Biology subjects

Paksa, A.

Publications and source records attributed to Paksa, A..

3 recordsLinked to original sources

bioRxiv2026

Repellency effects of nanoliposomal gels bearing Clove (Syzygium aromaticum) or Tea tree (Melaleuca alternifolia) essential oils against the main malaria vector, Anopheles stephensi

BackgroundThe development of safe and effective plant-based repellents is crucial to control malaria transmission, particularly given the spread of insecticide resistance in major vectors like Anopheles stephensi. Essential oils (EOs) are promising candidates, yet their high volatility and hydrophobicity limit their efficacy. This study aimed to design and evaluate nanoliposomal gels containing Syzygium aromaticum (clove) or Melaleuca alternifolia (tea tree) EOs to enhance their repellent durability against An. stephensi. MethodsThe chemical profiles of the EOs were determined via Gas Chromatography-Mass Spectrometry (GC-MS). Nanoliposomes bearing 3% of each EO were made ready with the ethanol injection method, and incorporated into a carboxymethyl cellulose (CMC) gel. Formulations were characterized for particle size, zeta potential, viscosity, and chemical interactions (FTIR). Repellent efficacy was evaluated using the arm-in-cage method, recording the complete protection time (CPT) for nanoliposomal gels (LipoGel 3%), in comparison with nonformulated EOs and the gold-standard repellent, DEET (40%). ResultsGC-MS analysis identified eugenol (79.51%) and terpinen-4-ol (73.53%) as the major constituents of clove and tea tree EOs, respectively. Nanoliposomes exhibited sizes of 82.3 {+/-} 3 nm (clove) and 102 {+/-} 4 nm (tea tree), with narrow size distributions. The clove LipoGel demonstrated a significantly enhanced CPT (341 {+/-} 17 min), which was statistically comparable to 40% DEET (351 {+/-} 16 min, P>0.05). In contrast, the nonformulated EOs resulted in only 45 min of protection, highlighting the critical role of the nanocarrier system. ConclusionThe nanoliposomal gel formulation, particularly containing clove EO, represents a potent and safe botanical alternative to conventional synthetic repellents. This approach offers a promising strategy for integrated vector management, warranting further field-based investigations.

zoology↗

bioRxiv2025

Self-amplifying mRNA expression is governed by mitochondrial machinery and ACSL4

RNA-based vaccines offer a superior efficacious and economic approach over traditional vaccines. However, current dose requirement and short half-life of conventional modified mRNA (modRNA) may hinder the development of more effective vaccines. Self-amplifying mRNA (saRNA) is a modality that has the potential to address these limitations by reducing delivery dosage and enhancing the duration of expression over modRNA. Despite marked success in preclinical studies, saRNA vaccines have thus far underperformed in most clinical trials. We hypothesized that non-optimal human cellular context limits saRNA expression, and that elucidating the factors underlying saRNA expression would be key in developing saRNA as a viable therapeutic modality. To identify factors involved in the regulation of saRNA, we performed a quasi-genome-wide CRISPR knockout screen, which revealed that saRNA expression in human cells is linked to mitochondrial function and governed by ACSL4. We validated these findings through pharmacological intervention and single gene editing, demonstrating that ACSL4-mediated regulation is unique to saRNA and does not impact modRNA. Moreover, we show that modulating ACSL4 leads to improved saRNA expression across multiple cell types. We demonstrate for the first time that mitochondrial function and ACSL4 play key roles in saRNA expression, providing insight for the development and implementation of saRNA as a therapeutic modality.

molecular biology↗

bioRxiv2024

Airway basal stem cells are necessary for the maintenance of functional intraepithelial airway macrophages.

Adult stem cells play a crucial role in tissue homeostasis and repair through multiple mechanisms. In addition to being able to replace aged or damaged cells, stem cells provide signals that contribute to the maintenance and function of neighboring cells. In the lung, airway basal stem cells also produce cytokines and chemokines in response to inhaled irritants, allergens, and pathogens, which affect specific immune cell populations and shape the nature of the immune response. However, direct cell-to-cell signaling through contact between airway basal stem cells and immune cells has not been demonstrated. Recently, a unique population of intraepithelial airway macrophages (IAMs) has been identified in the murine trachea. Here, we demonstrate that IAMs require Notch signaling from airway basal stem cells for maintenance of their differentiated state and function. Furthermore, we demonstrate that Notch signaling between airway basal stem cells and IAMs is required for antigen-induced allergic inflammation only in the trachea where the basal stem cells are located whereas allergic responses in distal lung tissues are preserved consistent with a local circuit linking stem cells to proximate immune cells. Finally, we demonstrate that IAM-like cells are present in human conducting airways and that these cells display Notch activation, mirroring their murine counterparts. Since diverse lung stem cells have recently been identified and localized to specific anatomic niches along the proximodistal axis of the respiratory tree, we hypothesize that the direct functional coupling of local stem cell-mediated regeneration and immune responses permits a compartmentalized inflammatory response.

cell biology↗