Translational research : the journal of laboratory and clinical medicine
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GV1001, a novel peptide derived from human telomerase reverse transcriptase, reportedly has anticancer and anti-inflammatory effects. Choroidal neovascularization (CNV) is a complex pathogenic process that involves angiogenesis, inflammation, cellular immunity, and other factors. This study was aimed at investigating the effect of GV1001 on laser-induced CNV in a rat model. ⋯ At 1 nM concentration, GV1001 had highest inhibitory effect on CNV and NF-κB signaling activation; moreover, it suppressed the levels of IL-1β, IL-6, and VEGF significantly. The present study demonstrates that GV1001 treatment led to significant suppression of laser-induced CNV, alongside inhibition of inflammatory processes including NF-κB activation and subsequent upregulation of proinflammatory cytokines. Therefore, this provides molecular evidence of potential validity of GV1001 treatment as a therapeutic strategy for neovascular age-related macular degeneration.
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A prothrombotic state is frequently observed in patients with cancer and contributes to the risks of venous thromboembolism (VTE), arterial thromboembolism (ATE), tumor progression, and death. Altered ex vivo properties of plasma clot formation and lysis have been observed in patients with cancer. The aim of this prospective study was to comprehensively characterize the relationship between plasma clot properties, inflammation, hypercoagulability, thrombotic complications, and mortality in patients with cancer using a tissue-factor-based turbidimetric assay of clot formation and lysis. ⋯ In a prospective analysis, altered parameters of clot formation identified cancer patients at high risk of ATE (Hazard ratio [HR] per doubling of peak absorbance: 4.43, 95% CI: 1.50-13.07, P = 0.007) and death (HR per doubling of peak absorbance: 2.73, 2.00-3.72, P< 0.0001); these findings were independent of other prognostic covariates. Contrarily, turbidity parameters were not associated with risk of VTE (HR per doubling of peak absorbance: 1.15, 0.66-2.01, P = 0.62). We conclude that patients with cancer have altered ex vivo properties of clot formation which predict risks of ATE and mortality but not VTE.
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Dilated cardiomyopathy (DCM) is a heart muscle disease characterized by ventricular dilation and systolic dysfunction in the absence of abnormal loading conditions or coronary artery disease. This cardiac disorder is a major health problem due to its high prevalence, morbidity, and mortality. DCM is a complex disease with a common phenotype but heterogeneous pathological mechanisms. ⋯ However, this field has not been reviewed in detail. Here, we summarize the evidence of intracellular and circulating miRNAs in DCM and their usefulness in the development of novel diagnostic, prognostic and therapeutic approaches, with a focus on DCM etiology. Although the findings are still preliminary, due to methodological and technical limitations and the lack of robust population-based studies, miRNAs constitute a promising tool to assist in the clinical management of DCM.
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Precision medicine has generated diagnoses for many patients with challenging undiagnosed disorders. Some individuals remain without a diagnosis despite comprehensive testing, and this impedes their treatment. This report addresses the role of personalized medicine in identifying effective therapy for an undiagnosed disease. ⋯ The patient's cultured fibroblasts were incubated with selected drugs, and cell proliferation was inhibited by hydroxychloroquine. Treatment of the patient with hydroxychloroquine conferred prolonged beneficial clinical effects, including stabilization of trismus and reduction of corticosteroid dose, C-reactive protein, and size of masses. This case represents an example of precision medicine applied to discover effective treatments for individuals with enigmatic undiagnosed disorders.
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The administration of geranylgeranyl pyrophosphate (GGPP) (or its precursor, geranylgeraniol [GGOH]) has been shown by several in vitro studies to be capable of abrogating statin-induced myotoxicity. Nonetheless, the potential of GGPP repletion to prevent statin-associated muscle symptoms (SAMS) in vivo is yet to be investigated. Therefore, this study aimed to evaluate the ability of GGOH to prevent SAMS in rodents. ⋯ Vascular relaxation was also maintained following treatment with GGOH. The findings of this study demonstrate that GGOH can prevent statin-induced skeletal muscle fatigue in rodents without causing adverse changes in cardiovascular function. Further studies to elucidate the exact mechanisms underlying the effects observed in this investigation are warranted.