Trung-Loc Ho

Prostate cancer (PCa) is the most general cancer in men and is often linked with distant metastasis in its later stages. The caffeic acid (CA) derivative, N-(4-methoxyphenyl)methylcaffeamide (MPMCA), demonstrates superior liver-protective effects compared to CA. Nevertheless, the functions of MPMCA on prostate cancer metastasis remain unclear. Here, we demonstrate that MPMCA blocks migration and invasion in prostate cancer cells without affecting cell viability. By suppressing the production of mesenchymal markers Vimentin, N-cadherin and β-catenin and upregulating the production of the epithelial marker Zonula Occludens-1 (ZO-1), MPMCA also controls Epithelial–Mesenchymal Transition (EMT). The Phosphoinositide 3-kinase (PI3K), Protein kinase B (AKT) and mechanistic target of rapamycin (mTOR) pathway has been documented to regulate MPMCA-inhibited cell motility. Transfection with Snail and Slug cDNA reverses MPMCA’s suppression of EMT, migration, and invasion in prostate cancer cells. Importantly, our in vivo data indicates that MPMCA reduces Snail and Slug expression and prostate cancer metastasis. Our evidence suggests that MPMCA is a novel therapeutic candidate for treating metastatic prostate cancer.

Introduction: Osteoclastogenesis, the differentiation of osteoclasts from monocyte/macrophage precursors, is essential for physiological bone remodeling but contributes to pathological bone loss in arthritis, osteoporosis, and bone metastasis when dysregulated. CXCL13 is a CXC chemokine well recognized for its role in immune regulation; however, its function in osteoclast biology remains undefined. This study aimed to investigate the effects of CXCL13 on RANKL-induced osteoclastogenesis. Methods: RAW264.7 cells were stimulated with RANKL to induce osteoclastogenesis. Osteoclast formation was evaluated by TRAP and F-actin ring staining, and quantitative real-time PCR (qPCR). GEO bioinformatic analysis revealed gene expression changes during RANKL-induced osteoclastogenesis. Mature osteoclast apoptosis was analyzed by cleaved caspase-3 immunofluorescence staining. MAPK and NF-κB signaling activation was examined by Western blotting and NF-κB luciferase reporter assays. Molecular docking and co-immunoprecipitation were performed to evaluate the interaction between CXCL13 and RANK. Results: CXCL13 inhibited RANKL-induced osteoclast formation, suppressed osteoclast marker expression, disrupted F-actin ring assembly, and promoted apoptosis in mature osteoclasts. Mechanistically, CXCL13 attenuated MAPK and NF-κB activation and blocked p65 nuclear translocation in a CXCR5-independent manner by competitively interfering with RANKL–RANK binding and downstream RANK–TRAF6 signaling. Discussion: These findings identify CXCL13 as a novel suppressor of osteoclastogenesis by interfering with RANKL–RANK signaling, unveiling an unrecognized regulatory role in osteoclast biology and suggesting potential therapeutic relevance for bone loss disorders.

Background: LUAD, the most common subtype of lung cancer, particularly in non-smokers, is significantly influenced by air pollution from fine particulate matter (PM). One suspected method by which PM contributes to cancer progression is through angiogenesis, which promotes tumor growth and metastasis. This study was conducted to explore the impact of long-term PM exposure on the progression of LUAD, focusing on angiogenesis promotion. Methods: We conducted an integrative bioinformatics analysis incorporating epidemiological and transcriptomic datasets from public repositories (TCGA and GEO) to evaluate differential VEGFA expression in LUAD tissues and its relationship to regional PM exposure. In vitro and in vivo assays using PM-adapted NSCLC cell lines and murine xenograft models served as secondary confirmatory experiments supporting the computational results. Results: Epidemiological analysis revealed a strong positive correlation between long-term PM exposure and lung adenocarcinoma mortality across U.S. states (r = 0.7638, p < 0.0001), underscoring a population-level impact. Bioinformatics analysis identified a significant upregulation of VEGFA in NSCLC tumors from regions with high PM levels, with VEGFA overexpression also associated with poorer patient survival. Gene ontology and pathway enrichment analyses implicated angiogenesis-related processes. These findings were supported by experimental models, in which long-term PM exposure on human and murine LUAD cell lines (A549, H1299, and LLC) induced VEGFA and p-ERK overexpression. Furthermore, PM-exposed cells enhanced angiogenesis processes, as evidenced by increased endothelial cell tube formation and migration in vitro, and promoted tumor vascularization in a xenograft model. These pro-angiogenesis effects were abrogated following inhibition of the MAPK signaling pathway or blockade of VEGFA. Conclusions: Our findings reveal a compelling molecular link between PM exposure and NSCLC progression, centered on VEGFA-driven angiogenesis and urging the need to reduce ambient PM exposure to mitigate its oncogenic impact.

Bone metastasis is a significant complication in advanced-stage cancers, especially breast and lung malignancies, profoundly influencing prognosis and quality of life. Osteolytic bone metastasis contains multiple interactions between cancer cells and the bone microenvironment, driving osteoclast-mediated bone resorption and deterioration while releasing growth factors that promote tumor progression. Current treatments, including surgery, radiation, and chemotherapy, often result in severe side effects, highlighting the need for effective, targeted therapies. Ugonin P, a natural compound derived from Helminthostachys zeylanica, known for its anti-inflammatory and anticancer properties. However, the effects of Ugonin P on osteolytic bone metastasis remain unclear. Our findings demonstrate that Ugonin P inhibits both RANKL-induced and lung and breast cancer-induced osteoclast formation. Bioinformatics analysis revealed that Midkine (MDK), a heparin-binding growth factor known to promote migration, is highly elevated in breast and lung cancer patients and is related with osteoclast formation. We further showed that MDK is involved in cancer-promoted osteoclastogenesis and that Ugonin P suppresses this process by upregulating miR-223-3p expression. Importantly, Ugonin P effectively blocks lung and breast cancer-facilitated osteolytic bone metastasis in vivo. These findings highlight Ugonin P as a promising therapeutic strategy for treating osteolytic bone metastasis.

Arthritis is a chronic inflammatory disease that causes joint damage, with osteoarthritis (OA) and rheumatoid arthritis (RA) being the most common types. Both conditions are characterized by cartilage degradation due to an imbalance between repair and breakdown processes. Chondrocytes, the key cells in articular cartilage, maintain its structure by producing an extracellular matrix rich in aggrecan and type II collagen (COL2). MicroRNAs (miRNAs), small noncoding RNAs, regulate genes critical for cartilage balance and are involved in the progression and treatment of OA and RA. Recently, herbal medicines have gained attention for arthritis treatment. Ugonin P, a flavonoid from Helminthostachys zeylanica Hook, is known for its antioxidant and anticancer effects, but its role in cartilage homeostasis is unclear. This study explores ugonin P's chondrogenic effects and its molecular mechanisms involving miRNA regulation. Analysis of Gene Expression Omnibus (GEO) data and clinical samples revealed reduced aggrecan and COL2 levels in OA and RA, while miR-3074-5p levels were elevated, suppressing these proteins. Ugonin P, without affecting cell viability, enhanced aggrecan and COL2 production and promoted chondrocyte differentiation by downregulating miR-3074-5p and activating MAPK pathways. These findings suggest ugonin P as a promising therapeutic candidate for arthritis management.

Osteoporosis is a usual bone disease in aging populations, principally in postmenopausal women. Anti-resorptive and anabolic drugs have been applied to prevent and cure osteoporosis and are associated to a different of adverse effects. Du-Zhong is usually applied in Traditional Chinese Medicine to strengthen bone, regulate bone metabolism, and treat osteoporosis. Chlorogenic acid is a major polyphenol in Du-Zhong. In the current study, chlorogenic acid was found to enhance osteoblast proliferation and differentiation. Chlorogenic acid also inhibits the RANKL-induced osteoclastogenesis. Notably, ovariectomy significantly decreased bone volume and mechanical properties in the ovariectomized (OVX) rats. Administration of chlorogenic acid antagonized OVX-induced bone loss. Taken together, chlorogenic acid seems to be a hopeful molecule for the development of novel anti-osteoporosis treatment.

Rheumatoid arthritis (RA) is a well‐known autoimmune disorder related with joint pain, joint swelling, cartilage and bone degradation as well as deformity. Fibroblast growth factor 23 (FGF23) is an endocrine factor of the FGF family primarily produced by osteocytes and osteoblasts, involves an essential effect in pathogenesis of RA. IL‐1β is a vital proinflammatory factor in the development of RA. However, the role of FGF23 on IL‐1β synthesis in RA has not been fully explored. Our analysis of database revealed higher levels of FGF23 and IL‐1β in RA samples compared with healthy controls. High‐throughput screening demonstrated that IL‐1β is a potential candidate factor after FGF23 treatment in RA synovial fibroblasts (RASFs). FGF23 concentration dependently promotes IL‐1β synthesis in RASFs. FGF23 enhances IL‐1β expression by activating the PI3K, Akt, and NF‐κB pathways. Our findings support the notion that FGF23 is a promising target in the remedy of RA.