SP1/CTR1 mediated oxidative stress-induced cuproptosis in intervertebral disk degeneration DOI Creative Commons
Yizhong Peng,

Xuanzuo Chen,

Kanglu Li

et al.

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: March 14, 2023

Abstract Intervertebral disk degeneration (IDD) is the primary pathology responsible for lower back pain. Oxidative stress-induced cell death plays a fundamental role in IDD pathogenesis. Cuproptosis recently discovered form of programmed dependent on copper availability. Whether cuproptosis involved progression remains unknown. Herein, we established vitro and vivo models to investigate presence mechanisms by which oxidative stress interacts with sensitivity nucleus pulposus cells (NPCs). We found that expression key regulator ferrodoxin-1 (FDX1) increased both rat human disks. Sublethal NPCs led FDX1 Cu 2+ at physiological concentrations, whereas knockdown inhibited death. Since homeostasis copper-induced cytotoxicity, investigated transport-related proteins, including importers (transporter transporter 1 [CTR1] ) efflux pumps (ATPase transporter, ATP7A, ATP7B). CTR1 ATP7A under stress, blocking significantly reduced stress/copper-induced Moreover, promoted specific protein (SP1) SP1-mediated transcription. SP1 inhibition improved viability decreased rates, was reversed administration elesclomol, ionophore. Importantly, preserved hydration alleviated tissue degeneration. This suggest mediates increasing flux through promotion study highlights importance provides promising therapeutic target treatment.

Language: Английский

Research Progress on the Mechanism of Sepsis Induced Myocardial Injury DOI Creative Commons

Cheng-Fei Bi,

Jia Liu,

Lishan Yang

et al.

Journal of Inflammation Research, Journal Year: 2022, Volume and Issue: Volume 15, P. 4275 - 4290

Published: July 1, 2022

Abstract: Sepsis is an abnormal condition with multiple organ dysfunctions caused by the uncontrolled infection response and one of major diseases that seriously hang over global human health. Besides, sepsis characterized high morbidity mortality, especially in intensive care unit (ICU). Among numerous subsequent injuries sepsis, myocardial injury most common complications main cause death septic patients. To better manage inpatients, it necessary to understand specific mechanisms induced (SIMI). Therefore, this review will elucidate pathophysiology SIMI from following certain mechanisms: apoptosis, mitochondrial damage, autophagy, excessive inflammatory response, oxidative stress pyroptosis, outline current therapeutic strategies potential approaches SIMI. Keywords: injury, mechanism, signaling pathway

Language: Английский

Citations

49
SP1/CTR1‐mediated oxidative stress‐induced cuproptosis in intervertebral disc degeneration DOI Creative Commons

Xuanzuo Chen,

Kanglu Li,

Yan Xiao

et al.

BioFactors, Journal Year: 2024, Volume and Issue: 50(5), P. 1009 - 1023

Published: April 10, 2024

Abstract Intervertebral disc degeneration (IDD) is an age‐related disease and responsible for low back pain. Oxidative stress‐induced cell death plays a fundamental role in IDD pathogenesis. Cuproptosis recently discovered form of programmed dependent on copper availability. Whether cuproptosis involved progression remains unknown. Herein, we established vitro vivo models to investigate the mechanisms by which oxidative stress interacts with sensitivity nucleus pulposus cells (NPCs). We found that ferredoxin‐1 (FDX1) content increased both rat human degenerated discs. Sublethal NPCs led FDX1 expression, tricarboxylic acid (TCA) cycle‐related proteins lipoylation aggregation, presence Cu 2+ at physiological concentrations, while knockdown inhibited death. Since homeostasis copper‐induced cytotoxicity, investigated transport‐related proteins, including importer (CTR1) efflux pumps (ATPase transporter, ATP7A, ATP7B). CTR1 ATP7A under stress, blocking reduced stress/copper‐induced TCA‐related protein aggregation Moreover, promoted expression specific 1 (SP1) SP1‐mediated transcription. SP1 inhibition decreased rates, preserved hydration, alleviated tissue degeneration. This suggests upregulates flux through promoting transcription, leading TCA cuproptosis. study highlights importance provides promising therapeutic target treatment.

Language: Английский

Citations

10
Interaction and Collaboration of SP1, HIF-1, and MYC in Regulating the Expression of Cancer-Related Genes to Further Enhance Anticancer Drug Development DOI Creative Commons
Kotohiko Kimura,

Tiffany L. B. Jackson,

Ru Chih C. Huang

et al.

Current Issues in Molecular Biology, Journal Year: 2023, Volume and Issue: 45(11), P. 9262 - 9283

Published: Nov. 17, 2023

Specificity protein 1 (SP1), hypoxia-inducible factor (HIF-1), and MYC are important transcription factors (TFs). SP1, a constitutively expressed housekeeping gene, regulates diverse yet distinct biological activities; is master regulator of all key cellular activities including cell metabolism proliferation; HIF-1, whose level rapidly increased when the local tissue oxygen concentration decreases, functions as mediator hypoxic signals. Systems analyses regulatory networks in cancer have shown that belong to group TFs function regulators cancer. Therefore, contributions these crucial development often overexpressed tumors, which indicates importance their roles Thus, proper manipulation by appropriate agents could strong negative impact on development. Under circumstances, naturally become major targets for anticancer drug Accordingly, there currently many SP1 or HIF-1 inhibitors available; however, designing efficient has been extremely difficult. Studies modulate expression each other collaborate regulate numerous genes. In this review, we provide an overview interactions collaborations HIF1A, regulation various cancer-related genes, potential implications therapy.

Language: Английский

Citations

14
Deciphering the molecular and cellular atlas of immune cells in septic patients with different bacterial infections DOI Creative Commons
Ping Sun, Mintian Cui,

Jiongjie Jing

et al.

Journal of Translational Medicine, Journal Year: 2023, Volume and Issue: 21(1)

Published: Nov. 2, 2023

Abstract Background Sepsis is a life-threatening organ dysfunction caused by abnormal immune responses to various, predominantly bacterial, infections. Different bacterial infections lead substantial variation in disease manifestation and therapeutic strategies. However, the underlying cellular heterogeneity mechanisms involved remain poorly understood. Methods Multiple bulk transcriptome datasets from septic patients with 12 types of were integrated identify signature genes for each infection. Signature mapped onto an large single-cell RNA (scRNA) dataset patients, subsets cells associated different sepsis types, multiple omics combined reveal molecular mechanisms. In addition, scRNA spatial data used signaling pathways sepsis-related cells. Finally, screening, optimization, de novo design conducted potential targeted drugs compounds. Results We elucidated among Escherichia coli ( E. ) sepsis, 19 epigenetic regulation metabolism identified, which DRAM1 was demonstrated promote autophagy glycolysis response upregulation confirmed independent cohort. Further, we showed that could maintain survival pro-inflammatory monocyte subset, C10_ULK1, induces systemic inflammation interacting other cell via resistin integrin blood kidney tissue, respectively. retapamulin identified optimized as drug treatment targeting gene, , inhibiting protein synthesis. Several also including nystatin C1QA Neisseria dalfopristin CTSD Streptococcus viridans sepsis. Conclusion Our study provides comprehensive overview various infections, providing insights inform development stratified therapies

Language: Английский

Citations

12
Pretreatment with Indole-3-Propionic Acid Attenuates Lipopolysaccharide-Induced Cardiac Dysfunction and Inflammation Through the AhR/NF-κB/NLRP3 Pathway DOI Creative Commons
Yiqiong Zhang, Shanshan Li, Xiaojuan Fan

et al.

Journal of Inflammation Research, Journal Year: 2024, Volume and Issue: Volume 17, P. 5293 - 5309

Published: Aug. 1, 2024

Patients with sepsis frequently develop septic cardiomyopathy, which is known to be closely related excessive inflammatory responses. Indole-3-propionic acid (IPA) a tryptophan metabolite anti-inflammatory properties that have been demonstrated in various studies. In this study, we investigated the underlying mechanisms and therapeutic role of IPA cardiomyopathy.

Language: Английский

Citations

4
Natural carbazole alkaloid murrayafoline A displays potent anti-neuroinflammatory effect by directly targeting transcription factor Sp1 in LPS-induced microglial cells DOI
Chaohua Li, Ying Zhou, Pengfei Tu

et al.

Bioorganic Chemistry, Journal Year: 2022, Volume and Issue: 129, P. 106178 - 106178

Published: Sept. 28, 2022

Language: Английский

Citations

17
MicroRNAs as regulators of cardiac dysfunction in sepsis: pathogenesis and diagnostic potential DOI Creative Commons
Zhen Liu, Feiyang Li,

Ningcen Li

et al.

Frontiers in Cardiovascular Medicine, Journal Year: 2025, Volume and Issue: 12

Published: Feb. 18, 2025

Sepsis, a life-threatening condition arising from an uncontrolled immune response to infection, can lead organ dysfunction, with severe inflammation potentially causing multiple failures. Sepsis-induced cardiac dysfunction (SIMD) is common and complication of sepsis, significantly increasing patient mortality. Understanding the pathogenesis SIMD crucial for improving treatment, microRNAs (miRNAs) have emerged as important regulators in this process. A comprehensive literature search was conducted PubMed, Science Direct, Embase databases up September 2024. The terms included ["miRNA" or "microRNA"] ["Cardiac" "Heart"] ["Sepsis" "Septic"], language limited English. After initial filtering by database engine, Excel software used further screen references. Duplicate articles, those without abstracts full texts, review/meta-analyses non-English articles were excluded. Finally, 106 relevant research data extraction analysis. complex involves mitochondrial oxidative stress, cardiomyocyte apoptosis pyroptosis, dysregulation myocardial calcium homeostasis, inhibitory factors, autonomic nervous regulation disorders, hemodynamic changes, structural alterations. miRNAs play diverse roles SIMD. They are involved regulating above-mentioned pathological processes. Although significant progress has been made understanding role SIMD, there still challenges. Some studies on limitations such small sample sizes failure account confounding factors. Research also faces issues like inconsistent measurement techniques unclear miRNA-target gene relationships. Moreover, translation miRNA-based into clinical applications hindered problems related miRNA stability, delivery mechanisms, off-target effects, long-term safety. In conclusion, potential diagnostic biomarkers. Further needed overcome existing challenges fully exploit diagnosis treatment

Language: Английский

Citations

0
Isolation, purification, characterization and immunomodulatory effects of polysaccharides from Dictyophora rubrovalvata waste DOI

Kaisheng Bao,

Mingyang Song, Shanshan Wang

et al.

Industrial Crops and Products, Journal Year: 2023, Volume and Issue: 206, P. 117754 - 117754

Published: Nov. 2, 2023

Language: Английский

Citations

9
Role of Specificity Protein 1 (SP1) in Cardiovascular Diseases: Pathological Mechanisms and Therapeutic Potentials DOI Creative Commons
Jie Ding,

Aminah I. Fayyaz,

Yuchuan Ding

et al.

Biomolecules, Journal Year: 2024, Volume and Issue: 14(7), P. 807 - 807

Published: July 7, 2024

In mammals, specificity protein 1 (SP1) was the first Cys2-His2 zinc finger transcription factor to be isolated within and Krüppel-like (Sp/KLF) gene family. SP1 regulates expression by binding Guanine–Cytosine (GC)-rich sequences on promoter regions of target genes, affecting various cellular processes. Additionally, activity is markedly influenced posttranslational modifications, such as phosphorylation, acetylation, glycosylation, proteolysis. implicated in regulation apoptosis, cell hypertrophy, inflammation, oxidative stress, lipid metabolism, plaque stabilization, endothelial dysfunction, fibrosis, calcification, other pathological These processes impact onset progression numerous cardiovascular disorders, including coronary heart disease, ischemia-reperfusion injury, cardiomyopathy, arrhythmia, vascular disease. emerges a potential for prevention therapeutic intervention cardiac ailments. this review, we delve into biological functions, pathophysiological mechanisms, clinical implications pathology offer valuable insights regulatory functions diseases unveil novel avenues treatment conditions.

Language: Английский

Citations

3
Exogenous fetuin‐A protects against sepsis‐induced myocardial injury by inhibiting oxidative stress and inflammation in mice DOI

V Sidheeque Hassan,

Mohd Hanifa,

Umashanker Navik

et al.

Fundamental and Clinical Pharmacology, Journal Year: 2023, Volume and Issue: 37(3), P. 607 - 617

Published: Jan. 17, 2023

Sepsis-induced myocardial injury is a consequence of septicemia and one the major causes death in intensive care units. A serum glycoprotein called fetuin-A secreted largely by liver, tongue, placenta, adipose tissue. Fetuin-A has variety biological pharmacological properties. The anti-inflammatory antioxidant shown its efficacy number inflammatory disorders including sepsis. However, protective role against sepsis-induced remains elusive. purpose this work to explore mouse models brought on cecal ligation puncture (CLP). CLP significantly induced assessed terms elevated markers (serum CK-MB, cTnI levels), (IL-6, TNF-α) serum, oxidative stress (increased MDA levels decreased reduced glutathione) heart tissue homogenate following 24 h puncture. Further, hematoxylin eosin (H&E) staining showed considerable histological alterations sepsis-developed mice. Interestingly, pretreatment (50 100 mg/kg) for 4 days before procedure improved was evaluated perspective reduction levels, IL-6, TNF-α animals. attenuated morphology dose-dependent manner. present study provides preliminary evidence that exerts protection cardiac dysfunction vivo via suppression inflammation damage.

Language: Английский

Citations

8