The JAK/STAT signaling pathway: from bench to clinic

Signal Transduction and Targeted Therapy, Год журнала: 2021, Номер 6(1)

Опубликована: Ноя. 26, 2021

Abstract The Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway was discovered more than a quarter-century ago. As fulcrum many vital cellular processes, the JAK/STAT constitutes rapid membrane-to-nucleus module induces expression various critical mediators cancer inflammation. Growing evidence suggests that dysregulation is associated with cancers autoimmune diseases. In this review, we discuss current knowledge about composition, activation, regulation pathway. Moreover, highlight role its inhibitors in

Язык: Английский

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Artesunate ameliorates irinotecan-induced intestinal injury by suppressing cellular senescence and significantly enhances anti-tumor activity

International Immunopharmacology, Год журнала: 2023, Номер 119, С. 110205 - 110205

Опубликована: Апрель 25, 2023

Язык: Английский

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Medicinal plants used for treatment of malaria by indigenous communities of Tororo District, Eastern Uganda

Tropical Medicine and Health, Год журнала: 2023, Номер 51(1)

Опубликована: Июнь 12, 2023

Malaria remains the leading cause of death in sub-Saharan Africa. Although recent developments such as malaria vaccine trials inspire optimism, search for novel antimalarial drugs is urgently needed to control mounting resistance Plasmodium species available therapies. The present study was conducted document ethnobotanical knowledge on plants used treat symptoms Tororo district, a malaria-endemic region Eastern Uganda.An carried out between February 2020 and September 12 randomly selected villages district. In total, 151 respondents (21 herbalists 130 non-herbalists) were using multistage random sampling method. Their awareness malaria, treatment-seeking behaviour herbal treatment practices obtained semi-structured questionnaires focus group discussions. Data analysed descriptive statistics, paired comparison, preference ranking informant consensus factor.A total 45 plant belonging 26 families 44 genera preparation medicines management its symptoms. most frequently mentioned Vernonia amygdalina, Chamaecrista nigricans, Aloe nobilis, Warburgia ugandensis, Abrus precatorius, Kedrostis foetidissima, Senna occidentalis, Azadirachta indica Mangifera indica. Leaves (67.3%) part while maceration (56%) major method remedy preparation. Oral route predominant mode administration with inconsistencies posology prescribed.This showed that identified medicinal Uganda, are potential sources new drugs. This provides basis investigating efficacy, phytochemistry toxicity unstudied high percentage use values validate their malaria.

Язык: Английский

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A concise review on Artemisia annua L.: A major source of diverse medicinal compounds

Industrial Crops and Products, Год журнала: 2022, Номер 184, С. 115072 - 115072

Опубликована: Май 18, 2022

Язык: Английский

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Medicinal Plants and Bioactive Phytochemical Diversity: A Fountainhead of Potential Drugs Against Human Diseases

Sustainable development and biodiversity, Год журнала: 2023, Номер unknown, С. 39 - 93

Опубликована: Янв. 1, 2023

Язык: Английский

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Recent advances in phytosomes for the safe management of cancer

Phytomedicine Plus, Год журнала: 2024, Номер 4(2), С. 100540 - 100540

Опубликована: Фев. 21, 2024

cancer is one of the foremost life-threatening diseases and managed by various strategies like surgery, radiotherapy, chemotherapy. Among all, chemotherapy most preferential strategy for management but faces certain limitations. Phytochemicals (PCs) have been considered potential chemotherapeutics chemopreventive agents their clinical application can be questionable because poor bioavailability stability. phytosomes are promising carriers to deliver anticancer PCs target site with improved stability owing unique properties. This comprehensive review discusses recent advances in loaded (covering period 2013-December 2023) overcome limitations PCs. initially, this covers that under trials along FDA-approved (especially management). Here, we excluded a) an experimental/preclinical or investigational stage; b) possess activity other than anticancer; c) exhibit combination drugs; d) PC-based drugs anticancer. Further, article mainly emphasizes Additionally, cancer, challenges, future directions also discussed. versatile alternatives boost PCs' therapeutic efficacy, bioavailability, specific targeting distinctive structural composition, which similar composition cell membranes enabling them close physiological systems. Moreover, these vesicular systems increase oral polar PCs, protect from physical chemical degradation, facilitate efficiency through stimuli-responsive sustained release Therefore, will help researchers develop a phytochemical-based drug delivery system successful cancer.

Язык: Английский

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Dihydroartemisinin enhances gefitinib cytotoxicity against lung adenocarcinoma cells by inducing ROS ‐dependent apoptosis and ferroptosis

The Kaohsiung Journal of Medical Sciences, Год журнала: 2023, Номер 39(7), С. 699 - 709

Опубликована: Апрель 14, 2023

Abstract The application of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs), such as gefitinib, has shifted lung cancer treatment from empirical chemotherapy to targeted molecular therapy. However, acquired drug resistance is inevitable in almost all non‐small cell (NSCLC) patients treated with gefitinib. Combined dihydroartemisinin (DHA) and gefitinib produced a better inhibitory effect on adenocarcinoma than alone; however, the specific mechanism remains unclear. In this study, we aimed assess underlying combination treatment. We prepared gefitinib‐resistant A549 cells investigated whether apoptosis ferroptosis were involved sensitizing DHA. Treatment 5 μM resulted rupturing floatation medium, while A549‐GR found be insusceptible DHA substantially inhibited proliferation dose‐dependent manner accompanied by increased ferroptosis. accumulated reactive oxygen species (ROS) was crucial for cells. Moreover, cellular autophagy significantly upregulated post‐DHA combined inhibition A549, H1975, HCC827 cells, ROS accumulation remarkable induction observed induced exhibited high toxicity when

Язык: Английский

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Mesenchymal–epithelial transition and AXL inhibitor TP-0903 sensitise triple-negative breast cancer cells to the antimalarial compound, artesunate

Scientific Reports, Год журнала: 2024, Номер 14(1)

Опубликована: Янв. 3, 2024

Abstract Triple-negative breast cancer (TNBC) is a difficult-to-treat, aggressive type. TNBC often associated with the cellular program of epithelial-mesenchymal transition (EMT) that confers drug resistance and metastasis. EMT reverse mesenchymal-epithelial (MET) programs are regulated by several signaling pathways which converge on group transcription factors, EMT- TFs. Therapy approaches could rely reversal to sensitise mesenchymal tumours compounds effective against epithelial cancers. Here, we show antimalarial ROS-generating compound artesunate (ART) exhibits higher cytotoxicity in than cell lines. Ectopic expression EMT-TF ZEB1 or depletion cells, respectively, reduced increased ART-generated ROS levels, DNA damage apoptotic death. In enhanced superoxide dismutase 2 (SOD2) glutathione peroxidase 8 (GPX8) implicated scavenging. Although SOD2 GPX8 levels were unaffected cells response depletion, stable knockdown total ROS. Receptor tyrosine kinase AXL maintains phenotype overexpressed TNBC. The clinically-relevant inhibitor TP-0903 induced MET synergised ART generate ROS, apoptosis cells. SOD2. Thus, sensitised ART, likely via different pathways. Synergistic interactions between indicate combination involving these can have therapeutic prospects for treatment.

Язык: Английский

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Basal–epithelial subpopulations underlie and predict chemotherapy resistance in triple-negative breast cancer

EMBO Molecular Medicine, Год журнала: 2024, Номер 16(4), С. 823 - 853

Опубликована: Март 13, 2024

Abstract Triple-negative breast cancer (TNBC) is the most aggressive subtype, characterized by extensive intratumoral heterogeneity, high metastasis, and chemoresistance, leading to poor clinical outcomes. Despite progress, mechanistic basis of these behaviors remains poorly understood. Using single-cell spatial transcriptome analysis, here we discovered basal epithelial subpopulations located within stroma that exhibit chemoresistance characteristics. The are defined distinct signature genes show a frequent gain in copy number an activated epithelial-to-mesenchymal transition program. A subset can accurately predict chemotherapy response associated with prognosis. Interestingly, among genes, elevated ITGB1 participates enhancing intercellular signaling while ACTN1 confers survival advantage foster chemoresistance. Furthermore, subjecting transcriptional signatures drug repurposing find chemoresistant tumors may benefit from inhibitors treatment-naive versus post-NAC patients. These findings shed light on providing best-in-class biomarker alternate therapeutic avenues for improved management TNBC patients resistant chemotherapy.

Язык: Английский

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Progress on the study of the anticancer effects of artesunate (Review)

Oncology Letters, Год журнала: 2021, Номер 22(5)

Опубликована: Авг. 27, 2021

Artesunate (ART) is a derivative of artemisinin that extracted from the wormwood plant Artemisia annua. ART an antimalarial drug has been shown to be safe and effective for clinical use. In addition its properties, attracting attention over recent years due reported inhibitory effects on cancer cell proliferation, invasion migration. Therefore, wider range potential applications than first hypothesized. The aim present review was summarize latest research progress possible anticancer ART, in order lay theoretical foundation further development as therapeutic option cancer.

Язык: Английский

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