Browsing by Author "Mendes, Karina"
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- Antimicrobial properties and bioactivity potential of smart nanoparticles for dental applicationsPublication . Correia, Bruna L.; Malekshiri, Moslem; Bartolomeu, Maria; Silva, Virgília; Oliveira, Ana; Noites, Rita; Cardoso, Miguel; Mendes, Karina; Gomes, Ana T. P. C.; Duarte, Ana Sofia
- D-2-hydroxyglutarate supports a tolerogenic phenotype with lowered major histocompatibility class II expression in non-malignant dendritic cells and acute myeloid leukemia cellsPublication . Hammon, Kathrin; Renner, Kathrin; Althammer, Michael; Voll, Florian; Babl, Nathalie; Decking, Sonja-Maria; Siska, Peter J.; Matos, Carina; Conejo, Zugey Elizabeth Cárdenas; Mendes, Karina; Einwag, Friederike; Siegmund, Heiko; Iberl, Sabine; Berger, Raffaela S.; Dettmer, Katja; Schoenmehl, Rebecca; Brochhausen, Christoph; Herr, Wolfgang; Oefner, Peter J.; Rehli, Michael; Thomas, Simone; Kreutz, MarinaD-2-hydroxyglutarate (D-2-HG) accumulates in primary acute myeloid leukemia (AML) patients with mutated isocitrate dehydrogenase (IDH) and other malignancies. D-2-HG suppresses antitumor T cell immunity but little is known about potential effects on non-malignant myeloid cells. Here we show that D-2-HG impairs human but not murine dendritic cell (DC) differentiation, resulting in a tolerogenic phenotype with low major histocompatibility (MHC) class II expression. In line, IDH-mutated AML blasts exhibited lower expression of HLA-DP and were less susceptible to lysis by HLA-DP-specific T cells. Interestingly, D-2-HG reprogrammed metabolism towards increased lactate production in DCs and AML besides its expected impact on DNA demethylation. Vitamin C accelerated DNA demethylation, but only the combination of vitamin C and glycolytic inhibition lowered lactate levels and supported MHC class II expression. Our results indicate an unexpected link between the immunosuppressive metabolites 2-HG and lactic acid and suggest a potentially novel therapeutic strategy with combinations of anti-glycolytic drugs and epigenetic modulators (hypomethylating agents) or other therapeutics for the treatment of AML.
- Exploring the inflammatory profile of homelessness population: a comprehensive analysis of individuals in two temporary shelters in LisbonPublication . Gomes, Ana T. P. C.; Mendes, Karina; Ferrito, Cândida; Andrade, Filipa; Neves-Amado, João; Resende, Ana; Santos, Paulo; Manso, Dina; Almeida, António; Vollrath, Antónia; Lopes, Rafaela; Barros, Marlene; Rosa, Nuno; Figueiredo, Amélia SimõesBackground: Homeless people are continuously facing adverse living conditions as poor access to basic nutrition, hygiene conditions and healthcare services, being at increased risk of severe infectious diseases as HIV and hepatitis as well as cardiovascular diseases and mental disorders. The characterization of homeless people’s health is fundamental to identify their health care needs. Considering that the aforementioned diseases are associated with chronic inflammatory processes, the main goal of this study was to characterize the inflammatory profile of a homeless population through quantification in saliva of a panel of inflammatory cytokines. Methods: The inflammatory profile was assessed in 114 individuals residing in two temporary shelters located in Lisbon and that accepted to participated in the study. Inflammatory proteins were quantified using a Multiplex Immunoassay approach. Data analysis was performed using the GraphPad Prism software and statistical significance among the groups was assessed using the nonparametric Mann–Whitney test. Results: Even though some protein levels might be masked by drug treatment, data analysis showed high levels of INF-ϒ, IL-10 and TNF-α in the infectious disease group, critical cytokines for the immune response against viruses and bacteria. Also, cytokines like IL-1β and IL-6 were detected at statistically significant levels in the cardiovascular disease group and all cytokines included in this study were quantified in the mental disorders group. Conclusion: These findings may help the healthcare services in the evaluation of treatment efficacy and disease monitoring, and in the development of effective public healthcare strategies and policy interventions to improve quality of life of the homeless population.
- Microbial DNA extraction methods for microbial screening - saliva vs biofilm comparisonPublication . Gomes, Ana T. P. C.; Pinto, Marla; Abrantes, Patrícia; Almeida, Rita; Mendes, Karina; Duarte, Ana S.; Silva, Raquel M.; Rosa, Nuno; Correia, Maria; Barros, Marlene
- Multiplex immunoassay for inflammatory proteins quantification in saliva – a methodologic approachPublication . Rosa, Nuno; Gomes, Ana T. P. C.; Mendes, Karina; Duarte, Ana S.; Silva, Raquel M. S.; Correia, Maria; Barros, Marlene
- O4 - Exploring the biological properties and regenerative potential of biomaterials using cell culture modelsPublication . Duarte, Ana Sofia; Correia, Bruna L.; Bartolomeu, Maria; Mendes, Karina; Gomes, Ana T. P. C.Life expectancy has improved signifcantly and, along with the declining birthrate, has contributed to the aging of populations, especially in industrialized countries. Alas, aging is intrinsically associated with the incidence of health problems including bone and tooth loss that require suitable solutions to support the quality of life. To meet these demands, signifcant research eforts have been undertaken to develop novel biomaterials, both orthopedic and dental implants. The feld of biomaterials for bone tissue engineering is increasingly evolving. The most recent generations of biomaterials have increasingly more activity and interaction with the biological environment and stimulate the regeneration of functional tissue. Natural polymers and compounds have been combined with each other to improve workability and are strategically integrated with ceramics or bioactive glasses to reinforce the structure of the fnal system, thus producing composites with a better mechanical performance. Our research group has been focused on the biological characterization of diferent added-value materials and composites, namely by evaluating their antimicrobial, biocompatibility, and regenerative properties. Some of our recent work results allowed us to conclude that marine fungal extracts, as well as sol–gel-derived bioactive glass nanoparticles, have inhibitory efects on the growth of C. albicans and E. faecalis (main pathogens in persistent root canal infections). Additionally, we have characterized cuttlefsh bone powders for endodontic applications. We are also committed to developing strategies for monitoring cell response to these biomaterials at the molecular level that could be used to follow infammation and osteoconduction.
- P9 - Antimicrobial properties and bioactivity potential of smart nanoparticles for dental applicationsPublication . Correia, Bruna L.; Malekshiri, Moslem; Bartolomeu, Maria; Silva, Virgília; Oliveira, Ana; Noites, Rita; Cardoso, Miguel; Mendes, Karina; Gomes, Ana T. P. C.; Duarte, Ana SofiaTooth decay is one of the greatest causes of tooth loss in the world. This not only afects the patient’s quality of life but also carries an economic burden associated with the need for multiple reinterventions. Endodontic treatment aims to preserve teeth by cleaning, disinfecting and flling/sealing the root canal. Despite the high success rate of endodontic treatment, failures do occur in a large number of cases. Several new biomaterials for dentistry have been developed, however their bioactivity is often misunderstood. Our work focuses on the biological characterization of novel bioactive glass nanoparticles, including the evaluation of their antimicrobial and biocompatibility properties. Candida albicans (ATCC 11225) and Enterococcus faecalis (ATCC 29212) were included to evaluate the antimicrobial potential by the drop plate method [1]. The cytotoxicity was tested using the MC3T3-E1 cell line, through the resazurin reduction assay. The novel bioactive glass nanoparticles demonstrated antimicrobial activity against C. albicans and E. faecalis, being able to inhibit their growth but also, in some incubation times, decreased the survival of these microorganisms. After 24 h of incubation of MC3T3-E1 osteoblast cells with bioactive glass nanoparticles conditioned medium, around 48% cell viability was achieved. These novel bioactive glass nanoparticles have shown promising properties which may fnd applications on diferent areas of clinical dentistry.
- Postmitotic differentiation of human monocytes requires cohesin-structured chromatinPublication . Minderjahn, Julia; Fischer, Alexander; Maier, Konstantin; Mendes, Karina; Nuetzel, Margit; Raithel, Johanna; Stanewsky, Hanna; Ackermann, Ute; Månsson, Robert; Gebhard, Claudia; Rehli, MichaelCohesin is a major structural component of mammalian genomes and is required to maintain loop structures. While acute depletion in short-term culture models suggests a limited importance of cohesin for steady-state transcriptional circuits, long-term studies are hampered by essential functions of cohesin during replication. Here, we study genome architecture in a postmitotic differentiation setting, the differentiation of human blood monocytes (MO). We profile and compare epigenetic, transcriptome and 3D conformation landscapes during MO differentiation (either into dendritic cells or macrophages) across the genome and detect numerous architectural changes, ranging from higher level compartments down to chromatin loops. Changes in loop structures correlate with cohesin-binding, as well as epigenetic and transcriptional changes during differentiation. Functional studies show that the siRNA-mediated depletion of cohesin (and to a lesser extent also CTCF) markedly disturbs loop structures and dysregulates genes and enhancers that are primarily regulated during normal MO differentiation. In addition, gene activation programs in cohesin-depleted MO-derived macrophages are disturbed. Our findings implicate an essential function of cohesin in controlling long-term, differentiation- and activation-associated gene expression programs.
- The epigenetic pioneer EGR2 initiates DNA demethylation in differentiating monocytes at both stable and transient binding sitesPublication . Mendes, Karina; Schmidhofer, Sandra; Minderjahn, Julia; Glatz, Dagmar; Kiesewetter, Claudia; Raithel, Johanna; Wimmer, Julia; Gebhard, Claudia; Rehli, MichaelThe differentiation of human blood monocytes (MO), the post-mitotic precursors of macrophages (MAC) and dendritic cells (moDC), is accompanied by the active turnover of DNA methylation, but the extent, consequences and mechanisms of DNA methylation changes remain unclear. Here, we profile and compare epigenetic landscapes during IL-4/GM-CSF-driven MO differentiation across the genome and detect several thousand regions that are actively demethylated during culture, both with or without accompanying changes in chromatin accessibility or transcription factor (TF) binding. We further identify TF that are globally associated with DNA demethylation processes. While interferon regulatory factor 4 (IRF4) is found to control hallmark dendritic cell functions with less impact on DNA methylation, early growth response 2 (EGR2) proves essential for MO differentiation as well as DNA methylation turnover at its binding sites. We also show that ERG2 interacts with the 5mC hydroxylase TET2, and its consensus binding sequences show a characteristic DNA methylation footprint at demethylated sites with or without detectable protein binding. Our findings reveal an essential role for EGR2 as epigenetic pioneer in human MO and suggest that active DNA demethylation can be initiated by the TET2-recruiting TF both at stable and transient binding sites.
- Unlocking the potential of probiotic administration in caries management: a systematic reviewPublication . Lopes, Pedro C.; Gomes, Ana T. P. C.; Mendes, Karina; Blanco, Letícia; Correia, Maria J.Background The use of prebiotics and/or probiotic bacteria with the potential to modulate the oral ecosystem may play an important role in the prevention and management of dental caries. To assess the evidence of the potential of pre/probiotics both in the prevention and treatment of dental caries, we focused on the PICO question “In individuals with caries, after probiotic administration, is there an improvement in outcomes directly related to caries risk and development?“. Methods An extensive systematic search was conducted in electronic databases PubMed, Web of Science, Scopus and Cochrane, to identify articles with relevant data. This systematic review included trials performed in Humans; published in English; including the observation of patients with caries, with clear indication of the probiotic used and measuring the outcomes directly involved with the cariogenic process, including the quantification of bacteria with cariogenic potential. To evaluate the methodological quality of the studies, the critical assessment tool from the Joanna Briggs Institute was used. Results Eight hundred and fifty articles, potentially relevant, were identified. Following PRISMA guidelines 14 articles were included in this systematic review. Outcomes such as reduction of cariogenic microorganism counts, salivary pH, buffer capacity, and caries activity were assessed. The probiotic most often referred with beneficial results in dental caries outcomes is Lacticaseibacillus rhamnosus. Regarding the most used administration vehicle, in studies with positive effects on the caries management, probiotic supplemented milk could be considered the best administration vehicle. Conclusions Evidence suggests a beneficial effect of probiotic supplemented milk (Lacticaseibacillus rhamnosus) as an adjuvant for caries prevention and management. However, comparable evidence is scarce and better designed and comparable studies are needed.