Widespread selenium deficiency in the brain of cases with Huntington's disease presents a new potential therapeutic target.

BACKGROUND: Huntington or Huntington's disease (HD) is an autosomal dominant neurodegenerative disease characterised by both progressive motor and cognitive dysfunction; its pathogenic mechanisms remain poorly understood and no treatment can currently slow, stop, or reverse its progression. There is some evidence of metallomic dysfunction in limited regions of the HD brain; we hypothesised that these alterations are more widespread than the current literature suggests and may contribute to pathogenesis in HD. METHODS: We measured the concentrations of eight essential metals (sodium, potassium, magnesium, calcium, iron, zinc, copper, and manganese) and the metalloid selenium across 11 brain regions in nine genetically confirmed, clinically manifest cases of HD and nine controls using inductively-coupled plasma mass spectrometry. Case-control differences were assessed by non-parametric Mann-Whitney U test (p < 0.05), risk ratios, E-values, and effect sizes. FINDINGS: We observed striking decreases in selenium levels in 11 out of 11 investigated brain regions in HD, with risk ratios and effect sizes ranging 2.3-9.0 and 0.7-1.9, respectively. Increased sodium/potassium ratios were observed in every region (risk ratio = 2.5-8.0; effect size = 1.2-5.8) except the substantia nigra (risk ratio = 0.25; effect size = 0.1). Multiple regions showed increased calcium and/or zinc levels, and localised decreases in iron, copper, and manganese were present in the globus pallidus, cerebellum, and substantia nigra, respectively. INTERPRETATION: The observed metallomic alterations in the HD brain may contribute to several pathogenic mechanisms, including mitochondrial dysfunction, oxidative stress, and blood-brain barrier dysfunction. Selenium supplementation may represent a potential, much-needed therapeutic pathway for the treatment of HD that would not require localised delivery in the brain due to the widespread presence of selenium deficiency in regions that show both high and low levels of neurodegeneration. FUNDING: In Acknowledgments, includes the Lee Trust, the Endocore Research Trust, Cure Huntington's Disease Initiative, the Oakley Mental Health Research Foundation, the Medical Research Council (MRC), the New Zealand Neurological Foundation, and others.

Successful Management of Severe Manganese Toxicosis in Two Dogs.

Manganese is a common component of human joint supplements and may be a source of ingestion and subsequent toxicosis in dogs. Although hepatotoxicity secondary to manganese toxicosis has been reported in dogs before, no descriptions of successful management of manganese toxicosis has been reported in veterinary literature. A 5 yr old spayed female Shetland sheepdog and a 5 yr old female Shetland sheepdog were evaluated following accidental ingestion of a joint supplement. Consultation with a toxicologist revealed concern for manganese toxicosis resulting in hepatic injury. Both dogs developed subsequent acute liver injury, despite decontamination and initial management with N-acetylcysteine and cholestyramine. The patients were managed with calcium ethylenediaminetetraacetic acid, paraaminosalicylic acid, allopurinol, Vitamin E, ginkgo biloba, and S-adenosylmethionine/silybin. Liver values returned to normal in both dogs. Manganese exposure was confirmed with urine manganese analysis in one dog and fecal examination in the other dog. A previous case report detailed the fatal manganese toxicosis in a dog; this case report describes the successful management of severe acute hepatic injury secondary to manganese toxicosis. The combination of medications used above may be used for successful treatment of manganese toxicosis in dogs.

Manganese-Based Tumor Immunotherapy.

As an essential micronutrient, manganese (Mn) participates in various physiological processes and plays important roles in host immune system, hematopoiesis, endocrine function, and oxidative stress regulation. Mn-based nanoparticles are considered to be biocompatible and show versatile applications in nanomedicine, in particular utilized in tumor immunotherapy in the following ways: 1) acting as a biocompatible nanocarrier to deliver immunotherapeutic agents for tumor immunotherapy; 2) serving as an adjuvant to regulate tumor immune microenvironment and enhance immunotherapy; 3) activating host's immune system through the cGAS-STING pathway to trigger tumor immunotherapy; 4) real-time monitoring tumor immunotherapy effect by magnetic resonance imaging (MRI) since Mn2+ ions are ideal MRI contrast agent which can significantly enhance the T1 -weighted MRI signal after binding to proteins. This comprehensive review focuses on the most recent progress of Mn-based nanoplatforms in tumor immunotherapy. The characteristics of Mn are first discussed to guide the design of Mn-based multifunctional nanoplatforms. Then the biomedical applications of Mn-based nanoplatforms, including immunotherapy alone, immunotherapy-involved multimodal synergistic therapy, and imaging-guided immunotherapy are discussed in detail. Finally, the challenges and future developments of Mn-based tumor immunotherapy are highlighted.

Dual Glutathione Depletion Enhanced Enzyme Catalytic Activity for Hyperthermia Assisted Tumor Therapy on Semi-Metallic VSe2/Mn-CS.

Semimetallic nanomaterials as photothermal agents for bioimaging and cancer therapy have attracted tremendous interest. However, the poor photothermal stability, low biocompatibility, and single component limit their therapeutic efficiency in cancer treatment. Here, manganese-doped VSe2 semimetallic nanosheets were prepared and subsequently modified with chitosan (named VSe2/Mn-CS NSs) for combined enzyme catalytic and photothermal therapy. VSe2/Mn-CS NSs show high photothermal property with a photothermal conversion efficiency of 34.61% upon 808 nm near-infrared laser irradiation. In the tumor microenvironment, VSe2/Mn-CS NSs can convert endogenous H2O2 into lethal hydroxyl radicals (•OH) to induce cancer cell apoptosis. The interaction between glutathione (GSH) and Se-Se bonds in VSe2/Mn-CS NSs results in the depletion of GSH level, and the valence states transition of manganese ions is also beneficial for the GSH consumption. This dual depletion of GSH markedly enhances the peroxidase (POD) activity, leading to the high •OH production and the improved therapeutic effect. What is more, the T1-weighted magnetic resonance and photoacoustic imaging endow VSe2/Mn-CS NSs with the ability to guide and track the treatment process. Our study provides a research strategy for the application of semimetallic nanomaterials in cancer diagnosis and treatment.

Construction and evaluation of curcumin upconversion nanocarriers decorated with MnO2 for tumor photodynamic therapy.

The limited tissue penetration depth and tumor hypoxic microenvironment have become the two pivotal obstacles that alleviate the antineoplastic efficacy in tumor photodynamic therapy (PDT). In the research, MnO2-decorated upconversion nanoparticles (UCSMn) have been designed to generate certain oxygen within the solid tumor, and also increase the light penetrating depth due to the optical conversion ability derived from upconversion nanoparticles. Furthermore, upconversion nanoparticles as the inner core are coated by mesoporous silica for the loading of curcumin as photosensitizer and chemotherapeutics, and then a MnO2 shell is proceeding to grow via redox method. When reaching the tumor tissue, the MnO2 nanoshells of UCSMn could be rapidly degraded into manganese ions (Mn2+) owing to the reaction with H2O2 in acidic tumor microenvironment, meanwhile producing oxygen and facilitating curcumin release. Once the tumor is illuminated by 980 nm light, the upconversion nanoparticles can transform the infrared light to visible light of 450 nm and 475.5 nm, which can be efficiently absorbed by curcumin, and then produce singlet oxygen to induce tumor cell apoptosis. Curcumin played a dual role which can not only be acted as a photosensitizer, but also a chemotherapeutic agent to further reinforce the antitumor activity. In short, the intelligent nanostructure has the potential to overcome the above-mentioned shortcomings existed in PDT and eventually do work well in the hypoxia tumors. MnO2-decorated upconversion nanoparticle to solve the tissue penetration and tumor hypoxic microenvironment for tumor photodynamic therapy.

Bioelements in the treatment of burn injuries - The complex review of metabolism and supplementation (copper, selenium, zinc, iron, manganese, chromium and magnesium).

Appropriate nutrition is a key component of burn treatment and should be regarded as an integral part of the therapeutic process in burn patients. A nutritional intervention plan should not only allow for adequate quantities of energy and protein but also carefully consider the supply of macro- and micronutrients. As a result of the severe inflammatory response, oxidative stress, and hypermetabolic state, accompanied by often extensive exudation in burn patients, there is a considerable loss of macro- and micronutrients, including essential trace elements. This leads to certain complications, involving e.g. more frequent infections and impaired wound healing. Our current body of knowledge is still insufficient, and the studies carried out to date focus for the most part on the imbalances in trace elements, such as copper (Cu), selenium (Se), and zinc (Zn). Nevertheless, there are many other trace elements involved in immune functions, regulating gene expression or antioxidant defense, and many of those have not been properly investigated in a clinical setting. Due to the insufficient amount of unambiguous literature data and relatively few, often dated, studies carried out with small patient groups, further evaluation of macro- and microelements in burn patients seems indispensable, e.g. to bring up to date local nutritional protocols.

A pH-responsive platform combining chemodynamic therapy with limotherapy for simultaneous bioimaging and synergistic cancer therapy.

Chemodynamic therapy (CDT) was widely exploited for cancer therapy and expected to replace traditional anticancer drug therapies. Generally, CDT needs to combine with extra therapeutic methods for obtaining the optimal therapeutic efficacy of cancer. Herein, a multifunctional theranostic platform combing CDT with limotherapy was developed via nanoselenium (nano-Se)-coated manganese carbonate-deposited iron oxide nanoparticle (MCDION-Se). MCDION-Se could release abundant of Mn2+ ions that catalyzed H2O2 into hydroxyl radicals (·OH) via a Fenton-like reaction, effectively inducing the apoptosis of cancer cells. Besides, nano-Se coated onto MCDION-Se also dramatically activated superoxide dismutase (SOD) and promoted the generation of superoxide anion radicals (SOARs) in tumor tissue. Subsequently, a high content of H2O2 was produced via SOD catalysis of SOARs, further enhancing CDT efficiency. Meanwhile, the nano-Se and Mn2+ ions inhibited the generation of adenosine triphosphate (ATP), thus starving cancer cells. In addition, in vitro and in vivo experiments showed that MCDION-Se could effectively enhance the contrast of tumor tissue and improve the quality of magnetic resonance imaging (MRI). Overall, this work provided a nanoplatform that combined CDT with limotherapy for cancer therapy and simultaneously utilized MRI for monitoring the treatment of tumors.

Eficacia y seguridad del uso de oligoelementos pediátricos endovenosos que aporten zinc, cobre, iodo, manganeso y selenio a recien nacidos o lactantes que reciben nutrición parenteral / Efficacy and safety of the use of intravenous pediatric trace elements that provide zinc, copper, iodine, manganese and selenium to newborns or infants receiving parenteral nutrition

INTRODUCCIÓN: En el Hospital Nacional Edgardo Rebagliati Martins ­ ESSALUD nacen aproximadamente 7 mil niños anualmente, de los cuales el 10 % requiere de una atención especial en la unidad de cuidados intensivos neonatales y donde también el 2.5 % son bebes prematuros que nacen con pesos menores de 1500 gramos y que requieren cuidados extremos como el de recibir soporte nutricional vía parenteral. La nutrición parenteral (NP) es una técnica de soporte vital y nutricional artificial, en la que los nutrientes se administran por vía endovenosa para cubrir las necesidades energéticas y mantener un estado nutricional adecuado en aquellos pacientes donde la vía enteral es insuficiente, inadecuada o está contraindicada. Existen diversas circunstancias o condiciones clínicas que hacen que un niño no pueda alimentarse de manera normal (vía oral) y deba recibir, vía parenteral, el soporte nutricional que necesita. Los elementos claves de una óptima nutrición, según la Organización Mundial de la Salud (OMS), están conformados por los macro y micronutrientes, estos últimos representados por las vitaminas, minerales y oligoelementos. Los oligoelementos son componentes químicos conformados principalmente por zinc, cobre, iodo, selenio, manganeso, entre otros, y que cumplen diversas funciones dentro del organismo entre las que destacan su participación en diversos sistemas enzimáticos. Actualmente, en EsSalud no se cuenta con soluciones de administración endovenosa que aporten oligoelementos en la NP para pacientes pediátricos. De este modo, los especialistas manifiestan la necesidad de contar con un suplemento nutricional que brinde estos elementos de acuerdo a las necesidades de cada paciente, y que, además, éste sea específicamente de uso pediátrico. TECNOLOGÍA SANITARIA DE INTERÉS: Los oligoelementos son micronutrientes o elementos químicos que en cantidades muy pequeñas resultan indispensables para diversas funciones dentro del organismo. Estos compuestos participan principalmente como catalizadores en sistemas enzimáticos (WHO, 1996). Estos son principalmente zinc, selenio, cobre, iodo y manganeso (NCBI, 1989), importantes para el presente dictamen. METODOLOGÍA: Se llevó a cabo una búsqueda sistemática de la literatura con respecto a la eficacia y seguridad del uso de oligoelementos pediátricos endovenosos que aporten zinc, cobre, iodo, manganeso y selenio a recién nacidos o lactantes que reciben nutrición parenteral. La búsqueda se inició revisando la información sobre el uso del medicamento de acuerdo con entidades reguladoras como: Food and Drug Administration (FDA); European Medicines Agency (EMA); Dirección General de Medicamentos y Drogas (DIGEMID); Organización Mundial de la Salud (OMS). Se realizó tanto una búsqueda sistemática como una búsqueda manual en las páginas web de grupos dedicados a la investigación y educación en salud que elaboran guías de práctica clínica descritas a continuación: National Guideline Clearinghouse (NGC); National Institute for Health and Care Excellence (NICE); Canadian Agency for Drugs and Technologies in Health (CADTH); Scottish Medicines Consortium (SMC). RESULTADOS: De acuerdo con la pregunta PICO, se llevó a cabo una búsqueda de evidencia científica relacionada al uso de oligoelementos pediátricos endovenosos que aporten zinc, cobre, iodo, manganeso y selenio a recién nacidos o lactantes que reciben nutrición parenteral. En la presente sinopsis se describe la evidencia disponible según el tipo de publicación, siguiendo lo indicado en los criterios de elegibilidad (GPC, ETS, RS, MA y ECA fase III). CONCLUSIONES: El presente dictamen tuvo como objetivo evaluar la mejor evidencia científica disponible hasta setiembre del 2019 en relación a la eficacia y seguridad del uso de oligoelementos pediátricos que aporten zinc, cobre, iodo, manganeso y selenio a pacientes pediátricos que reciben nutrición parenteral. La evidencia proveniente de dos RS y dos ECA, la cual también ha sido utilizada como evidencia en las GPC identificadas, sugieren de manera conjunta que el aporte de oligoelementos en la NP en neonatos y lactantes es necesario a fin de dar el soporte nutricional adecuado, tomando en consideración las concentraciones específicas para cada etapa de la vida, así como la edad gestacional al nacimiento, el peso al nacer y las condiciones fisiológicas de fondo. El aporte de cada oligoelemento trae beneficios específicos en cuanto a la función biológica que desempeñan cada uno dentro del organismo, entre los que se encuentran, optimización de las funciones bioquímicas relacionadas al crecimiento y desarrollo, mejora del sistema inmunológico, mejora del desarrollo neurológico. No obstante, el exceso o la falta de cada uno de los oligoelementos trae consigo consecuencias biológicas asociadas a toxicidad tales como, principalmente, problemas neurológicos (exceso de manganeso), mortalidad y problemas tiroideos (deficiencia de iodo), incremento de infecciones (deficiencia de zinc), y mayor de dependencia de oxígeno (deficiencia de selenio). Es necesario brindar el aporte específico requerido de oligoelementos a los neonatos y lactantes utilizando la mejor opción disponible comercialmente, que se ajuste a las necesidades recomendadas. Por lo expuesto, el Instituto de Evaluaciones de Tecnologías en Salud e Investigación - IETSI, aprueba el uso de oligoelementos pediátricos que aporten zinc, cobre, iodo, manganeso y selenio en neonatos y lactantes que reciben nutrición parenteral, según lo establecido en el Anexo N° 1. La vigencia del presente dictamen preliminar es de dos años a partir de la fecha de publicación. Así, la continuación de dicha aprobación estará sujeta a los resultados obtenidos de los pacientes que reciban este tratamiento y de nueva evidencia que pueda surgir en el tiempo.

Mn-Fe layered double hydroxide nanosheets: a new photothermal nanocarrier for O2-evolving phototherapy.

Iron-manganese layered double hydroxide nanosheets were developed as an effective photothermal nanocarrier for loading a photosensitizer. The catalase-like activity enables the nanosheets to decompose H2O2 into O2, overcoming tumor hypoxia and enhancing O2-dependent photodynamic therapy (PDT). The combination of PDT and photothermal therapy (PTT) can almost completely eliminate tumor tissues.

Topical micronutrients in atopic dermatitis-An evidence-based review.

The role of dietary factors is an important and controversial topic in the pathogenesis of atopic dermatitis (AD). Despite the preponderance of consumer products utilizing oral micronutrients supplementation for relief AD symptoms, less attention has been paid on the utility of topical micronutrients, specifically for individuals with AD. We review evidence on topical formulations of vitamins (A, B, C, D, and E) and trace minerals (magnesium, manganese, zinc, and iodine) for treatment of AD. While topical B, C, and E formulations appear to provide some benefit to AD individuals, topical vitamin A has no utility, and topical vitamin D may exacerbate symptoms. Magnesium, zinc, and iodine all appear to improve AD through anti-inflammatory and anti-microbial effects, though future studies must evaluate their use as monotherapy. The exposition of the effects that topical micronutrients have on AD offers an adjuvant treatment modality for this common inflammatory dermatosis.

Multifunctional Nanoflowers for Simultaneous Multimodal Imaging and High-Sensitivity Chemo-Photothermal Treatment.

Liver cancer is currently among the most challenging cancers to diagnose and treat. It is of prime importance to minimize the side effects on healthy tissues and reduce drug resistance for precise diagnoses and effective treatment of liver cancer. Herein, we report a facile but high-yield approach to fabricate a multifunctional nanomaterial through the loading of chitosan and metformin on Mn-doped Fe3O4@MoS2 nanoflowers. Mn-doped Fe3O4 cores are used as simultaneous T1/T2 magnetic resonance imaging (MRI) agents for sensitive and accurate cancer diagnosis, while MoS2 nanosheets are used as effective near-infrared photothermal conversion agents for potential photothermal therapy. The surface-functionalized chitosan was able not only to improve the dispersibility of Mn-doped Fe3O4@MoS2 nanoflowers in biofluids and increase their biocompatibility, but also to significantly enhance the photothermal effect. Furthermore, metformin loading led to high suppression and eradication of hepatoma cells when photothermally sensitized, but exhibited negligible effects on normal liver cells. Due to its excellent combination of T1/T2 MRI properties with sensitive chemotherapeutic and photothermal effects, our study highlights the promise of developing multifunctional nanomaterials for accurate multimodal imaging-guided, and highly sensitive therapy of liver cancer.

SLC39A8 deficiency: biochemical correction and major clinical improvement by manganese therapy.

PurposeSLC39A8 deficiency is a severe inborn error of metabolism that is caused by impaired function of manganese metabolism in humans. Mutations in SLC39A8 lead to impaired function of the manganese transporter ZIP8 and thus manganese deficiency. Due to the important role of Mn2+ as a cofactor for a variety of enzymes, the resulting phenotype is complex and severe. The manganese-dependence of ß-1,4-galactosyltransferases leads to secondary hypoglycosylation, making SLC39A8 deficiency both a disorder of trace element metabolism and a congenital disorder of glycosylation. Some hypoglycosylation disorders have previously been treated with galactose administration. The development of an effective treatment of the disorder by high-dose manganese substitution aims at correcting biochemical, and hopefully, clinical abnormalities.MethodsTwo SCL39A8 deficient patients were treated with 15 and 20 mg MnSO4/kg bodyweight per day. Glycosylation and blood manganese were monitored closely. In addition, magnetic resonance imaging was performed to detect potential toxic effects of manganese.ResultsAll measured enzyme dysfunctions resolved completely and considerable clinical improvement regarding motor abilities, hearing, and other neurological manifestations was observed.ConclusionHigh-dose manganese substitution was effective in two patients with SLC39A8 deficiency. Close therapy monitoring by glycosylation assays and blood manganese measurements is necessary to prevent manganese toxicity.

Microwave-Activated Mn-Doped Zirconium Metal-Organic Framework Nanocubes for Highly Effective Combination of Microwave Dynamic and Thermal Therapies Against Cancer.

Developing functional nanoagents for achieving the combination of microwave dynamic therapy (MDT) and microwave thermal therapy (MTT) is highly desirable due to the advantages of improving the therapeutic effect on tumors and minimizing the side effects. Metal-organic frameworks (MOFs), as emerging porous materials, exhibit many intriguing properties for application in biomedicine. Herein, new-style flexible Mn-doped zirconium metal-organic framework (Mn-ZrMOF) nanocubes (NCs) with the average size of about 60 nm were prepared easily by a one-pot hydrothermal method. Due to the strong inelastic collision of ions confined in a large number of micropores, the Mn-ZrMOF NCs were demonstrated to be an effective microwave-sensitive agent with a high thermal conversion efficiency up to 28.7%, which is the highest one of the recently reported microwave-sensitive agents. This is the first report of determining the microwave thermal conversion efficiency, which can be used to evaluate, compare, and predict the microwave sensitivity of different microwave-sensitive agents. More importantly, such Mn-ZrMOF NCs generate abundant reactive oxygen species (ROS) of hydroxyl radicals under microwave irradiation. As such, the Mn-ZrMOF NCs efficiently suppress the tumor cell growth in vivo and in vitro under mild microwave irradiation for the synergic effect of MTT and MDT. This work paves the way for developing nanoagents that are responsive to microwave irradiation, producing ROS and improving thermal effects to realize the noninvasive MTT and MDT treatment in clinics.

Trace Element Status (Zinc, Copper, Selenium, Iron, Manganese) in Patients with Long-Term Home Parenteral Nutrition.

BACKGROUND: The objective of the present study was to determine concentrations of zinc (Zn), copper (Cu), iron (Fe), selenium (Se) in blood plasma and manganese (Mn) in the whole blood in patients with long-term home parenteral nutrition (HPN) in comparison to the control group. PATIENTS AND METHODS: We examined 68 patients (16 men and 52 women) aged from 28 to 68 years on a long-term HPN lasting from 4 to 96 months. The short bowel syndrome was an indication for HPN. The daily doses of Zn, Cu, Fe, Se and Mn in the last 3 months were determined. RESULTS: No significant differences in blood plasma were found for Zn, Cu and Fe in patients with HPN and in the control group (p > 0.05). The concentration of Mn in whole blood was significantly increased in HPN patients (p < 0.0001), while Se concentration in these patients was significantly decreased (p < 0.005). The concentration of Mn in the whole blood of 16 patients with cholestasis was significantly increased compared to the patients without cholestasis (p < 0.001). The Cu concentration was increased with no statistical significance. CONCLUSION: In long-term HPN, the status of trace elements in the patients has to be continually monitored and the daily substitution doses of these elements have to be flexibly adjusted. Dosing schedule needs to be adjusted especially in cases of cholestatic hepatopathy. A discussion about the optimal daily dose of Mn in patients on HPN is appropriate. For clinical practice, the availability of a substitution mixture of trace elements lacking Mn would be advantageous.

Effects of chelated Zn/Cu/Mn on redox status, immune responses and hoof health in lactating Holstein cows.

To evaluate the effects of chelated Zn/Cu/Mn on redox status, immune responses and hoof health in lactating Holstein cows, 48 head in early lactation were divided into healthy or lame groups according to their gait score. Cows were fed the same amount of Zn/Cu/Mn as sulfate salts or in chelated forms for 180 days, and foot-and-mouth disease (FMD) vaccine was injected at day 90. The results showed that lame cows had lower antioxidant function, serum Zn/Mn levels, hair Cu levels, and hoof hardness. Moreover, increased antioxidant status, FMD antibody titers, serum and hair levels of Zn/Cu/Mn, and hoof hardness and decreased milk fat percent and arthritis biomarkers were observed in cows fed chelated Zn/Cu/Mn. In summary, supplementation with chelated Zn/Cu/Mn improved antioxidant status and immune responses, reduced arthritis biomarkers, and increased accumulation of Zn/Cu/Mn in the body and hoof hardness in dairy cows.

The Biochemical Role of Macro and Micro-Minerals in the Management of Diabetes Mellitus and its Associated Complications: A Review.

UNLABELLED: Diabetes mellitus is a chronic physiological glucose metabolic disorder. Its high prevalence globally has a significant impact on the quality of life. The management of diabetes includes non-pharmacological and glucose lowering agents. Although these methods are effective, they have drawbacks. This has led to a search for alternative therapy in macro and micro-minerals from dietary foods and plants. There is therefore a need to review, identify and classify their modes of action in diabetes mellitus therapy. MATERIALS AND METHODS: This review was carried out using comprehensive literature reports on the use of mineral elements in the management of diabetes. Empirical online searches were conducted for different elements that have been studied for their anti-diabetic potentials both in vivo and in vitro. The University of Fort Hare's online database was also used. RESULTS AND DISCUSSION: The results indicate that magnesium, molybdenum, zinc, vanadium and manganese facilitate glucose catabolism. Chromium, vanadium, zinc, molybdenum and magnesium can enhance insulin activity while molybdenum, manganese and zinc stimulate lipogenesis. Zinc and iron can modulate glucose, metabolizing enzymes in the gastrointestinal tract and limit oxidative stress, respectively. These agents have similar mechanisms to conventional drugs in ameliorating diabetic status and other associated complications. CONCLUSION: The mechanisms of these elements are well known, however, the synergetic effects of their combinations are still obscure. Literature on their safe dose(s) is still scanty. Evaluation of other useful macro and micro-minerals should also be undertaken. It is envisaged that the use of mineral supplements will promote good health in diabetics.

Recent advances in nanosized Mn-Zn ferrite magnetic fluid hyperthermia for cancer treatment.

This paper reviews the recent research and development of nanosized manganese zinc (Mn-Zn) ferrite magnetic fluid hyperthermia (MFH) for cancer treatment. Mn-Zn ferrite MFH, which has a targeted positioning function that only the temperature of tumor tissue with magnetic nanoparticles can rise, while normal tissue without magnetic nanoparticles is not subject to thermal damage, is a promising therapy for cancer. We introduce briefly the composition and properties of magnetic fluid, the concept of MFH, and features of Mn-Zn ferrite magnetic nanoparticles for MFH such as thermal bystander effect, universality, high specific absorption rate, the targeting effect of small size, uniformity of hyperthermia temperature, and automatic temperature control and constant temperature effect. Next, preparation methods of Mn-Zn ferrite magnetic fluid are discussed, and biocompatibility and biosecurity of Mn-Zn ferrite magnetic fluid are analyzed. Then the applications of nanosized Mn-Zn ferrite MFH in cancer are highlighted, including nanosized Mn-Zn ferrite MFH alone, nanosized Mn-Zn ferrite MFH combined with As2O3 chemotherapy, and nanosized Mn-Zn ferrite MFH combined with radiotherapy. Finally, the combination application of nanosized Mn-Zn ferrite MFH and gene-therapy is conceived, and the challenges and perspectives for the future of nanosized Mn-Zn ferrite MFH for oncotherapy are discussed.

Dual functional AuNRs@MnMEIOs nanoclusters for magnetic resonance imaging and photothermal therapy.

A novel dual functional theranosis platform is developed based on manganese magnetism-engineered iron oxide (MnMEIO) and gold nanorods (AuNRs) to combine magnetic resonance (MR) imaging and photothermal therapy in one nanocluster. The platform showed improved T2-weighted MR imaging and exhibited a near-infrared (NIR) induced temperature elevation due to the unique characteristics of AuNRs@MnMEIOs nanoclusters. The obtained dual functional spherical-shaped nanoclusters showed low cytotoxicity, and high cellular uptake efficiency. The AuNRs@MnMEIOs nanoclusters also demonstrated a 1.9 and 2.2 folds r2 relaxivity value higher than those of monodispersed MnMEIO and Resovist. In addition, in vivo MR imaging study found that the contrast enhancements were - 70.4 ± 4.3% versus - 7.5 ± 3.0% in Her-2/neu overexpression tumors as compared to the control tumors. More importantly, NIR laser irradiation to the tumor site resulted in outstanding photothermal therapeutic efficacy and without damage to the surrounding tissue. In additional, the prepared dual functional AuNRs@MnMEIOs display high stability and furthermore disperse even in the presence of external magnet, showing that AuNRs@MnMEIOs nanoclusters can be manipulated by an external magnetic field. Therefore, such nanoclusters combined MR imaging and photothermal therapeutic functionality can be developed as a promising nanosystem for effective cancer diagnosis and therapy.

Effects of oligoelements Se, Zn, and Mn plus Lachesis muta venom in experimental scleroderma.

Scleroderma, sclerosis of the skin, is a severe autoimmune disease refractant to all kind of treatments. To study the in vivo effects of a combination of three oligoelements selenium (Se), zinc (Zn), and manganese (Mn) plus Lachesis muta venom (O-LM) on the bleomycin (BLM)-induced scleroderma mouse experimental model. C3H mice were randomly divided into four groups: control (phosphate-buffered saline (PBS)), O-LM, BLM, and BLM + O-LM. All administrations were performed subcutaneously into the back of mice. BLM was injected 5 days per week for three consecutive weeks and O-LM was administered simultaneously with BLM from the beginning of the experiments and lasted for 3 weeks after the final BLM or PBS injection (for O-LM and BLM + O-LM groups), when animals were sacrificed and histopathological, immunohistochemical, thiobarbituric acid reactive species (TBARS) evaluation, and autoantibodies detection were determined. O-LM significantly reduced BLM-induced enhanced dermal thickness (605 ± 47 vs. 956 ± 59 µm, P < 0.01), collagen deposition, and mast cells infiltration (43.1 ± 1.0 vs. 102 ± 14.1 mast cells, P < 0.05). O-LM administration significantly blocked BLM-induced oxidative damage and the enhanced immunoreactive fibroblasts for α-smooth muscle actin while reduced BLM-induced autoantibodies that strongly react mainly with skin and spleen. O-LM significantly reduced BLM-induced scleroderma through the modulation of antioxidant and immunological pathways.

Synthesis, characterization, and anti-cancer activity of emodin-Mn(II) metal complex.

To synthesize and characterize a novel metal complex of Mn (II) with emodin, and evaluate its anti-cancer activity. The elemental analyses, IR, UV-vis, atomic absorption spectroscopy, TG-DSC, (1)H NMR, and (13)C NMR data were used to characterize the structure of the complex. The cytotoxicity of the complex against the human cancer cell lines HepG2, HeLa, MCF-7, B16, and MDA-MB-231 was tested by the MTT assay and flow cytometry. Emodin was coordinated with Mn(II) through the 9-C=O and 1-OH, and the general formula of the complex was Mn(II) (emodin)2·2H2O. In studies of the cytotoxicity, the complex exhibited significant activity, and the IC50 values of the complex against five cancer cell lines improved approximately three-fold compared with those of emodin. The complex could induce cell morphological changes, decrease the percentage of viability, and induce G0/G1 phase arrest and apoptosis in cancer cells. The coordination of emodin with Mn(II) can improve its anticancer activity, and the complex Mn(II) (emodin)2·2H2O could be studied further as a promising anticancer drug.