Influence of diimine bidentate ligand in the nitrosyl and nitro terpyridine ruthenium complex on the HSA/DNA interaction and antiviral activity.

Nitric oxide (NO) acts in different physiological processes, such as blood pressure control, antiparasitic activities, neurotransmission, and antitumor action. Among the exogenous NO donors, ruthenium nitrosyl/nitro complexes are potential candidates for prodrugs, due to their physicochemical properties, such as thermal and physiological pH stability. In this work, we proposed the synthesis and physical characterization of the new nitro terpyridine ruthenium (II) complexes of the type [RuII(L)(NO2)(tpy)]PF6 where tpy = 2,2':6',2″-terpyridine; L = 3,4-diaminobenzoic acid (bdq) or o-phenylenediamine (bd) and evaluation of influence of diimine bidentate ligand NH.NHq-R (R = H or COOH) in the HSA/DNA interaction as well as antiviral activity. The interactions between HSA and new nitro complexes [RuII(L)(NO2)(tpy)]+ were evaluated. The Ka values for the HSA-[RuII(bdq)(NO2)(tpy)]+ is 10 times bigger than HSA-[RuII(bd)(NO2)(tpy)]+. The sites of interaction between HSA and the complexes via synchronous fluorescence suppression indicate that the [RuII(bdq)(NO2)(tpy)]+ is found close to the Trp-241 residue, while the [RuII(bd)(NO2)(tpy)]+ complex is close to Tyr residues. The interaction with fish sperm fs-DNA using direct spectrophotometric titration (Kb) and ethidium bromide replacement (KSV and Kapp) showed weak interaction in the system fs-DNA-[RuII(bdq)(NO)(tpy)]+. Furthermore, fs-DNA-[RuII(bd)(NO2)(tpy)]+ and fs-DNA-[RuII(bd)(NO)(tpy)]3+ system showed higher intercalation constant. Circular dichroism spectra for fs-DNA-[RuII(bd)(NO2)(tpy)]+ and fs-DNA-[RuII(bd)(NO)(tpy)]3+, suggest semi-intercalative accompanied by major groove binding interaction modes. The [RuII(bd)(NO2)(tpy)]+ and [RuII(bd)(NO)(tpy)]3+ inhibit replication of Zika and Chikungunya viruses based in the nitric oxide release under S-nitrosylation reaction with cysteine viral.

Enhancing Methylene Blue Dye Removal using pyrolyzed Mytella falcata Shells: Characterization, Kinetics, Isotherm, and Regeneration through Photolysis and Peroxidation.

The potential of pyrolyzed Mytella falcata shells as an adsorbent for removing methylene blue dye molecules from aqueous solutions was investigated. The study found that the adsorbent produced at 600 °C of pyrolysis temperature, with an adsorbent mass of 0.5 g, particle diameter of 0.297-0.149 mm, and pH 12.0, demonstrated the highest dye molecule removal efficiency of 82.41%. The material's porosity was observed through scanning electron microscopy, which is favorable for adsorption, while Fourier-transform infrared spectroscopy and X-Ray diffraction analysis analyses confirmed the presence of calcium carbonate in the crystalline phases. The pseudo-second order model was found to be the best fit for the data, suggesting that the adsorption mechanism involves two steps: external diffusion and diffusion via the solid pores. The Redlich-Peterson isotherm model better represented the equilibrium data, and the methylene blue adsorption was found to be spontaneous, favorable, and endothermic. The hydrogen peroxide with UV oxidation was found to be the most efficient method of regeneration, with a regeneration percentage of 63% achieved using 600 mmol.L-1 of oxidizing agents. The results suggest that pyrolyzed Mytella falcata shells could serve as an ecologically viable adsorbent alternative, reducing the amount of waste produced in the local environment and at the same time removing pollutants from the water. The material's adsorption capacity remained almost constant in the first adsorption-oxidation cycles, indicating its potential for repeated use.

Gelatin Carbon Dots Interaction with Nitrosyl Ruthenium Complex: Fluorescence Quenching and Chemiluminescence Mechanisms.

Carbon dots (CDs) exhibit luminescence, biocompatibility, and higher water solubility. This material has been developed for biological applications, specifically in bioimaging. In this work, the gelatin carbon dots (CDg) was obtained from commercial gelatin using a hydrothermal method in domestic microwave, and the suppression fluorescent mechanism were enhanced by the addition of the [RuII(bdq)(NO)(tpy)]3+ (Rubdq-NO+) complex ion. After purification through a dialysis bag, the resulting CDs (CDg) exhibit fluorescent emission at 400 nm and maintained fluorescence stability in an aqueous solution (pH = 7) for 30 days under 5 ◦C. Fluorescence quenching studies revealed an electrostatic interaction between the negative charge from CDg (δ = - 20 mV) and the positively charged nitrosyl (NO+) ligand of the ruthenium complex (Rubdq-NO+), resulting in quenching of the CDg fluorescence due to the inner filter effects (IFE). The chemiluminescence reaction of CDg and Rubdq-NO-CDg in presence of norepinephrine (NOR) were evaluated. NOR in PBS are liable to undergo spontaneous oxidation to quinone form (NOR-quinone). CDg are believed interact with NOR-quinone and an electron transfer occur obtained CDg+ accompanied to green emission fluorescence (520 nm). While for Rubdq-NO-CDg in presence of NOR, the green emission occurs accompanied by NO0 release using DAF-2 probe.

Simple and cheap preparation of fluorescence paper sensor based in carbon dot for visual detection of chloramphenicol.

Carbon dots (CDs) are nanometer-scale particles produced from carbon sources that exhibit fluorescence emission. The present work presents the synthesis and characterization of CDs, as well as the sensing studies for the determination of chloramphenicol (CAP). CAP is an antibiotic used in human medicine and agriculture, and its indiscriminate use and inappropriate disposal have caused damage to human health and the environment. The carbonaceous precursor used in the synthesis of CDs was 3,4-diaminobenzoic acid (3,4-DABA) through the hydrothermal method via domestic microwave irradiation. The first synthesis procedure was carried out in the presence of water/ethanol (a-CDs) and the second in the presence of 1 mol/L sodium hydroxide/ethanol (b-CDs). The CDs were initially characterized in terms of spectroscopic properties in the ultraviolet and visible region (UV-visible), Fourier-transform infrared (FTIR) spectra, Raman spectroscopy, and fluorescence emission spectroscopy. Sensing studies for the antibiotic C were performed by fluorescence suppression in the presence of a- and b-CDs, as well as the precursor 3,4-DABA. The a- and b-CDs presented similar values of linear range 0.00080-0.0050 mg/ml and limit of detection (LOD) = 0.00030 mg/ml (0.30 ppm) for CAP. Then, a- and b-CDs were embedded in Whatman and Mellita® filter paper, and CAP sensing was evaluated through UV light excitation.

Polymeric Nanorepellent Systems Containing Geraniol and Icaridin Aimed at Repelling Aedes aegypti.

Repellents are among the leading products used against diseases transmitted by the Aedes aegypti mosquito. However, their indiscriminate use or high concentrations can cause severe adverse reactions, particularly in children and pregnant women. To protect them, nanotechnology is a promising tool to encapsulate active compounds against degradation, increase their effectiveness, and decrease their toxicity, as it can promote the modified release of the active compound. This study aimed to develop polymeric nanocapsules containing the repellent actives geraniol and icaridin using low concentrations of the active component, with the objective of promoting effective activity and greater safety against adverse reactions. The nanocapsules were developed by the interfacial deposition method, and the physicochemical properties of the nanocapsules were evaluated using dynamic light scattering (DLS), nanoparticle tracking analysis (NTA), zeta potential, differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), atomic force microscopy (AFM), release kinetics assay, and mathematical modeling. Cell viability was assessed by the MTT assay and genotoxicity analysis using the comet assay. The developed nanocapsules containing geraniol and icaridin showed mean diameters of 260 nm and 314 nm, respectively, with a polydispersity index < 0.2. The nanocapsules showed encapsulation efficiency values of 73.7 ± 0.1% for icaridin and 98.7 ± 0.1% for geraniol. Morphological analysis showed spherical nanocapsules with low polydispersity. The kinetic parameters calculated using the Korsmeyer−Peppas model indicated an anomalous release profile. Cell viability and genotoxicity analyses showed that the nanocapsules did not alter cell viability or damage DNA. The results demonstrate a promising nanostructured system with good physicochemical characteristics and good stability, with repellent activity against Aedes aegypti.

Clinical, radiographic, and genetic observations in 2 families with cleidocranial dysplasia.

The clinical, radiographic, and molecular alterations in 7 individuals belonging to 2 families with clinical characteristics of cleidocranial dysplasia (CCD) were investigated. The patients underwent karyotype and genetic sequencing examinations. Cytogenetic analysis did not demonstrate any alterations. The next-generation sequencing technique employed for the molecular analysis revealed sequence variations in the RUNX2 gene: c.568C>T (p.Arg190Trp) in exon 4 in family A and c.1205del (p.Pro402Argfs*82) in exon 9 in family B. Incomplete closure of anterior fontanels, hypoplastic clavicles, and dental changes were observed in all 7 patients. Uncommon clinical findings, such as partial hearing loss and bilateral clavicular agenesis, were noted in some patients. According to the literature consulted, this is the first time that the total absence of the pubic bone in a study subject is being reported. The variable expression among individuals of the same family and between families A and B suggests the absence of a genotype-phenotype relationship. Early diagnosis allows the dentist to minimize the effects of changes associated with CCD by monitoring and providing appropriate treatment, and the identification of genetic sequence variations enables appropriate family genetic counseling.

Influence of the capping of biogenic silver nanoparticles on their toxicity and mechanism of action towards Sclerotinia sclerotiorum.

BACKGROUND: Biogenic nanoparticles possess a capping of biomolecules derived from the organism employed in the synthesis, which contributes to their stability and biological activity. These nanoparticles have been highlighted for the control of phytopathogens, so there is a need to understand their composition, mechanisms of action, and toxicity. This study aimed to investigate the importance of the capping and compare the effects of capped and uncapped biogenic silver nanoparticles synthesized using the filtrate of Trichoderma harzianum against the phytopathogenic fungus Sclerotinia sclerotiorum. Capping removal, investigation of the composition of the capping and physico-chemical characterization of the capped and uncapped nanoparticles were performed. The effects of the nanoparticles on S. sclerotiorum were evaluated in vitro. Cytotoxicity and genotoxicity of the nanoparticles on different cell lines and its effects on nontarget microorganisms were also investigated. RESULTS: The capped and uncapped nanoparticles showed spherical morphology, with greater diameter of the uncapped ones. Functional groups of biomolecules, protein bands and the hydrolytic enzymes NAGase, ß-1,3-glucanase, chitinase and acid protease from T. harzianum were detected in the capping. The capped nanoparticles showed great inhibitory potential against S. sclerotiorum, while the uncapped nanoparticles were ineffective. There was no difference in cytotoxicity comparing capped and uncapped nanoparticles, however higher genotoxicity of the uncapped nanoparticles was observed towards the cell lines. Regarding the effects on nontarget microorganisms, in the minimal inhibitory concentration assay only the capped nanoparticles inhibited microorganisms of agricultural importance, while in the molecular analysis of the soil microbiota there were major changes in the soils exposed to the uncapped nanoparticles. CONCLUSIONS: The results suggest that the capping played an important role in controlling nanoparticle size and contributed to the biological activity of the nanoparticles against S. sclerotiorum. This study opens perspectives for investigations concerning the application of these nanoparticles for the control of phytopathogens.

Interaction of the nitrosyl ruthenium complex [RuII (NH.NHq-R)(tpy)NO]3+ with human serum albumin: a spectroscopic and computational investigation.

The interaction between two nitrosyl ruthenium complexes [Ru (NH.NHq-COOH)(tpy)NO](PF6 )3 (RuBDQ) and [Ru (NH.NHq-H)(tpy)NO](PF6 )3 (RuBD) and human serum albumin (HSA) was investigated using spectroscopic and computational methods. From fluorescence experiments, a dynamic quenching mechanism and binding constants at a single site demonstrated the higher stability of the RuBDQ-HSA system at 308 K compared with RuBD-HSA. Thermodynamic parameters indicated that binding of RuBDQ and RuBD to HSA was mainly driven by hydrophobic interaction and hydrogen bonding, respectively. Synchronous fluorescence and FT-IR results suggested that interactions between both nitrosyl ruthenium complexes and HSA affected protein conformation. Competition experiments revealed that RuBDQ and RuBD bound to Sudlow sites I and II, respectively. Molecular docking results showed that RuBDQ interacted with Ser-192 and Ala-291 residues via hydrogen bonding and polar contact, respectively, whereas RuBD associated with Asn-391 via a polar interaction. Noncovalent interaction results suggested that van der Waals interactions were the main binding forces for both systems, i.e. RuBDQ associated with Trp-214 via van der Waals interaction and with Ty-150 via dipole-dipole bonding, whereas RuBD associated with Tyr-452 via van der Waals forces. The Asp-391 residue interacted with the nitrosyl ligand via polar contact and the terpyridine ligand via van der Waals interaction.

Methylphenidate effects on mice odontogenesis and connections with human odontogenesis.

The purpose of this study is to evaluate the effects of Methylphenidate exposure on mice odontogenesis and connect them by bioinformatics with human odontogenesis. Thirty-two pregnant Swiss mice were divided into treated group and control group, which received, respectively, 5 mg/kg of Methylphenidate and saline solution from the 5th to the 17th day of pregnancy. The mouse embryos tooth germs were analyzed through optical microscopy, and the data collected were analyzed statistically by Fisher's exact test. The presence and similarity of Methylphenidate-associated genes (Pharmgkb database) in both organisms and their interaction with dental development genes (AmiGO2 database) were verified on STRING database. Rates of tooth germ malformations were higher in treated than in control group (Control: 18; Treated: 27; p = 0.035). Mouse embryo malformations were connected with 238 interactions between 69 dental development genes with 35 Methylphenidate genes. Fourteen interactions for four Methylphenidate genes with four dental development genes, with human experimental data, were connected with mouse phenotype data. By homology, the interactions and conservation of proteins/genes may indicate similar outcomes for both organisms. The exposure to Methylphenidate during pregnancy affected odontogenesis in mouse embryos and may affect human odontogenesis. The study of malformations in mice, with a bioinformatics approach, could contribute to understanding of the Methylphenidate effect on embryo development. These results may provide novel hypotheses for further testing and reinforce the FDA protocol: as Methylphenidate is included in category C, its use during pregnancy should be considered if the benefits outweigh the risks.

How can nanotechnology help to combat COVID-19? Opportunities and urgent need.

Incidents of viral outbreaks have increased at an alarming rate over the past decades. The most recent human coronavirus known as COVID-19 (SARS-CoV-2) has already spread around the world and shown R0 values from 2.2 to 2.68. However, the ratio between mortality and number of infections seems to be lower in this case in comparison to other human coronaviruses (such as severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV)). These outbreaks have tested the limits of healthcare systems and have posed serious questions about management using conventional therapies and diagnostic tools. In this regard, the use of nanotechnology offers new opportunities for the development of novel strategies in terms of prevention, diagnosis and treatment of COVID-19 and other viral infections. In this review, we discuss the use of nanotechnology for COVID-19 virus management by the development of nano-based materials, such as disinfectants, personal protective equipment, diagnostic systems and nanocarrier systems, for treatments and vaccine development, as well as the challenges and drawbacks that need addressing.

Description of rare mutations and a novel variant in Brazilian patients with Cystic Fibrosis: a case series from a referral center in the Bahia State.

Knowledge of the genetic profile of Cystic Fibrosis (CF) contributes to a better understanding of the genotype/phenotype relationship, particularly in mixed populations such as in Brazil. To describe clinical data of CF patients with rare or not yet observed CFTR gene mutations in Brazil. It was a case series of CF patients followed-up at a referral center. Clinical and laboratory data were obtained through medical records. Molecular analysis of the mutations was performed by conventional methods and/or by next-generation sequencing. Ten patients were studied, seven had five pathogenic mutations without previous description in Brazil (Q1100P, Y109C, A107P, E1409K and K162E), one of which has not yet been reported in patients with CF (A107P). Among the seven patients, three (two siblings) had the second mutant allele of rare occurrence among Brazilians patients (G1069R and 2307insA). Three other patients also had at least one rare variant (V201M, S466X and G1069R). The age of the CF diagnosis ranged from 1 to 190 months in the ten cases and the main clinical manifestations were respiratory symptoms and difficulty in gaining weight. All but one patient presented clinical and/or laboratory data compatible with pancreatic insufficiency. The identification of rare or not yet described CFTR mutations in patients with CF in Brazil highlights the high genetic heterogeneity in this population. Knowledge of the genotypic profile of Brazilian CF patients can contribute to the development of specific mutation panels for the genetic investigation targeting each region of the country, as well as helping to understand the complex genotype/phenotype relationship, especially in mixed populations.

Development of HA/Ag-NPs Composite Coating from Green Process for Hip Applications.

In the present study, biological hydroxyapatite (HA) was obtained from bovine bones through a thermal process. A total of 0% and 1% of silver nanoparticles (Ag-NPs) synthesized from Opuntia ficus (nopal) were added to the biological hydroxyapatite coatings using an atmospheric plasma spray (APS) on a Ti6Al4V substrate. Following this, its antimicrobial efficiency was evaluated against the following bacterial strains: Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa. This was conducted according to the Japanese Industrial Standard (JIS) Z2801:2000 "Antimicrobial Product-Test for Antimicrobial Activity and Efficacy". Scanning electron microscopy (SEM) showed that the silver nanoparticles (Ag-NPs) were evenly distributed on the coating surface. Energy dispersive X-ray spectroscopy (EDX) shows that apatite deposition occurs on a daily basis, maintaining a Ca/P rate between 2.12 and 1.45. Biocompatibility properties were evaluated with osteoblast-like cells (MC3T3-E1) by single-cell gel electrophoresis assay and Tali image cytometry.

An etiologic regulatory mutation in IRF6 with loss- and gain-of-function effects.

DNA variation in Interferon Regulatory Factor 6 (IRF6) causes Van der Woude syndrome (VWS), the most common syndromic form of cleft lip and palate (CLP). However, an etiologic variant in IRF6 has been found in only 70% of VWS families. To test whether DNA variants in regulatory elements cause VWS, we sequenced three conserved elements near IRF6 in 70 VWS families that lack an etiologic mutation within IRF6 exons. A rare mutation (350dupA) was found in a conserved IRF6 enhancer element (MCS9.7) in a Brazilian family. The 350dupA mutation abrogated the binding of p63 and E47 transcription factors to cis-overlapping motifs, and significantly disrupted enhancer activity in human cell cultures. Moreover, using a transgenic assay in mice, the 350dupA mutation disrupted the activation of MCS9.7 enhancer element and led to failure of lacZ expression in all head and neck pharyngeal arches. Interestingly, disruption of the p63 Motif1 and/or E47 binding sites by nucleotide substitution did not fully recapitulate the effect of the 350dupA mutation. Rather, we recognized that the 350dupA created a CAAAGT motif, a binding site for Lef1 protein. We showed that Lef1 binds to the mutated site and that overexpression of Lef1/ß-Catenin chimeric protein repressed MCS9.7-350dupA enhancer activity. In conclusion, our data strongly suggest that 350dupA variant is an etiologic mutation in VWS patients and disrupts enhancer activity by a loss- and gain-of-function mechanism, and thus support the rationale for additional screening for regulatory mutations in patients with CLP.

A modified MS-PCR approach to diagnose patients with Prader-Willi and Angelman syndrome.

Prader-Willi (PWS) and Angelman (AS) syndromes are clinically distinct neurodevelopmental genetic diseases with multiple phenotypic manifestations. They are one of the most common genetic syndromes caused by non-Mendelian inheritance in the form of genomic imprinting, and can be attributable to the loss of gene expression due to imprinting within the chromosomal region 15q11-q13. Clinical diagnosis of PWS and AS is challenging, and the use of molecular and cytomolecular studies is recommended to help in determining the diagnosis of these conditions. The methylation analysis is a sensible approach; however there are several techniques for this purpose, such as the methylation-sensitive polymerase chain reaction (MS-PCR). This study aims to optimize the MS-PCR assay for the diagnosis of potential PWS and AS patients using DNA modified by sodium bisulfite. We used the MS-PCR technique of PCR described by Kosaki et al. (1997) adapted with betaine. All different concentrations of betaine used to amplify the methylated and unmethylated chromosomal region 15q11-q13 on the gene SNRPN showed amplification results, which increased proportionally to the concentration of betaine. The methylation analysis is a technically robust and reproducible screening method for PWS and AS. The MS-PCR assures a faster, cheaper and more efficient method for the primary diagnosis of the SNRPN gene in cases with PWS and AS, and may detect all of the three associated genetic abnormalities: deletion, uniparental disomy or imprinting errors.

Nanotoxicity of graphene and graphene oxide.

Graphene and its derivatives are promising candidates for important biomedical applications because of their versatility. The prospective use of graphene-based materials in a biological context requires a detailed comprehension of the toxicity of these materials. Moreover, due to the expanding applications of nanotechnology, human and environmental exposures to graphene-based nanomaterials are likely to increase in the future. Because of the potential risk factors associated with the manufacture and use of graphene-related materials, the number of nanotoxicological studies of these compounds has been increasing rapidly in the past decade. These studies have researched the effects of the nanostructural/biological interactions on different organizational levels of the living system, from biomolecules to animals. This review discusses recent results based on in vitro and in vivo cytotoxicity and genotoxicity studies of graphene-related materials and critically examines the methodologies employed to evaluate their toxicities. The environmental impact from the manipulation and application of graphene materials is also reported and discussed. Finally, this review presents mechanistic aspects of graphene toxicity in biological systems. More detailed studies aiming to investigate the toxicity of graphene-based materials and to properly associate the biological phenomenon with their chemical, structural, and morphological variations that result from several synthetic and processing possibilities are needed. Knowledge about graphene-based materials could ensure the safe application of this versatile material. Consequently, the focus of this review is to provide a source of inspiration for new nanotoxicological approaches for graphene-based materials.

Preparation, characterization, cytotoxicity, and genotoxicity evaluations of thiolated- and s-nitrosated superparamagnetic iron oxide nanoparticles: implications for cancer treatment.

Iron oxide magnetic nanoparticles have been proposed for an increasing number of biomedical applications, such as drug delivery. To this end, toxicological studies of their potent effects in biological media must be better evaluated. The aim of this study was to synthesize, characterize, and examine the potential in vitro cytotoxicity and genotoxicity of thiolated (SH) and S-nitrosated (S-NO) iron oxide superparamagnetic nanoparticles toward healthy and cancer cell lines. Fe3O4 nanoparticles were synthesized by coprecipitation techniques and coated with small thiol-containing molecules, such as mercaptosuccinic acid (MSA) or meso-2,3-dimercaptosuccinic acid (DMSA). The physical-chemical, morphological, and magnetic properties of thiol-coating Fe3O4 nanoparticles were characterized by different techniques. The thiol groups on the surface of the nanoparticles were nitrosated, leading to the formation of S-nitroso-MSA- or S-nitroso-DMSA-Fe3O4 nanoparticles. The cytotoxicity and genotoxicity of thiolated and S-nitrosated nanoparticles were more deeply evaluated in healthy (3T3, human lymphocytes cells, and chinese hamster ovary cells) and cancer cell lines (MCF-7). The results demonstrated that thiol-coating iron oxide magnetic nanoparticles have few toxic effects in cells, whereas S-nitrosated-coated particles did cause toxic effects. Moreover, due to the superaramagnetic behavior of S-nitroso-Fe3O4 nanoparticles, those particles can be guided to the target site upon the application of an external magnetic field, leading to local toxic effects in the tumor cells. Taken together, the results suggest the promise of S-nitroso-magnetic nanoparticles in cancer treatment.

Ruthenium complexes as NO donors for vascular relaxation induction.

Nitric oxide (NO) donors are substances that can release NO. Vascular relaxation induction is among the several functions of NO, and the administration of NO donors is a pharmacological alternative to treat hypertension. This review will focus on the physicochemical description of ruthenium-derived NO donor complexes that release NO via reduction and light stimulation. In particular, we will discuss the complexes synthesized by our research group over the last ten years, and we will focus on the vasodilation and arterial pressure control elicited by these complexes. Soluble guanylyl cyclase (sGC) and potassium channels are the main targets of the NO species released from the inorganic compounds. We will consider the importance of the chemical structure of the ruthenium complexes and their vascular effects.

Identifying Genetic Etiology in Patients with Intellectual Disability: An Experience in Public Health Services in Northeastern Brazil.

Intellectual disability (ID) is considered a common neuropsychiatric disorder that affects up to 3% of the population. The etiologic origin of ID may be genetic, environmental, and multifactorial. Chromosomopathies are relatively common among the genetic causes of ID, especially in the most severe cases and those associated with dysmorphic features. Currently, the application of new molecular cytogenetics technologies has increasingly allowed the identification of microdeletions, microduplications, and unbalanced translocations as causes of ID. The objective of this study was to investigate the etiology of ID in patients admitted to a public hospital in Northeastern Brazil. In total, 119 patients with ID who had normal karyotypes and fragile X exams participated in this study. The patients were initially physically examined for microdeletion syndromes and then tested using fluorescence in situ hybridization (FISH), multiplex ligation-dependent probe amplification (MLPA), methylation-sensitive polymerase chain reaction (MS-PCR), and chromosome microarray analysis (CMA), according to clinical suspicion. Patients with no diagnoses after FISH, MLPA, and/or MS-PCR evaluations were subsequently tested by CMA. The rate of etiologic diagnoses of ID in the current study was 28%. FISH diagnosed 25 out of 79 tested (31%), MLPA diagnosed 26 out of 79 tested (32%), MS-PCR diagnosed 7 out of 20 tested (35%), and the single nucleotide polymorphism array diagnosed 6 out of 27 tested (22%). Although the CMA is the most complete and recommended tool for the diagnosis of microdeletions, microduplications, and unbalance translocations in patients with ID, FISH, MLPA, and MS-PCR testing can be used as the first tests for specific syndromes, as long as the patients are first physically screened clinically, especially in the public health networks system in Brazil, where resources are scarce.

Mutations in IRF6 cause Van der Woude and popliteal pterygium syndromes.

Interferon regulatory factor 6 (IRF6) belongs to a family of nine transcription factors that share a highly conserved helix-turn-helix DNA-binding domain and a less conserved protein-binding domain. Most IRFs regulate the expression of interferon-alpha and -beta after viral infection, but the function of IRF6 is unknown. The gene encoding IRF6 is located in the critical region for the Van der Woude syndrome (VWS; OMIM 119300) locus at chromosome 1q32-q41 (refs 2,3). The disorder is an autosomal dominant form of cleft lip and palate with lip pits, and is the most common syndromic form of cleft lip or palate. Popliteal pterygium syndrome (PPS; OMIM 119500) is a disorder with a similar orofacial phenotype that also includes skin and genital anomalies. Phenotypic overlap and linkage data suggest that these two disorders are allelic. We found a nonsense mutation in IRF6 in the affected twin of a pair of monozygotic twins who were discordant for VWS. Subsequently, we identified mutations in IRF6 in 45 additional unrelated families affected with VWS and distinct mutations in 13 families affected with PPS. Expression analyses showed high levels of Irf6 mRNA along the medial edge of the fusing palate, tooth buds, hair follicles, genitalia and skin. Our observations demonstrate that haploinsufficiency of IRF6 disrupts orofacial development and are consistent with dominant-negative mutations disturbing development of the skin and genitalia.

Silver nanoparticles: a brief review of cytotoxicity and genotoxicity of chemically and biogenically synthesized nanoparticles.

In recent years interest in silver nanoparticles and their applications has increased mainly because of the important antimicrobial activities of these nanomaterials, allowing their use in several industrial sectors. However, together with these applications, there is increasing concerning related to the biological impacts of the use of silver nanoparticles on a large scale, and the possible risks to the environment and health. In this scenario, some recent studies have been published based on the investigation of potential inflammatory effects and diverse cellular impacts of silver nanoparticles. Another important issue related to nanoparticle toxicity in biological media is the capacity for increased damage to the genetic material, since nanoparticles are able to cross cell membranes and reach the cellular nucleus. In this regard, there is increasing interest in the analysis of potential nanoparticle genotoxicity, including the effects of different nanoparticle sizes and methods of synthesis. However, little is known about the genotoxicity of different silver nanoparticles and their effects on the DNA of organisms; thus further studies in this field are required. This mini-review aims to present and to discuss recent publications related to genotoxicity and the cytotoxicity of silver nanoparticles in order to better understand the possible applications of these nanomaterials in a safe manner. This present work concludes that biogenic silver nanoparticles are generally less cyto/genotoxic in vivo compared with chemically synthesized nanoparticles. Furthermore, human cells were found to have a greater resistance to the toxic effects of silver nanoparticles in comparison with other organisms.