Search

Human immunodeficiency virus type-1 (HIV-1) associated comorbidities account for the majority of poor health outcomes in people living with HIV (PLWH) in the era of antiretroviral therapy. Lung-related comorbidities such as chronic obstructive pulmonary disease (COPD) and bacterial pneumonia are primarily responsible for increased morbidity and mortality in PLWH, even when compensated for smoking. Smokers and COPD patients demonstrate cilia shortening, attenuated ciliary beat frequency (CBF), dysfunctional ciliated cells along with goblet cell hyperplasia, and mucus hypersecretion. This is exacerbated by the fact that almost 60% of PLWH smoke tobacco, which can exacerbate inflammation and mucociliary clearance (MCC) dysfunction. This study shows that HIV Tat alters the microRNAome in airway epithelial cells and upregulates miR-34a-5p with consequent suppression of its target, Sirtuin 1 (SIRT1). SIRT1 is known to suppress Metalloproteinase 17 (ADAM17), a protease activating Notch signaling. HIV and cigarette smoke (CS) upregulate ADAM17. ADAM17 upregulation followed by SIRT1 suppression can lead to decreased ciliation, mucus hypersecretion, and attenuated MCC, a hallmark of chronic bronchitis in smokers and COPD. It is, therefore, essential to understand the pathophysiological mechanism resulting in acquired Notch dysregulation and its downstream impact on HIV-infected smokers. [ABSTRACT FROM AUTHOR]

RNA interference (RNAi) is a process in which small RNA molecules (such as small interfering RNAs or siRNAs) bind to specific messenger RNAs (mRNAs), leading to its degradation and inhibition of protein synthesis. Our studies have shown that RNAi can effectively silence genes involved in the replication of the Chikungunya virus (CHIKV) in cells. However, these investigations were performed only in laboratory settings and have yet to be tested in human clinical trials. Researchers need to conduct more research to determine the safety and efficacy of RNAi-based therapies as a therapeutic agent to treat viral infections. In this review, the history of evolution of siRNA as an inhibitor of protein synthesis, along with its current developments, is discussed based on our experience. Moreover, this review examines the hurdles and future implications associated with siRNA based therapeutic approaches. [ABSTRACT FROM AUTHOR]

microRNAs have emerged as essential regulators of health and disease, attracting significant attention from researchers across diverse disciplines. Following their identification as noncoding oligonucleotides intricately involved in post-transcriptional regulation of protein expression, extensive efforts were devoted to elucidating and validating their roles in fundamental metabolic pathways and multiple pathologies. Viral infections are significant modifiers of the host microRNAome. Specifically, the Human Immunodeficiency Virus (HIV), which affects approximately 39 million people worldwide and has no definitive cure, was reported to induce significant changes in host cell miRNA profiles. Identifying and understanding the effects of the aberrant microRNAome holds potential for early detection and therapeutic designs. This review presents a comprehensive overview of the impact of HIV on host microRNAome. We aim to review the cause-and-effect relationship between the HIV-induced aberrant microRNAome that underscores miRNA's therapeutic potential and acknowledge its limitations. [ABSTRACT FROM AUTHOR]

The proposed siRNA 2, siRNA 3 and siRNA 4 comprise 21-mer sequences, whereas the siRNA 1 is a 19 mer. All the four identified siRNAs of the target sequence were located in the S2 domain; three (siRNA 2, siRNA 3 and siRNA 4) in the region that is translated into the heptad repeat 1 (HR1), which plays a critical role in viral entry[[18]]. The siRNA 2, siRNA 3 and siRNA 4 were noted to be predicted from the siDirect 2.0 servers, while the siRNA 1 was predicted from Block-iT RNAi designer. [Extracted from the article]

A prominent research topic in contemporary advanced functional materials science is the production of smart materials based on polymers that may independently adjust their physical and/or chemical characteristics when subjected to external stimuli. Smart hydrogels based on poly( N -isopropylacrylamide) (PNIPAM) demonstrate distinct thermoresponsive features close to a lower critical solution temperature (LCST) that enhance their capability in various biomedical applications such as drug delivery, tissue engineering, and wound dressings. Nevertheless, they have intrinsic shortcomings such as poor mechanical properties, limited loading capacity of actives, and poor biodegradability. Formulation of PNIPAM with diverse functional constituents to develop hydrogel composites is an efficient scheme to overcome these defects, which can significantly help for practicable application. This review reports on the latest developments in functional PNIPAM-based smart hydrogels for various biomedical applications. The first section describes the properties of PNIPAM-based hydrogels, followed by potential applications in diverse fields. Ultimately, this review summarizes the challenges and opportunities in this emerging area of research and development concerning this fascinating polymer-based system deep-rooted in chemistry and material science., Competing Interests: The authors declare no conflict of interest.