bims-mistre 2025-04-13 papers

bims-mistre

Biomed News

on Mito stress

Issue of 2025–04–13
twenty-two papers selected by
Ellen Siobhan Mitchell, MitoQ

The development of mitochondria-targeted quercetin for rescuing Sertoli cells from oxidative stress.
The Protective Effect of Ellagic Acid and Its Metabolites Against Organ Injuries: A Mitochondrial Perspective.
Editorial: Targeting the aging mitochondria: mechanisms, methods, and therapeutic strategies.
Exploring mitochondrial dynamics and localization under cellular stress: A comprehensive insight.
Oxidative Stress and Redox Imbalance: Common Mechanisms in Cancer Stem Cells and Neurodegenerative Diseases.
Fatty acid binding proteins-mediated mitochondrial dysfunction in the development of age-related diseases: A review.
Unraveling the cGAS-STING pathway in Alzheimer's disease: A new Frontier in neuroinflammation and therapeutic strategies.
Diet induced insulin resistance is due to induction of PTEN expression.
Miro1- a key player in β-cell function and mitochondrial dynamics under diabetes mellitus.
Cardiac Energy Metabolism in Diabetes: Emerging Therapeutic Targets and Clinical Implications.
Exploring the nexus: Sleep disorders, circadian dysregulation, and Alzheimer's disease.
A review on bacteria-derived antioxidant metabolites: their production, purification, characterization, potential applications, and limitations.
Effects and Mechanisms of Steviol Glycosides on Glucose Metabolism: Evidence From Preclinical Studies.
Nampt as a new therapeutic target for modulating NAD+ levels in metabolic, cardiovascular and neurodegenerative diseases.
The Impact of Liraglutide, a GLP-1 Receptor Agonist, on High Glucose-Induced Inflammation, Apoptosis, Oxidative Stress, and NLRP3 Signaling.
Identifying blood mitochondrial DNA copy number as a biomarker for development of neurodegenerative diseases: Evidence from Mendelian randomization analysis.
Effect of probiotics on cognitive function and cardiovascular risk factors in mild cognitive impairment and Alzheimer's disease: an umbrella meta-analysis.
Perimenopausal depression: Targeting inflammation and oxidative stress (Review).
Withania somnifera Regulates Mitochondrial Biogenesis and Energetics in Rat Cortical Neurons: Role of BDNF and SIRT1.
Liraglutide attenuates high glucose-induced endothelial cell senescence and dysfunction via SIRT1-mediated deacetylation of p53/p65.
The Multifaceted Role of Neuroprotectin D1: Physiological, Pathophysiological, and Pharmacological Insights in Neurodegenerative Diseases.
Curcumin targets YAP1 to enhance mitochondrial function and autophagy, protecting against UVB-induced photodamage.

Res Pharm Sci. 2025 Feb;20(1): 109-120

The development of mitochondria-targeted quercetin for rescuing Sertoli cells from oxidative stress.

Satrialdi, Cellina Pratiwi, Ryan Novia Khaeranny, Diky Mudhakir.

   Background and purpose: The imbalance between reactive oxygen species (ROS) production and endogenous antioxidant capacity leads to oxidative stress, which may damage several cellular functions, particularly spermatogenesis. This condition is a leading cause of male infertility, so controlling ROS levels is crucial. The ROS level can be controlled by supporting the endogenous antioxidant system through antioxidant therapy. Mitochondria are the prime target for antioxidant therapy due to the majority of endogenous ROS produced in mitochondria and their critical role in providing energy during fertilization. This research aimed to develop mitochondria-targeted hybrid nanoplatforms by combining liposomes with dequalinium's mitochondriotropic agent (DQ) to deliver quercetin for targeted antioxidant therapy to mitochondria.
Experimental approach: The quercetin-loaded nanocarrier was constructed using the hydration method. We varied the concentration of DQ to investigate its impact on physical characteristics, encapsulation efficiency, intracellular trafficking, and in vitro antioxidant activity.
Findings/Results: The impact of different DQ densities on particle size, encapsulation efficiency, and mitochondria targeting was insignificant. However, lowering the DQ density reduced the zeta potential. Minimizing oxidative stress on TM4 cells was only achieved with low-density DQ (Q-LipoDQ LD), while high-density DQ (Q-LipoDQ HD) failed to mitigate the negative impact.
Conclusion and implications: According to the findings, LipoDQ LD preserves a promising potential as mitochondria-targeted nanoplatforms and validates the importance of mitochondria as a target for antioxidant therapy.

Keywords:  Antioxidant; Mitochondria-targeted drug delivery system; Sertoli cells; Therapy

DOI:  https://doi.org/10.4103/RPS.RPS_226_23
Food Sci Nutr. 2025 Apr;13(4): e70077

The Protective Effect of Ellagic Acid and Its Metabolites Against Organ Injuries: A Mitochondrial Perspective.

Sohrab Rahmani, Ali Roohbakhsh, Yazdan Hasani Nourian, Gholamreza Karimi.

  Mitochondria are essential for maintaining health, and dysfunction of them leads to various diseases. Their role is not limited to energy production but serves multiple mechanisms varying from calcium hemostasis, reactive oxygen species production, and regulation of apoptotic cell death. In recent years, several strategies have been developed to preserve mitochondria. Ellagic acid (EA) is a polyphenol extracted from many plants. The intestinal microflora converts EA to urolithins with high bioavailability. EA and urolithins exhibit mitochondrial-protective effects by regulating mitochondrial complexes, sirtuins, mitophagy, and mitochondrial antioxidant enzymes. This review highlights the mito-protective effects of EA and urolithins on mitochondrial injuries induced by various drugs and toxic compounds.

Keywords:  apoptosis; ellagic acid; mitochondria; oxidative stress

DOI:  https://doi.org/10.1002/fsn3.70077
Front Aging Neurosci. 2025 ;17 1591288

Editorial: Targeting the aging mitochondria: mechanisms, methods, and therapeutic strategies.

Zhiquan Li, Konstantinos Palikaras, Yuan Li, Vilhelm A Bohr.



Keywords:  FOXO; PGC-1α; cuproptosis; mitochondrial dysfunction; neurodegeneration; oxidative stress; reproductive aging; synapse

DOI:  https://doi.org/10.3389/fnagi.2025.1591288
J Biosci. 2025 ;pii: 23. [Epub ahead of print]50

Exploring mitochondrial dynamics and localization under cellular stress: A comprehensive insight.

Saloni Agarwal, Kavikumar Angamuthu Karuppusamy, Abhishek K Gupta.

Within a cell, the mitochondrion serves various functions, including ATP synthesis, generation of reactive oxygen species, maintenance of iron and calcium ion homeostasis, and apoptosis, all of which are essential for the cell's function. Recent studies have highlighted the significance of mitochondrial dynamics and spatial distribution in ensuring proper mitochondrial function and cell survival, particularly under various cellular stress conditions. Mitochondrial dynamics include various processes such as mitochondrial fission and fusion, mitophagy, mitochondrial biogenesis, and mitochondrial transport. This review article explores the impact of cellular stressors on mitochondrial dynamics and distribution. It also sheds light on the critical role of stress-induced alterations in mitochondrial dynamics and distribution from the perspective of cell survival.
Cells. 2025 Mar 29. pii: 511. [Epub ahead of print]14(7):

Oxidative Stress and Redox Imbalance: Common Mechanisms in Cancer Stem Cells and Neurodegenerative Diseases.

Nikhil Raj Selvaraj, Durga Nandan, Bipin G Nair, Vipin A Nair, Parvathy Venugopal, Rajaguru Aradhya.

  Oxidative stress (OS) is an established hallmark of cancer and neurodegenerative disorders (NDDs), which contributes to genomic instability and neuronal loss. This review explores the contrasting role of OS in cancer stem cells (CSCs) and NDDs. Elevated levels of reactive oxygen species (ROS) contribute to genomic instability and promote tumor initiation and progression in CSCs, while in NDDs such as Alzheimer's and Parkinson's disease, OS accelerates neuronal death and impairs cellular repair mechanisms. Both scenarios involve disruption of the delicate balance between pro-oxidant and antioxidant systems, which leads to chronic oxidative stress. Notably, CSCs and neurons display alterations in redox-sensitive signaling pathways, including Nrf2 and NF-κB, which influence cell survival, proliferation, and differentiation. Mitochondrial dynamics further illustrate these differences: enhanced function in CSCs supports adaptability and survival, whereas impairments in neurons heighten vulnerability. Understanding these common mechanisms of OS-induced redox imbalance may provide insights for developing interventions, addressing aging hallmarks, and potentially mitigating or preventing both cancer and NDDs.

Keywords:  antioxidant; autophagy; cancer stem cells; ferroptosis; mitochondrial dysfunction; neurodegenerative diseases; oxidative phosphorylation; oxidative stress; reactive oxygen species; redox imbalance

DOI:  https://doi.org/10.3390/cells14070511
Int J Biol Macromol. 2025 Apr 07. pii: S0141-8130(25)03465-8. [Epub ahead of print] 142913

Fatty acid binding proteins-mediated mitochondrial dysfunction in the development of age-related diseases: A review.

Xingxing Ren, Chaoyuan Jin, Qilin Li, Congyi Fu, Yu Fang, Zihang Xu, Zi Liang, Tianshi Wang.

  Fatty acid-binding proteins (FABPs) act as lipid chaperones and play a role in the pathological processes of various lipid signaling pathways. Mitochondria are crucial for the regulation of lipid metabolism. As an aging marker, lipid-mediated mitochondrial dysfunction has been observed in the etiology of numerous diseases, including neurodegenerative diseases, metabolic syndromes, cardiovascular diseases, and tumorigenesis. Members of the FABP family have been identified to regulate mitochondrial function. Targeting FABPs specifically may provide a promising approach to improve mitochondrial function and treat age-related diseases. This review summarizes the connection between FABPs and mitochondrial function and highlights certain FABPs involved in age-related diseases that hold significant therapeutic promise.

Keywords:  Aging; Cardiovascular diseases; FABPs; Metabolic syndromes; Mitochondria; Neurodegenerative diseases; Tumorigenesis

DOI:  https://doi.org/10.1016/j.ijbiomac.2025.142913
Neuroscience. 2025 Apr 02. pii: S0306-4522(25)00272-6. [Epub ahead of print]573 430-441

Unraveling the cGAS-STING pathway in Alzheimer's disease: A new Frontier in neuroinflammation and therapeutic strategies.

Arshdeep Kaur, Khadga Raj Aran.

  Alzheimer's disease (AD) is the most prevalent type of neurological disorder characterized by cognitive decline and memory loss, marked by the accumulation of amyloid beta (Aβ) plaques and hyperphosphorylated tau protein, causing extensive neuronal death and neuroinflammation. There is growing evidence that AD development extends beyond the neuronal compartment and has a major impact on the immunological functions of the brain. The cyclic GMP-AMP synthase (cGAS) detects cytosolic DNA, including pathogenic foreign DNA and self-DNA from cellular injury, triggering a type I interferon (IFN-I) response through activation of the stimulator of interferon genes (STING). The activation of the cGAS-STING pathway in response to mitochondrial dysfunction drives neuroinflammation in AD, which is mediated by the release of IFN-I cytokines. Furthermore, the release of oxidized mtDNA is necessary for the stimulation of the nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome, which is a family of protein complexes that macrophages can produce to induce inflammation. AD becomes severe by the stimulation of the cGAS-STING pathway, which results in sterile inflammation and microglial dysfunction. This review aims to explore the potential impact of the cGAS-STING signaling pathway in the pathogenesis and progression of AD. Additionally; after overviewing recent findings, this article highlights the molecular mechanism involved in the onset of disease and its modulation regarding the therapeutic approach of AD. Finally, deliberated a deep insight, the cGAS-STING axis could provide novel therapeutic avenues for slowing or halting the progression of AD, thereby offering new prospects for treatment development.

Keywords:  Alzheimer’s disease; Neuroinflammation; STING; Therapeutic targets; cGAS; mtDNA

DOI:  https://doi.org/10.1016/j.neuroscience.2025.04.001
bioRxiv. 2025 Mar 26. pii: 2025.03.25.645201. [Epub ahead of print]

Diet induced insulin resistance is due to induction of PTEN expression.

Radha Mukherjee, Priya Pancholi, Malvika Sharma, Hilla Solomon, Merna N Timaul, Claire Thant, Rory McGriskin, Omar Hayatt, Vladimir Markov, John D'Allara, Simona Bekker, Jacqueline Candelier, Sebastian E Carrasco, Elisa de Stanchina, Kiran Vanaja, Neal Rosen.

Insulin resistance is a condition associated with obesity, type 2 diabetes(T2D), hyperinsulinemia, hyperglycemia and defined by reduced sensitivity to insulin signaling. Molecular causes and early signaling events underlying insulin resistance are not well understood. Here we show that insulin activation of PI3K/AKT/mTOR signaling in insulin target tissues, causes mTORC1 induction of PTEN translation, a negative regulator of PI3K signaling. We hypothesized that insulin resistance is due to insulin dependent induction of PTEN that prevents further increases in PI3K signaling. In a diet induced animal model of obesity and insulin resistance, we show that PTEN levels are increased in fat, muscle, and liver. Hyperinsulinemia and PTEN induction are followed by hyperglycemia, severe glucose intolerance, and hepatic steatosis. In response to chronic hyperinsulinemia, PTEN remains increased, while AKT activity is induced transiently before settling down to a PTEN-high and AKT-low state in the tissues, predicted by computational modeling of the PTEN-AKT feedback loop. Treatment with PTEN and mTORC1 inhibitors prevent and reverse the effect of PTEN induction, rescue insulin resistance and increase PI3K/AKT signaling. Thus, we show that PTEN induction by increased insulin levels elevates feedback inhibition of the pathway causing insulin resistance, its associated phenotypes, and is a potential therapeutic target.

DOI: https://doi.org/10.1101/2025.03.25.645201
Mitochondrion. 2025 Apr 07. pii: S1567-7249(25)00036-4. [Epub ahead of print] 102039

Miro1- a key player in β-cell function and mitochondrial dynamics under diabetes mellitus.

Srikanth Kavyashree, Kannan Harithpriya, Kunka Mohanram Ramkumar.

  Mitochondrial health is crucial for the survival and function of β-cells, preserving glucose homeostasis and effective insulin production. Miro1, a mitochondrial Rho GTPase1 protein, plays an essential role in maintaining thequality of mitochondria by regulating calcium homeostasis and mitophagy. In this review, we aim to explore the dysfunction of Miro1 in type 2 diabetes mellitus (T2DM) and its contribution to impaired Ca2+ signaling, which increases oxidative stress in β-cells. This dysfunction is the hallmark of T2DM pathogenesis, leading to insufficient insulin production and poor glycemic control. Additionally, we discuss the role of Miro1 in modulating insulin secretion and inflammation, highlighting its effect on modulating key signaling cascades in β-cells. Altogether, enhancing Miro1 function and activity could alleviate mitochondrial dysfunction, reducing oxidative stress-mediated damage, and improving pancreatic β-cell survival. Targeting Miro1 by Small molecules or gene-editing approaches could provide effective strategies for restoring cell function and insulin secretion in diabetic individuals. Exploring the deeper knowledge of Miro1 functions and interactions could lead to novel therapeutic advances in T2DM management.

Keywords:  Diabetes Mellitus; Miro1; Mitochondrial Dynamics; RHOT1; β-cells

DOI:  https://doi.org/10.1016/j.mito.2025.102039
Am J Physiol Heart Circ Physiol. 2025 Apr 07.

Cardiac Energy Metabolism in Diabetes: Emerging Therapeutic Targets and Clinical Implications.

Archee Panwar, Sufyan Malik, Muhtasim Adib, Gary D Lopaschuk.

  Patients with diabetes are at an increased risk for developing diabetic cardiomyopathy and other cardiovascular complications. Alterations in cardiac energy metabolism in diabetic patients, including an increase in mitochondrial fatty acid oxidation and a decrease in glucose oxidation are important contributing factors to this increase in cardiovascular disease. A switch from glucose oxidation to fatty acid oxidation not only decreases cardiac efficiency due to increased oxygen consumption, but it can also increase reactive oxygen species production, increase lipotoxicity, and redirect glucose into other metabolic pathways that, combined, can lead to heart dysfunction. Currently, there is a lack of therapeutics available to treat diabetes-induced heart failure that specifically target cardiac energy metabolism. However, it is becoming apparent that part of the benefit of existing agents such as GLP-1 receptor agonists and sodium-glucose co-transporter 2 inhibitors may be related to their effects on cardiac energy metabolism. In addition, direct approaches aimed at inhibiting cardiac fatty acid oxidation or increasing glucose oxidation hold future promise as potential therapeutic approaches to treat diabetes-induced cardiovascular disease.

Keywords:  diabetic cardiomyopathy; fatty acid ß-oxidation; glucose oxidation; mitochondria

DOI:  https://doi.org/10.1152/ajpheart.00615.2024
Neuroscience. 2025 Apr 04. pii: S0306-4522(25)00268-4. [Epub ahead of print]574 21-41

Exploring the nexus: Sleep disorders, circadian dysregulation, and Alzheimer's disease.

Pratima Khandayataray, Meesala Krishna Murthy.

  We reviewed the connections among Alzheimer's disease (AD), sleep deprivation, and circadian rhythm disorders. Evidence is mounting that disrupted sleep and abnormal circadian rhythms are not merely symptoms of AD, but are also involved in accelerating the disease. Amyloid-beta (Aβ) accumulates, a feature of AD, and worsens with sleep deprivation because glymphatic withdrawal is required to clear toxic proteins from the brain. In addition, disturbances in circadian rhythm can contribute to the induction of neuroinflammation and oxidative stress, thereby accelerating neurodegenerative processes. While these interactions are bidirectional, Alzheimer's pathology further disrupts sleep and circadian function in a vicious cycle that worsens cognitive decline, which is emphasized in the review. The evidence that targeting sleep and circadian mechanisms may serve as therapeutic strategies for AD was strengthened by this study through the analysis of the molecular and physiological pathways. Further work on this nexus could help unravel the neurobiological mechanisms common to the onset of Alzheimer's and disrupted sleep and circadian regulation, which could result in earlier intervention to slow or prevent the onset of the disease.

Keywords:  Alzheimer’s disease; Circadian regulation; Circadian rhythms; Glymphatic withdrawal; Sleep deprivation

DOI:  https://doi.org/10.1016/j.neuroscience.2025.03.066
Arch Pharm Res. 2025 Apr 10.

A review on bacteria-derived antioxidant metabolites: their production, purification, characterization, potential applications, and limitations.

Nazli Pinar Arslan, Fakhrul Azad, Tugba Orak, Aysenur Budak-Savas, Serkan Ortucu, Pranav Dawar, Mustafa Ozkan Baltaci, Hakan Ozkan, Nevzat Esim, Mesut Taskin.

  Antioxidants are organic molecules that scavenge reactive oxygen species (ROS) and reactive nitrogen species (RNS), thereby maintaining cellular redox balance in living organisms. The human body synthesizes endogenous antioxidants, whereas humans obtain exogenous antioxidants from other organisms such as plants, animals, fungi, and bacteria. This review primarily focuses on the antioxidant potential of natural metabolites and extracts from five major bacterial phyla, including the well-studied Actinobacteria and Cyanobacteria, as well as less-studied Bacteroides, Firmicutes, and Proteobacteria. The literature survey revealed that the metabolites and the extracts with antioxidant activity can be obtained from bacterial cells and their culture supernatants. The metabolites with antioxidant activity include pigments, phycobiliproteins, polysaccharides, mycosporins-like amino acids, peptides, phenolic compounds, and alkaloids. Both metabolites and extracts demonstrate in vitro antioxidant capacity through radical-scavenging, metal-reducing, and metal-chelating activity assays. In in vivo models, they can scavenge ROS and RNS directly and/or indirectly eliminate them by enhancing the activities of antioxidant enzymes, such as catalase, superoxide dismutase, and glutathione peroxidase. Due to their antioxidant activities, they may find applications in the cosmetic industry as anti-aging agents for the skin and in medicine as drugs or supplements for combating oxidative stress-related disorders, such as neurodegenerative diseases and diabetes. The literature survey also elucidated that some metabolites and extracts with antioxidant activity also exhibited strong antimicrobial properties. Therefore, we consider that they may have future applications in the treatment of infectious diseases, the preparation of pathogen-free healthy foods, and the extension of food shelf life.

Keywords:   Actinobacteria ; Cyanobacteria ; Proteobacteria ; Exogenous antioxidants; Natural metabolites; Oxidative stress

DOI:  https://doi.org/10.1007/s12272-025-01541-5
Mol Nutr Food Res. 2025 Apr 08. e70014

Effects and Mechanisms of Steviol Glycosides on Glucose Metabolism: Evidence From Preclinical Studies.

Lili Kang, Changfa Zhang, Ruoting Wang, Kangjun Li, Xuerui Bai, Ningyu Qi, Hongying Qu, Guowei Li.

  The natural sweeteners of steviol glycosides (SGs) have been widely used as a substitute for sugar due to their high sweetness, low-calorie properties, and potential health benefits. Some studies reported that SGs could regulate glucose metabolism and prevent Type 2 diabetes mellitus (T2DM); however, the detailed mechanisms remained further elucidated. Therefore, in this review, we aimed to systematically summarize the effects and mechanisms of SGs on glucose metabolism based on evidence from preclinical studies. We searched PubMed and Web of Science (up to March 31, 2024), and included a total of 40 animal and 5 cell studies for review. Results showed that SGs could improve glucose metabolism by enhancing insulin secretion, simulating insulin effects, improving insulin resistance, advancing key enzyme activities, or regulating gut microbiota. To conclude, if further validated in clinical trials and population studies, the sugar substitute of SGs may serve as a potential nutritional strategy for effective prevention and treatment of T2DM.

Keywords:  Type 2 diabetes mellitus; glucose metabolism; insulin resistance; steviol glycosides; sweetener

DOI:  https://doi.org/10.1002/mnfr.70014
Can J Physiol Pharmacol. 2025 Apr 09.

Nampt as a new therapeutic target for modulating NAD+ levels in metabolic, cardiovascular and neurodegenerative diseases.

Ravikumar Manickam, Sandhya Santhana, Wanling Xuan, Kirpal S Bisht, Srinivas M Tipparaju.

NAD+ is an important cofactor involved in regulating many biochemical processes in cells. An imbalance in NAD+/NADH ratio is linked to many diseases. NAD+ is depleted in diabetes, cardiovascular and neurodegenerative diseases, and in aging, and is increased in tumor cells. NAD+ is generated in cells via the de novo, Preiss-Handler, and salvage pathways. Most of the cellular NAD+ is generated through Nampt activation, a key rate-limiting enzyme that is involved in the salvage pathway. Restoration of NAD+/NADH balance offers therapeutic advantages for improving tissue homeostasis and function. NAD+ is known to benefit and restore the body's physiological mechanisms, including DNA replication, chromatin and epigenetic modifications, and gene expression. Recent studies elucidate the role of NAD+ in cells utilizing transgenic mouse models. Translational new therapeutics are positioned to utilize the NAD+ restoration strategies for overcoming the drawbacks that exist in the pharmacological toolkit. The present review highlights the significance of Nampt-NAD+ axis as a major player in energy metabolism and provides an overview with insights into future strategies, providing pharmacological advantages to address current and future medical needs.

DOI: https://doi.org/10.1139/cjpp-2024-0400
Cell Biochem Biophys. 2025 Apr 11.

The Impact of Liraglutide, a GLP-1 Receptor Agonist, on High Glucose-Induced Inflammation, Apoptosis, Oxidative Stress, and NLRP3 Signaling.

Mustafa Gokce, Dilek Ozturk Civelek, Aylin Vidin Sen, Eray Metin Guler, Erkan Civelek, Birsel Sonmez Uydes Dogan, F Ilkay Alp Yildirim.

  Diabetes-related endothelial dysfunction, alteration in cell signaling, increased oxidative stress and activation of pro-inflammatory processes are the main causes of diabetes-related vascular complications. Glucagon-like peptide-1 (GLP-1) and its receptor (GLP-1R) play a crucial role in regulating glucose homeostasis, insulin secretion, and reducing inflammation. GLP-1R agonists have been explored for their potential in mitigating diabetes-related vascular dysfunction. The NOD-like receptor protein 3 (NLRP3) inflammasome, a key protein complex in immune response, activates caspase-1 and promotes proinflammatory cytokine secretion. High glucose levels activate NLRP3 in macrophages via reactive oxygen species and mitochondrial dysfunction. This study aims to investigate the effects of GLP-1 receptor agonist, Liraglutide, on cell proliferation, inflammation, oxidative stress and NLRP3-related signaling pathways in human umbilical vein endothelial cells (HUVEC) and human coronary artery endothelial cell (HCAEC) cultures. HUVEC and HCAEC were incubated with Liraglutide (10 and 100 nM, 48 h) either in normoglycemic (5.5 mM) or hyperglycemic (25 mM) condition. Cell proliferation, oxidative stress, mRNA and protein expressions of ASC, caspase-1, NLRP3 which are. components of NLRP3 inflammasome, were determined. Our results showed that, Liraglutide significantly reduced hyperglycemia-induced oxidative stress, mRNA and protein expressions of NLRP3 inflammasome and proinflammatory cytokine levels, as well as cell membrane damage in HUVEC and HCAEC. Our results indicate that Liraglutide may have the potential on preventing hyperglycemia-induced cellular damage by reducing inflammation and immune response activation both in human venous and arterial endothelial cells.

Keywords:  Endothelial dysfunction; Hyperglycemia; Inflammation; Liraglutide; NLRP3

DOI:  https://doi.org/10.1007/s12013-025-01742-1
Neuroscience. 2025 Apr 02. pii: S0306-4522(25)00274-X. [Epub ahead of print]573 421-429

Identifying blood mitochondrial DNA copy number as a biomarker for development of neurodegenerative diseases: Evidence from Mendelian randomization analysis.

Shizhen Lei, Yani Liu.

  Mitochondrial dysfunction has been associated with neurodegenerative diseases (NDDs). This study aimed to explore the association between blood mitochondrial DNA copy number (mtDNA-CN) and development of NDDs. This study was based on two-sample Mendelian randomization (MR) analysis. The genome wide association study (GWAS) data of NDDs including Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), age-related macular degeneration (AMD), multiple sclerosis (MS), Parkinson's disease (PD), primary open-angle glaucoma (POAG), and vascular dementia (VD) was obtained from FinnGen consortium. Inverse-variance weighted (IVW) was applied as the primary approach for MR estimation. MR results revealed that blood mtDNA-CN exhibited a significant relationship with the incidence of AD (IVW-P = 0.011, odds ratio [OR] = 0.65) and AMD (IVW-P = 0.038, OR = 0.64). However, there was no significant association observed between blood mtDNA-CN and other NDDs (IVW-P > 0.05). Our findings supported the relationship between mitochondrial dysfunction and development of AD and AMD, and that blood mtDNA-CN may serve as a potential biomarker for the incidence of these two NDDs.

Keywords:  Age-related macular degeneration; Alzheimer’s disease; Mendelian randomization; Mitochondrial DNA copy number; Neurodegenerative diseases

DOI:  https://doi.org/10.1016/j.neuroscience.2025.04.003
J Health Popul Nutr. 2025 Apr 08. 44(1): 109

Effect of probiotics on cognitive function and cardiovascular risk factors in mild cognitive impairment and Alzheimer's disease: an umbrella meta-analysis.

Bin Xiao, Lina Fu, Zhe Yang, Guran Yu.

   BACKGROUND: This umbrella meta-analysis evaluates the effects of probiotics on cognitive function and metabolic health in Alzheimer's disease (AD) and mild cognitive impairment (MCI) by synthesizing findings from meta-analyses of randomized controlled trials (RCTs), as existing evidence remains inconclusive.
METHODS: A systematic search was conducted in PubMed, Web of Science, and Scopus to identify meta-analyses of RCTs investigating the impact of probiotic supplementation on cognitive function and metabolic biomarkers. The random-effects model was used. Heterogeneity and publication bias were assessed.
RESULTS: Thirteen meta-analyses, comprising 3910 patients, were included. Probiotics significantly improved cognitive function in AD (SMD = 0.78, 95% CI: 0.33 to 1.23) and MCI (SMD = 0.43, 95% CI: 0.15 to 0.70). Probiotics also increased total antioxidant capacity (SMD = 0.40, 95% CI: 0.11 to 0.70) and reduced MDA (SMD = - 0.35, 95% CI: - 0.62 to - 0.09) and hs-CRP (SMD = - 0.59, 95% CI: - 0.87 to - 0.30). Insulin resistance improved, as reflected by decreased HOMA-IR (SMD = - 0.34, 95% CI: - 0.43 to - 0.26). No significant effects were observed on glutathione, nitric oxide, or lipid profiles.
CONCLUSION: Probiotic supplementation appears to enhance cognitive function and metabolic parameters in individuals with MCI and AD, likely through mechanisms involving inflammation reduction, oxidative stress modulation, and improved insulin sensitivity. Further high-quality RCTs are required to validate these findings and determine optimal probiotic formulations.

Keywords:  Alzheimer’s disease; Inflammation; Meta-analysis; Mild cognitive impairment; Oxidative stress; Probiotics

DOI:  https://doi.org/10.1186/s41043-025-00816-3
Mol Med Rep. 2025 Jun;pii: 161. [Epub ahead of print]31(6):

Perimenopausal depression: Targeting inflammation and oxidative stress (Review).

Yang Yu, Tianyang Yu, Kaili Liu, Yushuai Li, Yifeng Luan, Tianyi Yang, Wenzhong Li, Huifang Cong, Xiuhong Wu.

  Depressive disorder is a highly disabling condition that affects more than 300 million individuals worldwide, with women affected at a higher rate than men. With the aging of the population, the incidence of perimenopausal depression has risen markedly, seriously jeopardizing women's physical and mental health. Symptoms of perimenopausal depression include feelings of depression, stress, anxiety and endocrine dysfunctions, particularly hypogonadism and senescence. During perimenopause, estrogen and progesterone levels fluctuate erratically, adding to the risk of developing depression associated with perimenopause. As a result of these hormonal changes, proinflammatory mediators are produced and oxidative stress is induced, which finally leads to progressive neuronal damage. The present study mainly reviewed roles of neuroinflammation in perimenopausal depression and explained potential anti‑inflammatory and anti‑oxidative stress mechanisms for clinically effective therapeutic treatment.

Keywords:  inflammation; oxidative stress; perimenopausal depression; reactive oxygen species

DOI:  https://doi.org/10.3892/mmr.2025.13526
Mol Neurobiol. 2025 Apr 08.

Withania somnifera Regulates Mitochondrial Biogenesis and Energetics in Rat Cortical Neurons: Role of BDNF and SIRT1.

Sashaina E Fanibunda, Kowshik Kukkemane, Utkarsha Ghai, Ullas Kolthur-Seetharam, Lal Hingorani, Ashok D B Vaidya, Vidita A Vaidya.

  Withania somnifera, a psychoactive plant with putative neuroprotective actions, is used in Indian traditional medicine for the treatment of neuropsychiatric and neurodegenerative disorders. However, the key mechanisms underlying the pleiotropic actions of Withania somnifera on the nervous system remain poorly understood. Given converging evidence suggests a critical role for mitochondrial dysfunction in the pathophysiology of neuropsychiatric and neurodegenerative diseases, we hypothesized that Withania somnifera may exert pleiotropic effects via targeting mitochondria. Treatment with Withania somnifera root extract (RE) or the withanolide-withanoside rich fraction (WLS) enhanced cellular ATP levels in rat cortical neurons in vitro and in the neocortex in vivo. In vivo respirometry performed on mitochondria isolated from the neocortex following RE or WLS treatment revealed increased mitochondrial respiration and OxPhos efficiency. Furthermore, WLS treatment evoked increases in mitochondrial mass, and RE and WLS treatments enhanced expression of brain derived neurotrophic factor (BDNF) and Sirtuin 1 (SIRT1), both in vitro and in vivo. Pharmacological inhibitor studies support an important role for BDNF and SIRT1 in the mitochondrial effects of Withania somnifera. Experiments with distinct phytochemical components of WLS identified withanolide A and withanoside IV as key constituents that enhance mitochondrial biogenesis and neuroenergetics. The neuroprotective actions of WLS, withanolide A and withanoside IV against corticosterone-induced neuronal cell death in vitro, required signaling via BDNF and SIRT1. Collectively, these results indicate that Withania somnifera root extract and specific phytochemical constituents robustly influence mitochondria in cortical neurons, contributing to stress adaptation and neuroprotection via BDNF and SIRT1 signaling.

Keywords:  Ashwagandha; Mitochondria; Neocortex; Neuroprotection; Withanolide A; Withanoside IV

DOI:  https://doi.org/10.1007/s12035-025-04920-7
Tissue Cell. 2025 Apr 02. pii: S0040-8166(25)00162-4. [Epub ahead of print]95 102882

Liraglutide attenuates high glucose-induced endothelial cell senescence and dysfunction via SIRT1-mediated deacetylation of p53/p65.

Weili Zhong, Ying Yang, Yanru Wang.

  Endothelial aging is a critical pathogenic factor in various cardiovascular and metabolic disorders. Liraglutide (LIR), a glucagon-like peptide-1 receptor (GLP-1R) agonist used clinically to treat diabetes, controls blood sugar levels, and alleviates vascular stress, thereby protecting blood vessels. However, the mechanism by which it improves vascular aging remains to be elucidated. In this study, human umbilical vein endothelial cells were subjected to 30 mM glucose induction, followed by the addition of 1 μM LIR for 72 h. The findings indicated that LIR mitigated high glucose-induced endothelial cell senescence and downregulated the expression of markers linked to senescence, reactive oxygen species (ROS), and oxidative stress (p < 0.05). Additionally, it upregulated the expression of antioxidant markers and promoted angiogenesis and migration (p < 0.05). Western blot analysis of protein changes revealed that the therapeutic effects of LIR depend on SIRT1 and the acetylation of p53 and p65. Through SIRT1 overexpression and knockdown, we determined that SIRT1 regulates the acetylation of p53 and p65. Notably, the absence of SIRT1 diminished the therapeutic effects of LIR, whereas its overexpression enhanced these effects. Our findings suggest that high-glucose-induced endothelial cell aging and dysfunction may be involved in the pathogenesis of diabetic cardiovascular diseases (CVD). LIR treatment of high-glucose-induced vascular aging relies on the SIRT1-p53/p65 signaling axis. This study elucidates the mechanisms by which LIR ameliorates vascular aging and proposes a novel approach to mitigate vascular aging in elderly patients with diabetes.

Keywords:  Acetylation; Endothelial cell senescence; Liraglutide; Oxidative stress; P53/p65; SIRT1

DOI:  https://doi.org/10.1016/j.tice.2025.102882
Curr Neuropharmacol. 2025 Apr 07.

The Multifaceted Role of Neuroprotectin D1: Physiological, Pathophysiological, and Pharmacological Insights in Neurodegenerative Diseases.

Bushra Zia, Mariam Elmeky, Sheikh Azimullah, Niraj Kumar Jha, M F Nagoor Meeran, Shreesh K Ojha.

  Neuroprotectin D1 (NPD1) has emerged as an integral lipid mediator with significant implications for maintaining neurological health. Being derived from docosahexaenoic acid (DHA), NPD1 is a specialized pro-resolving lipid mediator (SPM), consisting of a unique structure that attributes potent anti-inflammatory and neuroprotective properties crucial for maintaining nervous system homeostasis. It exerts its actions through diverse mechanisms, including the inhibition of proinflammatory cytokines, modulation of apoptosis, and promotion of cellular survival pathways. The dysregulation or deficiency of NPD1 has been implicated in the onset and progression of several neurodegenerative diseases, such as Alzheimer's, Parkinson's, and stroke, underscoring its critical role in maintaining neuronal health and disease prevention. Abnormal NPD1 signalling is associated with neuroinflammation, oxidative stress, and neuronal apoptosis, which in turn contribute significantly to the progression of neurological disorders. Understanding these pathways offers insights into potential therapeutic strategies aimed at targeting NPD1 to mitigate neurodegenerative processes and facilitate neural repair. The efforts in developing NPD1 analogs or mimetics are focused on enhancing endogenous NPD1 levels, attenuating neuroinflammation, and preserving neuronal integrity in disease contexts. This review provides a comprehensive exploration of NPD1, encompassing its structural characteristics, biochemical pathways, physiological roles, pathophysiological implications, and potential therapeutic applications in neurological disorders. Further, research into elucidating the precise mechanisms of NPD1 reveals that its clinical efficacy is crucial for harnessing its full potential as a therapeutic tool for neuroprotection and neural repair.

Keywords:  Cyclooxygenases; NPD1; Neuroprotectin D1; Protectin D; docosahexaenoic acid; inflammatory cytokines; lipoxygenases; neurodegenerative diseases; neuroprotective; pro-resolving lipid mediators.

DOI:  https://doi.org/10.2174/011570159X365720250225080257
Front Immunol. 2025 ;16 1566287

Curcumin targets YAP1 to enhance mitochondrial function and autophagy, protecting against UVB-induced photodamage.

Quan Chen, Wenxin Lin, Yi Tang, Fengmei He, Bihua Liang, Jiaoquan Chen, Huaping Li, Huilan Zhu.

   Background: Ultraviolet B (UVB) radiation is a major environmental factor contributing to skin damage via DNA damage, oxidative stress, inflammation, and collagen degradation. It penetrates the epidermis, disrupts DNA integrity, and generates reactive oxygen species (ROS), activating pro-inflammatory pathways such as NF-κB and AP-1, and inducing matrix metalloproteinases (MMPs). These processes lead to structural skin changes, inflammation, and pigmentation disorders like melasma. Cumulative DNA damage from UVB also drives photocarcinogenesis, with nearly 90% of melanomas associated with UV radiation (UVR). Despite clinical interventions like phototherapy and antioxidants, effective treatments for UVB-induced damage remain limited due to side effects and efficacy issues.
Methods: This study investigates the protective effects of curcumin on UVB-induced skin damage using a mouse UVB irradiation model and HaCaT cells exposed to UVB in vitro. Skin damage was assessed through histopathological and immunohistochemical analyses. Cellular functional changes were evaluated using assays for cell viability, mitochondrial function, ROS levels, and apoptosis. Transcriptomic analysis was employed to elucidate the molecular mechanisms underlying curcumin's protective effects on HaCaT cells post-UVB exposure. This integrated approach provides a comprehensive understanding of curcumin's molecular-level protection against UVB-induced skin damage.
Results: Curcumin significantly alleviated UVB-induced skin lesions and inflammation in vivo. In vitro, it mitigated UVB-induced HaCaT cell damage, enhancing viability while reducing apoptosis and ROS levels. Transcriptomic analysis revealed that curcumin upregulated YAP signaling and mitochondrial autophagy while suppressing IL-18 expression.
Conclusion: Curcumin treatment markedly improved UVB-induced skin lesions and reduced epidermal inflammation and thickness in vivo. In vitro, curcumin intervention alleviated UVB-induced HaCaT cell damage, including reduced viability, increased apoptosis, elevated ROS and DNA damage, and enhanced inflammatory responses. Transcriptomic analysis demonstrated that curcumin upregulated the YAP signaling pathway and mitochondrial autophagy while inhibiting the IL-18 pathway. Further studies revealed that curcumin directly interacts with YAP1, promoting mitochondrial autophagy, an effect blocked by the YAP1 inhibitor Verteporfin. Additionally, curcumin enhances mitochondrial function through YAP1, maintaining mitochondrial integrity and preventing the release of mitochondrial DNA (mtDNA) and mitochondrial ROS (mtROS), thereby suppressing NLRP3/IL-18 pathway activation.

Keywords:  UVB; YAP1; autophagy; curcumin; mitochondrial; photoprotection; skin damage

DOI:  https://doi.org/10.3389/fimmu.2025.1566287