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An electronic cigarette is a rechargeable device that produces an inhaled aerosol containing varying levels of nicotine, and inorganic and organic toxicants and carcinogenic compounds. The aerosol is generated by heating a solution of propylene glycol and glycerin with nicotine and flavoring ingredients at a high temperature. The e-cigarette was developed and marketed as a safer alternative to the regular cigarette which is known to be injurious to human health. However, published studies suggest that the aerosol of e-cigarette can also have adverse health effects. The main objective of this review is to briefly describe some consequences of e-cigarette smoking, and to present data showing that the resulting increased oxidative stress and inflammation are likely to be involved in effecting to lung damage. Other organs are also likely to be affected. The aerosol contains varying amounts of organic and inorganic toxicants as well as carcinogens, which might serve as the source of such deleterious events. In addition, the aerosol also contains nicotine, which is known to be addictive. E-cigarette smoking releases these toxicants into the air leading to inhalation by nonsmokers in residential or work place areas. Unlike regular tobacco smoke, the long-term consequences of direct and secondhand exposure to e-cigarette aerosol have not been extensively studied but based on available data, e-cigarette aerosol should be considered harmful to human health.

Single-point mutation diseases in which substitution of one nucleotide with another in a gene occurs include familial Alzheimer's disease (fAD), familial Parkinson's disease (fPD), and familial Creutzfeldt-Jacob disease (fCJD) as well as Huntington's disease (HD), sickle cell anemia, and hemophilia. Inevitability of occurrence of these diseases is certain. However, the time of appearance of symptoms could be influenced by the diet, environment, and possibly other genetic factors. There are no effective approaches to delay the onset or progression of symptoms of these diseases. The fact that increased oxidative stress and inflammation significantly contribute to the initiation and progression of these point mutation diseases shows that antioxidants could be useful. The major objectives are (a) to present evidence that increased oxidative stress and chronic inflammation are associated with selected single-point mutation diseases, such as fAD, fPD, and fCJD, HD, sickle cell anemia, and hemophilia; (b) to describe limited studies on the role of individual antioxidants in experimental models of some of these diseases; and (c) to discuss a rationale for utilizing a comprehensive mixture of micronutrients, which may delay the development and progression of symptoms of above diseases by simultaneously reducing oxidative and inflammatory damages.Key teaching pointsSelected single-point mutation diseases and their pattern of inheritanceCharacteristics of each selected single-point mutation diseaseEvidence for increased oxidative stress and inflammation in each diseasePotential reasons for failure of single antioxidants in human studiesRationale for using a comprehensive mixture of micronutrients in delaying the onset and progression of single-point mutation diseases.

The appearance of excessive inflammatory activity is associated with onset of many disease states. Such non-productive responses are often the basis of the mortality consequent to incurring numerous disorders. The current outbreak of coronavirus disease 2019 caused by the virus "severe acute respiratory syndrome coronavirus 2" is a striking reflection of the inadequacy of current medical science to adequately address this issue. The usefulness of a range of materials of botanical origin in the attenuation of both chronic and acute inflammatory responses to various disease stressors is described. The properties of preparations of plant-based origin often parallel those of synthesized pharmacologics, but differ from them in some key respects. These differences can lead to more traditional preparations having distinct therapeutic advantages but also a number of specific shortcomings. The strengths and weaknesses of these materials are objectively contrasted with that of a more orthodox pharmacological approach. Each of these emphases in style has specific advantages and they should not be considered as competitors, but rather as accomplices in combating adverse states involving derangement of immune function.

This short overview focuses on the causation and treatment of type 2 diabetes (T2D). Emphasis is given to the historical basis of understanding this disease and the background leading to emergence of the central role of insulin. The strengths of insulin administration in the treatment of diabetes are profound, but these need to be balanced against several serious shortcomings of its extended use. Some alternative approaches to T2D management are considered. Insulin is no longer considered as the first choice for type 2 diabetes, and an expanding range of new therapeutic possibilities is emerging. While these may lack the potency of insulin, at a minimum, they allow a major reduction in the intensity of insulin use. In view of the rising worldwide incidence of this disease, it is imperative to develop safe and inexpensive means of limiting its potential for impairment of normal functioning.

Prion diseases are a group of incurable infectious terminal neurodegenerative diseases caused by the aggregated misfolded PrPsc in selected mammals including humans. The complex physical interaction between normal prion protein PrPc and infectious PrPsc causes conformational change from the α- helix structure of PrPc to the β-sheet structure of PrPsc, and this process is repeated. Increased oxidative stress is one of the factors that facilitate the conversion of PrPc to PrPsc. This overview presents evidence to show that increased oxidative stress and inflammation are involved in the progression of this disease. Evidence is given for the participation of redoxsensitive metals Cu and Fe with PrPsc inducing oxidative stress by disturbing the homeostasis of these metals. The fact that some antioxidants block the toxicity of misfolded PrPc peptide supports the role of oxidative stress in prion disease. After exogenous infection in mice, PrPsc enters the follicular dendritic cells where PrPsc replicates before neuroinvasion where they continue to replicate and cause inflammation leading to neurodegeneration. Therefore, reducing levels of oxidative stress and inflammation may decrease the rate of the progression of this disease. It may be an important order to reduce oxidative stress and inflammation at the same time. This may be achieved by increasing the levels of antioxidant enzymes by activating the Nrf2 pathway together with simultaneous administration of dietary and endogenous antioxidants. It is proposed that a mixture of micronutrients could enable these concurrent events thereby reducing the progression of human prion disease.

Many studies show that daily consumption of high-fiber diet reduces the risk of developing kidney stones, inflammatory disease, colon cancer and other malignancies, obesity, type II diabetes, and cardiovascular disease. Dietary fibers are non-digestible polysaccharides that are composed of complex carbohydrates. Based on their relative solubility in water, dietary fibers can be divided into insoluble and soluble forms. Soluble fibers absorb water to form a gel in the intestine. Soluble fibers with the exception of Psyllium are more readily fermentable by the colon probiotic bacteria than insoluble fibers. An important property of insoluble fibers is the ability to bind with carcinogens, mutagens, and other toxic chemicals that are formed during digestion of food, and eliminate them through the feces. Soluble fibers can be degraded to short-chain fatty acids, such as butyrate, propionate, and acetate by fermentation. This review discusses mechanisms of action of fibers and their beneficial effects on the GI tract as well as on other organs. Among short-chain fatty acids, butyrate has been most extensively studied and the effects of sodium butyrate on cell culture and animal models are discussed in order to emphasize its potential value in prevention of certain diseases.

Many studies show that daily consumption of high-fiber diet is associated with a reduced risk of developing kidney stones, inflammatory disease, colon cancer and other malignancies, obesity, type II diabetes, and cardiovascular disease. Dietary fibers are non-digestible polysaccharides that are composed of complex carbohydrates. Based on their relative solubility in water, dietary fibers can be divided into insoluble and soluble forms. An important property of insoluble fibers is their ability to bind with carcinogens, mutagens, and other toxic chemicals that are formed during digestion of food and eliminate them through the feces. Soluble fibers can often be degraded to short-chain fatty acids, such as butyrate, propionate, and acetate by microbial fermentation. This review discusses mechanisms of action of fibers and their beneficial effects on the GI tract as well as on other organs. Among short-chain fatty acids, butyrate has been most extensively studied and the effects of sodium butyrate on cell culture and animal models are discussed in order to emphasize its potential value in prevention of certain diseases.

Telomeres are a repeated sequence -of bases found at the ends of chromosomes. In humans, this sequence is TTAGGG, which is repeated over 2000 times. Telomeres protect the ends chromosomes from fusion with nearby chromosomes, and allow effective replication of DNA. Each time a cell divides, 25-200 base pairs are lost from the terminal sequence of chromosomes. By becoming truncated during cell division, telomeres protect essential genes from being shortened and thus inactivated. In addition, telomeres are sensitive to inflammation and oxidative stress, which can further promote telomere shortening. Reduction in the length of telomeres leads to the cessation of cell division and thus cellular senescence and apoptosis. This review discusses evidence for the role of oxidative stress and inflammation in regulating the length of telomeres in mammalian cells during senescence. Evidence is presented suggesting that antioxidants and anti-inflammatories can reduce the pace of shortening of telomere length during aging. The distinctive properties of transformed cells suggest that treatment with such materials will have a deleterious rather than a protective effect on such abnormal cells.

MicroRNAs (miRs) are small non-coding single-stranded RNAs that bind to their complimentary sequences in the 3'-untranslated regions (3'-UTRs) of the target mRNAs that prevent their translation into the corresponding proteins. Since miRs are strongly expressed in cells of inner ear and play a role in regulating their differentiation, survival and function, alterations in their expression may be involved in the pathogenesis of hearing disorders. Although increased oxidative stress and inflammation are involved in initiation and progression of hearing disorders, it is unknown whether the mechanisms of damage produced by these biochemical events on inner ear cells are mediated by altering the expression of miRs. In neurons and non-neuronal cells, reactive oxygen species (ROS) and pro-inflammatory cytokines mediate their damaging effects by altering the expression of miRs. Preliminary data indicate that a similar mechanism of damage on hair cells produced by oxidative stress may exist in this disease. Antioxidants protect against hearing disorders induced by ototoxic agents or adverse health conditions; however, it is unknown whether the protective effects of antioxidants in hearing disorders are mediated by changing the expression of miRs. Antioxidants protect mammalian cells against oxidative damage by changing the expression of miRs. Therefore, it is proposed that a similar mechanism of protection by antioxidants against stress may be found in hearing disorders. This review article discusses novel concepts: (a) alterations in the expression of miRs may be involved in the pathogenesis of hearing disorders; (b) presents evidence from neurons and glia cells to show that oxidative stress and pro-inflammatory cytokines mediate their damaging effects by altering the expression of miRs; and proposes that a similar mechanism of damage by these biochemical events may be found in hearing loss; and (c) present data to show that antioxidants protect mammalian cells against oxidative by altering the expression of miRs. A similar role of antioxidants in protecting against hearing disorders is put forward. New studies are proposed to fill the gaps in the areas listed above.

Huntington's disease (HD) is a progressive fatal dominant hereditary neurodegenerative disease of the brain, which primarily affects the cortex and the striatum. The disorder is typified by an expansion of more than 35 repeats of the nucleotide triplet cytosine- adenine-guanosine (CAG) which codes for the amino acid glutamine in the huntingtin gene. Despite studies of several decades, there are no effective means to block or postpone the appearance of symptoms of HD. Analysis of these studies led us to propose that increased oxidative stress and chronic inflammation are earliest events in the pathogenesis of HD, and together with excessive glutamate release, participate in the progression of the disease. This review briefly describes evidence for the involvement of oxidative stress, chronic inflammation and glutamate in the pathogenesis of HD. It is proposed that attenuation of these biochemical abnormalities together, may delay the appearance of symptoms of HD. In order to achieve this goal, the simultaneous activation of the nuclear transcriptional factor-2/antioxidant response elements (Nrf2/ARE) pathway that would enhance the transcription of target genes coding for antioxidant enzymes and phase-2-detoxifying enzymes, and an elevation of the levels of antioxidant compounds by supplementation may be needed. Normal mechanisms of activation of Nrf2 requiring reactive oxygen species (ROS) may be impaired in HD, but certain antioxidant compounds can activate Nrf2 without ROS. Use of a combination of micronutrients that can activate the Nrf2/ARE pathway and enhance the levels of antioxidant compounds is suggested.

Post-traumatic stress disorder (PTSD) is a complex mental disorder with psychological and emotional components, caused by exposure to single or repeated extreme traumatic events found in war, terrorist attacks, natural or man-caused disasters, and by violent personal assaults and accidents. Mild traumatic brain injury (TBI) occurs when the brain is violently rocked back and forth within the skull following a blow to the head or neck as in contact sports, or when in close proximity to a blast pressure wave following detonation of explosives in the battlefield. Penetrating TBI occurs when an object penetrates the skull and damages the brain, and is caused by vehicle crashes, gunshot wound to the head, and exposure to solid fragments in the proximity of explosions, and other combat-related head injuries. Despite clinical studies and improved understanding of the mechanisms of cellular damage, prevention and treatment strategies for patients with PTSD and TBI remain unsatisfactory. To develop an improved plan for treating and impeding progression of PTSD and TBI, it is important to identify underlying biochemical changes that may play key role in the initiation and progression of these disorders. This review identifies three common biochemical events, namely oxidative stress, chronic inflammation and excitotoxicity that participate in the initiation and progression of these conditions. While these features are separately discussed, in many instances, they overlap. This review also addresses the goal of developing novel treatments and drug regimens, aimed at combating this triad of events common to, and underlying, injury to the brain.

A link between Alzheimer's disease (AD) and an excess presence of oxidant free radicals in the brain has frequently been reported. It is generally assumed that such oxidative stress and related cellular damage is caused by inflammatory changes in the brain and is consequent to amyloid deposition. This review makes the argument that elevated oxidative stress in AD is an early causal event in the initiation and advancement of this disease. Oxidative stress can be decreased by enhancing antioxidant enzymes through activation of the cytoplasmic transcriptional factor (Nrf2)/ARE (antioxidant response element) pathway, and by dietary and endogenous antioxidant chemicals. Reduction in the binding ability of Nrf2 to ARE lowers antioxidant enzyme levels. Decreased levels of Nrf2 and augmentation of oxidative stress in AD suggest that the ROS-dependent mechanism of activating the Nrf2/ARE pathway has become unresponsive. A combination of agents that can either activate the Nrf2-ARE pathway by ROS-independent mechanisms, or by acting directly as antioxidant chemicals, may be necessary to reduce oxidative stress in AD. Earlier shortcomings of using individual antioxidants may be due to consideration of antioxidants as pharmacological agents, ignoring the fact that individual antioxidants can be transmuted in the highly oxidant milieu that is present in AD. Interactions between various cellular compartments may require simultaneous examination of more than one agent. The clinical utility of such a more integrative method can reveal interactive effects such as those found in nutritional research and this can compensate for any mechanistic shortcomings of simultaneous testing of more than a single agent.

Recently the relationship between oxidative stress and aging has been brought into question. It has been suggested that while oxidative events may play a role in the progression of age-related pathologies, it is not relevant to aging processes not involving specific diseases associated with senescence. The evidence in support of this concept is largely based on studies with the roundworm, Caenorhabditis elegans (C. elegans) that has been extensively used as a model system to study aging. This commentary evaluates data derived from C. elegans and documents that the preponderance of evidence from this species supports the role of pro-oxidant events as being a significant contributor to normal aging. Possible reasons for some anomalous findings conflicting with this concept, are discussed.