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  • Open Access

    ARTICLE

    Phenotypic Response Surfaces–Guided Optimization (PRS-OPT) of Propolis-Metformin-Regorafenib Combination Therapy for MASLD-Associated Hepatocellular Carcinoma

    Yi-Sian Huang1,2, Chung-Yung Ma1,2, Hsiao-Yuh Roan3, Cheng-Hsiung Chiang4, Hsiao-Hui Tsou4, Chen-Hui Chen3, Yi-Fan Lin2, Horng-Dar Wang2, Chiou-Hwa Yuh1,5,6,7,*

    Oncology Research, Vol.34, No.6, 2026, DOI:10.32604/or.2026.074145 - 21 May 2026

    Abstract Objectives: Hepatocellular carcinoma (HCC) arising in metabolic dysfunction–associated steatotic liver disease (MASLD) develops under lipid-rich stress and inflammatory remodeling, which can alter therapeutic windows. We aimed to determine whether phenotypic response surface–guided optimization (PRS-OPT) can nominate hepatocyte-sparing propolis–metformin–regorafenib (PMR) dose windows that retain antitumor activity under MASLD-like fatty-acid (FA) stress and translate to an in vivo immune endpoint. Methods: PMR combinations were profiled in hepatoma cell lines (PLC/PRF/5 and HepG2) and non-malignant hepatocytes (THLE-2) under FA-free and FA-enriched conditions. Quadratic response surfaces were fitted and used for constrained dose nomination, followed by in vitro validation. Cell-death contributions were… More >

  • Open Access

    ARTICLE

    CNPY2 Regulates Macrophage Polarization and Inflammatory Immune Responses via the TLR4/NF-κB Signaling Pathway to Alleviate Osteomyelitis of the Jaw

    Rihui Wang1,2,#, Wanlu Li3,#, Canyang Jiang1,2, Jianping Huang1,2, Kangwei Zhou1,2, Yan Jiang4,5, Junyang Zhang1,2, Li Huang1,2,*

    BIOCELL, Vol.50, No.5, 2026, DOI:10.32604/biocell.2026.075875 - 13 May 2026

    Abstract Background: Osteomyelitis of the jaw (OMJ) is a severe infectious bone disease. While Canopy FGF signaling regulator 2 (CNPY2) is known to regulate inflammatory diseases, its role in OMJ remains unclear. The study aimed to investigate the role of CNPY2 in the mandibular joint and its molecular mechanisms. Methods: An in vitro OMJ model was generated by stimulating RAW264.7 macrophages with S. aureus. CNPY2 knockdown and overexpression models were established using siRNA and plasmids. Functional assays assessed cell proliferation, migration, and invasion. Macrophage polarization, cytokine secretion, and osteoclast differentiation were analyzed. The CNPY2-Toll-Like Receptor 4 (TLR4)/Nuclear factor-kappa B… More > Graphic Abstract

    CNPY2 Regulates Macrophage Polarization and Inflammatory Immune Responses via the TLR4/NF-κB Signaling Pathway to Alleviate Osteomyelitis of the Jaw

  • Open Access

    REVIEW

    The Immune-Centric Revolution in the Treatment of Musculoskeletal Disease: Autologous PBMNC and PRP-PBMNC Enriched—A Narrative Review

    Andrea De Matthaeis1, Laura Rehak2,*, Maria Bianchi3, Rossana Putzulu3, Nicola Piccirillo3,4, Giulio Maccauro1

    BIOCELL, Vol.50, No.5, 2026, DOI:10.32604/biocell.2026.073783 - 13 May 2026

    Abstract For over two decades, mesenchymal stem cells (MSCs) have been recognised as the cornerstone of orthobiologic treatments for musculoskeletal diseases. However, clinical evidence increasingly indicates that MSC engraftment in inflamed tissues is minimal and transient, with effects mainly driven by paracrine and immunomodulatory mechanisms induced by macrophage efferocytosis. This evolving paradigm emphasises the immune system as the central orchestrator of tissue repair. Peripheral blood mononuclear cells (PBMNCs) have emerged as potent effectors of regenerative inflammation, mediating apoptotic cell clearance through efferocytosis, facilitating the transition of macrophages from pro-inflammatory (M1) to reparative (M2) phenotypes, and releasing… More >

  • Open Access

    ARTICLE

    Mistletoe Lectin Overcomes Macrophage-Mediated Chemo-Resistance in 3D Co-Culture Models of Triple-Negative Breast Cancer

    Chang-Eui Hong1,2,3, Su-Yun Lyu1,2,3,*

    BIOCELL, Vol.50, No.2, 2026, DOI:10.32604/biocell.2025.075574 - 14 February 2026

    Abstract Objective: Tumor-associated macrophages (TAMs) contribute to chemoresistance in triple-negative breast cancer (TNBC), yet strategies to reprogram TAMs while enhancing chemotherapy efficacy remain limited. This study investigated whether Viscum album L. var. coloratum agglutinin (VCA) could sensitize TNBC cells to doxorubicin (DOX) and modulate TAM-mediated chemoresistance in three-dimensional (3D) co-culture models. Methods: MDA-MB-231 TNBC cells were co-cultured with RAW264.7 macrophages in collagen-embedded 3D spheroids. Spheroid viability was assessed using an ATP-based luminescent assay. Cytokine secretion and epithelial-mesenchymal transition (EMT) markers were measured using ELISA and Western blotting. Drug synergy was evaluated using combination index (CI) calculations. Results: VCA-DOX More >

  • Open Access

    REVIEW

    How Do LncRNAs Talk to miRNAs? Decoding Their Dialogue in Atherosclerosis

    Yating Wei1, Hongkang Yao1, Xian Shi2, Hong Chen3, Rongzong Ye4,*, Chaoqian Li1,*

    BIOCELL, Vol.50, No.2, 2026, DOI:10.32604/biocell.2025.072780 - 14 February 2026

    Abstract Atherosclerosis, characterized by the formation of fibrofatty lesions in the arterial wall, remains a leading cause of global morbidity and mortality. Emerging evidence highlights the critical regulatory roles of long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) in atherogenesis. LncRNAs can function as competing endogenous RNAs (ceRNAs) by sponging miRNAs, thereby modulating the expression of downstream target mRNAs. This review summarizes current knowledge on lncRNA-miRNA-mRNA regulatory networks and their functional roles in the three major cell types involved in atherosclerotic plaque development: endothelial cells (ECs), vascular smooth muscle cells (VSMCs), and macrophages. In ECs, these networks More >

  • Open Access

    ARTICLE

    RP3-340N1.2 Knockdown Suppresses Proliferation and Migration by Downregulating IL-6 in Non-Small Cell Lung Cancer

    Hang Zhang1,#, Meng-Yuan Chu1,#, Guohui Lv1, You-Jie Li1, Xuhang Liu2, Fei Jiao1,*, Yun-Fei Yan1,*

    BIOCELL, Vol.50, No.1, 2026, DOI:10.32604/biocell.2025.068322 - 23 January 2026

    Abstract Objectives: Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality, with limited understanding of lncRNA-driven mechanisms in tumor progression. This study aimed to identify differentially expressed lncRNAs in NSCLC tissues and elucidate the functional role of the significantly upregulated RP3-340N1.2 in promoting malignancy. Methods: RNA sequencing was used to screen dysregulated lncRNAs. RP3-340N1.2 was functionally characterized via gain/loss-of-function assays in NSCLC cells, assessing proliferation, migration, and macrophage polarization. Mechanisms of interleukin 6 (IL-6) regulation were explored using cytokine profiling, Actinomycin D assays, and RNA Immunoprecipitation (RIP) assays to study RP3-340N1.2 interactions with… More >

  • Open Access

    ARTICLE

    SDHA Deficiency in Hepatocellular Carcinoma Promotes Tumor Progression through Succinate-Induced M2 Macrophage Polarization

    Xinyang Li1,2,3,#, Luyuan Ma1,2,3,#, Chuan Shen1,2,3, Ruolan Gu1,2,3, Shilong Dong1,2,3, Mingjie Liu1,2,3, Ying Xiao1,2,3, Wenpeng Liu1,2,3, Yuexia Liu1,2,3, Caiyan Zhao1,2,3,*

    Oncology Research, Vol.34, No.2, 2026, DOI:10.32604/or.2025.073179 - 19 January 2026

    Abstract Background: Hepatocellular carcinoma (HCC) is an aggressive and lethal malignancy. Metabolic reprogramming dynamically remodels the tumor microenvironment (TME) and drives HCC progression. This study investigated the mechanism through which metabolic reprogramming remodels the TME in HCC. Methods: HCC patient transcriptome data were subjected to bioinformatics analysis to identify differentially expressed genes and immune infiltration status. Immunohistochemical analysis was performed to determine the correlation between succinate dehydrogenase complex subunit A (SDHA) expression and M2 macrophage infiltration. SDHA-knockdown or SDHA-overexpressing HCC cells were used for in vitro experiments, including co-culturing, flow cytometry, and enzyme-linked immunosorbent assay. Western blotting… More >

  • Open Access

    ARTICLE

    Prognostic Value of Circulating Tumor Cells and Cancer Associated Macrophage-Like Cells in Metastatic Non-Small Cell Lung Cancer Patients: A Retrospective Exploratory Analysis

    Marco Siringo1,2,#,*, Michela De Meo1,#, Alain Jonathan Gelibter3, Chiara Nicolazzo4,5,§, Paola Gazzaniga5,§

    Oncology Research, Vol.34, No.2, 2026, DOI:10.32604/or.2025.069832 - 19 January 2026

    Abstract Objectives: Although immune checkpoint inhibitors (ICIs) and targeted therapies have reshaped treatment non-small cell lung cancer (NSCLC) paradigms, prognosis remains poor for many patients due to delayed diagnosis and resistance mechanisms. Liquid biopsy offers a minimally invasive approach to monitoring tumor evolution. Among circulating biomarkers, circulating tumor cells (CTCs) and cancer-associated macrophage-like cells (CAM-Ls) may provide complementary prognostic insights. The study aimed to evaluate the prognostic role of CTC and CAM-Ls dynamic in metastatic NSCLC patients. Methods: We retrospectively analyzed 77 patients with metastatic NSCLC who underwent CTC and CAM-L evaluation via the CellSearch® system… More >

  • Open Access

    ARTICLE

    AGPAT3 Regulates Immune Microenvironment in Osteosarcoma via Lysophosphatidic Acid Metabolism

    Shenghui Su, Yu Zeng, Jiaxin Chen, Xieping Dong*

    Oncology Research, Vol.34, No.1, 2026, DOI:10.32604/or.2025.070558 - 30 December 2025

    Abstract Background: Recent studies have shown glycerolipid metabolism played an essential role in multiple tumors, however, its function in osteosarcoma is unclear. This study aimed to explore the role of glycerolipid metabolism in osteosarcoma. Methods: We conducted bioinformatics analysis using data from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database and single-cell RNA sequencing. Least Absolute Shrinkage and Selection Operator (LASSO) regression was used to identify the Glycerolipid metabolism-related genes associated with the clinical outcome of osteosarcoma. Tumor-associated macrophages (TAMs) and their interactions with immune cells were examined through single-cell analysis and co-culture experiments.… More >

  • Open Access

    COMMENTARY

    CD47-Targeted Therapy in Cancer Immunotherapy: At a Crossroads of Promise and Challenge

    Xuejun Guo1,2, Yilin Fu3, Natalia Baran4,5, Wenxue Ma6,*

    Oncology Research, Vol.33, No.11, pp. 3375-3385, 2025, DOI:10.32604/or.2025.071708 - 22 October 2025

    Abstract Cluster of differentiation 47 (CD47), an immune checkpoint commonly referred to as the “don’t eat me” signal, plays a pivotal role in tumor immune evasion by inhibiting phagocytosis through interaction with signal regulatory protein alpha (SIRPα) on macrophages and dendritic cells (DCs). Although early enthusiasm drove broad clinical development, recent discontinuations of major CD47-targeted programs have prompted re-evaluation of its therapeutic potential. The purpose of this commentary is to contextualize the setbacks observed with first-generation CD47 inhibitors and to highlight strategies aimed at overcoming their limitations. Clinical challenges, including anemia, thrombocytopenia, suboptimal pharmacokinetics, and limited… More >

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