Engineered lung cell targeting and SLC7A11 siRNA expressing bacterial extracellular vesicles impair the progression of none‐small cell lung cancer

Bioengineering & Translational Medicine, Год журнала: 2025, Номер unknown

Опубликована: Апрель 16, 2025

Abstract Non‐small cell lung cancer (NSCLC) presents significant therapeutic challenges, often characterized by aggressive proliferation and metastasis. This study investigates the role of SLC7A11, a ferroptosis‐related gene, in NSCLC progression potential engineered bacterial extracellular vesicles (BEVs) expressing SLC7A11‐targeting siRNA as strategy. Using TCGA GEO databases, we identified that SLC7A11 was significantly upregulated tissues. Functional assays demonstrated knockdown lines (NCI‐H2122 NCI‐H647) via qPCR, Western blot, immunofluorescence resulted impaired proliferation, migration, invasion abilities. In vivo xenograft models further revealed inhibited tumor growth metastasis, corroborated histological analyses. To enhance targeted delivery siRNA, BEVs with targeting peptide, verifying their structure function through transmission electron microscopy (TEM) nanoparticle tracking analysis (NTA). toxicity assessments indicated safety for these bioengineered vesicles. Importantly, treatment BEVs‐LCTP‐siSLC7A11 not only tumorigenesis but also activated ferroptosis pathways, evidenced altered expression levels transferrin metastatic Our findings suggest promising approach to inhibit while activating ferroptosis, offering insights into novel strategies against cancer.

Язык: Английский

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Targeting AMPK as a potential treatment for hepatic fibrosis in MASLD

Trends in Pharmacological Sciences, Год журнала: 2025, Номер unknown

Опубликована: Апрель 1, 2025

Язык: Английский

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Rutin‐Associated Hepatoprotection: A Review of Mechanisms and Therapeutic Prospects

Basic & Clinical Pharmacology & Toxicology, Год журнала: 2025, Номер 136(6)

Опубликована: Май 13, 2025

Liver disorders pose a considerable global health challenge, accompanied by rising mortality rates. Current therapeutic strategies, though effective, often face limitations due to adverse effects and resistance, prompting the exploration of alternative treatments, particularly safer natural compounds. Rutin, widely available bioflavonoid, has emerged as promising candidate owing its varied pharmacological properties. We conducted comprehensive search on PubMed Web Science using following keywords: 'rutin', 'liver diseases', 'hepatoprotection', 'clinical observations', 'mechanisms, pharmacology' various combinations these terms. This review systematically examines rutin's potential in hepatic disorders, focusing molecular mechanisms, inflammatory pathways, oxidative stress hepatocellular protection. analyse existing evidence supporting hepatoprotective efficacy, identify cellular targets evaluate applications liver diseases. Our systematic analysis provides theoretical support for developing rutin-based therapies disease management identifies future research directions clinical applications.

Язык: Английский

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Apoptotic Bodies Restore NAD and Mitochondrial Homeostasis in Fibroblasts

Advanced Science, Год журнала: 2025, Номер unknown

Опубликована: Май 19, 2025

Abstract Fibrotic skin diseases are characterized by excessive fibroblast proliferation and pathological extracellular matrix deposition. As a pivotal coenzyme in cellular energetics, NAD homeostasis perturbation is implicated fibrosis. Multiple studies have demonstrated the therapeutic potential of mesenchymal stem cells (MSCs) against cutaneous fibrosis, while specific mechanism remains elusive. Herein, this work finds that although almost all MSCs undergo situ apoptosis within 24 h post‐subcutaneous administration, MSC‐derived apoptotic bodies (ABs) mediated potent anti‐fibrotic effects. Mechanistically, ABs can restore mitochondrial through NAMPT transfer, FOXO1 deacetylation enhancement, PINK1/PARKIN‐dependent mitophagy activation. To achieve penetration into hard fibrotic skin, permeable (pABs) constructed via metabolic glycoengineering copper‐free click chemistry techniques. In both keloid xenograft scleroderma murine models, pABs significantly penetrate collagen reduce summary, research establishes highly promising strategy for reversing fibrosis with matrix.

Язык: Английский

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Dehydroepiandrosterone (DHEA)-induced autophagy protects against lipotoxicity in hepatic cells

Molecular and Cellular Endocrinology, Год журнала: 2025, Номер 606, С. 112584 - 112584

Опубликована: Май 21, 2025

Язык: Английский

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Myogenic nano-adjuvant for orthopedic-related sarcopenia via mitochondrial homeostasis modulation in macrophage-myosatellite metabolic crosstalk

Journal of Nanobiotechnology, Год журнала: 2025, Номер 23(1)

Опубликована: Май 28, 2025

The decline in skeletal muscle mass and strength linked to aging, also known as sarcopenia, is strongly associated with disability, traumatic injury, metabolic disease patients. Meanwhile, sarcopenia increases the risk of adverse orthopedic perioperative complications including implant dislocation, infection, loosening, poor wound healing. Mitochondrial dyshomeostasis immune-myosatellite crosstalk one major pathological factors sarcopenia. To reduce incidence patients, we designed developed a nano-adjuvant based on two-dimensional layer double hydroxide (LDH) for sustained improvement systemic orthopedic-related Construction MgAlCo-LDH@UA (MACL@UA) was performed by introducing cobalt magnesium-aluminum LDH further loading urolithin A (UA). release magnesium ions UA promoted myocyte proliferation, angiogenesis improved mitochondrial homeostasis. Al acted an immunomodulatory adjuvant enhance between macrophages myosatellite cells, prompted macrophage-derived glutamine nourishment. Animal experiments confirmed that vaccination MACL@UA intensive significantly enhanced quadriceps rats. This offers solution long-term short-term significant reduction promising prospects clinical application commercial translation.

Язык: Английский

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SLC7A11 Silencing Modulates Ferroptosis and Autophagy to Reduce Sodium Arsenite-Induced Activation of Hepatic Stellate Cells

Опубликована: Июнь 17, 2024

Arsenic is a prevalent environmental pollutant with recognized carcinogenic properties. Liver fibrosis frequent consequence of arsenic poisoning, the activation hepatic stellate cells (HSCs) being central event. Solute Carrier Family 7 Member 11 (SLC7A11), pivotal regulator ferroptosis, may be involved in process arsenic-induced liver fibrosis. This study utilized lentiviral vector-mediated SLC7A11 silencing LX-2 (a type human cells) to establish an knockout cell model, which was then exposed sodium arsenite (NaAsO2). Protein interactions were assessed through Immunoprecipitation (IP), and protein levels evaluated via Western blot analysis. It found that NaAsO2 decreased cellular Fe2+ nuclear receptor co-activator 4 (NCOA4) expression, reversing these effects. Additionally, IP analysis revealed interaction between Beclin1 proteins NaAsO2. Silencing attenuated reduction Tumor p53(P53), p-mammalian target rapamycin (p-mTOR) levels, along rise Beclin1, Phosphorylated adenosine monophosphate activated kinase (p-AMPK), α-smooth muscle actin (α-SMA) Fibroblast protein-α (FAP) induced by Consequently, promoted reduced autophagy P53/AMPK/mTOR pathway, inhibited HSC NaAsO2, potentially mitigating

Язык: Английский

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USP4/CARM1 axis promotes the malignant transformation of breast cancer cells by upregulating SLC7A11 expression

Clinical Breast Cancer, Год журнала: 2024, Номер unknown

Опубликована: Окт. 1, 2024

Язык: Английский

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Functional anti-inflammatory mesoporous silica nanoplatform for Synergistic and Targeted abdominal aortic aneurysm treatment

Journal of Colloid and Interface Science, Год журнала: 2024, Номер 683, С. 1040 - 1054

Опубликована: Дек. 19, 2024

Язык: Английский

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Identification of novel key genes and signaling pathways in hypertrophic cardiomyopathy: evidence from bioinformatics and next generation sequencing data analysis

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Окт. 15, 2024

Abstract Hypertrophic cardiomyopathy (HCM) is a global health problem characterized by left ventricle become thick and stiff with effect of indication including chest pain, fluttering, fainting shortness breath. In this investigation, we aimed to identify diagnostic markers analyzed the therapeutic potential essential genes. Next generation sequencing (NGS) dataset GSE180313 was obtained from Gene Expression Omnibus (GEO) database used differentially expressed genes (DEGs) in HCM. DEGs were screened using DESeq2 Rbioconductor tool. Then, Ontology (GO) REACTOME pathway enrichment analyses performed. Moreover, protein-protein interaction (PPI) network constructed, module analysis Next, miRNA-hub gene regulatory TF-hub constructed analyzed. Finally, values hub assessed receiver operating characteristic (ROC) curve analysis. By performing analysis, total 958 (479 up regulated 479 down genes) successfully identified GSE180313, respectively. GO revealed that functions signaling pathways significantly enriched response stimulus, multicellular organismal process, metabolism extracellular matrix organization. The FN1, SOX2, TUBA4A, RPS2, TUBA1C, ESR1, SNCA, LCK, PAK1 APLNR might be associated gens FN1 TPM3, together corresponding predicted miRNAs (e.g., hsa-mir-374a-5p hsa-miR-8052), SH3KBP1 ESR1 TFs (e.g PRRX2 STAT3) found correlated This investigation could serve as basis for further understanding molecular pathogenesis targets

Язык: Английский

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