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  • ItemEditorial
    Preface
    (2022-01-01) de Sousa, Ângela Maria Almeida; Soares, Christiane Pienna [UNESP]; Chorilli, Marlus [UNESP]; University of Beira Interior; Universidade Estadual Paulista (UNESP)
  • ItemLivro
    Cancer Nanotechnology
    (2022-01-01) de Sousa, Ângela Maria Almeida; Soares, Christiane Pienna [UNESP]; Chorilli, Marlus [UNESP]; University of Beira Interior; Universidade Estadual Paulista (UNESP)
    Cancer nanotechnology is a growing, emerging area of cross-disciplinary research that aims to develop efficient, specific and noninvasive approaches to restore the health and well-being of all cancer patients through more effective diagnosis and treatment. This new volume serves as a fundamental guide to cutting-edge topics in cancer nanotechnology, including advances in therapy, the use of nanoparticles and nanomaterials, future directions for nanocarriers in cancer therapy, and the application of DNA and RNA nanovaccines. Organized into four sections, the volume presents an overview of research and innovation in the emerging field of nanotechnology as a powerful tool in the diagnosis, imaging and treatment of cancer. International experts author chapters addressing targets of cancer therapy, materials for cancer nanotechnology, strategies for cancer therapy using nanotechnology, and innovative nanotechnologies for cancer diagnosis and treatment. The volume will be useful for a broad audience, including cross-disciplinary researchers, trainees, health professionals, and experts in industry.
  • ItemResenha
    Photodynamic Therapy Can Modulate the Nasopharyngeal Carcinoma Microenvironment Infected with the Epstein–Barr Virus: A Systematic Review and Meta-Analysis
    (2023-05-01) Fornel, Diógenes Germano [UNESP]; Ferrisse, Túlio Morandin [UNESP]; de Oliveira, Analú Barros [UNESP]; Fontana, Carla Raquel [UNESP]; Universidade Estadual Paulista (UNESP)
    Nasopharyngeal carcinoma is a malignancy from epithelial cells predominantly associated with the Epstein–Barr virus (EBV) infection, and it is responsible for 140,000 deaths annually. There is a current need to develop new strategies to increase the efficacy of antineoplastic treatment and reduce side effects. Thus, the present study aimed to perform a systematic review and meta-analysis of the ability of photodynamic therapy (PDT) to modulate the tumor microenvironment and PDT efficacy in nasopharyngeal carcinoma treatment. The reviewers conducted all steps in the systematic review. PubMed, Science Direct, Scopus, Scielo, Lilacs, EMBASE, and the Cochrane library databases were searched. The OHAT was used to assess the risk of bias. Meta-analysis was performed with a random-effects model (α = 0.05). Nasopharyngeal carcinoma cells treated with PDT showed that IL-8, IL-1α, IL-1β, LC3BI, LC3BII, MMP2, and MMP9 levels were significantly higher than in groups that did not receive PDT. NF-ĸB, miR BART 1-5p, BART 16, and BART 17-5p levels were significantly lower in the PDT group than in the control group. Apoptosis levels and the viability of nasopharyngeal carcinoma cells (>70%) infected with EBV were effective after PDT. This treatment also increased LMP1 levels (0.28–0.50/p < 0.05) compared to the control group. PDT showed promising results for efficacy in killing nasopharyngeal carcinoma cells infected with EBV and modulating the tumor microenvironment. Further preclinical studies should be performed to validate these results.
  • ItemArtigo
    Membranolytic Activity Profile of Nonyl 3,4-Dihydroxybenzoate: A New Anti-Biofilm Compound for the Treatment of Dermatophytosis
    (2023-05-01) Costa-Orlandi, Caroline B. [UNESP]; Bila, Níura M. [UNESP]; Bonatti, Jean Lucas C. [UNESP]; Vaso, Carolina O. [UNESP]; Santos, Mariana B. [UNESP]; Polaquini, Carlos R. [UNESP]; Santoni Biasioli, Mariana M. [UNESP]; Herculano, Rondinelli D. [UNESP]; Regasini, Luis O. [UNESP]; Fusco-Almeida, Ana Marisa [UNESP]; Mendes-Giannini, Maria José S. [UNESP]; Universidade Estadual Paulista (UNESP); Universidade Estadual de Maringá (UEM)
    The ability of dermatophytes to live in communities and resist antifungal drugs may explain treatment recurrence, especially in onychomycosis. Therefore, new molecules with reduced toxicity that target dermatophyte biofilms should be investigated. This study evaluated nonyl 3,4-dihydroxybenzoate (nonyl) susceptibility and mechanism of action on planktonic cells and biofilms of T. rubrum and T. mentagrophytes. Metabolic activities, ergosterol, and reactive oxygen species (ROS) were quantified, and the expression of genes encoding ergosterol was determined by real-time PCR. The effects on the biofilm structure were visualized using confocal electron microscopy, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). T. rubrum and T. mentagrophytes biofilms were susceptible to nonyl and resistant to fluconazole, griseofulvin (all strains), and terbinafine (two strains). The SEM results revealed that nonyl groups seriously damaged the biofilms, whereas synthetic drugs caused little or no damage and, in some cases, stimulated the development of resistance structures. Confocal microscopy showed a drastic reduction in biofilm thickness, and transmission electron microscopy results indicated that the compound promoted the derangement and formation of pores in the plasma membrane. Biochemical and molecular assays indicated that fungal membrane ergosterol is a nonyl target. These findings show that nonyl 3,4-dihydroxybenzoate is a promising antifungal compound.
  • ItemArtigo
    Biocompatible anti-aging face mask prepared with curcumin and natural rubber with antioxidant properties
    (2023-07-01) de Souza Silva, Flávio Kunert [UNESP]; Costa-Orlandi, Caroline Barcelos [UNESP]; Fernandes, Mariza Aires [UNESP]; Pegorin Brasil, Giovana Sant'Ana [UNESP]; Mussagy, Cassamo Ussemane; Scontri, Mateus [UNESP]; Sasaki, Josana Carla da Silva [UNESP]; de Sousa Abreu, Ana Paula [UNESP]; Guerra, Nayrim Brizuela [UNESP]; Floriano, Juliana Ferreira [UNESP]; de Mendonça, Ricardo José; Caetano, Guilherme Ferreira; Farhadi, Neda; Gómez, Alejandro; Huang, Shuyi; Farias, Andressa Machado [UNESP]; Primo, Fernando Lucas [UNESP]; Li, Bingbing; Fusco-Almeida, Ana Marisa [UNESP]; Dokmeci, Mehmet Remzi; Jucaud, Vadim; Mendes-Giannini, Maria José Soares [UNESP]; Cardoso, Marcos Roberto; Herculano, Rondinelli Donizetti [UNESP]; Universidade Estadual Paulista (UNESP); Pontificia Universidad Católica de Valparaíso; Imperial College London; Federal University of Triangulo Mineiro (UFTM); University Center of Hermínio Ometto Foundation (FHO); Universidade de São Paulo (USP); Terasaki Institute for Biomedical Innovation (TIBI); California State University
    Natural rubber latex (NRL) is a biopolymer widely used in biomedical applications. In this work, we propose an innovative cosmetic face mask, combining the NRL's biological properties with curcumin (CURC), which has a high level of antioxidant activity (AA) to provide anti-aging benefits. Chemical, mechanical and morphological characterizations were performed. The CURC released by the NRL was evaluated by permeation in Franz cells. Cytotoxicity and hemolytic activity assays were performed to assess safety. The findings showed that the biological properties of CURC were preserved after loading in the NRL. About 44.2 % of CURC was released within the first six hours, and in vitro permeation showed that 9.36 % ± 0.65 was permeated over 24 h. CURC–NRL was associated with a metabolic activity higher than 70 % in 3 T3 fibroblasts, cell viability ≥95 % in human dermal fibroblasts, and a hemolytic rate ≤ 2.24 % after 24 h. Furthermore, CURC-NRL maintained the mechanical characteristics (range suitable) for human skin application. We observed that CURC-NRL preserved ~20 % antioxidant activity from curcumin-free after loading in the NRL. Our results suggest that CURC–NRL has the potential to be used in the cosmetics industry, and the experimental methodology utilized in this study can be applied to different kinds of face masks.
  • ItemArtigo
    Cytotoxic Activity of Baccharis trimera (Less.) DC. Essential Oil in Tumor Cell Lines and its Role in Associated Death Mechanisms
    (2023-01-01) Moro, Isabela Jacob [UNESP]; Carvalho, Flavio Alexandre [UNESP]; Moreira, Thais Fernanda [UNESP]; Souza, Felipe de Oliveira [UNESP]; da Silva, Alexander Alves [UNESP]; Politi, Flávio [UNESP]; Soares, Christiane Pienna [UNESP]; Dos Santos, André Gonzaga [UNESP]; Universidade Estadual Paulista (UNESP)
    This study evaluated the potential of Baccharis trimera essential oil (EO) and its components in cancer therapy through the application of cytotoxicity and cell death assays. Using gas chromatography analysis, the major components of the aerial parts of the essential oil were identified as (E)-caryophyllene (18.9%), bicyclogermacrene (15.6%), and germacrene D (10.5%). Baccharis trimera essential oil (5.8 μg/mL) and α-humulene (7.8 μg/mL) presented strong cytotoxic activity, while (E)-caryophyllene (11.5 μg/mL) and caryophyllene oxide (> 100.0 μg/mL) showed moderate and low activities, respectively, against MCF-7 cell lines. Against HepG2 cell lines, B. trimera essential oil (10.4 μg/mL), α-humulene (17.1 μg/mL), and caryophyllene oxide (19.4 μg/mL) exhibited moderate activity, while (E)-caryophyllene (52.3 μg/mL) displayed low activity against HepG2 cell lines. The selectivity index values of EO (MCF-7 and HepG2), α-humulene and (E)-caryophyllene (MCF-7), and caryophyllene oxide (HepG2) were found between 1.1 and 2.8, compared with MCF-10A cells. The annexin-V and Hoechst / propidium iodide assays performed with essential oil, (E)-caryophyllene, α-humulene, and caryophyllene oxide showed apoptosis and necrosis mechanisms for all cell lines. Based on these findings, B. trimera essential oil and its components can be considered as potential therapeutic agents against cancer.
  • ItemArtigo
    Zinc-Based Nanoparticles Reduce Bacterial Biofilm Formation
    (2023-03-01) Fulindi, Rafael Bianchini [UNESP]; Rodrigues, Juliana Domingues [UNESP]; Barbosa, Thulio Wliandon Lemos [UNESP]; Garcia, Ariana D. Goncalves; De Almeida La Porta, Felipe; Pratavieira, Sebastião; Chiavacci, Leila Aparecida [UNESP]; Junior, João Pessoa Araújo [UNESP]; Da Costa, Paulo Inácio [UNESP]; Martinez, Luis R.; Universidade Estadual Paulista (UNESP); University of Florida College of Dentistry; Federal Technological University of Paraná (UTFPR); Universidade de São Paulo (USP); University of Florida
    Biofilm formation is important for microbial survival in hostile environments and a phenotype that provides microorganisms with antimicrobial resistance. Zinc oxide (ZnO) and Zinc sulfide (ZnS) nanoparticles (NPs) present potential antimicrobial properties for biomedical and food industry applications. Here, we aimed to analyze, for the first time, the bactericidal and antibiofilm activity of ZnS NPs against Staphylococcus aureus, Klebsiella oxytoca, and Pseudomonas aeruginosa, all medically important bacteria in developed countries. We compared ZnS NPs antimicrobial activity to ZnO NPs, which have been extensively studied. Using the colorimetric XTT reduction assay to observe the metabolic activity of bacterial cells and the crystal violet assay to measure biofilm mass, we demonstrated that ZnS and ZnO had similar efficacy in killing planktonic bacterial cells and reducing biofilm formation, with S. aureus being more susceptible to both therapeutics than K. oxytoca and P. aeruginosa. Crystal violet staining and confocal microscopy validated that Zn NPs inhibit biofilm formation and cause architectural damage. Our findings provide proof of principle that ZnS NPs have antibiofilm activity, and can be potentially used in medical and food industry applications, such as treatment of wound infections or package coating for food preservation. IMPORTANCE Zinc (Zn)-based nanoparticles (NPs) can be potentially used in medical and food preservation applications. As proof of principle, we investigated the bactericidal and antibiofilm activity of zinc oxide (ZnO) and zinc sulfide (ZnS) NPs against medically important bacteria. Zn-based NPs were similarly effective in killing planktonic and biofilm-Associated Staphylococcus aureus, Klebsiella oxytoca, and Pseudomonas aeruginosa cells. However, S. aureus was more susceptible to these investigational therapeutics. Although further studies are warranted, our findings suggest the possibility of future use of Zn-based NPs in the treatment of skin infections or preservation of food.
  • ItemArtigo
    Development of red-luminescent hybrids as contrast agents for cell imaging: A correlation among surface, luminescence, and biological properties
    (2023-05-01) Santos, João Antonio Oliveira [UNESP]; Brito, Lorrane Davi [UNESP]; da Costa, Paulo Inácio [UNESP]; Pires, Ana Maria [UNESP]; Lima, Sergio Antonio Marques [UNESP]; Universidade Estadual Paulista (UNESP)
    TTA (2-thenoyltrifluoroacetone), DBM (dibenzoylmethane), and EPHEN (5,6-Epoxy-5,6-dihydro- [1,10] phenanthroline) have generated europium complexes with excellent red emission properties. However, for bio applications, these complexes have been grafted on the surface of silica nanoparticles (SNP), by different approaches, due to their low water solubility. Here, we report how three approaches influence the surface, luminescent, and biological properties of 50 and 170 nm-SNP functionalized with carboxylic acid or phenanthroline ligands, useful to anchor TTA and DBM-Eu-complexes. TTA-hybrids exhibited better photophysical properties over the DBM ones, although intermolecular interactions between TTA and silica surface groups are likely to influence their properties. Aiming at such biological application, approach 3 resulted in the luminescent PHEN-hybrids with the highest values of intrinsic (φEuEu) and absolute quantum yields (φEuL), color purity of 100%, and high sensibilization efficiency (η). However, depending on the approach used, different surface charges were observed for the hybrids that directly impacted their cytotoxicity in Huh 7.5 cells. The larger the size of the nanoparticle or the more positive its surface charge is, the lower the toxicity of the hybrid. Even considering the presence of the protein corona effect, estimated in DMEM medium, the initial surface charge, observed in the buffer solution, plays an important role in the nanoparticle-cell interaction. Confocal microscopy images revealed that the hybrids were internalized by cells regardless of their size and surface charge, and their luminescence was also detectable, making them promising candidates for cell imaging applications as luminescent contrast agents.
  • ItemArtigo
    Burden of Influenza and Respiratory Syncytial Viruses in Suspected COVID-19 Patients: A Cross-Sectional and Meta-Analysis Study
    (2023-03-01) Costa, Vivaldo Gomes da [UNESP]; Gomes, Ana Júlia Chaves [UNESP]; Bittar, Cíntia [UNESP]; Geraldini, Dayla Bott [UNESP]; Previdelli da Conceição, Pâmela Jóyce [UNESP]; Cabral, Ágata Silva [UNESP]; Carvalho, Tamara [UNESP]; Biselli, Joice Matos [UNESP]; Provazzi, Paola Jocelan Scarin [UNESP]; Campos, Guilherme Rodrigues Fernandes; Sanches, Paulo Ricardo da Silva [UNESP]; Costa, Paulo Inácio [UNESP]; Nogueira, Maurício Lacerda; Araujo, João Pessoa [UNESP]; Spilki, Fernando Rosado; Calmon, Marília Freitas [UNESP]; Rahal, Paula [UNESP]; Universidade Estadual Paulista (UNESP); Faculdade de Medicina de São José do Rio Preto (FAMERP); Universidade Feevale
    Non-SARS-CoV-2 respiratory viral infections, such as influenza virus (FluV) and human respiratory syncytial virus (RSV), have contributed considerably to the burden of infectious diseases in the non-COVID-19 era. While the rates of co-infection in SARS-CoV-2-positive group (SCPG) patients have been determined, the burden of other respiratory viruses in the SARS-CoV-2-negative group (SCNG) remains unclear. Here, we conducted a cross-sectional study (São José do Rio Preto county, Brazil), and we collected our data using a meta-analysis to evaluate the pooled prevalence of FluV and RSV among SCNG patients. Out of the 901 patients suspected of COVID-19, our molecular results showed positivity of FluV and RSV in the SCNG was 2% (15/733) and 0.27% (2/733), respectively. Co-infection with SARS-CoV-2 and FluV, or RSV, was identified in 1.7% of the patients (3/168). Following our meta-analysis, 28 studies were selected (n = 114,318 suspected COVID-19 patients), with a pooled prevalence of 4% (95% CI: 3–6) for FluV and 2% (95% CI: 1–3) for RSV among SCNG patients were observed. Interestingly, FluV positivity in the SCNG was four times higher (OR = 4, 95% CI: 3.6–5.4, p < 0.01) than in the SCPG. Similarly, RSV positivity was significantly associated with SCNG patients (OR = 2.9, 95% CI: 2–4, p < 0.01). For subgroup analysis, cold-like symptoms, including fever, cough, sore throat, headache, myalgia, diarrhea, and nausea/vomiting, were positively associated (p < 0.05) with the SCPG. In conclusion, these results show that the pooled prevalence of FluV and RSV were significantly higher in the SCNG than in the SCPG during the early phase of the COVID-19 pandemic.
  • ItemArtigo
    Hydroxyethylcellulose-Based Hydrogels Containing Liposomes Functionalized with Cell-Penetrating Peptides for Nasal Delivery of Insulin in the Treatment of Diabetes
    (2022-11-01) Von Zuben, Eliete de Souza [UNESP]; Eloy, Josimar Oliveira; Inácio, Maiara Destro [UNESP]; Araujo, Victor Hugo Sousa [UNESP]; Baviera, Amanda Martins [UNESP]; Gremião, Maria Palmira Daflon [UNESP]; Chorilli, Marlus [UNESP]; Universidade Estadual Paulista (UNESP); Federal University of Ceará
    Liposomes functionalized with cell-penetrating peptides are a promising strategy to deliver insulin through the nasal route. A hydrogel based on hydroxyethylcellulose (HEC) aqueous solution was prepared, followed by a subsequent addition of liposomes containing insulin solution functionalized with trans-activator of transcription protein of HIV-1 (TAT) or Penetratin (PNT). The formulations were characterized for rheological behavior, mucoadhesion, syringeability, in vitro release and in vivo efficacy. Rheological tests revealed non-Newtonian fluids with pseudoplastic behavior, and the incorporation of liposomes (HLI, HLITAT and HLIPNT) in hydrogels did not alter the behavior original pseudoplastic characteristic of the HEC hydrogel. Pseudoplastic flow behavior is a desirable property for formulations intended for the administration of drugs via the nasal route. The results of syringeability and mucoadhesive strength from HEC hydrogels suggest a viable vehicle for nasal delivery. Comparing the insulin release profile, it is observed that HI was the system that released the greatest amount while the liposomal gel promoted greater drug retention, since the liposomal system provides an extra barrier for the release through the hydrogel. Additionally, it is observed that both peptides tested had an impact on the insulin release profile, promoting a slower release, due to complexation with insulin. The in vitro release kinetics of insulin from all formulations followed Weibull’s mathematical model, reaching approximately 90% of release in the formulation prepared with HEC-based hydrogels. Serum insulin levels and the antihyperglycemic effects suggested that formulations HI and HLI have potential as carriers for insulin delivery by the nasal pathway, a profile not observed when insulin was administered by subcutaneous injection or by the nasal route in saline. Furthermore, formulations functionalized with TAT and PNT can be considered promoters of late and early absorption, respectively.
  • ItemArtigo
    In Vitro Antiglycation Potential of Erva-Baleeira (Varronia curassavica Jacq.)
    (2023-02-01) Rodrigues, Winner Duque [UNESP]; Cardoso, Felipe Nunes [UNESP]; Baviera, Amanda Martins [UNESP]; dos Santos, André Gonzaga [UNESP]; Universidade Estadual Paulista (UNESP)
    Background: Varronia curassavica Jacq. (Boraginaceae) is traditionally used in the treatment of inflammatory processes. The ethanolic extract of its leaves (EEVc) showed anti-inflammatory properties and low toxicity. Medicinal plants have aroused interest for their antiglycation activities. The formation and accumulation of advanced glycation end products (AGEs) are associated with several chronic diseases. The objective of this study was to evaluate the antiglycation potential of EEVc and two isolated compounds. Methods: The compounds brickellin and cordialin A were obtained by chromatographic methods and identified by spectrometric techniques. Analysis of fluorescent AGEs, biomarkers of amino acid residue oxidation, protein carbonyl groups and crosslink formation were performed in samples obtained from an in vitro model system of protein glycation with methylglyoxal. Results: EEVc, brickellin and cordialin A significantly reduced the in vitro formation of AGEs, and reduced the damage caused by oxidative damage to the protein. Conclusions: According to the results, EEVc, brickellin and cordialin A are potential candidates against AGEs formation, which opens the way to expand the therapeutic arsenal for many pathologies resulting from glycoxidative stress.
  • ItemArtigo
    Selective depletion of regulatory T cells enhances the immunogenicity of a recombinant-based vaccine against Sporothrix spp
    (2023-02-10) Batista-Duharte, Alexander [UNESP]; Téllez-Martínez, Damiana [UNESP]; Portuondo, Deivys Leandro [UNESP]; Carlos, Iracilda Zeppone [UNESP]; Universidade Estadual Paulista (UNESP)
    Introduction: Regulatory T cells (Tregs) have been shown to limit the protective immune response against pathogenic species of the fungus Sporothrix spp, the causal agent of sporotrichosis. However, the specific function of Tregs during vaccination against these fungi is known. Methods: We evaluated the effect of Tregs depletion on the immunogenicity of an experimental recombinant anti-Sporothrix vaccine, using the DEREG mice. In this model, only Foxp3(+) Tregs express eGFP and diphtheria toxin (DT) receptors, and transient Tregs depletion is achieved by DT administration. Results: Tregs depletion enhanced the frequency of specific IFNγ+ T cells (Th1 lymphocytes) and cytokine production after either the first or second vaccine dose. However, depletion of Tregs during the second dose caused greater stimulation of specific Th1 lymphocytes than depletion during the first dose. Similarly, the highest production of IgG, IgG1, and IgG2a anti rSsEno antibody was detected after Tregs depletion during boost immunization compared to the other immunized groups. Importantly, vaccine immunogenicity improvement after Tregs depletion also had an impact on the more efficient reduction of fungal load in the skin and liver after the challenge with S. brasiliensis in an experimental infection model. Interestingly, the reduction in fungal load was greatest in the Tregs depleted group during boosting. Discussion: Our results illustrate that Tregs restrict vaccine-induced immune response and their transient depletion could enhance anti-Sporothrix vaccine immunogenicity. Further studies are required to elucidate whether Tregs depletion may be a way to improve the efficacy of vaccination against Sporothrix spp.
  • ItemCapítulo de livro
    Polymicrobial biofilms: Impact on fungal pathogenesis
    (2022-01-01) Costa-Orlandi, Caroline Barcelos [UNESP]; Bila, Níura Madalena [UNESP]; Vaso, Carolina Orlando [UNESP]; da Silva Pires, Ana Carolina Moreira [UNESP]; de Matos Silva, Samanta [UNESP]; Medina Alarcón, Kaila Petronila [UNESP]; Marcos, Caroline Maria [UNESP]; Fusco-Almeida, Ana Marisa [UNESP]; Mendes-Giannini, Maria José Soares [UNESP]; Universidade Estadual Paulista (UNESP)
    The formation of sessile communities called biofilms is a significant factor in the chronicity of infections caused by different microorganisms, fungi, bacteria, viruses, or protozoa. This phenomenon is considered the major cause of persistent nosocomial infections, of high virulence and recalcitrant to treatments, especially in immunocompromised patients who use devices such as catheters, contact lenses, prostheses, heart valves, dentures, among others. The biofilm phenotype promotes several advantages to microorganisms caused by physical and genetic factors and protects against the host’s immune system through impaired activation of phagocytes and the complement system. In addition, for its eradication, it is necessary to increase the concentration of antibiotics from 100 to 1000 times compared with planktonic cells. It is known that persistent chronic infections in different parts of the human body such as lungs, oral cavity, middle ear, genitourinary tract, nails, surgical or chronic wounds originate from polymicrobial biofilms, which commonly lead to worse prognoses. Interactions between microorganisms are dependent on the environment in which they are found and are highly complex. They can compete antagonistically for nutrients and adhesion sites, but they can coexist in cooperative ways, supporting their mutual development neutrally or synergistically. This chapter will address aspects related to polymicrobial biofilms to unravel the exchange of functions in different interspecies or even in interkingdom conjunctions and their role in pathogenesis.
  • ItemArtigo
    Potential Use of Brazilian Green Propolis Extracts as New Photosensitizers for Antimicrobial Photodynamic Therapy against Cariogenic Microorganisms
    (2023-02-01) de Oliveira, Analú Barros [UNESP]; Ferrisse, Túlio Morandin [UNESP]; França, Gabriela Gomes [UNESP]; de Annunzio, Sarah Raquel [UNESP]; Kopp, Willian [UNESP]; Fontana, Carla Raquel [UNESP]; Brighenti, Fernanda Lourenção [UNESP]; Universidade Estadual Paulista (UNESP)
    The synergic effect of Streptococcus mutans and Candida albicans increases dental caries severity. Antimicrobial photodynamic therapy (aPDT) is a non-invasive treatment for antimicrobial aspects. However, the current photosensitizers (PS) have many downsides for dental applications. This study aimed to evaluate the efficiency of two different Brazilian green propolis (BGP-AF and BGP-AG) as PS for aPDT against these microorganisms. A single-species biofilm was irradiated with crude extracts and their fractions and controls. Such extracts showed the best results and were evaluated in dual-species biofilms. Photodegradation, reactive oxygen species (ROS), cytotoxicity, and color stability assays were also investigated. Reductions higher than 3 log10 CFU/mL (p < 0.0001) occurred for crude BGP in single- and dual-species biofilms. Singlet oxygen was produced in BGP (p < 0.0001). BGP-mediated aPDT delayed S. mutans and C. albicans regrowth after 24 h of treatment (p < 0.0001). Both BGP did not change the color of dental materials (p > 0.05). BGP-AF-mediated aPDT showed 72.41% of oral keratinocyte viability (p < 0.0001). BGP extracts may be used in aPDT against S. mutans and C. albicans. Specifically, BGP-AF may represent a promising PS for dental applications.
  • ItemCapítulo de livro
    Paracoccidioidomycosis: An Update from the Environment to Clinics
    (2022-01-01) de Oliveira, Haroldo Cesar; de Paula e Silva, Ana Carolina Alves [UNESP]; Marcos, Caroline Maria [UNESP]; de Fátima da Silva, Julhiany [UNESP]; Scorzoni, Liliana [UNESP]; Assato, Patricia Akemi [UNESP]; Rossi, Suélen Andreia; Fundação Oswaldo Cruz (Fiocruz-PR); Universidade Estadual Paulista (UNESP); Guarulhos University (UNG); Universidade de São Paulo (USP)
    Paracoccidioidomycosis is an endemic mycosis of great importance in Latin America caused by dimorphic fungi of the genus Paracoccidioides. Recent advances in the study of this mycosis reveal the Paracoccidioides genus as fungi that are difficult to treat and diagnose, with a great capacity to adapt and evade the environment of host cells, causing an invasive disease that is neglected in areas where it is endemic. This chapter aims to provide an overview of the fungi of this genus and the disease, bringing historical aspects and also the most recent advances in the study of this important mycosis, which has a great impact on public health in many countries in Latin America. This chapter will address issues such as the diversity of species of the Paracoccidioides genus, the thermal dimorphism, that allows the fungus to survive in the environment and the host, and its impact on the infectious process, virulence factors, and their relationship with the evasion capacity of the host immune system, as well as aspects associated with the disease such as clinical forms, pathogenesis, epidemiology, diagnosis and treatment.
  • ItemArtigo
    Extracellular lipids of Candida albicans biofilm induce lipid droplet formation and decreased response to a topoisomerase I inhibitor in dysplastic and neoplastic oral cells
    (2022-01-01) Marin-Dett, Freddy Humberto [UNESP]; Campanella, Jonatas Erick Maimoni [UNESP]; Trovatti, Eliane; Bertolini, Maria Célia [UNESP]; Vergani, Carlos Eduardo [UNESP]; Barbugli, Paula Aboud [UNESP]; Universidade Estadual Paulista (UNESP); Universidade de Araraquara (UNIARA)
    Objective: Some microorganisms, i.e., Candida albicans, have been associated with cancer onset and development, although whether the fungus promotes cancer or whether cancer facilitates the growth of C. albicans is unclear. In this context, microbial-derived molecules can modulate the growth and resistance of cancer cells. This study isolated extracellular lipids (ECL) from a 36-h Candida albicans biofilm incubated with oral dysplastic (DOK) and neoplastic (SCC 25) cells, which were further challenged with the topoisomerase I inhibitor camptothecin (CPT), a lipophilic anti-tumoral molecule. Methodology: ECL were extracted from a 36-h Candida albicans biofilm with the methanol/chloroform precipitation method and identified with Nuclear Magnetic Resonance (1H-NMR). The MTT tetrazolium assay measured ECL cytotoxicity in DOK and SCC 25 cells, alamarBlue™ assessed cell metabolism, flow cytometry measured cell cycle, and confocal microscopy determined intracellular features. Results: Three major classes of ECL of C. albicans biofilm were found: phosphatidylinositol (PI), phosphatidylcholine (PC), and phosphatidylglycerol (PG). The ECL of C. albicans biofilm had no cytotoxic effect on neither cell after 24 hours, with a tendency to disturb the SCC 25 cell cycle profile (without statistical significance). The ECL-induced intracellular lipid droplet (LD) formation on both cell lines after 72 hours. In this context, ECL enhanced cell metabolism, decreased the response to CPT, and modified intracellular drug distribution. Conclusion: The ECL (PI, PC, and PG) of 36-h Candida albicans biofilm directly interacts with dysplastic and neoplastic oral cells, highlighting the relevance of better understanding C. albicans biofilm signaling in the microenvironment of tumor cells.
  • ItemArtigo
    In Vitro Evaluation of Photodynamic Activity of Plant Extracts from Senna Species against Microorganisms of Medical and Dental Interest
    (2023-01-01) Oliveira, Analú Barros de [UNESP]; Ferrisse, Túlio Morandin [UNESP]; Annunzio, Sarah Raquel de [UNESP]; Franca, Maria Gleiziane Araújo; Silva, Maria Goretti de Vasconcelos; Cavalheiro, Alberto José [UNESP]; Fontana, Carla Raquel [UNESP]; Brighenti, Fernanda Lourenção [UNESP]; Universidade Estadual Paulista (UNESP); Federal University of Ceará
    Background: Bacterial resistance requires new treatments for infections. In this context, antimicrobial photodynamic therapy (aPDT) is an effective and promising option. Objectives: Three plant extracts (Senna splendida, Senna alata, and Senna macranthera) were evaluated as photosensitizers for aPDT. Methods: Cutibacterium acnes (ATCC 6919), Streptococcus mutans (ATCC 35668), Staphylococcus aureus (ATCC 25923), Escherichia coli (ATCC 25922), and Candida albicans (ATCC 90028) were evaluated. Reactive oxygen species production was also verified. Oral keratinocytes assessed cytotoxicity. LC-DAD-MS analysis identified the chemical components of the evaluated extracts. Results: Most species cultured in the planktonic phase showed total microbial reduction (>6 log10 CFU/mL/p < 0.0001) for all extracts. C. albicans cultured in biofilm showed total microbial reduction (7.68 log10 CFU/mL/p < 0.0001) for aPDT mediated by all extracts. Extracts from S. macranthera and S. alata produced the highest number of reactive oxygen species (p < 0.0001). The S. alata extract had the highest cell viability. The LC-DAD-MS analysis of active extracts showed one naphthopyrone and seven anthraquinones as potential candidates for photoactive compounds. Conclusion: This study showed that aPDT mediated by Senna spp. was efficient in microbial suspension and biofilm of microorganisms of medical and dental interest.
  • ItemResenha
    Nanotechnology-Based Approaches for Voriconazole Delivery Applied to Invasive Fungal Infections
    (2023-01-01) de Almeida Campos, Laís; Fin, Margani Taise; Santos, Kelvin Sousa [UNESP]; de Lima Gualque, Marcos William [UNESP]; Freire Cabral, Ana Karla Lima [UNESP]; Khalil, Najeh Maissar; Fusco-Almeida, Ana Marisa [UNESP]; Mainardes, Rubiana Mara; Mendes-Giannini, Maria José Soares [UNESP]; Midwest State University (UNICENTRO); Universidade Estadual Paulista (UNESP)
    Invasive fungal infections increase mortality and morbidity rates worldwide. The treatment of these infections is still limited due to the low bioavailability and toxicity, requiring therapeutic monitoring, especially in the most severe cases. Voriconazole is an azole widely used to treat invasive aspergillosis, other hyaline molds, many dematiaceous molds, Candida spp., including those resistant to fluconazole, and for infections caused by endemic mycoses, in addition to those that occur in the central nervous system. However, despite its broad activity, using voriconazole has limitations related to its non-linear pharmacokinetics, leading to supratherapeutic doses and increased toxicity according to individual polymorphisms during its metabolism. In this sense, nanotechnology-based drug delivery systems have successfully improved the physicochemical and biological aspects of different classes of drugs, including antifungals. In this review, we highlighted recent work that has applied nanotechnology to deliver voriconazole. These systems allowed increased permeation and deposition of voriconazole in target tissues from a controlled and sustained release in different routes of administration such as ocular, pulmonary, oral, topical, and parenteral. Thus, nanotechnology application aiming to delivery voriconazole becomes a more effective and safer therapeutic alternative in the treatment of fungal infections.
  • ItemArtigo
    Assessment of synergism between enzyme inhibition of Cu/Zn-SOD and antimicrobial photodynamic therapy in suspension and E. coli biofilm
    (2023-03-01) Surur, Amanda Koberstain [UNESP]; Momesso, Vinícius Medeiros [UNESP]; Lopes, Pedro Monteiro [UNESP]; Ferrisse, Túlio Morandin [UNESP]; Fontana, Carla Raquel [UNESP]; Universidade Estadual Paulista (UNESP)
    Background: Antimicrobial Photodynamic Therapy (aPDT) is a treatment based on the interaction between a photosensitizer (PS), oxygen and i a light source, resulting in the production of reactive oxygen species (ROS). There are two main types of reactions that can be triggered by this interaction: type I reaction, which can result in the production of hydrogen peroxide, superoxide anion and hydroxyl radical, and type II reaction, which is the Photodynamic Reaction, which results in singlet oxygen production. Antioxidant enzymes (e.g., catalase and superoxide dismutase) are agents that help prevent the damage caused by ROS and, consequently, reduce the effectiveness of aPDT. The aim of this study was to evaluate a possible synergism of the combined inhibition therapy of the enzyme Cu/Zn-Superoxide dismutase (SOD) and the methylene blue- and curcumin-mediated aPDT against Escherichia coli ATCC 25922, in suspension and biofilm. Methods: Kinetic assay of antimicrobial activity of diethydithiocarbamate (DDC) and Minimum Bactericidal Concentration (MIC) of DDC were performed to evaluate the behavior of the compound on bacterial suspension. Inhibition times of Cu/Zn-SOD, as well as DDC concentration, were evaluated via bacterial susceptibility to combined therapy in suspension and biofilm. Results: DDC did not present MIC at the evaluated concentrations. The inhibition time and Cu/Zn-SOD concentration with the highest bacterial reductions were 30 minutes and 1.2 μg/mL, respectively. Synergism occurred between DDC and MB-mediated aPDT, but not with CUR-mediated aPDT. Conclusions: The synergism between Cu/Zn-SOD inhibition and aPDT has been confirmed, opening up a new field of study full of possibilities.
  • ItemArtigo
    Regenerated cellulose sponge as sacrificial template for the synthesis of three-dimensional porous alumina-silica scaffold for tissue engineering
    (2023-07-01) Claro, Amanda Maria; Alves, Caroline Cássia; dos Santos, Kelvin Sousa [UNESP]; da Rocha, Euzane Gomes; de Lima Fontes, Marina; Monteiro, Gustavo Claro; de Carvalho, Gustavo Senra Gonçalves; Caiut, José Maurício Almeida; Moroz, Andrei [UNESP]; Ribeiro, Sidney José Lima [UNESP]; S. Barud, Hernane; University of Araraquara—UNIARA; Universidade de São Paulo (USP); Universidade Estadual Paulista (UNESP)
    Tissue engineering has emerged as a multidisciplinary field that aims to improve health and quality of life by restoring functions of tissues and organs. Cells and scaffolds are the two major components of tissue engineering. Scaffolds act as a support for cells, thus facilitating cell adhesion, proliferation, morphogenesis, differentiation, and extracellular matrix production. Since three-dimensional (3D) porous scaffolds can better simulate the native 3D architecture of in vivo systems than conventional 2D cultures, they are more appropriate to support tissue regeneration. This study aimed to use regenerated cellulose sponge (RCS) as sacrificial template for the synthesis of three-dimensional porous alumina-silica scaffold (ASS). RCS was coated with boehmite-GPTS (3-glycidoxypropyltrimethoxysilane) solution and dried at 60 °C for 12 h. The coated RCS was converted into porous alumina-silica scaffold via thermal treatment at 500 °C for 4 h in air. The materials were characterized by Fourier transform‐infrared (FT‐IR), X-Ray diffraction (XRD), thermogravimetric analysis (TGA) aluminum-27 and silicon-29 nuclear magnetic resonance (NMR), scanning electron microscopy, and energy dispersive X-ray spectroscopy (SEM-EDS). The MTT metabolism assays were used to evaluate indirectly cytocompatibility and cell proliferation using MCT3T3-E1, HDFa and HaCaT cells. The biological in vitro assays demonstrated that only RCS exhibited toxicity toward HDFa cells, although this behavior has been shown questionable once other studies have reported the non-cytotoxic, mutagenic and genotoxic potential of RCS. We believe that tests including clonogenic and mutagenic assays should be performed using HDFa cells in contact with RCS-derived extract in order to further investigate this behavior. The sponge materials have demonstrated different growth rate and adhesion to three different cell lines evaluated. Therefore, the employed sacrificial template approach presents as a viable alternative to produce 3D scaffolds for tissue engineering. Graphical abstract: [Figure not available: see fulltext.]