Gene, Год журнала: 2024, Номер 898, С. 148130 - 148130
Опубликована: Янв. 3, 2024
Язык: Английский
Molecular Cancer, Год журнала: 2022, Номер 21(1)
Опубликована: Янв. 28, 2022
Abstract N6-methyladenosine (m6A) methylation, the most common form of internal RNA modification in eukaryotes, has gained increasing attention and become a hot research topic recent years. M6A plays multifunctional roles normal abnormal biological processes, its role may vary greatly depending on position m6A motif. Programmed cell death (PCD) includes apoptosis, autophagy, pyroptosis, necroptosis ferroptosis, which involve breakdown plasma membrane. Based implications methylation PCD, regulators functional were comprehensively studied reported. In this review, we focus high-complexity links between different types PCD pathways, are then closely associated with initiation, progression resistance cancer. Herein, clarifying relationship is great significance to provide novel strategies for cancer treatment, potential prospect clinical application.
Язык: Английский
Процитировано
174
Frontiers in Immunology, Год журнала: 2023, Номер 14
Опубликована: Апрель 25, 2023
In the working-age population worldwide, diabetic retinopathy (DR), a prevalent complication of diabetes, is main cause vision impairment. Chronic low-grade inflammation plays an essential role in DR development. Recently, concerning pathogenesis DR, Nod-Like Receptor Family Pyrin Domain Containing 3 (NLRP3) inflammasome retinal cells has been determined as causal factor. eye, NLRP3 activated by several pathways (such ROS and ATP). The activation NPRP3 leads to secretion inflammatory cytokines interleukin-1β (IL-1β) interleukin-18 (IL-18), pyroptosis, rapid form lytic programmed cell death (PCD). Cells that undergo pyroptosis swell rapture, releasing more factors accelerating progression. This review focuses on mechanisms activate leading DR. present research highlighted some inhibitors NLRP3/pyroptosis novel therapeutic measures treatment.
Язык: Английский
Процитировано
51
Journal of Hematology & Oncology, Год журнала: 2023, Номер 16(1)
Опубликована: Июнь 22, 2023
Abstract Small RNAs (also referred to as small noncoding RNAs, sncRNA) are defined polymeric ribonucleic acid molecules that less than 200 nucleotides in length and serve a variety of essential functions within cells. RNA species include microRNA (miRNA), PIWI-interacting (piRNA), interfering (siRNA), tRNA-derived (tsRNA), etc. Current evidence suggest can also have diverse modifications their nucleotide composition affect stability well capacity for nuclear export, these relevant drive molecular signaling processes biogenesis, cell proliferation differentiation. In this review, we highlight the characteristics cellular modifications, current techniques reliable detection. We discuss how may be clinical applications diagnosis treatment human health conditions such cancer.
Язык: Английский
Процитировано
48
EMBO Molecular Medicine, Год журнала: 2024, Номер 16(2), С. 294 - 318
Опубликована: Янв. 31, 2024
Abstract Diabetic retinopathy (DR) is a leading cause of irreversible vision loss in working-age populations. Fat mass and obesity-associated protein (FTO) an N 6 -methyladenosine (m A) demethylase that demethylates RNAs involved energy homeostasis, though its influence on DR not well studied. Herein, we detected elevated FTO expression vitreous fibrovascular membranes patients with proliferative DR. promoted cell cycle progression tip formation endothelial cells (ECs) to facilitate angiogenesis vitro, mice, zebrafish. also regulated EC-pericyte crosstalk trigger diabetic microvascular leakage, mediated EC–microglia interactions induce retinal inflammation neurodegeneration vivo vitro. Mechanistically, affected EC features via modulating CDK2 mRNA stability m A-YTHDF2-dependent manner. up-regulation under conditions was driven by lactate-mediated histone lactylation. FB23-2, inhibitor FTO’s A activity, suppressed angiogenic phenotypes To allow for systemic administration, developed nanoplatform encapsulating FB23-2 confirmed targeting therapeutic efficiency mice. Collectively, our study demonstrates important function homeostasis DR, warrants further investigation as target patients.
Язык: Английский
Процитировано
30
Frontiers in Pharmacology, Год журнала: 2021, Номер 12
Опубликована: Июль 15, 2021
Background: The total flavones of Abelmoschus manihot (TFA), a compound that is extracted from manihot, has been widely used in China to reduce podocyte injury diabetic kidney disease (DKD). However, the mechanisms underlying therapeutic action this have yet be elucidated. Podocyte pyroptosis characterized by activation NLRP3 inflammasome and plays an important role inflammation-mediated kidneys. Regulation PTEN/PI3K/Akt pathway effective strategy for improving damage DKD. Previous research also shown N6-methyladenosine (m6A) modification involved DKD m6A-modified PTEN regulates PI3K/Akt pathway. In study, we investigated whether TFA alleviates targeting m6A modification-mediated NLRP3-inflammasome signaling. Methods: We MPC-5 cells under high glucose (HG) conditions investigate key molecules are injury, including detected alterations levels three methyltransferases modification. changes these podocytes with overexpression or knockdown methyltransferase-like (METTL)3. Results: Analysis showed MCC950 protected against HG-induced reducing protein expression gasdermin D, interleukin-1β, interleukin-18, increasing nephrin, ZO-1, WT1 podocalyxin. 740Y-P inhibited via inhibiting NIMA-related kinase7, NLRP3, ASC, caspase-1, p-PI3K p-Akt. improved HG-stimulated regulating METTL3-dependent Conclusion: Collectively, our data indicated could ameliorate HG adjusting This study provides better understanding how can protect
Язык: Английский
Процитировано
80
Molecular Medicine, Год журнала: 2021, Номер 27(1)
Опубликована: Сен. 9, 2021
N6-Methyladenosine (m6A) modification has been implicated in many bioprocesses. However, its functions diabetic nephropathy (DN) have not determined. Here, we investigated the role of METTL14, a key component m6A methyltransferase complex, DN.The expression METTL14 was detected DN patients and human renal glomerular endothelial cells (HRGECs). In vitro vivo experiments were performed to explore on high glocse-induced HRGECs injury mice. We also whether works by regulating α-klotho through modification.METTL14 highly expressed kidneys both at mRNA protein level. Overexpression increased ROS, TNF-α IL-6 levels apoptosis HRGECs. Conversely, silence decreased cell apoptosis. confirmed that down-regulated an m6A-dependent manner. addition, found aggravated inflammation db/db mice, which could partially rescued α-klotho.Our data revealed plays vital glucose-induced α-klotho.
Язык: Английский
Процитировано
73
Journal of Neuroinflammation, Год журнала: 2022, Номер 19(1)
Опубликована: Июль 14, 2022
Pyroptosis is a programmed cell death characterized by swift plasma membrane disruption and subsequent release of cellular contents pro-inflammatory mediators (cytokines), including IL-1β IL-18. It differs from other types such as apoptosis, autophagy, necroptosis, ferroptosis, NETosis in terms its morphology mechanism. As recently discovered form death, pyroptosis has been demonstrated to be involved the progression multiple diseases. Recent studies have also suggested that linked various ocular In this review, we systematically summarized discussed recent scientific discoveries involvement common diseases, diabetic retinopathy, age-related macular degeneration, AIDS-related human cytomegalovirus retinitis, glaucoma, dry eye disease, keratitis, uveitis, cataract. We organized new emerging evidence suggesting signaling pathways may potential therapeutic targets hoping provide summary overall intervention strategies relevant multi-dimensional evaluations for well offer valuable ideas further research development perspective pyroptosis.
Язык: Английский
Процитировано
64
Science Advances, Год журнала: 2022, Номер 8(18)
Опубликована: Май 4, 2022
Previously, we found that α-ketoglutaric acid (AKG) stimulates muscle hypertrophy and fat loss through 2-oxoglutarate receptor 1 (OXGR1). Here, demonstrated the beneficial effects of AKG on glucose homeostasis in a diet-induced obesity (DIO) mouse model, which are independent OXGR1. We also showed effectively decreased blood hepatic gluconeogenesis DIO mice. By using transcriptomic liver-specific
Язык: Английский
Процитировано
45
Cardiovascular Drugs and Therapy, Год журнала: 2022, Номер 37(3), С. 435 - 448
Опубликована: Янв. 23, 2022
Язык: Английский
Процитировано
39
Life Sciences, Год журнала: 2025, Номер 363, С. 123355 - 123355
Опубликована: Янв. 6, 2025
Язык: Английский
Процитировано
1