Activation of TRPC (Transient Receptor Potential Canonical) Channel Currents in Iron Overloaded Cardiac Myocytes.

Background: Arrhythmias and heart failure are common cardiac complications leading to substantial morbidity and mortality in patients with hemochromatosis, yet mechanistic insights remain incomplete. We investigated the effects of iron (Fe) on electrophysiological properties and intracellular Ca (Ca) handling in mouse left ventricular cardiomyocytes.

Methods: Cardiomyocytes were isolated from the left ventricle of mouse hearts and were superfused with Fe/8-hydroxyquinoline complex (5-100 μM).

Myeloid differentiation protein 2 mediates angiotensin II-induced inflammation and mesenchymal transition in vascular endothelium.

Angiotensin II (Ang II)-induced vascular inflammation and injury entails endothelial to mesenchymal transition (EndMT). Recent studies have shown that Ang II engages toll-like receptor 4 (TLR4) in the vasculature to mediate adverse effects. Here, we aimed to investigate whether myeloid differentiation protein 2 (MD2), an extracellular molecule indispensable for TLR4 activation, mediates Ang II-induced vascular injury and EndMT.

Silencing of lipocalin-2 improves cardiomyocyte viability under iron overload conditions via decreasing mitochondrial dysfunction and apoptosis.

This study aimed to investigate the mechanistic roles of LCN-2 and LCN-2 receptors (LCN-2R) as iron transporters in cardiomyocytes under iron overload condition. H9c2 cardiomyocytes were treated with either LCN-2 small interfering RNA (siRNA) or LCN-2R siRNA or L-type or T-type calcium channel (LTCC or TTCC) blockers, or iron chelator deferiprone (DFP). After the treatments, the cells were exposed to Fe or Fe , after that biological parameters were determined.

Cognitive impairment is associated with mitochondrial dysfunction in peripheral blood mononuclear cells of elderly population.

Cognitive impairment is commonly found in the elderly population. Evidence suggests that mitochondrial function in lymphocytes are potential biomarkers in the progression of neurodegeneration, as peripheral mitochondrial function is associated with mild cognitive impairment (MCI) in the elderly population. Therefore, we hypothesize that impaired mitochondrial ATP production and oxidative stress in peripheral blood mononuclear cells (PBMCs) are associated with cognitive impairment in the elderly population.

Effects of metformin on atrial and ventricular arrhythmias: evidence from cell to patient.

Metformin has been shown to have various cardiovascular benefits beyond its antihyperglycemic effects, including a reduction in stroke, heart failure, myocardial infarction, cardiovascular death, and all-cause mortality. However, the roles of metformin in cardiac arrhythmias are still unclear. It has been shown that metformin was associated with decreased incidence of atrial fibrillation in diabetic patients with and without myocardial infarction.

Not only metformin, but also D-allulose, alleviates metabolic disturbance and cognitive decline in prediabetic rats.

Background: Prediabetes can be characterized as obesity with metabolic disturbance, leading to cognitive decline and brain pathologies. D-allulose administration in obese animals decreased metabolic disturbance. However, the comparative effects of D-allulose and metformin on cognition and brain functions in the diet-induced prediabetic condition are unclear.

Donepezil attenuated cardiac ischemia/reperfusion injury through balancing mitochondrial dynamics, mitophagy, and autophagy.

Cardiac autonomic imbalance including sympathetic overactivity and diminished parasympathetic activity is associated with left ventricular (LV) dysfunction in cases of cardiac ischemia/reperfusion (I/R) injury. Electrical stimulation to increase vagal activity has been shown to reduce infarct size and decrease fatal arrhythmias in cardiac I/R injury. However, the benefits of a parasympathomimetic drug on the heart during I/R are unclear.

Neurotensin receptor 1 agonist provides neuroprotection in pre-diabetic rats.

Exogenous treatment of a neurotensin receptor 1 (NTR1) agonist exerted the neuroprotection in an obese and Alzheimer's model. However, the effects of NTR1 modulation on peripheral/hippocampal impairment and cognitive deficit following sustained HFD consumption are poorly understood. Forty rats received a normal diet (ND) or HFD for 16 weeks.

Contrast-induced nephropathy and oxidative stress: mechanistic insights for better interventional approaches.

Contrast-induced nephropathy (CIN) or contrast-induced acute kidney injury (CI-AKI) is an iatrogenic acute kidney injury observed after intravascular administration of contrast media for intravascular diagnostic procedures or therapeutic angiographic intervention. High risk patients including those with chronic kidney disease (CKD), diabetes mellitus with impaired renal function, congestive heart failure, intraarterial intervention, higher volume of contrast, volume depletion, old age, multiple myeloma, hypertension, and hyperuricemia had increased prevalence of CIN. Although CIN is reversible by itself, some patients suffer this condition without renal recovery leading to CKD or even end-stage renal disease which required long term renal replacement therapy.

Pharmacological inhibition of mitochondrial fission attenuates cardiac ischemia-reperfusion injury in pre-diabetic rats.

An increase in the number of fragmented mitochondria contributes to the pathogenesis of ischemia-reperfusion (I/R) injury. Also, mitochondrial fission has shown an increase in obese condition. However, the cardioprotective roles of a mitochondrial fission inhibitor in obesity with cardiac I/R injury are unclear.

The Protective and Reparative Role of Colony-Stimulating Factors in the Brain with Cerebral Ischemia/Reperfusion Injury.

Stroke is a debilitating disease and has the ability to culminate in devastating clinical outcomes. Ischemic stroke followed by reperfusion entrains cerebral ischemia/reperfusion (I/R) injury, which is a complex pathological process and is associated with serious clinical manifestations. Therefore, the development of a robust and effective poststroke therapy is crucial.

The possible roles of necroptosis during cerebral ischemia and ischemia / reperfusion injury.

Cell death is a process consequential to cerebral ischemia and cerebral ischemia/reperfusion (I/R) injury. Recent evidence suggest that necroptosis has been involved in the pathogenesis of ischemic brain injury. The mechanism of necroptosis is initiated by an activation of inflammatory receptors including tumor necrosis factor, toll like receptor, and fas ligands.

Myeloid differentiation factor 2 in the heart: Bench to bedside evidence for potential clinical benefits?

Cardiac inflammation has been involved in many pathological processes in the heart including cardiac hypertrophy, fibrosis, adverse remodeling, and dysfunction. Myeloid differentiation factor 2 (MD2) is a key mediating protein that has been shown to contribute to the inflammatory process. MD2 is required for the activation of TLR4 in the form of dimerization complex.

The Effect of Mindfulness-Based Intervention on Brain-Derived Neurotrophic Factor (BDNF): A Systematic Review and Meta-Analysis of Controlled Trials.

This systematic review aims to answer three questions. First, how much do mindfulness-based interventions (MBIs) affect peripheral brain-derived neurotrophic factor (BDNF)? Second, do mindfulness exercise-based interventions (exercise-MBIs) and mindfulness meditation-based interventions (meditation-MBIs) affect peripheral BDNF differently? Third, does the age of participants and the accumulative hours of MBI practice affect peripheral BDNF? We included randomized controlled trials comparing MBI and no intervention in adults (age >18 years) who reported peripheral BDNF. Database searches included PubMed, CINAHL, CENTRAL, PsyInfo, and Scopus.

D-allulose provides cardioprotective effect by attenuating cardiac mitochondrial dysfunction in obesity-induced insulin-resistant rats.

Purpose: Obesity-induced insulin resistant is associated with cardiovascular diseases via impairing cardiac mitochondria. Recently, D-allulose could protect β-islets and improve insulin resistance. However, the effects of D-allulose on the heart and cardiac mitochondrial function under obesity-induced insulin-resistant condition has not been investigated.

Influenza immunization does not predominantly alter levels of phenytoin, and cytochrome P-450 enzymes in epileptic patients receiving phenytoin monotherapy.

Objective: The study aims to test the effect of influenza vaccination on phenytoin, CYP2C9, and IFNγ levels in epileptic patients receiving phenytoin monotherapy METHODS: Thirty-one epileptic patients receiving stable-dose phenytoin monotherapy were enrolled onto the study. Serum concentrations of phenytoin, CYP2C9, and IFNγ were compared before and after influenza immunization. The participants were given 0.

Donepezil provides neuroprotective effects against brain injury and Alzheimer's pathology under conditions of cardiac ischemia/reperfusion injury.

Cardiac ischemia/reperfusion (I/R) injury induces brain pathology. Donepezil, a well-known acetylcholine esterase (AChE) inhibitor, has been proven to exert neuroprotective effects against several neurodegenerative diseases. However, the comprehensive mechanism regarding the therapeutic potential of donepezil on the brain under cardiac I/R injury remains obscure.

Impact of iron overload on bone remodeling in thalassemia.

Introduction: Iron overload, a state with excessive iron storage in the body, is a common complication in thalassemia patients which leads to multiple organ dysfunctions including the bone. Iron overload-induced bone disease is one of the most common and severe complications of thalassemia including osteoporosis. Currently, osteoporosis is still frequently found in thalassemia even with widely available iron chelation therapy.

Possible links between gut-microbiota and attention-deficit/hyperactivity disorders in children and adolescents.

An association between gut-microbiota and several neuropsychiatric conditions including autism, depression, anxiety, schizophrenia, and attention-deficit/hyperactivity disorder (ADHD) has been observed. Despite being the most prevalent neurodevelopmental disorders in children and adolescents worldwide, the etiology and curative approaches to treatment of ADHD remain unclear. There is a probability that gut-microbiota may contribute to ADHD via bidirectional communication between the gut and brain, a system known as the "gut-brain axis".

Aging, obese-insulin resistance, and bone remodeling.

Aging, obesity, and insulin resistance are known to cause the impairment of bone regulation, resulting in an imbalance in bone homeostasis and pathological bone. The natural deterioration associated with the aging process, including increased adipogenicity, menopause, andropause and alteration of mesenchymal stem cell fate have been shown to be potential causes of decreased bone density, resulting in osteoporosis, in which is a major risk factor of bone fracture in elderly people. Furthermore, functional limitations of the aging musculoskeletal system cause physical inactivity and increased adipogenicity.

Mitochondrial abnormalities in neurodegenerative models and possible interventions: Focus on Alzheimer's disease, Parkinson's disease, Huntington's disease.

Mitochondrial abnormalities in the brain are considered early pathological changes in neurogenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD) and Huntington's disease (HD). The mitochondrial dysfunction in the brain can be induced by toxic proteins, including amyloid-beta (Aβ), phosphorylated tau, alpha-synuclein (α-syn) and mutant huntingtin (mtHTT). These proteins cause mitochondrial genome damage, increased oxidative stress, decreased mitochondrial membrane permeability, and diminished ATP production.

Mitochondrial Fusion Promoter Alleviates Brain Damage in Rats with Cardiac Ischemia/Reperfusion Injury.

Background: Cardiac ischemia/reperfusion (I/R) injury induces brain damage through increased blood-brain barrier (BBB) breakdown, microglial hyperactivity, pro-inflammatory cytokines, amyloid-β deposition, loss of dendritic spines, brain mitochondrial dysfunction, and imbalanced mitochondrial dynamics. Previous studies demonstrated that mitochondrial fusion promoter reduced cardiac damage from cardiac I/R injury; however, following cardiac I/R injury, the roles of mitochondrial dynamics on the brain have not been investigated.

Objective: To investigate the effects of pharmacological modulation using mitochondrial fusion promoter (M1) in the brain of rats following cardiac I/R injury.

Potential Roles of Myeloid Differentiation Factor 2 on Neuroinflammation and Its Possible Interventions.

Neuroinflammation is the primary response by immune cells in the nervous system to protect against infection. Chronic and uncontrolled neuroinflammation triggers neuronal injury and neuronal death resulting in a variety of neurodegenerative disorders. Therefore, fine tuning of the immune response in the nervous system is now extensively considered as a potential therapeutic intervention for those diseases.

Acute metformin treatment provides cardioprotection via improved mitochondrial function in cardiac ischemia / reperfusion injury.

Cardiac ischemia/reperfusion (I/R) injury following reperfusion therapy in acute myocardial infarction results in mitochondrial dynamic imbalance and cardiomyocyte apoptosis. Although diabetic patients taking metformin have been shown to have a lower risk of myocardial infarction, the efficacy of the cardioprotection conferred by metformin regarding the mitochondrial function and dynamic in cardiac I/R injury are still inconclusive. In addition, the comparative effects between different doses of metformin given acutely prior to cardiac I/R injury have never been investigated.

Acute administration of metformin prior to cardiac ischemia/reperfusion injury protects brain injury.

Myocardial ischemia is the malperfusion of cardiac tissue due to a blockage in a coronary artery. Subsequent return of blood flow to the ischemic area of the heart, results in ischemia/reperfusion (I/R) injury in the heart and other organs, including the brain. Besides the cardioprotective effects of metformin on the heart against cardiac I/R injury, metformin also reduced neuronal injury in a stroke model.