Taibah University

As a barrier organ, the lungs are continuously exposed to environmental stimuli and rely on molecular sensors to detect and respond to these external cues. One such sensor is the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor traditionally recognized for its role in xenobiotic metabolism. However, this function is a relatively recent evolutionary adaptation of the AhR. Beyond its detoxification role, AhR has been implicated in developmental and homeostatic processes, as evidenced by defects in AhR-deficient mice. Despite this, the contribution of endogenous AhR activity to pulmonary homeostasis remains poorly defined. To address this gap, we leveraged high-resolution proteomics from lung tissue, bronchoalveolar lavage fluid (BALF), and extracellular vesicles (EVs) of AhR-expressing and AhR-knockout mice to define the role of AhR in shaping the pulmonary proteomic landscape. Our analysis reveals that each compartment exhibits a distinct proteomic signature and that AhR plays a central role dictating that composition within each compartment. Notably, AhR regulates proteins involved in epithelial barrier function, alveolar macrophage lipid handling, and the selective packaging of bioactive cargo into EVs. These findings identify AhR as a key regulator of structural and immune balance in the lung and uncover new functions of this receptor in maintaining pulmonary homeostasis. Furthermore, our work highlights the potential of EVs as sensitive indicators of AhR activity and offers new insight into therapeutic strategies targeting AhR signaling in respiratory disease.

o-Amino aryl carbonyl derivatives constitute an important class of intermediates in synthetic and medicinal chemistry owing to their tendency to undergo intramolecular condensation and cyclization under relatively mild conditions. The exceptional reactivity of these scaffolds makes them irreplaceable precursors for the production of a wide variety of nitrogen-containing heterocycles, such as quinolines, quinazolines, and benzodiazepines. Among this group of compounds, quinolines are particularly important due to their vast pharmacological potential and widespread use in pharmaceuticals, agrochemicals, and materials science. The review aims to provide an overview of recent developments in the synthesis, reactivity, and applications of quinolines derived from the cyclization of o-amino-substituted aryl carbonyl compounds, with a special focus on their involvement in green and sustainable chemistry strategies, such as solvent-free conditions and environmentally friendly catalytic systems.

Background: Patients with latent tuberculosis infection are mainly asymptomatic, but they still carry a notable risk of developing active TB, particularly when the host becomes immunosuppressed. Hence, appropriate diagnosis and management for LTBI are essential. Tuberculin skin test (TST) and interferon-gamma release assays (IGRAs) are among the most commonly utilized methods for detecting LTBI. Until now, no agreement has been established regarding the most effective diagnostic test, either TST or IGRA, so our study aims to evaluate the diagnostic utility of TST versus IGRA in detecting LTBI. Methods: An extensive literature search was executed in several databases from inception till June 2024. We included all the available studies that compared TST versus IGRA concurrently applied to the same study participants, utilizing one of the following proxy reference standards: previous contact with a tuberculosis patient, tuberculosis history, chest x-ray suggestive of tuberculosis, or a combination of them. The sensitivity (SN) and specificity (SP) were imputed with their 95% confidence interval (CI). A bivariate random-effects model within the OpenMeta-Analyst software was utilized for data analysis. Results: We included 39 studies, and our primary analysis regarding LTBI revealed that TST has an SN of 0.320 (95% CI [0.254-0.393]) and an SP of 0.808 (95% CI [0.752-0.854]). Nevertheless, the IGRA exhibited a higher SN estimated at 0.362 (95% CI [0.295-0.434]) and a lower SP estimated at 0.758 (95% CI [0.700-0.808]). Regarding the adult population, TST consistently showed a lower SN and a higher SP relative to IGRA. However, within the pediatric population, TST showed higher SN and lower SP when compared to IGRA. Furthermore, TST also showed a lower SN and a higher SP within hemodialysis and organ transplant patients than IGRA. Conclusions: Our diagnostic test meta-analysis revealed that TST was associated with a lower SN and a higher SP than IGRA. Clinicians should interpret these findings with caution, considering the substantial heterogeneity observed across the included studies, the reliance on proxy reference standards, the potential influence of BCG vaccination status, and the considerable overlap in confidence intervals between TST and IGRA estimates across most analyses.