Translational research : the journal of laboratory and clinical medicine
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Despite significant advances and the continuous development of novel, effective therapies to treat a variety of malignancies, cancer therapy-induced cardiotoxicity has been identified as a prominent cause of morbidity and mortality, closely competing with secondary malignancies. This unfortunate limitation has prompted the inception of the field of cardio-oncology with its purpose to provide the necessary knowledge and key information on mechanisms that support the use of the most efficacious cancer therapy with minimal or no interruption while paying close attention to preventing cardiovascular related morbidity and mortality. ⋯ In this review, we focus on describing the principal mechanisms for different classes of cancer therapies that lead to cardiotoxicity involving the NLRP3 inflammasome. We also summarize current evidence of cardio-protection with inflammasome inhibitors in the context of heart disease in general, and further highlight the potential application of this evidence for clinical translation in at risk patients for the purpose of preventing cancer therapy associated cardiovascular morbidity and mortality.
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The HepQuant SHUNT test quantifies hepatic functional impairment from the simultaneous clearance of cholate from the systemic and portal circulations for the purpose of monitoring treatment effects or for predicting risk for clinical outcome. Compartmental models are defined by distribution volumes and transfer rates between volumes to estimate parameters not defined by noncompartmental analyses. Previously, a noncompartmental analysis method, called the minimal model (MM), demonstrated reproducible and reliable measures of liver function (Translational Research 2021). ⋯ Acceptable reproducibility (ICC > 0.7) was observed for 6/6 and 5/6 hepatic disease indices for CM and MM, respectively. SHUNT, a measure of the absolute bioavailability, had ICC of 0.73 (0.60-0.83, P = 0.3095) for MM and 0.84 (0.76-0.90, P = 0.0012) for CM. The CM, but not the MM, allowed determination of anatomic shunt and hepatic extraction and improved the within individual reproducibility.
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Case Reports
Development of Strategies for Community Engaged Research Dissemination by Basic Scientists: A Case Study.
As depicted in the translational research continuum, dissemination of research findings to past research participants and the community-at-large is integral to improving health outcomes. Blocks in translation exist in which poor dissemination is a major contributor. Limited progress has been made on how to engage basic scientists at T1 and T2 phases to meaningfully disseminate study findings to community. ⋯ Finally, we provide competencies, informed by basic scientists, needed to engage in effective, community-engaged research dissemination. The activities, reflections, and competencies can be used by basic scientists and academic institutions as models to guide their community engaged research dissemination activities. This work supports the goal to bridge the translational research gap.
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Polycystic ovary syndrome (PCOS) is a common endocrine disorder of unknown etiology that occurs in women of reproductive age. Despite being considered to affect up to one-fifth of women in this cohort, the condition lacks generally accepted diagnostic biomarkers and options for targeted therapy. Hereby, we analyzed the diagnostic, therapeutic, and functional potential of a recently discovered miR-335-5p that was observed to be reduced in the follicular fluid (FF) of PCOS patients as compared with healthy women. ⋯ We identified SP1 as a miR-335-5p target gene by using the dual-luciferase reporter assay. Both the luciferase reporter assay and chromatin immunoprecipitation assay showed that SP1 bound to the promoter region of human CYP19A1 and inhibited its transcription. miR-335-5p increased the production of estradiol via the SP1/CYP19A1 axis in hGCs, thereby suggesting its mechanistic pathway of action. In conclusion, these results provide evidence that miR-335-5p may function as a mediator in the etiopathogenesis of PCOS, as well as has the potential as both a novel diagnostic biomarker and therapeutic target for PCOS.