Turbinaria ornata is a tropical brown algae (seaweed) known to have anti-inflammatory properties. In this study, we analyzed T. ornata extract (TOE) using liquid chromatography quadrupole time of flight mass spectrometry (LC-QTOF-MS) and nuclear magnetic resonance (NMR) and evaluated the in vivo efficacy of TOE against dextran sulfate sodium-induced chronic colitis in C57BL/6 mice. The bioactive fraction of TOE was administered orally daily for 6 weeks to mice under different treatments normal, colitis, and colitis + conventional drug (5-aminosalicylic acid, 5-ASA). Regarding clinical manifestation, the disease activity index and colon length of the colitis + TOE group were significantly reduced compared to those of the colitis group. The results of myeloperoxidase activity and histopathological examination showed similar results. Western blot analysis of colon tissues revealed that cyclooxygenase-2, tumor necrosis factor alpha (TNF-α), and phosphorylated signal transducer and activator of transcription-3 (p-STAT3) were significantly decreased in the colitis + 5-ASA group, whereas forkhead box P3 (FOXP3) was increased. qPCR results showed changes in T cell subsets; the administration of TOE upregulated regulatory T cell (Treg) expression, although T helper 17 cell (Th17) expression did not change significantly. Interestingly, the colitis + TOE group showed high levels of both Th1 and Th2 transcription factors, but the secreted cytokine interferon (IFN)-γ and interleukin (IL)-4 remained unchanged and somewhat reduced. Additionally, TNF-α gene expression was significantly reduced in the colitis + TOE group. IL-6 mRNA levels were also decreased, although not significantly. Four compounds were structurally elucidated using 1D- and 2D-NMR spectroscopy, and five compounds were fully identified or tentatively characterized using LC-QTOF-MS. In conclusion, TOE could alleviate chronic colitis via upregulation of Foxp3⁺ Treg cells and production of the anti-inflammatory cytokine IL-10, which directly inhibits macrophages and pro-inflammatory cytokine synthesis, leading to reduced colitis.

Membrane-free stem cell components (MFSCC) from basal adipose tissue-derived stem cells (ADSCs) are unknown for the treatment strategies in osteoarthritis (OA). OA has been considered to be associated with inflammatory damage and cartilage degradation. In this study, we intended to investigate the molecular mechanism of the anti-inflammation and cartilage protection effect of MFSCC in vitro (rat primary chondrocytes) and in vivo (rat OA model). The MFSCC treatment significantly inhibited interleukin-1α (IL-1α) stimulated inflammation and cartilage degradation. The MFSCC considerably reduced the levels of inflammatory factors such as iNOS, COX-2, NO, and PGE₂ and was suppressed NF-κB and MAPKs signaling pathways in IL-1α-stimulated rat chondrocytes. Additionally, biomarkers of OA such as MMP-9, COMP, and CTX-II decreased in the monosodium iodoacetate (MIA)-induced rat OA model by MFSCC treatment. In conclusion, the MFSCC was established to suppress IL-1α induced inflammation and cartilage degradation in vitro and in vivo. These findings provide new insight for understanding OA therapy using membrane-free stem cell approaches.

Crohn’s disease (CD) and ulcerative colitis (UC), collectively referred to as inflammatory bowel disease (IBD), are autoimmune diseases characterized by chronic inflammation within the gastrointestinal tract. Debromohymenialdisine is an active pyrrole alkaloid that is well known to serve as a stable and effective inhibitor of Chk2. In the present study, we attempted to investigate the anti-inflammatory properties of (10Z)-debromohymenialdisine (1) isolated from marine sponge Stylissa species using an intestinal in vitro model with a transwell co-culture system. The treatment with 1 attenuated the production and gene expression of lipopolysaccharide (LPS)-induced Interleukin (IL)-6, IL-1β, prostaglandin E2 (PGE2), and tumor necrosis factor-α in co-cultured THP-1 macrophages at a concentration range of 1–5 μM. The protein expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 were down-regulated in response to the inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) translocation into the nucleus in cells. In addition, we observed that 1 markedly promoted the nuclear translocation of nuclear factor erythroid 2 related factor 2 (Nrf2) and subsequent increase of heme oxygenase-1 (HO-1) expression. These findings suggest the potential use of 1 as a pharmaceutical lead in the treatment of inflammation-related diseases including IBD.

The inflammatory bowel diseases (IBD) cause chronic inflammation of the gastrointestinal tract and include ulcerative colitis (UC) and Crohn’s disease (CD). The prevalence of IBD has been increasing worldwide, and has sometimes led to irreversible impairment of gastrointestinal structure and function. In the present study, we successfully isolated a new phylloketal derivative, deacetylphylloketal (1) along with four known compounds from the sponge genus Phyllospongia. The anti-inflammatory properties of deacetylphylloketal (1) and phyllohemiketal A (2) were evaluated using an in vitro co-culture system that resembles the intestinal epithelial environment. A co-culture system was established that consisted of human epithelial Caco-2 cells and phorbol 12-myristate 13-acetate (PMA)-differentiated THP-1 macrophage cells. The treatment of co-cultured THP-1 cells with compounds 1 or 2 significantly suppressed the production and/or gene expression of lipopolysaccharide (LPS)-induced nitric oxide (NO), prostaglandin E2 (PGE2), Interleukin-6 (IL-6), IL-1β and Tumor Necrosis Factor alpha (TNF-α). The expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2 were down-regulated in response to inhibition of NF-kB translocation into the nucleus in cells. In addition, we observed that 1 and 2 markedly promoted the nuclear translocation of Nrf2 and subsequent increase in the expression of heme oxygernase (HO)-1. These findings suggest the potential use of sponge genus Phyllospongia and its metabolites as a pharmaceutical aid in the treatment of inflammation-related diseases including IBD.

Bisphenol A (BPA) is a typical environmental endocrine disruptor that exhibits estrogen-mimicking, hormone-like properties and can cause the collapse of bone homeostasis by an imbalance between osteoblasts and osteoclasts. Various BPA substitutes, structurally similar to BPA, have been used to manufacture ‘BPA-free’ products; however, the regulatory role of BPA alternatives in osteoclast differentiation still remains unelucidated. This study aimed to investigate the effects of these chemicals on osteoclast differentiation using the mouse osteoclast precursor cell line RAW 264.7. Results confirmed that both BPA and its alternatives, bisphenol F and tetramethyl bisphenol F (TMBPF), were nontoxic to RAW 264.7 cells. In particular, tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cell staining and activity calculation assays revealed that TMBPF enhanced osteoclast differentiation upon stimulation of the receptor activator of nuclear factor-kappa B ligand (RANKL). Additionally, TMBPF activated the mRNA expression of osteoclast-related target genes, such as the nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), tartrate-resistant acid phosphatase (TRAP), and cathepsin K (CtsK). Western blotting analysis indicated activation of the mitogen-activated protein kinase signaling pathway, including phosphorylation of c-Jun N-terminal kinase and p38. Together, the results suggest that TMBPF enhances osteoclast differentiation, and it is critical for bone homeostasis and skeletal health.

Breast cancer is a highly heterogeneous disease; hence, it is crucial to understand its biology and identify new targets for the development of effective treatments. Galectin-1 is known to play an oncogenic role in breast cancer progression. It is known that oncogenic factors can influence cancer progression through interactions with miRNAs. The purpose of this study is to identify the clinical significance and biological role of galectin-1 and miR-22-3p in cancer progression according to the molecular subtype of breast cancer. We analyzed the expression of galectin-1 and miR-22-3p using cancer tissues and the correlation with clinical pathological characteristics. In addition, we investigated the regulation of the cell cycle and EMT processes of cancer progression through the galectin-1/miR-22-3p axis using cell lines of different breast cancer subtypes. miR-22-3p negatively regulates galectin-1 expression and the two molecules have opposite patterns of oncogenic and tumor-suppressive functions, respectively; furthermore, these two molecules are associated with metastasis-free survival. Cell experiments showed that miR-22-3p overexpression and galectin-1 knockdown inhibited the proliferation and invasion of breast cancer cells. Galectin-1 regulates different cancer progression pathways depending on the molecular subtype. In hormone receptor-positive breast cancer cells, galectin-1 knockdown mainly inhibited cell cycle-related substances and induced G0/G1 arrest, whereas in triple-negative breast cancer cells, it suppressed molecules related to the epithelial–mesenchymal transition pathway. In conclusion, the miR-22-3p/galectin-1 axis regulates different cancer metastasis mechanisms depending on the specific molecular subtype of breast cancer, and miR-22-3p/galectin-1 axis modulation may be a novel target for molecular subtype-specific personalized treatment.