An Investigation of Fibulin-2 in Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is the most common inherited heart muscle disease, with a prevalence of at least 1 in 500 in the general population. The disease is pleiotropic and is characterized by an increased stiffness of the myocardium, partly due to changes in the extracellular matrix (ECM), with elevated levels of interstitial fibrosis. Myocardial fibrosis is linked to impaired diastolic function and possibly phenotypic heterogeneity of HCM. The ECM consists of a very large number of proteins, which actively interact with each other as well as with myocardial cells. The role of other multiple components of the ECM in HCM has not been defined. Fibulin-2 is a glycoprotein component of the ECM, which plays an important role during embryogenesis of the heart; however, its role in adult myocardium has not been adequately studied. We here describe, for the first time, abnormal expression of fibulin-2 in the myocardium in patients with HCM as compared to normal controls. This abnormal expression was localized in the cytoplasm of myocardial cells and in the interstitial fibroblasts. In addition, fibulin-2 levels, measured by ELISA, were significantly elevated in the serum of patients with HCM as compared to normal controls.

Molecular toxicity of Benzo(a)pyrene mediated by elicited oxidative stress infer skeletal deformities and apoptosis in embryonic zebrafish.

Benzo(a)pyrene (BaP) has become an integral component of disposed of plastic waste, organic pollutants, and remnants of combustible materials in the aquatic environment due to their persistent nature. The accumulation and integration of these polycyclic aromatic hydrocarbons (PAHs) have raised concern to human health and ecological safety. This study assessed the BaP-induced in vivo molecular toxicity with embryonic zebrafish inferred by oxidative stress and apoptosis. BaP was found to induce morphological and physiological abnormalities like delayed hatching (p < 0.05). Computational analysis demonstrated the high-affinity interaction of BaP with the zebrafish hatching enzyme (ZHE1) with Arg, Cys, Ala, Tyr, and Phe located at the active site revealing the influence of BaP on delayed hatching due to alteration of the enzyme structure. RT-PCR analysis revealed significant down-regulation of the skeletal genes Sox9a, SPP1/OPN, and Col1a1 (p < 0.05) genes. The cellular investigations unraveled that the toxicity of BaP extends to the skeletal regions of zebrafish (head, backbone, and tail) because of the elicited oxidative stress leading to apoptosis. The study extended the horizon of understanding of BaP toxicity at the molecular level which will enhance the indulgent and designing of techniques for better ecological sustainability.

Crosstalk between mitochondrial dysfunction, oxidative stress, and age related neurodegenerative disease: Etiologies and therapeutic strategies.

Mitochondrial function is vital for normal cellular processes. Mitochondrial damage and oxidative stress have been greatly implicated in the progression of aging, along with the pathogenesis of age-related neurodegenerative diseases (NDs), such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. Although antioxidant therapy has been proposed for the prevention and treatment of age-related NDs, unraveling the molecular mechanisms of mitochondrial dysfunction can lead to significant progress in the development of effective treatments against such diseases. Aging is associated with the generation and accumulation of reactive oxygen species (ROS) that are the major contributors to oxidative stress. Oxidative stress is caused because of the imbalance between the production of ROS and their oxidation, which can affect the mitochondrial respiratory chain function, thereby altering the membrane permeability and calcium homeostasis, along with increasing the heteroplasmic mtDNA and weakening the mitochondrial defense systems. Mitochondrial dysfunction mainly affects mitochondrial biogenesis and dynamics that are prominent in several age-related NDs. Mitochondrial dysfunction has a crucial role in the pathophysiology of age-related NDs. Several mitochondria targeted strategies, such as enhancing the antioxidant bioavailability via novel delivery systems, identifying unique mitochondrial proteins as specific drug targets, investigating the signaling pathways of mitochondrial biogenesis and dynamics, and identifying effective natural products are potentially effective to counteract mitochondrial dysfunction-related NDs.