The Role of Hypoxia-Inducible Factor-1 Alpha in Renal Disease

Molecules, Journal Year: 2022, Volume and Issue: 27(21), P. 7318 - 7318

Published: Oct. 28, 2022

Partial pressure of oxygen (pO2) in the kidney is maintained at a relatively stable level by unique and complex functional interplay between renal blood flow, glomerular filtration rate (GFR), consumption, arteriovenous shunting. The vulnerability this interaction renders vulnerable to hypoxic injury, leading different diseases. Hypoxia has long been recognized as an important factor pathogenesis acute injury (AKI), especially ischemia/reperfusion injury. Accumulating evidence suggests that hypoxia also plays role progression chronic disease (CKD) CKD-related complications, such anemia, cardiovascular events, sarcopenia. In addition, cancer linked deregulation pathways. Renal utilizes various molecular pathways respond adapt changes oxygenation. Particularly, hypoxia-inducible (HIF) (including HIF-1, 2, 3) shown be activated major protective response hypoxia. HIF-1 heterodimer composed oxygen-regulated HIF-1α subunit constitutively expressed HIF-1β subunit. diseases, critical characteristic protective, but it negative effect, This review summarizes mechanisms regulation disease.

Language: Английский

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Hypoxia: syndicating triple negative breast cancer against various therapeutic regimens

Frontiers in Oncology, Journal Year: 2023, Volume and Issue: 13

Published: July 10, 2023

Triple-negative breast cancer (TNBC) is one of the deadliest subtypes (BC) for its high aggressiveness, heterogeneity, and hypoxic nature. Based on biological clinical observations TNBC related mortality very worldwide. Emerging studies have clearly demonstrated that hypoxia regulates critical metabolic, developmental, survival pathways in TNBC, which include glycolysis angiogenesis. Alterations to these accelerate stem cells (CSCs) enrichment immune escape, further lead tumor invasion, migration, metastasis. Beside this, also manipulates epigenetic plasticity DNA damage response (DDR) syndicate progression. Hypoxia fundamentally creates low oxygen condition responsible alteration Hypoxia-Inducible Factor-1alpha (HIF-1α) signaling within microenvironment, allowing tumors survive making them resistant various therapies. Therefore, there an urgent need society establish target-based therapies overcome resistance limitations current treatment plan TNBC. In this review article, we thoroughly discussed plausible significance HIF-1α as a target therapeutic regimens such chemotherapy, radiotherapy, immunotherapy, anti-angiogenic therapy, adjuvant therapy photodynamic adoptive cell combination therapies, antibody drug conjugates vaccines. Further, reviewed here intrinsic mechanism existing issues targeting while improvising strategies. This highlights discusses future perspectives major alternatives by hypoxia-induced signaling.

Language: Английский

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Targeting hypoxic and acidic tumor microenvironment by nanoparticles: A review

Journal of Drug Delivery Science and Technology, Journal Year: 2024, Volume and Issue: 96, P. 105660 - 105660

Published: April 12, 2024

Language: Английский

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Glutathione-Dependent Pathways in Cancer Cells

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(15), P. 8423 - 8423

Published: Aug. 1, 2024

The most abundant tripeptide—glutathione (GSH)—and the major GSH-related enzymes—glutathione peroxidases (GPxs) and glutathione S-transferases (GSTs)—are highly significant in regulation of tumor cell viability, initiation development, its progression, drug resistance. high level GSH synthesis different cancer types depends not only on increasing expression key enzymes γ-glutamyl cycle but also changes transport velocity precursor amino acids. ability GPxs to reduce hydroperoxides is used for cellular each member GPx family has a mechanism action site maintaining redox balance. GSTs catalyze conjugation electrophilic substances reduction organic take part signaling pathways. By catalyzing S-glutathionylation target proteins, are involved processes, including metabolism (e.g., glycolysis PPP), signal transduction, transcription regulation, development resistance anticancer drugs. In this review, recent findings synthesis, roles functions GPxs, GST isoforms discussed, along with search inhibitors treatment.

Language: Английский

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Tumor energy metabolism: implications for therapeutic targets

Molecular Biomedicine, Journal Year: 2024, Volume and Issue: 5(1)

Published: Nov. 29, 2024

Abstract Tumor energy metabolism plays a crucial role in the occurrence, progression, and drug resistance of tumors. The study tumor has gradually become an emerging field treatment. Recent studies have shown that epigenetic regulation is closely linked to metabolism, influencing metabolic remodeling biological traits cells. This review focuses on primary pathways explores therapeutic strategies target these pathways. It covers key areas such as glycolysis, Warburg effect, mitochondrial function, oxidative phosphorylation, adaptability Additionally, this article examines regulator SWI/SNF complex specifically its interactions with glucose, lipids, amino acids. Summarizing aimed at pathways, including inhibitors mitochondrial-targeted drugs, exploitation vulnerabilities, recent developments related complexes potential targets. clinical significance, challenges, future directions research are discussed, overcome resistance, combination therapy, application new technologies.

Language: Английский

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Hypoxia expedites the progression of papillary thyroid carcinoma by promoting the CPT1A‐mediated fatty acid oxidative pathway

Drug Development Research, Journal Year: 2024, Volume and Issue: 85(2)

Published: March 7, 2024

Abstract Hypoxia has been reported to promote the proliferation and migration of thyroid cancer, while special mechanism was still unclear. HIF‐1α/carnitine palmitoyl‐transferase 1A (CPT1A) found be associated with papillary carcinoma (PTC) but biological role CPT1A in PTC not explored. The effects hypoxia carnitine expression on cells were determined by cell counting kit‐8 assay, detection oxidative stress, inflammation response mitochondrial membrane motential (MMP). Oil Red O staining free fatty acids performed assess status lipid metabolism. Flow cytometric analysis apoptosis. Quantitative polymerase chain reaction (qPCR) western blot applied investigate expressions HIF‐1α molecules involved function. significantly increased or without treatment. overexpression silencing promoted inhibited viability, further repressed viability. In addition, alleviates hypoxia‐induced elevated MMP. enhanced palmitic acid‐induced decreased growth, metabolic capacity acid suppressed Animal experiments showed that tumor reduced deposition, stress inflammation, as well enhancing function indicators. However, opposite both vitro vivo. induces high HIF‐1α/CPT1A, thereby reprogramming metabolism for adapting environment, meanwhile inhibiting damage apoptosis caused stress.

Language: Английский

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Resistance of Lenvatinib in Hepatocellular Carcinoma

Current Cancer Drug Targets, Journal Year: 2022, Volume and Issue: 22(11), P. 865 - 878

Published: April 30, 2022

Lenvatinib is a multikinase inhibitor which mainly hinders liver cancer proliferation by inhibiting angiogenesis. In 2018, was approved for the first-line treatment of patients with advanced hepatocellular carcinoma [HCC] in United States, European Union, Japan, and China. has been established as sorafenib replacement drug higher objective response rate [ORR], longer progression-free survival [PFS], time to progression [TTP]. resistance during become increasingly common recent years. Accordingly, it necessary determine factors associated explore solutions. this review, we sought mechanisms methods reduce summarized achievements treatment.

Language: Английский

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LncRNA MALAT1 Promotes PPARα/CD36-Mediated Hepatic Lipogenesis in Nonalcoholic Fatty Liver Disease by Modulating miR-206/ARNT Axis

Frontiers in Bioengineering and Biotechnology, Journal Year: 2022, Volume and Issue: 10

Published: June 13, 2022

Long non-coding RNAs (lncRNAs) are known to play crucial roles in nonalcoholic fatty liver disease (NAFLD). This research sought explore mechanisms by which lncRNA MALAT1 regulates the progression of NAFLD. Thus, order detect function NAFLD, vitro and vivo model NAFLD were established. Then, acid uptake triglyceride level investigated BODIPY labeled-fatty assay Oil red O staining, respectively. The expressions MALAT1, miR-206, ARNT, PPARα CD36 detected western blotting qPCR. Dual luciferase, RIP ChIP used validate relation among ARNT PPARα. data revealed expression was up-regulated knockdown suppressed FFA-induced lipid accumulation hepatocytes. Meanwhile, upregulated through binding with miR-206. Moreover, miR-206 inhibitor reversed effects decreased FFA-treated Furthermore, could inhibit via promoter. Knockdown significantly downregulated CD36, while these phenomena. regulated PPARα/CD36 -mediated hepatic regulation miR-206/ARNT axis. MALAT1/miR-206/ARNT might serve as a therapeutic target against

Language: Английский

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An appraisal of the current status of inhibition of glucose transporters as an emerging antineoplastic approach: Promising potential of new pan-GLUT inhibitors

Frontiers in Pharmacology, Journal Year: 2022, Volume and Issue: 13

Published: Nov. 1, 2022

Neoplastic cells displayed altered metabolism with accelerated glycolysis. Therefore, these need a mammoth supply of glucose for which they display an upregulated expression various transporters (GLUT). Thus, novel antineoplastic strategies focus on inhibiting GLUT to intersect the glycolytic lifeline cancer cells. This review focuses current status inhibition scenarios. The inhibitors belong both natural and synthetic small inhibitory molecules category. As neoplastic express multiple isoforms, it is necessary use pan-GLUT inhibitors. Nevertheless, also that such exert their action at low concentration so normal healthy are left unharmed minimal injury caused other vital organs systems body. Moreover, approaches emerging from combining chemotherapeutic agents potentiate action. A new inhibitor named glutor, piperazine-one derivative, has shown potent owing its exerted nanomolar concentrations. discusses merits limitations existing approach possible future outcomes.

Language: Английский

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Herba Patriniae and its component Isovitexin show anti-colorectal cancer effects by inducing apoptosis and cell-cycle arrest via p53 activation

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 168, P. 115690 - 115690

Published: Nov. 6, 2023

Colorectal cancer (CRC) is the most prevalent of digestive tract. Herba Patriniae (also known as Bai Jiang Cao, HP) have been widely used to manage diarrhea, ulcerative colitis, and several cancers, including CRC. Nonetheless, molecular mechanisms underlying pharmacological action HP on CRC remain unclear. This study investigated against using network pharmacology analysis in vitro vivo experiments. The results revealed nine bioactive compounds HP. Furthermore, 3460 CRC-related targets identified active were predicted from Gene Expression Omnibus (GEO) database. 65 common through intersection two related targets. Moreover, ten hub genes, CDK4, CDK2, CDK1, CCND1, CCNB1, CCNA2, MYC, E2F1, CHEK1, CDKN1A topological analysis. Meanwhile, GO KEGG pathway that core target genes majorly enriched p53 HIF-1 signaling pathways. promoted apoptosis suppressed cell proliferation by activating a dose-dependent manner, while similar effect was observed for Isovitexin (the primary component HP). Overall, this provides valuable insights into its CRC, providing theoretical foundation additional experimental verification clinical application.

Language: Английский

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