Translational research : the journal of laboratory and clinical medicine
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Nuclear NADPH oxidase-4 (Nox4) is a key component of metabolic reprogramming and is often overexpressed in renal cell carcinoma (RCC). However, its prognostic role in RCC remains unclear. Here we examined the significance of nuclear Nox4 on disease progression and development of drug resistance in advanced RCC. ⋯ Our data support an important prognostic role of Nox4 mediated regulation of RCC independent of other competing variables. Nox4 localizes to the nucleus in high-grade, high-stage RCC. Higher nuclear Nox4 has prognostic significance for disease progression, poor survival, and development of drug resistance in RCC.
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Despite the success of anti-retroviral therapy (ART) in transforming HIV into a manageable disease, it has become evident that long-term ART will not eliminate the HIV reservoir and cure the infection. Alternative strategies to eradicate HIV infection, or at least induce a state of viral control and drug-free remission are therefore needed. Therapeutic vaccination aims to induce or enhance immunity to alter the course of a disease. In this review we provide an overview of the current state of therapeutic HIV vaccine research and summarize the obstacles that the field faces while highlighting potential ways forward for a strategy to cure HIV infection.
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Chronic obstructive pulmonary disease (COPD) increases the risk of atrial fibrillation (AF), however, its arrhythmogenic mechanisms are unclear. This study investigated the effects of COPD on AF triggers (pulmonary veins, PVs) and substrates (atria), and their potential underlying mechanisms. Electrocardiographic, echocardiographic, and biochemical studies were conducted in control rabbits and rabbits with human leukocyte elastase (0.3 unit/kg)-induced COPD. ⋯ H89 (10 μM), KN93 (1 μM), and KB-R7943 (10 μM) significantly suppressed burst firing and delayed afterdepolarizations in the PVs of the rabbits with COPD. Moreover, compared with the control rabbits, those with COPD had lower expression levels of the β1 adrenergic receptor, Cav 1.2, and Na+/Ca2+ exchanger in the PVs; Cav 1.2 in the LA; and hyperpolarization-activated cyclic nucleotide-gated K+ channel 4 in the SAN. COPD increases atrial arrhythmogenesis by modulating the distinctive electrophysiological characteristics of the PVs, LA, and SAN.