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Sonia Moreno-Grau Itziar de Rojas Isabel Hernández Inés Quintela Laura Montrreal Montserrat Alegret Begoña Hernández-Olasagarre Laura Madrid Antonio González-Perez Olalla Maroñas Maitée Rosende-Roca Ana Mauleón Liliana Vargas Asunción Lafuente Carla Abdelnour Octavio Rodríguez-Gómez Silvia Gil Miguel Ángel Santos-Santos Agustín Ruiz 《Alzheimer's & dementia》2019,15(10):1333-1347
IntroductionLarge variability among Alzheimer's disease (AD) cases might impact genetic discoveries and complicate dissection of underlying biological pathways.MethodsGenome Research at Fundacio ACE ([email protected]) is a genome-wide study of dementia and its clinical endophenotypes, defined based on AD's clinical certainty and vascular burden. We assessed the impact of known AD loci across endophenotypes to generate loci categories. We incorporated gene coexpression data and conducted pathway analysis per category. Finally, to evaluate the effect of heterogeneity in genetic studies, [email protected] series were meta-analyzed with additional genome-wide association study data sets.ResultsWe classified known AD loci into three categories, which might reflect the disease clinical heterogeneity. Vascular processes were only detected as a causal mechanism in probable AD. The meta-analysis strategy revealed the ANKRD31-rs4704171 and NDUFAF6-rs10098778 and confirmed SCIMP-rs7225151 and CD33-rs3865444.DiscussionThe regulation of vasculature is a prominent causal component of probable AD. [email protected] meta-analysis revealed novel AD genetic signals, strongly driven by the presence of clinical heterogeneity in the AD series. 相似文献
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Nancy Vargas-Mendoza Jazm n Garc a-Machorro Marcelo Angeles-Valencia Marlet Mart nez-Archundia Eduardo Osiris Madrigal-Santill n ngel Morales-Gonz lez Liliana Anguiano-Robledo Jos A Morales-Gonz lez 《World journal of gastroenterology : WJG》2021,27(34):5630-5665
Coronavirus disease 2019 (COVID-19), which is caused by severe acute respi ratory syndrome-coronavirus-2 (SARS-CoV-2), has affected millions of people globally. It was declared a pandemic by the World Health Organization in March 2020. The hyperinflammatory response to the entry of SARS-CoV-2 into the host through angiotensin-converting enzyme 2 is the result of a “cytokine storm” and the high oxidative stress responsible for the associated symptomatology. Not only respiratory symptoms are reported, but gastrointestinal symptoms (diarrhea, vomiting, and nausea) and liver abnormalities (high levels of aspartate amino transferase, alanine aminotransferase transaminases, and bilirubin) are observed in at least 30% of patients. Reduced food intake and a delay in medical services may lead to malnutrition, which increases mortality and poor outcomes. This review provides some strategies to identify malnutrition and establishes nutri tional approaches for the management of COVID-19 and liver injury, taking energy and nutrient requirements and their impact on the immune response into account. The roles of certain phytochemicals in the prevention of the disease or as promising target drugs in the treatment of this disease are also considered. 相似文献
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Liliana Tavares Adi Lador Miguel Valderrbano 《Methodist DeBakey Cardiovascular Journal》2021,17(1):49
Sleep apnea is highly associated with atrial fibrillation (AF), and both diseases are highly prevalent in the United States. The mechanistic underpinnings that contribute to their association remain uncertain, but numerous possible mechanisms have been proposed, including dysfunction of the cardiac autonomic nervous system (ANS). Studies have reported that apnea induces hyperactivity of the ANS, leading to increases in AF susceptibility. This review compiles the latest evidence on the role of the ANS in sleep-apnea-induced AF. 相似文献
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Maciej Zacharski Alicja Tomaszek Liliana Kiczak Maciej Ugorski Jacek Bania Urszula Pasławska Ilona Rybinska Ewa Anita Jankowska Adrian Janiszewski Piotr Ponikowski 《Journal of cardiac failure》2021,27(6):682-692
BackgroundSteroid hormones play an important role in heart failure (HF) pathogenesis, and clinical data have revealed disordered steroidogenesis in male patients with HF. However, there is still a lack of studies on steroid hormones and their receptors during HF progression. Therefore, a porcine model of tachycardia-induced cardiomyopathy corresponding to HF was used to assess steroid hormone concentrations in serum and their nuclear receptor levels in heart tissue during the consecutive stages of HF.Methods and ResultsMale pigs underwent right ventricular pacing and developed a clinical picture of mild, moderate, or severe HF. Serum concentrations of dehydroepiandrosterone, testosterone, dihydrotestosterone, estradiol, aldosterone, and cortisol were assessed by enzyme-linked immunosorbent assay. Androgen receptor, estrogen receptor alpha, mineralocorticoid receptor, and glucocorticoid receptor messenger RNA levels in the left ventricle were determined by qPCR.The androgen level decreased in moderate and severe HF animals, while the corticosteroid level increased. The estradiol concentration remained stable. The quantitative real-time polymerase chain reaction revealed the downregulation of androgen receptor in consecutive stages of HF and increased expression of mineralocorticoid receptor messenger RNA under these conditions.ConclusionsIn the HF pig model, deteriorated catabolic/anabolic balance, manifested by upregulation of aldosterone and cortisol and downregulation of androgen signaling on the ligand level, was augmented by changes in steroid hormone receptor expression in the heart tissue. 相似文献
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Costan Victor Vlad Ciocan-Pendefunda Constantin-Catalin Ciofu Mihai Liviu Boisteanu Otilia Timofte Daniel Vasile Gheorghe Liliana Bogdanici Camelia Preda Cristina 《Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie》2020,258(10):2313-2320
Graefe's Archive for Clinical and Experimental Ophthalmology - The purpose of this study is to share our experience on the use of different orbital decompression techniques, as well as the... 相似文献
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Ana Clara Cristvo Filipa L. Campos Goun Je Marta Esteves Subhrangshu Guhathakurta Lichuan Yang M. Flint Beal Beatriz M. Fonseca Antonio J. Salgado Joo Queiroz Nuno Sousa Liliana Bernardino Gilberto Alves Kyung‐Sik Yoon Yoon‐Seong Kim 《The European journal of neuroscience》2020,52(4):3242-3255
Animal models of human diseases are crucial experimental tools to investigate the mechanisms involved in disease pathogenesis and to develop new therapies. In spite of the numerous animal models currently available that reproduce several neuropathological features of Parkinson disease (PD), it is challenging to have one that consistently recapitulates human PD conditions in both motor behaviors and biochemical pathological outcomes. Given that, we have implemented a new paradigm to expose rats to a chronic low dose of paraquat (PQ), using osmotic minipumps and characterized the developed pathologic features over time. The PQ exposure paradigm used lead to a rodent model of PD depicting progressive nigrostriatal dopaminergic neurodegeneration, characterized by a 41% significant loss of dopaminergic neuron in the substantia nigra pars compacta (SNpc), a significant decrease of 18% and 40% of dopamine levels in striatum at week 5 and 8, respectively, and a significant 1.5‐fold decrease in motor performance. We observed a significant increase of microglia activation state, sustained levels of α‐synucleinopathy and increased oxidative stress markers in the SNpc. In summary, this is an explorative study that allowed to characterize an improved PQ‐based rat model that recapitulates cardinal features of PD and may represent an attractive tool to investigate several mechanisms underlying the various aspects of PD pathogenesis as well as for the validation of the efficacy of new therapeutic approaches that targets different mechanisms involved in PD neurodegeneration. 相似文献
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