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Item (MeOPhSe)2, a synthetic organic selenium compound, inhibits virulence factors of Candida krusei: Adherence to cervical epithelial cells and biofilm formation(Elsevier GmbH.) Siqueira, Victor Mendes de; Silva, Bruna Graziele Marques da; Passos, Juliene Cristina da Silva; Pinto, Ana Paula; Rocha, João Batista Teixeira da; Silva, Carlos Alberto; Costa, Maricília SilvaBackground: Systemic candidiasis is produced by Candida albicans or non-albicans Candida species, opportunistic fungi that produce both superficial and invasive infections. Despite the availability of a wide range of antifungal agents for the treatment of candidiasis, failure of therapy is observed frequently, which opens new avenues in the field of alternative therapeutic strategies. Methods: The effects of p,p′ -methoxyl-diphenyl diselenide [(MeOPhSe)2], a synthetic organic selenium (organochalcogen) compound, were investigated on virulence factors of C. krusei and compared with its antifungal effects on the virulence factors related to adhesion to cervical epithelial cell surfaces with C. albicans. Results: (MeOPhSe)2, a compound non-toxic in epithelial (HeLa) and fibroblastic (Vero) cells, inhibited the growth in a dose-dependent manner and changed the kinetics parameters of C. krusei and, most importantly, extending the duration of lag phase of growth, inhibiting biofilm formation, and changing the structure of biofilm. Also, (MeOPhSe)2 reduced C. albicans and C. krusei adherence to cervical epithelial cells, an important factor for the early stage of the Candida-host interaction. The reduction was 37.24 ± 2.7 % in C. krusei (p = 0.00153) and 32.84 ± 3.2 % in C. albicans (p = 0.0072) at 20 μM (MeOPhSe)2, and the effect is in a concentration-dependent manner. Surprisingly, the antifungal potential on adhesion was similar between both species, indicating the potential of (MeOPhSe)2 as a promising antifungal drug against different Candida infections. Conclusion: Overall, we demonstrated the potential of (MeOPhSe)2 as an effective antifungal drug against the virulence factors of Candida species.Item Local envenomation caused by a bioactive peptide fraction of Bothrops jararaca snake venom induces leukocyte influx in the lung and changes in pulmonary mechanics(Elsevier) Silva, Carlos Alberto; Querobino, Samyr Machado; Silva, Cesar Augusto Melo; Costa, Maricilia Silva; Oliveira, Luis Vicente Franco; Zamuner, Stella ReginaThe crude venom of the Bothrops jararaca snake (Bj-CV) is a complex mixture of biologically active proteins that includes a variety of peptides in the low molecular weight fraction (Bj-PF). We investigated how an intramuscular injection of Bj-CV (1.2 mg kg−1) and Bj-PF (0.24 mg kg−1) influenced lung mechanics and lung and muscle inflammation in male Swiss mice 15 min, 1, 6, and 24 h after inoculation. Pressure dissipation against lung resistive components (ΔP1) rose significantly from 1 to 24 h after Bj-CV and 6–24 h after Bj-PF inoculation. Both Bj-CV and Bj-PF increased the total pressure variation of the lung (ΔPtot) 24 h after injection. Lung static elastance increased significantly after injection in all time periods investigated by Bj-CV and from 6 to 24 h by Bj-PF. Lung static elastance increased significantly after injection in all time periods investigated by Bj-CV and from 6 to 24 h by Bj-PF. Furthermore, intramuscular inoculation of Bj-CV and Bj-PF resulted in an increase in muscle and pulmonary inflammation, as evidenced by an increase in leukocyte influx when compared to the control group. Finally, both Bj-CV and Bj-PF cause acute lung injury, as shown by pulmonary inflammation and decreased lung mechanics. Furthermore, the fact that Bj-PF produces mechanical alterations in the lungs and muscular inflammation implies that non-enzymatic compounds can cause inflammation.Item Diphenyl diselenide suppresses key virulence factors of Candida krusei, a neglected fungal pathogen(Taylor & Francis) Silva, Bruna Graziele Marques da; Pinto, Ana Paula; Passos, Juliene Cristina da Silva; Rocha, João Batista Teixeira da; Silva, Carlos Alberto; Costa, Maricilia SilvaCandida krusei is a candidiasis etiological agent of relevance in the clinical setting because of its intrinsic resistance to fluconazole. Also, it has opened up new paths in the area of alternative therapeutic techniques. This project demonstrated the effects of diphenyl diselenide (PhSe)2 and p-cloro diphenyl diselenide (pCl-PhSe)2, two organochalcogen compounds, on relevant virulence factors for the early stage of the C. krusei host interaction and infection process. Both com- pounds inhibited adherence of C. krusei to both polystyrene surfaces and cervical epithelial cells and biofilm formation; the structure of the biofilm was also changed in a dose-dependent man- ner. In addition, both compounds inhibited C. krusei growth, but (PhSe)2 significantly increased the time duration of the lag phase and delayed the start of the exponential phase in growth kinetics. (PhSe)2 has more potential antifungal activity than (pCl-PhSe)2 in inhibiting the adher- ence to epithelial cells, biofilm formation, and growth of C. krusei.Item (PhSe)2 and (pCl-PhSe)2 organochalcogen compounds inhibit Candida albicans adhesion to human endocervical (HeLa) cells and show anti- biofilm activities(Taylor & Francis) Silva, Bruna Marques da; Braga, Marília Toledo; Passos, Juliene Cristina da Silva; Carvalho, Moisés Lopes; Rosseti, Isabela Bueno; Amorim, Laís Mayara Machado de; Rocha, João Batista Teixeira da; Silva, Carlos Alberto; Costa, Maricilia SilvaAdhesion capacity on biological surfaces and biofilm formation is considered an important step in the infection process by Candida albicans. The ability of (PhSe)2 and (pCl-PhSe)2, two synthetic organic selenium (organochalcogen) compounds, to act on C. albicans virulence factors related to adhesion to human endocervical (HeLa) cell surfaces and their anti-biofilm activities was ana- lyzed. Both organochalcogen compounds inhibited C. albicans adhesion to HeLa cells, depend- ent on compound concentrations. (PhSe)2 (at 20 mM; p 1⁄4 0.0012) was significantly more effective than (pCl-PhSe)2 (at 20 mM; p 1⁄4 0.0183) compared with the control. (PhSe)2 inhibited biofilm for- mation and decreased biofilm viability in both early and mature biofilms more efficiently than (pCl-PhSe)2. Overall, the organochalcogen compounds, especially (PhSe)2, were demonstrated to be effective antifungal drugs against C. albicans virulence factors related to epithelial cell surface adhesion and the formation and viability of biofilms.Item Anti‐inflammatory effect of photobiomodulation in the brain following local peripheral carrageenan‐induced inflammation(Springer) Silva, Carlos Alberto; Calvi, Gabriela de Souza; Feliciano, Regiane dos Santos; Silva Junior, José Antônio; Costa, Maricilia SilvaPurpose Photobiomodulation (PBM) has been suggested as a potential anti-inflammatory therapy, presenting excellent outcomes for several disorders. Reduction in COX-2 mRNA expression in subplantar and brain tissues by PBM was dem- onstrated, using the classic model of oedema formation and hyperalgesia induced by Carrageenan (Carr). This work inves- tigated the effect of PBM on mRNA expression of key inflammation-related genes (IL-1β, mPGES-1, mPGES-2 and EP) in subplantar and brain tissues obtained from rats receiving Carr. Methods The animals were treated with Carr, treated with PBM after 1 h and sacrificed after 1, 3 and 6 h. The light source used was a diode laser, with output power of 30 mW and a wavelength of 660 nm. The laser beam illuminated an area of 0.785 cm2, resulting in an energy dosage of 7.5 J/cm2, applied for 196 s. IL-1β, mPGES-1, mPGES-2 and EP mRNAs were determined by RT-PCR. Results It was observed a reduction in IL-1β expression as in subplantar tissue as in brain parenchyma in animals treated with PBM. In addition, the expression of both mPGES-1 and mPGES-2 mRNA was decreased after PBM. Conclusion These results suggested that PBM could reduce the production of IL-1β and subsequently decreasing the effects of PGE2. Therefore, the possible mechanism by which PBM alleviates hyperalgesia could involve its ability to decrease the expression of inflammatory markers in the CNS, reducing the production of PGE2 in the spinal cord.Item Small Structural Differences in Proline-Rich Decapeptides Have Specific Effects on Oxidative Stress-Induced Neurotoxicity and L-Arginine Generation by Arginosuccinate Synthase(MDPI) Silva, Carlos Alberto; Silva, Brenda Rufino; Silva, Julio Cezar Araujo; Silva, Felipe Assumpção da Cunha e; Kodama, Roberto Tadashi; Silva, Wilmar Dias da; Costa, Maricilia Silva; Portaro, Fernanda Calheta Vieirantroduction. The proline-rich decapeptide 10c (Bj-PRO-10c; ENWPHPQIPP) from the Bothrops jararaca snake modulates argininosuccinate synthetase (AsS) activity to stimulate L-arginine metabolite production and neuroprotection in the SH-SY5Y cell line. The relationships between structure, interactions with AsS, and neuroprotection are little known. We evaluated the neuro- protective effects of Bj-PRO-10c and three other PROs (Bn-PRO-10a, Bn-PRO-10c > Bn-PRO-10a-MK > Bn-PRO-10a. The structure of PROs and their correlations with enzyme activity revealed that histidine (H5) and glutamine (Q7) in Bj-PRO-10c potentiated their affinity for AsS. Conclusions. Our investigation provides the first insights into the structure and molecular interactions of PROs with AsS, which could possibly further their neuropharmacological applications.Item The arrangement of dual-species biofilms of Candida albicans and Issatchenkia orientalis can be modified by the medium: effect of Voriconazole(Taylor & Francis) Passos, Juliene Cristina da Silva; Rodrigues, Ana Beatriz Furtado; Silva, Carlos Alberto; Costa, Maricilia SilvaBoth Candida albicans and Issatchenkia orientalis have been isolated from different types of infections over the years. They have the ability to form communities of microorganisms known as biofilms. It has been demonstrated that the medium employed in studies may affect the biofilm development. The aim of this study was to investigate the arrangement of dual-species biofilms of C. albicans and I. orientalis cultivated on either RPMI-1640 or Sabouraud Dextrose Broth (SDB), as well as the inhibitory effect of Voriconazole (VRC). For the experiments performed, ATCC strains were used, and yeast-mixed suspensions were inoculated in 96-well plates with either RPMI-1640 or SDB, in the presence or absence of VRC. The results were observed by counting the number of CFU obtained from scraping off the biofilms produced and plating the content on CHROMagar Candida medium. It was observed that for all conditions tested the medium chosen affected the arrangement of dual-species biofilms: when RPMI-1640 was used, there was a prevalence of C. albicans, while the opposite was noted when SDB was used. It could be suggested that the medium and environment could regulate interactions between both yeast species, including the response to different antifungal drugs.