Physical and mechanical properties of ocular thin films: a systematic review and meta-analysis.

The ocular thin film presents a potential solution for addressing challenges to ocular drug delivery. In this review, we summarise the findings of a comprehensive review analysing 336 formulations from 68 studies. We investigated the physical and mechanical properties of ocular thin films, categorised into natural polymer-based, synthetic polymer-based, and combined polymer films. The results showed that the type of polymers used impacted mucoadhesion force, moisture absorption:moisture loss ratio, pH, swelling index, and elongation percentage. Significant relationships were found between these properties within each subgroup. The results also highlighted the influence of plasticisers on elongation percentage, mucoadhesion force, swelling index, and moisture absorption:moisture loss ratio. These findings have implications for designing and optimising ocular drug formulations and selecting appropriate plasticisers to achieve formulations with the desired properties.

Correlation of Myeloid-Derived Suppressor Cell Expansion with Upregulated Transposable Elements in Severe COVID-19 Unveiled in Single-Cell RNA Sequencing Reanalysis.

Some studies have investigated the potential role of transposable elements (TEs) in COVID-19 pathogenesis and complications. However, to the best of our knowledge, there is no study to examine the possible association of TE expression in cell functions and its potential role in COVID-19 immune response at the single-cell level. In this study, we reanalyzed single-cell RNA seq data of bronchoalveolar lavage (BAL) samples obtained from six severe COVID-19 patients and three healthy donors to assess the probable correlation of TE expression with the immune responses induced by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in COVID-19 patients. Our findings indicate that the expansion of myeloid-derived suppressor cells (MDSCs) may be a characteristic feature of COVID-19. Additionally, a significant increase in TE expression in MDSCs was observed. This upregulation of TEs in COVID-19 may be linked to the adaptability of these cells in response to their microenvironments. Furthermore, it appears that the identification of overexpressed TEs by pattern recognition receptors (PRRs) in MDSCs may enhance the suppressive capacity of these cells. Thus, this study emphasizes the crucial role of TEs in the functionality of MDSCs during COVID-19.

The role of transposable elements in aging and cancer.

Transposable elements (TEs) constitute a large portion of the human genome. Various mechanisms at the transcription and post-transcription levels developed to suppress TE activity in healthy conditions. However, a growing body of evidence suggests that TE dysregulation is involved in various human diseases, including age-related diseases and cancer. In this review, we explained how sensing TEs by the immune system could induce innate immune responses, chronic inflammation, and following age-related diseases. We also noted that inflammageing and exogenous carcinogens could trigger the upregulation of TEs in precancerous cells. Increased inflammation could enhance epigenetic plasticity and upregulation of early developmental TEs, which rewires the transcriptional networks and gift the survival advantage to the precancerous cells. In addition, upregulated TEs could induce genome instability, activation of oncogenes, or inhibition of tumor suppressors and consequent cancer initiation and progression. So, we suggest that TEs could be considered therapeutic targets in aging and cancer.

A systems pharmacology approach to identify the autophagy-inducing effects of Traditional Persian medicinal plants.

Aging is correlated with several complex diseases, including type 2 diabetes, neurodegeneration diseases, and cancer. Identifying the nature of this correlation and treatment of age-related diseases has been a major subject of both modern and traditional medicine. Traditional Persian Medicine (TPM) embodies many prescriptions for the treatment of ARDs. Given that autophagy plays a critical role in antiaging processes, the present study aimed to examine whether the documented effect of plants used in TPM might be relevant to the induction of autophagy? To this end, the TPM-based medicinal herbs used in the treatment of the ARDs were identified from modern and traditional references. The known phytochemicals of these plants were then examined against literature for evidence of having autophagy inducing effects. As a result, several plants were identified to have multiple active ingredients, which indeed regulate the autophagy or its upstream pathways. In addition, gene set enrichment analysis of the identified targets confirmed the collective contribution of the identified targets in autophagy regulating processes. Also, the protein-protein interaction (PPI) network of the targets was reconstructed. Network centrality analysis of the PPI network identified mTOR as the key network hub. Given the well-documented role of mTOR in inhibiting autophagy, our results hence support the hypothesis that the antiaging mechanism of TPM-based medicines might involve autophagy induction. Chemoinformatics study of the phytochemicals using docking and molecular dynamics simulation identified, among other compounds, the cyclo-trijuglone of Juglans regia L. as a potential ATP-competitive inhibitor of mTOR. Our results hence, provide a basis for the study of TPM-based prescriptions using modern tools in the quest for developing synergistic therapies for ARDs.

Dynamic modeling of signal transduction by mTOR complexes in cancer.

Signal integration has a crucial role in the cell fate decision and dysregulation of the cellular signaling pathways is a primary characteristic of cancer. As a signal integrator, mTOR shows a complex dynamical behavior which determines the cell fate at different cellular processes levels, including cell cycle progression, cell survival, cell death, metabolic reprogramming, and aging. The dynamics of the complex responses to rapamycin in cancer cells have been attributed to its differential time-dependent inhibitory effects on mTORC1 and mTORC2, the two main complexes of mTOR. Two explanations were previously provided for this phenomenon: 1-Rapamycin does not inhibit mTORC2 directly, whereas it prevents mTORC2 formation by sequestering free mTOR protein (Le Chatelier's principle). 2-Components like Phosphatidic Acid (PA) further stabilize mTORC2 compared with mTORC1. To understand the mechanism by which rapamycin differentially inhibits the mTOR complexes in the cancer cells, we present a mathematical model of rapamycin mode of action based on the first explanation, i.e., Le Chatelier's principle. Translating the interactions among components of mTORC1 and mTORC2 into a mathematical model revealed the dynamics of rapamycin action in different doses and time-intervals of rapamycin treatment. This model shows that rapamycin has stronger effects on mTORC1 compared with mTORC2, simply due to its direct interaction with free mTOR and mTORC1, but not mTORC2, without the need to consider other components that might further stabilize mTORC2. Based on our results, even when mTORC2 is less stable compared with mTORC1, it can be less inhibited by rapamycin.