the photoacoustic signal is enhanced corresponding to an increase in time, concentration, and temperature. During in vivo testing, nanoparticles were injected into tumor-bearing nude mice through the caudal vein, and photoacoustic signals were detected from the tumor, reaching a peak in 4 h, and then gradually disappearing. There was no damage to the skin or subcutaneous tissue from laser radiation. Our developed gas-generating nanomaterial, NH4HCO3 nanomaterial, is feasible, effective, safe, and inexpensive. Therefore, it is a promising material to be used in clinical PAI.