Effects of high glutamate concentrations on mitochondria of human neuroblastoma SH-SY5Y cells.

Background: The excess amount of glutamate in neurons is associated with the excitotoxicity and neurodegenerative diseases. Glutamate induces neurotoxicity primarily by immense influx of Ca arising from overstimulation of the NMDA subtype of glutamate receptors. The neuronal death induced by the overstimulation of glutamate receptors depends critically on a sustained increase in mitochondrial Ca influx and impairment in mitochondrial functions.

Congenital Lung Malformations: Experience From a Tertiary Care Center in India.

Background: There are limited data on congenital lung malformations (CLM) and their clinical course from developing countries.

Methods: A 10-year retrospective chart review of records of children with CLM attending pediatric chest clinic at an Indian tertiary care center was conducted.

Results: Among the 48 children (24 boys) included in the review, the malformations included congenital lung ypoplasia/agenesis in 24 (50%), cystic pulmonary airway malformation in 9 (19%), bronchogenic/foregut cyst in 8 (18%), and congenital lobar emphysema in 4 (9%).

Increased oxidative stress and mitochondrial impairments associated with increased expression of TNF-α and caspase-3 in palmitic acid-induced lipotoxicity in myoblasts.

Saturated fatty acids, whose circulating levels are markedly increased in the body, significantly affect the growth and functions of skeletal muscle. These fatty acids may exert a detrimental effect on the undifferentiated skeletal myoblasts that may adversely affect their differentiation. In the present study, the exposure of myoblasts to excess palmitic acid caused an elevation of tumor necrosis factor-α expression and an increase in reactive oxygen species levels consistent with the enhanced inflammation and oxidative stress.

Cognitive impairments in type 2 diabetes, risk factors and preventive strategies.

Mild cognitive impairment (MCI) is a modifiable risk factor in progression of several diseases including dementia and type 2 diabetes. If cognitive impairments are not reversed at an early stage of appearance of symptoms, then the prolonged pathogenesis can lead to dementia and Alzheimer's disease (AD). Therefore, it is necessary to detect the risk factors and mechanism of prevention of cognitive dysfunction at an early stage of disease.

Downregulation of sirtuin 3 by palmitic acid increases the oxidative stress, impairment of mitochondrial function, and apoptosis in liver cells.

Elevated levels of saturated fatty acids show a strong cytotoxic effect in liver cells. Sirtuin 3 (SIRT3), a mitochondrially localized member of NAD -dependent deacetylase has been shown to protect hepatocytes against the oxidative stress. The role of SIRT3 on the cytotoxicity caused by fatty acids in liver cells is not fully understood.

Synaptosomal and mitochondrial oxidative damage followed by behavioral impairments in streptozotocin induced diabetes mellitus: restoration by Malvastrum tricuspidatum.

Synaptosomal and mitochondrial impairments in the brain of diabetic individual manifest metabolic risk factors that most likely affect the brain functions. Diabetes is associated with the structural and functional alterations of the brain and neuronal loss leading to cognitive and other behavioral impairments, thus reducing the quality of life. The biochemical mechanisms underlying the diabetes-associated behavioral decline are poorly understood.

Metabolic enzymes dysregulation in heart failure: the prospective therapy.

The heart failure accounts for the highest mortality rate all over the world. The development of preventive therapeutic approaches is still in their infancy. Owing to the extremely high energy demand of the heart, the bioenergetics pathways need to respond efficiently based on substrate availability.

Study of apoptosis-related interactions in colorectal cancer.

Abnormalities in apoptotic functions contribute to the pathogenesis of colorectal cancer. In this study, molecular interactions behind the apoptotic regulation have been explored. For this purpose, enrichment analysis was performed considering microRNAs (miRNAs) that putatively target TP53 and altered during colon cancer.

Increase in oxidative stress and mitochondrial impairment in hypothalamus of streptozotocin treated diabetic rat: Antioxidative effect of Withania somnifera.

Hypothalamus, the primary brain region for glucose sensing, is severely affected by oxidative stress in diabetes mellitus. Oxidative stress in this region of brain may cause severe impairment in neuronal metabolic functions. Mitochondria are prominent targets of oxidative stress and the combination of increased oxidative stress and mitochondrial dysfunctions may further decline hypothalamic neuronal functions.

Identification and Pharmacological Analysis of High Efficacy Small Molecule Inhibitors of EGF-EGFR Interactions in Clinical Treatment of Non-Small Cell Lung Carcinoma: a Computational Approach.

Inhibition of EGFR-EGF interactions forms an important therapeutic rationale in treatment of non-small cell lung carcinoma. Established inhibitors have been successful in reducing proliferative processes observed in NSCLC, however patients suffer serious side effects. Considering the narrow therapeutic window of present EGFR inhibitors, the present study centred on identifying high efficacy EGFR inhibitors through structure based virtual screening strategies.

Neurodegenerative diseases: From available treatments to prospective herbal therapy.

Neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and many others represent a relevant health problem with age worldwide. Efforts have been made in recent years to discover the mechanism of neurodegenerative diseases and prospective therapy that can help to slow down the effects of the aging and prevent these diseases. Since pathogenesis of these diseases involves multiple factors therefore the important task for neuroscientists is to identify such multiple factors and prevent age-associated neurodegenerative diseases.

Enhanced sensitivity of double gate junctionless transistor architecture for biosensing applications.

In the present work, we demonstrate the potential of double gate junctionless (JL) architecture for enhanced sensitivity for detecting biomolecules in cavity modulated field effect transistors (FETs). The higher values of body factor, achieved in asymmetric gate operation under impact ionization is utilized for enhanced sensing margin which is nearly five times higher than compared to symmetrical mode operation. The intrinsic detection sensitivity is evaluated in terms of threshold voltage change, and the ratio of drain current in the presence and absence of biomolecules in JL nanotransistors.

Flavonoid-based therapies in the early management of neurodegenerative diseases.

During the past several years, there has been enormous progress in the understanding of the causative factors that initiate neuronal damage in various neurodegenerative diseases, including Alzheimer disease, Parkinson disease, multiple sclerosis, amyotrophic lateral sclerosis, and Huntington disease. Preventing neuronal damage and neuronal death will have a huge clinical benefit. However, despite major advances in causative factors that trigger these neurodegenerative diseases, to date there have been no therapies available that benefit patients who suffer from these diseases.

Mitochondrial sirtuins: emerging roles in metabolic regulations, energy homeostasis and diseases.

The energy production and metabolic homeostasis are well-orchestrated networks of carbohydrate, lipid and protein metabolism. These metabolic pathways are integrated by a key cytoplasmic organelle, the mitochondria, leading to production of many metabolic intermediates and harvest cellular energy in the form of ATP. Sirtuins are a highly conserved family of proteins that mediate cellular physiology and energy demands in response to metabolic inputs.

Efficiency of mitochondrially targeted gallic acid in reducing brain mitochondrial oxidative damage.

Oxidative stress is associated with mitochondrial impairments. Supplying mitochondria with potent antioxidants can reduce oxidative stress—induced mitochondrial impairment. Gallic acid can be used to reduce oxidative burden in mitochondria.

Flavonoids in modulation of cell survival signalling pathways.

Flavonoids, a family of polyphenols, generally found in various fruits and vegetables, as well as in many plant beverages such as tea, pomegranate juice, raspberry, blueberries, and red wine. Recently, studies on flavonoids have attracted scientific attention as a potential nutritional strategy to prevent a broad range of chronic disorders. Many studies suggest that consumption of these flavonoids in sufficient amount plays neuroprotective, cardioprotective, anti-inflammatory, and chemopreventive roles.

Curcumin reduces oxidative damage by increasing reduced glutathione and preventing membrane permeability transition in isolated brain mitochondria.

Mitochondria are critical regulators of energy metabolism and programmed cell death pathways. Mitochondria are also the major site for the production of reactive oxygen species which make this organelle more susceptible to oxidative damage and impairments of mitochondrial functions. Antioxidants have been of limited therapeutic success to ameliorate the toxic effects of oxidative stress in mitochondria.

Statins lower calcium-induced oxidative stress in isolated mitochondria.

Statins are widely used cholesterol-lowering agents that exert cholesterol-independent effects including antioxidative. The present study delineates the effects of statins, atorvastatin, and simvastatin on oxidative stress and functions of mitochondria that are the primary cellular sources of oxidative stress. In isolated rat liver mitochondria, both the statins prevented calcium-induced cytochrome c release, lipid peroxidation, and opening of the mitochondrial membrane permeability transition (MPT).

Dietary restriction lowers endogenous levels of oxidative stress in different brain regions of adult mice.

Increase in the cellular burden of oxidative stress is critically involved in various pathological manifestations of aging, including age-related neurological disorders. Dietary restriction can lower reactive oxygen species formation, and thereby lower oxidative damage in the brain. The brain consists of a diverse group of neurons with varying functions.

Amyloid-β as a modulator of synaptic plasticity.

Alzheimer's disease is associated with synapse loss, memory dysfunction, and pathological accumulation of amyloid-β (Aβ) in plaques. However, an exclusively pathological role for Aβ is being challenged by new evidence for an essential function of Aβ at the synapse. Aβ protein exists in different assembly states in the central nervous system and plays distinct roles ranging from synapse and memory formation to memory loss and neuronal cell death.

Importance of cytochrome c redox state for ceramide-induced apoptosis of human mammary adenocarcinoma cells.

Background: Ceramides are intracellular lipid mediator implicated in various cellular responses, including oxidative stress and programmed cell death. Studies demonstrated strong links between ceramide and the mitochondria in the regulation of apoptosis. However, the mechanism of apoptosis induced by ceramides is not fully understood.

Alpha-synuclein overexpression and aggregation exacerbates impairment of mitochondrial functions by augmenting oxidative stress in human neuroblastoma cells.

Overexpression of alpha-synuclein and oxidative stress has been implicated in the neuronal cell death in Parkinson's disease. Alpha-synuclein associates with mitochondria and excessive accumulation of alpha-synuclein causes impairment of mitochondrial functions. However, the mechanism of mitochondrial impairment caused by alpha-synuclein is not fully understood.

mAtNOS1 induces apoptosis of human mammary adenocarcinoma cells.

mAtNOS1 is a novel gene recently reported in mammalian genome with functions that are not fully understood. The present study shows that in human mammary adenocarcinoma MCF-7 cells, mAtNOS1 expression increases mitochondrial nitric oxide and calcium. Our study further shows that overexpression of mAtNOS1 induces apoptosis in MCF-7 cells by increasing mitochondrial protein tyrosine nitration and cytochrome c release.

Age-related decreases in NAD(P)H and glutathione cause redox declines before ATP loss during glutamate treatment of hippocampal neurons.

Age-related glutamate excitotoxicity depends in an unknown manner on active mitochondria, which are key determinants of the cellular redox potential. Compared with embryonic and middle-aged neurons, old-aged rat hippocampal neurons have a lower resting reduced nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) and a lower redox ratio (NAD(P)H/flavin adenine nucleotide). Glutamate treatment resulted in an initial increase in NAD(P)H concentrations in all ages, followed by a profound calcium-dependent, age-related decline in NAD(P)H concentration and redox ratio.

Detection assays for determination of mitochondrial nitric oxide synthase activity; advantages and limitations.

Nitric oxide (NO) is a reactive radical synthesized by members of the NO synthase (NOS) family, including mitochondrial-specific NOS (mtNOS). Some of the assays used for the determination of cytoplasmic NOS activity have been utilized to detect mtNOS activity. However, it seems that many of those assays need to be adjusted and optimized to detect NO in the unique environment of mitochondria.