An overview of mild traumatic brain injuries and emerging therapeutic targets DOI Creative Commons

John P. Bielanin,

Shamseldin Metwally, Satya S. Paruchuri

et al.

Neurochemistry International, Journal Year: 2023, Volume and Issue: 172, P. 105655 - 105655

Published: Dec. 9, 2023

The majority of traumatic brain injuries (TBIs), approximately 90%, are classified as mild (mTBIs). Globally, an estimated 4 million occur each year from concussions or mTBIs, highlighting their significance a public health crisis. TBIs can lead to substantial long-term consequences, including increased risk developing Alzheimer's Disease, Parkinson's Disease (PD), chronic encephalopathy (CTE), and nearly doubling one's suicide. However, the current management mTBIs in clinical practice available treatment options limited. There exists unmet need for effective therapy. This review addresses various aspects based on most up-to-date literature review, with goal stimulating translational research identify new therapeutic targets improve our understanding pathogenic mechanisms. First, we provide summary mTBI symptomatology diagnostic parameters such Glasgow Coma Scale (GCS) classifying concussions, well utility alternative parameters, imaging techniques like MRI diffusion tensor (DTI) serum biomarkers S100B, NSE, GFAP, UCH-L1, NFL, t-tau. Our highlights several pre-clinical concussion models employed study underlying cellular mechanisms involved mTBI-related pathogenesis, axonal damage, demyelination, inflammation, oxidative stress. Finally, examine selection currently under investigation models. These may hold promise translation address pressing more treatments mTBIs.

Language: Английский

Targeting ROS in cancer: rationale and strategies DOI
Christophe Glorieux, Shihua Liu, Dunyaporn Trachootham

et al.

Nature Reviews Drug Discovery, Journal Year: 2024, Volume and Issue: 23(8), P. 583 - 606

Published: July 9, 2024

Language: Английский

Citations

118
The Influence of Gut Microbiota on Oxidative Stress and the Immune System DOI Creative Commons

C Kunst,

Stephan Schmid,

M Michalski

et al.

Biomedicines, Journal Year: 2023, Volume and Issue: 11(5), P. 1388 - 1388

Published: May 8, 2023

The human gastrointestinal tract is home to a complex microbial community that plays an important role in the general well-being of entire organism. gut microbiota generates variety metabolites and thereby regulates many biological processes, such as regulation immune system. In gut, bacteria are direct contact with host. major challenge here prevent unwanted inflammatory reactions on one hand other ensure system can be activated when pathogens invade. Here REDOX equilibrium utmost importance. This controlled by either directly or indirectly via bacterial-derived metabolites. A balanced microbiome sorts for stable balance, whereas dysbiosis destabilizes this equilibrium. An imbalanced status affects disrupting intracellular signaling promoting responses. we (i) focus most common reactive oxygen species (ROS) (ii) define transition from state oxidative stress. Further, (iii) describe ROS regulating Thereafter, (iv) examine influence homeostasis how shifts pro- anti-oxidative cellular conditions suppress promote responses inflammation.

Language: Английский

Citations

76
Nanomaterials‐Induced Redox Imbalance: Challenged and Opportunities for Nanomaterials in Cancer Therapy DOI Creative Commons

Xumeng Wu,

Ziqi Zhou, Kai Li

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(16)

Published: Feb. 21, 2024

Abstract Cancer cells typically display redox imbalance compared with normal due to increased metabolic rate, accumulated mitochondrial dysfunction, elevated cell signaling, and accelerated peroxisomal activities. This may regulate gene expression, alter protein stability, modulate existing cellular programs, resulting in inefficient treatment modalities. Therapeutic strategies targeting intra‐ or extracellular states of cancer at varying state progression trigger programmed death if exceeded a certain threshold, enabling therapeutic selectivity overcoming resistance radiotherapy chemotherapy. Nanotechnology provides new opportunities for modulating their excellent designability high reactivity. Various nanomaterials are widely researched enhance highly reactive substances (free radicals) production, disrupt the endogenous antioxidant defense systems, both. Here, physiological features described challenges illustrated. Then, that classified elaborated upon based on ability target regulations. Finally, future perspectives this field proposed. It is hoped review guidance design nanomaterials‐based approaches involving therapy, especially cancers resistant chemotherapy, etc.

Language: Английский

Citations

26
Mitochondrial Dysfunction in HFpEF: Potential Interventions Through Exercise DOI
Xinxin Cui, Michail Spanos, Cuimei Zhao

et al.

Journal of Cardiovascular Translational Research, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 25, 2025

Language: Английский

Citations

2
The role of HIF-1α in hypoxic metabolic reprogramming in osteoarthritis DOI Creative Commons
Jie Zhang,

Peng Gao,

Weirong Chang

et al.

Pharmacological Research, Journal Year: 2025, Volume and Issue: unknown, P. 107649 - 107649

Published: Feb. 1, 2025

The joint dysfunction caused by osteoarthritis (OA) is increasingly becoming a major challenge in global healthcare, and there currently no effective strategy to prevent the progression of OA. Therefore, better elucidating relevant mechanisms OA occurrence development will provide theoretical basis for formulating new prevention control strategies. Due long-term exposure cartilage tissue hypoxic microenvironment joints, metabolic reprogramming changes occur. Hypoxia-inducible factor-1alpha (HIF-1α), as core gene regulating hypoxia response vivo, plays an important regulatory role metabolism chondrocytes. HIF-1α adapts such glycolysis, oxidative phosphorylation (OXPHOS), amino acid metabolism, lipid In addition, also regulates macrophage polarization synovial inflammation, chondrocytes degeneration extracellular matrix (ECM) degradation, subchondral bone remodeling angiogenesis OA, affects pathophysiological Consequently, regulation has become therapeutic target this article reviews mechanism affecting chondrocyte reprogramming, focusing on summarizes potential ingredients or targets targeting order more beneficial treatment clinical drugs.

Language: Английский

Citations

2
Reactive Oxygen Species: A Crosslink between Plant and Human Eukaryotic Cell Systems DOI Open Access
Wei Guo, Yadi Xing, Xiumei Luo

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(17), P. 13052 - 13052

Published: Aug. 22, 2023

Reactive oxygen species (ROS) are important regulating factors that play a dual role in plant and human cells. As the first messenger response organisms, ROS coordinate signals growth, development, metabolic activity pathways. They also can act as an alarm mechanism, triggering cellular responses to harmful stimuli. However, excess cause oxidative stress-related damage oxidize organic substances, leading malfunctions. This review summarizes current research status mechanisms of eukaryotic cells, highlighting differences similarities between two elucidating their interactions with other reactive substances ROS. Based on similar regulatory pathways kingdoms, this proposes future developments provide opportunities develop novel strategies for treating diseases or creating greater agricultural value.

Language: Английский

Citations

35
NOX4 as a critical effector mediating neuroinflammatory cytokines, myeloperoxidase and osteopontin, specifically in astrocytes in the hippocampus in Parkinson's disease DOI Creative Commons
Napissara Boonpraman,

Sunmi Yoon,

Chae Young Kim

et al.

Redox Biology, Journal Year: 2023, Volume and Issue: 62, P. 102698 - 102698

Published: April 10, 2023

Oxidative stress and mitochondrial dysfunction have been believed to play an important role in the pathogenesis of aging neurodegenerative diseases, including Parkinson's disease (PD). The excess reactive oxygen species (ROS) increases with age causes a redox imbalance, which contributes neurotoxicity PD. Accumulating evidence suggests that NADPH oxidase (NOX)-derived ROS, especially NOX4, belong NOX family is one major isoforms expressed central nervous system (CNS), associated progression We previously shown NOX4 activation regulates ferroptosis via astrocytic dysfunction. through astrocytes. However, it remains unclear why increase diseases leads astrocyte cell death by certain mediators. Therefore, this study was designed evaluate how hippocampus involved PD comparing MPTP-induced mouse model compared human patients. could detect dominantly elevated levels α-synuclein during neuroinflammatory cytokines, myeloperoxidase (MPO) osteopontin (OPN), were upregulated particularly Intriguingly, suggested direct intercorrelation MPO OPN hippocampus. Upregulation induces suppressing five protein complexes electron transport (ETC) level 4-HNE leading Overall, our findings indicate elevation cooperated inflammatory cytokines aberration hippocampal astrocytes

Language: Английский

Citations

27
Dietary Polyphenols, Microbiome, and Multiple Sclerosis: From Molecular Anti-Inflammatory and Neuroprotective Mechanisms to Clinical Evidence DOI Open Access
Giuliana La Rosa, Maria Serena Lonardo, Nunzia Cacciapuoti

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(8), P. 7247 - 7247

Published: April 14, 2023

Multiple sclerosis (MS) is a multifactorial, immune-mediated disease caused by complex gene-environment interactions. Dietary factors modulating the inflammatory status through control of metabolic and pathways composition commensal gut microbiota, are among main environmental involved in pathogenesis MS. There no etiological therapy for MS drugs currently used, often accompanied major side effects, represented immunomodulatory substances capable modifying course disease. For this reason, nowadays, more attention paid to alternative therapies with natural anti-inflammatory antioxidant as adjuvants classical therapies. Among beneficial effects on human health, polyphenols assuming an increasing interest due their powerful antioxidant, anti-inflammatory, neuroprotective effects. Beneficial properties CNS achieved direct depending ability cross blood-brain barrier indirect exerted part via interaction microbiota. The aim review examine literature about molecular mechanism underlying protective experiments conducted vitro animal models Significant data have been accumulated resveratrol, curcumin, luteolin, quercetin, hydroxytyrosol, therefore we will focus results obtained these polyphenols. Clinical evidence use adjuvant restricted smaller number substances, mainly curcumin epigallocatechin gallate. In last review, clinical trial studying patients also be revised.

Language: Английский

Citations

22
Factors Influencing Venous Remodeling in the Development of Varicose Veins of the Lower Limbs DOI Open Access
Łukasz Gwoździński, Anna Pieniążek, Krzysztof Gwoździński

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(3), P. 1560 - 1560

Published: Jan. 26, 2024

One of the early symptoms chronic venous disease (CVD) is varicose veins (VV) lower limbs. There are many etiological environmental factors influencing development insufficiency (CVI), although genetic and family history play a key role. All these induce changes in hemodynamic system limbs leading to blood stasis, hypoxia, inflammation, oxidative stress, proteolytic activity matrix metalloproteinases (MMPs), microcirculation and, consequently, remodeling wall. The aim this review present current knowledge on CVD, including pathophysiology mechanisms related vein wall remodeling. Particular emphasis has been placed describing role inflammation stress involvement extracellular hemoglobin as pathogenetic VV. Additionally, active substances used treatment VV were discussed.

Language: Английский

Citations

14
Diabetic Retinopathy: New Treatment Approaches Targeting Redox and Immune Mechanisms DOI Creative Commons
Qi Tang, Francesco Buonfiglio, Elsa Wilma Böhm

et al.

Antioxidants, Journal Year: 2024, Volume and Issue: 13(5), P. 594 - 594

Published: May 12, 2024

Diabetic retinopathy (DR) represents a severe complication of diabetes mellitus, characterized by irreversible visual impairment resulting from microvascular abnormalities. Since the global prevalence continues to escalate, DR has emerged as prominent area research interest. The development and progression encompass complex interplay pathological physiological mechanisms, such high glucose-induced oxidative stress, immune responses, vascular endothelial dysfunction, well damage retinal neurons. Recent years have unveiled involvement genomic epigenetic factors in formation mechanisms. At present, extensive explores potential biomarkers cytokines, molecular cell therapies, antioxidant interventions, gene therapy for treatment. Notably, certain drugs, anti-VEGF agents, antioxidants, inhibitors inflammatory protein kinase C (PKC)-β inhibitors, demonstrated promising outcomes clinical trials. Within this context, review article aims introduce recent on highlight current progress field, with particular focus emerging experimental treatment strategies targeting redox signaling pathways.

Language: Английский

Citations

13