Dual FGFR-targeting and pH-activatable ruthenium-peptide conjugates for targeted therapy of breast cancer.

Dysregulation of Fibroblast Growth Factor Receptors (FGFRs) signaling has been associated with breast cancer, yet employing FGFR-targeted delivery systems to improve the efficacy of cytotoxic agents is still sparsely exploited. Herein, we report four new bi-functional ruthenium-peptide conjugates (RuPCs) with FGFR-targeting and pH-dependent releasing abilities, envisioning the selective delivery of cytotoxic Ru complexes to FGFR(+)-breast cancer cells, and controlled activation at the acidic tumoral microenvironment. The antiproliferative potential of the RuPCs and free Ru complexes was evaluated in four breast cancer cell lines with different FGFR expression levels (SKBR-3, MDA-MB-134-VI, MCF-7, and MDA-MB-231) and in human dermal fibroblasts (HDF), at pH 6.8 and pH 7.4 aimed at mimicking the tumor microenvironment and normal tissues/bloodstream pHs, respectively. The RuPCs showed higher cytotoxicity in cells with higher level of FGFR expression at acidic pH. Additionally, RuPCs showed up to 6-fold higher activity in the FGFR(+) breast cancer lines compared to the normal cell line. The release profile of Ru complexes from RuPCs corroborates the antiproliferative effects observed. Remarkably, the cytotoxicity and releasing ability of RuPCs were shown to be strongly dependent on the conjugation of the peptide position in the Ru complex. Complementary molecular dynamic simulations and computational calculations were performed to help interpret these findings at the molecular level. In summary, we identified a lead bi-functional RuPC that holds strong potential as a FGFR-targeted chemotherapeutic agent.

Lead to hit ruthenium-cyclopentadienyl anticancer compounds: Cytotoxicity against breast cancer cells, metabolic stability and metabolite profiling.

The successful choice of hit compounds during drug development programs involves the integration of structure-activity relationship (SAR) studies with pharmacokinetic determinations, including metabolic stability assays and metabolite profiling. A panel of nine ruthenium-cyclopentadienyl (RuCp) compounds with the general formula [Ru(η5-C5H4R)(PPh3)(bipyR')]+ (with R = H, CHO, CH2OH; R' = H, CH3, CH2OH, CH2Biotin) has been tested against hormone-dependent MCF-7 and triple negative MDA-MB-231 breast cancer cells. In general, all compounds showed important cytotoxicity against both cancer cell lines and were able to inhibit the formation of MDA-MB-231 colonies in a dose-dependent manner, while showing selectivity for cancer cells over normal fibroblasts. Among them, four compounds stood out as lead structures to be further studied. Cell distribution assays revealed their preference for the accumulation at cell membrane (Ru quantification by ICP-MS) and the mechanism of cell death seemed to be mediated by apoptosis. Potential structural liabilities of lead compounds were subsequently flagged upon in vitro metabolic stability assays and metabolite profiling. The implementation of this integrated strategy led to the selection of RT151 as a promising hit compound.

A hitchhikers' guide to the terminology of accreditation processes for health professionals and institutions.

Accreditation processes for health care professions are designed to ensure that individuals and programs in these fields meet established standards of quality and effectiveness. The accelerating pace of globalization in the health care professions has increased the need for a shared understanding of the vocabulary of evaluation, assessment, and accreditation. The psychometric principles of valid and reliable assessment are commonly accepted, but the terminology is confusing. We believe that all stakeholders - evaluators, faculty, students but also the community - will benefit from a shared language and common set of definitions. We recognize that not all readers will agree with the definitions we propose, but we hope that this guide will help to ensure clarity, consistency, transparency, and fairness, and that it will promote through the stimulation of a debate greater collaboration across national and international boundaries.

Exploiting click-chemistry: backbone post-functionalisation of homoleptic gold(I) 1,2,3-triazole-5-ylidene complexes.

The synthesis of a homoleptic azide-functionalised Au(I) bis-1,2,3-triazole-5-ylidene complex is reported, starting from a backbone-modified 1,2,3-triazolium salt ligand precursor. The incorporated azide handle allows for a straightforward modification of the complex according to click-chemistry protocols without impacting the steric shielding around the metal center, demonstrating the superiority of the presented triazole ligand framework over imidazole based systems. Employing the SPAAC and the CuAAC reactions, post-modification of the complex is facilitated with two model substrates, while retaining very high antiproliferative activity (nanomolar range IC50 values) in A2780 and MCF-7 human cancer cells.

The Effects of Stress on Hippocampal Neurogenesis and Behavior in the Absence of Lipocalin-2.

Lipocalin-2 (LCN2) is an acute phase protein able to bind iron when complexed with bacterial siderophores. The recent identification of a mammalian siderophore also suggested a physiological role for LCN2 in the regulation of iron levels and redox state. In the central nervous system, the deletion of LCN2 induces deficits in neural stem cells proliferation and commitment, with an impact on the hippocampal-dependent contextual fear discriminative task. Additionally, stress is a well-known regulator of cell genesis and is known to decrease adult hippocampal cell proliferation and neurogenesis. Although voluntary running, another well-known regulator of neurogenesis, is sufficient to rescue the defective hippocampal neurogenesis and behavior in LCN2-null mice by promoting stem cells' cell cycle progression and maturation, the relevance of LCN2-regulated hippocampal neurogenesis in response to stress has never been explored. Here, we show a lack of response by LCN2-null mice to the effects of chronic stress exposure at the cellular and behavioral levels. Together, these findings implicate LCN2 as a relevant mediator of neuronal plasticity and brain function in the adult mammalian brain.

Astrocytes Undergo Metabolic Reprogramming in the Multiple Sclerosis Animal Model.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system that presents a largely unknown etiopathology. The presence of reactive astrocytes in MS lesions has been described for a long time; however, the role that these cells play in the pathophysiology of MS is still not fully understood. Recently, we used an MS animal model to perform high-throughput sequencing of astrocytes' transcriptome during disease progression. Our data show that astrocytes isolated from the cerebellum (a brain region typically affected in MS) showed a strong alteration in the genes that encode for proteins related to several metabolic pathways. Specifically, we found a significant increase in glycogen degradation, glycolytic, and TCA cycle enzymes. Together with these alterations, we detected an upregulation of genes that characterize "astrocyte reactivity". Additionally, at each disease time point we also reconstructed the morphology of cerebellum astrocytes in non-induced controls and in EAE animals, near lesion regions and in the normal-appearing white mater (NAWM). We found that near lesions, astrocytes presented increased length and complexity compared to control astrocytes, while no significant alterations were observed in the NAWM. How these metabolic alterations are linked with disease progression is yet to be uncovered. Herein, we bring to the literature the hypothesis of performing metabolic reprogramming as a novel therapeutic approach in MS.

Evaluation of the Antiproliferative Properties of CpRu Complexes Containing N-Methylated Triazaphosphaadamantane Derivatives.

Piano-stool-{CpRu} complexes containing 1,3,5-triaza-7-phosphaadamantane (PTA), N-methyl-1,3,5-triaza-7-phosphaadamantane (mPTA), and 3,7-dimethyl-1,3,7-triaza-5-phosphabyciclo[3.3.1]nonane (dmoPTA) were evaluated as drugs against breast cancer. The evaluated compounds include two new examples of this family, the complexes [RuCp(DMSO-κS)(HdmoPTA)(PPh3)](CF3SO3)2 (8) and [RuCp(PPh3)2-µ-dmoPTA-1κP-2κ2N,N'-PdCl2](CF3SO3) (11), which have been synthesized and characterized by NMR, IR, and single-crystal X-ray diffraction. The cytotoxic activity of compounds was evaluated against MDA-MB-231 breast cancer cells, and the three most active complexes were further tested against the hormone-dependent MCF-7 breast cancer cell line. Their cell death mechanism and ruthenium uptake were also evaluated, as well as their binding ability to human serum albumin.

Relações de amizade nos transtornos alimentares: revisão integrativa da literatura / Friendship relationships in eating disorders: an integrative literature review / Relaciones de amistad en los trastornos alimentarios: revisión integradora

Ainda é desconhecido o papel da amizade enquanto constitutiva da rede de apoio social nos transtornos alimentares (TAs). Esta revisão integrativa teve por objetivo analisar a produção científica sobre relações de amizade em pessoas com TAs. Foram consultadas as bases PubMed/MEDLINE, LILACS, PsycINFO, Web of Science e EMBASE, de 2010 a 2020. Dos 1126 artigos recuperados, 15 preencheram os critérios de elegibilidade. A maioria tem abordagem qualitativa e delineamento transversal, sem indicar referencial teórico. Aspectos qualitativos das relações de amizade foram associados com redução da frequência e intensidade de sintomas quando o vínculo era considerado de boa qualidade. Já amizades que envolviam comentários depreciativos e influências negativas acerca do corpo e hábitos alimentares foram considerados fatores de risco para desencadeamento dos transtornos. Investir na qualidade dos relacionamentos entre pares pode contribuir para fortalecer a rede de proteção social e reduzir a vulnerabilidade psicossocial de adolescentes com risco para desenvolver TAs. (AU)

There is still little knowledge about the role of friendship within the social support network in eating disorders (EDs). This integrative review aimed to analyze the scientific production about friendship relationships in people with EDs. The literature review was conducted using the PubMed/MEDLINE, LILACS, PsycINFO, Web of Science, and EMBASE databases in the period from 2010 to 2020. Among the 1126 articles retrieved, 15 met the eligibility criteria, most with a qualitative approach and cross-sectional design, without indicating a theoretical framework. The qualitative aspects of friendship were associated with a reduced frequency and intensity of symptoms when the bond was considered to be of good quality. On the other hand, friendships that involved derogatory comments and negative influences related to body image and eating habits emerged as potential risk factors for triggering disorders. Investing in the quality of peer relationships can contribute to strengthening the social safety net and reducing the psychosocial vulnerability of adolescents at higher risk for developing EDs. (AU)

El papel de la amistad como constitutiva de la red de apoyo social en los trastornos alimentarios (TAs) es aún desconocido. Este estudio tiene como objetivo analizar la producción científica sobre las relaciones de amistad en personas con TAs. Se consultaron las bases PubMed/MEDLINE, LILACS, PsycINFO, Web of Science e EMBASE, entre 2010 y 2020. De los 1126 artículos recuperados, 15 cumplían los criterios de elegibilidad. La mayoría tiene enfoque cualitativo y diseño transversal, sin indicar el marco teórico. Los aspectos cualitativos de las relaciones de amistad se asociaron con una menor frecuencia/intensidad de los síntomas cuando el vínculo se consideraba de buena calidad. Amistades que implicaban comentarios despectivos e influencias negativas sobre el cuerpo y los hábitos alimentarios se consideraron factores de riesgo. Invertir en la calidad de las relaciones entre pares puede contribuir a reforzar la red de protección social y reducir la vulnerabilidad de adolescentes con riesgo de desarrollar TAs. (AU)

Comparison between intraoral scanning and direct visual analysis for the assessment of developmental defects of enamel.

OBJECTIVE: To compare direct visual analysis (DVA) and intraoral scanning (IOS) for the assessment of developmental defects of the enamel (DDE). METHODS: Thirty-nine extracted permanent human teeth with DDE were selected by an experienced examiner and digitised using IOS. The scanning was recorded using the OBS Studio software parallel to the IOS software to obtain a coloured high-definition MP4 file of the process. Two other experienced, blinded, and calibrated examiners randomly analysed the same teeth through DVA and IOS. A third examiner resolved any disagreements between the two examiners. Descriptive statistics were used to analyse the frequencies of the scores. Cohen's kappa test was used to determine whether the DVA scores were different from those assigned using IOS. Spearman's test was used to verify non-random examiner errors. The Chi-square test was used to compare score frequencies. Statistical significance was set at p <0.05. RESULTS: Scores indicating more severe and extended DDE (p <0.05) were more frequently assigned with IOS than with DVA (IOS: 25.64%, 25.64%, 38.46%, and 35.90% between one-third to two-third of the lingual, occlusal, mesial, and distal surfaces, respectively; vs. DVA: 10.26%, 7.69%, 15.38%, and 10.26% for the respective aforementioned tooth surfaces). Contrarily, 'no visible enamel defect' was significantly less assigned for IOS than for DVA (IOS: 15.38%, 43.59%, 35.90%, 15.38%, and 17.95% for buccal, lingual, occlusal, mesial, and distal surfaces, respectively; vs. DVA: 38.46%, 66.67%, 56.41%, 51.28%, and 43.59% for the respective aforementioned tooth surfaces). Kappa agreement ranged from fair to moderate when comparing DVA and IOS; the correlation between both methods was positive, indicating that the examiners assigned the scores properly and the differences arose from employing different methods. CONCLUSION: The assessment of DDE differed depending on the method used. IOS scores indicated more severe and extended DDE than DVA scores. Clinical investigation is the next step in validating the use of IOS for DDE diagnosis. CLINICAL SIGNIFICANCE: This study showed that DDE can be assessed differently using IOS. It is clinically relevant as it directly affects the determination of the severity of the defect and dental treatment planning.

The selection of indicator species of birds and mammals for the monitoring of restoration areas in a highly fragmented forest landscape.

Indicator species are frequently used to monitor restoration areas. However, species of conservation concern are usually absent in highly fragmented landscapes, making the selection of indicator species a challenging task. Here, we select indicator species of birds and mammals to be used for the evaluation of restoration sites in a highly fragmented landscape, the Capivara-Taquaruçu Dams region located in north Paraná, Brazil. By using the Index of Biotic Integrity (IBI), we show that the Capivara-Taquaruçu Dams landscape has low IBI values and bird richness when compared with two other landscapes in the north of Paraná. Therefore, we used the Individual Indicate Value to identify birds and mammals associated with forest fragments in the Capivara-Taquaruçu Dams landscape. Six bird and four mammal species were selected as indicators of forest fragments, none of which were of conservation concern. However, monitoring of these species could help evaluate the recovery of restoration sites in the Capivara-Taquaruçu Dams region. Lastly, several species of birds and mammals were frequently recorded in the restoration sites, including vulnerable species such as the lowland tapir (Tapirus terrestris). This is indicative that restoration sites can be important habitats in highly fragmented landscapes despite the loss of biodiversity.

Learning the Biochemical Basis of Axonal Guidance: Using Caenorhabditis elegans as a Model.

AIM: Experimental models are a powerful aid in visualizing molecular phenomena. This work reports how the worm Caenorhabditis elegans (C. elegans) can be effectively explored for students to learn how molecular cues dramatically condition axonal guidance and define nervous system structure and behavior at the organism level. Summary of work: A loosely oriented observational activity preceded detailed discussions on molecules implied in axonal migration. C. elegans mutants were used to introduce second-year medical students to the deleterious effects of gene malfunctioning in neuron response to extracellular biochemical cues and to establish links between molecular function, nervous system structure, and animal behavior. Students observed C. elegans cultures and associated animal behavior alterations with the lack of function of specific axon guidance molecules (the soluble cue netrin/UNC-6 or two receptors, DCC/UNC-40 and UNC-5H). Microscopical observations of these strains, in combination with pan-neuronal GFP expression, allowed optimal visualization of severely affected neurons. Once the list of mutated genes in each strain was displayed, students could also relate abnormal patterns in axon migration/ventral and dorsal nerve cord neuron formation in C. elegans with mutated molecular components homologous to those in humans. SUMMARY OF RESULTS: Students rated the importance and effectiveness of the activity very highly. Ninety-three percent found it helpful to grasp human axonal migration, and all students were surprised with the power of the model in helping to visualize the phenomenon.

Age-related changes in mice behavior and the contribution of lipocalin-2.

Aging causes considerable changes in the nervous system, inducing progressive and long-lasting loss of physiological integrity and synaptic plasticity, leading to impaired brain functioning. These age-related changes quite often culminate in behavioral dysfunctions, such as impaired cognition, which can ultimately result in various forms of neurodegenerative disorders. Still, little is known regarding the effects of aging on behavior. Moreover, the identification of factors involved in regenerative plasticity, in both the young and aged brain, is scarce but crucial from a regenerative point of view and for our understanding on the mechanisms that control the process of normal aging. Recently, we have identified the iron-trafficking protein lipocalin-2 (LCN2) as novel regulator of animal behavior and neuronal plasticity in the young adult brain. On the other hand, others have proposed LCN2 as a biological marker for disease progression in neurodegenerative disorders such as Alzheimer's disease and multiple sclerosis. Still, and even though LCN2 is well accepted as a regulator of neural processes in the healthy and diseased brain, its contribution in the process of normal aging is not known. Here, we performed a broad analysis on the effects of aging in mice behavior, from young adulthood to middle and late ages (2-, 12-, and 18-months of age), and in the absence of LCN2. Significant behavioral differences between aging groups were observed in all the dimensions analyzed and, in mice deficient in LCN2, aging mainly reduced anxiety, while sustained depressive-like behavior observed at younger ages. These behavioral changes imposed by age were further accompanied by a significant decrease in cell survival and neuronal differentiation at the hippocampus. Our results provide insights into the role of LCN2 in the neurobiological processes underlying brain function and behavior attributed to age-related changes.

Copper(I)-Thiosemicarbazone Complexes with Dual Anticancer and Antiparasitic Activity.

Four new Cu(I) complexes of the general formula [Cu(PP)(LL)][BF4 ], in which PP is a phosphane ligand (triphenylphosphane or 1,2-bis(diphenylphosphano)ethane (dppe)) and LL is a bioactive thiosemicarbazone ligand (4-(methyl)-1-(5-nitrofurfurylidene)thiosemicarbazone) or 4-(ethyl)-1-(5-nitrofurfurylidene)thiosemicarbazone) were synthesized and fully characterized by classical analytical and spectroscopic methods. The anti-trypanosome and anticancer activities were investigated in vitro on Trypanosoma cruzi and in two human cancer cell lines (ovarian OVCAR3 and prostate PC3). To test the selectivity toward parasites and cancer cells, the cytotoxicity on normal monkey kidney VERO and human dermal fibroblasts HDF cells was also evaluated. The new heteroleptic complexes were more cytotoxic on T. cruzi and chemoresistant prostate PC3 cells than the benchmark drugs nifurtimox and cisplatin. The compounds also showed a high level of cellular internalization by the OVCAR3 cells and, in particular, those containing the dppe phosphane showed activation of the cell death mechanism via apoptosis. On the other hand, the production of reactive oxygen species induced by these complexes was not evident.

Health-related quality of life in children with cerebral palsy associated with congenital Zika infection.

OBJECTIVE: To describe the health-related quality of life (QOL) in children with cerebral palsy (CP) associated with congenital Zika infection. METHODS: Cross-sectional study of a consecutive series of children, followed in a referral multicentric rehabilitation network in Brazil. We invited the caregivers to respond to the Brazilian version of the Caregiver Priorities & Child Health Index of Life with Disabilities (CPCHILDTM) questionnaire. Statistical analysis was performed with the Statistical Package for the Social Sciences (SPSS) 26.0™. We used absolute and relative frequencies for categorical variables and mean and standard deviation for continuous variables. RESULTS: The sample consisted of 193 children, at mean age of 50.3±7.6 months. We observed a predominance of children with cerebral palsy (CP) with Gross Motor Function Classification System (GMFCS) level V (93.7%). Epilepsy (88.4%) was the most common comorbidity. CPCHILDTM mean scores were activities of daily living (ADL)/personal care 43.2±12.6; positioning, transferring and mobility 33.7±16.5; comfort and emotions 84.4±15.2; communication and social interaction (CoSI) 48.2±24.3; health 70.9±17.1; and overall quality of life (OQOL) 72.1±17.1. Total score was 54.8±11.3. CONCLUSIONS: Among children with cerebral palsy (CP) related to congenital Zika syndrome, the quality of life (QOL) scores were very similar to other populations with cerebral palsy (CP). The activities of positioning, transferring and mobility had the greatest impact on health-related quality of life (QOL). Rehabilitation strategies and public policies should prioritize aspects related to mobility for this population.

Cone-beam computed tomography study of mandibular morphology and tooth compensation in asymmetrical patients.

INTRODUCTION: This study evaluated mandibular morphology and transverse dental compensation between symmetrical and asymmetrical subjects, allocated according to sagittal skeletal patterns. In addition, the hypothesis that mandibular morphology and dental compensations differed between symmetrical/asymmetrical groups and also among the different types of sagittal skeletal patterns was tested. METHODS: Cone-beam computed tomography images of 96 patients were included in this study and were divided into 2 groups according to the degree of menton deviation: a symmetrical group with deviation up to 2.0 mm (n = 48; mean age, 15 ± 6 years), and an asymmetrical group with deviation from 3.5 mm (n = 48; mean age, 16 ± 8 years). The 2 groups were divided in accordance with the ANB angle: Class I, II, and III. Skeletal and dental measurements were performed. Intergroup and intragroup analyses were carried out, using a 2-way analysis of variance to assess the interaction of factors: symmetry and sagittal skeletal pattern; and the Student t test for differences between deviated (Dv) and nondeviated (NDv) sides. RESULTS: Symmetrical/asymmetrical groups and Class I, II, and III groups were similar in relation to demographic aspects (P = 0.412 and P = 0.357 for sex and age, respectively). Asymmetrical patients had higher values for body length and mandibular ramus and condyle height on the NDv side (P = 0.011, P = 0.024, and P = 0.001, respectively). When comparing the different skeletal patterns, patients with a Class III relationship demonstrated higher values for mandibular ramus height. Intergroup analysis showed no differences in dental parameters. In the comparison between the sides, the asymmetrical group showed a significant difference in canine inclination (P = 0.008), mandibular ramus height (P = 0.004), condyle height (P = 0.010) and gonion to midsagittal plane distance (P = 0.018). CONCLUSIONS: Asymmetrical subjects showed higher values for canine inclination and mandibular body, ramus and condylar height on the NDv side. The hypothesis was partially confirmed that mandibular morphology and dental compensations are different between symmetrical/asymmetrical groups and among different sagittal skeletal patterns.

Block Copolymer Micelles Encapsulating Au(III) Bis(Dithiolene) Complexes as Promising Nanostructures with Antiplasmodial Activity.

Block copolymer micelles (BCMs) can be used to improve the solubility of lipophilic drugs and increase their circulation half-life. Hence, BCMs assembled from MePEG-b-PCL were evaluated as drug delivery systems of gold(III) bis(dithiolene) complexes (herein AuS and AuSe) to be employed as antiplasmodial drugs. These complexes exhibited remarkable antiplasmodial activity against liver stages of the Plasmodiumberghei parasite, and low toxicity in a model of zebrafish embryos. To improve the complexes' solubility, BCMs were loaded with AuS, AuSe, and the reference drug primaquine (PQ). PQ-BCMs (Dh = 50.9 ± 2.8 nm), AuSe-BCMs (Dh = 87.1 ± 9.7 nm), and AuS-BCMs (Dh = 72.8 ± 3.1 nm) were obtained with a loading efficiency of 82.5%, 55.5%, and 77.4%, respectively. HPLC analysis and UV-Vis spectrophotometry showed that the compounds did not suffer degradation after encapsulation in BCMs. In vitro release studies suggest that AuS/AuSe-BCMs present a more controlled release compared with PQ-loaded BCMs. The antiplasmodial hepatic activity of the drugs was assessed in vitro and results indicate that both complexes present higher inhibitory activity than PQ, although encapsulated AuS and AuSe presented lower activity than their non-encapsulated counterparts. Nevertheless, these results suggest that the use of BCMs as delivery vehicles for lipophilic metallodrugs, particularly AuS and AuSe, could enable the controlled release of complexes and improve their biocompatibility, constituting a promising alternative to conventional antimalarial treatments.

Antitumoral and Antimicrobial Activities of Block Copolymer Micelles Containing Gold Bisdithiolate Complexes.

Gold(III) bisdithiolate complexes have been reported as potential antimicrobial and antitumoral agents. The complex [Au(cdc)2]- (cdc=cyanodithioimido carbonate) displayed antimicrobial and outstanding antitumor activity against the ovarian cancer cells A2780 and A2780cisR, which are sensitive and resistant to cisplatin, respectively. However, poor water solubility may hamper its clinical use. Block copolymer micelles (BCMs) may solubilize hydrophobic drugs, improving their bioavailability and circulation time in blood. Aiming to provide water solubility, prolonged availability, and enhanced therapeutic indexes, BCMs loaded with [Au(cdc)2]- were synthesized and characterized. The BCM-[Au(cdc)2] micelles were prepared with a loading efficiency of 64.6% and a loading content of 35.3 mg [Au(cdc)2]-/gBCM. A hydrodynamic diameter of 77.31 ± 27.00 nm and a low polydispersity index of 0.18 indicated that the micelles were homogenous and good candidates for drug delivery. Cytotoxic activity studies against A2780/A2780cisR cells showed that BCM-[Au(cdc)2] maintained relevant cytotoxic activity comparable to the cytotoxicity observed for the same concentration of gold complexes. The Au uptake in A2780 cells, determined by PIXE, was ca. 17% higher for BCMs-[Au(cdc)2] compared to [Au(cdc)2]-. The BCMs-[Au(cdc)2] presented antimicrobial activity against S. aureus Newman and C. glabrata CBS138. These results evidenced the potential of BCM-[Au(cdc)2] for drug delivery and its promising anticancer and antimicrobial activities.

Electromyographic analysis of the stomatognathic system of children with Molar-incisor hypomineralization.

INTRODUCTION: Molar-incisor hypomineralization (MIH) is a qualitative defect of dental enamel that affects one or more permanent first molars, with or without involvement of the incisor teeth. This condition leads to challenges to dental care and treatment planning. AIM: Based on the hypothesis that children who have MIH possibly present alterations in postural and masticatory activities and considering the absence of studies investigating these parameters, the present study evaluated the functionality of the stomatognathic system considering the mentioned aspects. MATERIALS: The comparison of individuals with (MIHG; n = 32) and without MIH (CG; n = 32) was evaluated by electromyographic activity of the masseter and temporal muscles (right and left), as well as evaluation of the masticatory cycles during habitual mastication. RESULTS: MIHG showed muscle hyperactivity in postural and dynamic conditions compared to the CG; higher electromyographic values for MIHG when compared to CG in the following postural conditions: at rest for the right temporal (p = 0.00) and left temporal muscles (p = 0.03); in the protrusion to the right temporal muscle (p = 0.02); in the right laterality for the right masseter (p = 0.00) and left temporal muscles (p = 0.01); in the left laterality for the right masseter (p = 0.03) and left temporal (p = 0.04) muscles. In dynamic conditions with consistent food, significance was observed for the left temporal (p = 0.01); and with soft food for the right (p = 0.01) and left temporal muscles (p = 0.04). CONCLUSIONS: Children with MIH seem to have impaired functionality of the stomatognathic system. Children with MIH have alterations in the stomatognathic system.

Cell Uptake of Steroid-BODIPY Conjugates and Their Internalization Mechanisms: Cancer Theranostic Dyes.

Estradiol-BODIPY linked via an 8-carbon spacer chain and 19-nortestosterone- and testosterone-BODIPY linked via an ethynyl spacer group were evaluated for cell uptake in the breast cancer cell lines MCF-7 and MDA-MB-231 and prostate cancer cell lines PC-3 and LNCaP, as well as in normal dermal fibroblasts, using fluorescence microscopy. The highest level of internalization was observed with 11ß-OMe-estradiol-BODIPY 2 and 7α-Me-19-nortestosterone-BODIPY 4 towards cells expressing their specific receptors. Blocking experiments showed changes in non-specific cell uptake in the cancer and normal cells, which likely reflect differences in the lipophilicity of the conjugates. The internalization of the conjugates was shown to be an energy-dependent process that is likely mediated by clathrin- and caveolae-endocytosis. Studies using 2D co-cultures of cancer cells and normal fibroblasts showed that the conjugates are more selective towards cancer cells. Cell viability assays showed that the conjugates are non-toxic for cancer and/or normal cells. Visible light irradiation of cells incubated with estradiol-BODIPYs 1 and 2 and 7α-Me-19-nortestosterone-BODIPY 4 induced cell death, suggesting their potential for use as PDT agents.