Exploring the interplay between mitochondrial dysfunction, early life adversity and bipolar disorder.

Objective: Mitochondria are essential for energy production and reactive oxygen species (ROS) generation, with changes in ROS levels or energy demands affecting mitochondrial DNA (mtDNA) copy numbers, indicating mitochondrial function. Early life adversity (ELA) affects mitochondrial dynamics, influencing long-term health. Both ELA and mitochondrial abnormalities have been independently associated with bipolar disorder (BD).

Erinacine A-Enriched Mycelium Ethanol Extract Lessens Cellular Damage in Cell and Models of Spinocerebellar Ataxia Type 3 by Improvement of Nrf2 Activation.

Spinocerebellar ataxia type 3 (SCA3), caused by the abnormal expansion of polyglutamine (polyQ) in the ataxin-3 protein, is one of the inherited polyQ neurodegenerative diseases that share similar genetic and molecular features. Mutant polyQ-expanded ataxin-3 protein is prone to aggregation in affected neurons and is predominantly degraded by autophagy, which is beneficial for neurodegenerative disease treatment. Not only does mutant polyQ-expanded ataxin-3 increase susceptibility to oxidative cytotoxicity, but it also hampers antioxidant potency in neuronal cells.

Astragaloside IV reduces mutant Ataxin-3 levels and supports mitochondrial function in Spinocerebellar Ataxia Type 3.

This study investigated the therapeutic effects of astragaloside IV (AST) on spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph disease (MJD), a neurodegenerative disorder. Human neuroblastoma SK-N-SH cells expressing mutant ataxin-3 protein with 78 CAG repeats (MJD78) were employed as an in vitro model. Protein expression analysis demonstrated that AST treatment reduced mutant ataxin-3 protein expression and aggregation by enhancing the autophagic process in MJD78 cells.

Sphingolipid Metabolism Is Associated with Cardiac Dyssynchrony in Patients with Acute Myocardial Infarction.

Aim: Sphingolipids are a class of complex and bioactive lipids that are involved in the pathological processes of cardiovascular disease. Fabry disease is an X-linked storage disorder that results in the pathological accumulation of glycosphingolipids in body fluids and the heart. Cardiac dyssynchrony is observed in patients with Fabry disease and left ventricular (LV) hypertrophy.

Formoterol Acting via β2-Adrenoreceptor Restores Mitochondrial Dysfunction Caused by Parkinson's Disease-Related UQCRC1 Mutation and Improves Mitochondrial Homeostasis Including Dynamic and Transport.

Formoterol, a β2-adrenergic receptor (β2AR) agonist, shows promise in various diseases, but its effectiveness in Parkinson's disease (PD) is debated, with unclear regulation of mitochondrial homeostasis. This study employed a cell model featuring mitochondrial ubiquinol-cytochrome c reductase core protein 1 (UQCRC1) variants associated with familial parkinsonism, demonstrating mitochondrial dysfunction and dynamic imbalance, exploring the therapeutic effects and underlying mechanisms of formoterol. Results revealed that 24-h formoterol treatment enhanced cell proliferation, viability, and neuroprotection against oxidative stress.

Diabetes ketoacidosis and Recurrent Childhood Stroke-like Episodes.

A 13-year and 4-month-old girl was brought to the emergency department due to fever, dizziness,vomiting, and blurred vision. Laboratory data revealed hyperglycemia with an HbA1C of 7.3 percent, ketonuria, and lactic acidosis.

A pilot study: handgrip as a predictor in the disease progression of SCA3.

Background: Spinocerebellar ataxia type 3 (SCA3) is an inherited, autosomal, and rare neurodegenerative disease. Serum/plasma biomarkers or functional magnetic resonance imaging used to assess progression, except for neurological examinations, is either inconvenient or expensive. Handgrip strength (HGS) may be considered as a biomarker to predict the progress of SCA3 and align with the alteration of plasma neurofilament light chain (NfL) and Scale for the Assessment and Rating of Ataxia (SARA).

Association of leukocyte mitochondrial DNA copy number with longitudinal C-reactive protein levels and survival in older adults: a cohort study.

Background: Systemic chronic inflammation occurs with age. The association of the leukocyte mitochondrial DNA copy number, a measure of mitochondrial function in aging, with the temporal profile of serum high-sensitivity C-reactive protein and mortality risk remains uncertain. The objectives of this study were to examine the association of the leukocyte mitochondrial DNA copy number with longitudinal high-sensitivity C-reactive protein levels and the association of the longitudinal high-sensitivity C-reactive protein levels with mortality risk.

The relationship between pulse pressure with plasma PCSK9 and interleukin-6 among patients with acute ischemic stroke and dyslipidemia.

Background And Purpose: A high plasma concentration of proprotein convertase subtilisin/kexin type 9 is characteristic of a prothrombotic state in cardiovascular diseases. Elevated inflammatory markers, such as interleukin-6, are associated with worse outcomes after ischemic stroke. We aimed to study the role of plasma PCSK9 and IL-6 in acute ischemic stroke with dyslipidemia.

Coenzyme Q10 Supplementation Increases Removal of the Polyglutamine Repeat, Reducing Cerebellar Degeneration and Improving Motor Dysfunction in Murine Spinocerebellar Ataxia Type 3.

Coenzyme Q10 (CoQ10), a well-known antioxidant, has been explored as a treatment in several neurodegenerative diseases, but its utility in spinocerebellar ataxia type 3 (SCA3) has not been explored. Herein, the protective effect of CoQ10 was examined using a transgenic mouse model of SCA3 onset. These results demonstrated that a diet supplemented with CoQ10 significantly improved murine locomotion, revealed by rotarod and open-field tests, compared with untreated controls.

Regulation of mitochondrial fusion and mitophagy by intra-tumoral delivery of membrane-fused mitochondria or Midiv-1 enhances sensitivity to doxorubicin in triple-negative breast cancer.

Increasing mitochondrial fusion by intra-tumoral grafting of membrane-fused mitochondria created with Pep-1 conjugation (P-Mito) contributes to breast cancer treatment, but it needs to be validated. Using mitochondrial division inhibitor-1 (Mdivi-1, Mdi) to disturb mitochondrial dynamics, we showed that the antitumor action of P-Mito in a mouse model of triple-negative breast cancer depends upon mitochondrial fusion and that Mdi treatment alone is ineffective. P-Mito significantly enhanced Doxorubicin (Dox) sensitivity by inducing mitochondrial fusion and mitophagy, and the same efficiency was also achieved with Mdi by inhibiting mitophagy.

In Vitro Efficacy and Molecular Mechanism of Curcumin Analog in Pathological Regulation of Spinocerebellar Ataxia Type 3.

Unlike other nuclear factor erythroid-2-related factor 2 (Nrf2) activators, the mechanism of action of curcumin analog, ASC-JM17 (JM17), in regulating oxidative homeostasis remains unknown. Spinocerebellar ataxia type 3 (SCA3) is an inherited polyglutamine neurodegenerative disease caused mainly by polyglutamine neurotoxicity and oxidative stress. Presently, we compared actions of JM17 with those of known Nrf2 activators, omaveloxolone (RTA-408) and dimethyl fumarate (DMF), using human neuroblastoma SK-N-SH cells with stable transfection of full-length ataxin-3 protein with 78 CAG repeats (MJD78) to clarify the resulting pathological mechanism by assaying mitochondrial function, mutant ataxin-3 protein toxicity, and oxidative stress.

Altered glucose metabolism and its association with carbonic anhydrase 8 in Machado-Joseph Disease.

Machado-Joseph disease (MJD), also known as spinocerebellar ataxia type 3 (SCA3), is an autosomal dominant neurodegenerative disease. This disorder is caused by polyglutamine (polyQ)-containing mutant ataxin-3, which tends to misfold and aggregate in neuron cells. We previously demonstrated a protective function of carbonic anhydrase 8 (CA8) in MJD disease models and a decreased glycolytic activity associated with down-regulated CA8 in a human osteosarcoma (OS) cell model.

IGF-1 as a Potential Therapy for Spinocerebellar Ataxia Type 3.

Although the effects of growth hormone (GH) therapy on spinocerebellar ataxia type 3 (SCA3) have been examined in transgenic SCA3 mice, it still poses a nonnegligible risk of cancer when used for a long term. This study investigated the efficacy of IGF-1, a downstream mediator of GH, in vivo for SCA3 treatment. IGF-1 (50 mg/kg) or saline, once a week, was intraperitoneally injected to SCA3 84Q transgenic mice harboring a human ATXN3 gene with a pathogenic expanded 84 cytosine-adenine-guanine (CAG) repeat motif at 9 months of age.

UQCRC1 engages cytochrome c for neuronal apoptotic cell death.

Human ubiquinol-cytochrome c reductase core protein 1 (UQCRC1) is an evolutionarily conserved core subunit of mitochondrial respiratory chain complex III. We recently identified the disease-associated variants of UQCRC1 from patients with familial parkinsonism, but its function remains unclear. Here we investigate the endogenous function of UQCRC1 in the human neuronal cell line and the Drosophila nervous system.

Transcriptomic and Metabolic Network Analysis of Metabolic Reprogramming and IGF-1 Modulation in SCA3 Transgenic Mice.

Spinocerebellar ataxia type 3 (SCA3) is a genetic neurodegenerative disease for which a cure is still needed. Growth hormone (GH) therapy has shown positive effects on the exercise behavior of mice with cerebellar atrophy, retains more Purkinje cells, and exhibits less DNA damage after GH intervention. Insulin-like growth factor 1 (IGF-1) is the downstream mediator of GH that participates in signaling and metabolic regulation for cell growth and modulation pathways, including SCA3-affected pathways.

Intranasal delivery of mitochondria for treatment of Parkinson's Disease model rats lesioned with 6-hydroxydopamine.

The feasibility of delivering mitochondria intranasally so as to bypass the blood-brain barrier in treating Parkinson's disease (PD), was evaluated in unilaterally 6-OHDA-lesioned rats. Intranasal infusion of allogeneic mitochondria conjugated with Pep-1 (P-Mito) or unconjugated (Mito) was performed once a week on the ipsilateral sides of lesioned brains for three months. A significant improvement of rotational and locomotor behaviors in PD rats was observed in both mitochondrial groups, compared to sham or Pep-1-only groups.

Comparison of mitochondrial transplantation by using a stamp-type multineedle injector and platelet-rich plasma therapy for hair aging in naturally aging mice.

The mechanism of hair loss caused by aging is related to mitochondrial dysfunction. Pep-1-mediated mitochondrial transplantation is a potential therapeutic application for mitochondrial disorders, but its efficacy against hair aging remains unknown. This study compared platelet-rich plasma (PRP) therapy with mitochondrial transplantation for hair restoration and examined the related regulation in naturally aging mice.

Growth hormone rescue cerebellar degeneration in SCA3 transgenic mice.

Spinocerebellar ataxia type 3 (SCA3) is a fatal neurodegenerative disease for which no identified effective treatment or prevention methods exist. However, low-dose growth hormone (GH) therapy, as a potential off-label use, may deter the progress of SCA3. SCA3 15Q and SCA3 84Q transgenic mice harboring a YAC transgene that expresses the human ATXN3 gene with a pathogenic expanded 15 CAG repeat and 84 CAG repeat motif, respectively, were recruited.

Antitumor Actions of Intratumoral Delivery of Membrane-Fused Mitochondria in a Mouse Model of Triple-Negative Breast Cancers.

Background: The transfer of whole mitochondria has been demonstrated to be beneficial for treating breast cancer because it induces apoptosis and drug sensitivity; however, in vivo evidence of this benefit remains scant. The present study compared the transplantation of mitochondria with instinctive (Mito) and membrane-fused morphologies induced by Pep-1 conjugation (P-Mito) using a mouse model of triple-negative breast cancers.

Materials And Methods: Mice with advanced severe immunodeficiency received orthotopic implantation of MDA-MB-231 human breast cancer cells followed by transplants of 5-bromo-2'-deoxyuridine (BrdU)-labeled Mito or P-Mito (200 μg [10 μg/μL]) through intratumoral injection at multiple points once a week for 4 weeks.

Radical Scavenging and Antiproliferative Effects of Cordycepin-Rich Ethanol Extract from Brown Rice-Cultivated Cordyceps militaris (Ascomycetes) Mycelium on Breast Cancer Cell Lines.

The yield and efficacy of bioactive compounds from Cordyceps militaris fruiting bodies and its fermented grains usually vary with the strain used. In this study, we compared the antiproliferative, apoptotic, and antioxidative properties of ethanolic extracts of fruiting bodies and solid-stated fermented rice (FRE) from two wild-type strains of C. militaris applied to human breast cancer cell lines.

Association of cyclophilin A level and pulse pressure in predicting recurrence of cerebral infarction.

Cyclophilin A (CypA), secreted from vascular smooth muscle cells and inflammatory cells in response to oxidative stress, promotes vascular atherosclerosis and development of carotid stenosis. Increased concentration of plasma CypA in acute cerebral infarction was demonstrated clinically. The primary aim of this study was to investigate the prognostic impact between CypA level and outcome in patients with acute ischemic stroke.