Artigos - Biologia - IBILCE

URI Permanente para esta coleção


Submissões Recentes

Agora exibindo 1 - 20 de 1522
  • ItemArtigo
    The Dimeric Peptide (KKYRYHLKPF)2K Shows Broad-Spectrum Antiviral Activity by Inhibiting Different Steps of Chikungunya and Zika Virus Infection
    (2023-05-01) Ayusso, Gabriela Miranda ; Lima, Maria Letícia Duarte ; da Silva Sanches, Paulo Ricardo ; Santos, Igor Andrade ; Martins, Daniel Oliveira Silva ; da Conceição, Pâmela Jóyce Previdelli ; Carvalho, Tamara ; da Costa, Vivaldo Gomes ; Bittar, Cíntia ; Merits, Andres ; Santos-Filho, Norival Alves ; Cilli, Eduardo Maffud ; Jardim, Ana Carolina Gomes ; de Freitas Calmon, Marilia ; Rahal, Paula ; Universidade Estadual Paulista (UNESP) ; Universidade Federal de Uberlândia (UFU) ; The Rockefeller University ; University of Tartu
    Chikungunya virus (CHIKV) and Zika virus (ZIKV) are important disease-causing agents worldwide. Currently, there are no antiviral drugs or vaccines approved to treat these viruses. However, peptides have shown great potential for new drug development. A recent study described (p-BthTX-I)2K [(KKYRYHLKPF)2K], a peptide derived from the Bothropstoxin-I toxin in the venom of the Bothrops jararacussu snake, showed antiviral activity against SARS-CoV-2. In this study, we assessed the activity of this peptide against CHIKV and ZIKV and its antiviral action in the different stages of the viral replication cycle in vitro. We observed that (p-BthTX-I)2K impaired CHIKV infection by interfering with the early steps of the viral replication cycle, reducing CHIKV entry into BHK-21 cells specifically by reducing both the attachment and internalization steps. (p-BthTX-I)2K also inhibited the ZIKV replicative cycle in Vero cells. The peptide protected the cells against ZIKV infection and decreased the levels of the viral RNA and the NS3 protein of this virus at viral post-entry steps. In conclusion, this study highlights the potential of the (p-BthTX-I)2K peptide to be a novel broad-spectrum antiviral candidate that targets different steps of the replication cycle of both CHIKV and ZIKV.
  • ItemArtigo
    The degradation of chicken feathers by Ochrobactrum intermedium results in antioxidant and metal chelating hydrolysates and proteolytic enzymes for staphylococcal biofilm dispersion
    (2023-06-01) de Menezes, Cíntia Lionela Ambrosio ; Boscolo, Maurício ; da Silva, Roberto ; Gomes, Eleni ; da Silva, Ronivaldo Rodrigues ; Universidade Estadual Paulista (UNESP)
    The increase in the generation of chicken feathers, due to the large production of the poultry industry, has created the need to search for ecologically safer ways to manage these residues. As a sustainable alternative for recycling keratin waste, we investigated the ability of the bacterium Ochrobactrum intermedium to hydrolyze chicken feathers and the valorization of the resulting enzymes and protein hydrolysate. In submerged fermentation with three different inoculum sizes (2.5, 5.0, and 10.0 mg of bacterial cells per 50 mL of medium), the fastest degradation of feathers was achieved with 5.0 mg cells, in which a complete decomposition of the substrate (96 h) and earlier peaks of keratinolytic and caseinolytic activities were detected. In the resulting protein hydrolysate, we noticed antioxidant and Fe2+ and Cu2+ chelating activities. ABTS scavenging, Fe3+-reducing ability and metal chelating activities of the fermentative samples followed the same trend of feather degradation; as feather mass decreased in the media, these activities increased. Furthermore, we noticed about 47% and 60% dispersion of established 7-day biofilms formed by S. aureus after enzymatic treatment for 5 h and 24 h, respectively. These findings highlight the potential use of this bacterium as an environmentally friendly alternative to treat this poultry waste and offer valuable products.
  • ItemArtigo
    The impacts of exposure to bisphenol A in the adult female prostate Meriones unguiculatus
    (2023-08-01) Bedolo, Carolina Marques ; Ruiz, Thalles Fernando Rocha ; Amaro, Gustavo Matheus ; Vilamaior, Patricia Simone Leite ; Leonel, Ellen Cristina Rivas ; Taboga, Sebastião Roberto ; Campos, Silvana Gisele Pegorin de ; Universidade Estadual Paulista (UNESP) ; Universidade Estadual de Campinas (UNICAMP) ; Universidade Federal de Goiás (UFG)
    The female prostate is associated with the urogenital system and presents homology in morphological terms with the male prostate. Due to its responsiveness to endogenous hormones, this gland is under a constant risk of developing prostatic pathologies and neoplasia when exposed to certain exogenous compounds. Bisphenol A (BPA) is an endocrine disruptor found in different plastic and resin products. Studies have emphasized the effects of perinatal exposure to this compound on different hormone-responsive organs. However, there have been few studies highlighting the influence on female prostate morphology of perinatal exposure to BPA. The objective of this study was to describe the histopathological alterations caused by perinatal exposure to BPA (50 µg/kg) and 17-β estradiol (E2) (35 µg/kg) in the prostate of adult female gerbils. The results showed that E2 and BPA induced proliferative lesions in the female prostate and acted along similar pathways by modulating steroid receptors in the epithelium. BPA was also found to be a pro-inflammatory and pro-angiogenic agent. The impacts of both agents were marked in the prostatic stroma. An increase in the thickness of the smooth muscle layer and a decrease in AR expression were observed, but no alterations in the expression of ERα and ERβ, leading to estrogenic sensitivity of the prostate. However, a peculiar response of the female prostate was to diminish the collagen frequency under BPA exposure correlated to smooth muscle layer. These data therefore indicate the development of features related to estrogenic and non-estrogenic tissue repercussions by BPA perinatally exposure in gerbil female prostate.
  • ItemArtigo
    Functional characteristics of an α-L-arabinofuranosidase secreted by the basidiomycete Coriolopsis byrsina
    (2023-01-01) de Oliveira Nascimento, Carlos Eduardo ; de Menezes, Cíntia Lionela Ambrosio ; Boscolo, Maurício ; da Silva, Roberto ; Gomes, Eleni ; da Silva, Ronivaldo Rodrigues ; Universidade Estadual Paulista (UNESP)
    α-L-arabinofuranosidases can be produced by fungi, bacteria, and plants and are responsible for the cleavage of α-1,2, α-1,3, and α-1,5 glycosidic bonds in arabinose residues. Few recent studies have focused on the production of these enzymes by species of basidiomycetes. In the present study, we purified an α-L-arabinofuranosidase from the fungus Coriolopsis byrsina and evaluated its functional biochemical properties. The purified enzyme had an estimated molecular mass of 55 kDa with maximum activity at pH 3.5–4.5 and 50 °C, stability in the range of pH 3–8 at 4 °C for 24 h, and from 10 to 60 °C for 1 h. The enzyme was also stable in 5–10% ethanol after 24 h at 28 °C, retaining more than 60% activity. A negative effect on catalysis was noted for all evaluated ions, especially Fe3+ and Hg2+, retaining 25% and 33% activity, respectively, at 10 mmol L−1, and L-arabinose, with 50% activity at 0.2 mol L−1 and 30% at 0.9 mol L−1. The enzyme was active on p-nitrophenyl-α-L-arabinofuranoside (pNPA), p-nitrophenyl-β-D-xylopyranoside, linear 1,5 α-L-arabinan and xylan from beechwood. Kinetic assays under pNPA substrate indicated a KM of 3.45 ± 0.9 mmol L−1 and Vmax of 198.2 ± 24 μmol min−1 mg−1. These findings can serve as a reference for further tests of this enzyme aimed at improving the aroma of beverages and formulating enzyme cocktails for plant biomass degradation.
  • ItemArtigo
    Identification of Zika Virus NS1-Derived Peptides with Potential Applications in Serological Tests
    (2023-03-01) Prudencio, Carlos Roberto ; Gomes da Costa, Vivaldo ; Rocha, Leticia Barboza ; da Costa, Hernan Hermes Monteiro ; Orts, Diego José Belato ; da Silva Santos, Felipe Rocha ; Rahal, Paula ; Lino, Nikolas Alexander Borsato ; da Conceição, Pâmela Jóyce Previdelli ; Bittar, Cintia ; Machado, Rafael Rahal Guaragna ; Durigon, Edison Luiz ; Araujo, João Pessoa ; Polatto, Juliana Moutinho ; da Silva, Miriam Aparecida ; de Oliveira, Joyce Araújo ; Mitsunari, Thais ; Pereira, Lennon Ramos ; Andreata-Santos, Robert ; de Souza Ferreira, Luís Carlos ; Luz, Daniela ; Piazza, Roxane Maria Fontes ; Instituto Adolfo Lutz ; Universidade Estadual Paulista (UNESP) ; Instituto Butantan ; Universidade de São Paulo (USP)
    Zika virus (ZIKV), a mosquito-borne pathogen, is an emerging arbovirus associated with sporadic symptomatic cases of great medical concern, particularly among pregnant women and newborns affected with neurological disorders. Serological diagnosis of ZIKV infection is still an unmet challenge due to the co-circulation of the dengue virus, which shares extensive sequence conservation of structural proteins leading to the generation of cross-reactive antibodies. In this study, we aimed to obtain tools for the development of improved serological tests for the detection of ZIKV infection. Polyclonal sera (pAb) and a monoclonal antibody (mAb 2F2) against a recombinant form of the ZIKV nonstructural protein 1 (NS1) allowed the identification of linear peptide epitopes of the NS1 protein. Based on these findings, six chemically synthesized peptides were tested both in dot blot and ELISA assays using convalescent sera collected from ZIKV-infected patients. Two of these peptides specifically detected the presence of ZIKV antibodies and proved to be candidates for the detection of ZIKV-infected subjects. The availability of these tools opens perspectives for the development of NS1-based serological tests with enhanced sensitivity regarding other flaviviruses.
  • ItemArtigo
    Karyotype Evolution in Triatominae (Hemiptera, Reduviidae): The Role of Chromosomal Rearrangements in the Diversification of Chagas Disease Vectors
    (2023-04-01) Reis, Yago Visinho dos ; de Oliveira, Jader ; Madeira, Fernanda Fernandez ; Ravazi, Amanda ; Oliveira, Ana Beatriz Bortolozo de ; Bittinelli, Isadora da Silva ; Delgado, Luiza Maria Grzyb ; de Azeredo-Oliveira, Maria Tercília Vilela ; Rosa, João Aristeu da ; Galvão, Cleber ; Alevi, Kaio Cesar Chaboli ; Universidade Estadual Paulista (UNESP) ; Universidade de São Paulo (USP) ; Instituto Oswaldo Cruz (FIOCRUZ)
    Several cytogenetic studies have already been performed in Triatominae, such that different karyotypes could be characterized (ranging from 2n = 21 to 25 chromosomes), being the changes in the number of chromosomes related mainly to fusion and fission events. These changes have been associated with reproductive isolation and speciation events in other insect groups. Thus, we evaluated whether different karyotypes could act in the reproductive isolation of triatomines and we analyzed how the events of karyotypic evolution occurred along the diversification of these vectors. For this, experimental crosses were carried out between triatomine species with different karyotypes. Furthermore, based on a phylogeny with 88 triatomine taxa (developed with different molecular markers), a reconstruction of ancestral karyotypes and of anagenetic and cladogenetic events related to karyotypic alterations was performed through the ChromoSSE chromosomal evolution model. All crosses performed did not result in hybrids (prezygotic isolation in both directions). Our modeling results suggest that during Triatominae diversification, at least nine cladogenetic events may be associated with karyotype change. Thus, we emphasize that these alterations in the number of chromosomes can act as a prezygotic barrier in Triatominae (karyotypic isolation), being important evolutionary events during the diversification of the species of Chagas disease vectors.
  • ItemResenha
    β-glucosidase: An overview on immobilization and some aspects of structure, function, applications and cost
    (2023-07-01) Mól, Paula Chequer Gouveia ; Júnior, José Carlos Quilles ; Veríssimo, Lizzy Ayra Alcântara ; Boscolo, Mauricio ; Gomes, Eleni ; Minim, Luis Antonio ; Da Silva, Roberto ; Universidade Estadual Paulista (UNESP) ; Universidade de São Paulo (USP) ; Federal University of Lavras ; Federal University of Vicosa
    β-glucosidases constitute a heterogeneous group of well-characterized and biologically important hydrolytic enzymes which act on different substrates. They have been widely utilized in biotechnology. Nowadays, immobilized β-glucosidase has become one of the most important biocatalytic systems used for many industrial purposes, especially in the biofuel, food, pharmaceutical and beverage industries. Immobilized β-glucosidase has the advantages of usually being chemically and thermally more stable, easily separated from the product, possible to reuse and can replace chemical catalysts in some industrial applications. From both a scientific and application point of view, interest in developing new support materials and new protocols for β-glucosidase immobilization has grown. This review focused on originality and novelty on how an immobilization system for β-glucosidases should be and what is missing for really efficient applications. For that, the main methods used for the immobilization of β-glucosidase and the description of the different support materials, with emphasis on their advantages and disadvantages; the main physical-chemical characteristics of immobilized enzymes; the applications of the pure or mixed immobilized enzyme; and a discussion on the β-glucosidase market and cost are presented. Finally, the overall conclusion is given along with a mention of perspectives and future directions.
  • ItemArtigo
    Bisphenol A disruption promotes mammary tumor microenvironment via phenotypic cell polarization and inflammatory response
    (2023-06-01) Ruiz, Thalles F. R. ; Colleta, Simone J. ; dos Santos, Diego D. ; Castro, Nayara F. C. ; Cabral, Ágata S. ; Calmon, Marilia F. ; Rahal, Paula ; Gil, Cristiane D. ; Girol, Ana Paula ; Vilamaior, Patricia S. L. ; Leonel, Ellen C. R. ; Taboga, Sebastião R. ; Universidade Estadual Paulista (UNESP) ; Universidade de São Paulo (USP) ; University Center Padre Albino (UNIFIPA) ; Universidade Federal de Goiás (UFG)
    Inflammation in the established tumor microenvironment (TME) is often associated with a poor prognosis of breast cancer. Bisphenol A (BPA) is an endocrine-disrupting chemical that acts as inflammatory promoter and tumoral facilitator in mammary tissue. Previous studies demonstrated the onset of mammary carcinogenesis at aging when BPA exposure occurred in windows of development/susceptibility. We aim to investigate the inflammatory repercussions of BPA in TME in mammary gland (MG) during neoplastic development in aging. Female Mongolian gerbils were exposed to low (50 µg/kg) or high BPA (5000 µg/kg) doses during pregnancy and lactation. They were euthanized at 18 months of age (aging) and the MG were collected for inflammatory markers and histopathological analysis. Contrarily to control MG, BPA induced carcinogenic development mediated by COX-2 and p-STAT3 expression. BPA was also able to promote macrophage and mast cell (MC) polarization in tumoral phenotype, evidenced by pathways for recruitment and activation of these inflammatory cells and tissue invasiveness triggered by tumor necrosis factor-alpha and transforming growth factor-beta 1 (TGF-β1). Increase of tumor-associated macrophages, M1 (CD68 + iNOS+) and M2 (CD163+) expressing pro-tumoral mediators and metalloproteases was observed; this aspect greatly contributed to stromal remodeling and invasion of neoplastic cells. In addition, the MC population drastically increased in BPA-exposed MG. Tryptase-positive MCs increased in disrupted MG and expressed TGF-β1, contributing to EMT process during carcinogenesis mediated by BPA. BPA exposure interfered in inflammatory response by releasing and enhancing the expression of mediators that contribute to tumor growth and recruitment of inflammatory cells that promote a malignant profile.
  • ItemArtigo
    Xylose consumption and ethanol production by Pichia guilliermondii and Candida oleophila in the presence of furans, phenolic compounds, and organic acids commonly produced during the pre-treatment of plant biomass
    (2023-06-01) da Silva, Ronivaldo Rodrigues ; Zaiter, Mohammed Anas ; Boscolo, Maurício ; da Silva, Roberto ; Gomes, Eleni ; Universidade Estadual Paulista (UNESP)
    For 2G ethanol production, pentose fermentation and yeast tolerance to lignocellulosic hydrolyzate components are essential to improve biorefinery yields. Generally, physicochemical pre-treatment methodologies are used to facilitate access to cellulose and hemicellulose in plant material, which consequently can generate microbial growth inhibitory compounds, such as furans, weak acids, and phenolic compounds. Because of the unsatisfactory yield of wild-type Saccharomyces cerevisiae during pentose fermentation, the search for xylose-fermenting yeasts tolerant to microbial growth inhibitors has gained attention. In this study, we investigated the ability of the yeasts Pichia guilliermondii G1.2 and Candida oleophila G10.1 to produce ethanol from xylose and tolerate the inhibitors furfural, 5-hydroxymethylfurfural (HMF), acetic acid, formic acid, ferulic acid, and vanillin. We demonstrated that both yeasts were able to grow and consume xylose in the presence of all single inhibitors, with greater growth limitation in media containing furfural, acetic acid, and vanillin. In saline medium containing a mixture of these inhibitors (2.5–3.5 mM furfural and HMF, 1 mM ferulic acid, 1–1.5 mM vanillin, 10–13 mM acetic acid, and 5–7 mM formic acid), both yeasts were able to produce ethanol from xylose, similar to that detected in the control medium (without inhibitors). In future studies, the proteins involved in the transport of pentose and tolerance to these inhibitors need to be investigated.
  • ItemArtigo
    Photodynamic therapy reduces cell viability, migration and triggers necroptosis in prostate tumor cells
    (2023-01-01) de Melo Gomes, Laura Calazans ; de Oliveira Cunha, Amanda Branquinho ; Peixoto, Luiz Felipe Fernandes ; Zanon, Renata Graciele ; Botelho, Françoise Vasconcelos ; Silva, Marcelo José Barbosa ; Pinto-Fochi, Maria Etelvina ; Góes, Rejane Maira ; de Paoli, Flávia ; Ribeiro, Daniele Lisboa ; Universidade Federal de Uberlândia (UFU) ; São José Do Rio Preto-São Paulo ; Universidade Estadual Paulista (UNESP) ; Federal University of Juiz de Fora-UFJF
    Prostate cancer is the most common cancer in American men, aside from skin cancer. As an alternative cancer treatment, photodynamic laser therapy (PDT) can be used to induce cell death. We evaluated the PDT effect, using methylene blue as a photosensitizer, in human prostate tumor cells (PC3). PC3 were subjected to four different conditions: DMEM (control); laser treatment (L—660 nm, 100 mW, 100−2); methylene blue treatment (MB—25 μM, 30 min), and MB treatment followed by low-level red laser irradiation (MB-PDT). Groups were evaluated after 24 h. MB-PDT treatment reduced cell viability and migration. However, because MB-PDT did not significantly increase the levels of active caspase-3 and BCL-2, apoptosis was not the primary mode of cell death. MB-PDT, on the other hand, increased the acid compartment by 100% and the LC3 immunofluorescence (an autophagy marker) by 254%. Active MLKL level, a necroptosis marker, was higher in PC3 cells after MB-PDT treatment. Furthermore, MB-PDT resulted in oxidative stress due to a decrease in total antioxidant potential, catalase levels, and increased lipid peroxidation. According to these findings, MB-PDT therapy is effective at inducing oxidative stress and reducing PC3 cell viability. In such therapy, necroptosis is also an important mechanism of cell death triggered by autophagy. Graphical Abstract: [Figure not available: see fulltext.]
  • ItemArtigo
    High SARS-CoV-2 tropism and activation of immune cells in the testes of non-vaccinated deceased COVID-19 patients
    (2023-12-01) Costa, Guilherme M. J. ; Lacerda, Samyra M. S. N. ; Figueiredo, André F. A. ; Wnuk, Natália T. ; Brener, Marcos R. G. ; Andrade, Lídia M. ; Campolina-Silva, Gabriel H. ; Kauffmann-Zeh, Andrea ; Pacifico, Lucila G. G. ; Versiani, Alice F. ; Antunes, Maísa M. ; Souza, Fernanda R. ; Cassali, Geovanni D. ; Caldeira-Brant, André L. ; Chiarini-Garcia, Hélio ; de Souza, Fernanda G. ; Costa, Vivian V. ; da Fonseca, Flavio G. ; Nogueira, Maurício L. ; Campos, Guilherme R. F. ; Kangussu, Lucas M. ; Martins, Estefânia M. N. ; Antonio, Loudiana M. ; Bittar, Cintia ; Rahal, Paula ; Aguiar, Renato S. ; Mendes, Bárbara P. ; Procópio, Marcela S. ; Furtado, Thiago P. ; Guimaraes, Yuri L. ; Menezes, Gustavo B. ; Martinez-Marchal, Ana ; Orwig, Kyle E. ; Brieño-Enríquez, Miguel ; Furtado, Marcelo H. ; Universidade Federal de Minas Gerais (UFMG) ; Clínica MF Fertilidade Masculina ; Faculdade de Medicina de São Jose do Rio Preto ; University of Texas Medical Branch ; University of Pittsburgh School of Medicine ; Centro de Desenvolvimento da Tecnologia Nuclear-CDTN/CNEN ; Universidade Estadual Paulista (UNESP)
    Background: Cellular entry of SARS-CoV-2 has been shown to rely on angiotensin-converting enzyme 2 (ACE2) receptors, whose expression in the testis is among the highest in the body. Additionally, the risk of mortality seems higher among male COVID-19 patients, and though much has been published since the first cases of COVID-19, there remain unanswered questions regarding SARS-CoV-2 impact on testes and potential consequences for reproductive health. We investigated testicular alterations in non-vaccinated deceased COVID-19-patients, the precise location of the virus, its replicative activity, and the immune, vascular, and molecular fluctuations involved in the pathogenesis. Results: We found that SARS-CoV-2 testicular tropism is higher than previously thought and that reliable viral detection in the testis requires sensitive nanosensors or RT-qPCR using a specific methodology. Through an in vitro experiment exposing VERO cells to testicular macerates, we observed viral content in all samples, and the subgenomic RNA’s presence reinforced the replicative activity of SARS-CoV-2 in testes of the severe COVID-19 patients. The cellular structures and viral particles, observed by transmission electron microscopy, indicated that macrophages and spermatogonial cells are the main SARS-CoV-2 lodging sites, where new virions form inside the endoplasmic reticulum Golgi intermediate complex. Moreover, we showed infiltrative infected monocytes migrating into the testicular parenchyma. SARS-CoV-2 maintains its replicative and infective abilities long after the patient’s infection. Further, we demonstrated high levels of angiotensin II and activated immune cells in the testes of deceased patients. The infected testes show thickening of the tunica propria, germ cell apoptosis, Sertoli cell barrier loss, evident hemorrhage, angiogenesis, Leydig cell inhibition, inflammation, and fibrosis. Conclusions: Our findings indicate that high angiotensin II levels and activation of mast cells and macrophages may be critical for testicular pathogenesis. Importantly, our findings suggest that patients who become critically ill may exhibit severe alterations and harbor the active virus in the testes.
  • ItemResenha
    The Mongolian Gerbil as a Useful Experimental Model in Reproductive Biology
    (2023-01-01) Ruiz, Thalles Fernando Rocha ; Vilamaior, Patricia Simone Leite ; Grigio, Vitor ; Colleta, Simone Jacovaci ; Zucão, Mariele Ilario ; de Campos, Silvana Gisele Pegorin ; dos Santos, Fernanda Cristina Alcântara ; Biancardi, Manoel Francisco ; Perez, Ana Paula Silva ; Taboga, Sebastião Roberto ; Leonel, Ellen Cristina Rivas ; Universidade Estadual Paulista (UNESP) ; Universidade Federal de Goiás (UFG) ; Federal University of Jataí ; Universidade Estadual de Campinas (UNICAMP)
    Ultimately, the Mongolian gerbils (Meriones unguiculatus) have acquired a relevant role in biological and biomedical experiments alongside other rodents. The use of gerbils in research has been mainly oriented to physiological and pharmacological studies, with special attention to nervous, digestive, and auditory systems as well as microbiology and parasitology. Ultimately, gerbils have also been applied for studying carcinogenesis in different organs and systems, since these animals show a natural propensity to develop spontaneous proliferative lesions, especially in steroid-responsive organs. This characteristic shed light on the reproductive aspects of this rodent model regarding morphological features in male and female individuals. This review of literature summarizes the significance of this model as an alternative to the use of inbred mice and rats in reproductive experimental research, highlighting recent findings. Gerbils have contributed to the expansion of knowledge in prostate biology in male and female individuals, providing studies related to prostatic morphogenesis and neoplasia. In the testes, spermiogenesis occurs in 15 steps, differently from other experimental models. Also, the complete maturation of the testis-epididymal complex occurs between the second and third months. Mammary gland alterations related to the estrous cycle and pregnancy were described, as well as its modulation under endogenous and exogenous estrogenic compounds. The ovaries frequently present ovarian cysts. Furthermore, this organ shows predominantly interstitial steroidogenic glands in the stroma, especially at aging. Adrenal gland shows a large size compared to other animals, presenting three distinct zones with a remarkable role in steroidogenesis.
  • ItemArtigo
    High-lipid nutritional environment in different ontogenetic periods induce developmental programming of rat prostate at aging
    (2023-01-01) Scarpelli, Tatiane Pereira ; Pytlowanciv, Eloisa Zanin ; Pinto-Fochi, Maria Etelvina ; Taboga, Sebastião Roberto ; Góes, Rejane Maira ; Universidade Estadual Paulista (UNESP) ; Universidade Estadual de Campinas (UNICAMP) ; União das Faculdades dos Grandes Lagos (UNILAGO)
    Maternal obesity and high-fat diet (HFD) affect permanently prostate histophysiology in adulthood, but the consequences during aging are unknown. Here, we evaluated the prostate alterations in middle-aged rats subjected to a high-lipid nutritional environment (HLE) in different ontogenetic periods. Wistar rats (56 weeks of age) were assigned into groups exposed to standard nutrition (C) or HLE during gestation (G), gestation and lactation (GL), from lactation onward (L), from weaning onward (W) and from gestation onward (AL). HLE in the periods after weaning consisted of HFD (20% fat), and during gestation and lactation it also included previous maternal obesity induced by the HFD. HLE increased total cholesterol and triglyceride levels in all groups and led to insulin resistance in GL and AL and obesity in L. Serum testosterone levels decreased ~67% in GL, ~146% in L and W, and ~233% in AL. Histological and stereological analysis revealed an increment of the stromal compartment and collagen fibers in the prostates of all HLE groups, as well as degenerative lesions, such as cell vacuolation and prostate concretions. HLE aggravated acinar atrophy in G, GL, and L, and in AL it reached more than 50% of the prostate area for most animals. The foci of prostatic intraepithelial neoplasia increased in AL. Tissue expression of androgen receptor did not vary among groups, except for a higher stromal expression for G and GL. Even when restricted to gestation and lactation, HLE induces diffuse acinar atrophy in the aging prostate and worsens degenerative and premalignant lesions when it continues throughout life.
  • ItemArtigo
    Morphological, Cytological and Molecular Studies and Feeding and Defecation Pattern of Hybrids from Experimental Crosses between Triatoma sordida and T. rosai (Hemiptera, Triatominae)
    (2022-11-01) Vicente, Roberto Dezan ; Madeira, Fernanda Fernandez ; Borsatto, Kelly Cristine ; Garcia, Ariane Cristina Caris ; Cristal, Daniel Cesaretto ; Delgado, Luiza Maria Grzyb ; Bittinelli, Isadora de Freitas ; De Mello, Denis Vinicius ; Dos Reis, Yago Visinho ; Ravazi, Amanda ; Galvão, Cleber ; De Azeredo-Oliveira, Maria Tercília Vilela ; Da Rosa, João Aristeu ; De Oliveira, Jader ; Alevi, Kaio Cesar Chaboli ; Universidade Estadual Paulista (UNESP) ; Instituto Oswaldo Cruz (FIOCRUZ) ; Universidade de São Paulo (USP)
    Under laboratory conditions, Triatoma rosai and T. sordida are able to cross and produce hybrids. In the face of climate and environmental changes, the study of hybrids of triatomines has evolutionary and epidemiological implications. Therefore, we performed morphological, cytological and molecular studies and characterized the feeding and defecation pattern of hybrids from crosses between T. sordida and T. rosai. The morphological characterization of the female genitalia of the hybrids showed that characteristics of both parental species segregated in the hybrids. Cytogenetic analyzes of hybrids showed regular metaphases. According to molecular studies, the mitochondrial marker Cytochrome B (CytB) related the hybrids with T. sordida and the nuclear marker Internal Transcribed Spacer 1 (ITS-1) related the hybrids with T. rosai. Both parents and hybrids defecated during the blood meal. Thus, the hybrids resulting from the cross between T. sordida and T. rosai presented segregation of phenotypic characters of both parental species, 100% homeology between homeologous chromosomes, phylogenetic relationship with T sordida and with T. rosai (with CytB and ITS-1, respectively), and, finally, feeding and defecation patterns similar to the parents.
  • ItemArtigo
    Trends in evolution of the Triatomini tribe (Hemiptera, Triatominae): reproductive incompatibility between four species of geniculatus clade
    (2022-12-01) dos Reis, Yago Visinho ; de Oliveira, Jader ; Madeira, Fernanda Fernandez ; Ravazi, Amanda ; de Oliveira, Ana Beatriz Bortolozo ; de Mello, Denis Vinicius ; Campos, Fabricio Ferreira ; de Azeredo-Oliveira, Maria Tercília Vilela ; da Rosa, João Aristeu ; Galvão, Cleber ; Alevi, Kaio Cesar Chaboli ; Universidade Estadual Paulista (UNESP) ; Universidade de São Paulo (USP) ; Laboratório Nacional e Internacional de Referência em Taxonomia de Triatomíneos
    Background: The geniculatus clade, composed by the rufotuberculatus, lignarius, geniculatus and megistus groups, relates evolutionarily the species of the genus Panstrongylus and Nesotriatoma. Several studies have shown that triatomine hybrids can play an important role in the transmission of Chagas disease. Natural hybrids between species of the geniculatus clade have never been reported to our knowledge. Thus, carrying out experimental crosses between species of the geniculatus clade can help to elucidate the taxonomic issues as well as contribute to the epidemiological knowledge of this group. Methods: Experimental crosses were carried out between species of the megistus and lignarius groups to evaluate the reproductive compatibility between them. A phylogenetic reconstruction was also performed with data available in GenBank for the species of the geniculatus clade to show the relationships among the crossed species. Results: Phylogenetic analysis grouped the species of the geniculatus clade into four groups, as previously reported. In the interspecific crosses performed there was no hatching of eggs, demonstrating the presence of prezygotic barriers between the crossed species and confirming their specific status. Conclusions: In contrast to the other groups of the Triatomini tribe, as well as the Rhodniini, there are prezygotic barriers that prevent the formation of hybrids between species of the megistus and lignarius groups. Thus, the geniculatus clade may represent an important evolutionary model for Triatominae, highlighting the need for further studies with greater sample efforts for this clade (grouping the 17 species of Panstrongylus and the three of Nesotriatoma). Graphical Abstract: [Figure not available: see fulltext.].
  • ItemArtigo
    The use of Artificial Intelligence in predicting Respiratory Syncytial Virus-inhibiting flavonoids
    (2023-01-01) Lopes, B. R.P. ; Albertini, T. T. ; Costa, M. F. ; Ferreira, A. S. ; Toledo, K. A. ; Rocha, J. C. ; Universidade Estadual Paulista (UNESP)
    Human Respiratory Syncytial Virus (hRSV) infection results in death and hospitalization of thousands of people worldwide each year. Unfortunately, there are no vaccines or specific treatments for hRSV infections. Screening hundreds or even thousands of promising molecules is a challenge for science. We integrated biological, structural, and physicochemical properties to train and to apply the concept of artificial intelligence (AI) able to predict flavonoids with potential anti-hRSV activity. During the training and simulation steps, the AI produced results with hit rates of more than 83%. The better AIs were able to predict active or inactive flavonoids against hRSV. In the future, in vitro and/or in vivo evaluations of these flavonoids may accelerate trials for new anti-RSV drugs, reduce hospitalizations, deaths, and morbidity caused by this infection worldwide, and be used as input in these networks to determine which parameter is more important for their decision.
  • ItemArtigo
    Antiviral Activity of Quercetin Hydrate against Zika Virus
    (2023-04-01) Saivish, Marielena Vogel ; Menezes, Gabriela de Lima ; da Silva, Roosevelt Alves ; Fontoura, Marina Alves ; Shimizu, Jacqueline Farinha ; da Silva, Gislaine Celestino Dutra ; Teixeira, Igor da Silva ; Mistrão, Natalia Franco Bueno ; Hernandes, Victor Miranda ; Rahal, Paula ; Sacchetto, Lívia ; Pacca, Carolina Colombelli ; Marques, Rafael Elias ; Nogueira, Maurício Lacerda ; Faculdade de Medicina de São José do Rio Preto ; Centro Nacional de Pesquisa em Energia e Materiais (CNPEM) ; Universidade Federal do Rio Grande do Norte ; Universidade Federal de Jataí ; Universidade Estadual Paulista (UNESP) ; Faceres Medical School ; The University of Texas Medical Branch
    Zika virus (ZIKV) has re-emerged in recent decades, leading to outbreaks of Zika fever in Africa, Asia, and Central and South America. Despite its drastic re-emergence and clinical impact, no vaccines or antiviral compounds are available to prevent or control ZIKV infection. This study evaluated the potential antiviral activity of quercetin hydrate against ZIKV infection and demonstrated that this substance inhibits virus particle production in A549 and Vero cells under different treatment conditions. In vitro antiviral activity was long-lasting (still observed 72 h post-infection), suggesting that quercetin hydrate affects multiple rounds of ZIKV replication. Molecular docking indicates that quercetin hydrate can efficiently interact with the specific allosteric binding site cavity of the NS2B-NS3 proteases and NS1-dimer. These results identify quercetin as a potential compound to combat ZIKV infection in vitro.
  • ItemArtigo
    Climate and Environmental Changes and Their Potential Effects on the Dynamics of Chagas Disease: Hybridization in Rhodniini (Hemiptera, Triatominae)
    (2023-04-01) Ravazi, Amanda ; Oliveira, Jader de ; Madeira, Fernanda Fernandez ; Nunes, Giovana Menezes ; Reis, Yago Visinho dos ; Oliveira, Ana Beatriz Bortolozo de ; Azevedo, Luísa Martins Sensato ; Galvão, Cleber ; Azeredo-Oliveira, Maria Tercília Vilela de ; Rosa, João Aristeu da ; Alevi, Kaio Cesar Chaboli ; Universidade Estadual Paulista (UNESP) ; Universidade de São Paulo (USP) ; Instituto Oswaldo Cruz (FIOCRUZ)
    Chagas disease affects about eight million people. In view of the issues related to the influence of anthropogenic changes in the dynamics of the distribution and reproductive interaction of triatomines, we performed experimental crosses between species of the Rhodniini tribe in order to evaluate interspecific reproductive interactions and hybrid production capacity. Reciprocal crossing experiments were conducted among Rhodnius brethesi × R. pictipes, R. colombiensis × R. ecuadoriensis, R. neivai × R. prolixus, R. robustus × R. prolixus, R. montenegrensis × R. marabaensis; R. montenegrensis × R. robustus, R. prolixus × R. nasutus and R. neglectus × R. milesi. With the exception of crosses between R. pictipes ♀ × R. brethesi ♂, R. ecuadoriensis ♀ × R. colombiensis ♂ and R. prolixus ♀ × R. neivai ♂, all experimental crosses resulted in hybrids. Our results demonstrate that both allopatric and sympatric species produce hybrids, which can generate concern for public health agencies in the face of current anthropogenic events. Thus, we demonstrate that species of the Rhodniini tribe are capable of producing hybrids under laboratory conditions. These results are of great epidemiological importance and raise an important discussion about the influence of climatic and environmental interactions on Chagas disease dynamics.
  • ItemArtigo
    Synergistic actions of Alpelisib and Melatonin in breast cancer cell lines with PIK3CA gene mutation
    (2023-07-01) de Godoy, Bianca Lara Venâncio ; Moschetta-Pinheiro, Marina Gobbe ; Chuffa, Luiz Gustavo de Almeida ; Pondé, Noam Falbel ; Reiter, Russel J. ; Colombo, Jucimara ; Zuccari, Debora Aparecida Pires de Campos ; Faculdade de Medicina de São José do Rio Preto – FAMERP ; Universidade Paulista – UNIP ; Universidade Estadual Paulista (UNESP) ; IQVIA Biotech ; Long School of Medicine
    Aims: Breast cancer (BC) presents high mortality rate and about 25–46 % have mutation in the PIK3CA gene. Alpelisib is a PI3K inhibitor that acts on p110α, which is a subunit of the PI3K protein. The melatonin shown important anti-neoplastic effects and may increase the effectiveness of chemotherapy. This study evaluated the synergistic action of Alpelisib and Melatonin in BC lines carrying the H1047R mutation in PIK3CA, relative to the cellular dynamics and the PI3K/AKT/mTOR pathway. Main methods: MDA-MB-468 (triple-ernegative), MDA-MB-453 (H1047R PIK3CA, HER2+) and T-47D cells (H1047R PIK3CA, ER+/PR+) were divided into four treatment groups: control; Melatonin (1 mM); Alpelisib (1 μM); and Alpelisib (1 μM) + Melatonin (1 mM). Cell viability and migration were investigated using the MTT assay and Transwell assay, respectively. Protein expression of PI3K, p-AKT, mTOR, HIF-1α, and caspase-3, was verified using immunocytochemistry. Key findings: MTT assay revealed that MDA-MB-453 and T-47D showed reduction in cell viability in all groups, especially in the MDA-MB-453 treated with Melatonin + Alpelisib. MDA-MB-468 presents reduction in cell migration only with Melatonin, while in the lines with mutation, the treatment of Melatonin + Alpelisib caused inhibition of cell migration. PI3K, p-AKT, mTOR and HIF-1α were inhibited after treatment with Melatonin + Alpelisib in MDA-MB-453 and T-47D lines. The expression of caspase-3 increased in all groups in MDA-MB-453 and T-47D cells, being the increase more pronounced in the Melatonin + Alpelisib group. Significance: These results indicate that the combined use of Melatonin and Alpelisib may be more effective in inhibiting BC in women carrying the PIK3CA gene mutation than either treatment alone.
  • ItemArtigo
    Condyloma acuminata: An evaluation of the immune response at cellular and molecular levels
    (2023-04-01) Stuqui, Bruna ; Provazzi, Paola Jocelan Scarin ; Lima, Maria Leticia Duarte ; Cabral, Ágata Silva ; Leonel, Ellen Cristina Rivas ; Candido, Natalia Maria ; Taboga, Sebastião Roberto ; da Silva, Marcia Guimarães ; de Oliveira Lima, Flávio ; Melli, Patrícia Pereira dos Santos ; Quintana, Silvana Maria ; de Freitas Calmon, Marilia ; Rahal, Paula ; Universidade Estadual Paulista (UNESP) ; Universidade Federal de Goiás (UFG) ; Universidade de São Paulo (USP)
    Condyloma acuminata (CA) is a benign proliferative disease mainly affecting in non-keratinized epithelia. Most cases of CA are caused by low-risk human papillomavirus (HPV), mainly HPV 6 and 11. The aim of the current study was to highlight the candidate genes and pathways associated with immune alterations in individuals who did not spontaneously eliminate the virus and, thus, develop genital warts. Paraffin-embedded condyloma samples (n = 56) were analyzed by immunohistochemistry using antibodies against CD1a, FOXP3, CD3, CD4, CD8, and IFN-γ. The immunomarkers were chosen based on the evaluation of the innate and adaptive immune pathways using qPCR analysis of 92 immune-related genes, applying a TaqMan Array Immune Response assay in HPV 6 or HPV 11 positive samples (n = 27). Gene expression analysis revealed 31 differentially expressed genes in CA lesions. Gene expression validation revealed upregulation of GZMB, IFNG, IL12B, and IL8 and downregulation of NFATC4 and IL7 in CA samples. Immunohistochemical analysis showed increased FOXP3, IFN-γ, CD1a, and CD4 expression in CA than in the control tissue samples. In contrast, CD3 and CD8 expression was decreased in CA lesion samples. Increased levels of pro-inflammatory cytokines in HPV-positive patients compared with HPV-negative patients seem to reflect the elevated immunogenicity of HPV-positive CA lesions. Host defense against HPV begins during the early stages of the innate immune response and is followed by activation of T lymphocytes, which are mainly represented by CD4+ and regulatory T cells. The low CD8+ T cell count in CA may contribute to this recurrent behavior. Additional studies are needed to elucidate the mechanism of host defense against HPV infection in CA.