Kolon Life Science (South Korea)

Skin aging is characterized by fibroblast senescence, extracellular matrix (ECM) degradation, and impaired wound healing, driven by oxidative stress and telomere dysfunction. Here, we investigated the anti-aging effects of a standardized microwave-assisted propolis extract (MAPE) in both H2O2-induced and replicative senescence models of human dermal fibroblasts (HDFs). MAPE significantly reduced reactive oxygen species (ROS) accumulation and enhanced antioxidant gene expression (NQO1, GCLM), indicating activation of NRF2-dependent defense pathways. It suppressed senescence markers (CDKN2A, CDKN1A, IL6), decreased SA-β-gal activity, and attenuated inflammaging. Moreover, MAPE inhibited MMP1 expression, restored COL1A1, and improved fibroblast wound closure, thereby maintaining ECM homeostasis. Importantly, MAPE modulated Wnt/β-catenin signaling by upregulating WNT3A and LEF1 while suppressing DKK1, and increased TERT expression, suggesting involvement of telomerase-related regulatory pathways. These effects resembled those of CHIR99021, a canonical Wnt activator, while providing additional antioxidant protection. Together, our findings suggest that MAPE is a propolis-derived bioactive ingredient that counteracts fibroblast senescence through coordinated modulation of NRF2 and Wnt/β-catenin-TERT signaling pathways, supporting its potential as a cosmeceutical ingredient for mitigating skin aging.

ABSTRACT Suction‐based in vivo cutaneous DNA transfection is a newly developed, cost‐effective method that produces high transfection efficiency. This method has shown robust immunogenic responses following SARS‐CoV‐2 DNA vaccination in both pre‐clinical studies and clinical trials. The current work investigates suction‐based transfection and immune activation on a detailed, cellular level. The spatiotemporal patterns of antigen expression in rat skin following suction‐induced delivery of a pEGFP‐N1 plasmid and a SARS‐CoV‐2 DNA vaccine are evaluated via immunofluorescence staining, which demonstrates early and prolonged expression. The epidermis is identified as the primary location of transfection, and the transfected cells are primarily epidermal keratinocytes. Early immune response is assessed by detection of major histocompatibility complex class II‐positive (MHC‐II + ) cells following suction‐induced DNA vaccination.

The activation of hair follicle dermal papilla cells (HFDPCs), a critical target of hair loss relief, can be achieved through the upregulation of proliferation, the stimulation of hair inducibility, and the inhibition of cellular senescence. Veratric acid (VA) is a major benzoic acid found in fruits and vegetables. The biological activity of VA on HFDPCs remains to be elucidated. In this study, we investigated the capacity of VA for hair loss mitigation. An MTT assay, Ki67 staining, quantitative RT-PCR (qRT-PCR), and a Western blot analysis were performed to confirm the proliferative effect of VA. Hair inductivity was determined through a cell aggregation assay and ALP staining. Annexin V/PI staining was performed to confirm the anti-apoptotic effect of VA. The inhibitory effect of VA on cellular senescence was confirmed by a β-galactosidase (β-gal) assay and qRT-PCR using replicative senescence and oxidative stress-induced senescence models. As a result, VA dose-dependently upregulated the proliferation of HFDPCs, the expression of growth factors, and β-catenin protein levels. VA also dose-dependently increased ALP activity and cell aggregation and decreased apoptotic cells through the regulation of BCL2 and BAX expression. Moreover, VA reduced β-gal activity and the senescence-associated secretory phenotype (SASP) in a dose-dependent manner in senescent HFDPCs. These findings suggest that VA may serve as a potential therapeutic agent for alleviating hair loss by targeting multiple pathways involved in HFDPC activation.

Purpose: Unnecessary prostate biopsies for detecting prostate cancer (PCa) should be minimized. Therefore, this study developed a machine learning (ML) model to predict PCa in Korean men and evaluated its usability.Materials and Methods: We retrospectively analyzed clinical data from 928 patients who underwent prostate biopsies at Kangwon National University Hospital between May 2013 and May 2023. Of these, 377 (41.6%) were diagnosed with PCa, and 551 (59.4%) did not have cancer. For external validation, clinical data from 385 patients aged 48–89 years who underwent prostate biopsies from September 2005 to September 2023 at Wonju Severance Christian Hospital were also included. Twenty-two clinical features were used to develop an ML model to predict PCa. Features were selected based on their contributions to model performance, leading to the inclusion of 15 features. A meta-learner was constructed using logistic regression to predict the probability of PCa, and the classifier was trained and validated on randomly extracted training and test sets at an 8:2 ratio.Results: The prostate health index, prostate volume, age, nodule on digital rectal examination, and prostate-specific antigen were the top 5 features for predicting PCa. The area under the receiver operating characteristic curve (AUC) of the meta-learner logistic regression model was 0.89, and the accuracy, sensitivity, and specificity were 0.828, 0.711, and 0.909, respectively. Our model also showed excellent prediction performance for high-grade PCa, with a Gleason score of 7 or higher and an AUC of 0.903. Furthermore, we evaluated the performance of the model using external cohort clinical data and achieved an AUC of 0.863.Conclusions: Our ML model excelled in predicting PCa, specifically clinically significant PCa. Although extensive cross-validation in other clinical cohorts is needed, this ML model is a promising option for future diagnostics.

The genus Potyvirus (the family Potyviridae) is the largest group of plant-infecting viruses transmitted by aphids. Through high-throughput RNA sequencing analysis of asymptomatic samples of Aconitum carmichaelii, a significant medicinal herb in Asia, we identified the genome sequences of two RNA viruses, tentatively named Aconitum potyvirus 1 (AcoPV1) and Aconitum potyvirus 2 (AcoPV2). The genomes of AcoPV1 and AcoPV2 encode polyproteins composed of 3,069 and 3,054 amino acids, respectively. Sequence comparisons and phylogenetic analyses established that AcoPV1 and AcoPV2 represent unique, novel members within the genus Potyvirus. The estimated RNA polymerase slippage rates at the GAAAAAA motif, responsible for the production of P3N-PIPO or P3N-ALT trans-frame fusion proteins, were 0.79% in AcoPV1 and 1.38% in AcoPV2. The RNA reads of AcoPV1 and AcoPV2 were predominantly found in the leaf and flower tissues, indicating potential feeding preferences of vectors for these viruses. These findings demonstrate the effectiveness of high-throughput RNA sequencing in not only uncovering novel potyviruses, but also in elucidating their genomic dynamics within host plants.

In the present study, the effect(s) of the immunomodulatory drug GLS-1027 on various cell types involved in inflammation were investigated. GLS-1027 reduced LPS-stimulated secretion of pro-inflammatory cytokines by macrophage or monocytic cells and cell lines. This reduction was likely due in part to decreased activation of NF-κB family transcription factors and inhibition of p38 MAPK signaling in GLS-1027-treated cells. Independent from its effects on macrophages, GLS-1027 inhibited dendritic cell maturation and differentiation of naïve CD4+ T cells into Th17 cells, reducing the production of typical pro-inflammatory cytokines associated with both processes. In vivo administration of GLS-1027 prevented the development of type 1 diabetes in NOD mice which correlated with reduced serum levels of IL17A in GLS-1027 treated animals and reduced ex vivo production of IL17A from both spleen and lymph-node cells. Overall, our data show that GLS-1027 can reduce inflammation through multiple actions, including the reduction of pro-inflammatory cytokine production by innate immune cells, the inhibition of dendritic cells maturation, and the inhibition of Th17 cells polarization.