Gluten-Free Diet Alters the Gut Microbiome in Women with Autoimmune Thyroiditis.

The gut microbiome may contribute to the development of autoimmune diseases, such as autoimmune thyroiditis (AIT). Diet has a critical impact on the gut microbiome, and it has been shown that a gluten-free diet can negatively affect its composition. A gluten-free diet is popular among patients, and therefore the aim of this study was to check whether it affects thyroid function and gut microbiome composition in AIT. Thirty-one women with AIT complied with a gluten-free diet for 8 weeks. After the first 4 weeks, participants were divided into two groups: the first group received gluten in capsules and the other one-rice starch (placebo). Blood and stool samples were examined before diet (T0), after 4 weeks (T1) and after 8 weeks of diet (T2). The only significant difference in blood parameters was observed between T1 and T2 in the placebo group for the thyroid peroxidase antibody level. After the first 4 weeks, a significant increase in Desulfobacterota, Proteobacteria, Prevotella and Parasutterella and a significant decrease in Actinobacteriota, Coriobacteriaceae and Bifidobacterium were observed. The detected microbiome alterations may indicate increasing inflammation; however, further research is required, and for now, a gluten-free diet should be used cautiously in AIT.

Biocompatible antibiotic-loaded mesoporous silica/bioglass/collagen-based scaffolds as bone drug delivery systems.

Local delivery of antibiotics has gained increasing interest in the treatment of osteomyelitis due to its effectiveness and safety. Since the regeneration of bone tissue at the site of infection is as important as bacterial eradication, implantable drug delivery systems should not only release the drugs in a proper manner but also exert the osseointegration capability. Herein, we present an implantable drug delivery system in a scaffold form with a unique set of features for local treatment of osteomyelitis. For the first time, collagen type I, ciprofloxacin-loaded mesoporous silica, and bioglass were combined to obtain scaffolds using the molding method. Drug-loaded mesoporous silica was blended with polydimethylsiloxane to prolong the drug release, whereas bioglass served as a remineralization agent. Collagen-silica scaffolds were evaluated in terms of physicochemical properties, drug release rate, mineralization potential, osteoblast response in vitro, antimicrobial activity, and biological properties using an in vivo preclinical model - chick embryo chorioallantoic membrane (CAM). The desirable multifunctionality of the proposed collagen-silica scaffolds was confirmed. They released the ciprofloxacin for 80 days, prevented biofilm development, and induced hydroxyapatite formation. Moreover, the resulting macroporous structure of the scaffolds promoted osteoblast attachment, infiltration, and proliferation. Collagen-silica scaffolds were also biocompatible and effectively integrated with CAM.

Bioglass obtained via one-pot synthesis as osseointegrative drug delivery system.

Osseointegration is a fundamental process during which implantable biomaterial integrates with host bone tissue. The surgical procedure of biomaterial implantation is highly associated with the risk of bacterial infection. Thus, the research continues for biodegradable bone void fillers which are able to stimulate the bone tissue regeneration and locally deliver the antibacterial agent. Herein, we obtained bifunctional bioglass (BG) using novel, preoptimized, rapid one-pot synthesis. Following the ISO Standards, the influence of the obtained BG on osteoblast-mediated phenomena, such as osteoconduction and osteoinduction was assessed and compared to two commercial materials: bioactive glass powder 45S and bioactive glass powder 85S. Direct-contact tests revealed osteoblast adhesion to BG particles; whereas, tests on extracts confirmed high viability of cells incubated with BG extract. Analyses of gene expression, alkaline phosphatase activity, and calcium phosphates deposition confirmed the stimulation of early and late stages of osteoblast differentiation and mineralization. Additionally, an extended evaluation of intracellular calcium fluctuations revealed a possible correlation between osteoblast calcium uptake and extracellular matrix mineralization. Moreover, proposed bioglass exhibited satisfactory doxycycline adsorption capacity and release profile. The obtained results confirmed the bifunctionality of the proposed BG and indicated its potential as osseointegrative bone drug delivery system.

Assessment of the Mineral Composition and the Selected Physicochemical Parameters of Dietary Supplements Containing Green Tea Extracts.

Our aim was to assess the mineral composition as well as the physicochemical quality of green tea-based dietary supplements (capsules and tablets) with respect to average weight, size and shape, friability, breaking force and disintegration time. Products were analysed by flame atomic absorption spectrometry for Ca, K, Mg, Na, Cr, Cu, Fe, Zn, Mn, Pb and Cd. Approximately 60% of the analysed supplements met the requirements of European and Polish regulations. The dietary supplements passed weight variation tests, but not all products had compliant capsule sizes. One product in tablet form failed the friability test, and eleven dietary supplements in tablet form failed the disintegration test. The supplements were characterised by a varied elemental composition, with the highest values found for Ca, Fe, Zn and Mn. The recommended daily allowance realisation for Fe and Zn in two dietary supplements (capsule form) exceeded 100%. As a result of the estimation of the monthly intake of toxic metals, it was concluded that the tested products do not pose a risk to consumer health. Significant relationships (p < 0.001) were found for K, Mg, Na, Cu, Fe, Mn and Zn. The application of factor and cluster analyses allowed the verification of the similarity of green tea extracts contained in dietary supplements to the natural raw material, green tea leaves, used as a reference material.

Antioxidant-Loaded Mesoporous Silica-An Evaluation of the Physicochemical Properties.

The dangerous effects of oxidative stress can be alleviated by antioxidants­substances with the ability to prevent damage caused by reactive oxygen species. The adsorption of antioxidants onto nanocarriers is a well-known method that might protect them against rough environ-mental conditions. The aim of this study was to investigate the adsorption and desorption of gallic acid (GA), protocatechuic acid (PCA), chlorogenic acid (CGA), and 4-hydroxybenzoic acid (4-HBA) using commercially available mesoporous silica materials (MSMs), both parent (i.e., SBA-15 and MCM-41) and surface functionalized (i.e., SBA-NH2 and SBA-SH). The MSMs loaded with active compounds were characterized using Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy with energy-dispersive X-ray spectroscopy (SEM-EDX), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), thermoporometry (TPM), and powder X-ray diffraction (XRD). High-performance liquid chromatography (HPLC-CAD) was used to evaluate the performance of the adsorption and desorption processes. The antioxidant potential was investigated using the Folin−Ciocalteu (FC) spectrophotometric method. Among the studied MSMs, the highest adsorption of GA was observed for amine-modified SBA-15 mesoporous silica. The adsorption capacity of SBA-NH2 increased in the order of PCA, 4-HBA < GA < CGA. Different desorption effectiveness levels of the adsorbed compounds were observed with the antioxidant capacity preserved for all investigated compounds.

Evaluation of Physicochemical Properties of Beetroot-Based Dietary Supplements.

In the European Union, no specific requirements for the physicochemical parameters of dietary supplements have been established, contrary to the United States of America. This research aimed to assess the selected physical parameters of 31 commercially available beetroot-based dietary supplements in the form of tablets and capsules following the United States Pharmacopoeia (USP) guidelines and the Food and Drug Administration (FDA) recommendations. There was also estimated zinc and iron content by atomic absorption spectroscopy with flame detection. Results showed that nine products did not meet the USP requirements. Seven supplements needed more than 30 min to disintegrate. Two products in the form of tablets did not pass the friability test because of cracking. The hardness values varied significantly between manufacturers, demonstrating values from 59.1 to 455.8 N. The iron-enriched supplements differed significantly in iron content compared with the manufacturers' declaration (84.91-140.69%). Inappropriate quality of dietary supplements, which may constitute a potential risk to consumers, can be related to the lack of specific regulations in Europe; hence, similar to the USA requirements should be considered in the European Union. The work emphasizes the need to better control the quality of dietary supplements before they are introduced to the European market.

The influence of biologics on the microbiome in immune-mediated inflammatory diseases: A systematic review.

BACKGROUND: Immune-mediated inflammatory diseases (IMIDs) are a group of several chronic disorders with elusive pathogenesis that results in dysregulation of the normal immune response and leads to organ-specific or systemic inflammation. There are many reports on gastrointestinal or skin dysbiosis in patients with IMIDs; however, it is not clear whether dysbiosis is a cause or a result of the observed inflammation. We aimed to determine whether treatment of IMIDs patients with biologics affects their microbiota in comparison with baseline or placebo. METHODS: We searched for studies in MEDLINE, Embase, Scopus, and Web of Science. Due to both high heterogeneity and lacking data, vote-counting and structured tables were used to summarize the data. RESULTS AND LIMITATIONS: A total of 25 longitudinal human studies with 816 IMIDs patients receiving biologics were included. Data on α-diversity change are inconclusive. Most evidence supports the increase in all α-diversity metrics in responding inflammatory bowel disease (IBD) patients; however, vote counting did not confirm the significance of the directional change. In case of ß-diversity, treatment with biologics made patients' microbiome more similar to the microbiome of healthy controls in 5 out of 7 studies. The changes in taxa abundance and predicted functionality of microbiome were systematically summarized. Limited number and quality of the included studies highly restricted the conclusions of the study. CONCLUSIONS: Local inflammation may play pivotal role in the gut microbiome disruption in IMIDs patients. The effect of the biologics on human microbiota should be evaluated in randomized controlled trials and transparently reported.

Mesoporous Silica-Bioglass Composite Pellets as Bone Drug Delivery System with Mineralization Potential.

For decades, local bone drug delivery systems have been investigated in terms of their application in regenerative medicine. Among them, inorganic polymers based on amorphous silica have been widely explored. In this work, we combined two types of amorphous silica: bioglass and doxycycline-loaded mesoporous silica MCM-41 into the form of spherical granules (pellets) as a bifunctional bone drug delivery system. Both types of silica were obtained in a sol-gel method. The drug adsorption onto the MCM-41 was performed via adsorption from concentrated doxycycline hydrochloride solution. Pellets were obtained on a laboratory scale using the wet granulation-extrusion-spheronization method and investigated in terms of physical properties, drug release, antimicrobial activity against Staphylococcus aureus, mineralization properties in simulated body fluid, and cytotoxicity towards human osteoblasts. The obtained pellets were characterized by satisfactory mechanical properties which eliminated the risk of pellets cracking during further investigations. The biphasic drug release from pellets was observed: burst stage (44% of adsorbed drug released within the first day) followed by prolonged release with zero-order kinetics (estimated time of complete drug release was 19 days) with maintained antimicrobial activity. The progressive biomimetic apatite formation on the surface of the pellets was observed. No cytotoxic effect of pellets towards human osteoblasts was noticed.

Microwave-Assisted Fabrication of Mesoporous Silica-Calcium Phosphate Composites for Dental Application.

Herein, the microwave-assisted wet precipitation method was used to obtain materials consisting of mesoporous silica (SBA-15) and calcium orthophosphates (CaP). Composites were prepared through immersion of mesoporous silica in different calcification coating solutions and then exposed to microwave radiation. The composites were characterized in terms of molecular structure, crystallinity, morphology, chemical composition, and mineralization potential by Fourier-transform infrared spectroscopy (FTIR), powder X-ray diffraction (XRD), and scanning electron microscopy equipped with energy-dispersive X-ray spectroscopy (SEM-EDX). The application of microwave irradiation resulted in the formation of different types of calcium orthophosphates such as calcium deficient hydroxyapatite (CDHA), octacalcium phosphate (OCP), and amorphous calcium phosphate (ACP) on the SBA-15 surface, depending on the type of coating solution. The composites for which the progressive formation of hydroxyapatite during incubation in simulated body fluid was observed were further used in the production of final pharmaceutical forms: membranes, granules, and pellets. All of the obtained pharmaceutical forms preserved mineralization properties.

Mesoporous silica pellets as bifunctional bone drug delivery system for cefazolin.

For decades, bone drug delivery systems dedicated for osteomyelitis treatment have been investigated as bifunctional materials that exhibit prolonged drug release and mineralization potential. Herein, composite-type pellets based on cefazolin-loaded amino-modified mesoporous silica SBA-15 and microwave-assisted hydroxyapatite were investigated as potential bone drug delivery system in vitro. Pellets were obtained by granulation, extrusion and spheronization methods in laboratory scale and studied in terms of physical properties, drug release, mineralization potential, antimicrobial activity and cytotoxicity towards human osteoblasts. The obtained pellets were characterized for hardness and friability which indicated the pellets durability during further investigations. Prolonged (5-day) release of cefazolin from pellets was observed. The pellets exhibited mineralization potential in simulated body fluid, i.e., a continuous layer of bone-like apatite was formed on the surface of pellets after 28 days of incubation. An antimicrobial assay of pellets revealed an antibacterial effect against Staphylococcus aureus strain during 6 days. No cytotoxic effects of pellets towards human osteoblasts were observed. The obtained results proved that proposed pellets appear to have potential applications as bone drug delivery systems.

Biphasic composite of calcium phosphate-based mesoporous silica as a novel bone drug delivery system.

We reported the new biphasic composites of calcium phosphate and mesoporous silica material (CaP@MSi) in the form of powders and pellets as a potential bone drug delivery system for doxycycline hydrochloride (DOX). The CaP@MSi powders were synthesized by cationic surfactant-templating method. The effects of 10, 20, and 30% CaP content in the CaP@MSi powders on the molecular surface structure, the cytotoxicity against osteoblast cells in vitro, and the mineralization potential in simulated body fluid were investigated. The CaP@MSi characterized by the highest mineralization potential (30% CaP content) were used for DOX adsorption and pelletization process. The CaP which precipitated in the CaP@MSi composites was characterized as calcium-deficient with the Ca:P molar ratio between 1.0 and 1.2. The cytotoxicity assays demonstrated that the CaP content in MSi increases osteoblasts viability indicating the CaP@MSi (30% CaP content) as the most biocompatible. The combination of CaP and MSi was an effective strategy to improve the mineralization potential of parent material. Upon immersion in simulated body fluid, the CaP of composite converted into the bone-like apatite. The obtained pellets preserved the mineralization potential of CaP@MSi and provided the prolonged 5-day DOX release. The obtained biphasic CaP@MSi composites seem to have an application potential as bone-specific drug delivery system.

The Effect of Polydimethylsiloxane-Ethylcellulose Coating Blends on the Surface Characterization and Drug Release of Ciprofloxacin-Loaded Mesoporous Silica.

In this study, we obtained novel solid films composed of ciprofloxacin-loaded mesoporous silica materials (CIP-loaded MCM-41) and polymer coating blends. Polymer coating blends were composed of ethylcellulose (EC) with various levels of polydimethylsiloxane (PDMS, 0, 1, 2% (v/v)). The solid films were prepared via the solvent-evaporation molding method and characterized by using scanning electron microscopy (SEM), optical profilometry, and wettability analyses. The solid-state of CIP present in the solid films was studied using X-ray diffraction (XRD) and differential scanning calorimetry (DSC). The release profiles of CIP were examined as a function of PDMS content in solid films. The surface morphology analysis of solid films indicated the progressive increase in surface heterogeneity and roughness with increasing PDMS content. The contact angle study confirmed the hydrophobicity of all solid films and significant impact of both PDMS and CIP-loaded MCM-41 on surface wettability. DSC and XRD analysis confirmed the presence of amorphous/semi-crystalline CIP in solid films. The Fickian diffusion-controlled drug release was observed for the CIP-loaded MCM-41 coated with PDMS-free polymer blend, whereas zero-order drug release was noticed for the CIP-loaded MCM-41 coated with polymer blends enriched with PDMS. Both the release rate and initial burst of CIP decreased with increasing PDMS content.

Silica-Polymer Composites as the Novel Antibiotic Delivery Systems for Bone Tissue Infection.

Bone tissue inflammation, osteomyelitis, is commonly caused by bacterial invasion and requires prolonged antibiotic therapy for weeks or months. Thus, the aim of this study was to develop novel silica-polymer local bone antibiotic delivery systems characterized by a sustained release of ciprofloxacin (CIP) which remain active against Staphylococcus aureus for a few weeks, and do not have a toxic effect towards human osteoblasts. Four formulations composed of ethylcellulose (EC), polydimethylsiloxane (PDMS), freeze-dried CIP, and CIP-adsorbed mesoporous silica materials (MCM-41-CIP) were prepared via solvent-evaporation blending method. All obtained composites were characterized in terms of molecular structure, morphological, and structural properties by using Fourier Transform Infrared Spectroscopy (FTIR), scanning electron microscopy equipped with energy-dispersive X-ray spectroscopy (SEM/EDX), and X-ray diffraction (XRD), thermal stability by thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC), and in vitro antibiotic release. The antibacterial activity against Staphylococcus aureus (ATCC 6538) as well as the in vitro cytocompatibility to human osteoblasts of obtained composites were also examined. Physicochemical results confirmed the presence of particular components (FTIR), formation of continuous polymer phase onto the surface of freeze-dried CIP or MCM-41-CIP (SEM/EDX), and semi-crystalline (composites containing freeze-dried CIP) or amorphous (composites containing MCM-41-CIP) structure (XRD). TGA and DSC analysis indicated the high thermal stability of CIP adsorbed onto the MCM-41, and higher after MCM-41-CIP coating with polymer blend. The release study revealed the significant reduction in initial burst of CIP for the composites which contained MCM-41-CIP instead of freeze-dried CIP. These composites were also characterized by the 30-day activity against S. aureus and the highest cytocompatibility to human osteoblasts in vitro.

Surface-Activated Fibre-Like SBA-15 as Drug Carriers for Bone Diseases.

Here, we report an inorganic hexagonally ordered mesoporous fibre-like carrier made of silica as an effective drug delivery system with mineralisation potential. Fibre-like SBA-15 has been modified by employing a simple surface activation (rehydroxylation) procedure. The surface-rehydroxylated fibre-like SBA-15 (SBA-15-R) was used to investigate the possible mechanism of hydroxyapatite (HA) nucleation and deposition onto silica's surface after immersion in simulated body fluid (SBF). Amorphous calcium phosphate, Ca-deficient HA and bone-like HA deposits were observed on SBA-15-R surface consecutively after 7, 14 and 21 days of immersion in SBF. Accordingly, our low-angle XRD, STEM and N2 adsorption/desorption results indicated that deposited ions were mostly located at the silica's surface and could modify the size of the mesopores. The SBA-15-R was studied in vitro as the potential bioactive drug delivery system using doxorubicin (DOX) as a model water-soluble and anticancer drug. The adsorbed DOX molecules were mostly located at the pore walls and pore openings, likely together with the silanol groups. The DOX release was diffusion-controlled and relatively slower in SBF (pH = 7.4) than in phosphate-buffered solution (pH = 5.0), most probably due to both the stronger electrostatic interactions occurring between the DOX and the SBA-15-R and the simultaneous deposition of calcium and phosphates ions from SBF.

Preparation and in vitro characterisation of bioactive mesoporous silica microparticles for drug delivery applications.

The aim of this study was to evaluate the surface mineralization activity and in vitro drug behaviour potential of new mesoporous silica microparticles (MSM). The unmodified MSM (MSM-0%Ca) and calcium-modified MSM (MSM-5%Ca, MSM-15%Ca, MSM-25%Ca) were prepared using the self-assembling method. Calcium diethoxide was used as a calcium precursor. Doxorubicin hydrochloride (DOX), used as an anticancer model drug, was selected to the drug loading and release studies. The DOX loading into the microparticles was performed by liquid adsorption process. The self-formation of carbonate hydroxyapatite (C-Hap) on the MSM surface was examined under in vitro biomimetic conditions. The samples were characterised by means of scanning-transmission electron microscopy (STEM) and energy dispersive X-ray spectrometry, powder X-ray diffraction, Fourier transform infrared spectroscopy, and nitrogen adsorption-desorption measurements. The results indicated an inverse relationship--while increasing the total amount of calcium in the MSM composition the surface area and pore volume decrease with a simultaneous increase in the pore size. This was correlated with a progressive increase in the surface mineralization ability--especially its initial promotion, and in the decrease in MSM drug loading efficiency. The release rate of the DOX can be effectively tailored by varying the amount of calcium, where the elution rate of DOX increases with an increasing amount of the Ca precursor.