Aryl hydrocarbon receptor: Linking environment to aging process in elderly patients with asthma.

ABSTRACT: Aging is a significant risk factor for various diseases, including asthma, and it often leads to poorer clinical outcomes, particularly in elderly individuals. It is recognized that age-related diseases are due to a time-dependent accumulation of cellular damage, resulting in a progressive decline in cellular and physiological functions and an increased susceptibility to chronic diseases. The effects of aging affect not only the elderly but also those of younger ages, posing significant challenges to global healthcare. Thus, understanding the molecular mechanisms associated with aging in different diseases is essential. One intriguing factor is the aryl hydrocarbon receptor (AhR), which serves as a cytoplasmic receptor and ligand-activated transcription factor and has been linked to the aging process. Here, we review the literature on several major hallmarks of aging, including mitochondrial dysfunction, cellular senescence, autophagy, mitophagy, epigenetic alterations, and microbiome disturbances. Moreover, we provide an overview of the impact of AhR on these hallmarks by mediating responses to environmental exposures, particularly in relation to the immune system. Furthermore, we explore how aging hallmarks affect clinical characteristics, inflammatory features, exacerbations, and the treatment of asthma. It is suggested that AhR signaling may potentially play a role in regulating asthma phenotypes in elderly populations as part of the aging process.

Effective delivery of miR-511-3p with mannose-decorated exosomes with RNA nanoparticles confers protection against asthma.

Our previous studies have shown that miR-511-3p treatment has a beneficial effect in alleviating allergic airway inflammation. Here, we sought to explore its therapeutic potential in animal models and gain a deeper understanding of its therapeutic value for asthma. miR-511-3p knockout mice (miR-511-3p-/-) were generated by CRISPR/Cas and showed exacerbated airway hyper-responsiveness and Th2-associated allergic airway inflammation compared with wild-type (WT) mice after exposed to cockroach allergen. RNA nanoparticles with mannose decorated EV-miR-511-3p were also created by loading miR-511-3p mimics into the mannose decorated EVs with engineered RNA nanoparticle PRNA-3WJ (Man-EV-miR-511-3p). Intra-tracheal inhalation of Man-EV-miR-511-3p, which could effectively penetrate the airway mucus barrier and deliver functional miR-511-3p to lung macrophages, successfully reversed the increased airway inflammation observed in miR-511-3p-/- mice. Through microarray analysis, complement C3 (C3) was identified as one of the major targets of miR-511-3p. C3 was increased in LPS-treated macrophages but decreased after miR-511-3p treatment. Consistent with these findings, C3 expression was elevated in the lung macrophages of an asthma mouse model but decreased in mice treated with miR-511-3p. Further experiments, including miRNA-mRNA pulldown and luciferase reporter assays, confirmed that miR-511-3p directly binds to C3 and activates the C3 gene. Thus, miR-511-3p represents a promising therapeutic target for asthma, and RNA nanotechnology reprogrammed EVs are efficient carriers for miRNA delivery for disease treatment.

COVID-associated cystitis: the culprit behind the bladder woes post-COVID infection? A review.

PURPOSE: SARS-CoV-2 had a significant impact on public health since its declaration as a pandemic. It is linked to a high rate of multiple organ dysfunction syndrome (MODS) and a slew of long-term symptoms that are yet to be thoroughly investigated. Among these, genitourinary symptoms of an overactive bladder (increased frequency, urgency, and nocturia) have recently been identified and labeled as COVID-associated cystitis (CAC). This current research is performed to review this phenomenon. METHODS: A literature search was performed in MEDLINE, Cochrane, and Google Scholar databases and 185 articles were obtained in total, including reviews and trials involving CAC, which were screened using various methods, and 42 articles were gathered for the review. RESULTS: Among its multitude of symptoms, overactive bladder (OAB) leads to poorer outcomes. The inflammatory mediator-based theory and the ACE-2 receptor-based theory are two probable theories for how it harms the bladder urothelium. The expression of ACE-2 receptors during the pathogenesis of CAC warrants further investigation as ACE modulation may reveal more information about COVID-19 complications. Other comorbidities, immunocompromised patients, or patients with a history of urinary tract infections can also exacerbate this condition. CONCLUSION: The scarce literature collected related to CAC gives us an insight into the symptomatology, pathophysiology, and possible treatment plans. Treatment choices are diverse among COVID-19-afflicted and unaffected patients for treating urinary symptoms which highlights the importance to distinguish between the two. CAC shows greater prevalence and morbidity when linked to other conditions, thereby warranting future developments in it.