Exploring Infantile Epileptic Spasm Syndrome: A Proteomic Analysis of Plasma Using the Data-Independent Acquisition Approach DOI Creative Commons

Haohua Huang,

Dezhi Cao, Yan Hu

et al.

Journal of Proteome Research, Journal Year: 2024, Volume and Issue: 23(10), P. 4316 - 4326

Published: June 10, 2024

This study aimed to identify characteristic proteins in infantile epileptic spasm syndrome (IESS) patients' plasma, offering insights into potential early diagnostic biomarkers and its underlying causes. Plasma samples were gathered from 60 patients with IESS 40 healthy controls. Data-independent acquisition proteomic analysis was utilized differentially expressed (DEPs). These DEPs underwent functional annotation through Gene Ontology (GO) the Kyoto Encyclopedia of Genes Genomes (KEGG) pathway enrichment analyses. set (GSEA) employed for both GO (GSEA-GO) KEGG (GSEA-KEGG) analyses examine gene expression profiles. Receiver operating (ROC) curves assessed biomarkers' discriminatory capacity. A total 124 identified mainly linked pathways, encompassing chemokines, cytokines, oxidative detoxification. GSEA-GO GSEA-KEGG indicated significant genes associated cell migration, focal adhesion, phagosome pathways. ROC curve demonstrated that combination PRSS1 ACTB, PRSS3, alone exhibited AUC values exceeding 0.7. elucidated contribution detoxification, phagosomes pathogenesis. The ACTB holds promise as diagnosis IESS.

Language: Английский

Mitochondrial dysfunction and neurological disorders: A narrative review and treatment overview DOI
Eman E. Alshial,

Muhammad Idris Abdulghaney,

Al-Hassan Soliman Wadan

et al.

Life Sciences, Journal Year: 2023, Volume and Issue: 334, P. 122257 - 122257

Published: Nov. 8, 2023

Language: Английский

Citations

52
The interplay between microbiota and brain-gut axis in epilepsy treatment DOI Creative Commons
Hanxiao Zhu, Wei Wang, Yun Li

et al.

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

Published: Jan. 26, 2024

The brain-gut axis plays a vital role in connecting the cognitive and emotional centers of brain with intricate workings intestines. An imbalance microbiota-mediated extends far beyond conditions like Irritable Bowel Syndrome (IBS) obesity, playing critical development progression various neurological disorders, including epilepsy, depression, Alzheimer’s disease (AD), Parkinson’s (PD). Epilepsy, disorder characterized by unprovoked seizures, affects approximately 50 million people worldwide. Accumulating evidence suggests that rebuilding gut microbiota through interventions such as fecal transplantation, probiotics, ketogenic diets (KD) can benefit drug-resistant epilepsy. disturbances could contribute to toxic side effects antiepileptic drugs drug resistance epilepsy patients. These findings imply potential impact on suggest targeting microbiota, KD, hold promise for managing treating However, full extent importance treatment is not yet fully understood, many aspects this field remain unclear. Therefore, article aims provide an overview clinical animal supporting regulatory pathways within may be influenced Furthermore, we will discuss recent advancements treatment, antiseizure drugs, all from perspective microbiota.

Language: Английский

Citations

20
Poly (ADP-Ribose) polymerase 1 and parthanatos in neurological diseases: From pathogenesis to therapeutic opportunities DOI Creative Commons
Xiaoxue Xu, Bowen Sun, Chuansheng Zhao

et al.

Neurobiology of Disease, Journal Year: 2023, Volume and Issue: 187, P. 106314 - 106314

Published: Oct. 1, 2023

Poly (ADP-ribose) polymerase-1 (PARP-1) is the most extensively studied member of PARP superfamily, with its primary function being facilitation DNA damage repair processes. Parthanatos a type regulated cell death cascade initiated by PARP-1 hyperactivation, which involves multiple subroutines, including accumulation ADP-ribose polymers (PAR), binding PAR and apoptosis-inducing factor (AIF), release AIF from mitochondria, translocation AIF/macrophage migration inhibitory (MIF) complex, massive MIF-mediated fragmentation. Over past few decades, role in central nervous system health disease has received increasing attention. In this review, we discuss biological functions neural proliferation differentiation, memory formation, brain ageing, epigenetic regulation. We then elaborate on involvement PARP-1-dependant parthanatos various neuropathological processes, such as oxidative stress, neuroinflammation, mitochondrial dysfunction, excitotoxicity, autophagy damage, endoplasmic reticulum (ER) stress. Additional highlight contains PARP-1's implications initiation, progression, therapeutic opportunities for different neurological illnesses, neurodegenerative diseases, stroke, autism spectrum disorder (ASD), sclerosis (MS), epilepsy, neuropathic pain (NP). Finally, emerging insights into repurposing inhibitors management diseases are provided. This review aims to summarize exciting advancements critical disorders, may open new avenues options targeting or parthanatos.

Language: Английский

Citations

29
Advances in the mTOR signaling pathway and its inhibitor rapamycin in epilepsy DOI Creative Commons
Wei Zhao, Cong Xie, Xu Zhang

et al.

Brain and Behavior, Journal Year: 2023, Volume and Issue: 13(6)

Published: May 23, 2023

Abstract Introduction Epilepsy is one of the most common and serious brain syndromes has adverse consequences on a patient's neurobiological, cognitive, psychological, social wellbeing, thereby threatening their quality life. Some patients with epilepsy experience poor treatment effects due to unclear pathophysiological mechanisms syndrome. Dysregulation mammalian target rapamycin (mTOR) pathway thought play an important role in onset progression some epilepsies. Methods This review summarizes mTOR signaling pathogenesis prospects for use inhibitors. Results The functions as vital mediator development through diverse mechanisms, indicating that it great potential effective therapy. excessive activation leads structural changes neurons, inhibits autophagy, exacerbates neuron damage, affects mossy fiber sprouting, enhances neuronal excitability, increases neuroinflammation, closely associated tau upregulation epilepsy. A growing number studies have demonstrated inhibitors exhibit significant antiepileptic both clinical applications animal models. Specifically, rapamycin, specific inhibitor TOR, reduces intensity frequency seizures. Clinical tuberous sclerosis complex shown function reducing seizures improving this disease. Everolimus, chemically modified derivative been approved added other medicines. Further explorations are needed evaluate therapeutic efficacy application value Conclusions Targeting provides promising prospect

Language: Английский

Citations

28
Molecular regulation and therapeutic implications of cell death in pulmonary hypertension DOI Creative Commons
Enze Wang,

Sijing Zhou,

Daxiong Zeng

et al.

Cell Death Discovery, Journal Year: 2023, Volume and Issue: 9(1)

Published: July 12, 2023

Abstract Pulmonary hypertension (PH) is a clinical and pathophysiological syndrome caused by changes in pulmonary vascular structure or function that results increased resistance arterial pressure, it characterized endothelial dysfunction, artery media thickening, remodeling, right ventricular hypertrophy, all of which are driven an imbalance between the growth death cells. Programmed cell (PCD), different from necrosis, active cellular mechanism activated response to both internal external factors precisely regulated More than dozen PCD modes have been identified, among apoptosis, autophagy, pyroptosis, ferroptosis, necroptosis, cuproptosis proven be involved pathophysiology PH varying degrees. This article provides summary regulatory patterns their potential effects on PH. Additionally, describes current understanding this complex interconnected process analyzes therapeutic targeting specific as molecular targets.

Language: Английский

Citations

19
Role and mechanisms of autophagy, ferroptosis, and pyroptosis in sepsis-induced acute lung injury DOI Creative Commons

Yao Shen,

Yingying He, Ying Pan

et al.

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

Published: Aug. 5, 2024

Sepsis-induced acute lung injury (ALI) is a major cause of death among patients with sepsis in intensive care units. By analyzing model sepsis-induced ALI using lipopolysaccharide (LPS) and cecal ligation puncture (CLP), treatment methods strategies to protect against were discussed, which could provide an experimental basis for the clinical ALI. Recent studies have found that imbalance autophagy, ferroptosis, pyroptosis key mechanism triggers ALI, regulating these mechanisms can improve injuries caused by LPS or CLP. This article summarized reviewed regulatory networks their important roles process LPS/CLP-induced sepsis, discusses possible targeted drugs above effects, describes dilemma prospects, provides new perspectives future

Language: Английский

Citations

8
Chinese herbal medicine and its active compounds in attenuating renal injury via regulating autophagy in diabetic kidney disease DOI Creative Commons
Peng Liu, Wenhui Zhu, Yang Wang

et al.

Frontiers in Endocrinology, Journal Year: 2023, Volume and Issue: 14

Published: March 3, 2023

Diabetic kidney disease (DKD) is the main cause of end-stage renal worldwide, and there a lack effective treatment strategies. Autophagy highly conserved lysosomal degradation process that maintains homeostasis energy balance by removing protein aggregates damaged organelles. Increasing evidence suggests dysregulated autophagy may contribute to glomerular tubulointerstitial lesions in under diabetic conditions. Emerging studies have shown Chinese herbal medicine its active compounds ameliorate injury regulating autophagy. In this review, we summarize dysregulation or insufficiency cells, including podocytes, mesangial proximal tubular epithelial key mechanism for development DKD, focus on protective effects compounds. Moreover, systematically reviewed DKD regulated herb compound preparations, single compounds, so as provide new drug candidates clinical DKD. Finally, also candidate targets Therefore, further research with regulation their great significance realization targeted therapies

Language: Английский

Citations

16
The role of LncRNA-mediated autophagy in cancer progression DOI Creative Commons

Zi-Yuan Liu,

Jiaming Tang,

Meng-Qi Yang

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 12

Published: June 12, 2024

Long non-coding RNAs (lncRNAs) are a sort of transcripts that more than 200 nucleotides in length. In recent years, many studies have revealed the modulatory role lncRNAs cancer. Typically, linked to variety essential events, such as apoptosis, cellular proliferation, and invasion malignant cells. Simultaneously, autophagy, an intracellular degradation mechanism eukaryotic cells, is activated respond multiple stressful circumstances, for example, nutrient scarcity, accumulation abnormal proteins, organelle damage. Autophagy plays both suppressive promoting roles Increasingly, unveiled how dysregulated expression can disrupt autophagic balance, thereby contributing cancer progression. Consequently, exploring interplay between autophagy holds promising implications clinical research. this manuscript, we methodically compiled advances molecular mechanisms briefly summarized lncRNA-mediated axis.

Language: Английский

Citations

6
Trpm2 deficiency in microglia attenuates neuroinflammation during epileptogenesis by upregulating autophagy via the AMPK/mTOR pathway DOI Creative Commons
Chen Chen, Tao Zhu,

Lifen Gong

et al.

Neurobiology of Disease, Journal Year: 2023, Volume and Issue: 186, P. 106273 - 106273

Published: Aug. 28, 2023

Epilepsy is one of the most common neurological disorders. Neuroinflammation involving activation microglia and astrocytes constitutes an important mechanism in epileptogenesis. Transient receptor potential melastatin 2 (TRPM2) a calcium-permeable, non-selective cation channel that plays pathological roles various inflammation-related diseases. Our previous study demonstrated Trpm2 knockout exhibits therapeutic effects on pilocarpine-induced glial neuroinflammation. However, whether TRPM2 pathogenic role this process underlying molecular mechanisms remained undetermined. Here, we demonstrate previously unknown for microglial attenuated kainic acid (KA)-induced activation, inflammatory cytokines production hippocampal paroxysmal discharges, whereas exhibited no significant effects. Furthermore, discovered these were mediated by upregulated autophagy via adenosine monophosphate activated protein kinase (AMPK)/mammalian target rapamycin (mTOR) pathway microglia. Thus, our findings highlight deleterious temporal lobe epilepsy.

Language: Английский

Citations

11
Dexmedetomidine Alleviates Ischemia/Reperfusion-Associated Acute Kidney Injury by Enhancing Autophagic Activity via the α2-AR/AMPK/mTOR Pathway DOI Creative Commons

Biying Zhou,

Jing Yang,

Rui-Rui Luo

et al.

Frontiers in Bioscience-Landmark, Journal Year: 2023, Volume and Issue: 28(12), P. 323 - 323

Published: Dec. 1, 2023

Background: Dexmedetomidine (DEX) reportedly protects against ischemia-reperfusion (I/R) injury and associated damage to the kidneys, but underlying mechanisms have yet be established. Methods: Unilateral nephrectomy was performed in Wistar rats, remaining kidney clamped for 1 h prior reperfusion establish an experimental model system. These animals were then randomized into Sham, DEX + I/R, ATI (Altepamizole, α2-adrenergic receptor inhibitor) 3-MA (3-methyladenine, autophagy I/R groups. Serum renal function biomarkers, acute (AKI) histopathological scores, serum inflammatory factors, redox markers of autophagic flux, autophagosome numbers assessed. Levels proteins related pathway, including mTOR AMPK, also analyzed. Results: creatinine urea nitrogen levels group significantly elevated over those sham control as AKI cytokine concentrations (IL-6, IL-1β, TNF-α), oxidative stress biomarker malondialdehyde (MDA). All these parameters reduced relative rats. rats exhibited significant decreases flux-related biomarkers controls, while administration partially restored normal flux Acute suppress expression AMPK increasing expression, reversed effects. The beneficial impact on I/R-associated ablated by or administration. Conclusions: analyses provide strong evidence ability protect via α2-AR/AMPK/mTOR pathway-mediated enhancement activity.

Language: Английский

Citations

10