Effects of Chronic Exposure to Molybdate and Tetrathiomolybdate Supplementation of Water on Immature Rats Acutely Infected with Nippostrongylus brasiliensis. 1. Effects on Outcome of Infection and Host Health.

Low molybdate (MoO4) exposure via drinking water in mature rats infected with Nippostrongylus brasiliensis raised liver and plasma copper (Cu) concentrations. The possibility that anthelmintic effects were attributable to conversion of MoO4 to tetrathiomolybdate (MoS4) in a non-ruminant species was investigated by giving three groups of 18 immature rats drinking water containing 70 mg Mo l-1 as MoO4 (group A), 5 mg Mo l-1 as MoS4 (group B) or no supplement (group C), while receiving a commercial cubed diet. After 41 days, 12 rats from each group were inoculated subcutaneously with 2,000 L3-stage N. brasiliensis larvae. Subgroups were killed 7, 8 or 9 days post infection (dpi), when adult worms are normally expelled, and enzyme markers for the inflammatory response to infection were measured in plasma or liver. Male rats given MoS4 prior to infection grew more slowly than those given MoO4. Eight dpi, females given MoS4 had lost more bodyweight than those in group C, while those given MoO4 had gained weight. Mean worm counts at 7 dpi were 160, 65 and 250 ± 30.6 (SE), respectively, in groups C, A and B, and differed significantly from each other (P <0.05) but only rats given MoO4 remained infected 9 dpi (mean worm count 52 ± 16.4): Faecal egg counts followed a broadly similar pattern. Both Mo sources pre-empted increases in liver and duodenal superoxide dismutase activity, induced by infection 7 and 9 dpi, respectively, in group C and enlarged the femur: neither source prevented hypertrophy of the small intestine and a rise in serum mast cell protease concentration caused by infection. Since data for plasma Cu concentration and caeruloplasmin oxidase activity, reported separately, indicated MoO4 was thiolated in vivo, differences between Mo sources may be attributable to differences in the degree of thiolation, extent of thiomolybdate exposure and rates of thiomolybdate degradation at critical times in host or parasite development.

Impact on Glucose Homeostasis: Is Food Biofortified with Molybdenum a Workable Solution? A Two-Arm Study.

Diabetes is expected to increase up to 700 million people worldwide with type 2 diabetes being the most frequent. The use of nutritional interventions is one of the most natural approaches for managing the disease. Minerals are of paramount importance in order to preserve and obtain good health and among them molybdenum is an essential component. There are no studies about the consumption of biofortified food with molybdenum on glucose homeostasis but recent studies in humans suggest that molybdenum could exert hypoglycemic effects. The present study aims to assess if consumption of lettuce biofortified with molybdenum influences glucose homeostasis and whether the effects would be due to changes in gastrointestinal hormone levels and specifically Peptide YY (PYY), Glucagon-Like Peptide 1 (GLP-1), Glucagon-Like Peptide 2 (GLP-2), and Gastric Inhibitory Polypeptide (GIP). A cohort of 24 people was supplemented with biofortified lettuce for 12 days. Blood and urine samples were obtained at baseline (T0) and after 12 days (T2) of supplementation. Blood was analyzed for glucose, insulin, insulin resistance, ß-cell function, and insulin sensitivity, PYY, GLP-1, GLP-2 and GIP. Urine samples were tested for molybdenum concentration. The results showed that consumption of lettuce biofortified with molybdenum for 12 days did not affect beta cell function but significantly reduced fasting glucose, insulin, insulin resistance and increased insulin sensitivity in healthy people. Consumption of biofortified lettuce did not show any modification in urine concentration of molybdenum among the groups. These data suggest that consumption of lettuce biofortified with molybdenum improves glucose homeostasis and PYY and GIP are involved in the action mechanism.

Controlled decoration of nanoceria on the surface of MoS2nanoflowers to improve the biodegradability and biocompatibility inDrosophila melanogastermodel.

In recent years, nanozymes based on two-dimensional (2D) nanomaterials have been receiving great interest for cancer photothermal therapy. 2D materials decorated with nanoparticles (NPs) on their surface are advantageous over conventional NPs and 2D material based systems because of their ability to synergistically improve the unique properties of both NPs and 2D materials. In this work, we report a nanozyme based on flower-like MoS2nanoflakes (NFs) by decorating their flower petals with NCeO2using polyethylenimine (PEI) as a linker molecule. A detailed investigation on toxicity, biocompatibility and degradation behavior of fabricated nanozymes in wild-typeDrosophila melanogastermodel revealed that there were no significant effects on the larval size, morphology, larval length, breadth and no time delay in changing larvae to the third instar stage at 7-10 d for MoS2NFs before and after NCeO2decoration. The muscle contraction and locomotion behavior of third instar larvae exhibited high distance coverage for NCeO2decorated MoS2NFs when compared to bare MoS2NFs and control groups. Notably, the MoS2and NCeO2-PEI-MoS2NFs treated groups at 100µg ml-1covered a distance of 38.2 mm (19.4% increase when compared with control) and 49.88 mm (no change when compared with control), respectively. High-resolution transmission electron microscopy investigations on the new born fly gut showed that the NCeO2decoration improved the degradation rate of MoS2NFs. Hence, nanozymes reported here have huge potential in various fields ranging from biosensing, cancer therapy and theranostics to tissue engineering and the treatment of Alzheimer's disease and retinal therapy.

Co-Delivery of Doxorubicin and Chloroquine by Polyglycerol Functionalized MoS2 Nanosheets for Efficient Multidrug-Resistant Cancer Therapy.

2D MoS2 has shown a great potential in biomedical applications, due to its superior loading capacity, photothermal property, and biodegradation. In this work, polyglycerol functionalized MoS2 nanosheets with photothermal and pH dual-stimuli responsive properties are used for the co-delivery of doxorubicin and chloroquine and treatment of multidrug-resistant HeLa (HeLa-R) cells. The polyglycerol functionalized MoS2 nanosheets with 80 nm average size show a high biocompatibility and loading efficiency (≈90%) for both drugs. The release of drugs from the nanosheets at pH 5.5 is significantly promoted by laser irradiation leading to efficient destruction of incubated HeLa-R cells. In vitro evaluation shows that the designed nanoplatform has a high ability to kill HeLa-R cells. Confocal experiments demonstrate that the synthesized drug delivery system enhances the cellular uptake of DOX via folic acid targeting ligand. Taking advantage of the combined properties including biocompatibility and targeting ability as well as high loading capacity and photothermal release, this multifunctional nanosystem is a promising candidate for anticancer therapy.

Intelligent Molybdenum Disulfide Complexes as a Platform for Cooperative Imaging-Guided Tri-Mode Chemo-Photothermo-Immunotherapy.

Design of new nanoplatforms that integrates multiple imaging and therapeutic components for precision cancer nanomedicine remains to be challenging. Here, a facile strategy is reported to prepare polydopamine (PDA)-coated molybdenum disulfide (MoS2 ) nanoflakes as a nanocarrier to load dual drug cisplatin (Pt) and 1-methyl-tryptophan (1-MT) for precision tumor theranostics. Preformed MoS2 nanoflakes are coated with PDA, modified with methoxy-polyethylene glycol (PEG)-amine, and loaded with 1-MT and Pt. The formed functional 1-MT-Pt-PPDA@MoS2 (the second P stands for PEG) complexes exhibit good colloidal stability and photothermal conversion efficiency (47.9%), dual pH-, and photothermal-sensitive drug release profile, and multimodal thermal, computed tomography and photoacoustic imaging capability. Due to the respective components of Pt, MoS2 , and 1-MT that can block the immune checkpoint associated to tumoral indoleamine 2,3-dioxygenase-induced tryptophan metabolism, tri-mode chemo-photothermo-immunotherapy of tumors can be realized. In particular, under the near infrared laser irradiation, fast release of both drugs can be facilitated to achieve cooperative tumor therapy effect, and the combined immunogenic cell death induced by the dual-mode chemo-photothermo treatment and the 1-MT-induced immune checkpoint blockade can boost enhanced antitumor immune response to generate significant cytotoxic T cells for tumor killing. The developed 1-MT-Pt-PPDA@MoS2 complexes may be used as an intelligent nanoplatform for cooperative precision imaging-guided combinational tumor therapy.

Decrease lysyl oxidase activity in hearts of copper-deficient bovines.

BACKGROUND: Lysyl oxidase (LOX) is a metalloenzyme that requires Cu as a cofactor and it is responsible for the formation of collagen and elastin cross-linking. The objective of this work was to measure the LOX enzyme activity in the heart of bovines with Cu deficiency induced by high molybdenum and sulfur levels in the diet. METHODS: Eighteen myocardial samples were obtained from Cu-deficient (n = 9) and control (n = 9) Holstein bovines during two similar assays. The samples were frozen in liquid nitrogen and stored at -70 °C to measure enzymatic activity. A commercial kit was used, following producer instructions. RESULTS: The results showed that LOX activity from the hearts of Cu-deficient bovines is 29 % lower than the ones of control bovines, being this difference statistically significant (p = 0.03). CONCLUSION: To our knowledge, this is the first report that determined LOX enzymatic activity in bovine heart of Cu-deficient animals. The microscopic alterations found in these animals in our previous work, could be explained by a diminished LOX activity. The results are in agreement with other authors, who found a relationship between LOX activity and dietary Cu intake. The information provided by this work could help to clarify the pathogenesis of cardiac lesions in cattle with dietary Cu deficiency.

Lymphoscintigraphy in the Time of COVID-19: Effect of Molybdenum-99 Shortage on Feasibility of Sentinel Node Mapping.

Background: In the current study, we reported our experience on sentinel node mapping of breast cancer patients during the extreme shortage of Mo99-Tc99m generators using Tc-99m phytate. Methods and Results: During the period from March 7, 2019, to April 18, 2020, due to disruption of molybdenum supply chain, we used low specific activity Tc-99m pertechnetate elute (0.5-2 mCi of 99mTcO4 in 5 mL) for each kit preparation. Two or three intradermal periareolar injections were done for each patient (0.02-0.1 mCi/0.2 mL for each injection). Immediately following injection, dynamic lymphoscintigraphy was done. Surgery was done the same day of injection and the axillary sentinel node was sought using a gamma probe. Overall, 35 patients were included in the study. The specific activity of the Tc-99m elute (in 5 mL) used for kit preparation was 2 mCi/10 mg in four, 1.5 mCi/10 mg in eight, 1.25 mCi/10 mg in eight, 1 mCi/10 mg in three, 0.75 mCi/10 mg in five, and 0.5 mCi/10 mg of 99mTc-Phytate in seven patients. For the first four groups of patients, we used two 0.2 mL injections, while in the latter two groups, three 0.2 mL injections were used. At least one sentinel node was detected in all patients but three in whom axilla was involved. Conclusion: Sentinel node biopsy can be achieved with low specific activity of Tc-99m elute at the time of Mo99-Tc-99m generator shortage. If special personal protection is used, sentinel node mapping can be done in nuclear medicine departments with excellent results despite the COVID-19 pandemic and disruption of generator shipment.

Comparative analysis of biological effects of molybdenum(IV) sulfide in the form of nano- and microparticles on human hepatoma HepG2 cells grown in 2D and 3D models.

Significance of MoS2 nanoparticles as a lubricant or drug carriers indicates the need to assess their safety. In the study we analyzed the effects of MoS2 nano- and microparticles and their internalization in vitro, using 2D and 3D culture models of human hepatoma HepG2 cell line. MoS2 micro- and nanoparticles were characterized with high resolution electron microscopy (HR-SEM), X-ray diffraction (XRD) and Energy Dispersive X-Ray Spectroscopy (EDS). The cells were exposed to a range of concentrations of the nano-and microparticles suspensions (maximum of 250 µg/mL) for 72 h. Cell viability was assessed using WST-1 reduction test and LDH release assay. Particle internalization was analyzed using scanning transmission electron microscopy (STEM). The nanoparticles were internalized into the 2D and 3D cultured cells, in spheroids more efficiently into the outer layer. For microparticles mainly particles of less than 1 µm in diameter underwent internalization. This process, however, did not affect cell viability as measured with the WST-1 and LDH assays. STEM observation showed well preserved integrity of the cell membrane and no apparent cytotoxic effect. Although the particles seemed to be safely sequestered in vacuoles or the cytoplasm, their fate and eventual biological effects are not certain and deserve further studies.

Photothermal augment stromal disrupting effects for enhanced Abraxane synergy chemotherapy in pancreatic cancer PDX mode.

Cancer-associated fibroblasts (CAFs) are crucial for forming the desmoplastic stroma that is associated with chemoresistance in pancreatic ductal adenocarcinoma (PDAC). In the clinic, depleting dense stroma in PDAC tumor tissue is a promising chemotherapeutic strategy. In this study, we report that the local hyperthermia can reduce the number of CAFs in the PDAC PDX mouse mode, which further augments chemotherapeutic efficiency in the PDAC therapy. To achieve this goal, a photothermal-chemotherapeutic agent termed as Abraxane@MoSe2 as a vehicle-saving theranostic probe is prepared by simply mixing an FDA-approved Abraxane and hydrophobic MoSe2 nanosheets via electrostatic and hydrophobic interactions. After labeling with indocyanine green (ICG) dye on the Abraxane@MoSe2, a relatively high fluorescence signal (near infrared second (NIR II)) in PDX tumors can be obtained, which can be precisely imaging-guide local photothermal-chemotherapy upon the 808 nm laser irradiation in vivo. Importantly, the synergy therapeutic efficiency in PDAC is enhanced by the photothermal effect reduction of the number of CAFs, which is confirmed viaα-SMA and vimentin immunofluorescence analysis. This combined therapeutic strategy may provide a new sight for PDAC therapy.

The influence of MoO3-NPs on agro-morphological criteria, genomic stability of DNA, biochemical assay, and production of common dry bean (Phaseolus vulgaris L.).

Molybdenum is considered one of the most important micronutrients applied as a foliar fertilizer for common dry bean. In this study, molybdenum oxide nanoparticles (MoO3-NPs) were applied in different concentrations (0, 10, 20, 30 and 40 ppm) over two sequent seasons, 2018 and 2019, to investigate their effect on the plant morphological criteria, yield, and the genomic stability of DNA. The results showed that the application of 40 ppm MoO3-NPs as a foliar fertilizer showed preferable values of plant morphological criteria, such as the number of leaves and branches per plant, as well as the fresh and dry weight with regard to the common bean plant. In addition, the seed yield increased by 82.4% and 84.1% with 40 ppm, while the shoot residue increased by 32.2% and 32.1% with 20 ppm of MoO3-NPs during two seasons, 2018 and 2019, respectively. Furthermore, the common bean treated with 20 and 40 ppm MoO3-NPs had positive unique bands with ISSR primer 848 at 1400 bp (Rf 0.519) and with primer ISSR2M at 200 bp (Rf 0.729), respectively. In addition, SDS-PAGE reveald some proteins in seedlings which were absent in the flowering stage at 154, 102, 64, 37 and 34 KDa, which may be due to differences in plant proteins required for metabolic processes in each stage. In conclusion, the application of 40 ppm MoO3-NPs was more effective on the productivity of the common bean plants.

Preparation of injectable temperature-sensitive chitosan-based hydrogel for combined hyperthermia and chemotherapy of colon cancer.

The purpose of this study was to design an injectable hydrogel with temperature-sensitive property for safe and high efficient in vivo colon cancer hyperthermia and chemotherapy. Chitosan (CS) solution was injected into the tumor at room temperature and automatically gelled after warming to body temperature in the present of ß-glycerophosphate (ß-GP). Combined localized tumor photothermal and chemotherapy were achieved by dissolving photothermal material MoS2/Bi2S3-PEG (MBP) nanosheets and drug molecule doxorubicin (DOX) into the hydrogel, and the gel system could encapsulate DOX and MBP nanosheets and prevent them from entering the blood circulation and damaging normal tissues and cells. More importantly, the CS/MBP/DOX (CMD) hydrogel exhibited a photothermal efficiency of 22.18% and 31.42% in the first and second near infrared light (NIR I and NIR II) biowindows respectively at a low MBP concentration (0.5 mg/mL). Besides, the release of the DOX from CMD hydrogel was controllable since the gel temperature could be governed by NIR laser irradiation. Moreover, the chitosan-based hydrogel had antibacterial effects. The designed composite hydrogel is anticipated to act as a platform for the high efficient treatment of tumors owing to the different penetration depths of NIR I and NIR II.

Pluronic F127-functionalized molybdenum oxide nanosheets with pH-dependent degradability for chemo-photothermal cancer therapy.

Traditional cancer therapies carry a risk of serious side effects and toxicity. Developing an alternative treatment modality that is highly effective, has low toxicity and is noninvasive is urgently required. Here, we exploited molybdenum oxide (MoOx) nanosheets as a drug carrier and degradable photothermal agent to provide a chemo-photothermal combination cancer therapy. The MoOx nanosheets were synthesized by a one-pot hydrothermal method and then modified with pluronic F127 to improve physiological stability and biocompatibility. The F127-modified nanosheets (MoOX@F127) showed ultrahigh drug loading efficiency (DLE) of doxorubicin (DOX) (DLE%; 65%, W(load DOX)/[W(load DOX) + WMoOx@F127]), strong near-infrared (NIR) absorption and desirable pH-dependent degradability. After intravenous injection, MoOx@F127 nanosheets were degraded at physiological pH and were rapidly excreted from normal organs, while they were effectively accumulated and retained long-term in the more acidic tumor tissue. This simultaneously ensured effective tumor ablation after NIR irradiation and avoided long-term retention and toxicity in vivo. Compared to chemotherapy or photothermal therapy alone, in vitro and in vivo tumor ablation studies have shown a notably improved synergistic effect of the combination therapy. Our study presents a multifunctional nanosystem with a desirable degradability for chemo-photothermal combination cancer therapy that has great potential in biomedical applications.

Translocation, biotransformation-related degradation, and toxicity assessment of polyvinylpyrrolidone-modified 2H-phase nano-MoS2.

Nano-MoS2 has been extensively investigated in materials science and biomedicine. However, the effects of different methods of exposure on their translocation, biosafety, and biotransformation-related degradability remain unclear. In this study, we combined the advantages of synchrotron radiation (SR) X-ray absorption near-edge structure (XANES) and high-resolution single-cell SR transmission X-ray microscopy (SR-TXM) with traditional analytical techniques to investigate translocation, precise degraded species/ratio, and correlation between the degradation and toxicity levels of polyvinylpyrrolidone-modified 2H-phase MoS2 nanosheets (MoS2-PVP NSs). These NSs demonstrated different biodegradability levels in biomicroenvironments with H2O2, catalase, and human myeloperoxidase (hMPO) (H2O2 < catalase < hMPO). The effects of NSs and their biodegraded byproducts on cell viability and 3D translocation at the single-cell level were also assessed. Toxicity and translocation in mice via intravenous (i.v.), intraperitoneal (i.p.), and intragastric (i.g.) administration routes guided by fluorescence (FL) imaging were investigated within the tested dosage. After i.g. administration, NSs accumulated in the gastrointestinal organs and were excreted from feces within 48 h. After i.v. injection, NSs showed noticeable clearance due to their decreased accumulation in the liver and spleen within 30 days when compared with that in the i.p. group, which exhibited slight accumulation in the spleen. This work paves the way for understanding the biological behaviors of nano-MoS2 using SR techniques that provide more opportunities for future applications.

Nutri-priming as an efficient means to improve the agronomic performance of molybdenum in common bean (Phaseolus vulgaris L.).

Microelements play important roles in improving crop productivity and quality. Two traditional methods of providing micronutrients are soil and foliar application, yet the cost involved and phytotoxicity risks poses a major challenge in most global agricultural areas. Nutri-priming represents thus a very promising and viable alternative to ensure that the plants' requirements for micronutrients are met. This paper explores the Mo-priming effects on the germination, growth and yield components of common bean (Phaseolus vulgaris L.). In order to accomplish this research objective, our study is divided in two phases. The first phase seeks to determine the effects of two durations (5 and 10 h) of Mo-priming on the germination parameters. Then, a greenhouse pot experiment was conducted with primed seeds showing better germination performance to assess the effects of Mo-priming on certain parameters related to biological nitrogen fixation and crop yield. Five seed pretreatments were studied, namely, 0, 0.025, 0.05, 0.1 and 0.2% of ammonium heptamolybdate ((NH4)6Mo7O24.4H2O). Unprimed seeds treated with or without the recommended dose through a soil application were used as controls. Hydropriming is sufficient to improve seed germination performance. However, 0.1% Mo-priming for 10 h improved the net CO2 assimilation rate, chlorophyll content and biological nitrogen fixation. Six times more nitrogen was fixed (65.8 kg ha-1) in these plants than in the controls. Additionally, grain yield increased by 115% compared to the negative control. Thus, compared to soil intake, nutri-priming was a very efficient experimental method.

Impacts of Mo application on biological nitrogen fixation and diazotrophic communities in a flooded rice-soil system.

Molybdenum (Mo) deficiency in the farmland of China may limit biological nitrogen fixation (BNF), however, the impact of Mo application on BNF capacities and diazotrophic communities in rice-soil systems is unclear. In this experiment, treatments in a 6.7 atom% 15N2-labelling field-based growth chamber for 74 days and treatments in a 99 atom% 15N2-labelling microcosm experiment for 40 days combined with 16S rRNA gene sequencing and DNA-stable isotope probing (SIP) were used to investigate the impacts of Mo application on BNF and diazotrophic communities. Our results showed that under the condition that no nitrogen (N) fertilizer was applied, Mo application (500 g sodium molybdate ha-1) significantly increased N2 fixation in a rice-Inceptisol system, from 22.3 to 53.1 kg N ha-1. Mo application significantly increased the number of nifH gene copies and the relative abundance of cyanobacteria in both growth chamber and microcosm experiments. Among cyanobacteria, the relative abundances of the most abundant genera Leptolyngbya and Microcoleus were significantly increased by Mo application. 15N2-DNA-SIP further demonstrated that Leptolyngbya and Microcoleus incorporated 15N2. Mo application greatly increased BNF in Mo-deficient paddy field (≤0.068 mg kg-1) and stimulated the growth of cyanobacteria. These results indicated that Mo application in Mo-deficient paddy field could be a useful measure to increase soil N input under no N fertilization.

Trace Element Provision in Parenteral Nutrition in Children: One Size Does Not Fit All.

Routine administration of trace elements is recognised as a standard of care in children requiring parenteral nutrition. However, there is a lack of global consensus regarding trace elements provision and dosing in pediatric parenteral nutrition. This review provides an overview of available evidence regarding trace elements supply and posology in parenteral nutrition in neonates and children. Trace elements provision in children should be tailored to the weight and clinical condition of the child with emphasis on those at risk of toxicity or deficiency. Based on current evidence, there is a need to review the formulation of commercial solutions that contain multiple-trace elements and to enable individual trace elements additives to be available for specific indications. Literature supports the removal of chromium provision whereas manganese and molybdenum supplementation are debated. Preterm neonates may have higher parenteral requirements in iodine, selenium and copper than previously recommended. There is growing support for the routine provision of iron in long-term parenteral nutrition. Further studies on trace elements contamination of parenteral nutrition solutions are needed for a range of trace elements.

WTX101 - an investigational drug for the treatment of Wilson disease.

INTRODUCTION: Wilson disease (WD) is a genetic disorder in which excess toxic copper accumulates in the liver, brain, and other tissues leading to severe and life-threatening symptoms. Copper overload can be assessed as non-ceruloplasmin-bound copper non-ceruloplasmin-bound copper (NCC) in blood. Current therapies are limited by efficacy, safety concerns, and multiple-daily dosing. Areas covered: This article reviews the literature on WTX101 (bis-choline tetrathiomolybdate), an oral first-in-class copper-protein-binding agent in development for the treatment of WD. Expert opinion: In a proof-of-concept phase II trial, once-daily WTX101 over 24 weeks rapidly lowered NCC levels and this was accompanied by improved neurological status without apparent initial drug-induced paradoxical worsening, reduced disability, stable liver function, with a favorable safety profile. WTX101 directly removes excess copper from intracellular hepatic copper stores and also forms an inert tripartite complex with copper and albumin in the circulation and promotes biliary copper excretion. These mechanisms may explain the rapid biochemical and clinical improvements observed. A phase III trial of WTX101 is ongoing and results are eagerly awaited to confirm if WTX101 can improve the treatment of this devastating disease.

Effect of sodium molybdate supplementation on high concentrations of Cu in liver of yearling bulls.

AIM: To determine the impact of sodium molybdate treatment, given weekly, on concentrations of Cu in liver, activity of liver enzymes, and weight gain over 4 weeks, in yearling bulls with elevated concentrations of Cu in liver. METHODS: The study was carried on two commercial grazing farms in the Otago region of New Zealand in yearling Friesian bulls (n=150 on Farm A and n=49 on Farm B) with mean concentration of Cu in liver >3,000 µmol/kg fresh weight. On Day 0, all animals were weighed and half were systematically allocated to treatment with sodium molybdate (3 mg/kg liveweight on Farm A and 7 mg/kg liveweight on Farm B); the remainder received no treatment (Control). Sodium molybdate was given as a drench weekly for 4 weeks and all animals were weighed again on Day 28. Ten animals on each farm (five from each treatment group) were systematically selected for blood sampling and liver biopsies on Days 0 and 28. Samples were analysed for concentrations of Cu in plasma, vitamin B12 in serum, activities of γ-glutamyl transferase, aspartate aminotransferase and glutamate dehydrogenase in serum, and concentrations of Cu and vitamin B12 in liver. Separate multivariable linear models were used to compare the change in outcome variables between Days 0 and 28 between bulls that had been drenched with sodium molybdate or not. RESULTS: On Farm A, mean concentrations of Cu in liver on Day 28, as a percentage of concentrations on Day 0, for the control group was 55 (95% CI=40-73)% and for the treatment group was 73 (95% CI=43-111)%. On Farm B, the equivalent mean for the control group was 75 (95% CI=42-131)% and for the treatment group was 85 (95% CI=38-134)%. The multivariable linear models indicated that the changes in concentrations of Cu in liver, activities of liver enzymes and weight gain between Days 0 and 28 did not differ between the bulls treated or not with sodium molybdate (p>0.18). CONCLUSIONS AND CLINICAL RELEVANCE: Treatment with sodium molybdate in one bolus at weekly intervals for 4 weeks did not affect concentrations of Cu in liver, activity of liver enzymes or weight gain in animals with high concentrations of Cu liver on two farms.

Molybdenum cluster loaded PLGA nanoparticles: An innovative theranostic approach for the treatment of ovarian cancer.

We evaluate poly (d,l-lactide-co-glycolide) (PLGA) nanoparticles embedding inorganic molybdenum octahedral cluster for photodynamic therapy of cancer (PDT). Tetrabutyl ammonium salt of Mo6Br14 cluster unit, (TBA)2Mo6Br14, presents promising photosensitization activity in the destruction of targeted cancer cells. Stable cluster loaded nanoparticles (CNPs) were prepared by solvent displacement method showing spherical shapes, zeta potential values around -30 mV, polydispersity index lower than 0.2 and sizes around 100 nm. FT-IR and DSC analysis revealed the lack of strong chemical interaction between the cluster and the polymer within the nanoparticles. In vitro release study showed that (TBA)2Mo6Br14 was totally dissolved in 20 min, while CNPs were able to control the release of encapsulated cluster. In vitro cellular viability studies conducted on A2780 ovarian cancer cell line treated up to 72 h with cluster or CNPs did not show any sign of toxicity in concentrations up to 20 µg/ml. This concentration was selected for photo-activation test on A2780 cells and CNPs were able to generate oxygen singlet resulting in a decrease of the cellular viability up to 50%, respectively compared to non-activated conditions. This work presents (TBA)2Mo6Br14 as a novel photosensitizer for PDT and suggests PLGA nanoparticles as an efficient delivery system intended for tumor targeting.

Assessment of ovarian follicles and serum reproductive hormones in molybdenum trioxide nanoparticles treated rats / Evaluación de folículos ováricos y hormonas reproductivas en suero de ratas tratadas con nanopartículas de trióxido de molibdeno

SUMMARY: Special features of nanoparticles have resulted in their widespread use. Small molybdenum trioxide (MoO 3) nanoparticles can translocate from the entry portals into the circulatory and lymphatic systems and ultimately to body tissues and organs depending on their composition and size. In this research, sixty Wistar rats weighting 180-250 g were divided into 6 groups (n=10) randomly: Group 1 (Control) did not receive any medicine. Group 2 (Sham) received intraperitoneal normal saline for 35 days on a daily basis. Groups 3, 4, 5 and 6 received 50, 100, 200, and 300 mg/kg MoO3, respectively, the same way in the sham group and at the same interval. At the end of the experiment, the rats were weighted again and anesthetised. Then blood samples were taken from their hearts to determine the serum levels of estrogen, progesterone, and gonadotropins. Their ovaries were removed and ovarian volume, follicular diameter, number of each follicle type, and oocyte volume were determined. Results indicated that MoO3 nanoparticles strongly reduced body and ovarian weights in the rats. Moreover, a significant decrease was observed in ovarian volume, the number of follicle types, oocyte volume and follicular diameter. The nanoparticles increased the number of atretic follicles via ovarian tissue structure. MoO3 nanoparticles decreased serum estrogen level and increased serum level of FSH that was associated with disruption in the regulation of progesterone and LH secretion. The findings showed that MoO3 nanoparticles could bear negative effects on ovarian structure and function.

RESUMEN: Las características específicas de las nanopartículas han dado lugar a su uso generalizado. Las pequeñas nanopartículas de trióxido de molibdeno (MoO3) pueden penetrar los sistemas circulatorios y linfáticos y, en última instancia, dependiendo de su composición y tamaño, también los tejidos y órganos del cuerpo. En esta investigación se dividieron 60 ratas Wistar con un peso de 180-250 g en 6 grupos (n = 10) aleatoriamente: el Grupo 1 (Control) no recibió ningún medicamento. El Grupo 2 (Sham) recibió solución salina normal intraperitoneal durante 35 días diariamente. Los grupos 3, 4, 5 y 6 recibieron 50, 100, 200 y 300 mg / kg de MoO3 respectivamente, de la misma manera en el grupo simulado, y en el mismo intervalo. Concluyendo el experimento, las ratas se pesaron nuevamente y fueron anestesiadas. Luego se tomaron muestras de sangre de los corazones para determinar los niveles séricos de estrógeno, progesterona y gonadotropinas. Se retiraron los ovarios y se determinó el volumen ovárico, el diámetro folicular, el número de cada tipo de folículo y el volumen de ovocitos. Los resultados indicaron que las nanopartículas de MoO3 redujeron significativamente los pesos corporal y ovárico en las ratas. Además, se observó una disminución importante en el volumen ovárico, el número de tipos de folículos, el volumen de ovocitos y el diámetro folicular. Las nanopartículas aumentaron el número de folículos auriculares a través de la estructura del tejido ovárico. Las nanopartículas de MoO 3 disminuyeron el nivel sérico de estrógeno y aumentaron el nivel sérico de FSH que se asoció con la interrupción en la regulación de la progesterona y la secreción de LH. Los hallazgos mostraron que las nanopartículas de MoO 3 podrían tener efectos negativos sobre la estructura y la función ovárica.