A Lipidated Peptide with Mitochondrial Membrane Localization in Human A549 Lung Cells: From Enhanced Cell-Penetrating Properties to Biological Activity Mechanism.

Here, a lipidated peptide Pal-pHK-pKV with self-assembly properties and the ability to provoke the disruption of the mitochondrial voltage-dependent anion channel-1 protein (VDAC1)-hexokinase-II (HK-II) complex is reported. The effects of the peptide pHK (N-terminal 15-amino acid fragment of HK-II that specifically binds VDAC1) are compared to those of a designed biomimetic amphiphilic pHK-pKV conjugate (pHK coupled with a cell-penetrating peptide pKV) and Pal-pHK-pKV (a lipidated conjugate modified with a hydrophobic palmitic (Pal) alkyl chain). The Pal-pHK-pKV exhibits a stronger interaction with the membrane as compared to pHK-pKV, which is demonstrated by the Langmuir-Blodgett technique and two-photon excitation microscopy. The amphiphilic peptide derivatives are cytotoxic to the A549 cells, but Pal-pHK-pKV is more cytotoxic. The inhibitory effects of the pHK derivatives on the A549 cells growth are investigated through induced apoptosis pathway, depolarized mitochondrial membrane potential, inhibited glycolysis, and activated caspase. The results of the immunofluorescence evidence the specific mitochondrial targeting by those derivatives.

The Feasibility and Safety of Interventional Occlusion Treatment of Intracristal Ventricular Septal Defects: Clinical Report of 56 Cases.

BACKGROUND: To investigate the feasibility and safety of the O eccentric shape occluder in the interventional occlusion treatment of intracristal ventricular septal defect (IVSD). METHODS: A retrospective analysis of the clinical data of 56 IVSD patients treated by interventional occlusion at our center, as well as recording of their intraoperative and postoperative status, was performed. RESULTS: Of the 56 patients, a total of 48 patients underwent successful occlusion during the first surgical attempt. Four patients were transferred to the Surgery Department after occlusion when the largest occluder failed because of large defects. Two patients exhibited aortic valve regurgitation; 1 patient had mild regurgitation, which was not worsened after 6 months of follow-up. One patient had severe aortic regurgitation, and 2 days after the operation, the patient underwent a second operation. One patient exhibited a residual shunt, which was above the occluder; after 1 year of follow-up, re-occlusion was successful and eliminated the shunt. One patient developed complete right bundle branch block. CONCLUSION: Most IVSD interventional occlusion treatments are feasible and safe.

Myocardial infarction accelerates glomerular injury and microalbuminuria in diabetic rats via local hemodynamics and immunity.

BACKGROUND: Clinically, approximately one-third of patients with chronic heart failure (CHF) exhibit some degree of renal dysfunction. This renal dysfunction is referred to as cardiorenal syndrome (CRS) and plays an important role in the poor prognosis of CHF. Mounting evidence suggests that diabetes is the most common underlying risk factor for CRS. However, the underlying pathophysiological mechanisms are poorly understood. METHODS: We performed the following comparisons in two separate protocols: 1) surgically induced myocardial infarction rats (MI, n=10), sham operation rats (Ctr, n=10) and MI rats treated with Fasudil, a Rho-kinase inhibitor (MI+Fas, n=9); and 2) STZ-induced type 1 diabetic rats (DB, n=10), DB+MI rats (n=10) and DB+MI rats treated with Fasudil (DB+MI+Fas, n=9). Renal hemodynamics and vasoconstrictor reactivity were evaluated using the DMT myograph system. Renal immunity was evaluated by flow cytometry, electron microscopy, immunofluorescence, etc. RESULTS: Twelve weeks after the operation, compared with DB or MI rats, DB+MI rats exhibited the following characteristics: 1) significantly increased glomerular enlargement, fibrosis, glomerulosclerosis, podocyte injury and microalbuminuria; 2) significantly increased vasoconstrictor reactivity of the renal interlobular arteries and renal venous pressure; 3) significantly increased infiltration of CD3+ and CD4+ T cells and decreased Treg/Th17 ratios; and 4) significantly increased glomerular deposition of IgG and C4. In contrast, rats with MI only showed mildly accelerated glomerular remodeling and microalbuminuria, with little change in renal hemodynamics and immunity. Fasudil treatment significantly improved the renal lesions in DB+MI rats but not MI rats. CONCLUSIONS: Post-MI cardiac dysfunction significantly accelerated glomerular remodeling, podocyte injury and microalbuminuria in STZ-induced diabetic rats. These changes were accompanied by altered local hemodynamics and immunity.

Transcatheter closure with use of the SHSMA occluder in 180 patients with congenital heart defects: preliminary results.

Transcatheter closure of congenital heart defects with the use of septal occluders has been widely accepted as a preferred treatment; however, the high cost of these devices limits their clinical application in some countries. Few clinical data are available regarding lower-cost products. Accordingly, we evaluated the efficacy and safety of the Chinese-made Shanghai Shape Memory Alloy (SHSMA) occluder in patients with congenital heart defects. From December 2001 through December 2008, a total of 180 patients with congenital heart defects (ages, 3-68 yr; mean age, 17.35 ± 13.22 yr) underwent transcatheter closure with use of the SHSMA occluder: 73 had atrial septal defects; 64, ventricular septal defects; 40, patent ductus arteriosus; and 3, complex congenital defects. The mean diameters of the defects were 20 ± 7.6 mm (atrial septal), 4.9 ± 2.1 mm (ventricular septal), and 5.6 ± 2.2 mm (patent ductus arteriosus). The procedural success rates were 98.6% for atrial defects, 98.4% for ventricular defects, and 100% for patent ductus arteriosus and for complex defects. The overall incidences of sequelae were 5.5%, 9.4%, 2.5%, and 0, respectively. Six months postprocedurally, complete occlusion was associated with a significant decrease in the right ventricular Tei index in atrial septal defect patients (P < 0.05) and with improvement of body mass index in 11 children. These results suggest that the SHSMA occluder is a safe, effective device for the transcatheter closure of congenital heart defects. For confirmation, a randomized controlled trial with more patients and a longer follow-up period is warranted.