Construction of an efferocytosis-related long non-coding ribonucleic acid scoring system to predict clinical outcome and immunotherapy response in pancreatic adenocarcinoma.

Background: Efferocytosis suppresses antitumour immune responses by inducing the release and secretion of cytokines. Long non-coding ribonucleic acids (lncRNAs) have various functions in different forms of programmed cell death and in immune regulation. This study aims to explore the potential role of efferocytosis-related lncRNAs as biomarkers in pancreatic adenocarcinoma (PAAD). Methods: Transcriptome profiles, simple nucleotide variations and clinical data of patients with PAAD were extracted from The Cancer Genome Atlas (TCGA) database. Co-expression algorithms identified efferocytosis-related lncRNAs. The efferocytosis-related lncRNA scoring system (ERLncSys) was established using Cox regression and the Least Absolute Shrinkage and Selection Operator algorithm. Additionally, Kaplan-Meier (K-M) curves, Cox regression, receiver operating characteristic (ROC) curves and clinical parameter stratification analyses were used to evaluate ERlncSys. Moreover, ERlncSys was explored through Gene Set Variation Analysis, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. Furthermore, the TIMER platform, ESTIMATE algorithm, single sample Gene Set Enrichment Analysis and immune checkpoint analysis were utilised to explore the predictive power of ERlncSys for the tumour immune microenvironment (TIME). Finally, a consensus clustering algorithm identified distinct molecular profiles among patients with PAAD, aiding in the identification of potential beneficiaries for immunotherapy. Results: K-M, Cox regression and ROC analyses confirmed the robust prognostic efficacy of ERlncSys. Clinical stratification analysis indicated the broad applicability of ERlncSys in PAAD. Additionally, mmunological analyses indicated that ERlncSys can determine immune cell infiltration status in the TIME. Furthermore, consensus clustering analysis based on ERlncSys divided the TCGA-PAAD cohort into two clusters. Cluster 1 exhibited characteristics consistent with an immune 'hot tumour' compared to cluster 2, suggesting cluster 1 is a more suitable population for immune checkpoint inhibitor therapy. Conclusion: The established ErlncSys aids in predicting the prognosis and understanding the TIME landscape of patients with PAAD. In turn, it facilitates the identification of optimal candidates for immunotherapy. This study introduces novel insights into the potential value of efferocytosis-related lncRNAs as biomarkers in PAAD.

Elaeagnus L gum polysaccharides alleviate the impairment of barrier function in the dry skin model mice.

BACKGROUND: Dry skin is a common skin condition caused by reduction of water-holding capacity, which is regulated by skin barrier function. Dry skin can also be a symptom that indicates a more serious diagnosis. There are a number of moisturizers on the market, which play an important role in dermatologic and cosmetic therapies. However, the demand for these products with good and therapeutic efficiency is still growing. AIMS: It remains necessary to investigate the effects of Elaeagnus L gum polysaccharides (EAP), which are prepared from gum of Elaeagnus angustifolia L. on the epidermal permeability barrier function and their possible underlying mechanisms. PATIENTS/METHODS: EAP were purified, analyzed, and tested on human keratinocyte cell line (HaCaT) and then on the skin in vivo to evaluate their antiinflammatory activities and their impacts on impaired skin barrier function. RESULTS: Histological analyses revealed that topical administration with EAP effectively attenuated dryness-like skin condition, including less percutaneous water loss rate, less infiltrate inflammation cells, and less epidermal thickening. Moreover, EAP inhibited the production of various inflammatory mediators and increased AQP-3, FLG, and LOR expression. CONCLUSION: Our results indicated that EAP enhances epidermal permeability barrier function, and they can be used as a promising adjuvant agent in skin care cosmetics and in treating some skin disorders characterized by cutaneous inflammation and abnormal barrier function.

Fucoidan from Undaria pinnatifida Ameliorates Epidermal Barrier Disruption via Keratinocyte Differentiation and CaSR Level Regulation.

The epidermal barrier acts as a line of defense against external agents as well as helps to maintain body homeostasis. The calcium concentration gradient across the epidermal barrier is closely related to the proliferation and differentiation of keratinocytes (KCs), and the regulation of these two processes is the key to the repair of epidermal barrier disruption. In the present study, we found that fucoidan from Undaria pinnatifida (UPF) could promote the repair of epidermal barrier disruption in mice. The mechanistic study demonstrated that UPF could promote HaCaT cell differentiation under low calcium condition by up-regulating the expression of calcium-sensing receptor (CaSR), which could then lead to the activation of the Catenin/PLCγ1 pathway. Further, UPF could increase the expression of CaSR through activate the ERK and p38 pathway. These findings reveal the molecular mechanism of UPF in the repair of the epidermal barrier and provide a basis for the development of UPF into an agent for the repair of epidermal barrier repair.

Alpha- and gamma-mangostins exhibit anti-acne activities via multiple mechanisms.

Objective: Acne is a chronic skin disease that involves four key pathogenic factors: excess sebum production, ductal epidermal hyperproliferation, Propionibacterium acnes (P. acnes) colonization, and skin inflammation. Mangostins are well-known for their anti-bacterial and anti-inflammatory effects, suggesting that mangostins may have therapeutic potential for acne. The present study aimed to explore the anti-acne effects of mangostins from the perspective of multiple pathogenic mechanisms of acne. Methods: The effects of α- and γ-mangostins on the growth of P. acnes and lipase activity were analyzed. Their effects on P. acnes-induced keratinocyte proliferation were examined by CCK-8. The expression of inflammatory genes and activation of NF-κB and MAPK signaling pathways were detected by quantitative real-time PCR and western blotting, respectively. Results: Alpha- and γ-mangostins not only inhibited the growth of P. acnes, but also reduced the proliferation of keratinocytes induced by heat-killed P. acnes. Furthermore, α- and γ-mangostins were able to suppress P. acnes-induced expression of pro-inflammatory cytokines, including TNF-α, IL-1ß, and IL-6 in keratinocytes by inhibiting the activation of NF-κB and MAPK signaling pathways. Discussion and conclusions: Mangostins appeared to possess multiple anti-acne activities, including the inhibition of P. acnes growth, regulation of keratinocytes proliferation, and attenuation of skin inflammatory reaction. Hence, mangostins might be developed into a potential therapeutic agent for the treatment of acne.