Park HM, et al. Immune Netw. 2024 Jun;24(3):e27. https://doi.org/10.4110/in.2024.24.e27

This paper explores the enhancement of pharmacological outcomes through the combined use of melatonin and polydeoxyribonucleotide (PDRN), hypothesizing that their simultaneous application might surpass the effectiveness of individual use. Melatonin is a hormone that modulates sleep, oxidative stress and inflammation, and exerts analgesic and anti-inflammatory effects. Conversely, PDRN is well-known for its significant contributions to tissue regeneration and its role in promoting angiogenesis. This article details the pharmacological effects and mechanisms of each compound, suggesting that their integration could amplify their individual benefits, particularly in the realms of wound healing and various medical applications. This paper seeks to provide a comprehensive analysis of the interactions between melatonin and PDRN by reviewing existing studies, thereby paving the way for novel therapeutic strategies. It emphasizes the need for further clinical trials and research to optimize the use of this combination for the improved treatment of diverse cellular or tissue conditions. In conclusion, further research is needed to optimize combination therapies involving melatonin and PDRN, with the goal of confirming their enhanced benefits when used together. In conclusion, further research is necessary to optimize combination therapies involving melatonin and PDRN to confirm their enhanced benefits when used in conjunction. This review emphasizes the importance of exploring their potential synergistic effects and developing effective therapeutic strategies across various medical disciplines.

Background/Objectives: Honokiol (HK), a bioactive phenolic compound, exhibits significant anti-cancer properties. This study aimed to investigate the anti-cancer effects of HK in colorectal cancer (CRC) cells by focusing on its direct interaction with heat shock protein 27 (Hsp27) as a molecular target, and to elucidate the underlying mechanisms involved. Methods: HK was isolated via silica/ODS chromatography. Anchorage-independent growth of CRC cells was quantified using a soft agar assay with increasing HK concentrations. Apoptosis and cell cycle were analyzed by flow cytometry, and cell viability by MTS assay. Hsp27 binding to HK was validated by pull-down assay with HK-conjugated Sepharose 4B beads. Hsp27 knockdown was performed using lentiviral shRNA in CRC cells. Molecular docking of HK-Hsp27 interaction employed Schrödinger Suite 2016. Protein expressions, including chaperone and apoptotic proteins, were evaluated by Western blotting. Results: HK dose-dependently suppressed anchorage-independent growth of CRC cells and induced G₀/G₁ arrest. It triggered apoptosis through cytochrome c release, PARP cleavage, and Bcl-2 downregulation. HK directly bound to the α-crystallin domain of Hsp27 at Asn102 and His103 residues, confirmed by computational molecular docking and site-directed mutagenesis. Hsp27 knockdown in CRC cells dramatically reduced anchorage-independent growth. HK markedly decreased Hsp27 protein levels while having less effect on other heat shock proteins in CRC cells. Conclusions: HK exerts anti-cancer effects in CRC cells, associated with Hsp27 inhibition, resulting in suppressed cell growth and increased apoptosis. This interaction between HK and Hsp27 may support a mechanistic foundation supporting the potential utility of HK as a natural therapeutic agent for CRC.

Exposure to particulate matter (PM) in the air harms human health. Most studies on particulate matter’s (PM) effects have primarily focused on respiratory and cardiovascular diseases. Recently, IL-32θ, one of the IL-32 isoforms, has been demonstrated to modulate cancer development and inflammatory responses. This study revealed that one-point mutated IL-32θ (A94V) plays an important role in attenuating skin inflammation. IL-32θ (A94V) inhibited PM-induced COX-2, a pro-inflammatory cytokine GM-CSF and CYP1A1 in PM-exposed human keratinocytes HaCaT cells. IL-32θ (A94V) modulating effects were mediated via down-regulating ERK/p38/NF-κB/ AP-1 and AhR/ARNT signaling pathways. Our study indicates that PM triggers skin inflammation by upregulating COX-2, GM-CSF and CYP1A1 expression. IL-32θ (A94V) suppresses the expressions of COX-2, GM-CSF, and CYP1A1 by blocking the nuclear translocation of NF-κB and AP-1, as well as inhibiting the activation of the AhR/ARNT signaling pathway. Our findings offer valuable insights into developing therapeutic strategies and potential drugs to mitigate PM-induced skin inflammation by inhibiting the ERK/p38/NF-κB/AP-1 and AhR/ARNT signaling pathways.