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Coenzyme Q10 (CoQ10) is an essential component of the electron transport chain. It also acts as an antioxidant in cellular membranes. It can be endogenously produced in all cells by a specialized mitochondrial pathway. CoQ10 deficiency, which can result from aging or insufficient enzyme function, has been considered to increase oxidative stress. Some drugs, including statins and bisphosphonates, often used by older individuals, can interfere with enzymes responsible for endogenous CoQ10 synthesis. Oral supplementation with high doses of CoQ10 can increase both its circulating and intracellular levels and several clinical trials observed that its administration provided beneficial effects on different disorders such as cardiovascular disease and inflammation which have been associated with low CoQ10 levels and high oxidative stress. Moreover, CoQ10 has been suggested as a promising therapeutic agent to prevent and slow the progression of other diseases including metabolic syndrome and type 2 diabetes, neurodegenerative and male infertility. However, there is still a need for further studies and well-designed clinical trials involving a large number of participants undergoing longer treatments to assess the benefits of CoQ10 for these disorders. [ABSTRACT FROM AUTHOR]

Gut microbes share a symbiotic relationship with humans and perform several metabolic and physiological functions essential for human survival. It has been established in several scientific studies that obesity and other metabolic complications are always associated with disturbed gut microbiota profile, also called gut dysbiosis. In recent years, bariatric surgery has become a treatment of choice for weight loss, and it forms an important part of obesity management strategies across the globe. Interestingly, bariatric surgery has been shown to alter gut microbiota profile and synthesize short-chain fatty acids by gut microbes. In other words, gut microbes play a crucial role in better clinical outcomes associated with bariatric surgery. In addition, gut microbes are important in reducing weight and lowering the adverse events post-bariatric surgery. Therefore, several prebiotics, probiotics and postbiotics are recommended for patients who underwent bariatric surgery procedures for better clinical outcomes. The present review aims to understand the possible association between gut microbes and bariatric surgery and present scientific evidence showing the beneficial role of gut microbes in improving therapeutic outcomes of bariatric surgery. [ABSTRACT FROM AUTHOR]

Bariatric surgery or weight loss surgery has been in practice for achieving significant weight loss in patients who have failed to achieve weight loss after pharmacological interventions. The rising cases of obesity are a triggering factor for more bariatric surgeries worldwide. Interestingly, sustained weight loss achieved post-bariatric surgery offers metabolic advantages, and patients show improved glucose and lipid metabolisms. Bariatric surgery is directly linked to higher incidences of vitamin, mineral, and trace element deficiencies, thus making patients susceptible to anemia, osteoporosis, and cardiomyopathy. Reduced nutrient absorption capacity, dietary changes, dietary restriction, and altered gastrointestinal tract morphology are some reasons for nutritional deficiency observed in post-bariatric surgery procedures. Micro-and-macronutrient deficiency observed in patients during the postoperative phase requires continuous monitoring of nutritional parameters. Therefore, adequate multivitamin and mineral supplements become essential to prevent/overcome micronutrient deficiencies. Bariatric surgery also raises the risk of small for gestational age (SGA) babies. Hence, a 12 − 24 months gap is recommended between bariatric surgery and pregnancy to achieve desired weight loss targets. The topic of this review is the impact of bariatric surgery procedures on vitamin and mineral absorption and the role of dietary supplements in maintaining a healthy nutritional balance during the postoperative phase. [ABSTRACT FROM AUTHOR]

Prostate disorders are commonplace in medicine, especially in older men, with prostatitis, benign prostatic hyperplasia, and prostate cancer being the most abundant pathologies. The complexity of this organ, however, turns treatment into a challenge. In this review, we aim to provide insight into the efficacy of alternative treatments, which are not normally used in conventional medicine, with a particular focus on nutrients. In order to understand why and how nutrition can be beneficial in diseases of the prostate, we give an overview of the known characteristics and features of this organ. Then, we provide a summary of the most prevalent prostate illnesses. Finally, we propose nutrition-based treatment in each of these prostate problems, based on in-depth research concerning its effects in this context, with an emphasis on surgery. Overall, we plead for an upgrade of this form of alternative treatment to a fully recognized mode of therapy for the prostate. [ABSTRACT FROM AUTHOR]

Douglas Van Anden Frost (1910-1989) was a visionary in nutrition science, leaving an enduring legacy that reshaped the understanding of essential nutrients. From his early work on factor W and the discovery of niacin, which eradicated pellagra, to pioneering investigations into selenium's multifaceted role, Frost's unconventional thinking and meticulous research have significantly impacted human health. Collaborating with biochemist Raymond Shamberger (1934-2022), Frost challenged prevailing notions about selenium's carcinogenic potential, demonstrating its anticarcinogenic properties through groundbreaking research. Beyond the laboratory, Frost's work influences public health policies, emphasizing the interconnectedness of nutrients. This paper explores Frost's trajectory, emphasizing the importance of questioning paradigms, interdisciplinary insights, and dedicated experimentation in advancing nutrition science. Frost's enduring inspiration reminds us of the transformative power of curiosity in unraveling the mysteries of human health. [ABSTRACT FROM AUTHOR]

Abstract Neurodegenerative ocular disorders mostly develop with aging and present great complications in the quality of life. Glaucoma and age-related macular degeneration (ARMD) rank as the third and fourth leading causes of blindness and low vision. Oxidative stress is one factor in the pathogenesis of neurodegenerative eye disease. In addition, ocular ischemia and neuroinflammation play an important role. It can be hypothesized that the influence of antioxidants through diet or oral supplementation can counteract the harmful effects of reactive oxygen species accumulated secondary to oxidative stress, ischemia, and inflammation. A range of studies has been published over the past decades focusing on the possible adjuvant effect of antioxidants in ARMD, while there were fewer reports on the potential role of antioxidants in glaucoma. Although certain reports demonstrated positive results, others were discouraging. As there is a controversy between the studies favoring and disfavoring supplementation with different types of antioxidants, it is important to revise the existing evidence on the role of antioxidants in neurodegenerative ocular disorders with a special focus on glaucoma and ARMD. [ABSTRACT FROM AUTHOR]

Probiotics, live microorganisms with potential health benefits, have gained significant research interest for their impact on gut microbiota and neuroprotection. This paper highlights insights from two collaborative studies focusing on probiotics' multifaceted role in addressing autism spectrum disorder (ASD) and mitigating glutamate excitotoxicity. In the first study (Meguid et al., 2022), probiotic supplementation in children with ASD increased Bifidobacterium and Lactobacillus colony counts, reduced anxiety, and improved sleep, suggesting a therapeutic potential for ASD symptoms. The second study (El-Ansary et al., 2018) explored neuroprotective effects, revealing probiotics' ability to restore γ-aminobutyric acid (GABA) and magnesium (Mg2+) levels, mitigating glutamate excitotoxicity. Safety assessments indicated well-tolerated probiotic use in both studies. Future research should focus on personalized probiotic interventions and mechanistic studies to unlock probiotics' full potential in neurodevelopment and neuroprotection. [ABSTRACT FROM AUTHOR]

Homeopathy, an alternative treatment method based on the principle of "like cures like," has gained attention in recent years. This paper focuses on Bufo Rana, a homeopathic remedy prepared from the poison of the Bufo toad. We explore the process of potentization and dosage in homeopathy, discussing the various potencies and the influence of Avogadro's number. Furthermore, we provide an overview of Bufo species, their historical depictions in art, and the toxicological properties of bufotenine, tryptamine, and bufotoxin found in Bufo toads. The clinical consequences of the Bufo species' venom, including neurological manifestations and cardiac arrhythmias, and the therapeutic use of Bufo Rana in mental and neurological conditions are discussed. We summarize Bufo Rana's symptoms and therapeutic relationships based on William Boericke's materia medica. Further research is warranted to investigate the efficacy and safety of Bufo Rana and its role in treating specific conditions. [ABSTRACT FROM AUTHOR]

Calcium is involved in bone metabolism, regulation of nerve signaling, and release of neurotransmitters. Phosphorus is a structural component of ATP, participates in metabolic energy regulation, and ensures stability to biological membranes and cells. Vitamin D and vitamin K are important for intestinal absorption and renal excretion of calcium and phosphorus. Vitamin D plays a regulatory role in bone formation, carbohydrate metabolism, immune responses, and cardiovascular regulation. Research has linked vitamin D deficiency to the development of diabetes mellitus, hypertension, cancer, and osteoporosis. Vitamin K has been associated with a reduced risk of osteoporosis, cancer, and cardiovascular diseases (due to improved vascular elasticity). This review highlights the importance of vitamins D and K in the metabolism of calcium and phosphorus and explores various molecular mechanisms that help maintain the system's mineral homeostasis. Moreover, the paper reviews the enzyme nattokinase's role in thrombotic prevention due to its fibrinolytic activity. [ABSTRACT FROM AUTHOR]

Non-communicable diseases (NCD) are the slow-motion disasters with imminent global health care burden. The current dietary management for NCD is dominated by the calorie balance model. Apart from the quantitative balance of calorie, healthy bioenergetics requires temporal eating and fasting rhythms, and the subsequent switching for different metabolic fuels. We herein term these three bioenergetic attributes, i.e., caloric balance, diurnal eating-fasting rhythm, and metabolic flexibility, as the metabolic tempo. These three attributes are intertwined with each other; alteration of one attribute affects one or more other attributes. Lifestyle-induced disrupted metabolic tempo presents a high flux of mixed carbon substrates to mitochondria, with the resulting congestion and indecisiveness of metabolic switches. Such indecisiveness impairs metabolic flexibility, promotes anabolism, and accumulates the energy storage pools. The triggers from hypoxic inducible factor expression could further promote the metabolic gridlock and adipocyte maladaptation. The maladaptive adipocytes lead to ectopic fat deposition, increased circulating lipid levels, insulin resistance, and chronic systemic inflammation. These continuum set stages for clinical NCDs. We propose that the restoration of all tempo attributes through the combined diet-, time-, and calorie-restricted interventions could be the preferred strategy for NCD management. [ABSTRACT FROM AUTHOR]

Methylmercury (MeHg) is a global environmental pollutant with neurotoxic effects. Exposure to MeHg via consumption of seafood and fish can severely impact fetal neurobehavioral development even when MeHg levels in maternal blood are as low as about 5 μg/L, which the mother tolerates well. Persistent motor dysfunctions and cognitive deficits may result from trans-placental exposure. The present review summarizes current knowledge on the mechanisms of MeHg toxicity during the period of nervous system development. Although cerebellar Purkinje cells are MeHg targets, the actions of MeHg on thiol components in the neuronal cytoskeleton as well as on mitochondrial enzymes and induction of disturbances of glutamate signaling can impair extra-cerebellar functions, also at levels well tolerated by adult individuals. Numerous herbal substances possess neuroprotective effects, predominantly represented by natural polyphenolic molecules that might be utilized to develop natural drugs to alleviate neurotoxicity symptoms caused by MeHg or other Hg compounds. [ABSTRACT FROM AUTHOR]

The current review provides an up-to-date analysis of scientific data on astaxanthin (ASX) sources and experimental studies on its health benefits as a potent antioxidant in the aging process. ASX is a liposoluble carotenoid nutrient and reddish-orange pigment, naturally synthesized by numerous microalgae, yeasts, and bacteria as secondary metabolites. Provides a reddish hue to redfish and shellfish flesh that feed on ASX-producing microorganisms. The microalga Haematococcus pluvialis is the most important source for its industrial bioproduction. Due to its strong antioxidant properties, numerous investigations reported that natural ASX is a more significant antioxidant agent than other antioxidants, such as vitamin C, vitamin E, and β-carotene. Furthermore, several data show that ASX possesses important nutraceutical applications and health benefits, especially in healthy aging processes. However, further studies are needed for a deeper understanding of the potential mechanisms through which ASX could lead to its effective role in the healthy aging process, such as supporting brain health and skin homeostasis. This review highlights the current investigations on the effective role of ASX in oxidative stress, aging mechanisms, skin physiology, and central nervous system functioning, and shows the potential clinical implications related to its consumption. [ABSTRACT FROM AUTHOR]

Elevated plasma levels of homocysteine (Hcy) are a recognized risk factor for stroke. This relationship represents one aspect of the debated 'Hcy hypothesis'. Elevated Hcy may be an independent and treatable cause of atherosclerosis and thrombotic vascular diseases. Further observations indicate that proper dietary supplementation with B-vitamins decreases total plasma Hcy concentrations and may be an effective intervention for stroke prevention. Metabolic vitamin B12 deficiency is a nutritional determinant of total Hcy and stroke risk. Genetic factors may link B vitamins with stroke severity due to the impact on Hcy metabolism of polymorphism in the genes coding for methylenetetrahydrofolate reductase, methionine-synthase, methionine synthase reductase, and cystathionine β-synthase. Several meta-analyses of large randomized controlled trials exist. However, they are not completely in agreement about B vitamins' role, particularly folic acid levels, vitamin B12, and B6, in lowering the homocysteine concentrations in people at high stroke risk. A very complex relationship exists between Hcy and B vitamins, and several factors appear to modify the preventive effects of B vitamins in stroke. This review highlights the regulating factors of the active role of B vitamins active in stroke prevention. Also, inputs for further large, well-designed studies, for specific, particularly sensitive subgroups are given. [ABSTRACT FROM AUTHOR]

Aging is a very complex process that is accompanied by a degenerative impairment in many of the major functions of the human body over time. This inevitable process is influenced by hereditary factors, lifestyle, and environmental influences such as xenobiotic pollution, infectious agents, UV radiation, diet-borne toxins, and so on. Many external and internal signs and symptoms are related with the aging process and senescence, including skin dryness and wrinkles, atherosclerosis, diabetes, neurodegenerative disorders, cancer, etc. Oxidative stress, a consequence of the imbalance between pro- and antioxidants, is one of the main provoking factors causing aging-related damages and concerns, due to the generation of highly reactive byproducts such as reactive oxygen and nitrogen species during the metabolism, which result in cellular damage and apoptosis. Antioxidants can prevent these processes and extend healthy longevity due to the ability to inhibit the formation of free radicals or interrupt their propagation, thereby lowering the level of oxidative stress. This review focuses on supporting the antioxidant system of the organism by balancing the diet through the consumption of the necessary amount of natural ingredients, including vitamins, minerals, polyunsaturated fatty acids (PUFA), essential amino acids, probiotics, plants' fibers, nutritional supplements, polyphenols, some phytoextracts, and drinking water. [ABSTRACT FROM AUTHOR]

Aging is characterized by an imbalance between damage inflicted by reactive oxygen species (ROS) and the antioxidative defenses of the organism. As a significant nutritional factor, the trace element selenium (Se) may remodel gradual and spontaneous physiological changes caused by oxidative stress, potentially leading to disease prevention and healthy aging. Se is involved in improving antioxidant defense, immune functions, and metabolic homeostasis. An inadequate Se status may reduce human life expectancy by accelerating the aging process or increasing vulnerability to various disorders, including immunity dysfunction, and cancer risk. This review highlights the available studies on the effective role of Se in aging mechanisms and shows the potential clinical implications related to its consumption. The main sources of organic Se and the advantages of its nanoformulations were also discussed. [ABSTRACT FROM AUTHOR]

Chronic exposure to arsenic (As) compounds leads to its accumulation in the body, with skin lesions and cancer being the most typical outcomes. Treating As-induced diseases continues to be challenging as there is no specific, safe, and efficacious therapeutic management. Therapeutic and preventive measures available to combat As toxicity refer to chelation therapy, antioxidant therapy, and the intake of natural dietary compounds. Although chelation therapy is the most commonly used method for detoxifying As, it has several side effects resulting in various toxicities such as hepatotoxicity, neurotoxicity, and other adverse consequences. Drugs of plant origin and natural dietary compounds show efficient and progressive relief from As-mediated toxicity without any particular side effects. These natural compounds have also been found to aid the elimination of As from the body and, therefore, can be more effective than conventional therapeutic agents in ameliorating As toxicity. This review provides an overview of the recently updated knowledge on treating As poisoning through natural dietary compounds. This updated information may serve as a basis for defining novel prophylactic and therapeutic formulations. [ABSTRACT FROM AUTHOR]

Background: Anthropogenic risk factors contribute worldwide to an unfavorable environmental situation, which in the population can lead to cancer and other environmental-related diseases. Heavy metals accumulate in tissues and affect human health. Objectives: This review evaluates data for the possible role of uranium (U), barium (Ba), and lead (Pb) in the cancer development in people living in the Malwa Region of Punjab, India. Methods: A literature search was performed using the databases PubMed, Google Scholar, and Scopus. Publications in English were included. Preference was given to studies of high methodological quality (systematic reviews and surveys of studies of various designs). The results of cross-sectional studies were taken into account. Discussion: A study has shown that cancer patients in the Malwa region of Punjab, India have unexpectedly high concentrations of U, Ba, and Pb in hair. We hypothesize that higher hair concentrations of U and other bone-seeking elements in hair of cancer patients may be due to the release of these elements from the skeleton, partly because of the patients age (following the menopause in women) and partly due to disease factors such as bed rest, bone metastases, and enhanced glucocorticoid secretion. Conclusions: Further research is needed to distinguish the effect of age on bone-seeking elements from real disease associations, regardless of the relationship with the pathology is a causal one or not. [ABSTRACT FROM AUTHOR]

Bariatric surgery is an effective option for managing obesity and has gained general acceptance among patients in recent years. Generally, despite the high caloric intake, a bad nutritional habit of obese people results in the deficiency of several vitamins, minerals, and trace elements essential for body metabolism and normal physiological processes. Additionally, the current bariatric surgical approaches such as sleeve gastrectomy (SG), Roux-en-Y-gastric bypass (RYGB), laparoscopic adjustable gastric banding (LAGB), and jejunoileal bypass (JIB) can cause or exacerbate these deficiencies. Based on several reports, it appears that the various bariatric surgical procedures affect nutrient absorption differently. Being purely restrictive, LAGB and SG affect the absorption of iron, selenium, and vitamin B12, while RYGB, JIB, and biliopancreatic diversion have a more profound impact on the absorption of essential vitamins, minerals, and trace elements. Nutritional deficiencies in vitamins, minerals, and trace elements may follow bariatric surgery and are associated with clinical manifestations and diseases, including anemia, ataxia, hair loss, and Wernicke encephalopathy. The present review summarizes some of the major vitamin and micronutrient deficiencies associated with bariatric surgery, particularly those presented post-surgically. To avoid any adverse consequences of vitamin and trace element deficiency, proper monitoring and tests are recommended at any stage, from pre- to post-surgery (periodical check-up), followed by specific and individual nutritional supplementation treatments and a proper healthy diet. [ABSTRACT FROM AUTHOR]

Autoimmunity is a multifaceted disorder influenced by both genetic and environmental factors, and metal exposure has been implicated as a potential catalyst, especially in autoimmune diseases affecting the central nervous system. Notably, metals like mercury, lead, and aluminum exhibit well-established neurotoxic effects, yet the precise mechanisms by which they elicit autoimmune responses in susceptible individuals remain unclear. Recent studies propose that metal-induced autoimmunity may arise from direct toxic effects on immune cells and tissues, coupled with indirect impacts on the gut microbiome and the blood-brain barrier. These effects can activate self-reactive T cells, prompting the production of autoantibodies, inflammatory responses, and tissue damage. Diagnosing metal-induced autoimmunity proves challenging due to nonspecific symptoms and a lack of reliable biomarkers. Treatment typically involves chelation therapy to eliminate excess metals and immunomodulatory agents to suppress autoimmune responses. Prevention strategies include lifestyle adjustments to reduce metal exposure and avoiding occupational and environmental risks. Prognosis is generally favorable with proper treatment; however, untreated cases may lead to autoimmune disorder progression and irreversible organ damage, particularly in the brain. Future research aims to identify genetic and environmental risk factors, enhance diagnostic precision, and explore novel treatment approaches for improved prevention and management of this intricate and debilitating disease. • Metal exposure, e.g., Hg and Pb, links to autoimmune diseases impacting the CNS, posing diagnostic and treatment challenge • Metal-induced autoimmunity, complex and impacting diverse organs, is influenced by genetic and environmental factors. • The intricate mechanisms of metal-induced autoimmunity in immune cells and tissues are unclear • Chelation therapy and immunomodulatory agents are crucial for treating metal-induced autoimmunity • Treatment involves avoiding causative metals, immunosuppressive medications, and lifestyle changes for symptom management. • Individual outcomes vary, highlighting the need for appropriate care for a healthy life. • Understanding genetics and environment is key for research, diagnostics, and innovative treatments in metal-induced autoimmunity. [ABSTRACT FROM AUTHOR]

• Low GSH metabolism is linked to the pathophysiology of Parkinson's disease (PD). • It is unclear if GSH deficiency is an etiological factor in PD or a consequence of it. • In the future, external modulation of GSH levels may be used in the treatment of PD. • More research is needed on active neuroprotective and anti-neuroinflammatory agents. Redox dysfunctions and neuro-oxidative stress play a major role in the pathophysiology and progression of Parkinson's disease (PD). Glutathione (GSH) and the reduced/oxidized glutathione (GSH/GSSG) ratio are lowered in oxidative stress conditions and may lead to increased oxidative toxicity. GSH is involved not only in neuro-immune and neuro-oxidative processes, including thiol redox signaling, but also in cell proliferation and differentiation and in the regulation of cell death, including apoptotic pathways. Lowered GSH metabolism and a low GSH/GSSG ratio following oxidative stress are associated with mitochondrial dysfunctions and constitute a critical factor in the neuroinflammatory and neurodegenerative processes accompanying PD. This review provides indirect evidence that GSH redox signaling is associated with the pathophysiology of PD. Nevertheless, it has not been delineated whether GSH redox imbalances are a causative factor in PD or whether PD-associated pathways cause the GSH redox imbalances in PD. The results show that antioxidant approaches, including neuroprotective and anti-neuroinflammatory agents, which neutralize reactive oxygen species, may have therapeutic efficacy in the treatment of PD and its progression. [ABSTRACT FROM AUTHOR]

The role of glutathione in autism spectrum disorder (ASD) is emerging as a major topic, due to its role in the maintenance of the intracellular redox balance. Several studies have implicated glutathione redox imbalance as a leading factor in ASD, and both ASD and many other neurodevelopmental disorders involve low levels of reduced glutathione (GSH), high levels of oxidized glutathione (GSSG), and abnormalities in the expressions of glutathione-related enzymes in the blood or brain. Glutathione metabolism, through its impact on redox environment or redox-independent mechanisms, interferes with multiple mechanisms involved in ASD pathogenesis. Glutathione-mediated regulation of glutamate receptors [e.g., N-methyl- d -aspartate (NMDA) receptor], as well as the role of glutamate as a substrate for glutathione synthesis, may be involved in the regulation of glutamate excitotoxicity. However, the interaction between glutathione and glutamate in the pathogenesis of brain diseases may vary from synergism to antagonism. Modulation of glutathione is also associated with regulation of redox-sensitive transcription factors nuclear factor kappa B (NF-κB) and activator protein 1 (AP-1) and downstream signaling (proinflammatory cytokines and inducible enzymes), thus providing a significant impact on neuroinflammation. Mitochondrial dysfunction, as well as neuronal apoptosis, may also provide a significant link between glutathione metabolism and ASD. Furthermore, it has been recently highlighted that glutathione can affect and modulate DNA methylation and epigenetics. Review analysis including research studies meeting the required criteria for analysis showed statistically significant differences between the plasma GSH and GSSG levels as well as GSH:GSSG ratio in autistic patients compared with healthy individuals (P = 0.0145, P = 0.0150 and P = 0.0202, respectively). Therefore, the existing data provide a strong background on the role of the glutathione system in ASD pathogenesis. Future research is necessary to investigate the role of glutathione redox signaling in ASD, which could potentially also lead to promising therapeutics. Image 1 • Glutathione (GSH) redox imbalance is a key factor in autism spectrum disorder (ASD). • GSH metabolism interferes with multiple mechanisms involved in ASD pathogenesis. • In ASD, plasma GSH and GSSG levels and their ratio is different from neurotypical controls. [ABSTRACT FROM AUTHOR]

• Children with autism spectrum disorder (ASD) frequently have gastrointestinal symptoms. • The intestinal microbiota may be different in ASD patients compared to controls. • In ASD, a connection may exist between the gut microbiome, GI symptoms, and behavior. • The gut-brain axis may affect brain development and behaviors. There is an emerging body of evidence associating children having autism spectrum disorder (ASD) with gastrointestinal (GI) symptoms, such as abdominal pain, chronic diarrhea, constipation, vomiting, gastroesophageal reflux, intestinal infections, and increased intestinal permeability. Moreover, in many studies, large differences in the composition of intestinal microbiota and metabolic products between ASD patients and controls were reported. Deepening the role and the biology of the gut microbiome may be fundamental to elucidate the onset of GI symptoms in ASD individuals and their etiopathogenetic causes. The gut-brain axis may affect brain development and behaviors through the neuroendocrine, neuroimmune, and autonomic nervous systems. [ABSTRACT FROM AUTHOR]

Arsenic (As) is widely used in the modern industry, especially in the production of pesticides, herbicides, wood preservatives, and semiconductors. The sources of As such as contaminated water, air, soil, but also food, can cause serious human diseases. The complex mechanism of As toxicity in the human body is associated with the generation of free radicals and the induction of oxidative damage in the cell. One effective strategy in reducing the toxic effects of As is the usage of chelating agents, which provide the formation of inert chelator–metal complexes with their further excretion from the body. This review discusses different aspects of the use of metal chelators, alone or in combination, in the treatment of As poisoning. Consideration is given to the therapeutic effect of thiol chelators such as meso-2,3-dimercaptosuccinic acid, sodium 2,3-dimercapto-1-propanesulfonate, 2,3-dimercaptopropanol, penicillamine, ethylenediaminetetraacetic acid, and other recent agents against As toxicity. The review also considers the possible role of flavonoids, trace elements, and herbal drugs as promising natural chelating and detoxifying agents. [ABSTRACT FROM AUTHOR]

Uranium (U) has no known essential biological functions. Furthermore, it is well known for its toxicity, radioactivity, and carcinogenic potency. Impacts on human health due to U exposure have been studied extensively by many researchers. Chronic exposure to low-level U isotopes (radionuclides) may be interlinked with cancer etiology and at high exposure levels, also kidney disease. Other important issues covered U and fertilizers, and also U in soils or human tissues as an easily measurable indicator element in a pathophysiological examination. Furthermore, phosphate fertilization is known as the important source of contamination with U in the agricultural land, mainly due to contamination in the phosphate rock applied for fertilizer manufacture. Therefore, long-term usage of U-bearing fertilizers can substantially increase the concentration of U in fertilized soils. It should also be noted that U is an active redox catalyst for the reaction between DNA and H2O2. This review is aimed to highlight a series on various hydro-geochemical aspects in different water sources and focused on the comparison of different U contents in the drinking water sources and presentation of data in relation to health issues. [ABSTRACT FROM AUTHOR]

The essential and naturally occurring transition metal manganese (Mn) is present in the soil, water, air, and various foods. Manganese can accumulate in the brain if the Mn intake or exposure is excessive and this can result in neurotoxic effects. Manganese is important for the proper activation of different metabolic and antioxidant enzymes. There are numerous Mn importers and exporters. However, the exact transport mechanism for Mn is not fully understood. On the other hand, iron (Fe) is another well-known essential metal, which has redox activity in addition to chemical characteristics resembling those of Mn. Existing data show that interactions occur between Fe and Mn due to certain similarities regarding their mechanisms of the absorption and the transport. It has been disclosed that Mn-specific transporters, together with Fe transporters, regulate the Mn distribution in the brain and other peripheral tissues. In PC12 cells, a significant increase of transferrin receptor (TfR) mRNA expression was linked to Mn exposure and accompanied by elevated Fe uptake. In both humans and animals, there is a strong relationship between Fe and Mn metabolism. In the present review, special attention is paid to the interaction between Mn and Fe. In particular, Fe and Mn distribution, as well as the potential molecular mechanisms of Mn-induced neurotoxicity in cases of Fe deficiency, are discussed. [ABSTRACT FROM AUTHOR]

Arsenic is a well-known natural environmental contaminant distributed in food, water, air, and soil. The developmental toxicity of arsenic exposure is a significant concern in large parts of the world. Unlike acute toxic exposure, the classical dose–response relationship is not adequate for estimating the possible impact of chronic low-level arsenic exposure. The real-life risk and impact assessments require the consideration of the co-exposure to multiple toxins, individual genetic and nutritional predisposition, and the particularly vulnerable stages of the neurodevelopment. This context shifts the assessment model away from the 'one-exposure-for-one-health-effect.' We underscore the need for a comprehensive risk assessment that takes into account all relevant determinants. We aim to elaborate a model that can serve as a basis for an understanding of complex interacting factors in a long-lasting and ongoing low-level arsenic exposure, to identify, protect, and support the children at risk. [ABSTRACT FROM AUTHOR]

Mercury (Hg), a highly toxic environmental pollutant, shows harmfulness which still represents a big concern for human health, including hazards to fertility and pregnancy outcome. Research has shown that Hg could induce impairments in the reproductive function, cellular deformation of the Leydig cells and the seminiferous tubules, and testicular degeneration as well as abnormal menstrual cycles. Some studies investigated spontaneous abortion and complicated fertility outcome due to occupational Hg exposure. Moreover, there is a relation between inhaled Hg vapour and reproductive outcome. This MiniReview evaluates the hypothesis that exposure to Hg may increase the risk of reduced fertility, spontaneous abortion and congenital deficits or abnormalities. [ABSTRACT FROM AUTHOR]

Background: Human α‐fucosidase (EC 3.2.1.51) is a hydrolase the importance of which has been increasing in the latest years. However, data about its plasma level in children with autoimmune disorders, particularly Sjögren's syndrome (SS), are lacking. In this study, the plasma activity of L‐α‐fucosidase‐1 (α‐L‐FUCA‐1) was assayed in hospitalized children and adults and its association with SS and other rheumatic disorders further evaluated. Methods: In total 73 Hungarian hospitalized patients, 32 children (2.5‐10 years) and 41 adults (32‐68 years), were enrolled in the study and underwent plasma assay of α‐L‐FUCA1 activity. Linear regression, Durbin‐Watson (DW), and Pearson tests were evaluated to investigate the relationship between α‐L‐FUCA‐1 plasma levels and autoimmune manifestations. Results: α‐L‐FUCA‐1 correlated with SS both in children (2‐sided t test, P = 0.0023) and in adults (2‐sided t test, P = 0.00035). Linear regressions showed that in other rheumatic disorders, α‐L‐FUCA1 did not show any differential distribution related to the particular pathology (r = 0.2042, P = 0.1531, DW test = 2.2139 positive), while this trend was radically opposite for patients with SS (r = 0.1462, P = 0.0032, DW test = 1.3664, negative). Conclusions: Alterations in plasma level of α‐L‐FUCA‐1 were significantly associated with SS. This preliminary result should encourage further research on α‐L‐FUCA‐1 as a possible differential serological marker of SS. [ABSTRACT FROM AUTHOR]

Alpha lipoic acid (α-LA) and its reduced form dihydrolipoic acid (DHLA) have been historically considered as excellent anti-oxidants and oxidative stress scavengers. Upon oxidation with reactive oxygen species (ROS) and pro-oxidants, α-LA may be reconstituted from DHLA and other reduced forms. Oxidative stress is one of the fundamental causes of functional degeneration, autophagy and apoptosis leading to cytotoxicity and loss of cell survival, often due to exposure to xenobiotics, pollutants, heavy metals, and other environmental and endogenous toxicants. α-LA and DHLA can react with these molecules to strengthen the primary antioxidant defense system during cell injury. The compound α-LA is suggested for heavy metal detoxification, in particular for supporting the mercury (Hg) detoxifying process. Mercury is one of the major environmental toxicant, particularly noxious even upon limited exposure. Oxidative stress pathways have been identified as a key upstream event for Hg-induced toxicity in humans and animals. However, very few existing drugs to date can successfully prevent or reduce Hg toxicity. Although several thiol-based chelators, such as British Anti-Lewisite (2,3-dimercaptopropanol, BAL), meso-2,3-dimercaptosuccinic acid (DMSA), and sodium 2,3-dimercapto-1-propanesulfonate (DMPS), have shown promise for ameliorating Hg intoxication. In this review, the potential role of α-LA and DHLA in scavenging toxic metals and other xenobiotics is discussed, focusing especially on the mechanisms of actions of α-LA and DHLA as potential antioxidants towards Hg-induced toxicity. Unlabelled Image • Alpha-lipoic (ALA) and dihydrolipoic acid (DHLA) are useful detoxifying drug metabolites. • As cofactors, ALA and DHLA have a central function in the mitochondrial energy metabolism. • ALA and DHLA can increase the excretion of methylmercury from cells. • They are natural substances that can mimic and replace synthetic chelators. [ABSTRACT FROM AUTHOR]

Numerous studies have reported neurobehavioural effects in dental personnel occupationally exposed to chronic low levels of mercury (Hg). Hg exposure from dental work may also induce various chronic conditions such as elevation of amyloid protein expression, deterioration of microtubules and increase or inhibition of transmitter release at motor nerve terminal endings. Therefore, clinical studies of Hg toxicity in dentistry may provide new knowledge about disturbed metal homeostasis in neurodegenerative diseases such as Alzheimer's disease, multiple sclerosis and mood disorders. The purpose of this MiniReview is to evaluate the evidence of possible relevance between Hg exposure in dentistry and idiopathic disturbances in motor functions, cognitive skills and affective reactions, as well as dose‐response relationships. [ABSTRACT FROM AUTHOR]

Abstract Chronic fatigue syndrome (CFS) is known as a multi-systemic and complex illness, which induces fatigue and long-term disability in educational, occupational, social, or personal activities. The diagnosis of this disease is difficult, due to lacking a proper and suited diagnostic laboratory test, besides to its multifaceted symptoms. Numerous factors, including environmental and immunological issues, and a large spectrum of CFS symptoms, have recently been reported. In this review, we focus on the nutritional intervention in CFS, discussing the many immunological, environmental, and nutritional aspects currently investigated about this disease. Changes in immunoglobulin levels, cytokine profiles and B- and T- cell phenotype and declined cytotoxicity of natural killer cells, are commonly reported features of immune dysregulation in CFS. Also, some nutrient deficiencies (vitamin C, vitamin B complex, sodium, magnesium, zinc, folic acid, l -carnitine, l -tryptophan, essential fatty acids, and coenzyme Q 10) appear to be important in the severity and exacerbation of CFS symptoms. This review highlights a far-driven analysis of mineral and vitamin deficiencies among CFS patients. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social interaction, verbal and non-verbal communication, and stereotypic behaviors. Many studies support a significant relationship between many different environmental factors in ASD etiology. These factors include increased daily exposure to various toxic metal-based environmental pollutants, which represent a cause for concern in public health. This article reviews the most relevant toxic metals, commonly found, environmental pollutants, i.e., lead (Pb), mercury (Hg), aluminum (Al), and the metalloid arsenic (As). Additionally, it discusses how pollutants can be a possible pathogenetic cause of ASD through various mechanisms including neuroinflammation in different regions of the brain, fundamentally occurring through elevation of the proinflammatory profile of cytokines and aberrant expression of nuclear factor kappa B (NF-κB). Due to the worldwide increase in toxic environmental pollution, studies on the role of pollutants in neurodevelopmental disorders, including direct effects on the developing brain and the subjects’ genetic susceptibility and polymorphism, are of utmost importance to achieve the best therapeutic approach and preventive strategies. [ABSTRACT FROM AUTHOR]

The association between the plasma levels of trace elements, such as copper (Cu), zinc (Zn) and selenium (Se), in people with autism spectrum disorder (ASD), has attracted the interest of many physicians in the very recent years, because the impaired homeostatic regulation of trace elements, including their levels in the bloodstream and their potential neurotoxicity, contribute to the onset and exacerbation of ASD. In this study, we investigated 23 pediatric subjects (≤ 18 yrs old, both sexes) with ASD, all residents in the city of Campo Grande in Brazil, by searching for their micronutrient levels in plasma in relation with metabolic and nutrition biomarkers. Aside for the few evidence reported, generally, the Brazilian cohort of ASD children here examined did not show a marked difference in micro-nutrient intake in relation with their resident geographical area and their dietary habit or metabolic state, although a slight difference in the levels of magnesium and phosphorus was retrieved due to sex difference. [ABSTRACT FROM AUTHOR]

Fibromyalgia (FM) is a complex chronic condition of unknown etiology, characterized by deep and widespread pain, sleep problems, cognitive impairment, fatigue, and other well-known functional symptoms. Recently, it has been proposed that an imbalance of nutritive components, including essential metal ions and vitamins, might play a critical role in the development of FM. Muscle pain has been associated with deficiencies in amino acids, magnesium, selenium, vitamins B and D, as well as with the harmful effects of heavy metals, such as mercury, cadmium, and lead. Research indicates that patients deficient in certain essential nutrients may develop dysfunction of pain inhibitory mechanisms together with fatigue and other FM symptoms. Additionally, mercury and other toxic elements may interfere with the bioavailability of essential nutrients. This review examines the many effects of metals and vitamins in pain evaluation of FM patients. Dietary guidance is therefore critical for FM patients to help them in correcting a suboptimal or deficient intake of essential nutrients. When optimal levels of nutrition are achieved, pain levels are usually lowered. Additional research is recommended in the field of FM and nutrition to disclose further possible relationships. [ABSTRACT FROM AUTHOR]

Abstract: Several studies have reported that nature‐derived antioxidants may prevent free radicals over‐production and therefore control the onset and prevent the exacerbation of different kinds of diseases caused by oxidative stress and redox‐derived stressors, including ageing, fundamentally by suppressing the oxidative by‐products‐mediated degradation. Naturally derived antioxidants exert their anti‐ageing action via a panoply of signalling systems, many of which engaging reactive oxygen and nitrogen species scavenging, with the Nrf2/Keap1‐ARE system and improving the many survival genes and functions (such as the pathway mTOR/Foxo/SIRT1) able to slow cellular senescence. Most of the research in this field has evaluated the regulative effects and even pathways of herbal extracts with antioxidant property in the ageing process, and various age‐related disorders such as cardiovascular disease, ischaemia‐reperfusion injury, coronary and myocardial circulatory perfusion, peripheral vascular resistance, and even neurodegenerative disorders are prevented plant phytochemicals often via their antioxidant potential. A much more complex ability to interact with survival functions makes these compounds successfully active in preventing ageing‐related disorders. This report aimed to discuss in more detail some selected medicinal plants including Allium sativum, Aloe vera, Crataegus spp., Cynara scolymus, Eleutherococcus senticosus, Ginkgo biloba, Hippophae rhamnoides, Panax ginseng, Rosmarinus officinalis, Schizandra chinensis, Vitis vinifera and seaweeds in the prevention of ageing‐related pathologies. A systematic overview of the relevant information in the antioxidant function of the many herbal products reviewed here for the control of the ageing process is proposed, to provide a new horizon on the design of anti‐ageing herbal medicines. [ABSTRACT FROM AUTHOR]

Mammalian thioredoxin reductase (TrxR) is a selenoprotein with three existing isoenzymes (TrxR1, TrxR2, and TrxR3), which is found primarily intracellularly but also in extracellular fluids. The main substrate thioredoxin (Trx) is similarly found (as Trx1 and Trx2) in various intracellular compartments, in blood plasma, and is the cell’s major disulfide reductase. Thioredoxin reductase is necessary as a NADPH-dependent reducing agent in biochemical reactions involving Trx. Genetic and environmental factors like selenium status influence the activity of TrxR. Research shows that the Trx/TrxR system plays a significant role in the physiology of the adipose tissue, in carbohydrate metabolism, insulin production and sensitivity, blood pressure regulation, inflammation, chemotactic activity of macrophages, and atherogenesis. Based on recent research, it has been reported that the modulation of the Trx/TrxR system may be considered as a new target in the management of the metabolic syndrome, insulin resistance, and type 2 diabetes, as well as in the treatment of hypertension and atherosclerosis. In this review evidence about a possible role of this system as a marker of the metabolic syndrome is reported. [ABSTRACT FROM AUTHOR]

This article reviews the clinical use of the metal chelators sodium 2,3-dimercapto-1-propanesulfonate (DMPS), meso-2,3-dimercaptosuccinic acid (DMSA), and calcium disodium edetate (CaEDTA, calcium EDTA) in overexposure and poisonings with salts of lead (Pb), mercury (Hg), and arsenic (As). DMSA has considerably lower toxicity than the classic heavy metal antagonist BAL (2,3-dimercaptopropanol) and is also less toxic than DMPS. Because of its adverse effects, CaEDTA should be replaced by DMSA as the antidote of choice in treating moderate Pb poisoning. Combination therapy with BAL and CaEDTA was previously recommended in cases of severe acute Pb poisoning with encephalopathy. We suggest that BAL in such cases acted as a shuttling Pb transporter from the intra- to the extracellular space. The present paper discusses if a combination of the extracellularly distributed DMSA with the ionophore, Monensin may provide a less toxic combination for Pb mobilization by increasing both the efflux of intracellularly deposited Pb and the urinary Pb excretion. Anyhow, oral therapy with DMSA should be continued with several intermittent courses. DMPS and DMSA are also promising antidotes in Hg poisoning, whereas DMPS seems to be a more efficient agent against As poisoning. However, new insight indicates that a combination of low-dosed BAL plus DMPS could be a preferred antidotal therapy to obtain mobilization of the intracerebral deposits into the circulation for subsequent rapid urinary excretion. [ABSTRACT FROM AUTHOR]

The role of flavonoids in the survival machinery of cells has come in the spotlight due to the recent evidence of their effect on the relationship mitochondria-ER stress-proteasome, including the intracellular mechanisms of autophagy and apoptosis. Numerous experimental animal investigations and even human clinical studies have highlighted the major role of these natural compounds in the economy of life and their deep relationship with autotrophic organisms in the evolutionary space. Their role as anti-oxidant and oxidative stress preventive molecules has to date been investigated extensively in the literature. Despite this great amount of promising evidence, many concerns, however, remain, most of which dealing with biochemistry, bioavailability, pharmacokinetics, and interaction of flavonoids with gut microbiome, issues that make difficult any good attempt to introduce these molecules in the human healthcare systems as possible, encouraging therapeutic substances. This review tries to address and elucidate these items. [ABSTRACT FROM AUTHOR]

Mercury (Hg) is a persistent bio-accumulative toxic metal with unique physicochemical properties of public health concern since their natural and anthropogenic diffusions still induce high risk to human and environmental health. The goal of this review was to analyze scientific literature evaluating the role of global concerns over Hg exposure due to human exposure to ingestion of contaminated seafood (methyl-Hg) as well as elemental Hg levels of dental amalgam fillings (metallic Hg), vaccines (ethyl-Hg) and contaminated water and air (Hg chloride). Mercury has been recognized as a neurotoxicant as well as immunotoxic and designated by the World Health Organization as one of the ten most dangerous chemicals to public health. It has been shown that the half-life of inorganic Hg in human brains is several years to several decades. Mercury occurs in the environment under different chemical forms as elemental Hg (metallic), inorganic and organic Hg. Despite the raising understanding of the Hg toxicokinetics, there is still fully justified to further explore the emerging theories about its bioavailability and adverse effects in humans. In this review, we describe current research and emerging trends in Hg toxicity with the purpose of providing up-to-date information for a better understanding of the kinetics of this metal, presenting comprehensive knowledge on published data analyzing its metabolism, interaction with other metals, distribution, internal doses and targets, and reservoir organs. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) as a neurodevelopmental disorder is characterized by impairments in social interaction, communication, and restricted, repetitive behavior. Several and reproducible studies have suggested that oxidative stress may represent one of the primary etiological mechanism of ASD that can be targeted for therapeutic intervention. In the present study, multiple regression and combined receiver operating characteristic (ROC) analysis were used to search for a relationship between impaired energy and oxidative metabolic pathways in the etiology of ASD and to find the linear combination that maximizes the partial area under a ROC curve for a pre-identified set of markers related to energy metabolism and oxidative stress. Thirty children with ASD and 30 age and gender matched controls were enrolled in the study. Using either spectrophotometric or ELISA-colorimetric assay, levels of lipid peroxides, vitamin E, vitamin C, glutathione (GSH)/glutathione disulfide (GSSG) together with the enzymatic activity of catalase, plasma glutathione peroxidase (GPx), and blood superoxide dismutase (SOD), were measured in peripheral blood samples, as biomarkers related to oxidative stress. Creatine kinase, ectonucleotidases (ADPase and ATPase) Na/K (ATPase), lactate, inorganic phosphate, and levels of adenosine monophosphate (AMP), adenosine diphosphate (ADP), and adenosine triphosphate (ATP) together with adenylate energy charge, were also measured as markers of impaired energy metabolism. Statistical analysis using ROC curves, multiple and logistic regression were performed. A remarkable increase in the area under the curve for most of the combined markers, representing both energy impaired metabolism or oxidative stress, was observed by using combined ROC analyses. Moreover, higher specificity and sensitivity of the combined markers were also reported. The present study indicated that the measurement of the predictive value of selected biomarkers related to energy metabolism and oxidative stress in children with ASD using ROC analysis should lead to the better identification of the etiological mechanism of ASD associated with metabolism and diet. Agents with activity against the impaired metabolic pathway associated with ASD including the metabolic defects and involved enzymes hold a promise as a novel therapy for ASD. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that can cause significant social, communication and behavioral challenges. Environmental contribution to ASD is due in large part to the sensitivity of the developing brain to external exposures such as lead (Pb), and mercury (Hg) as toxic heavy metals or due to a poor detoxification ability as the phenotype of this disorder. Selenium (Se) as an antioxidant element that counteracts the neurotoxicity of Hg, and Pb, presumably through the formation of nontoxic complexes. In the present study, Pb, Hg, and Se were measured in red blood cells (RBCs) of 35 children with ASD and 30 age- and gender-matched healthy control children using atomic absorption spectrometry. Receiver Operating Characteristics (ROC) analysis of the obtained data was performed to measure the predictive value of their absolute and relative concentrations. The obtained data demonstrates a significant elevation of Hg and Pb together with a significant decrease in the Se levels in RBCs of patients with ASD when compared to the healthy controls. The ratios of Se to both Pb and Hg were remarkably altered, being indicative of heavy metal neurotoxicity in patients with ASD. In conclusion, the present study indicates the importance of Se for prevention and/or therapy of heavy metal neurotoxicity. [ABSTRACT FROM AUTHOR]

This systematic review and meta-analysis is based on randomized controlled trials evaluating the effect of physical activity on weight loss in adults undergoing bariatric surgery. The study compared certain biomarkers for individuals with and without physical activity after bariatric surgery. Secondary, the study identified potential successful interventions for the target population. PubMed, Embase, OVID, CINAHL, and Cochrane Library were searched from January 2000 to December 2020. Intervention studies on the effect of physical activity in adults after bariatric surgery were selected, included, and analyzed following the PRISMA guidelines. The primary outcome was weight loss followed by selected biomarkers. Two independent reviewers extracted data and conducted quality assessments. Of the 11 studies included, six reported BMI, two reported fat-free mass, three reported fat mass, two reported waist-hip ratio, and two reported waist circumference. Six studies measuring change from baseline BMI reported a significant intervention effect: SMD = −0.93 (-1.65;-0.20) with high heterogeneity of included trials (I2 = 72%). There was no significant difference between control and intervention groups for other outcomes. BMI as a measure of physical activity positively impacts the target population. Large-scale studies with better criteria and a longer evaluation follow-up may finalize pronounced outcomes. [ABSTRACT FROM AUTHOR]

Uranium (U) is a chemo-toxic, radiotoxic and even a carcinogenic element. Due to its radioactivity, the effects of U on humans health have been extensively investigated. Prolonged U exposure may cause kidney disease and cancer. The geological distribution of U radionuclides is still a great concern for human health. Uranium in groundwater, frequently used as drinking water, and general environmental pollution with U raise concerns about the potential public health problem in several areas of Asia. The particular paleo-geological hallmark of India and other Southern Asiatic regions enhances the risk of U pollution in rural and urban communities. This paper highlights different health and environmental aspects of U as well as uptake and intake. It discusses levels of U in soil and water and the related health issues. Also described are different issues of U pollution, such as U and fertilizers, occupational exposure in miners, use and hazards of U in weapons (depleted U), U and plutonium as catalysts in the reaction between DNA and H 2 O 2, and recycling of U from groundwater to surface soils in irrigation. For use in medical geology and U research, large databases and data warehouses are currently available in Europe and the United States. [ABSTRACT FROM AUTHOR]

Manganese (Mn) is the fifth most abundant metal on earth. Although it is a well understood essential trace element, in excess, Mn is neurotoxic. Initial toxic symptoms associated with Mn are of psychiatric nature and are clinically defined as locura manganica . Neurological signs of Mn toxicity include dystonia, progressive bradykinesia, and disturbance of gait, slurring, and stuttering of speech with diminished volume. Studies indicate that children who ingested Mn in the drinking water (WMn) at or above a level of 0.241 mg/L for a minimum of three years performed more poorly in school as measured by mastery of language, mathematics, and in their overall grade average. The Mn-exposed children also performed more poorly on a battery of neurobehavioral tests. It was also found a significant association between higher WMn and lower cognitive performance, verbal function, and full-scale intelligence quotient (IQ) scores. Young children appear to make up a vulnerable group in exposed populations. Toxicity of WMn is a problem particularly in areas of industrial waste or where Mn is leaching from the soil into public drinking water. Practical and cost-effective approaches are available to remove Mn from drinking water. It is crucial to protect developing brains against Mn toxicity. [ABSTRACT FROM AUTHOR]

Purpose Vitamin D is a fascinating and attractive molecule that has gained particular attention in medicine in recent years. Its immunomodulatory and anti-inflammatory potential might resemble the activity of many nature-derived molecules (eg, flavonoids), but its role in biology was selected during a long evolutionary pathway to dampen the damaging effect of cell stress response and of the immune reaction. In this sense, this molecule can be considered an ancient hormone that serves, in its primary role, as a pro-survival agent. The goal of this review was to elucidate this topic. Methods The article reviews current literature on the field, focusing on issues regarding the role of vitamin D in immunity. Findings Vitamin D participates in the survival machinery used by the cell, and in particular it plays a major role in synchronizing calcium oscillatory signaling to allow cell autophagy or apoptosis during a stress response. Implications Vitamin D should be better highlighted in its molecular action and vitamin D receptor genomics to conceive a more suited therapeutic supplementation protocol in clinics. [ABSTRACT FROM AUTHOR]

Alpha-bisabolol is a plant-derived sesquiterpene alcohol recently associated with a supposed anti-cancer action due to its ability to induce BID-related apoptosis. The molecule, which enters the cell through lipid rafts, may also interact with kisspeptin receptor 1, which has recently been associated with tumor mobility and invasiveness. This evidence suggests the possibility that α-bisabolol might act on the epithelial−mesenchymal transition mechanism, closely associated with the desmoplastic reaction of adipose tissue surrounding a pancreatic ductal adenocarcinoma. This review addresses the issue on the basis of the most recent reported literature in the field. [ABSTRACT FROM AUTHOR]

Mercury (Hg) is an environmental toxicant being present in the environment as elemental Hg (Hg 0 ), inorganic and organic Hg compounds. The nervous system is supposed to be the key target for Hg toxicity. Research indicates that selenium (Se) may be used as a protective agent against Hg neurotoxicity. Therefore, the aim of this review is to examine new implications of the molecular biology of Hg neurotoxicity, and specifically to focus on the influence of Se compounds and interfering thiols on Hg neurotoxicity at the molecular level. Mercury and Se form stable coordination compounds, and Hg species are characterized by higher affinity to selenol groups as compared to thiol groups. Therefore, Se-containing molecules are targets for Hg binding that may at least partially mediate the biological outcome of Hg-Se interaction. Molecular interaction between these elements also involves mutual interaction between Hg and various selenoproteins. Experimental data demonstrate that Se treatment modifies brain Hg retention, modulates neurotoxicity and oxidative stress in the nervous tissue of animals. Human data also indicate that molecular interaction between Hg and Se may have a significant influence on neurodevelopment, brain functioning, and neurodegeneration. It is hypothesized that the effectiveness of Se protection against Hg neurotoxicity may be determined by the dose of elements as well as their particular chemical forms. Further studies are required to estimate the intimate mechanisms of Hg and Se interaction in vivo . [ABSTRACT FROM AUTHOR]

In this article the Proteasome, Endoplasmic Reticulum and Mitochondria (PERM) hypothesis is discussed. The complex machinery made by three homeostatic mechanisms involving the proteasome (P), endoplasmic reticulum (ER) and mitochondria (M) is addressed in order to elucidate the beneficial role of many xenobiotics, either trace metals or phytochemicals, which are spread in the human environment and in dietary habits, exerting their actions on the mechanisms underlying cell survival (apoptosis, cell cycle regulation, DNA repair and turnover, autophagy) and stress response. The "PERMhypothesis" suggests that xenobiotics can modulate this central signaling and the regulatory engine made fundamentally by the ER, mitochondria and proteasome, together with other ancillary components such as peroxisomes, by acting on the energetic balance, redox system and macromolecule turnover. In this context, reactive species and stressors are fundamentally signalling molecules that could act as negative-modulating signals if PERM-mediated control is offline, impaired or dysregulated, as occurs in metabolic syndrome, degenerative disorders, chronic inflammation and cancer. Calcium is an important oscillatory input of this regulation and, in this hypothesis, it might play a role in maintaining the correct rhythm of this PERM modulation, probably chaotic in its nature, and guiding cells to a more drastic decision, such as apoptosis. The commonest effort sustained by cells is to maintain their survival balance and the proterome has the fundamental task of supporting this mechanism. Mild stress is probably the main stimulus in this sense. Hormesis is therefore re-interpreted in the light of this hypothetical model and that experimental evidence arising from flavonoid and hormesis reasearch. [ABSTRACT FROM AUTHOR]