Airbrushed nanofibers with bioactive core and antibacterial shell for wound healing application.

Acute and chronic wounds are vulnerable to infection and delayed healing and require critical care and advanced wound protection. To overcome the challenges, dual therapy of antibacterial and growth factors will be a novel wound care strategy. The present study explores airbrushed core-shell nanofiber for dual delivery of epidermal growth factor (EGF) and amoxicillin (AMOX) in a sustained manner. A blend of polycaprolactone (PCL)-polyethylene oxide (PEO) was used to prepare the shell compartment for amoxicillin loading and poly-DL-lactide (PDLLA) core for EGF loading by using a customized airbrush setup. Characterization result shows a uniform distribution of nanofibers ranging between 200 and 500 nm in diameter. Amoxicillin loading in the shell compartment offers an initial burst release followed by a sustained release for up to 14 days. Whereas EGF in the core part shows a continuous sustained release throughout the release study.In-vitrostudy indicates the biocompatibility of EGF-AMOX loaded core-shell nanofibers with human dermal fibroblast cell (HDF) cells and a higher cellular proliferation compared to control samples. Gene expression data show an increase in fold change of collagen I and tropoelastin expression, indicating the regenerative properties of EGF-AMOX encapsulated nanofiber. The combination of bioactive core (EGF) and antibiotic shell (amoxicillin) in an airbrushed nanofibrous scaffold is a novel approach, which is the first time explored to deliver sustainable therapy to treat skin wounds. Our results demonstrate that PCL-PEO-Amoxicillin/PDLLA-EGF-loaded core-shell nanofibers are promising dual therapy scaffolds to deliver effective skin wound care, with the possibility of direct deposition on the wound.

Understanding the Role of Toll-Like Receptors 9 in Breast Cancer.

Breast cancer is a significant global issue, ranking as the second most common cancer among women worldwide and a leading cause of cancer-related deaths. Although the exact causes of this increase remain unclear, factors such as genetics, epigenetics, obesity, sedentary lifestyle, tobacco use, and vitamin D deficiency have been implicated. The Toll-like receptor 9 (TLR9) is recognized for its role in inflammation and innate immunity; however, its specific involvement in breast cancer pathogenesis requires further investigation. This study aims to systematically review the existing literature on TLR9 expression in normal and cancerous breast tissue, providing current knowledge and identifying gaps. Relevant articles in English were from PubMed, Scopus, and Google Scholar, with the inclusion criteria focusing on studies evaluating TLR9 mRNA and protein expression. The review found that TLR9 mRNA and protein exhibit variable expressions in both normal and cancerous breast tissue, highlighting the need for further research to clarify TLR9's role in breast cancer.

Modulation of blood T cell polyfunctionality and HVEM/BTLA expression are critical determinants of clinical outcome in anti-PD1-treated metastatic melanoma patients.

The need for reliable biomarkers to predict clinical benefit from anti-PD1 treatment in metastatic melanoma (MM) patients remains unmet. Several parameters have been considered in the tumor environment or the blood, but none has yet achieved sufficient accuracy for routine clinical practice. Whole blood samples from MM patients receiving second-line anti-PD1 treatment (NCT02626065), collected longitudinally, were analyzed by flow cytometry to assess the immune cell subsets absolute numbers, the expression of immune checkpoints or ligands on T cells and the functionality of innate immune cells and T cells. Clinical response was assessed according to Progression-Free Survival (PFS) status at one-year following initiation of anti-PD1 (responders: PFS > 1 year; non-responders: PFS ≤ 1 year). At baseline, several phenotypic and functional alterations in blood immune cells were observed in MM patients compared to healthy donors, but only the proportion of polyfunctional memory CD4+ T cells was associated with response to anti-PD1. Under treatment, a decreased frequency of HVEM on CD4+ and CD8+ T cells after 3 months of treatment identified responding patients, whereas its receptor BTLA was not modulated. Both reduced proportion of CD69-expressing CD4+ and CD8+ T cells and increased number of polyfunctional blood memory T cells after 3 months of treatment were associated with response to anti-PD1. Of upmost importance, the combination of changes of all these markers accurately discriminated between responding and non-responding patients. These results suggest that drugs targeting HVEM/BTLA pathway may be of interest to improve anti-PD1 efficacy.