Integrated network toxicology, molecular docking, and in vivo experiments to elucidate molecular mechanism of aflatoxin B1 hepatotoxicity

Ecotoxicology and Environmental Safety, Год журнала: 2024, Номер 275, С. 116278 - 116278

Опубликована: Апрель 1, 2024

Due to the rise in temperature and sea level caused by climate change, detection rate of aflatoxin B1 (AFB1) food crops has increased dramatically, frequency severity aflatoxicosis humans animals are also increasing. AFB1 strong hepatotoxicity, causing severe liver damage even cancer. However, mechanism hepatotoxicity remains unclear. By integrating network toxicology, molecular docking vivo experiments, this research was designed explore potential mechanisms AFB1. Thirty-three intersection targets for AFB1-induced were identified using online databases. PI3K/AKT1, MAPK, FOXO1 signaling pathways, apoptosis significantly enriched. In addition, proteins ALB, AKT1, PIK3CG, MAPK8, HSP90AA1, PPARA, MAPK1, EGFR, FOXO1, IGF1 exhibited good affinity with significant pathological changes occurred mice. induction expression levels ERK, decreased levsls PI3K AKT1. Moreover, treatment an increase Caspase3 expression, a decrease Bcl2/Bax ratio. combining toxicology study confirms first time that promotes pathway inactivating PI3K/AKT1 activating EGFR/ERK hence aggravating hepatocyte apoptosis. This provides new strategies studying toxicity environmental pollutants possible development hepatoprotective drugs.

Язык: Английский

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Emerging role of immunogenic cell death in cancer immunotherapy: Advancing next-generation CAR-T cell immunotherapy by combination

Cancer Letters, Год журнала: 2024, Номер 598, С. 217079 - 217079

Опубликована: Июнь 25, 2024

Язык: Английский

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Crosstalk of pyroptosis and cytokine in the tumor microenvironment: from mechanisms to clinical implication

Molecular Cancer, Год журнала: 2024, Номер 23(1)

Опубликована: Ноя. 30, 2024

In the realm of cancer research, tumor microenvironment (TME) plays a crucial role in initiation and progression, shaped by complex interactions between cells surrounding non-cancerous cells. Cytokines, as essential immunomodulatory agents, are secreted various cellular constituents within TME, including immune cells, cancer-associated fibroblasts, themselves. These cytokines facilitate intricate communication networks that significantly influence initiation, metastasis, suppression. Pyroptosis contributes to TME remodeling promoting release pro-inflammatory sustaining chronic inflammation, impacting processes such escape angiogenesis. However, challenges remain due interplay among cytokines, pyroptosis, along with dual effects pyroptosis on progression therapy-related complications like cytokine syndrome. Unraveling these complexities could strategies balance inflammatory responses while minimizing tissue damage during therapy. This review delves into crosstalk elucidating their contribution metastasis. By synthesizing emerging therapeutic targets innovative technologies concerning this aims provide novel insights enhance treatment outcomes for patients.

Язык: Английский

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Recent Advancements in Metallic Au- and Ag-Based Chitosan Nanocomposite Derivatives for Enhanced Anticancer Drug Delivery

Molecules, Год журнала: 2024, Номер 29(10), С. 2393 - 2393

Опубликована: Май 19, 2024

The rapid advancements in nanotechnology the field of nanomedicine have potential to significantly enhance therapeutic strategies for cancer treatment. There is considerable promise enhancing efficacy therapy through manufacture innovative nanocomposite materials. Metallic nanoparticles been found release anticancer medications that are loaded onto them, resulting a sustained release, hence reducing dosage required drug administration and preventing their buildup healthy cells. combination with biocompatible materials offers new prospects development advanced therapies exhibit enhanced selectivity, reduced adverse effects, improved patient outcomes. Chitosan (CS), polysaccharide possessing distinct physicochemical properties, exhibits favorable attributes controlled delivery due its biocompatibility biodegradability. nanocomposites heightened stability, biocompatibility, prolonged characteristics medicines. incorporation gold (Au) into chitosan results manifestation photothermal characteristics, whereas inclusion silver (Ag) boosts antibacterial capabilities synthesized nanocomposite. objective this review investigate recent progress utilization Ag Au nanoparticles, or thereof, within matrix modified derivatives purpose delivery. research findings deliver various drugs, such as doxorubicin, 5-Fluroacil, curcumin, paclitaxel, 6-mercaptopurine, were investigated. Moreover, modifications carried out on phase surfaces targeting loading efficiency, pH sensitivity highlighted. In addition, challenges perspectives could motivate further related applications summarized.

Язык: Английский

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Ferroptosis and cuproptosis: Metal-dependent cell death pathways activated in response to classical chemotherapy – Significance for cancer treatment?

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Год журнала: 2024, Номер 1879(4), С. 189124 - 189124

Опубликована: Май 25, 2024

Apoptosis has traditionally been regarded as the desired cell death pathway activated by chemotherapeutic drugs due to its controlled and non-inflammatory nature. However, recent discoveries of alternative pathways have paved way for immune-stimulatory treatment approaches in cancer. Ferroptosis (dependent on iron) cuproptosis copper) hold promise selective cancer targeting overcoming drug resistance. Copper ionophores iron-bearing nano-drugs show potential clinical therapy single agents adjuvant treatments. Here we review up-to-date evidence involvement metal ion-dependent cytotoxicity classical (alkylating agents, topoisomerase inhibitors, antimetabolites, mitotic spindle inhibitors) their combinations with ferroptosis inducers, indicating prospects, advantages, obstacles use.

Язык: Английский

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Targeting regulated cell death: Apoptosis, necroptosis, pyroptosis, ferroptosis, and cuproptosis in anticancer immunity

Journal of Translational Internal Medicine, Год журнала: 2025, Номер 13(1), С. 10 - 32

Опубликована: Фев. 1, 2025

In the evolving landscape of cancer treatment, strategic manipulation regulated cell death (RCD) pathways has emerged as a crucial component effective anti-tumor immunity. Evidence suggests that tumor cells undergoing RCD can modify immunogenicity microenvironment (TME), potentially enhancing its ability to suppress progression and metastasis. this review, we first explore mechanisms apoptosis, necroptosis, pyroptosis, ferroptosis, cuproptosis, along with crosstalk between these modalities. We then discuss how processes activate antigen-presenting cells, facilitate cross-priming CD8+ T trigger immune responses, highlighting complex effects novel forms on TME biology. Furthermore, summarize potential drugs nanoparticles induce or inhibit emerging their therapeutic roles in treatment. Finally, put forward existing challenges future prospects for targeting anti-cancer Overall, review enhances our understanding molecular biological impacts RCD-based therapies, providing new perspectives strategies

Язык: Английский

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Decoding ferroptosis: Revealing the hidden assassin behind cardiovascular diseases

Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 176, С. 116761 - 116761

Опубликована: Май 23, 2024

The discovery of regulatory cell death processes has driven innovation in cardiovascular disease (CVD) therapeutic strategies. Over the past decade, ferroptosis, an iron-dependent form regulated by excessive lipid peroxidation, been shown to drive development multiple CVDs. This review provides insights into evolution concept similarities and differences with traditional modes programmed (e.g., apoptosis, autophagy, necrosis), as well core mechanisms ferroptosis (including cystine/glutamate transporter blockade, imbalance iron metabolism, peroxidation). In addition, it not only a detailed role its potential widely studied CVDs such coronary atherosclerotic heart disease, myocardial infarction, ischemia/reperfusion injury, failure, cardiomyopathy, aortic aneurysm but also overview phenomenon perspectives lesser-addressed cardiac valvulopathy, pulmonary hypertension, sickle disease. article aims integrate this knowledge provide comprehensive view wide range progress strategies field.

Язык: Английский

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Advances in stimuli-responsive polymeric hydrogels for anticancer drug delivery: A review

Journal of Drug Delivery Science and Technology, Год журнала: 2024, Номер 102, С. 106394 - 106394

Опубликована: Ноя. 8, 2024

Язык: Английский

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Nicotinamide riboside alleviates sweeteners-induced brain and cognitive impairments in immature mice

Food & Function, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Nicotinamide riboside alleviated cognitive impairment induced by sucrose/aspartame, which might be related to neuroinflammation, pyroptosis, oxidative stress, apoptosis and autophagy.

Язык: Английский

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Antibody-DNA nanostructure conjugate enables targeted delivery of gemcitabine to tumor and improves the anti-tumor efficacy

Journal of Controlled Release, Год журнала: 2025, Номер 381, С. 113613 - 113613

Опубликована: Март 9, 2025

Язык: Английский

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