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.

Nutraceuticals and Their Contribution to Preventing Noncommunicable Diseases.

The high rate of deaths around the world from noncommunicable diseases (NCDs) (70%) is a consequence of a poor diet lacking in nutrients and is linked to lifestyle and environmental conditions that together trigger predisposing factors. NCDs have increased 9.8% of public health spending worldwide, which has been increasing since 2000. Hence, international organizations such as the WHO, the Pan American Health Organization, and the Food and Agriculture Organization of the United Nations have been developing strategic plans to implement government and economic policies to strengthen programs in favor of food security and nutrition. A systematic review is presented to document an analysis of the origin and characteristics of obesity, cardiovascular disease, chronic respiratory diseases, diabetes, and cancers affecting a large part of the world's population. This review proposes a scientifically based report of functional foods including fruits, vegetables, grains, and plants, and how their bioactive compounds called nutraceuticals-when consumed as part of a diet-benefit in the prevention and treatment of NCDs from an early age. Multifactorial aspects of NCDs, such as culture and eating habits, are limitations to consider from the clinical, nutritional, and biochemical points of view of everyone who suffers from them.

Design and in silico analysis of a whole-cell biosensor able to kill methicillin-resistant Staphylococcus aureus.

The rise of methicillin-resistant Staphylococcus aureus (MRSA) infections has gained concern throughout the world over the past decades. Alternative therapeutic agents to antibiotics are rapidly growing to impede the proliferation of MRSA-caused infections. Lately, synthetic biology techniques have developed whole-cell biosensors by designing gene circuitry capable of sensing quorum-sensing (QS) molecules of pathogens and triggering expression of an antimicrobial moiety that kills MRSA and therefore prevents its further proliferation. Here, an E. coli was engineered in silico to act as a whole-cell biosensor that senses QS molecules from MRSA and triggers the expression of a bacteriocin that kills MRSA. To achieve this functionality, biosensor and bacteriocin modules were constructed and assembled into a vector. Both modules were codon-optimized to increase the yield production of the recombinant proteins. We then demonstrate in silico that the construction of a dual biosensor-killer plasmid, which holds two genetical modules known as biosensor and bacteriocin modules, enables the recombinant host to sense QS molecules from MRSA. Our designed whole-cell biosensor demonstrates in silico its ability to produce and secrete the bacteriocin as a function of the external concentration of autoinducer peptide from MRSA. These in silico results unravel the possibility of designing antimicrobial smarter therapeutics against resistant pathogens.

Bacteriocins: An Overview of Antimicrobial, Toxicity, and Biosafety Assessment by in vivo Models.

The world is facing a significant increase in infections caused by drug-resistant infectious agents. In response, various strategies have been recently explored to treat them, including the development of bacteriocins. Bacteriocins are a group of antimicrobial peptides produced by bacteria, capable of controlling clinically relevant susceptible and drug-resistant bacteria. Bacteriocins have been studied to be able to modify and improve their physicochemical properties, pharmacological effects, and biosafety. This manuscript focuses on the research being developed on the biosafety of bacteriocins, which is a topic that has not been addressed extensively in previous reviews. This work discusses the studies that have tested the effect of bacteriocins against pathogens and assess their toxicity using in vivo models, including murine and other alternative animal models. Thus, this work concludes the urgency to increase and advance the in vivo models that both assess the efficacy of bacteriocins as antimicrobial agents and evaluate possible toxicity and side effects, which are key factors to determine their success as potential therapeutic agents in the fight against infections caused by multidrug-resistant microorganisms.