Translational research : the journal of laboratory and clinical medicine
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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.
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Abundant intraperitoneal (IP) accumulation of extracellular mucus in patients with appendiceal mucinous carcinoma peritonei (MCP) causes compressive organ dysfunction and prevents delivery of chemotherapeutic drugs to cancer cells. We hypothesized that reducing extracellular mucus would decrease tumor-related symptoms and improve chemotherapeutic effect in patient-derived models of MCP. Mucolysis was achieved using a combination of bromelain (BRO) and N-acetylcysteine (NAC). ⋯ Conversion of solid mucinous tumors into mucinous ascites decreases tumor bulk and allows for minimally invasive drainage of liquified tumors. Lysis of extracellular mucus removes the protective mucinous coating surrounding cancer cells and improves chemotherapeutic drug delivery/efficacy in cancer cells. Our data provide a preclinical rationale for the clinical evaluation of BRO + NAC as a therapeutic strategy for MCP.