N6-methyladenosine regulates metabolic remodeling in kidney aging through transcriptional regulator GLIS1 DOI Creative Commons
Xu Li, Shuo Chen, Qiuling Fan

и другие.

BMC Biology, Год журнала: 2024, Номер 22(1)

Опубликована: Дек. 31, 2024

Age-related kidney impairment, characterized by tubular epithelial cell senescence and renal fibrosis, poses a significant global public health threat. Although N6-methyladenosine (m6A) methylation is implicated in various pathological processes, its regulatory mechanism aging remains unclear. An m6A-mRNA epitranscriptomic microarray was performed to identify genes with abnormal m6A modifications aged human tissues. Histological, immunohistochemical, immunofluorescent staining, western blot, RT-qPCR were employed examine the biological functions of targeted methyltransferases both vivo vitro. RNA immunoprecipitation, chromatin ribosomal luciferase reporter assays used investigate specific interactions between methyltransferases, genes, their downstream signals. Significantly lower modification levels observed GLIS1, identified as "metabolic remodeling factor," showed significantly reduced protein modifications. The downregulation GLIS1 induced fibrosis shifting metabolic from fatty acid oxidation (FAO) glycolysis. Additionally, methylated mRNA regulated expression METTL3 YTHDF1. Silencing METTL3/YTHDF1 weakened translation disrupted balance FAO Our findings suggest that activated YTHDF1-dependent manner, leads regulating shift This provides promising therapeutic target for aging.

Язык: Английский

Senolytic procyanidin C1 alleviates renal fibrosis by promoting apoptosis of senescent renal tubular epithelial cells DOI Open Access
Yu Gan, Kangning Wang, Xiang Chen

и другие.

The FASEB Journal, Год журнала: 2025, Номер 39(2)

Опубликована: Янв. 29, 2025

Abstract Renal fibrosis is a common pathological process in various chronic kidney diseases. The accumulation of senescent renal tubular epithelial cells (TECs) tissues plays an important role the development fibrosis. Eliminating TECs has been proven to effectively reduce Procyanidin C1 (PCC1) senolytic by specifically eliminating and extending its overall lifespan. However, whether PCC1 can alleviate unilateral ureteral obstruction (UUO)‐induced associated therapeutic mechanisms remains unclear. Here, we observed marked increase within obstructed human tissue demonstrated positive correlation between UUO‐induced mice. We found that reduced number TECs, restored regenerative phenotype kidneys with fibrosis, improved repair after injury. In vitro, cleared HK2 inducing apoptosis via ANGPTL4/NOX4 signaling. Incubation culture medium from promoted fibroblast activation, whereas impeded profibrotic effects downregulating senescence‐associated secretory (SASP) factors cells. Therefore, alleviated interstitial not only clearing improving but also indirectly attenuating myofibroblast activation reducing level SASP. summary, may be novel agent for treating

Язык: Английский

Процитировано

1
Cornuside as a promising therapeutic agent for diabetic kidney disease: Targeting regulation of Ca2+ disorder-mediated renal tubular epithelial cells apoptosis DOI

Gai Gao,

Xuan Su, Shu-Yan Liu

и другие.

International Immunopharmacology, Год журнала: 2025, Номер 149, С. 114190 - 114190

Опубликована: Фев. 3, 2025

Язык: Английский

Процитировано

1
Natural Product-Derived Senotherapeutics: Extraction and Biological Evaluation Techniques DOI
Harris Pratsinis, Eleni Mavrogonatou, Sevasti‐Kiriaki Zervou

и другие.

Methods in molecular biology, Год журнала: 2025, Номер unknown, С. 315 - 359

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

1
Boeravinone C ameliorates lipid accumulation and inflammation in diabetic kidney disease by activating PPARα signaling DOI

Zhuoqing Cheng,

Honghong Zhan,

Han Yuan

и другие.

Journal of Ethnopharmacology, Год журнала: 2025, Номер unknown, С. 119398 - 119398

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

0
Senolytic elimination of senescent cells improved periodontal ligament stem cell-based bone regeneration partially through inhibiting YAP DOI
Linglu Jia, Han Xiao,

Zhenghao Hao

и другие.

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Год журнала: 2025, Номер 1872(3), С. 119921 - 119921

Опубликована: Фев. 18, 2025

Язык: Английский

Процитировано

0
Dasatinib and Quercetin Mitigate Age‐Related Alveolar Bone Inflammaging and Neutrophil Infiltration DOI Open Access

Jie Tang,

Jingya Li,

Zeyu Hou

и другие.

Oral Diseases, Год журнала: 2025, Номер unknown

Опубликована: Март 6, 2025

Age-related alveolar bone resorption poses a major dental health challenge, yet its mechanisms and treatments are poorly understood. This study investigates the impact of dasatinib quercetin (D + Q) treatment on senescent cells (SnCs), senescence-associated secretory phenotype (SASP), neutrophil infiltration in aged bone, aiming to develop new strategies for combating age-related resorption. C57BL/6 mice (2 18 months) were used examine resorption, inflammaging, infiltration. Aged received D Q assess therapeutic effects. Key measurements included cementoenamel junction crest (CEJ-ABC) distance, periodontal ligament (PDL) thickness, osteometabolism markers, SnCs accumulation, SASP expression, showed increased CEJ-ABC atrophied ligament, unbalanced osteometabolism, along with elevated SnCs, SASP, neutrophils compared young controls. improved these conditions by reducing enhancing health, boosting metabolism. It also lowered expression markers. effectively mitigates aging clearing lowering levels, aggregation, presenting novel approach

Язык: Английский

Процитировано

0
Combination of dasatinib and quercetin promotes osteogenic differentiation and stemness maintenance of hPDLSCs via YAP/TAZ DOI Creative Commons

Yunge Qiu,

Yajun Zhao, Linglu Jia

и другие.

Animal Cells and Systems, Год журнала: 2025, Номер 29(1), С. 19 - 29

Опубликована: Март 12, 2025

Human periodontal ligament stem cells (hPDLSCs) are candidate seed for tissue regeneration. Enhancing the stemness maintenance and osteogenic differentiation potential of hPDLSCs is conducive to their role in The combination dasatinib quercetin, a type senolytic, has been reported affect cell senescence. However, whether it can regulate hPDLSCs, related mechanisms, remain unknown. present study analyzed optimal concentrations quercetin found that enhanced promoted expression stemness-related markers hPDLSCs. levels TAZ YAP were improved when incubated with quercetin. osteogenesis-promoting effects plus partly attenuated was knocked down, on suppressed inhibited. Taken together, promotes YAP/TAZ may be involved this process. This hold promise improving function

Язык: Английский

Процитировано

0
The role of redox signaling in mitochondria and endoplasmic reticulum regulation in kidney diseases DOI Creative Commons
Omar Emiliano Aparicio‐Trejo, Estefani Yaquelin Hernández‐Cruz, Laura María Reyes-Fermín

и другие.

Archives of Toxicology, Год журнала: 2025, Номер unknown

Опубликована: Апрель 11, 2025

Abstract Kidney diseases are among the fastest worldwide growing pathologies. This growth together with their high mortality rate emphasizes importance of generating vital information about mechanism involved in pathophysiology to determine possible therapeutic targets. Recently, mitochondrial damage and implication reactive oxygen spices (ROS) signaling redox homeostasis have emerged as a hub point pathologic renal ROS low levels necessary maintain cell processes well mitochondria its association other organelles, especially endoplasmic reticulum (ER). However, how interacts interferes cellular has not been fully integrated. Furthermore, higher concentrations, these promotes pathways linked disease progression like, biogenesis reduction, ER stress, calcium overload, inflammation, death fibrosis. Therefore, aim this review is describe molecular mechanisms influence on homeostasis, focusing lipid metabolism ß-oxidation, biogenesis, inflammations, stress effects alteration genesis development disease, emphasis acute kidney injury (AKI) chronic (CKD).

Язык: Английский

Процитировано

0
Berberine and health outcomes: an overview of systematic reviews DOI Creative Commons

Lan-Jun Shi,

Wenya Wang, Chunxia Jing

и другие.

BMC Complementary Medicine and Therapies, Год журнала: 2025, Номер 25(1)

Опубликована: Апрель 23, 2025

Berberine is an isoquinoline alkaloid isolated from Chinese herb coptis chinensis and other berberis plants which can be used to treat a wide range of chronic diseases. However, the current research evidence on therapeutic effects berberine has not been summarized. We aimed synthesize systematic review (SRs) for treatment diverse conditions. A comprehensive search Cochrane Library, PubMed, EMBASE, Web Science, CNKI, Wanfang, VIP, SinoMed was performed database inception April 11, 2024. SRs were included evaluated. The methodological quality reporting each SR assessed using AMSTAR-2 tool PRISMA checklist, respectively. appraised based GRADE. Fifty-four analyzed. Overall, associations found between 70 health outcomes concerned with 9 improved most these diseases: 78% (25/32) cardiovascular disease outcomes, 92.59% (25/27) type 2 diabetes mellitus 94.74% (18/19) gastrointestinal disorders 72.22% (13/18) polycystic ovary syndrome (PCOS) 86.67% (13/15) non-alcoholic fatty liver (NAFLD) 92.31% (12/13) schizophrenia 90.91% (10/11) metabolic 57.14% (4/7) obesity 100.00% (6/6) dyslipidemia outcomes. There high overlap primary studies (CCA > 15%) in PCOS, NAFLD, obesity, schizophrenia. Only one rated as while eight low forty-five very according AMSTAR-2. Regarding quality, Item 14, 15, 21, 22 poorly reported terms PRSMA assessment. For GRADE, evidence, twenty-two moderate 110 quality. Current suggests that beneficial people Specifically, significantly improves diabetes, disorders, schizophrenia, syndrome, caution needed considering shortcomings relevant system reviews included.

Язык: Английский

Процитировано

0
Dasatinib and Quercetin Combination Increased Kidney Damage in Acute Folic Acid-Induced Experimental Nephropathy DOI Creative Commons

Antonio Battaglia-Vieni,

Vanessa Marchant, Lucía Tejedor-Santamaría

и другие.

Pharmaceuticals, Год журнала: 2025, Номер 18(6), С. 822 - 822

Опубликована: Май 30, 2025

Background/Objectives: Acute kidney injury (AKI) remains an unsolved medical problem due to the lack of effective treatments, high mortality, and increased susceptibility progression chronic disease (CKD), especially in elderly. Cellular senescence has been described AKI, CKD, aging proposed as a promising therapeutic target. The senolytic drug combination dasatinib plus quercetin (D&Q) is beneficial some pathological conditions, including experimental but there are no data for AKI. Methods: effect D&Q was tested folic acid-induced nephrotoxicity (FAN-AKI), murine AKI model. Results: pretreatment did not prevent renal dysfunction acute phase FAN-AKI, determined by serum creatinine BUN levels at 48 h. Moreover, gene expression damage biomarkers Lcn2 Havcr1, Cdkn1a gene, which encodes p21, genes encoding components senescent cell secretome were significantly response treatment. number p21-positive cells injured kidneys similar untreated or D&Q-treated FAN mice. In addition, downregulation antiaging factor Klotho damaged kidneys. Conclusions: treatment protective exacerbating deleterious responses. These results suggest caution when exploring clinical translation activity.

Язык: Английский

Процитировано

0