Green Synthesis of Zinc Oxide Nanoparticles Using Acmella caulirhiza Leaf Extract: Characterization and Assessment of Antibacterial, Antioxidant, Anti-inflammatory and Hemolytic Properties

Deleted Journal, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 20, 2025

Language: Английский

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Neoadjuvant apatinib addition to sintilimab and carboplatin-taxane based chemotherapy in patients with early triple-negative breast cancer: the phase 2 NeoSAC trial

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: Feb. 6, 2025

Abstract We aimed to evaluate the efficacy and safety of adding apatinib, sintilimab chemotherapy in neoadjuvant treatment early triple-negative breast cancer (TNBC). In phase 2 NeoSAC trial, patients with TNBC received six cycles sintilimab, nab-paclitaxel, carboplatin followed by surgery. The primary endpoint was pathological complete response (pCR) rate. Specimens collected pre-neoadjuvant therapy post-surgery were retained for comprehensive analysis predictive biomarkers impact on tumor microenvironment. Among 34 enrolled patients, 24 achieved pCR (70.6%; 95% confidence interval (CI), 53.0-85.3), 79.4% (95% CI, 65.1-93.7) had residual burden 0-I. Imaging evaluation showed 21 responses (61.8%) 13 partial (38.2%). most common grade 3-4 adverse events leukopenia (47%), neutropenia (36%), thrombocytopenia (24%). 36-month disease-free survival rate stood at 94.1% a median follow-up 39.1 months. Notably, baseline high ImmuneScore, immune cell infiltration, enrichment interferon-related pathways correlated pCR. Comparison data revealed that group treated this novel regimen exhibited an upregulation distinct subsets, thereby activating Moreover, higher oxeiptosis scores associated increased likelihood achieving Following therapy, decrease score, whereas non-pCR increase. Our study suggests combined nab-paclitaxel promising clinical activity manageable profile merits further study. ClinicalTrials.gov registration: NCT04722718.

Language: Английский

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Targeting the mevalonate pathway potentiates NUAK1 inhibition-induced immunogenic cell death and antitumor immunity

Cell Reports Medicine, Journal Year: 2025, Volume and Issue: unknown, P. 101913 - 101913

Published: Jan. 1, 2025

The induction of immunogenic cell death (ICD) impedes tumor progression via both cell-intrinsic and -extrinsic mechanisms, representing a robust therapeutic strategy. However, ICD-targeted therapy remains to be explored optimized. Through kinome-wide CRISPR-Cas9 screen, NUAK family SNF1-like kinase 1 (NUAK1) is identified as potential target. ICD-provoking effect NUAK1 inhibition depends on the production reactive oxygen species (ROS), consequent downregulation nuclear factor erythroid 2-related 2 (NRF2)-mediated antioxidant gene expression. Moreover, mevalonate pathway/cholesterol biosynthesis, activated by spliced form X-box binding protein (XBP1s) downstream ICD-induced endoplasmic reticulum (ER) stress, functions negative feedback mechanism. Targeting pathway with CRISPR knockout or 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) inhibitor simvastatin amplifies inhibition-mediated ICD antitumor activity, while cholesterol dampens ROS ICD, therefore also suppression. combination statin enhances efficacy anti-PD-1 therapy. Collectively, our study unveils promise blocking mevalonate-cholesterol in conjunction immunotherapy.

Language: Английский

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High-Throughput Screening Strategy and Metal–Organic Framework-Based Multifunctional Controlled-Release Nanomaterial for Osteoarthritis Therapy

ACS Nano, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 19, 2025

Osteoarthritis (OA) is a prevalent degenerative disease that lacks effective therapy. Oxidative stress one of the major factors contributing to OA; however, treatments targeting oxidative are still lacking. In current study, we established an stress-induced cell death model in chondrocytes vitro and screened drugs may suppress death. Ethyl gallate (EG) was identified as most potent drug against out more than 600 natural product library. Application without appropriate delivery system for OA therapy have drawbacks such low bioavailability, short action time, poor efficacy. Herein, poly-His6-zinc assembly (PZA), pH-responsive metal–organic framework (MOF) loaded with EG (EG@PZA) designed It demonstrated EG@PZA lysosome escape property, which dramatically increases utilization EG. Furthermore, showed enhanced release capability acidic microenvironment. vivo studies effectively suppresses extracellular matrix degradation, ferroptosis, senescence also ameliorates destabilization medial meniscus (DMM) mouse vivo. Together, study become potential controlled-release nanomaterial

Language: Английский

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Ex Vivo Biosafety and Efficacy Assessment of Advanced Chlorin e6 Nanoemulsions as a Drug Delivery System for Photodynamic Antitumoral Application

Molecules, Journal Year: 2025, Volume and Issue: 30(3), P. 544 - 544

Published: Jan. 25, 2025

The photosensitizer (PS) in the Photodynamic Therapy (PDT) field represents a key factor, being directly connected to therapeutic efficacy of process. Chlorin e6 is second-generation photosensitizer, approved by FDA with most desired clinical properties for PDT applications, presenting high reactive oxygen species (ROS) generation and proven anticancer properties. However, hydrophobicity major limitation, leading poor biodistribution. To overcome this condition, present work developed an up-to-date nanoemulsion incorporating Ce6 new nanosystem (Ce6/NE). A comprehensive study physicochemical properties, stability, fluorescence characteristics, vitro release profile, vivo ex biocompatibility, was established. nanoemulsions showed particle size stability over six months, no spectroscopic or photophysical alterations. Uptake studies demonstrated internalization Ce6/NE monolayers, biocompatibility at lowest concentrations. HET-CAM assay, however, revealed higher range, also indicating Ce6/NE’s potential cancer treatment through antiangiogenic studies. These findings highlight use promising modulated nanotechnology that promotes low toxicity, bioavailability, site-specific delivery.

Language: Английский

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Platycodon grandiflorum-derived extracellular vesicles suppress triple-negative breast cancer growth by reversing the immunosuppressive tumor microenvironment and modulating the gut microbiota

Journal of Nanobiotechnology, Journal Year: 2025, Volume and Issue: 23(1)

Published: Feb. 7, 2025

Despite the approval of several artificial nanotherapeutics for treatment triple-negative breast cancer (TNBC), significant challenges, including unsatisfactory therapeutic outcomes, severe side effects, and high cost large-scale production, still restrict their long-term application. In contrast, plant-derived extracellular vesicles (PEVs) exhibit promising potential in therapy due to negligible systemic toxicity, bioavailability cost- effectiveness. this study, we developed an alternative strategy inhibit TNBC via Platycodon grandiflorum (PG)-derived (PGEVs). The PGEVs were isolated by ultracentrifugation sucrose gradient centrifugation method contained adequate functional components such as proteins, lipids, RNAs active molecules. exhibited remarkable stability, tolerating acidic digestion undergoing minimal changes simulated gastrointestinal fluid. They efficiently taken up tumor cells induced increased production reactive oxygen species (ROS), leading cell proliferation inhibition apoptosis, particularly line 4T1. Additionally, facilitated polarization tumor-associated macrophages (TAMs) toward M1 phenotype secretion pro-inflammatory cytokines. Further vivo investigations revealed that accumulated 4T1 tumors exerted effects through boosting anti-tumor immune responses modulating gut microbiota whether administered orally or intravenously (i.v.). conclusion, these findings highlight a natural, biocompatible efficient nanotherapeutic candidate treating TNBC.

Language: Английский

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Oxidative Stress and Redox Imbalance: Common Mechanisms in Cancer Stem Cells and Neurodegenerative Diseases

Cells, Journal Year: 2025, Volume and Issue: 14(7), P. 511 - 511

Published: March 29, 2025

Oxidative stress (OS) is an established hallmark of cancer and neurodegenerative disorders (NDDs), which contributes to genomic instability neuronal loss. This review explores the contrasting role OS in stem cells (CSCs) NDDs. Elevated levels reactive oxygen species (ROS) contribute promote tumor initiation progression CSCs, while NDDs such as Alzheimer’s Parkinson’s disease, accelerates death impairs cellular repair mechanisms. Both scenarios involve disruption delicate balance between pro-oxidant antioxidant systems, leads chronic oxidative stress. Notably, CSCs neurons display alterations redox-sensitive signaling pathways, including Nrf2 NF-κB, influence cell survival, proliferation, differentiation. Mitochondrial dynamics further illustrate these differences: enhanced function supports adaptability whereas impairments heighten vulnerability. Understanding common mechanisms OS-induced redox imbalance may provide insights for developing interventions, addressing aging hallmarks, potentially mitigating or preventing both

Language: Английский

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Polydatin enhances oxaliplatin-induced cell death by activating NOX5-ROS-mediated DNA damage and ER stress in colon cancer cells

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 9, 2025

Polydatin (3,4',5-trihydroxy-3-β-d-glucopyranoside, PD) is known for its antioxidant and anti-inflammatory properties. Oxaliplatin (OXA)-based chemotherapy the first-line treatment metastatic recurrent colorectal cancer (CRC). However, lack of selectivity normal cells often results in side effects. Consequently, search anti-cancer components with high efficacy low cytotoxicity has become a significant focus recent years. The anti-tumor effects PD, OXA or their combination were assessed by cell viability, colony formation, wound-healing assays. Reactive oxygen species (ROS) generation was measured flow cytometry DNA damage immunofluorescence assay. relative gene protein expressions analyzed quantitative real time-PCR (qRT-PCR) Western blot Molecular docking analysis predicted interaction between PD potential targets. We found that exerted anti-CRC activity promoting Nicotinamide Adenine Dinucleotide Phosphate (NADPH) oxidase 5 (NOX5)-mediated ROS production, activating endoplasmic reticulum (ER) stress, inducing damage. Knocking down NOX5 attenuated inhibition proliferation forming ability induced colon reversed expression C/EBP-homologous (CHOP) transcription factor 4 (ATF4) proteins. In addition, synergistically activities ER stress signaling pathway. could be an effective strategy certain patients CRC.

Language: Английский

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Anticancer Potential of Ampelopsis cantoniensis Extract: Inducing Apoptosis, Cell Cycle Arrest, and Targeting Cancer Stem Cells in HepG2 Liver Cancer Cells

Biocatalysis and Agricultural Biotechnology, Journal Year: 2025, Volume and Issue: unknown, P. 103521 - 103521

Published: Feb. 1, 2025

Language: Английский

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Mushrooms as Nutritional Powerhouses: A Review of Their Bioactive Compounds, Health Benefits, and Value-Added Products

Foods, Journal Year: 2025, Volume and Issue: 14(5), P. 741 - 741

Published: Feb. 22, 2025

Mushrooms are known to be a nutritional powerhouse, offering diverse bioactive compounds that promote and enhance health. provide distinguishable taste aroma an essential source of vitamin D2, B complex, hydroxybenzoic acids (HBAs) hydroxycinnamic (HCAs), terpenes, sterols, β-glucans. Edible mushroom varieties such as Hericium erinaceus, Ganoderma sp., Lentinula edodes recognized functional foods due their remarkable potential for disease prevention promotion overall health well-being. These have antioxidants, anti-inflammatory, cytoprotective, cholesterol-lowering, antidiabetic, antimicrobial, anticancer properties, well controlling blood pressure, being immunity booster, strengthening bone properties. In addition, they contain non-digestible oligosaccharides (NDOs) ergothioneine, substrate gut microflora. Supplementing our daily meals with those can add value food, providing benefits. Novel edible mushrooms investigated explore substances therapeutic benefit human The scientific community (mycologists) is currently studying the prospects unlocking full advantages mushrooms. This review aims knowledge culturing conditions, potential, value-added products 11 varieties.

Language: Английский

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