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Cocktail-like alginate-derived carbonized nanogels with diverse moieties attenuate tumor metastasis via potential multi-pathway modulation

2026-08-10T03:27:56Z

標題: Cocktail-like alginate-derived carbonized nanogels with diverse moieties attenuate tumor metastasis via potential multi-pathway modulation 作者: Wang, Chen-Yow; Mao, Ju-Yi; Unnikrishnan, Binesh; Chan, Kai-Min; Sarkar, Saumyadip; Lin, Lin; Hsu, Pang-Hung; Huang, Yu-Fen; Harroun, Scott G.; Huang, Chih-Ching; Chen, Shiow-Yi 摘要: Carbonized nanomaterials possess diverse functional moieties that complicate biomedical use but also confer multi-target therapeutic potential. Here, carbonized nanogels (CNGs) were synthesized from sodium alginate (Alg) via mild pyrolysis, yielding ultrasmall graphene-like domains embedded in a crosslinked nanogel matrix enriched with bioactive moieties. These features endowed Alg-CNGs with antioxidative, anti-inflammatory, and membrane-perturbing properties, enabling modulation of cellular signaling relevant to cancer progression. In vitro, Alg-CNGs suppressed epithelial-mesenchymal transition in 4T1 triple-negative breast cancer cells by increasing E-cadherin and decreasing N-cadherin and vimentin, thereby attenuating EMT-associated motility as evidenced by reduced migration/invasion and marked perturbation of actin organization and adhesion-related dynamics. Quantitative proteomics coupled with Ingenuity Pathway Analysis further indicated attenuation of metastasis-associated networks, including RhoA/Rac1/Cdc42-integrin signaling and PI3K/AKT, PTEN, and ERK/ MAPK pathways. In an orthotopic breast cancer model, Alg-CNGs accumulated selectively in tumors and reduced pulmonary metastasis by 90% without systemic toxicity. Structure-function analysis indicated that phenolic, lactone, and quinone moieties on the CNGs may contribute to regulating oxidative stress, actin remodeling, and receptor-mediated signaling. These findings demonstrate that Alg-CNGs exert cocktail-like" multifunctional actions

Adiponectin improves clozapine-induced lipid accumulation and inflammation without affecting insulin resistance

2026-08-10T03:12:10Z

標題: Adiponectin improves clozapine-induced lipid accumulation and inflammation without affecting insulin resistance 作者: Tsai, I-Lun; Lin, Shih-Chao; Lin, Lin; Tsai, Pei-Shan; Chen, Shiow-Yi 摘要: Clozapine, an atypical antipsychotic, is effective for treatment-resistant schizophrenia but frequently causes metabolic adverse effects, including hepatic lipid accumu-lation, inflammation and insulin resistance. Adiponectin, an adipocyte-derived cytokine with anti-inflammatory and insulin-sensitizing properties, may counteract these effects; however, its ability to mitigate clozapine-induced hepatic alterations remains unclear. This study examined whether adiponectin overexpression reduces clozapine-induced lipid accumulation, inflammatory signaling, and whether it restores insulin-related Akt signaling in human HepG2 liver cells. Cells were treated with 25 mu M clozapine for 24 or 48 h, and adiponectin was overexpressed by plasmid transfection. Lipid accumulation was quantified by BODIPY staining. AdipoR1 and AdipoR2 expression was analyzed by qPCR, and protein levels of FASN, phosphorylated NF-kappa B, and phosphorylated Akt were assessed by Western blotting. Clozapine increased lipid accumulation, upregulated FASN, and reduced AdipoR1 and AdipoR2 expression. Adiponectin overexpression significantly decreased lipid levels, which was associated with reduced NF-kappa B phosphorylation, suggesting attenuation of inflammatory signaling. However, adiponectin did not restore insulin-stimulated Akt phosphorylation. In summary, adiponectin selectively reduced clozapine-induced lipid accumulation and inflammatory signaling in HepG2 cells, whereas impaired insulin-stimulated Akt phosphorylation remained unchanged under the present experimental conditions. These findings indicate a selective protective role of adiponectin and suggest its potential as a modulator of clozapine-induced metabolic side effects.

Carbonization of citrus-derived flavonoids exhibits enhanced anti-coronavirus infection in vitro and in vivo

2026-08-10T03:11:57Z

標題: Carbonization of citrus-derived flavonoids exhibits enhanced anti-coronavirus infection in vitro and in vivo 作者: Lin, Lin; Lai, Pei-Chun; Hsu, Chun-Ru; Huang, Dong-Ming; Kehn-Hall, Kylene; Huang, Chih-Ching; Chen, Shiow-Yi; Lin, Shih-Chao 摘要: Orange peel waste from juice processing has long been an environmental challenge. The abundant bioactive flavonoids, such as hesperidin and naringin, within the peel waste have attracted significant scientific interest. However, the low biocompatibility and the requirement for high effective concentrations to exert bioactivities hinder the capability and utility of these citrus-derived flavonoids. This study aimed to transform orange waste into a high-value product by enhancing the antiviral activity against coronavirus infection. The coronavirus pandemic, caused by SARS-CoV-2, has had a devastating impact on our quality of life and resulted in significant casualties. In this study, we modified and converted raw flavonoids into carbonized gel-like macromolecules and assessed their antiviral activity in cells infected with human coronavirus HCoV-229E. We found that hesperidinand naringin-derived macromolecules exhibited greater anti-HCoV-229E effects and significantly reduced virus-induced cell death compared with raw flavonoids. These promising results from the in vitro model motivated the evaluation of flavonoid-macromolecule treatments in a mouse model of coronavirus infection, where they lessened weight loss and improved appearance and behavior. Our findings confirmed that novel antiviral candidates can be developed from resourceful agricultural plants and demonstrated that agricultural wastes, such as orange peels, can be further modified into biomedical products to diversify the available antimicrobial remedies. Overall, this work highlights a waste-to-value strategy for discovering urgently needed antiviral agents to bolster the resilience of our society against emerging and re-emerging coronavirus infections in the future.

Antiviral effects of Sarcodia suae water extracts against vesicular stomatitis virus infection

2024-11-01T09:18:29Z

標題: Antiviral effects of Sarcodia suae water extracts against vesicular stomatitis virus infection 作者: Chang, Tsai-Fei; Lin, Chiou-Feng; Wu, Shan-Ying; Lin, Lin; Lai, Pei-Chun; Liao, Chen-Ting; Woodson, Caitlin; Chen, Shiow-Yi; Lee, Po-Tsang; Lee, Meng-Chou; Lin, Shih-Chao 摘要: Marine algae, a rich source of bioactive substances, have long been utilized in biomedical and veterinary sciences. This study breaks new ground by assessing the antiviral therapeutic potential of water extracts from four algal species - Colaconema formosanum, Caulerpa microphysa, Gelidium amansii and Sarcodia suae - against vesicular stomatitis virus (VSV) infection. The standout among these was Sarcodia suae water extract (SSWE), which not only significantly repressed VSV replication and enhanced cell survival without cytotoxic effects, but also demonstrated its antiviral activity through interference with viral attachment, entry, RNA replication, and egress, and reduced VSV-induced autophagy in Mv1Lu cells during the late stages of infection. The EC50 of SSWE was 0.422 +/- 0.14 mg ml(-1). The cytotoxicity assay confirmed the high biocompatibility of SSWE. This study identifies SSWE as a promising natural antiviral agent and elucidates its mechanisms of action, highlighting the need for further research to optimize its use in controlling VSV-related diseases.