Geroscience and pathology: a new frontier in understanding age-related diseases

Pathology & Oncology Research, Год журнала: 2024, Номер 30

Опубликована: Фев. 23, 2024

Geroscience, a burgeoning discipline at the intersection of aging and disease, aims to unravel intricate relationship between process pathogenesis age-related diseases. This paper explores pivotal role played by geroscience in reshaping our understanding pathology, with particular focus on These diseases, spanning cardiovascular cerebrovascular disorders, malignancies, neurodegenerative conditions, significantly contribute morbidity mortality older individuals. We delve into fundamental cellular molecular mechanisms underpinning aging, including mitochondrial dysfunction senescence, elucidate their profound implications for various Emphasis is placed importance assessing key biomarkers biological age within realm pathology. also scrutinize interplay senescence cancer biology as central area focus, underscoring its paramount significance contemporary pathological research. Moreover, we shed light integration anti-aging interventions that target processes, such senolytics, mitochondria-targeted treatments, influence epigenetic regulation domain pathology In conclusion, concepts research heralds transformative paradigm shift disease promises breakthroughs prevention treatment.

Язык: Английский

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Rapamycin inhibits B16 melanoma cell viability in vitro and in vivo by inducing autophagy and inhibiting the mTOR/p70‑S6k pathway

Oncology Letters, Год журнала: 2024, Номер 27(4)

Опубликована: Фев. 2, 2024

Rapamycin is an immunosuppressant that has been shown to prevent tumor growth following organ transplantation. However, its exact mode of antitumor action remains unknown. The present study used the B16‑F10 (B16) murine melanoma model explore mechanism rapamycin, and it was revealed rapamycin reduced B16 cell viability in vitro vivo. In addition, vivo, results western blotting showed Bcl2 expression, enhanced protein expression levels cleaved caspase 3 Bax, indicating can induce apoptosis cells. Furthermore, cycle analysis induced arrest in G₁ phase, based on reduction CDK1, cyclin D1 CDK4, as well increase percentage cells phase. also significantly increased number autophagosomes cells, determined by transmission electron microscopy. RT‑qPCR upregulated microtubule‑associated light chain (LC3) Beclin‑1, while downregulating p62 thus could trigger cellular autophagy. combination with chloroquine (CQ) further LC3 compared CQ group, suggesting autophagy blocked phosphorylation p70 ribosomal S6 kinase (p70‑S6k) mammalian target (mTOR) proteins may exert effect inhibiting mTOR/p70‑S6k pathway. conclusion, inhibit inducing G1 phase apoptosis. effects in vivo, signaling pathway be involved this process.

Язык: Английский

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GBP2 enhances paclitaxel sensitivity in triple‑negative breast cancer by promoting autophagy in combination with ATG2 and inhibiting the PI3K/AKT/mTOR pathway

International Journal of Oncology, Год журнала: 2024, Номер 64(4)

Опубликована: Фев. 6, 2024

Chemoresistance is a major challenge in treating triple‑negative breast cancer (TNBC); chemotherapy remains the primary approach. The present study aimed to elucidate role of guanylate‑binding protein 2 (GBP2) activating autophagy TNBC and its impact on sensitivity cells paclitaxel (PTX). Transfection with lentivirus was performed establish cell lines stable, high GBP2 expression. mRNA levels expression were evaluated utilizing reverse transcription‑quantitative PCR western blotting, respectively. Autophagy using immunoblotting, transmission electron microscopy fluorescence microscopy. PI3K/AKT/mTOR pathway proteins their phosphorylation detected by co‑localization analysis evaluate association between autophagy‑related (ATG2). BALB/c NUDE mice subcutaneously injected wild‑type/overexpressing MDA‑MB‑231 cells. Low TNBC, which associated poor prognosis. Overexpression suppressed growth, especially enhanced TNBC. Forced significantly increased PTX cells, addition inhibitors reversed this effect. serves as prognostic marker exerts notable inhibitory It functions critical regulator activated co‑acting ATG2 inhibiting pathway, contributes increasing PTX. Therefore, promising therapeutic target for enhancing treatment.

Язык: Английский

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Breast Cancer Chemoresistance: Insights into the Regulatory Role of lncRNA

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(21), С. 15897 - 15897

Опубликована: Ноя. 2, 2023

Long noncoding RNAs (lncRNAs) are a subclass of composed more than 200 nucleotides without the ability to encode functional proteins. Given their involvement in critical cellular processes such as gene expression regulation, transcription, and translation, lncRNAs play significant role organism homeostasis. Breast cancer (BC) is second most common worldwide evidence has shown relationship between aberrant lncRNA BC development. One main obstacles control multidrug chemoresistance, which associated with deregulation multiple mechanisms efflux transporter activity, mitochondrial metabolism reprogramming, epigenetic regulation well apoptosis autophagy. Studies have large number pathways. However, underlying mechanism not clearly elucidated. In this review, we present principal chemoresistance that can be directly or indirectly regulated by lncRNA, highlighting importance controlling chemoresistance. Understanding these deep detail may interest clinical outcome patients could used therapeutic targets overcome therapy resistance.

Язык: Английский

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Investigate of LOC101928988 Regulatory Effect on the DAPK2 Transcription in Breast Tumors

Cancer Reports, Год журнала: 2025, Номер 8(2)

Опубликована: Фев. 1, 2025

ABSTRACT Background The World Health Organization has mentioned breast cancer holds the highest incidence rate among all types of globally. Death‐associated protein kinase 2 ( DAPK2 ) is a serine/threonine linked to various forms malignancy, such as cancer. This assumes pivotal function in multitude cellular mechanisms, including apoptosis, autophagy, and cell migration. Aims study aimed LOC101928988 regulatory effect on expression Methods In this study, 38 paired tumoral normal tissues were selected from patients. Quantitative real‐time PCR was used analyze . interactions its intermediate elements with predicted by docking analysis. Results downregulated tumor compared control group. Further analysis revealed significant positive correlation between levels adjacent tissues. A comparison gene different grades, stages, HER2 statuses showed findings. ROC curve 77% 72% AUC for BC tissue, respectively. Conclusions Overall, our results suggest that alterations may be involved initiation progression It also been reported probably role regulating through interaction transcription factors.

Язык: Английский

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Global trends and research hotspots in nanodrug delivery systems for breast cancer therapy: a bibliometric analysis (2013–2023)

Discover Oncology, Год журнала: 2025, Номер 16(1)

Опубликована: Март 6, 2025

Nanomedicine offers fresh approaches for breast cancer treatment, countering traditional limitations. The nanodrug delivery system's precision and biocompatibility hold promise, yet integration hurdles remain. This study reviews nano systems in therapy from 2013 to 2023, guiding future research directions. In this study, we conducted a comprehensive search on Web of Science database (Guilin Medical University purchase edition) downloaded literature related the field published between 2023. We analyzed these publications using R software, VOSviewer, CiteSpace software. reviewed 2632 documents, showing steady publication increase peaking at 408 2022. China, USA, India, Iran were prominent publishing. Chinese Academy Sciences Tabriz key collaboration centers. Notably, Journal Controlled Release Biomaterials ranked among top 10 journals citations, establishing their representation. Key terms like "breast cancer," "nanoparticles," "drug delivery," "in-vitro," "delivery" widely used. Research focused optimizing drug targeting, utilizing tumor microenvironment delivery, improving efficiency. system, as an innovative approach, numerous advantages has garnered global attention researchers. provides analysis status hotspots within realm therapy, offering valuable insights domain.

Язык: Английский

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Autophagy: The convergence point of aging and cancer

Biochemistry and Biophysics Reports, Год журнала: 2025, Номер 42, С. 101986 - 101986

Опубликована: Март 28, 2025

Язык: Английский

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Jatrophone: a cytotoxic macrocylic diterpene targeting PI3K/AKT/NF-κB pathway, inducing apoptosis and autophagy in resistant breast cancer cells

BMC Complementary Medicine and Therapies, Год журнала: 2023, Номер 23(1)

Опубликована: Авг. 22, 2023

Abstract Background Breast cancer is a prevalent malignant tumor that affects women worldwide. The primary challenge in treating breast combating drug resistance, which contributes to relapse and metastasis. Jatrophone unique macrocyclic jatrophane diterpene found various Jatropha Euphorbia species. It possesses diverse biological pharmacological activities, including anticancer activity. However, it unclear whether jatrophone can overcome resistance cancer. Methods This study includes the investigation of cytotoxicity on doxorubicin-resistant cells (MCF-7 ADR ) underlying molecular mechanisms. effects cell viability were determined using sulforhodamine B (SRB) assay, while flow cytometry was used evaluate cycle progression, apoptosis, autophagy. A scratch assay conducted observe migration, western blotting measure downstream protein levels (PI3K, AKT, NF-κB). Unpaired Student’s t-tests for comparison between two groups results analyzed by one-way ANOVA with Tukey- Kremer post hoc test. Results shown exhibited potent cytotoxic activity MCF-7 dose-dependent manner, an IC 50 value 1.8 µM. also significantly induced S G/M phase arrest. Interestingly, both early late apoptotic death, as well autophagic negligible necrosis. Furthermore, treatment diminished migration cells. At level, down-regulated expression PI3K, NF-κB. β . Conclusions suggest decreases proliferation MCF-7/ADR at low micromolar concentration; induces arrest; promotes apoptotic, death; inhibits EMT; works mechanism involving inhibition PI3K/Akt/ NF-κB pathway. These findings provide evidence potential be promising lead compound targeting could further investigated its clinical application chemotherapy adjuvant.

Язык: Английский

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The potential therapeutic effect of melatonin in oxaliplatin combination therapy against chemoresistant colorectal cancer cells

Molecular Biology Reports, Год журнала: 2024, Номер 51(1)

Опубликована: Фев. 24, 2024

Язык: Английский

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Autophagy and radiotherapy in esophageal cancer: modulating treatment sensitivity and overcoming challenges

ONCOLOGIE, Год журнала: 2024, Номер 26(5), С. 687 - 699

Опубликована: Авг. 13, 2024

Abstract Esophageal cancer (ESCA) is one of the most fatal gastrointestinal cancers worldwide. ESCA often diagnosed in its middle or late stages since first symptoms are not identifiable. The use radiotherapy, either alone conjunction with surgical intervention and chemotherapy, essential to achieve a positive prognosis. Radiotherapy an component treatment for ESCA. Autophagy, prevalent biological phenomenon, has twofold impact on incidence, progression, response malignant tumors. This review explores intricate mechanisms by which autophagy modulates radiation sensitivity ESCA, including effects DNA repair, oxidative stress responses, apoptosis. We provide comprehensive analysis recent advancements modulation autophagy, focusing inhibitors inducers enhance radiotherapy efficacy. discuss how such as chloroquine 3-methyladenine can overcome resistance blocking autophagic processes, while like rapamycin sensitize cells radiotherapy-induced cell death. Additionally, we examine potential therapeutic benefits combining regulation existing modalities, offering new strategies improve patient outcomes. highlights critical role underscores promise autophagy-targeted therapies enhancing effectiveness thereby providing novel avenue overcoming improving prognosis patients.

Язык: Английский

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