OBJECTIVES: To investigate the effects of dihydroartemisinin (DHA) combined with doxorubicin (DOX) on proliferation and apoptosis of triple-negative breast cancer cells and explore the underlying molecular mechanism. METHODS: MDA-MB-231 cells were treated with 50, 100 or 150 μmol/L DHA, 0.5 μmol/L DOX, or with 50 μmol/L DHA combined with 0.5 μmol/L DOX. The changes in proliferation and survival of the treated cells were examined with MTT assay and colony-forming assay, and cell apoptosis was analyzed with flow cytometry. Western blotting was performed to detect the changes in protein expression levels of PCNA, cleaved PARP, Bcl-2, Bax, STAT3, p-STAT3, HIF-1α and survivin. RESULTS: The IC₅₀ of DHA was 131.37±29.87 μmol/L in MDA-MB-231 cells. The cells with the combined treatment with DHA and DOX showed significant suppression of cell proliferation. Treatment with DHA alone induced apoptosis of MDA-MB-231 cells in a dose-dependent manner, but the combined treatment produced a much stronger apoptosis-inducing effect than both DHA and DOX alone. DHA at 150 μmol/L significantly inhibited clone formation of MDA-MB-231 cells, markedly reduced cellular expression levels of PCNA, p-STAT3, HIF-1α and survivin proteins, and obviously increased the expression level of cleaved PARP protein and the Bax/Bcl-2 ratio, and the combined treatment further reduced the expression level of p-STAT3 protein and increased the Bax/Bcl-2 ratio. CONCLUSIONS DHA combined with DOX produces significantly enhanced effects for inhibiting cell proliferation and inducing apoptosis in MDA-MB-231 cells possibly as result of DHA-mediated negative regulation of the STAT3/HIF-1α pathway.
Humans ; STAT3 Transcription Factor/metabolism* ; Apoptosis/drug effects* ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Doxorubicin/pharmacology* ; Triple Negative Breast Neoplasms/metabolism* ; Cell Line, Tumor ; Artemisinins/pharmacology* ; Female ; Cell Proliferation/drug effects* ; Signal Transduction/drug effects* ; Survivin

OBJECTIVE: The present study investigated the cytoprotective effects of a Pogonatherum paniceum extract prepared with 80% ethanol (PPE) using synchrotron radiation-based Fourier transform infrared (SR-FTIR) microspectroscopy and determined its phytochemical profile. METHODS: The volatile and polyphenolic compounds in PPE were characterized using gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry, respectively. The antioxidant capacity of PPE was evaluated using chemical and cell-based assays. The SR-FTIR microspectroscopy was performed to evaluate the cytoprotective effect of PPE by identifying changes in macromolecule composition in tert-butyl hydroperoxide (tBuOOH)-induced oxidative damage in RAW264.7 cells. RESULTS: A total of 48 volatile compounds and 28 polyphenol components were found in PPE. PPE exhibited a high potential for antioxidant activity by scavenging the intracellular reactive oxygen species in tBuOOH-induced oxidative damage in RAW264.7 cells. PPE treatment also significantly protected RAW264.7 cells against tBuOOH-induced toxicity and restored cell viability. The SR-FTIR analysis revealed that tBuOOH increased the lipid and ester lipid content in RAW264.7 cells. The PPE exerted a cytoprotective effect by decreasing the levels of lipid and ester lipid compounds that had been elevated by tBuOOH in RAW264.7 cells. These findings indicate that PPE has cytoprotective potential due to its ability to inhibit endogenous reactive oxygen species. CONCLUSION This study extends the current knowledge on the phytochemistry of PPE and its antioxidant and cytoprotective effects. These findings support the use of SR-FTIR microspectroscopy to determine the cytoprotective effects of natural products. PPE extract may be a candidate compound for new therapeutics and nutraceuticals that target the prevention of oxidative stress-associated diseases. Please cite this article as: Dunkhunthod B, Thumanu K, Teethaisong Y, Sittisart P, Sittisart P. Cytoprotective activity of Pogonatherum paniceum (Lam.) Hack. ethanolic extract evaluated by synchrotron radiation-based Fourier transform infrared microspectroscopy. J Integr Med. 2025; 23(2): 182-194.
Animals ; Mice ; Spectroscopy, Fourier Transform Infrared/methods* ; Plant Extracts/chemistry* ; RAW 264.7 Cells ; Synchrotrons ; Oxidative Stress/drug effects* ; Antioxidants/pharmacology* ; Ethanol/chemistry* ; Poaceae/chemistry* ; Cell Survival/drug effects* ; Cytoprotection/drug effects* ; Reactive Oxygen Species/metabolism* ; tert-Butylhydroperoxide

Bio-mineralization has emerged as a promising strategy to enhance vaccine immunogenicity. This study optimized the calcium phosphate (CaP) mineralization process of foot-and-mouth disease virus-like particles (FMD VLPs) to achieve high mineralization efficiency and scalability. Key parameters, including concentrations of Ca²⁺, HPO₄^2-, NaCl, and VLPs, as well as stirring speed, were systematically optimized. Stability of the scaled-up reaction system and immunogenicity of the mineralized vaccine were evaluated. Optimal conditions [25.50 mmol/L Ca(NO₃)₂, 15 mmol/L Na₂HPO₄, 300 mmol/L NaCl, 0.75 mg/mL VLPs, and 1 500 r/min] yielded CaP-mineralized VLPs (VLPs-CaP) with high mineralization efficiency, uniform morphology, and a favorable particle size. Scaling up the reaction by 25 folds maintained consistent mineralization efficiency and particle characteristics. Immunization in mice demonstrated that VLPs-CaP induced higher titers of specific antibodies and neutralizing antibodies than unmineralized VLPs (P < 0.05). Higher IgG2a/IgG1 ratio and enhanced IFN-γ secretion (P < 0.05) further indicated robust cellular immune responses. We establish a stable and scalable protocol for VLPs-CaP, providing a theoretical and technical foundation for developing high-efficacy VLPs-CaP vaccines.
Vaccines, Virus-Like Particle/immunology* ; Immunogenicity, Vaccine ; Calcium Phosphates/chemistry* ; Foot-and-Mouth Disease Virus ; Biomineralization ; Particle Size ; Animals ; Mice ; Antibodies, Neutralizing/blood* ; Antibodies, Viral/blood* ; Immunity, Cellular

OBJECTIVE: To summarize the research progress of bioactive scaffolds in the repair and regeneration of osteoporotic bone defects. METHODS: Recent literature on bioactive scaffolds for the repair of osteoporotic bone defects was reviewed to summarize various types of bioactive scaffolds and their associated repair methods. RESULTS: The application of bioactive scaffolds provides a new idea for the repair and regeneration of osteoporotic bone defects. For example, calcium phosphate ceramics scaffolds, hydrogel scaffolds, three-dimensional (3D)-printed biological scaffolds, metal scaffolds, as well as polymer material scaffolds and bone organoids, have all demonstrated good bone repair-promoting effects. However, in the pathological bone microenvironment of osteoporosis, the function of single-material scaffolds to promote bone regeneration is insufficient. Therefore, the design of bioactive scaffolds must consider multiple factors, including material biocompatibility, mechanical properties, bioactivity, bone conductivity, and osteogenic induction. Furthermore, physical and chemical surface modifications, along with advanced biotechnological approaches, can help to improve the osteogenic microenvironment and promote the differentiation of bone cells. CONCLUSION With advancements in technology, the synergistic application of 3D bioprinting, bone organoids technologies, and advanced biotechnologies holds promise for providing more efficient bioactive scaffolds for the repair and regeneration of osteoporotic bone defects.
Humans ; Tissue Scaffolds/chemistry* ; Bone Regeneration ; Osteoporosis/therapy* ; Tissue Engineering/methods* ; Biocompatible Materials/chemistry* ; Printing, Three-Dimensional ; Calcium Phosphates/chemistry* ; Osteogenesis ; Ceramics ; Cell Differentiation ; Hydrogels ; Bioprinting ; Bone and Bones

OBJECTIVE: To review the research progress of strontium (Sr) modified β-tricalcium phosphate composite biomaterials (SrTCP) promoting osteogenesis through immune regulation, and provides reference and theoretical support for the further development and research of SrTCP bone repair materials in bone tissue engineering in the future. METHODS: The literature about SrTCP promoting osteogenesis through immune regulation at home and abroad in recent years was extensively reviewed, and the preparation methods, immune mechanism and application of promoting osteogenesis were summarized and analyzed. RESULTS: The preparation methods of SrTCP include solid-state reaction sintering method, solution combustion quenching method, direct doping method, ion substitution method, etc. SrTCP has immune regulatory effects, which can play an immune regulatory role in inducing macrophage polarization, inducing angiogenesis and anti oxidative stress to promote osteogenesis. CONCLUSION At present, studies have shown that SrTCP can promote bone defect repair through immune regulation. Subsequent studies can start from the control of the optimal repair concentration and release rate of Sr, and further clarify the specific mechanism of SrTCP in promoting angiogenesis and anti oxidative stress, which is helpful to develop new materials for bone defect repair.
Calcium Phosphates/pharmacology* ; Strontium/pharmacology* ; Biocompatible Materials/pharmacology* ; Humans ; Osteogenesis/drug effects* ; Tissue Engineering/methods* ; Bone Substitutes/pharmacology* ; Bone Regeneration/drug effects* ; Animals ; Tissue Scaffolds/chemistry* ; Neovascularization, Physiologic/drug effects* ; Macrophages/immunology*

OBJECTIVE: To investigate the antioxidant and osteogenic induction capabilities of calcium phosphate nanoflowers (hereinafter referred to as nanoflowers) in vitro at different concentrations. METHODS: Nanoflowers were prepared using gelatin, tripolyphosphate, and calcium chloride. Their morphology, microstructure, elemental composition and distribution, diameter, and molecular constitution were characterized using scanning electron microscopy, transmission electron microscopy, Fourier transform infrared spectroscopy, and energy-dispersive spectroscopy. Femurs and tibias were harvested from twelve 4-week-old Sprague Dawley rats, and bone marrow mesenchymal stem cells (BMSCs) were isolated and cultured using the whole bone marrow adherent method, followed by passaging. The third passage cells were identified as stem cells by flow cytometry and then co-cultured with nanoflowers at concentrations of 0, 0.4, 0.8, 1.2, 1.6, 2.0, 2.4, 2.8, 3.2, and 3.6 mg/mL. Cell counting kit 8 (CCK-8) assay was performed to screen for the optimal concentration that demonstrated the best cell viability, which was subsequently used as the experimental concentration for further studies. After co-culturing BMSCs with the screened concentration of nanoflowers, the biocompatibility of the nanoflowers was verified through live/dead cell staining, scratch assay, and cytoskeleton staining. The antioxidant capacity was assessed by using reactive oxygen species (ROS) fluorescence staining. The in vitro osteoinductive ability was evaluated via alkaline phosphatase (ALP) staining, alizarin red staining, and immunofluorescence staining of osteocalcin (OCN) and Runt-related transcription factor 2 (RUNX2). All the above indicators were compared with the control group of normally cultured BMSCs without the addition of nanoflowers. RESULTS: Scanning electron microscopy revealed that the prepared nanoflowers exhibited a flower-like structure; transmission electron microscopy scans discovered that the nanoflowers possessed a multi-layered structure, and high-magnification images displayed continuous atomic arrangements, with the nanoflower diameter measuring (2.00±0.25) μm; energy-dispersive spectroscopy indicated that the nanoflowers contained elements such as C, N, O, P, and Ca, which were uniformly distributed across the flower region; Fourier transform infrared spectroscopy analyzed the absorption peaks of each component, demonstrating the successful preparation of the nanoflowers. Through CCK-8 screening, the concentrations of 0.8, 1.2, and 1.6 mg/mL were selected for subsequent experiments. The live/dead cell staining showed that nanoflowers at different concentrations exhibited good cell compatibility, with the 1.2 mg/mL concentration being the best (P<0.05). The scratch assay results indicated that the cell migration ability in the 1.2 mg/mL group was superior to the other groups (P<0.05). The cytoskeleton staining revealed that the cell morphology was well-extended in all concentration groups, with no significant difference compared to the control group. The ROS fluorescence staining demonstrated that the ROS fluorescence in all concentration groups decreased compared to the control group after lipopolysaccharide induction (P<0.05), with the 1.2 mg/mL group showing the weakest fluorescence. The ALP staining showed blue-purple nodular deposits around the cells in all groups, with the 1.2 mg/mL group being significantly more prominent. The alizarin red staining displayed orange-red mineralized nodules around the cells in all groups, with the 1.2 mg/mL group having more and denser nodules. The immunofluorescence staining revealed that the expressions of RUNX2 and OCN proteins in all concentration groups increased compared to the control group, with the 1.2 mg/mL group showing the strongest protein expression (P<0.05). CONCLUSION The study successfully prepares nanoflowers, among which the 1.2 mg/mL nanoflowers exhibits excellent cell compatibility, antioxidant properties, and osteogenic induction capability, demonstrating their potential as an artificial bone substitute material.
Animals ; Osteogenesis/drug effects* ; Mesenchymal Stem Cells/drug effects* ; Calcium Phosphates/pharmacology* ; Rats, Sprague-Dawley ; Rats ; Antioxidants/chemistry* ; Cells, Cultured ; Cell Differentiation/drug effects* ; Nanostructures/chemistry* ; Tissue Engineering/methods* ; Bone Marrow Cells/cytology* ; Coculture Techniques ; Tissue Scaffolds/chemistry* ; Male ; Biocompatible Materials/chemistry* ; Cell Survival ; Core Binding Factor Alpha 1 Subunit/metabolism* ; Cell Proliferation

Ferroptosis, an iron-dependent form of regulated cell death, is mechanistically characterized by disrupted iron homeostasis, lipid peroxidation, and compromised antioxidant defense systems. Recent studies have demonstrated that artemisinin and its derivatives, such as dihydroartemisinin and artesunate, exhibit therapeutic potential against lymphatic system malignancies through ferroptosis induction. These compounds exert their antitumor effects by modulating critical regulatory proteins including SLC7A11, GPX4, and STAT3, as well as activating pivotal signaling pathways such as ATF4-CHOP and SREBP2-IPP-GPX4 axes. Notably, synergistic therapeutic effects have been observed when artemisinin derivatives are combined with conventional chemotherapeutic agents or targeted therapies, demonstrating enhanced tumor-suppressive activity and circumvention of drug resistance mechanisms. This review systematically summarizes recent advancements in understanding the ferroptosis-mediated antitumor mechanisms of artemisinin compounds in lymphoid malignancies, with particular emphasis on their molecular targets and clinical translational potential.
Humans ; Ferroptosis/drug effects* ; Artemisinins/therapeutic use* ; Signal Transduction

Per- and polyfluoroalkyl substances (PFAS) have recently been shown to affect human health at low levels in the blood, according to epidemiological evidence. Consequently, human exposure to these chemicals should be strictly controlled to prevent health risks. This review reports on the potential sources of PFAS using Japan as an example. Tap water has attracted attention as a source of exposure to PFAS. PFAS have also been detected in the air, in household dust, and in consumer products. Furthermore, in the general population, diet is the most common source of exposure, and there is particular concern about human exposure to PFAS accumulated in seafood. Continuous monitoring is important for appropriate management of exposure for both humans and the environment.
Seafood/toxicity* ; Fluorocarbons/toxicity* ; Japan ; Drinking Water/standards* ; Air Pollutants/toxicity* ; Humans ; Dust/analysis* ; Environmental Exposure/standards* ; Food Contamination/analysis* ; Environmental Pollutants/toxicity* ; Water Pollutants, Chemical/toxicity*

To address the limitations of traditional minimally invasive thermal ablation technology such as poor conformability, carbonization and electromagnetic radiation, this paper proposes a steam thermal ablation technology that uses saturated steam internal energy to replace the traditional electromagnetic radiation energy. Through the steam thermal ablation system and the steam thermal ablation needle designed based on simulation, the ex vivo pig liver experiments were carried out. The results have the characteristics of the maximum ablation axis ratio (short diameter / long diameter) and non-carbonization with the same type of thermal ablation technology. Based on the near-infrared light, in this paper the curative effect of the reduced scattering coefficient of the steam thermal ablation results was evaluated. The reduced scattering coefficients of the coagulation area all exceeded 16, reaching the completely damaged state, which verified that the steam thermal ablation can effectively inactivate the tumor cells.
Steam ; Animals ; Swine ; Liver Neoplasms/surgery* ; Ablation Techniques/methods* ; Liver/surgery* ; Equipment Design

Bone repair remains an important target in tissue engineering, making the development of bioactive scaffolds for effective bone defect repair a critical objective. In this study, β-tricalcium phosphate (β-TCP) scaffolds incorporated with processed pyritum decoction (PPD) were fabricated using three-dimensional (3D) printing-assisted freeze-casting. The produced composite scaffolds were evaluated for their mechanical strength, physicochemical properties, biocompatibility, in vitro pro-angiogenic activity, and in vivo efficacy in repairing rabbit femoral defects. They not only demonstrated excellent physicochemical properties, enhanced mechanical strength, and good biosafety but also significantly promoted the proliferation, migration, and aggregation of pro-angiogenic human umbilical vein endothelial cells (HUVECs). In vivo studies revealed that all scaffold groups facilitated osteogenesis at the bone defect site, with the β-TCP scaffolds loaded with PPD markedly enhancing the expression of neurogenic locus Notch homolog protein 1 (Notch1), vascular endothelial growth factor (VEGF), bone morphogenetic protein-2 (BMP-2), and osteopontin (OPN). Overall, the scaffolds developed in this study exhibited strong angiogenic and osteogenic capabilities both in vitro and in vivo. The incorporation of PPD notably promoted the angiogenic-osteogenic coupling, thereby accelerating bone repair, which suggests that PPD is a promising material for bone repair and that the PPD/β-TCP scaffolds hold great potential as a bone graft alternative.
Calcium Phosphates/chemistry* ; Animals ; Bone Regeneration ; Rabbits ; Tissue Scaffolds ; Printing, Three-Dimensional ; Humans ; Human Umbilical Vein Endothelial Cells ; Neovascularization, Physiologic ; Osteogenesis ; Tissue Engineering/methods* ; Biomimetic Materials ; Cell Proliferation ; Angiogenesis