Ubiquitin-dependent proteolysis, a therapeutic strategy: An interface between health and disease

All eukaryotic cells have a system in place called the ubiquitin-dependent proteolysis system to control protein degradation;nevertheless, any flaws in this system can initiate numerous fatal diseases, including cancer, metabolic problems, neurological disorders and diseases. These health complications interlink with faults in ubiquitin-dependent proteolysis. Ubiquitin assists as a post-translational targeting signal for altering the structure, localization of other proteins, features and functioning styles of the cells and tissues. The ubiquitin ligase standardizes the specific nature of the ubiquitination features and cellular response. The ubiquitin ligase is a critical element of the enzymatic cascade that regulates the part of the multipubiquitin chain to the target or labile protein. Consequently, the attachment of the ubiquitin topology is crucial for regulating healthy growth, differentiation, and protection of cells from damage by xenobiotics, infections, mutations, and environmental stresses. Protein degradation is adopted by the cells as a route to enduringly deactivate proteins. The 26S proteasome is responsible for ATP-dependent protein failure in the cytoplasm and nuclei of eukaryotes. Most proteins are covalently associated with a multi-ubiquitin chain and engage the 26S proteasome. In the testes, the ubiquitin ligases E1, E2, E3, and UBC4 are dynamic. Here, prompt and large protein alterations are essential for a cell to respond to its environment, and a complex web of interrelated events, including control over synthesis, localization, and degradation. The regulator of the cell cycle, receptor processing, growth management, and stress response are all subject to intracellular proteolysis. This chapter focuses on (I) the significant contribution of ubiquitination in the cellular signaling pathways that contract with these external influences;(II) the mechanisms of ubiquitination-deubiquitination that offer the system its high level of selectivity, (III) the role of ubiquitin-dependent degradation in initiating diseases in humans and forthcoming clinical claims developed to employ the cell's built-in proteolytic machinery to cure diseases;(IV) to examine imaginable clinical practices fashioned to exploit the body's own proteolytic machinery to cure the diseases, and analyze the effectiveness of vaccinations, antibodies, and other possible therapies that aim to block SARS-CoV-2 entrance pathways. Lastly, the authors include the most important unanswered queries pertaining to this crucial route. © 2023 Nova Science Publishers, Inc.

Association between multiple respiratory viral infections and pediatric intensive care unit admission among infants with bronchiolitis.

BACKGROUND: It is unclear whether multiple respiratory viral infections are associated with more severe bronchiolitis requiring pediatric intensive care unit (PICU) admission. We aimed to identify the association between multiple respiratory viral infections and PICU admission among infants with bronchiolitis. METHODS: We performed a 1:1 case-control study enrolling previously healthy full-term infants (≤12 months) with bronchiolitis admitted to the PICU as cases and those to the general pediatric ward as controls from 2015 to 2017. Multiplex polymerase chain reaction (PCR) was used for detection of the respiratory viruses. We summarized the characteristics of infants admitted to the PICU and the general pediatric unit. Multivariable logistic regression analysis was used to fit the association between multiple respiratory viral infections (≥2 strains) and PICU admission. RESULTS: A total of 135 infants admitted to the PICU were compared with 135 randomly selected control infants admitted to the general pediatric unit. The PICU patients were younger (median: 2.2 months, interquartile range: 1.3-4.2) than the general ward patients (median: 3.2 months, interquartile range: 1.6-6.4). Respiratory syncytial virus (74.1%), rhinovirus (28.9%), and coronavirus (5.9%) were the most common viruses for bronchiolitis requiring PICU admission. Patients with bronchiolitis admitted to the PICU tended to have multiple viral infections compared with patients on the general ward (23.0% vs. 10.4%, P<0.001). In the multivariable logistic regression analysis, bronchiolitis with multiple viral infections was associated with higher odds of PICU admission (adjusted odds ratio: 2.56, 95% confidence interval: 1.17-5.57, P=0.02). CONCLUSION: Infants with multiviral bronchiolitis have higher odds of PICU admission compared with those with a single or nondetectable viral infection.