Is the Cis-Element CACCC-Box a Master Regulatory Element during Cardiovascular Disease? A Bioinformatics Approach from the Perspective of the Krüppel-like Family of Transcription Factors.

The CACCC-box motif emerges as a pivotal cis-regulatory element implicated in diverse developmental processes and diseases, particularly cardiovascular diseases (CVDs). This study centers on the intricate interplay between the CACCC-box and its binding proteins such as: the Krüppel-Like Family (KLF) of transcription factors as primary effectors in the context of CVDs. Our analysis was through a bioinformatics approach, which revealed significant transcriptional activity among KLF subgroup 2, exhibiting the highest number of interactions focusing on the established roles: pluripotency, cancer, and cardiovascular development and diseases. Our analysis reveals KLF's interactions with GATA4, MEF2C, NKX2.5 and other ~90 potential genes that participate in the regulation of the hypertrophic environment (or CVDs' Environment). Also, the GO analysis showed that genes containing the motif CACCC were enriched for multiple CVDs; in combination with STRING analysis, these results pointed to a link between KLFs and these diseases. The analysis further identifies other potential CACCC-box binding factors, such as SP family members, WT1, VEZF1, and -SALL4, which are implicated in cardiac contraction, remodeling, and inflammation processes.

A panoramic view of hospitalized young children in the metropolitan area of the valley of Mexico during COVID-19.

Objectives: This work provides an overview of young children's (aged 0-9) infectious diseases epidemiology, by exploring the link between various comorbid conditions, COVID-19, and death rate. Methods: Public data on hospitalized young children was obtained from national databases of the Mexican health care system from 2020-2022. Data included age, year of entry, gender, the time between admission to death (hospitalization time), date of death, comorbidities, and admissions to the intensive care unit. Children were separated into age groups and frequencies were calculated. Binary regression models were developed to determine the correlation of comorbidities and COVID-19 to death as calculated by odds ratios (OR). Results: From 2020-2022, there were 11,815 hospitalizations among young children, of which 15.98% were due to COVID-19, 2.55% of hospitalizations resulted in fatalities from which 32.45% of deaths were COVID-19 related. The highest case-calculated fatality ratio of COVID-19 infected young children was estimated at 7.04% by early 2020, but dropped to 2.11% by the end of the second semester of 2022. The most frequent comorbidities associated with their hospitalization and death for the general population were intubation (OR: 17.967), pneumonia (OR: 2.263), diabetes (OR: 7.301), cardiovascular diseases (OR: 1.528) and COVID-19 (OR: 261). For the COVID-19-positive group, the most impactful comorbidities were intubation (OR: 20.232), pneumonia (OR: 3.057), and diabetes (OR: 12.824). Conclusion: Children's hospitalizations and deaths were common during the pandemic; wherein major comorbidities played an important role. Therefore, effective comorbidity management and vaccination programs are essential to reduce hospitalizations and deaths among young children.

The Involvement of Krüppel-like Factors in Cardiovascular Diseases.

Krüppel-like factors (KLFs) are a set of DNA-binding proteins belonging to a family of zinc-finger transcription factors, which have been associated with many biological processes related to the activation or repression of genes, inducing cell growth, differentiation, and death, and the development and maintenance of tissues. In response to metabolic alterations caused by disease and stress, the heart will undergo cardiac remodeling, leading to cardiovascular diseases (CVDs). KLFs are among the transcriptional factors that take control of many physiological and, in this case, pathophysiological processes of CVD. KLFs seem to be associated with congenital heart disease-linked syndromes, malformations because of autosomal diseases, mutations that relate to protein instability, and/or loss of functions such as atheroprotective activities. Ischemic damage also relates to KLF dysregulation because of the differentiation of cardiac myofibroblasts or a modified fatty acid oxidation related to the formation of a dilated cardiomyopathy, myocardial infarctions, left ventricular hypertrophy, and diabetic cardiomyopathies. In this review, we describe the importance of KLFs in cardiovascular diseases such as atherosclerosis, myocardial infarction, left ventricle hypertrophy, stroke, diabetic cardiomyopathy, and congenital heart diseases. We further discuss microRNAs that have been involved in certain regulatory loops of KLFs as they may act as critical in CVDs.