Translational research : the journal of laboratory and clinical medicine
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Iron plays a key role in secondary neuronal injury after intracerebral hemorrhage (ICH), and hepcidin is able to reduce brain iron in iron-overloaded rats by down-regulating iron transport proteins including ferroportin 1 and transferrin receptor 1. These led us to hypothesize that hepcidin might reduce iron-mediated neurotoxicity by inhibiting iron accumulation in ICH brain. ⋯ The findings collectively showed that hepcidin could effectively attenuate iron-mediated secondary neuronal injury after ICH in rats. This naturally existing protein can potentially be developed into a therapeutic drug for the treatment of ICH patients.
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Metformin is the first-line medication for treatment of type 2 diabetes and has been shown to reduce heart damage and death. However, mechanisms by which metformin protects human heart remain debated. The aim of the study was to evaluate the cardioprotective effect of metformin on cardiomyocytes derived from human-induced pluripotent stem cells (hiPSC-CMs) and mitochondria isolated from human cardiac tissue. ⋯ Thus, in human heart, metformin might improve cardioprotection due to its biphasic effect on mitochondria: at low concentrations, it activates mitochondrial biogenesis via AMPK signaling and increases the OCR; at high concentrations, it inhibits the respiration by directly affecting the activity of complex I, reduces oxidative stress and delays mPTP formation. Moreover, metformin at high concentrations causes metabolic reprogramming by enhancing glycolysis and glutaminolysis. These effects can be a beneficial adjunct to patients with impaired endogenous cardioprotective responses.
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Despite significant morbidity among infants with single ventricle heart disease (SVHD), clinical monitoring is limited by poor understanding of the underlying pathobiology. Proteomics can identify novel biomarkers and important pathways in complex disease. No prior study has evaluated whether the proteome of SVHD infants differs from healthy controls, how it shifts after stage 2 palliation, or whether differences can predict post-operative outcomes. ⋯ Proteomic analysis identifies significant changes among SVHD infants pre- and post-stage 2, and healthy controls. Tissue inhibitor of metalloproteinase-1, nidogen-1, and matrix metalloproteinase 7 levels are higher in SVHD cases with greater morbidity suggesting an important role for regulation of extracellular matrix production. Proteomic profiling may identify high-risk SVHD infants.
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The prevalence of chronic kidney disease (CKD) in the worldwide population is currently estimated between 11% and 13%. Adequate renal clearance is compromised in these patients and the accumulation of a large number of uremic retention solutes results in an irreversible worsening of renal function which can lead to end stage renal disease (ESRD). Approximately three million ESRD patients currently receive renal replacement therapies (RRTs), such as hemodialysis, which only partially restore kidney function, as they are only efficient in removing mainly small, unbound solutes from the circulation while leaving larger and protein-bound uremic toxins (PBUTs) untouched. ⋯ In this review, we address several strategies currently being explored toward reducing PBUT concentrations, including clinical and medical approaches, therapeutic techniques, and recent developments in RRT technology. These include preservation of renal function, limitation of colon derived PBUTs, oral sorbents, adsorbent RRT technology, and use of albumin displacers. Despite the promising results of the different approaches to promote enhanced removal of a small percentage of the more than 30 identified PBUTs, on their own, none of them provide a treatment with the required efficiency, safety and cost-effectiveness to prevent CKD-related complications and decrease mortality and morbidity in ESRD.
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Coronary artery bypass grafting (CABG) is the standard treatment modality in revascularization of the myocardium. However, the graft failure remains the major complication following CABG procedure. Involvement of mitochondrial damage-associated molecular patterns (mt-DAMPs) in the pathogenesis of vein-graft failure is largely unknown. ⋯ Hypoxia in cultured smooth muscle cells (SMCs) significantly upregulated all mitochondrial biomarkers and mt-DAMPs compared to normoxia. The increased reactive oxygen species (ROS) content and compromised membrane integrity in the hypoxic SMCs correlated well with increased mt-DAMPs in the graft and associated tissues, suggesting a possible role of mt-DAMPs in the pathogenesis of graft failure. These findings suggest that the pathological signals elicited by mt-DAMPs could reveal targets for better therapeutic approaches and diagnostic strategies in the management of CABG graft failure.