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Biometals such as copper, zinc and iron have key biological functions, however, aberrant metabolism can lead to detrimental effects on cell function and survival. These biometals have important roles in the brain, driving cellular respiration, antioxidant activity, intracellular signaling and many additional structural and enzymatic functions. There is now considerable evidence that abnormal biometal homeostasis is a key feature of many neurodegenerative diseases and may have an important role in the onset and progression of disorders such as Alzheimer’s, Parkinson’s, prion and motor neuron diseases. Recent studies also support biometal roles in a number of less common neurodegenerative disorders. The role of biometals in a growing list of brain disorders is supported by evidence from a wide range of sources including molecular genetics, biochemical studies and biometal imaging. These studies have spurred a growing interest in understanding the role of biometals in brain function and disease as well as the development of therapeutic approaches that may be able to restore the altered biometal chemistry of the brain. These approaches range from genetic manipulation of biometal transport to chelation of excess metals or delivery of metals where levels are deficient. A number of these approaches are offering promising results in cellular and animal models of neurodegeneration with successful translation to pre-clinical and clinical trials. At a time of aging populations and slow progress in development of neurotherapeutics to treat age-related neurodegenerative diseases, there is now a critical need to further our understanding of biometals in neurodegeneration. This issue covers a broad range of topics related to biometals and their role in neurodegeneration. It is hoped that this will inspire greater discussion and exchange of ideas in this crucial area of research and lead to positive outcomes for sufferers of these neurodegenerative diseases.

Iron --- Zinc --- Copper --- Manganese --- Metals --- Brain --- Neurons --- neurodegenerative disease --- Alzheimer's disease

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Early in the 80’s date the first observations on the existence of hormonal steroids that may be synthesized and act in the nervous system. In order to refer to these endogenous steroids, proved important to control both central and peripheral nervous system, it was proposed the term “neurosteroids” (NSs). Over the years, their importance in regulating the physiological functions of neuronal and glial cells increased progressively. These steroids can be involved in several pathophysiological conditions such as depression, anxiety, premenstrual syndrome (PMS), schizophrenia and Alzheimer disease. Among the different classes of NSs, the progestagens revealed particularly important. The progesterone metabolite 5a-pregnan-3a-ol-20-one, also named tetrahydroprogesterone or allopregnanolone (ALLO) was one of the first most important steroid that was originally shown to act as neurosteroid. ALLO is synthesized through the action of the 5aR-3a-HSD, which converts P into DHP and subsequently, via a bidirectional reaction, into ALLO. NSs exert complex effects in the nervous system through ‘classic’, genomic, and ‘non-classic’, non-genomic actions. ALLO displays a rapid ‘non-genomic’ effect, which mainly involves the potent modulation of the GABA type A (GABA-A) receptor function. Recently a membrane receptor has been identified as target for ALLO effects, i.e. the membrane progesterone receptors (mPRs) that are able to activate a signalling cascade through G protein dependent mechanisms. By these ways, ALLO is able to modulate several cell functions, acting as neurogenic molecule on neural progenitor cells, as well as by activating proliferation and differentiation of glial cells in the central and peripheral nervous system. In this topic, we review the most recent acquisitions in the field of neurosteroids, focusing our attention on ALLO because its effects on the physiology of neurons and glial cells of the central and peripheral nervous system are intriguing and could potentially lead to the development of new strategies for neuroprotection and/or regeneration of injured nervous tissues and for the treatment of neuropsychiatric disorders.

neurosteroid --- Tetrahydroprogesterone --- GABA A receptor --- Membrane progesterone receptor --- Non genomic action --- ganaxolone --- neuropsychiatric disorder --- neurodegenerative disease --- Pain --- PKC epsilon

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Amyotrophic lateral sclerosis (ALS) is a rapidly progressive, devastating and fatal disease characterized by selective loss of upper and lower motor neurons of the cerebral cortex, brainstem, spinal cord and muscle atrophy. In spite of many years of research, the pathogenesis of ALS is still not well understood. ALS is a multifaceted genetic disease, in which genetic susceptibility to motor neuron death interacts with environmental factors and there is still no cure for this deleterious disease. At present, there is only one FDA approved drug, Riluzole which according to past studies only modestly slows the progression of the disease, and improves survival by up to three months. The suffering of the ALS patients, and their families is enormous and the economic burden is colossal. There is therefore a pressing need for new therapies. Different molecular pathways and pathological mechanisms have been implicated in ALS. According to past studies, altered calcium homeostasis, abnormal mitochondrial function, protein misfolding, axonal transport defects, excessive production of extracellular superoxide radicals, glutamate-mediated excitotoxicity, inflammatory events, and activation of oxidative stress pathways within the mitochondria and endoplasmic reticulum can act as major contributor that eventually leads to loss of connection between muscle and nerve ultimately resulting to ALS. However, the detailed molecular and cellular pathophysiological mechanisms and origin and temporal progression of the disease still remained elusive. Ongoing research and future advances will likely advance our improve understanding about various involved pathological mechanism ultimately leading to discoveries of new therapeutic cures. Importantly, clinical biomarkers of disease onset and progression are thus also urgently needed to support the development of the new therapeutic agents and novel preventive and curative strategies. Effective translation from pre-clinical to clinical studies will further require extensive knowledge regarding drug activity, bioavailability and efficacy in both the pre-clinical and clinical setting, and proof of biological activity in the target tissue. During the last decades, the development of new therapeutic molecules, advance neuroimaging tools, patient derived induced stem cells and new precision medicine approaches to study ALS has significantly improved our understanding of disease. In particular, new genetic tools, neuroimaging methods, cellular probes, biomarker study and molecular techniques that achieve high spatiotemporal resolution have revealed new details about the disease onset and its progression. In our effort to provide the interested reader, clinician and researchers a comprehensive summaries and new findings in this field of ALS research, hereby we have created this electronic book which comprises of twenty seven chapters having various reviews, perspective and original research articles. All these chapters and articles in this book not only summarize the cutting-edge techniques, approaches, cell and animal models to study ALS but also provide unprecedented coverage of the current developments and new hypothesis emerging in ALS research. Some examples are novel genetic and cell culture based models, mitochondria-mediated therapy, oxidative stress and ROS mechanism, development of stem cells and mechanism-based therapies as well as novel biomarkers for designing and testing effective therapeutic strategies that can benefit ALS patients who are at the earlier stages in the disease. I am extremely grateful to all the contributors to this book and want to thank them for their phenomenal efforts. Amyotrophic lateral sclerosis (ALS) is a rapidly progressive, devastating and fatal disease characterized by selective loss of upper and lower motor neurons of the cerebral cortex, brainstem, spinal cord and muscle atrophy. In spite of many years of research, the pathogenesis of ALS is still not well understood. ALS is a multifaceted genetic disease, in which genetic susceptibility to motor neuron death interacts with environmental factors and there is still no cure for this deleterious disease. At present, there is only one FDA approved drug, Riluzole which according to past studies only modestly slows the progression of the disease, and improves survival by up to three months. The suffering of the ALS patients, and their families is enormous and the economic burden is colossal. There is therefore a pressing need for new therapies. Different molecular pathways and pathological mechanisms have been implicated in ALS. According to past studies, altered calcium homeostasis, abnormal mitochondrial function, protein misfolding, axonal transport defects, excessive production of extracellular superoxide radicals, glutamate-mediated excitotoxicity, inflammatory events, and activation of oxidative stress pathways within the mitochondria and endoplasmic reticulum can act as major contributor that eventually leads to loss of connection between muscle and nerve ultimately resulting to ALS. However, the detailed molecular and cellular pathophysiological mechanisms and origin and temporal progression of the disease still remained elusive. Ongoing research and future advances will likely advance our improve understanding about various involved pathological mechanism ultimately leading to discoveries of new therapeutic cures. Importantly, clinical biomarkers of disease onset and progression are thus also urgently needed to support the development of the new therapeutic agents and novel preventive and curative strategies. Effective translation from pre-clinical to clinical studies will further require extensive knowledge regarding drug activity, bioavailability and efficacy in both the pre-clinical and clinical setting, and proof of biological activity in the target tissue. During the last decades, the development of new therapeutic molecules, advance neuroimaging tools, patient derived induced stem cells and new precision medicine approaches to study ALS has significantly improved our understanding of disease. In particular, new genetic tools, neuroimaging methods, cellular probes, biomarker study and molecular techniques that achieve high spatiotemporal resolution have revealed new details about the disease onset and its progression. In our effort to provide the interested reader, clinician and researchers a comprehensive summaries and new findings in this field of ALS research, hereby we have created this electronic book which comprises of twenty seven chapters having various reviews, perspective and original research articles. All these chapters and articles in this book not only summarize the cutting-edge techniques, approaches, cell and animal models to study ALS but also provide unprecedented coverage of the current developments and new hypothesis emerging in ALS research. Some examples are novel genetic and cell culture based models, mitochondria-mediated therapy, oxidative stress and ROS mechanism, development of stem cells and mechanism-based therapies as well as novel biomarkers for designing and testing effective therapeutic strategies that can benefit ALS patients who are at the earlier stages in the disease. I am extremely grateful to all the contributors to this book and want to thank them for their phenomenal efforts.

Amyotrophic lateral sclerosis (ALS) --- Motor neuron disease (MND) --- Superoxide dismutase 1 (SOD1) --- Mitochondria --- excitotoxicity --- Ca2+ signaling --- Riluzole --- neurodegenerative disease --- multidrug therapy --- multifactorial disease

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This collection of review articles authored by international experts pulls together current information about the role of mitochondria in aging and diseases of aging. Mitochondria are vitally important cellular organelles and undergo their own aging process becoming less efficient in aged animals including humans. These changes have wide-ranging significance contributing to immune dysfunction (autoimmunity and immune deficiency), inflammation, delayed healing, skin and retinal damage, cancer and most of the degenerative diseases of aging. Mitochondrial aging predisposes to drug toxicity in the geriatric population and to many of the features of normal aging. The research detailed in this book summarizes current understanding of the role of mitochondria in the complex molecular changes of aging, moving on to specific diseases of aging. Mitochondrial dysfunction is an important target for development of treatments for aging and disease. The last article details how exercise is a treatment and combats many features of the aging process.

aging --- mitochondria --- inflammation --- innate immunity --- adaptive immunity --- immunosenescence --- cell danger response --- healing cycle --- mitochondria --- purinergic signaling --- metabokines --- sphingolipids --- integrated cell stress response --- de-emergence --- crabtree effect --- pasteur effect --- coenzyme Q10 --- aging --- age-related diseases --- mitochondrial dysfunction --- mitochondria --- skin --- ageing --- reactive oxygen species --- photoageing --- 25(OH)D --- 1,25(OH)2D --- aging --- cytokines --- inflammation --- morbidity and mortality --- prevention --- reactive oxygen species --- ultraviolet --- aging --- mitochondria --- retina --- optic nerve --- diabetic retinopathy --- age-related macular degeneration --- glaucoma --- drug-induced mitochondrial toxicity --- polypharmacy --- aging --- mitochondrial dysfunction --- insulin resistance --- type 2 diabetes --- mitochondrial transfer --- exosomes --- mitochondrial --- genetic mutations --- cardiovascular disease --- heart failure --- cardiomyopathy --- mitochondria --- cancer --- nucleotide metabolism --- DNA damage --- NAD+ --- mitochondria --- ALS --- axonal transport --- mitophagy --- SOD1 --- Miro1 --- PINK1 --- Parkin --- multiple sclerosis --- mitochondria --- neuroinflammation --- neurodegeneration --- Parkinson’s disease --- mitochondria --- ageing --- neurodegenerative disease --- Alzheimer’s disease --- eIF2? --- metabolism --- mitochondria --- proteostasis --- stress response --- aging --- exercise --- mitochondria --- aerobic --- ROS --- inflammation --- senescence --- lysosome --- autophagy --- mitophagy --- n/a

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The present Special Issue, “Innovative Extraction Techniques and Hyphenated Instrument Configuration for Complex Matrices Analysis”, aims to collect and to disseminate some of the most significant and recent contributions in the interdisciplinary area of innovative extraction procedures from complex matrices followed by validated analytical methods using hyphenated instrument configurations to support the optimization of the whole process and the scale-up possibility

branched-chain keto acids --- serum --- muscle --- HPLC-Q-TOF/MS --- wood --- odor --- volatile organic compounds --- gas chromatography-olfactometry --- Wuyi Rock tea --- quality --- UPLC-QTOF MS --- UPLC-QqQ MS --- metabolite profiling --- metabolomics --- cluster analysis --- cultivars --- Lycium ruthenicun --- flavonoid --- ruthenicunoid A --- SIRT1 --- Asphodeline lutea --- HPLC-PDA --- heavy metals --- tyrosinase --- diabetes --- neurodegenerative disease --- color analysis --- pigments --- MAE --- HPLC-PDA --- SFE --- Thymus algeriensis --- rare earth elements --- flow injection --- inductively coupled plasma-mass spectrometry --- seawater --- Hericium erinaceuns mycelium --- high-speed counter-current chromatography (HSCCC) --- genistein --- daidzein --- Fe3O4 --- modification --- alginate --- alkaloid --- ultrasound assisted extraction --- gelatin --- actinidin --- bovine hide --- physicochemical properties --- gel strength --- Semen Cuscutae --- ultra-high-performance liquid chromatography coupled to electrospray ionization mass spectrometry --- chlorogenic acids --- flavonoids --- steamed Panax notoginseng --- saponins --- extraction --- optimization --- antioxidant activity --- response surface methodology --- hematopoiesis --- microwave processing --- response surface methodology --- minor ginsenosides --- blood-enriching activity --- hemostatic activity --- ionic liquids --- sample preparation --- microextraction --- solid-phase microextraction --- dispersive liquid-liquid microextraction --- single-drop microextraction --- stir bar sorptive extraction --- stir cake sorptive extraction --- rosuvastatin --- metformin --- HILIC --- LC-MS --- therapeutic drug monitoring --- oolong tea --- Tieguanyin tea cultivar --- metabolite profiling --- UPLC-QTOF MS --- metabolomics --- Ajuga genevensis --- near-infrared spectroscopy --- dry extract --- fluid bed process --- microNIR --- in-line monitoring --- total polyphenolic content --- antioxidant --- flavonoids --- mouse melanoma B16 cells --- Panax notoginseng --- surfactant --- n/a --- ultra-high-performance liquid chromatography tandem mass spectrometry --- GHB --- GHB glucuronide --- nails --- endogenous values --- walnut septum --- polyphenols --- phytosterols --- HPLC-MS/MS --- Ultra-Turrax extraction --- biological activity --- antioxidant activity --- experimental design --- optimization --- phytochemicals