NAT10-mediated ac4C acetylation of TFRC promotes sepsis-induced pulmonary injury through regulating ferroptosis

Molecular Medicine, Journal Year: 2024, Volume and Issue: 30(1)

Published: Sept. 9, 2024

Language: Английский

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Identification and mechanistic analysis of shared biomarkers and pathogenesis in acute pancreatitis and sepsis based on differential gene expression and protein interaction networks

Functional & Integrative Genomics, Journal Year: 2025, Volume and Issue: 25(1)

Published: April 17, 2025

Acute pancreatitis (AP) is a common gastrointestinal inflammatory disease that requires hospitalization, with 40-70% of patients in moderate to severe stages potentially developing sepsis, which closely related high mortality rates and poor prognosis. Therefore, early identification AP at risk sepsis crucial for reducing mortality. This study aims identify core genes associated provide new warning management acute pancreatitis. The utilized the GSE54514, GSE57065, GSE95233, GSE194331 datasets analysis, employing weighted gene co-expression network analysis (WGCNA) protein-protein interaction (PPI) construction. Six were identified using two machine learning methods validated GSE3644 GSE28750 datasets. revealed (NDUFA1, COX7A2, COX7B, UQCRQ, SNRPG, NDUFA4) are oxidative phosphorylation (OxPhos) pathway, significant differences observed immune cell composition between patients. SNRPG may play role progression from by regulating NDUFA4, linking it cellular metabolism redox balance. newly their molecular mechanisms important clinical insights into offering research directions future therapeutic strategies. Clinical trial number: was approved Ethics Committee (Municipal Hospital affiliated Taizhou University), accordance Declaration Helsinki. Approval LWSL202400220.

Language: Английский

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NAT10 Regulates LPS-Induced Inflammation via Stabilization of N4-Acetylated PTX3 mRNA in Human Dental Pulp Stem Cells

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(9), P. 4325 - 4325

Published: May 2, 2025

Severe dental pulp inflammation can lead to tissue lysis and destruction, underscoring the necessity for effective treatment of pulpitis. N-acetyltransferase 10 (NAT10)-mediated N4-acetylcytidine (ac4C) modification has recently emerged as a key regulator in inflammatory processes. However, whether NAT10 affects response human stem cells (hDPSCs) remains unelucidated. In this study, elevated expression was observed pulpitis tissues LPS-stimulated hDPSCs. Knockdown led reduced gene lower reactive oxygen species (ROS) production hDPSCs, while chemotactic migration macrophages also suppressed. Similar results were when hDPSCs treated with Remodelin, an inhibitor NAT10. Differentially expressed genes identified through RNA sequencing significantly enriched signaling pathways after depletion. Among differential genes, pentraxins 3 (PTX3) potential target due presence ac4C site its known ability regulate inflammation. The mRNA protein levels PTX3 NAT10-deficient cells, along decrease stability. Exogenous supplementation partially reversed inhibition induced by knockdown. Further evidence vivo revealed that Remodelin attenuated severity rats summary, these data indicated deficiency inhibited stability further hDPSC inflammation, might be therapeutic agent capping.

Language: Английский

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Identification of VDAC1 as a mitochondria-related target of Duchenne muscular dystrophy based on bioinformatics analysis and in vitro experiments

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 158, P. 114836 - 114836

Published: May 12, 2025

Language: Английский

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The possible mechanisms of ferroptosis in sepsis-associated acquired weakness

Frontiers in Physiology, Journal Year: 2024, Volume and Issue: 15

Published: March 27, 2024

Sepsis is a life-threatening organ dysfunction caused by dysregulated host response to infection, and its morbidity mortality rates are increasing annually. It an independent risk factor for intensive care unit-acquired weakness (ICU-AW), which common complication of patients in ICU. This situation also known as sepsis-associated acquired (SAW), it can be more than 60% with sepsis. The outcomes SAW often prolonged mechanical ventilation, extended hospital stays, increased ICUs. pathogenesis unclear, effective clinical treatment not available. Ferroptosis iron-dependent type cell death unique morphological, biochemical, genetic features. Unlike other forms such autophagy, apoptosis, necrosis, ferroptosis primarily driven lipid peroxidation. Cells undergo during sepsis, further enhances the inflammatory response. process leads death, well multi-organ failure. Recently, there have been sporadic reports suggesting that associated ferroptosis, but exact pathophysiological mechanisms remain unclear. Therefore, we reviewed possible offer new strategies prevent treat SAW.

Language: Английский

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GSDMD knockout alleviates sepsis-associated skeletal muscle atrophy by inhibiting IL18/AMPK signaling

Shock, Journal Year: 2024, Volume and Issue: 62(4), P. 565 - 573

Published: Sept. 3, 2024

ABSTRACT Background: Sepsis commonly leads to skeletal muscle atrophy, characterized by substantial weakness and degeneration, ultimately contributing an adverse prognosis. Studies have shown that programmed cell death is important factor in the progression of loss sepsis. However, precise role mechanism pyroptosis atrophy are not yet fully comprehended. Therefore, we aimed examine action effector protein GSDMD recognized cellular mouse models Methods: The levels N-GSDMD were evaluated 2, 4, 8 days after cecal ligation puncture. was produced mice lacked Gsdmd gene (Gsdmd knockout) with normal (wild-type) using a procedure called degree muscular gastrocnemius tibialis anterior muscles assessed 72 h surgery septic model. In addition, architecture muscles, expression, markers associated pathways leading examined from various groups surgery. vitro investigations entailed use siRNA suppress expression C2C12 cells, followed stimulation these cells lipopolysaccharide evaluate impact downregulation on related signaling cascades. Results: This study has demonstrated protein, known as “executive” pyroptosis, plays crucial advancement mice. markedly higher compared control group. knockout exhibited notable enhancements survival, strength, body weight Deletion reduced wasting caused conducted living organisms ( vivo ) laboratory conditions absence decreases indicators sepsis blocking IL18/AMPK pathway. Conclusion: results this demonstrate lack beneficial effect reducing activation inhibiting ubiquitin-proteasome system autophagy pathways. our research provides vital insights into sepsis-related wasting, which could potentially lead development therapeutic interventional approaches for preventing atrophy.

Language: Английский

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Polygonatum sibiricum polysaccharide ameliorates skeletal muscle aging and mitochondrial dysfunction via PI3K/Akt/mTOR signaling pathway

Phytomedicine, Journal Year: 2024, Volume and Issue: 136, P. 156316 - 156316

Published: Dec. 9, 2024

Sarcopenia is currently a life-threatening disease for the elderly. Polygonatum sibiricum polysaccharide (PSP) has anti-oxidative stress and anti-inflammatory effects. However, effects of PSP on skeletal muscle aging, myoblast differentiation mitochondrial dysfunction through PI3K/Akt/mTOR signaling pathway not been explored. To explore related mechanisms dysfunction. The chemical components were determined using UHPLC-MS/MS method. common targets biological pathways between sarcopenia investigated by network pharmacology analysis. In vitro C2C12 cells experiments performed to reveal myotube differentiation, damage. addition, in vivo designed with mouse model D-gal-induced aging evaluate ameliorative impact mass function. mainly included 466 bioactive components. had 278 analysis, which associated function pathway. experiment indicated that significantly enhanced viability down-regulating p21, p53, p16, MuRF1 Atrogin-1and up-regulating MyoD, Myogenin, MyHC. addition LY294002, inhibitor, partially reversed anti-aging PSP. also improved membrane potential decreased ROS levels upregulating phosphorylation experimental data strength, endurance, (quadriceps gastrocnemius) cross-sectional area (CSA) D-gal induced mice. exhibits significant atrophy, as well activating Our study uniquely investigates specific focus pathway, highlights novel therapeutic agent sarcopenia, offering an alternative current treatment strategies.

Language: Английский

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Impact of Alpha-Ketoglutarate on Skeletal Muscle Health and Exercise Performance: A Narrative Review

Nutrients, Journal Year: 2024, Volume and Issue: 16(22), P. 3968 - 3968

Published: Nov. 20, 2024

AKG, a central metabolite in the Krebs cycle, plays vital role cellular energy production and nitrogen metabolism. This review explores AKG's potential therapeutic applications skeletal muscle health exercise performance, focusing on its mechanisms for promoting regeneration counteracting atrophy. A literature search was conducted using PubMed, Web of Science, Scopus databases, yielding 945 articles published up to 31 October 2024. Of these, 112 peer-reviewed met inclusion criteria formed basis this review. AKG supports recovery by stimulating satellite cells (MuSCs) macrophage polarization, aiding repair reducing fibrosis. Additionally, shows promise preventing atrophy enhancing protein synthesis, inhibiting degradation pathways, modulating inflammatory responses, making it relevant conditions like sarcopenia, cachexia, injury recovery. For athletes active individuals, supplementation has enhanced endurance, reduced fatigue, supported faster post-exercise Despite promising preliminary findings, research gaps remain understanding long-term effects, optimal dosage, specific particularly across diverse populations. Further research, including large-scale clinical trials, is essential clarify optimize application as agent diseases an enhancer physical performance. aims provide comprehensive overview benefits identify future directions both sports settings.

Language: Английский

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Identification of ferroptosis-associated genes and potential pharmacological targets in sepsis-induced myopathy

Heliyon, Journal Year: 2024, Volume and Issue: 10(7), P. e29062 - e29062

Published: March 30, 2024

The role of Ferroptosis in the course sepsis-induced myopathy is yet unclear. objective our work to identify key genes connected with and investigate possible pharmaceutical targets related this process. This research aims provide new insights into management myopathy.

Language: Английский

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Molecular mechanisms of Sepsis attacking the immune system and solid organs

Frontiers in Medicine, Journal Year: 2024, Volume and Issue: 11

Published: Aug. 29, 2024

Remarkable progress has been achieved in sepsis treatment recent times, the mortality rate of experienced a gradual decline as result prompt administration antibiotics, fluid resuscitation, and implementation various therapies aimed at supporting multiple organ functions. However, there is still significant room for improvement. The septic patients, 22.5%, unacceptably high, accounting 19.7% all global deaths. Therefore, it crucial to thoroughly comprehend pathogenesis order enhance clinical diagnosis methods. Here, we summarized classic mechanisms progression, activation signal pathways, mitochondrial quality control, imbalance pro-and anti- inflammation response, diseminated intravascular coagulation (DIC), cell death, presented latest research findings each mechanism identify potential therapeutic targets within mechanism.

Language: Английский

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