Controlled Calcium Oxalate Crystals Obtained by Electrocrystallization on Electrospun Polycaprolactone Fibers Loaded with Zarzaparrilla ( Herreria stellata ).

Calcium oxalate (CaOx) is known to grow on organic matrices and is often associated with the formation of kidney stones. Therefore, it is crucial to understand the nucleation and growth mechanisms. This study investigates the role of electrospun polycaprolactone (PCL)-loaded zarzaparrilla (ZP) (Herreria stellata) in the electrocrystallization (EC) of CaOx. Electrospinning (ES) was used to prepare PCL meshes with random (R) and aligned (A) fiber orientations. CaOx particles were grown directly on conductive tin indium oxide (ITO) glass modified with electrospun ZP-loaded PCL meshes by EC. The CaOx crystals after EC were measured by chronopotentiometry (CP), optical microscopy (OM), scanning electron microscopy (SEM), and X-ray diffraction (XRD), which showed that the ZP additive and PCL fiber orientations are key factors for CaOx nucleation.

Conformational Changes of Poly(Maleic Anhydride-alt-styrene) Modified with Amino Acids in an Aqueous Medium and Their Effect on Cytocompatibility and Hemolytic Response.

The conformational changes of poly(maleic anhydride-alt-styrene) (PSMA) modified with different amino acids (PSMA-Aa) were studied in an aqueous medium as a function of ionic strength and pH. The specific viscosity of PSMA-Aa decreased with increasing salt concentration due to a more compact conformation. There was a decrease in surface tension with increasing concentrations of the modified polyelectrolyte having a greater effect for the PSMA modified with l-phenylalanine at pH 7.0, demonstrating a greater surface-active character. The conformational changes were also confirmed by molecular dynamics studies, indicating that PSMA-Aa exhibits a compact structure at pH 4.0 and a more extended structure at pH 7.0. On the other hand, the conformational changes of PSMA-Aa were related to its biological response, where the higher surface-active character of the PSMA modified with l-phenylalanine correlates very well with the higher hemolytic activity observed in red blood cells, in which the surface-active capacity supports lytic potency in erythrocytes. The cytocompatibility assays indicated that there were no significant cytotoxic effects of the PSMA-Aa. Additionally, in solvent-accessible surface area studies, it was shown that the carboxylate groups of the PSMA modified with l-phenylalanine are more exposed to the solvent at pH 7.0 and high salt concentrations, which correlates with lower fluorescence intensity, reflecting a loss of mitochondrial membrane potential. It is concluded that the study of the conformational changes in PE modified with amino acids is essential for their use as biomaterials and relevant to understanding the possible effects of PE modified with amino acids in biological systems.

Association Study between DUF1220 Copy Number and Severity of Social Impairment in Sex-balanced Simplex Cases of Autism.

Introduction: Copy number variations (CNVs), which are genetic factors responsible for human evolution, have emerged as underlying pathogenic factors for a number of diseases such as autism spectrum disorders (ASD). DUF1220 coding sequences have been shown to be positively associated with the severity of symptoms in familial/multiplex cases of autism. However, this association has not been confirmed in simplex autism, and the potential impact of gender/sex has not been studied. Methods: Using saliva samples taken from Iranian children with non-syndromic simplex autism, different ethnicity/race and genetic backgrounds from previous studies, we assessed the association between DUF1220 CNVs and Autism Diagnostic Interview-Revised (ADI-R) domain scores in both males and females. Results: In the male and female combined group with autism, in line with previous reports, our findings showed that there were no significant associations between DUF1220 CNVs with either total ADI-R score, social, communication, or repetitive diagnostic scores in simplex autism cases. Interestingly, however, in sex classified groups, despite the insignificant results, our findings in girls with autism showed a negative trend between DUF1220 CNVs and severity of symptoms for the social interaction and communication domains. By contrast, in male children with autism, the results showed a positive trend. Conclusion: It seems that association of DUF1220 CNV with the severity of symptoms in simplex children with autism may follow a sexually dimorphic pattern that needs to be re-examined in prospective studies.

Sexual Dimorphism in Telomere Length in Childhood Autism.

Autism spectrum disorders (ASD) are strikingly more prevalent in males, but the molecular mechanisms responsible for ASD sex-differential risk are poorly understood. Abnormally shorter telomeres have been associated with autism. Examination of relative telomere lengths (RTL) among non-syndromic male (N = 14) and female (N = 10) children with autism revealed that only autistic male children had significantly shorter RTL than typically-developing controls (N = 24) and paired siblings (N = 10). While average RTL of autistic girls did not differ significantly from controls, it was substantially longer than autistic boys. Our findings indicate a sexually-dimorphic pattern of RTL in childhood autism and could have important implications for RTL as a potential biomarker and the role/s of telomeres in the molecular mechanisms responsible for ASD sex-biased prevalence and etiology.

Electrical Properties of Polyetherimide-Based Nanocomposites Filled with Reduced Graphene Oxide and Graphene Oxide-Barium Titanate-Based Hybrid Nanoparticles.

The electrical properties of nanocomposites based on polyetherimide (PEI) filled with reduced graphene oxide (rGO) and a graphene oxide hybrid material obtained from graphene oxide grafted with poly(monomethyl itaconate) (PMMI) modified with barium titanate nanoparticles (BTN) getting (GO-g-PMMI/BTN) were studied. The results indicated that the nanocomposite filled with GO-g-PMMI/BTN had almost the same electrical conductivity as PEI (1 × 10-11 S/cm). However, the nanocomposite containing 10 wt.% rGO and 10 wt.% GO-g-PMMI/BTN as fillers showed an electrical conductivity in the order of 1 × 10-7 S/cm. This electrical conductivity is higher than that obtained for nanocomposites filled with 10% rGO (1 × 10-8 S/cm). The combination of rGO and GO-g-PMMI/BTN as filler materials generates a synergistic effect within the polymeric matrix of the nanocomposite favoring the increase in the electrical conductivity of the system.

Electrocrystallization of Calcium Oxalate on Electrospun PCL Fibers Loaded with Phytic Acid as a Template.

Crystallization occurs widely in living organisms where different organs could associate with the calcification process, such as the formation of calcium oxalate (CaOx) calculi in the urinary tract. However, the pathogenesis and the role of an inhibitor in the pathological processes involved in urolithiasis is poorly understood. Therefore, the use of phytic acid (PA) as an inhibitor for the organic fibrillar matrix is a novel approach to inhibit the formation of pathological CaOx crystals. Herein, electrospun polymer fiber meshes of polycaprolactone (PCL) with random (R) and aligned (A) fiber orientations containing PA were prepared by electrospinning, and their role as a 3D organic template in in vitro CaOx crystallization was investigated. CaOx crystals were generated on conductive tin indium oxide (ITO)-modified glass with R-PCL and A-PCL fibers in the presence of PA through an electrocrystallization (EC) procedure. This study provides a simple electrochemical approach to evaluate the role of PA as an inhibitor in the nucleation of pathological CaOx crystals. The resulting CaOx crystals were analyzed by chrono-potentiometry, optical microscopy (OM), scanning electron microscopy (SEM), and X-ray diffraction (XRD). We found that PA and the fiber orientations are key factors in the nucleation and crystal growth of CaOx, achieving the stabilization of healthy CaOx crystal and the inhibition of the pathological crystal form.

Thermally Reduced Graphene Oxide/Thermoplastic Polyurethane Nanocomposites: Mechanical and Barrier Properties.

This work consists of studying the influence of two thermally reduced graphene oxides (TRGOs), containing oxygen levels of 15.8% and 8.9%, as fillers on the barrier properties of thermoplastic polyurethane (TPU) nanocomposites prepared by melt-mixing processes. The oxygen contents of the TRGOs were obtained by carrying out the thermal reduction of graphene oxide (GO) at 600 °C and 1000 °C, respectively. The presence and contents of oxygen in the TRGO samples were determined by XPS and their structural differences were determined by using X-ray diffraction analysis and Raman spectroscopy. In spite of the decrease of the elongation at break of the nanocomposites, the Young modulus was increased by up to 320% with the addition of TRGO. The barrier properties of the nanocomposites were enhanced as was evidenced by the decrease of the permeability to oxygen, which reached levels as low as -46.1%.

In Vitro Hyperthermia Evaluation of Electrospun Polymer Composite Fibers Loaded with Reduced Graphene Oxide.

Electrospun meshes (EM) composed of natural and synthetic polymers with randomly or aligned fibers orientations containing 0.5% or 1% of thermally reduced graphene oxide (TrGO) were prepared by electrospinning (ES), and their hyperthermia properties were evaluated. EM loaded with and without TrGO were irradiated using near infrared radiation (NIR) at 808 nm by varying the distance and electric potential recorded at 30 s. Morphological, spectroscopic, and thermal aspects of EM samples were analyzed by using SEM-EDS, Raman and X-ray photoelectron (XPS) spectroscopies, X-ray diffraction (XRD), and NIR radiation response. We found that the composite EM made of polyvinyl alcohol (PVA), natural rubber (NR), and arabic gum (AG) containing TrGO showed improved hyperthermia properties compared to EM without TrGO, reaching an average temperature range of 42-52 °C. We also found that the distribution of TrGO in the EM depends on the orientation of the fibers. These results allow infering that EM loaded with TrGO as a NIR-active thermal inducer could be an excellent candidate for hyperthermia applications in photothermal therapy.

Electrical Properties of Poly(Monomethyl Itaconate)/Few-Layer Functionalized Graphene Oxide/Lithium Ion Nanocomposites.

Poly(monomethyl itaconate) is outstanding because it is a glassy and dielectric polymer obtained from sustainable feedstock. Consequently, the study of the properties of its nanocomposites has gained importance. Herein, the electrical properties of nanocomposites based on poly(monomethyl itaconate) and functionalized few-layer graphene oxide (FGO) in the presence and absence of lithium ions (Li+) are studied. Not only did the electrical conductivities of the nanocomposites present values as high as 10-5 Scm-1, but also the dielectric permittivity of nanocomposites with (FGO) content lower than the percolation threshold was twice that of the pristine polymer, without presenting a drastic increase of the loss tangent. By contrast, nanocomposites containing Li+ ions presented significant increases of the permittivity with concomitant increases of the loss tangent. Moreover, it was determined that the presence of Li+ ions influenced the charge transport in the composites because of its ionic nature.

SEBS-Grafted Itaconic Acid as Compatibilizer for Elastomer Nanocomposites Based on BaTiO3 Particles.

Itaconic acid (IA) is an organic acid produced by the fermentation of sugars with aspergillus. It has been identified as one of the top 12 building-block chemicals. Here, we report the use of IA as a possible substitute to petroleum-based compatibilizers in polymer composite. We applied this study to thermoplastic elastomers based on styrene copolymers, since they are commonly used in blends and composites. Poly(styrene-b-ethylene-butylene-b-styrene) (SEBS) was grafted with 2.6 wt.% of itaconic acid (SEBS-g-IA) prepared by a reactive melt-mixing process, and was subsequently used to prepare composites filled with BaTiO3.). IA was successfully grafted as demonstrated by FTIR and XRD. SEBS-g-IA composites presented better mechanical properties, achieving an increase of Young modulus up to 80% compared with the neat polymer. This was ascribed to better dispersion and compatibility with the filler. Additionally, SEBS-g-IA showed increased dielectric permittivity, i.e., showed increased polarity, which indicates that it could potentially be used as a modifier for specialized polymers.

Functionalized Multiwalled CNTs in Classical and Nonclassical CaCO3 Crystallization.

Multiwalled carbon nanotubes (MWCNTs) are interesting high-tech nanomaterials. MWCNTs oxidized and functionalized with itaconic acid and monomethylitaconate were demonstrated to be efficient additives for controlling nucleation of calcium carbonate (CaCO3) via gas diffusion (GD) in classical as well as nonclassical crystallization, yielding aragonite and truncated calcite. For the first time, all amorphous calcium carbonate (ACC) proto-structures, such as proto calcite-ACC, proto vaterite-ACC and proto aragonite-ACC, were synthesized via prenucleation cluster (PNC) intermediates and stabilized at room temperature. The MWCNTs also showed concentration-dependent nucleation promotion and inhibition similar to biomolecules in nature. Incorporation of fluorescein-5-thiosemicarbazide (5-FTSC) dye-labeled MWCNTs into the CaCO3 lattice resulted in fluorescent hybrid nanosized CaCO3. We demonstrate that functionalized MWCNTs offer a good alternative for controlled selective crystallization and for understanding an inorganic mineralization process.

Synthesis of fluorinated graphene oxide by using an easy one-pot deoxyfluorination reaction.

The fluorination of two types of graphene oxides conducted by an easy and scalable deoxyfluorination reaction is reported. This reaction was carried out using diethylaminodifluorosulfinium tetrafluoroborate, a stable compound and an efficient reagent for replacing oxygenated functional groups of graphene oxide by fluoride. The graphene oxide produced by the Hummers' method (GOH) showed lower reactivity than that produced by the Brodie's method (GOB). X-ray photoelectron spectroscopy indicated that the highest fluorination degree achieved was 4.7 at.% when GOB was used, and the CF character corresponds to semi-ionic bonds. Additionally, a partial reduction of GO was concomitant with the functionalization reaction. The deoxyfluorination reaction changed the crystalline structure of GO, favoring the reconstruction of Csp2 structure of the graphene lattice and reducing the number of stacked layers. The fluorination led to the modification of the electronic band structure of this material, increasing the band gap from 2.05 eV for GOB to 3.88 eV for fluorinated GOB, while for GOH the low flurionation led to a slight increase of the band gap, from 3.48 eV to 3.57 eV.

Thymol nanoemulsions incorporated in quinoa protein/chitosan edible films; antifungal effect in cherry tomatoes.

Thymol nanoemulsions were produced by spontaneous emulsification, ultrasound, and a combination of both methods. The best result in terms of size and polydispersion was spontaneous emulsification where thymol was efficiently encapsulated, the nanoemulsions inhibited Botrytis cinerea at 110 ppm of thymol. A 10% dilution of this nanoemulsion in water was used to prepare quinoa-chitosan films. The film microstructure was porous and heterogeneous. The tensile strength of the film was significantly lower but its mean elongation at break was similar to that of the control film. The water vapour permeability was similar to that of the control film. The effect of nanoemulsion-thymol-quinoa protein/chitosan coating on mould growth in inoculated cherry tomatoes was evaluated. Compared with control samples (tomatoes without coating and those coated with quinoa protein/chitosan), tomatoes with this coating and inoculated with B. cinerea showed a significant decrease in fungal growth after 7 days at 5 °C.

Selection of Suitable Reference Genes for Analysis of Salivary Transcriptome in Non-Syndromic Autistic Male Children.

Childhood autism is a severe form of complex genetically heterogeneous and behaviorally defined set of neurodevelopmental diseases, collectively termed as autism spectrum disorders (ASD). Reverse transcriptase quantitative real-time PCR (RT-qPCR) is a highly sensitive technique for transcriptome analysis, and it has been frequently used in ASD gene expression studies. However, normalization to stably expressed reference gene(s) is necessary to validate any alteration reported at the mRNA level for target genes. The main goal of the present study was to find the most stable reference genes in the salivary transcriptome for RT-qPCR analysis in non-syndromic male childhood autism. Saliva samples were obtained from nine drug naïve non-syndromic male children with autism and also sex-, age-, and location-matched healthy controls using the RNA-stabilizer kit from DNA Genotek. A systematic two-phased measurement of whole saliva mRNA levels for eight common housekeeping genes (HKGs) was carried out by RT-qPCR, and the stability of expression for each candidate gene was analyzed using two specialized algorithms, geNorm and NormFinder, in parallel. Our analysis shows that while the frequently used HKG ACTB is not a suitable reference gene, the combination of GAPDH and YWHAZ could be recommended for normalization of RT-qPCR analysis of salivary transcriptome in non-syndromic autistic male children.

Mobile DNA Elements: The Seeds of Organic Complexity on Earth.

Mobile DNA or transposable elements (TEs) are genomic sequences capable of moving themselves independently into different parts of the genome. Viral invasion of eukaryotic genomes is assumed to be the main source of TEs. Selfish transposition of these elements could be a serious threat to the host cell, as they can insert themselves into the middle of coding genes and/or induce genomic instability. In response, through millions of years of evolution, cells have come up with various mechanisms such as genomic imprinting, DNA methylation, heterochromatin formation, and RNA interference to deactivate them. Interestingly, these processes have also greatly contributed to important cellular functions involved in cell differentiation, development, and differential gene expression. Propagation of TE copies during the course of evolution have resulted in increasing the genome size and providing proper space and flexibility in shaping the genome by creating new genes and establishing essential cellular structures such as heterochromatin, centromere, and telomeres. Yet, these elements are mostly labeled for playing a role in pathogenesis of human diseases. Here, we attempt to introduce TEs as factors necessary for making us human rather than just selfish sequences or obligatory guests invading our DNA.

P53 gene codon 72 polymorphism in patients with oral squamous cell carcinoma in the population of northern Iran

OBJECTIVES: Squamous cell carcinoma is the most common cancer of the oral cavity, and several etiologic factors are involved in its development. Single nucleotide polymorphism (SNP) of the P53 gene codon 72 (P53c72) changes the structure of the protein and affects its activity. The prevalence of P53c72 different genotypes, which seems to vary with race and geographic location, has shown a strong correlation with many types of human cancers. The aim of this study was to investigate the correlation between P53c72 polymorphism and risk of oral squamous cell carcinoma (OSCC) in the heavily populated Gilan Province in northern Iran. Design of Study: This case-control study was done on 55 paraffin-embedded samples from OSCC patients and 100 samples of non-dysplastic oral cavity lesions. The P53c72 genotypes were determined using the ARMS-PCR method. SPSS-15 software was used for statistical analysis. RESULTS: There were no significant statistical differences found between the prevalence of different P53c72 genotypes in the OSCC group vs. the control. However, the Pro/Pro genotype in OSCC samples showed a strong correlation with age, as 70% of such patients were below 50 years old. Interestingly, a large portion (40%) of the patients with the Pro/Pro genotype had the tumor in the lip area. CONCLUSIONS: Although P53c72 polymorphism does not appear to be a predisposing factor for OSCC in the population of Northern Iran, the Pro/Pro genotype could be considered as a risk factor for OSCC in adults below 50 years old and the anatomical location of the tumor

Inclusion and functionalization of polymers with cyclodextrins: current applications and future prospects.

The numerous hydroxyl groups available in cyclodextrins are active sites that can form different types of linkages. They can be crosslinked with one another, or they can be derivatized to produce monomers that can form linear or branched networks. Moreover, they can form inclusion complexes with polymers and different substrates, modifying their physicochemical properties. This review shows the different applications using polymers with cyclodextrins, either by forming inclusion complexes, ternary complexes, networks, or molecularly imprinted polymers (MIPs). On one hand, the use of cyclodextrins enhances the properties of each polymer, and on the other the use of polymers decreases the amount of cyclodextrins required in different formulations. Both cyclodextrins and polymers contribute synergistically in several applications such as pharmacological, nutritional, environmental, and other industrial fields. The use of polymers based on cyclodextrins is a low cost easy to use potential tool with great future prospects.

P53 gene codon 72 polymorphism in patients with oral squamous cell carcinoma in the population of northern Iran.

OBJECTIVES: Squamous cell carcinoma is the most common cancer of the oral cavity, and several etiologic factors are involved in its developing. Single nucleotide polymorphism (SNP) of the P53 gene codon 72 (P53c72) changes the structure of the protein and affects its activity. The prevalence of P53c72 different genotypes, which seems to vary with race and geographic location, has shown a strong correlation with many types of human cancers. The aim of this study was to investigate the correlation between P53c72polymorphism and risk of oral squamous cell carcinoma (OSCC) in the heavily populated Gilan Province in northern Iran. DESIGN OF STUDY: This case-control study was done on 55 paraffin-embedded samples from OSCC patients and 100 samples of non-dysplastic oral cavity lesions. The P53c72 genotypes were determined using the ARMS-PCR method. SPSS-15 software was used for statistical analysis. RESULTS: There were no significant statistical differences found between the prevalence of different P53c72 genotypes in the OSCC group vs. the control. However, the Pro/Pro genotype in OSCC samples showed a strong correlation with age, as 70% of such patients were below 50 years old. Interestingly, a large portion (40%) of the patients with the Pro/Pro genotype had the tumor in the lip area. CONCLUSIONS: Although P53c72 polymorphism does not appear to be a predisposing factor for OSCC in the population of Northern Iran, the Pro/Pro genotype could be considered as a risk factor for OSCC in adults below 50 years old and the anatomical location of the tumor.

Preparation and bioactive properties of novel bone-repair bionanocomposites based on hydroxyapatite and bioactive glass nanoparticles.

Bionanocomposites based on ceramic nanoparticles and a biodegradable porous matrix represent a promising strategy for bone repair applications. The preparation and bioactive properties of bionanocomposites based on hydroxyapatite (nHA) and bioactive glass (nBG) nanoparticles were presented. nHA and nBG were synthesized with nanometric particle size using sol-gel/precipitation methods. Composite scaffolds were prepared by incorporating nHA and nBG into a porous alginate (ALG) matrix at different particle loads. The ability of the bionanocomposites to induce the crystallization of the apatite phase from simulated body fluid (SBF) was systematically evaluated using X-ray diffraction (XRD), scanning electron microscopy with energy dispersive X-ray analysis, and Fourier transform infrared spectroscopy. Both nHA/ALG and nBG/ALG composites were shown to notably accelerate the process of crystallization and growth of the apatite phase on the scaffold surfaces. For short immersion times in SBF, nBG (25%)-based nanocomposites induced a higher degree of apatite crystallization than nHA (25%)-based nanocomposites, probably due to the more reactive nature of the BG particles. Through a reinforcement effect, the nanoparticles also improve the mechanical properties and stability in SBF of the polymer scaffold matrix. In addition, in vitro biocompatibility tests demonstrated that osteoblast cells are viable and adhere well on the surface of the bionanocomposites. These results indicate that nHA- and nBG-based bionanocomposites present potential properties for bone repair applications, particularly oriented to accelerate the bone mineralization process.

Molecular analysis of the RET proto-oncogene key exons in patients with medullary thyroid carcinoma: a comprehensive study of the Iranian population.

BACKGROUND: Germ-line mutations of RET proto-oncogene are the known cause of hereditary medullary thyroid carcinoma (MTC), which account for approximately 25% of all MTC cases and occur as multiple endocrine neoplasia type 2 syndromes. Here, we present the first comprehensive genetic screening and analysis of MTC among Iranian families. METHODS: A total of 55 patients with MTC (male to female ratio=1:1.6; average age of disease onset = 33 ± 13 years) from 53 independent families participated in this study. All of the patients had undergone total thyroidectomy between 1999 and 2006, and 51 of them were clinically characterized as apparently sporadic cases. Genomic DNA samples were obtained and following highly-specific polymerase chain reaction amplification of the 6 RET key exons (10, 11, 13, 14, 15, and 16) were subjected to direct DNA sequencing without a requirement for a purification step. RESULTS: Sequence analysis revealed that 9 (17.6%) of the apparently sporadic cases (from 8 kindreds) carried an RET germ-line mutation. Of the seven different mutations identified among all of the families studied, five were in the cysteine codons, with Cys634Arg having the highest prevalence (45.5%) among the afflicted families. Mutation carriers have an earlier age of onset (21 ± 6) versus the sporadic cases (37 ± 12). CONCLUSIONS: This is the first comprehensive genetic screening and analysis of MTC among Iranian families. The results further confirm the need and advantages of DNA sequencing for identification of hereditary MTC cases. There does not seem to be a meaningful correlation between single nucleotide polymorphism patterns and the average age of disease onset. Geographical distribution of the sporadic cases, however, shows a significant concentration toward the Northern regions of the country, noticeably the provinces situated directly to the south of the Caspian Sea.