Quantitative skin exposure assessment of metals: A case study.

This article provides guidance into the quantitative risk assessment of skin exposures to metals. The use of wipe sampling methodologies has been shown to be standardised and effective for skin exposure assessment to metals. However, there is a lack of guidance documents and frameworks available to evaluate the level of health risk to workers from skin exposures to metals. Adverse health effects from exposures to metals have been described in the literature (Fernández-Nieto et al. 2006; Herman et al. 2006; Kreiss et al. 1996). Monitoring of workplace exposures typically focuses on the assessment of respiratory exposures. To provide a safe workplace there is a need to ensure all routes of exposure are risk assessed and controlled. The goal of this article was to develop skin (surface) exposure limits to metals, using the construction industry as a test environment, to quantitatively assess worker health risk of skin exposures to metals. This research concluded it was not feasible to establish single quantitative skin exposure limits to metals due to the many assumptions surrounding dermal exposures. A range of acceptable exposure limits are presented.

In situ activation of therapeutics through bioorthogonal catalysis.

Bioorthogonal chemistry refers to any chemical reactions that can occur inside of living systems without interfering with native biochemical processes, which has become a promising strategy for modulating biological processes. The development of synthetic metal-based catalysts to perform bioorthogonal reactions has significantly expanded the toolkit of bioorthogonal chemistry for medicinal chemistry and synthetic biology. A wide range of homogeneous and heterogeneous transition metal catalysts (TMCs) have been reported, mediating different transformations such as cycloaddition reactions, as well as bond forming and cleaving reactions. However, the direct application of 'naked' TMCs in complex biological media poses numerous challenges, including poor water solubility, toxicity and catalyst deactivation. Incorporating TMCs into nanomaterials to create bioorthogonal nanocatalysts can solubilize and stabilize catalyst molecules, with the decoration of the nanocatalysts used to provide spatiotemporal control of catalysis. This review presents an overview of the advances in the creation of bioorthogonal nanocatalysts, highlighting different choice of nano-scaffolds, and the therapeutic and diagnostic applications.

A single luminescence center ultra-broadband near-infrared LiScGeO4:Cr phosphor for biological tissue penetration.

In this work, in order to meet the application of near-infrared phosphor-converted light emitting diodes (pc-LEDs), an ultra-broadband emission phosphor, LiScGeO4:Cr, was synthesized. Its FWHM reaches 335 nm, and its emission spectrum ranges from 800 nm to 1650 nm, which almost covers the entire near-infrared second window (NIR-II). The broadband emission is thought to be caused by the 4T2 → 4A2 transition of the Cr3+ ion. This transition occurs due to the olivine structure of the crystal, which causes the Cr3+ ions to inhabit a low-symmetric crystal field, and the crystal field strength is very weak. NIR pc-LEDs were fabricated by combining a 460 nm blue LED with this phosphor, which penetrates 4 cm thick beef. The results indicate that there may be a potential application for this phosphor in the field of biological tissue penetration and non-destructive testing.

Exposure to metals premixed with microplastics increases toxicity through bioconcentration and impairs antioxidant defense and cholinergic response in a marine mysid.

Coexistence of metals and microplastics (MPs) in aquatic environments represents a growing concern; however, little is known regarding the risks associated with their combined effects. Here, the effects of five metals (As, Cd, Cu, Pb, and Zn), alone or combined with MPs for various premixing durations (30 and 60 days), on the juvenile and adult stages of the marine mysid Neomysis awatschensis were evaluated. The toxicity (50% lethal concentration for 96 h) and bioconcentration of metals premixed with MPs were measured, and their effects on the antioxidant defense and cholinergic systems were examined. Metal toxicity increased with increasing premixing period with MPs, and juveniles were more sensitive to exposure to metals premixed with MPs than adults. Metal bioconcentration in the mysid body increased following co-exposure with MPs. Metals premixed with MPs significantly increased intracellular malondialdehyde content at both stages but decreased glutathione content in juveniles. At both stages, catalase and superoxide dismutase activity was suppressed following co-exposure to metals and MPs, except under the Cu treatment. Moreover, co-exposure inhibited acetylcholinesterase activity at both stages, suggesting cholinergic impairment. Taken together, metals and MPs produce synergistic detrimental effects on marine mysids in a stage-specific manner. Further studies are warranted to elucidate the role of MPs as a vector for contaminants and stimulator of toxicity in aquatic organisms.

Evidence-Based Recommendations for an Optimal Prenatal Supplement for Women in the U.S., Part Two: Minerals.

The levels of many essential minerals decrease during pregnancy if un-supplemented, including calcium, iron, magnesium, selenium, zinc, and possibly chromium and iodine. Sub-optimal intake of minerals from preconception through pregnancy increases the risk of many pregnancy complications and infant health problems. In the U.S., dietary intake of minerals is often below the Recommended Dietary Allowance (RDA), especially for iodine and magnesium, and 28% of women develop iron deficiency anemia during their third trimester. The goal of this paper is to propose evidence-based recommendations for the optimal level of prenatal supplementation for each mineral for most women in the United States. Overall, the evidence suggests that optimal mineral supplementation can significantly reduce a wide range of pregnancy complications (including anemia, gestational hypertension, gestational diabetes, hyperthyroidism, miscarriage, and pre-eclampsia) and infant health problems (including anemia, asthma/wheeze, autism, cerebral palsy, hypothyroidism, intellectual disability, low birth weight, neural tube defects, preterm birth, rickets, and wheeze). An evaluation of 180 commercial prenatal supplements found that they varied widely in mineral content, often contained only a subset of essential minerals, and the levels were often below our recommendations. Therefore, there is a need to establish recommendations on the optimal level of mineral supplementation during pregnancy.

Biosensitive and antibacterial coatings on metallic material for medical applications.

Metallic materials are commonly used for load-bearing implants and as internal fixation devices. It is customary to use austenitic stainless steel, especially surgical grade type 316L SS as temporary and Ti alloys as permanent implants. However, long-term, poor bonding with bone, corrosion, and release of metal ions, such as chromium and nickel occur. These ions are powerful allergens and carcinogens and their uncontrolled leaching may be avoided by surface coatings. Therefore, bioactive glasses (BGs) became a vital biomedical material, which can form a biologically active phase of hydroxycarbonate apatite on their surface when in contact with physiological fluids. To reduce the high coefficient of friction and the brittle nature of BGs, polymers are normally incorporated to avoid the high-temperature sintering/densification of ceramic-only coatings. For medical application, electrophoretic deposition (EPD) is now used for polymer (organic) and ceramic (inorganic) components at room temperature due to its simplicity, control of coating thickness and uniformity, low cost of equipment, ability to coat substrates of intricate shape and to supply thick films in composite form, high purity of deposits as well as no phase transformation during coating. Although extensive research has been conducted on polymer/inorganic composite coatings, only some studies have reported multifunctional properties, such as biological antibacterial activity, enhanced cell adhesion, controlled drug release ability, and mechanical properties. This review will focus on biodegradable coatings, including zien, chitosan, gelatin, cellulose loaded with antibacterial drugs/metallic ions/natural herbs on biostable substrates (PEEK/PMMA/PCL/PLLA layers), which have the potential of multifunctional coating for metallic implants.

Autophagy Modulated by Inorganic Nanomaterials.

With the rapid development of nanotechnology, inorganic nanomaterials (NMs) have been widely applied in modern society. As human exposure to inorganic NMs is inevitable, comprehensive assessment of the safety of inorganic NMs is required. It is well known that autophagy plays dual roles in cell survival and cell death. Moreover, inorganic NMs have been proven to induce autophagy perturbation in cells. Therefore, an in-depth understanding of inorganic NMs-modulated autophagy is required for the safety assessment of inorganic NMs. This review presents an overview of a set of inorganic NMs, consisting of iron oxide NMs, silver NMs, gold NMs, carbon-based NMs, silica NMs, quantum dots, rare earth oxide NMs, zinc oxide NMs, alumina NMs, and titanium dioxide NMs, as well as how each modulates autophagy. This review emphasizes the potential mechanisms underlying NMs-induced autophagy perturbation, as well as the role of autophagy perturbation in cell fate determination. Furthermore, we also briefly review the potential roles of inorganic NMs-modulated autophagy in diagnosis and treatment of disease.

Synthesis of multimodal polymersomes for targeted drug delivery and MR/fluorescence imaging in metastatic breast cancer model.

The objective of the current study is to design and delivery of targeted PEG-PCL nanopolymersomes encapsulated with Gadolinium based Quantum Dots (QDs) and Doxorubicin (DOX) as magnetic resonance-florescence imaging and anti-cancer agent. Diagnostic and therapeutic efficiency of the prepared theranostic formulation was evaluated in vitro and in vivo. Hydrophobic QDs based on indium-copper-gadolinium-zinc sulfide were synthesized and characterized extensively. Hydrophobic QDs and hydrophilic DOX were loaded in PEG-PCL polymersomes through double emulsion method. Drug release pattern was studied in both citrate (pH 5.4) and phosphate (pH 7.4) buffer during 10 days. Both fluorescence and magnetic properties of bare QDs and prepared formulations were studied entirely. AS1411 DNA aptamer was covalently attached to the surface of polymersomal formulation in order to prepare targeted drug delivery system. Cellular cytotoxicity and cellular uptake analysis were performed in both nucleolin positive (MCF7 and 4T1) and nucleolin negative (CHO) cell lines. After in vitro evaluations, anti-tumor efficiency and diagnostic capability of the formulation was investigated in 4T1 tumor baring mice. Scanning emission electron microscopy (SEM) confirmed spherical shape and around 100 nm size of prepared formulations. Transmission electron microscopy (HRTEM) showed crystal shape of QDs with size of 2-3 nm. Drug release study obtained controlled release of encapsulated DOX and stability of formulation in physiologic condition. MTT and flow cytometry results demonstrated that AS1411 aptamer could enhance both toxicity and cellular uptake in nucleolin overexpressing cell lines (P < 0.05). Moreover, aptamer targeted formulation could increase survival rate and tumor inhibitory growth effect in 4T1 tumor baring mice (P < 0.05). Our results verify that aptamer targeted polymersomes loaded with non-toxic QDs as a diagnostic agent and DOX as an anti-cancer drug, could provide a theranostic platform with the purpose of optimization of treatment process and minimization of systemic side effects.

Late-life Cardiac Injury in Rats following Early Life Exposure to Lead: Reversal Effect of Nutrient Metal Mixture.

Early-life exposure to lead (Pb) can lead to health effects in later life. The neurotoxic effects of Pb have been well documented but its effects on the heart are poorly elucidated. We examined the late life cardiac impairments resulting from developmental exposure to Pb. Further, we investigated the protective effect of the nutrient metal mixture containing calcium (Ca), zinc (Zn) and iron (Fe) against Pb-induced long-term effects on cardiac functions.Male albino rats were lactationally exposed to 0.2% Pb-acetate or 0.2% Pb-acetate together nutrient metal mixture as 0.02% in drinking water of the mother from PND 1 to PND 21. The results showed increased levels of serum total cholesterol (TC), triglycerides (TG), low-density lipoproteins (LDLs) and lactate dehydrogenase (LDH) activity at postnatal day (PND) 28 [young], 4 months [adult] and 18 months [old] age group rats. Most notably, exposure to Pb decreased the activities of mitochondrial superoxide dismutase (SOD), thioredoxin reductase (TrxR), aconitase (Acon), isocitrate dehydrogenase (ICDH), xanthine oxidase (XO) and total antioxidant status while the MDA levels increased in all selected age groups of rats. The histological findings showed an age-dependent response to Pb exposure evidenced by extensive degeneration and necrosis in cardiac muscle, disruption in muscle connectivity, hemorrhage, and mononuclear cell infiltration. Co-administration of nutrient metal mixture reversed the Pb-induced cardiac impairments as reflected in the recovery of the chosen sensitive markers of oxidative stress, reduced Pb levels and cardiac tissue changes. In conclusion, the data demonstrate that early-life exposure to Pb continuously influence the cardiac mitochondrial functions from early life to older age and further suggesting that adequate intake of nutrient metals may be potential therapeutic treatment for Pb intoxication.

Injectable and Radiopaque Liquid Metal/Calcium Alginate Hydrogels for Endovascular Embolization and Tumor Embolotherapy.

Improved endovascular embolization can contribute to assistant treatment for patients. However, many traditional embolic materials, such as metal microcoils or liquid embolic agents, are associated with limitations of coil migration or recanalization. Herein, as the first trial, an injectable and radiopaque liquid metal/calcium alginate (LM/CA) hydrogel is introduced and fabricated as a candidate for endovascular embolization and tumor embolotherapy through developing LM droplets as radiopaque units into biocompatible calcium alginate cross-linked network. The adoption of LM droplets makes hydrogels radiopaque under X-ray and CT scan, which significantly facilitates the tracking of material location during surgical vascular operation. In addition, in vitro and in vivo experiments prove that such smart hydrogel could convert from liquid to solid rapidly via cross-linking, showing pretty flexible and controllable functions. Benefiting from these properties, the hydrogel can be performed in blood vessels through injection via syringes and then served as an embolic material for endovascular embolization procedures. In vivo experiments demonstrate that such hydrogels can occlude arteries and block blood flow until they ultimately lead to ischemic necrosis of tumors and partial healthy tissues. Overall, the present LM/CA hydrogels are promising to be developed as new generation embolic materials for future tumor embolotherapy.

The Cumulative Risk of Chemical and Nonchemical Exposures on Birth Outcomes in Healthy Women: The Fetal Growth Study.

Metals, stress, and sociodemographics are commonly studied separately for their effects on birth outcomes, yet often jointly contribute to adverse outcomes. This study analyzes two methods for measuring cumulative risk to understand how maternal chemical and nonchemical stressors may contribute to small for gestational age (SGA). SGA was calculated using sex-specific fetal growth curves for infants of pregnant mothers (n = 2562) enrolled in the National Institute of Child Health and Human Development (NICHD) Fetal Growth Study. The exposures (maternal lead, mercury, cadmium, Cohen's perceived stress, Edinburgh depression scores, race/ethnicity, income, and education) were grouped into three domains: metals, psychosocial stress, and sociodemographics. In Method 1 we created cumulative risk scores using tertiles. Method 2 employed weighted quantile sum (WQS) regression. For each method, logistic models were built with three exposure domains individually and race/ethnicity, adjusting for age, parity, pregnancy weight gain, and marital status. The adjusted effect of overall cumulative risk with three domains, was also modeled using each method. Sociodemographics was the only exposure associated with SGA in unadjusted models ((odds ratio) OR: 1.35, 95% (confidence interval) CI: 1.08, 1.68). The three cumulative variables in adjusted models were not significant individually, but the overall index was associated with SGA (OR: 1.17, 95% CI: 1.02, 1.35). In the WQS model, only the sociodemographics domain was significantly associated with SGA. Sociodemographics tended to be the strongest risk factor for SGA in both risk score and WQS models.

Dietary Intake of Essential, Toxic, and Potentially Toxic Elements from Mussels (Mytilus spp.) in the Spanish Population: A Nutritional Assessment.

The levels of forty-three elements were determined in fresh, preserved, and frozen mussels (n = 208) with the purpose of evaluating their contribution to the recommended dietary intake of essential elements and their potential risk to Spanish consumers' health. We found relevant differences in the element content in relation to the mode of conservation of mussels as well as in relation to their geographical origin, brand, or mode of production. According to our estimates, mussels are important contributors to the intake of most essential elements, contributing almost 70% of daily requirements of Se, 30-35% of Mo, Zn, and Co, and around 15% of Fe. At the same time, the pattern of average consumption of mussels in Spain does not seem to imply an excessive risk associated with any of the 36 toxic elements studied. However, it should be noted that, in the high percentile of consumption the exposure to Cd and As may be high, in particular that associated with the consumption of fresh and/or frozen mussels. According to the results of this study, a moderate consumption of mussels can be recommended as a valuable and safe source of trace elements.

Oral bioaccessibility of metal(loid)s in dust materials from mining areas of northern Namibia.

Ore mining and processing in semi-arid areas is responsible for the generation of metal(loid)-containing dust, which is easily transported by wind to the surrounding environment. To assess the human exposure to dust-derived metal(loid)s (As, Cd, Cu, Pb, Sb, Zn), as well as the potential risks related to incidental dust ingestion, we studied mine tailing dust (n = 8), slag dust (n = 5) and smelter dust (n = 4) from old mining and smelting sites in northern Namibia (Kombat, Berg Aukas, Tsumeb). In vitro bioaccessibility testing using extraction in simulated gastric fluid (SGF) was combined with determination of grain-size distributions, chemical and mineralogical characterizations and leaching tests conducted on original dust samples and separated PM10 fractions. The bulk and bioaccessible concentrations of the metal(loid)s were ranked as follows: mine tailing dusts < slag dusts ≪ smelter dusts. Extremely high As and Pb bioaccessibilities in the smelter dusts were caused by the presence of highly soluble phases such as arsenolite (As2O3) and various metal-arsenates unstable under the acidic conditions of SGF. The exposure estimates calculated for an adult person of 70 kg at a dust ingestion rate of 50 mg/day indicated that As, Pb (and also Cd to a lesser extent) grossly exceeded tolerable daily intake limits for these contaminants in the case of slag and smelter dusts. The high risk for smelter dusts has been acknowledged, and the safety measures currently adopted by the smelter operator in Tsumeb are necessary to reduce the staff's exposure to contaminated dust. The exposure risk for the local population is only important at the unfenced disposal sites at Berg Aukas, where the PM10 exhibited high levels of bioaccessible Pb.

Micronutrient Intake And Perceived Barriers Among Anaemic Pregnant Women In Aceh, Indonesia.

BACKGROUND: Estimating vitamin, mineral intakes related to anaemia and describing perception regard pregnancy diet, accessibility to foodstuff among first ANC visitor of anaemic pregnant women aged above 20 years in Province Aceh, Indonesia. METHODS: A cross sectional mixmethod of quantitatively and focus group discussion (FGD) was conducted at two municipalities having more than 40% anaemic pregnancy. One hundred fifty-eight anaemic pregnant women were interviewed regarding socio-demographic and three days of 24-hours food recall, in addition to FGD at each municipality using FGD guidelines about nutritional anaemia. Food recall data was analysed using software NutriSurvey Indonesia, deficiency is defined as daily intake below 77% recommended dietary allowances (RDA) Indonesia. The FGD result was analysed by content analysis and clarified with representative quotes. RESULTS: Prevalence of deficiencies intake were folate (98.7%), vitamin B6 (91.1%), vitamin B2 (90.5%), iron (89.2%), zinc (87.3%), vitamin E (84.8%), vitamin C (79.7%), vitamin A (74.1%), copper (67.1%) and vitamin B12 (30.4%). Anaemic pregnant women noticed to consume more amount of food during pregnancy, and preferred to access foodstuff at shop nearby the house. CONCLUSIONS: Other than low iron intake, more than 90% anaemic pregnant women were also deficiency in folate, vitamin B6 and vitamin B2. Perceived of less acknowledgement about affordable cost micronutrient-rich food, high cost of quality-food, sufficient to varieties foodstuff at neighbourhood shop prevents them from making correct food choices subsequently barrier to the food access and intake.

Nano-engineered delivery systems for cancer imaging and therapy: Recent advances, future direction and patent evaluation.

Cancer is the second highest cause of death worldwide. Several therapeutic approaches, such as conventional chemotherapy, antibodies and small molecule inhibitors and nanotherapeutics have been employed in battling cancer. Amongst them, nanotheranostics is an example of successful personalized medicine bearing dual role of early diagnosis and therapy to cancer patients. In this review, we have focused on various types of theranostic polymer and metal nanoparticles for their role in cancer therapy and imaging concerning their limitation, future application such as dendritic cell cancer vaccination, gene delivery, T-cell activation and immune modulation. Also, some of the recorded patent applications and clinical trials have been illustrated. The impact of the biological microenvironment on the biodistribution and accumulation of nanoparticles have been discussed.

Clinically Relevant Herb-Micronutrient Interactions: When Botanicals, Minerals, and Vitamins Collide.

The ability of certain foods to impair or augment the absorption of various vitamins and minerals has been recognized for many years. However, the contribution of botanical dietary supplements (BDSs) to altered micronutrient disposition has received little attention. Almost half of the US population uses some type of dietary supplement on a regular basis, with vitamin and mineral supplements constituting the majority of these products. BDS usage has also risen considerably over the last 2 decades, and a number of clinically relevant herb-drug interactions have been identified during this time. BDSs are formulated as concentrated plant extracts containing a plethora of unique phytochemicals not commonly found in the normal diet. Many of these uncommon phytochemicals can modulate various xenobiotic enzymes and transporters present in both the intestine and liver. Therefore, it is likely that the mechanisms underlying many herb-drug interactions can also affect micronutrient absorption, distribution, metabolism, and excretion. To date, very few prospective studies have attempted to characterize the prevalence and clinical relevance of herb-micronutrient interactions. Current research indicates that certain BDSs can reduce iron, folate, and ascorbate absorption, and others contribute to heavy metal intoxication. Researchers in the field of nutrition may not appreciate many of the idiosyncrasies of BDSs regarding product quality and dosage form performance. Failure to account for these eccentricities can adversely affect the outcome and interpretation of any prospective herb-micronutrient interaction study. This review highlights several clinically relevant herb-micronutrient interactions and describes several common pitfalls that often beset clinical research with BDSs.

Preliminary clinical application of integrated 125I seeds stents in the therapy of malignant lower biliary tract obstruction.

PURPOSE: To evaluate the clinical efficacy of percutaneous trans-hepatic integrated 125I seed stents implantation for malignant lower biliary tract obstruction. METHODS: Thirty-two patients with malignant lower biliary obstruction were randomly divided into two groups. One group underwent the therapy with integrated 125I seed stents (Test group, n = 13), and another group received conventional metal stents implantation for treatment (Control group, n = 19). The pre- and post-operative changes in biochemical indices, white blood cell count, IgG level, stent patency, survival time, tumor size and complications were compared between the two groups. RECIST 1.1 (Response Evaluation Criteria In Solid Tumors) was used to evaluate therapeutic effects. The average follow-up time was 12.3 months. RESULTS: The differences between pre- and post-operative (30 days) intragroup biochemical indices had statistically significant difference (P < 0.05), but there were no significant differences (P > 0.05) in leukocyte counts and IgG levels. As to the median time of stent patency and patients' survival, there were significant differences (P < 0.05) between Control and Test groups (3.9 months vs. 8.1 months, 139 days vs. 298 days, respectively). Three months after the operation, the average tumor size was reduced in the Test group, but was increased in the Control group (P < 0.05). There was no significant difference in the incidence of complications between the two groups. The evaluation results using RECIST 1.1 showed that there were statistically significant differences between the two groups in terms of the rates of remission, control, and progression (χ2 = 17.5, P < 0.05). CONCLUSIONS: The study indicates that integrated 125I seed stents are effective in reducing jaundice symptoms, inhibiting tumor growth, improving stent patency and prolonging patient survival, which may serve as a safer and more feasible method in treating malignant lower biliary obstruction with minimal invasiveness.

Metals Differentially Activate Ovarian Cancer G Protein-Coupled Receptor 1 in Various Species.

Human, mouse, and zebrafish ovarian cancer G protein-coupled receptors (OGR1s) are activated by both metals and extracellular protons. In the present study, we examined whether pig, rat, chicken, and Xenopus OGR1 homologs could sense and be activated by protons and metals. We found that all homologs stimulated serum response element (SRE)-driven promoter activities when they are stimulated by protons. On the other hand, metals differentially activated the homologs. The results using chimeric receptors of human and zebrafish OGR1s indicate that the specificity of the metal-induced activation lies in the extracellular region. These results suggest that protons are an evolutionally conserved agonist of OGR1. However, the types of metals that activated the receptor differed among the homologs.

pH-sensitive release of insulin-loaded mesoporous silica particles and its coordination mechanism.

In this work, we investigated the feasibility of employing metal ion that coordinated with amino group grafted mesoporous silica as a pH-sensitive release carrier of insulin. Mesoporous silica particles were firstly grafted with amino groups. After coordination of metal ions onto the surface of mesoporous pore, insulin was loaded onto mesoporous silica particles through coordination bonds with metal ions. Insulin-loaded mesoporous silica particle with an acid sensitivity between the pH range of physiological environment (pH 7.4) and diabetic acidosis (pH 7.0) and with an insulin encapsulation rate of 74.50% was identified by investigating the influence factors of pH response value. The morphology of particles was confirmed by different analytical methods, indicating that insulin-loaded mesoporous silica particles maintained the rod-like and orderly hexagonal phase mesoporous structure. The coordination mechanism results showed that half of the amino groups on the carrier were coordinated with Cu2+, and insulin was successfully coordinated with Cu2+ without any damage on the secondary structure. The amount of insulin coordination with Cu2+ was positively correlated with the pH of the reaction solution. The cytotoxicity result shows that SBA15-NH2-Cu2+-Ins was biocompatible with cells in the concentration ranging from 25 to 100 µg·mL-1. In vivo study preformed on rats showed that the insulin-loaded particles elicited a period hypoglycemic response. Furthermore, fluorescence and UV methods revealed that insulin-loaded mesoporous silica particles had no significant effect on the secondary structure of serum albumin.

Effect of nutritional supplement on bone marrow-derived mesenchymal stem cells from aplastic anaemia.

Aplastic anaemia (AA) is characterised by pancytopenia resulting from a marked reduction in haemopoietic stem cells (HSC). The regulation of haemopoiesis depends on the interaction between HSC and various cells of the bone marrow (BM) microenvironment, including BM-derived mesenchymal stromal cells (BMSC). The purpose of this study was to analyse the biological effect of nutritional supplement (NS), a dietary supplement consisting of thirty-six compounds: amino acids, nucleotides, vitamins and micronutrients on the BMSC of AA rats. The AA rat model was established by irradiating X-ray (2·5 Gy) and intraperitoneal injections of cyclophosphamide (35 mg/kg; Sigma) and chloramphenicol (35 mg/kg; Sigma). Then AA rats were fed with NS in a dose-dependent manner (2266·95, 1511·3, 1057·91 mg/kg d) by intragastric administration. The effect of NS on the BMSC of AA rats was analysed. As compared with AA rats, NS treatment significantly improved these peripheral blood parameters and stimulated the proliferation of total femoral nucleated cells. NS treatment affected proliferative behaviour of BMSC and suppressed BMSC differentiation to adipocytes. Furthermore, NS treatment of AA rats accelerated osteogenic differentiation of BMSC and enhanced bone mineral density. Co-incubation of HSC with mesenchymal stromal cells and serum from AA rats subjected to high-dose NS markedly improved the yield of CD34+cells. Protein microarray analysis revealed that there were eleven differentially expressed proteins in the NS group compared with the AA rat group. The identified specific NS might be implicated in rehabilitation of BMSC in AA rats, suggesting their potential of nutritional support in AA treatment.