Ovarian survival after transplantation is key to determining the success and efficacy of ovarian tissue cryopreservation and transplantation (OTCP). However, non-invasive monitoring of ovarian survival in the early stages of...
Aim: To investigate the pattern of left ventricular (LV) function and myocardial perfusion and their relationship in dilated cardiomyopathy (DCM) patients using layer-specific speckle tracking imaging (STI) and layer-specific myocardial contrast echocardiography (MCE).Material and Methods: Thirty DCM patients and 30 controls were recruited and underwent STI and MCE examination. The peak values of longitudinal strain (LS), circumferential strain (CS) of each layer of LV were recorded and compared between groups. Additionally, cross-sectional area of a microvessel (A) and average myocardial microvascular lesion (β) of each layer were measured, myocardial blood flow (MBF) was estimated using A Â β, above parameters were compared between two groups.
Results:The LS of endo-(LS endo ), mid-(LS mid ) and epicardium (LS epi ), as well as CS of endo-(RS endo ), mid-(RS mid ), (LS epi ) epicardium and LS endo/epi, CS endo/epi were significantly decreased in DCM patients. More importantly, DCM patients demonstrated decreased A, β and A Â β in all three myocardium layers and A endo/epi, β endo/epi, A Â β endo/epi compared to the controls. The time to peak and the cardiac cycle required to reach the peak were prolonged in DCM patients (p < 0.05). Longitudinal strain parameters of each layer had a negative relationship with perfusion parameter A and this relationship was strongest between LSendo and Aendo (r = 0.690, p < 0.01).
Conclusions:The cardiac strain and, more importantly, coronary microcirculation perfusion was impaired in each layer in DCM patients. The longitudinal function of the LV myocardium was closely related to changes in myocardial microcirculation perfusion.
To prepare a new type of dual-target microbubble loaded with anti-miR-33 (ANM33). Methods: Carrier core nanobubbles (NBs) were prepared by thin film hydration, and microbubbles loaded with PM1 (PCNBs) were prepared by grafting DSPE-PEG2000maleimide-PM1 onto the NB surface. ANM33 was connected via electrostatic adsorption and covalent bonding, and hyaluronic acid (HA) was covalently connected. PM1 and HA were the targets, and ANM33 was the intervention drug. To evaluate the general physical and chemical properties of the prepared dual-target microbubbles loaded with ANM33 (HA-PANBs), we observed their morphology, particle size and surface potential while monitoring their stability and in vitro imaging ability, evaluated their toxic effect on cells and verified their ability to target cells. Results: HA-PANBs had a regular morphology and good stability. The average particle size measured by a Malvern potentiometer was 1421.75±163.23 nm, and the average surface potential was −5.51±1.87 mV. PM1 and ANM33 were effectively connected to the NBs. The PM1, ANM33, and HA binding reached 89.0±1.1%, 65.02±5.0%, and 61.4±3.5%, respectively, and the maximum binding reached 2 µg, 5 µg, and 7 µg/10 8 microbubbles, respectively. HA-PANBs had no obvious toxic effects on cells, and their ability to continuously enhance imaging in vitro persisted for more than 15 minutes, obviously targeting foam cells in the early stage of AS. Conclusion: HA-PANBs are ideal ultrasound contrast agents. The successful, firm connection of PM1 and HA to the NBs significantly increased the amount of carried ANM33. When microbubbles prepared with 2:4:7 PM1:ANM33:HA were used as a contrast agent, they had a high ANM33 carrying capacity, stable physical properties, and significantly enhanced imaging and targeting of foam cells in the early stage of AS.
Aim: Significantly reduced expression of Ca2+-ATPase 2a (SERCA2a) and Connexin 43 (Cx43) which play important roles in regulating mechano-electrical function was found in an ischemic heart. Bone marrow mesenchymal stem cells (BMSCs) transplantation brings with a weak improvement of ischemic heart in cardiac contractility and anti-arrhythmias effect. The aim of this study was to recover mechano-electrical function of ischemic heart through combining stem cell therapy with SERCA2a/Cx43 co-delivery by biotinylated microbubbles (BMBs) via ultrasound targeted microbubble destruction (UTMD).Methods: Dual gene-loaded BMBs were developed through conjugating SERCA2a-adenovirous (S-Ad) and Cx43-adenovious (C-Ad) onto BMBs via biotin-avidin linkage. UTMD was used to mediate the local co-delivery of S-Ad and C-Ad into the infarct zone where BMSCs were transplanted. The expression of SERCA2a and Cx43 gene, neovascularization in the infarct area and mechano-electrical function of rats were detected. Results: UTMD-mediated dual gene delivery could significantly enhance the expression of SERCA2a/Cx43 genes in the infarct zone receiving BMSCs transplantation. Significantly improved neovascularization was observed. More importantly, UTMD-mediated dual gene delivery greatly improved cardiac function and reduced arrhythmia in these myocardial infarct (MI) hearts transplanted with BMSCs. Conclusions: BMSCs-based dual gene therapy can effectively improve cardiac mechano-electrical function and reduce arrhythmia in heart with MI. It is necessary to rebuild the gene network in damaged heart rather than supply a single gene. BMSCs transplantation combined with localized dual-gene delivery by UTMD might point out a novel strategy to recover mechano-electrical function of ischemic heart.
Given the miR-33’s mechanistic relationships with multiple etiological factors in the pathogenesis of atherosclerosis (AS), we investigated the therapeutic potentials of dual-targeted microbubbles (HA-PANBs) in foam cell-specific release of anti-miR-33 (ANM33) oligonucleotides, resulting in the early prevention of AS progression and severity. The intracellular localization, loading optimization, and therapeutic effects of HA-PANBs were examined in detail in a co-cultured cell model of phagocytosis. Compared with non-targeting nanobubbles (NBs) and single-targeted microbubbles as controls, HA-PANBs efficiently delivered the ANM33 specifically to foam cells via sustained release, exhibiting its clinical value in mediating RNA silencing. Moreover, when used at a dose of 12 µg/mL HA-PANBs per 107 cells for 48 h, a higher release rate and drug efficacy were observed. Therefore, HA-PANBs, effectively targeting early AS foam cells, may represent a novel and optimal gene therapy approach for AS management.
As our previous study shown, the therapeutic effect of double genes
(SERCA2a and Cx43) on heart failure after myocardial infarction (MI)
were better than that of single gene (SERCA2a or Cx43) therapy on the
basis of bone marrow stem cells (BMSCs) transplantation. Based on
previous research, the aim of this study was to investigate the optimize
ratio of co-delivery of SERCA2a and Cx43 genes for MI therapy after
biotinylated microbubbles (BMBs) transplantation via ultrasonic-targeted
microbubble destruction (UTMD). Forty rats underwent left anterior
descending (LAD) ligation and BMSCs injection into the infarct and
border zones. Four weeks later, double genes of SERCA2a and Cx43 with
different ratios (1:1, 1:2 and 2:1) were co-delivered into the infarcted
heart via the UTMD. Cardiac mechano-electrical function was determined
at 4-wk after gene delivery, and the hearts of the rats were harvested
for measurement of MI size and detection of SERCA2a and Cx43 expression.
Q-PCR analysis of the expression of Nkx2.5 and GATA4 in the myocardial
infarct zone and measurement of neovascularization in infarcted heart.
After comparing the therapeutic effects of different co-gene ratios, the
SERCA2a/Cx43-1:2 group shown remarkable cardiac electrical stability and
strengthen the role of anti-arrhythmia. In conclusion, the optimum ratio
of SERCA2a/Cx43 gene is 1:2, which take advantageous in maintaining
cardiac electrophysiological stability.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.