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1.
Implications of Manganese in Chronic Acquired Hepatocerebral Degeneration.
Rajoriya, N, Brahmania, M, J Feld, J
Annals of hepatology. 2019;(1):274-278
Abstract
Neurological symptoms can be one of the over-riding symptoms in patients with liver cirrhosis. Patients can present with subtle changes in mood or neurological function due to hepatic encephalopathy (HE), to more severe presentations including stupor and coma. While HE, in its severe form, can be clinically easy to diagnose, more subtle forms may be more difficult to recognize. Other neurological diseases may indeed be overlooked in the context of cirrhosis or confuse the physician regarding the diagnosis. Chronic acquired hepatocerebral degeneration (CAHD) is an uncommon problem occurring in patients with cirrhosis characterised by a Parkinsonian-like neurological presentation with damage to the brain secondary to manganese (Mn) deposition. Here we describe a case of a patient with a neurological presentation of liver disease with a review of the current CAHD literature. In conclusion, CAHD is a rare condition occurring in liver cirrhosis that should always be considered in patients with neurological manifestations of chronic liver disease.
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2.
The interplay between Mn and Fe in Deinococcus radiodurans triggers cellular protection during paraquat-induced oxidative stress.
Santos, SP, Yang, Y, Rosa, MTG, Rodrigues, MAA, De La Tour, CB, Sommer, S, Teixeira, M, Carrondo, MA, Cloetens, P, Abreu, IA, et al
Scientific reports. 2019;(1):17217
Abstract
The bacterium Deinococcus radiodurans is highly resistant to several stress conditions, such as radiation. According to several reports, manganese plays a crucial role in stress protection, and a high Mn/Fe ratio is essential in this process. However, mobilization of manganese and iron, and the role of DNA-binding-proteins-under-starved-conditions during oxidative-stress remained open questions. We used synchrotron-based X-ray fluorescence imaging at nano-resolution to follow element-relocalization upon stress, and its dependency on the presence of Dps proteins, using dps knockout mutants. We show that manganese, calcium, and phosphorus are mobilized from rich-element regions that resemble electron-dense granules towards the cytosol and the cellular membrane, in a Dps-dependent way. Moreover, iron delocalizes from the septum region to the cytoplasm affecting cell division, specifically in the septum formation. These mechanisms are orchestrated by Dps1 and Dps2, which play a crucial role in metal homeostasis, and are associated with the D. radiodurans tolerance against reactive oxygen species.
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3.
Serum iron, Magnesium, Copper, and Manganese Levels in Alcoholism: A Systematic Review.
Grochowski, C, Blicharska, E, Baj, J, Mierzwińska, A, Brzozowska, K, Forma, A, Maciejewski, R
Molecules (Basel, Switzerland). 2019;(7)
Abstract
The aim of this paper was to review recent literature (from 2000 onwards) and summarize the newest findings on fluctuations in the concentration of some essential macro- and microelements in those patients with a history of chronic alcohol abuse. The focus was mainly on four elements which the authors found of particular interest: Iron, magnesium, copper, and manganese. After independently reviewing over 50 articles, the results were consistent with regard to iron and magnesium. On the other hand, data were limited, and in some cases contradictory, as far as copper and manganese were concerned. Iron overload and magnesium deficiency are two common results of an excessive and prolonged consumption of alcohol. An increase in the levels of iron can be seen both in the serum and within the cells, hepatocytes in particular. This is due to a number of factors: Increased ferritin levels, lower hepcidin levels, as well as some fluctuations in the concentration of the TfR receptor for transferrin, among others. Hypomagnesemia is universally observed among those suffering from alcoholism. Again, the causes for this are numerous and include malnutrition, drug abuse, respiratory alkalosis, and gastrointestinal problems, apart from the direct influence of excessive alcohol intake. Unfortunately, studies regarding the levels of both copper and manganese in the case of (alcoholic) liver disease are scarce and often contradictory. Still, the authors have attempted to summarize and give a thorough insight into the literature available, bearing in mind the difficulties involved in the studies. Frequent comorbidities and mutual relationships between the elements in question are just some of the complications in the study of this topic.
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4.
Corynoxine B ameliorates HMGB1-dependent autophagy dysfunction during manganese exposure in SH-SY5Y human neuroblastoma cells.
Yan, D, Ma, Z, Liu, C, Wang, C, Deng, Y, Liu, W, Xu, B
Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association. 2019;:336-348
Abstract
Manganese (Mn) has recently come into the limelight as an important environmental risk factor for neurodegenerative disorders. Although multiple neurotoxicity of Mn have been extensively studied, the exact mechanism of Mn-induced autophagic dysregulation is still poorly understood. The main aim of this study was to explore the role of cytosolic high-mobility group box 1 (HMGB1)-dependent autophagy in Mn-induced autophagic dysregulation and neurotoxicity. SH-SY5Y cells were treated with culture solution (control) and three different concentrations of Mn (50, 100, and 200 μM) for 24 h to detect the effect of Mn on HMGB1-dependent autophagy. We found Mn could increase the HMGB1 mRNA level and its cytosolic translocation and dysregulate autophagy, and Mn-induced alpha-synuclein overexpression interfered with the interaction of HMGB1 and Beclin1, to subsequently promote Beclin1 binding to Bcl2. Another important finding was the neuroprotective role of corynoxine B (Cory B) in Mn-induced autophagic dysregulation and neurotoxicity. We set up six experimental groups: control (culture solution); 200 μM Mn treatment; 100 μM Cory B-alone treatment; and three different pretreated concentrations of Cory B (25, 50, and 100 μM). Our results showed that Cory B ameliorated Mn-induced autophagic dysregulation and neurotoxicity partly by dissociating HMGB1 from alpha-synuclein and inhibiting mTOR signaling.
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5.
Genetic Disorders of Manganese Metabolism.
Anagianni, S, Tuschl, K
Current neurology and neuroscience reports. 2019;(6):33
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Abstract
PURPOSE OF REVIEW This article provides an overview of the pathogenesis, clinical presentation and treatment of inherited manganese transporter defects. RECENT FINDINGS Identification of a new group of manganese transportopathies has greatly advanced our understanding of how manganese homeostasis is regulated in vivo. While the manganese efflux transporter SLC30A10 and the uptake transporter SLC39A14 work synergistically to reduce the manganese load, SLC39A8 has an opposing function facilitating manganese uptake into the organism. Bi-allelic mutations in any of these transporter proteins disrupt the manganese equilibrium and lead to neurological disease: Hypermanganesaemia with dystonia 1 (SLC30A10 deficiency) and hypermanganesaemia with dystonia 2 (SLC39A14 deficiency) are characterised by manganese neurotoxicity while SLC39A8 mutations cause a congenital disorder of glycosylation type IIn due to Mn deficiency. Inherited manganese transporter defects are an important differential diagnosis of paediatric movement disorders. Manganese blood levels and MRI brain are diagnostic and allow early diagnosis to avoid treatment delay.
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6.
Serum levels of copper, iron, and manganese in women with pregnancy, miscarriage, and primary infertility.
Skalnaya, MG, Tinkov, AA, Lobanova, YN, Chang, JS, Skalny, AV
Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS). 2019;:124-130
Abstract
BACKGROUND Iron (Fe), copper (Cu), and manganese (Mn) play a significant role in female reproduction and fetal development. At the same time, high levels of metals may exert toxic effects. Correspondingly, both excess and deficiency of essential trace elements were shown to be associated with female infertility and adverse pregnancy outcome, although the existing data are rather contradictory. Therefore, the objective of the present study was to reveal the potential role of altered iron, copper, and manganese status in female reproductive health problems through assessment of serum metal levels in healthy non-pregnant and pregnant women, as well as patients with miscarriage and primary infertility. METHODS A total of 150 healthy controls, 169 pregnant women (II trimester of pregnancy), 75 women with miscarriage, and 91 patients with primary infertility were enrolled. Serum metal levels were assessed using ICP-MS. RESULTS Pregnant women are characterized by a significant increase in serum Cu an Mn levels by 40% (p < 0.001) and 16% (p = 0.043) as compared to the controls, respectively. Serum Cu levels in women with miscarriage and infertility were 30% and 35% lower than those in pregnant women (p < 0.001). No significant difference in serum iron levels were observed between the control and pregnant women. Women who had miscarriage were characterized by 13% (p = 0.042) higher serum Fe levels as compared to the pregnant ones. Multiple regression analysis demonstrated that serum copper levels was significantly associated both with pregnancy (β = 0.436; p < 0.001) and reproductive health problems in women (β = -0.272; p < 0.001). The latter was improved significant after adjustment for serum Fe and Mn levels, age, and BMI (β = -0.431; p < 0.001). The model incorporating serum Cu, Fe, Mn, and anthropometric parameters accounted for 23% of variability in reproductive status (p < 0.001). CONCLUSIONS It is proposed that the lack of pregnancy-associated increase in metal levels in miscarriage and infertility may be indicative of at least partial role of metal insufficiency in impaired pregnancy and reproductive function in general. However, detailed clinical studies as well as experimental investigations are required for assessment of the potential causes and mechanisms of the observed associations.
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7.
The effects of manganese exposure from drinking water on school-age children: A systematic review.
Iyare, PU
Neurotoxicology. 2019;:1-7
Abstract
The aim of this study was to analyse the published literature on the potential effects of manganese exposure from drinking water on school-age children, with emphasis on cognitive, and neurodevelopment and behavioural effects. A systematic review of up-to-date scientific evidence published from 2006 to 2017 was conducted using Science Direct. A further search was carried out using PubMed and Web of Science. A total of 21 studies were reviewed and categorised into 12 cognitive and 9 neurodevelopment and behavioural effects. The most utilised cognitive test was the Wechsler Intelligence Scale for Children (WISC) or some subtests from it. 10 of the 12 studies on cognitive effects reported an adverse effect of manganese exposure from drinking water on children. 3 out of the 9 studies on neurodevelopment and behavioural effects reported that manganese exposure from drinking water was associated with poorer neurobehavioural performances in school children. 4 others implied the presence of some sex-specific associations with manganese exposure. 1 study suggested that children suffering from attention deficit hyperactivity disorder (ADHD) may be more susceptible to manganese exposure. Another study suggested that manganese was a beneficial nutrient as well as a neurotoxicant. Regardless of the limitations of the studies analysed, the adverse effects of manganese exposure from drinking water on school-aged children is sufficiently demonstrated. Further investigation into the subject to address inconsistencies in existing studies is recommended.
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8.
Manganese-Doped Cerium Oxide Nanocomposite Induced Photodynamic Therapy in MCF-7 Cancer Cells and Antibacterial Activity.
Atif, M, Iqbal, S, Fakhar-E-Alam, M, Ismail, M, Mansoor, Q, Mughal, L, Aziz, MH, Hanif, A, Farooq, WA
BioMed research international. 2019;:7156828
Abstract
In this experimental approach, we explored the structures, morphologies, phototoxicities, and antibacterial activities of undoped and Mn-doped ceria nanocomposite materials, Mn x Ce1-x O2. The Mn x Ce1-x O2 nanocomposites were synthesized by employing a soft chemical route. Our prime focus was on the influence of different factors, both physical and chemical, i.e., the concentration of manganese in the product, size of the nanocomposite, drug dose, and incubation time, on the bacterial strains. Different bacterial strains were selected as experimental biological models of the antibacterial activity of the manganese-doped cerium oxide nanocomposite. In addition to the photodynamic response, the adenocarcinoma cell line (MCF-7) was also studied. Based on cell viability losses and bacterial inhibition analyses, the precise mechanisms of apoptosis or necrosis of 5-ALA/PpIX-exposed MCF-7 cells under 630 nm red lights and under dark conditions were elucidated. It was observed that the undoped nanocomposites had lower cytotoxicities and inhibitions compared with those of the doped nanocomposites towards pathogens. The antibacterial activity and effectiveness for photodynamic therapy were enhanced in the presence of the manganese-doped ceria nanocomposite, which could be attributed to the correlation of the maximum reactive oxygen species generation for targeted toxicity and maximum antioxidant property in bacteria growth inhibition. The optimized cell viability dose and doping concentration will be beneficial for treating cancer and bacterial infections in the future.
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9.
A review of the implications and challenges of manganese removal from mine drainage.
Neculita, CM, Rosa, E
Chemosphere. 2019;:491-510
Abstract
Manganese (Mn) is the third most abundant transition metal in the Earth's crust. Decades of increasing worldwide mining activities have inevitably led to the release of large amounts of this metal into the environment. Mine drainage, either acidic or neutral, often contains high levels of Mn, which have potentially detrimental effects on ecosystems and receiving water bodies. This review provides a comprehensive assessment of the main implications and challenges of Mn treatment in mine drainage. With this aim, the beneficial and adverse effects of Mn on ecosystems and human health are presented first. A comparison of background and mine effluents Mn contents is also provided, further stressing the need for Mn removal from mine drainage. Several technical options to address Mn contamination in acid and neutral mine drainage, and the challenges associated with Mn removal, are subsequently discussed. Thus, this paper presents up-to-date knowledge on the available physicochemical and biological processes deemed operative in Mn removal during mine drainage treatment and their limitations considering the distinctive behavior of Mn. The discussion is further extended to passive treatment systems, which are the most commonly implemented systems for mine drainage treatment on abandoned or closed mine sites, and highlights both their design criteria and operation requirements, as well as the factors that influence Mn removal efficiency. Finally, new perspectives on future research and development needs are identified to address the challenges in Mn removal during mine drainage treatment.
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10.
A case of dystonia with polycythemia and hypermanganesemia caused by SLC30A10 mutation: a treatable inborn error of manganese metabolism.
Tavasoli, A, Arjmandi Rafsanjani, K, Hemmati, S, Mojbafan, M, Zarei, E, Hosseini, S
BMC pediatrics. 2019;(1):229
Abstract
BACKGROUND Manganese is a critical trace element that not only has antioxidant properties, but also is essential for various metabolic pathways and neurotransmitters production. However, it can be toxic at high levels, particularly in the central nervous system. Manganese intoxication can be acquired, but an inherited form due to autosomal-recessive mutations in the SLC30A10 gene encoding a Mn transporter protein has also been reported recently. These mutations are associated with significant failure of manganese excretion and its storage in the liver, brain (especially basal ganglia), and other peripheral tissues, resulting in toxicity. CASE PRESENTATION A 10-year-old boy from consanguineous parents presented with a history of progressive truncal instability, gait difficulty, and frequent falls for 2 months. He had dystonia, rigidity, ataxia, dysarthria, bradykinesia and a plethoric skin. Investigations showed polycythemia, low serum iron and ferritin levels, and increased total iron binding capacity. A brain MRI revealed symmetric hyperintensities in the basal ganglia and dentate nucleuses on TI images that were suggestive of brain metal deposition together with clinical manifestations. Serum calcium and copper levels were normal, while the manganese level was significantly higher than normal values. There was no history of environmental overexposure to manganese. Genetic testing showed a homozygous missense mutation in SLC30A10 (c.C1006T, p.His336Tyr) and Sanger sequencing confirmed a homozygous state in the proband and a heterozygous state in the parents. Regular treatment with monthly infusions of disodium calcium edetate and oral iron compounds resulted in decreased serum manganese and hemoglobin levels to normal values, significant resolution of MRI lesions, and partial improvement of neurological symptoms during 6 months of follow-up. CONCLUSION The syndrome of hepatic cirrhosis, dystonia, polycythemia, and hypermanganesemia caused by SLC30A10 mutation is a treatable inherited metal deposition syndrome. The patient may only have pure neurological without hepatic manifestations. Although this is a rare and potentially fatal inborn error of metabolism, early diagnosis and continuous chelation therapy might improve the symptoms and prevent disease progression.