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  • ItemArtigo
    High Selectivity of 8-Hydroxyquinoline on Leishmania (Leishmania) and Leishmania (Viannia) Species Correlates with a Potent Therapeutic Activity In Vivo
    (2023-05-01) Lima, Sarah Kymberly Santos de [UNESP]; Jesus, Jéssica Adriana [UNESP]; Raminelli, Cristiano; Laurenti, Márcia Dalastra; Passero, Luiz Felipe Domingues [UNESP]; Universidade Estadual Paulista (UNESP); Universidade de São Paulo (USP); Universidade Federal de São Paulo (UNIFESP)
    Leishmaniasis is a neglected disease caused by protozoa of the genus Leishmania, which causes different clinical manifestations. Drugs currently used in the treatment such as pentavalent antimonial and amphotericin B cause severe side effects in patients, and parasite resistance has been reported. Thus, it is necessary and urgent to characterize new and effective alternative drugs to replace the current chemotherapy of leishmaniasis. In this regard, it has been experimentally demonstrated that quinoline derivatives present significative pharmacological and parasitic properties. Thus, the aim of this work was to demonstrate the leishmanicidal activity of 8-hydroxyquinoline (8-HQ) in vitro and in vivo. The leishmanicidal activity (in vitro) of 8-HQ was assayed on promastigote and intracellular amastigote forms of L. (L.) amazonensis, L. (L.) infantum chagasi, L. (V.) guyanensis L. (V.) naiffi, L. (V.) lainsoni, and L. (V.) shawi. Additionally, the levels of nitric oxide and hydrogen peroxide were analyzed. The therapeutic potential of 8-HQ was analyzed in BALB/c mice infected with a strain of L. (L.) amazonensis that causes anergic cutaneous diffuse leishmaniasis. In vitro data showed that at 24 and 72 h, 8-HQ eliminated promastigote and intracellular amastigote forms of all studied species and this effect may be potentialized by nitric oxide. Furthermore, 8-HQ was more selective than miltefosine. Infected animals treated with 8-HQ by the intralesional route dramatically reduced the number of tissue parasites in the skin, and it was associated with an increase in IFN-γ and decrease in IL-4, which correlated with a reduction in inflammatory reaction in the skin. These results strongly support the idea that 8-HQ is an alternative molecule that can be employed in the treatment of leishmaniasis, given its selectivity and multispectral action in parasites from the Leishmania genus.
  • ItemArtigo
    Proposing Specific Neuronal Epithelial-to-Mesenchymal Transition Genes as an Ancillary Tool for Differential Diagnosis among Pulmonary Neuroendocrine Neoplasms
    (2022-12-01) Prieto, Tabatha Gutierrez; Baldavira, Camila Machado; Machado-Rugolo, Juliana [UNESP]; Olivieri, Eloisa Helena Ribeiro; da Silva, Eduardo Caetano Abilio; Ab’ Saber, Alexandre Muxfeldt; Takagaki, Teresa Yae; Capelozzi, Vera Luiza; Universidade de São Paulo (USP); Universidade Estadual Paulista (UNESP); AC Camargo Cancer Center; Barretos Cancer Hospital; Fundação Oncocentro do Estado de São Paulo (FOSP)
    Pulmonary neuroendocrine neoplasms (PNENs) are currently classified into four major histotypes, including typical carcinoid (TC), atypical carcinoid (AC), large cell neuroendocrine carcinoma (LCNEC), and small cell lung carcinoma (SCLC). This classification was designed to be applied to surgical specimens mostly anchored in morphological parameters, resulting in considerable overlapping among PNENs, which may result in important challenges for clinicians’ decisions in the case of small biopsies. Since PNENs originate from the neuroectodermic cells, epithelial-to-mesenchymal transition (EMT) gene expression shows promise as biomarkers involved in the genotypic transformation of neuroectodermic cells, including mutation burden with the involvement of chromatin remodeling genes, apoptosis, and mitosis rate, leading to modification in final cellular phenotype. In this situation, additional markers also applicable to biopsy specimens, which correlate PNENs subtypes with systemic treatment response, are much needed, and current potential candidates are neurogenic EMT genes. This study investigated EMT genes expression and its association with PNENs histotypes in tumor tissues from 24 patients with PNENs. PCR Array System for 84 EMT-related genes selected 15 differentially expressed genes among the PNENs, allowing to discriminate TC from AC, LCNEC from AC, and SCLC from AC. Functional enrichment analysis of the EMT genes differentially expressed among PNENs subtypes showed that they are involved in cellular proliferation, extracellular matrix degradation, regulation of cell apoptosis, oncogenesis, and tumor cell invasion. Interestingly, four EMT genes (MAP1B, SNAI2, MMP2, WNT5A) are also involved in neurological diseases, in brain metastasis, and interact with platinum-based chemotherapy and tyrosine–kinase inhibitors. Collectively, these findings emerge as an important ancillary tool to improve the strategies of histologic diagnosis in PNENs and unveil the four EMT genes that can play an important role in driving chemical response in PNENs.
  • ItemArtigo
    Primary Cutaneous Cryptococcosis Caused by Cryptococcus gatti in an Elderly Patient
    (2022-09-01) Belda, Walter; Casolato, Ana T. S.; Luppi, Juliana B.; Passero, Luiz Felipe D. [UNESP]; Criado, Paulo R.; Universidade de São Paulo (USP); Universidade Estadual Paulista (UNESP); Fundação Universitária do ABC (FUABC)
    According to the spread of Cryptococcus sp., fungal infections can be classified as primary or secondary. In primary cutaneous cryptococcosis, the fungi are restricted to the skin of the patients, without systemic involvement. The incidence of primary cutaneous cryptococcosis is high in patients with immunosuppression, and this type of infection is rarely observed in patients who are immunocompetent. In the present case report, a patient who is immunocompetent and has systemic comorbidity reported that, after skin trauma, ulcerovegetative lesions appeared in the right upper arm; the etiologic agent was identified as Cryptococcus gatti, serotype B. The cutaneous lesions healed completely after 5 months of fluconazole treatment.
  • ItemArtigo
    Technical modification of indirect immunofluorescent antibody test using filter paper blood eluates
    (1973-01-01) De Franco, Marcello F.; Chamma, L. G.
    An indirect immunofluorescence test using small discs (0.4 cm in diameter) cut from blood smears on filter paper is described. Discs plus three drops of phosphate-buffered saline are laid on antigenic areas on slides, which are then incubated. During incubation, eluted antibodies react with antigen. The method was tested with 10 eluates from healthy persons and with 30 eluates from three groups of 10 patients with Chagas’ disease, schistosomiasis Mansoni and South American blastomycosis, respectively. Sera from the same blood samples were tested also by conventional indirect immunofluorescence tests. Both tests gave similar results. The method proposed is useful as a rapid qualitative screening test when dealing with a large number of samples. © 1973 S. Karger AG, Basel.
  • ItemArtigo
    Fibrosis in canine transmissible venereal tumor after chemotherapy with vincristine
    (2023-01-01) do Prado Duzanski, Anderson [UNESP]; Feo, Haline Ballestero [UNESP]; Flórez, Luis Mauricio Montoya; Dinau, Fernando Carmona [UNESP]; Paiva, Bruna Ribeiro [UNESP]; Brandão, Cláudia Valéria Seullner [UNESP]; Rocha, Noeme Sousa [UNESP]; Universidade Estadual Paulista (UNESP); Universidad Nacional de Colombia
    The canine transmissible venereal tumor is type of transmissible cancer that occurs naturally through allogenic cellular transplants. Commonly diagnosed in the genital area of sexually active dogs, the tumor typically responds well to vincristine sulfate chemotherapy, although there are cases of resistance to the drug correlated with the tumoral phenotype. We describe herein a case of fibrosis in an area affected by the tumor in a dog after vincristine chemotherapeutic treatment that was associated with an idiosyncratic reaction to the drug.
  • ItemArtigo
    PTEN Immunohistochemistry: A New Approach for Diagnosis of Intestinal Neuronal Dysplasia Type B
    (2023-05-01) Terra, Simone Antunes [UNESP]; de Arruda Lourenção, Pedro Luiz Toledo [UNESP]; Rodrigues, Maria Aparecida Marchesan [UNESP]; Universidade Estadual Paulista (UNESP)
    Context.—Intestinal neuronal dysplasia type B (IND B) is a complex entity involving the enteric nervous system, clinically manifested with constipation in infancy. Diagnosis has been established by histopathologic analysis of rectal biopsies. However, the criteria for the diagnosis have been questioned and modified, hindering diagnostic practice. Objective.—To analyze the applicability of PTEN immunohistochemistry in the diagnosis of IND B and to compare with control cases and cases of Hirschsprung disease (HD). Design.—PTEN immunohistochemical expression was analyzed in colorectal samples from 29 cases of IND B and compared with 4 control cases and 6 cases of HD. The pattern of PTEN immunoexpression was analyzed in glial cells of the submucosal and myenteric nerve plexuses and in neural fibrils of the muscularis propria using a scoring system. Results.—Marked reduction or absence of PTEN expression was observed in glial cells of the submucosal nerve plexuses in all cases of the IND B group and in the myenteric nerve plexuses in 28 of 29 cases (96.5%). Lack of PTEN expression was detected in neural fibrils within the muscularis propria in 21 of 29 cases (72%) of the IND B group. PTEN expression was positive in the same neural structures of the control and HD groups. Conclusions.—PTEN immunohistochemistry may be a valuable tool in the diagnostic evaluation of IND B. Lack of or reduction of PTEN expression in neural fibrils within the muscularis propria suggests that involvement of the neuromuscular junction may be a key event in the pathogenesis of the motility disturbance occurring in IND B.
  • ItemArtigo
    Intestinal microbiome characterization of adult Brazilian men with psoriasis compared to omnivore and vegetarian controls
    (2023-01-01) Polo, Tatiana Cristina Figueira [UNESP]; Lai, Mariana Righetto de Ré [UNESP]; Miot, Luciane Donida Bartoli [UNESP]; Bento, Giovana Fernanda Cosi [UNESP]; Silva, Márcia Guimarães da [UNESP]; Marques, Silvio Alencar [UNESP]; Miot, Hélio Amante [UNESP]; Universidade Estadual Paulista (UNESP)
    Background: Psoriasis is a chronic inflammatory disease associated with systemic inflammation and comorbidities. Changes in the composition of the intestinal microbiome are involved in the pathogenesis of inflammatory diseases and metabolic syndrome. Characterizing the intestinal microbiome of patients with psoriasis may be relevant for the understanding of its clinical course and comorbidity prevention. Objective: To characterize the intestinal microbiome of men with psoriasis compared to omnivore and vegetarian controls (without psoriasis). Method: Cross-sectional study of 42 adult males: 21 omnivores with psoriasis; and controls: 14 omnivores and 7 vegetarian individuals. The characterization of the intestinal microbiome was performed by metagenomic analysis. Serum levels of lipopolysaccharide-binding protein (LPB) and C-reactive protein (CRP) were evaluated. Results: The groups differed from each other regarding nutritional aspects and microbiome; individuals with psoriasis had a higher consumption of protein and lower consumption of fibers. Levels of LPB, CRP, and the Firmicutes/Bacteroidetes ratio were higher in the group with psoriasis than in the vegetarian group (p < 0.05). The genera Prevotella, Mogibacterium, Dorea, Bifidobacterium and Coprococcus, differed in the group with psoriasis compared to vegetarians; the genera Mogibacterium, Collinsella and Desulfovibrio differed from omnivores. A microbiome pattern linked to psoriasis (plsPSO) was identified, which was associated with higher LPB levels (rho = 0.39; p = 0.02), and lower dietary fiber intake (rho = −0.71; p < 0.01). Study limitations: Only adult men were evaluated. Conclusion: A difference was identified in the intestinal microbiome of adult men with psoriasis when compared to healthy omnivores and vegetarian controls. The identified microbiome pattern was correlated with dietary fiber intake and serum levels of LPB.
  • ItemCarta
    Gut microbiome diversity and serum levels of lipopolysaccharide-bound protein (LPB) in men with psoriasis under different systemic therapies
    (2023-01-01) de Ré Lai, Mariana Righetto [UNESP]; Polo, Tatiana Cristina Figueira [UNESP]; Miot, Luciane Donida Bartoli [UNESP]; Bento, Giovana Fernanda Cosi [UNESP]; da Silva, Márcia Guimaraes [UNESP]; Miot, Hélio Amante [UNESP]; Universidade Estadual Paulista (UNESP)
  • ItemArtigo
    Covariates of vaginal microbiota and pro-inflammatory cytokine levels in women of reproductive age
    (2023-04-18) Novak, J. [UNESP]; Ferreira, C. S.T. [UNESP]; Golim, M. A. [UNESP]; Silva, M. G. [UNESP]; Marconi, C. [UNESP]; Universidade Estadual Paulista (UNESP); Universidade Federal do Paraná (UFPR)
    This study aimed to assess the correlation between covariates of the vaginal microbiota and local levels of proinflammatory cytokines in women of reproductive age presenting four molecularly defined bacterial community-state types (CSTs). We enrolled 133 non-pregnant women who attended primary care health clinics for routine Pap-testing. Molecular profiling of vaginal microbiota was performed by V3-V4 16S rRNA sequencing. The covariates of vaginal microbiota included were: vaginal pH, total bacterial cell count, diversity (Shannon index), -richness and dominant taxa abundances. Levels of interleukin (IL)-1β, IL-6, IL-8, and tumour necrosis factor (TNF-α) were measured by enzyme-linked immunosorbent assays in supernatants of cervicovaginal fluids. Nonparametric Kruskal-Wallis test was used to compare microbiota covariates and cytokines among different CSTs. Spearman's tests were performed to assess correlations across the measured parameters. A total of 96 (72.2%) participants had CSTs dominated by Lactobacillus spp. (Lactobacillus crispatus CST I, n=38; Lactobacillus gasseri CST II, n=20; and Lactobacillus iners CST III, n=38). A total of 37 (27.8%) presented the Lactobacillus-depleted CST IV. Total bacterial count was higher in CST II (1.29E+05, 3.40E+04-6.69E+05) compared to other Lactobacillus-dominated CSTs (p=0.0003). The highest values of microbiota diversity (1.85; 0.23-2.68) and richness (27.0; 5.0-37.0) were observed in CST IV (P<0.0001). Lower levels of IL-1β were observed in CST I (5.4; 0.0-3,256) when compared to CST III (51.7; 0.0-2,616) and to CST IV (56.2; 0.0-3,407) (P=0.008). Levels of IL-6 were higher in CST II (4.13; 0-131.4) than in CST IV (0.0-58.27) (P=0.02). Correlation tests showed an overall distinct profile of CST II when compared to other Lactobacillusdominated CSTs, particularly regarding the correlation between total bacterial load and cytokines (r>0.39). In conclusion, this study provides evidence of a single pro-inflammatory signature of L. gasseri-dominated microbiota in response to bacterial load. Further studies evaluating a broader range of inflammation markers are warranted.
  • ItemArtigo
    Protective Effects of Omega-3 Supplementation against Doxorubicin-Induced Deleterious Effects on the Liver and Kidneys of Rats
    (2023-04-01) Espírito Santo, Sara Gomes [UNESP]; Monte, Marina Gaiato [UNESP]; Polegato, Bertha Furlan [UNESP]; Barbisan, Luís Fernando [UNESP]; Romualdo, Guilherme Ribeiro [UNESP]; Universidade Estadual Paulista (UNESP)
    Anthracycline doxorubicin (DOX) is still widely used as a chemotherapeutic drug for some solid tumors. Although DOX is highly effective, its side effects are limiting factors, such as cardio, nephro and hepatotoxicity. As such, approaches used to mitigate these adverse effects are highly encouraged. Omega 3 (ω-3), which is a class of long-chain polyunsaturated fatty acids, has been shown to have anti-inflammatory and antioxidant effects in preclinical bioassays. Thus, we evaluated the protective effects of ω-3 supplementation on hepatotoxicity and nephrotoxicity induced by multiple DOX administrations in rodents. Male Wistar rats (10 rats/group) were treated daily with ω-3 (400 mg/kg/day) by gavage for six weeks. Two weeks after the first ω-3 administration, the rats received DOX (3.5 mg/kg, intraperitoneal, 1×/week) for four weeks. DOX treatment reduced body weight gain increased systemic genotoxicity and caused liver-related (increase in serum ALT levels, thickness of the Glisson’s capsule, compensatory proliferation and p65 levels) and kidney-related (increase in serum urea and creatinine levels, and incidence of tubular dilatation) deleterious outcomes. In contrast, ω-3 supplementation was safe and abrogated the DOX-related enhancement of systemic genotoxicity, serum urea and creatinine levels. Furthermore, ω-3 intervention reduced by 50% the incidence of kidney histological lesions while reducing by 40–50% the p65 protein level, and the proliferative response in the liver induced by DOX. Our findings indicate that ω-3 intervention attenuated the DOX-induced deleterious effects in the liver and kidney. Therefore, our findings may inspire future mechanistical investigations and clinical interventions with ω-3 on the reported outcomes.
  • ItemArtigo
    Circulating Extracellular Vesicles microRNAs Are Altered in Women Undergoing Preterm Birth
    (2023-03-01) Ramos, Bruna Ribeiro Andrade [UNESP]; Tronco, Júlia Abbade [UNESP]; Carvalho, Márcio [UNESP]; Felix, Tainara Francini [UNESP]; Reis, Patrícia Pintor [UNESP]; Silveira, Juliano Coelho; Silva, Márcia Guimarães [UNESP]; Universidade Estadual Paulista (UNESP); University of Western São Paulo (UNOESTE); Universidade de São Paulo (USP)
    Preterm labor (PTL) and preterm premature rupture of membranes (PPROM) lead to high perinatal morbidity/mortality rates worldwide. Small extracellular vesicles (sEV) act in cell communication and contain microRNAs that may contribute to the pathogenesis of these complications. We aimed to compare the expression, in sEV from peripheral blood, of miRNAs between term and preterm pregnancies. This cross-sectional study included women who underwent PTL, PPROM, and term pregnancies, examined at the Botucatu Medical School Hospital, SP, Brazil. sEV were isolated from plasma. Western blot used to detect exosomal protein CD63 and nanoparticle tracking analysis were performed. The expression of 800 miRNAs was assessed by the nCounter Humanv3 miRNA Assay (NanoString). The miRNA expression and relative risk were determined. Samples from 31 women—15 preterm and 16 term—were included. miR-612 expression was increased in the preterm groups. miR-612 has been shown to increase apoptosis in tumor cells and to regulate the nuclear factor κB inflammatory pathway, processes involved in PTL/PPROM pathogenesis. miR-1253, miR-1283, miR378e, and miR-579-3p, all associated with cellular senescence, were downregulated in PPROM compared with term pregnancies. We conclude that miRNAs from circulating sEV are differentially expressed between term and preterm pregnancies and modulate genes in pathways that are relevant to PTL/PPROM pathogenesis.
  • ItemArtigo
    Condyloma acuminata: An evaluation of the immune response at cellular and molecular levels
    (2023-04-01) Stuqui, Bruna [UNESP]; Provazzi, Paola Jocelan Scarin [UNESP]; Lima, Maria Leticia Duarte [UNESP]; Cabral, Ágata Silva [UNESP]; Leonel, Ellen Cristina Rivas; Candido, Natalia Maria [UNESP]; Taboga, Sebastião Roberto [UNESP]; da Silva, Marcia Guimarães [UNESP]; de Oliveira Lima, Flávio [UNESP]; Melli, Patrícia Pereira dos Santos; Quintana, Silvana Maria; de Freitas Calmon, Marilia [UNESP]; Rahal, Paula [UNESP]; 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.
  • ItemEditorial
    Editorial: State of the art in immunopathologic mechanisms underlying preterm birth pathways and biomarkers for prematurity prediction
    (2023-01-01) Ramos, Bruna Ribeiro de Andrade [UNESP]; Polettini, Jossimara; Silva, Márcia Guimarães da [UNESP]; Universidade Estadual Paulista (UNESP); University of Western São Paulo (Unoeste); Federal University of Fronteira Sul
  • ItemArtigo
    Postoperative serum magnesium levels as a predictor for the need for calcium replacement after total thyroidectomy: a prospective study
    (2023-01-01) Soares, Carlos Segundo Paiva [UNESP]; de Oliveira, Cristiano Claudino; Koga, Katia Hiromoto [UNESP]; Moriguchi, Sonia Marta [UNESP]; Terra, Simone Antunes [UNESP]; Tagliarini, José Vicente [UNESP]; Mazeto, Gláucia Maria Ferreira da Silva [UNESP]; Universidade Estadual Paulista (UNESP); A.C.Camargo Cancer Center
    Objective: Our aim was to assess the ability of serum magnesium (Mg), measured on the first postoperative day (Mg1PO), to predict the need for calcium (Ca) replacement in patients undergoing total thyroidectomy (TT). Subjects and methods: Eighty patients undergoing TT, with Mg1PO and PTH dosage in the first (PTH1h) and eighth (PTH8h) hours after TT, were evaluated for the need for Ca replacement. Data were evaluated by uni/multivariate logistic regression and Receiver Operating Characteristic (ROC) curve. Results: 32 patients (40%) required Ca replacement. Median PTH1h, PTH8h and Mg1PO were higher in the no replacement group: 17 versus (vs) 3 pg/mL (p < 0.001), 18.2 vs 3.0 pg/mL (p < 0.001) and 2 vs 1.6 mg/dL (p < 0.001), respectively. Mg1PO was the isolated predictor for this replacement (odds ratio = 0.0004, 95% confidence interval: 0.000003-0.04; p = 0.001), with the cut-off value of 1.8 mg/dL showing sensitivity and specificity of 78.1% and 87.5%, respectively. Conclusions: In this group of patients, serum Mg1PO was the isolated predictor for the need for Ca replacement. Arch Endocrinol Metab. 2023;67(3):355-60.
  • ItemArtigo
    Molecular Phylogenetic Analysis of Paracoccidioides Species Complex Present in Paracoccidioidomycosis Patient Tissue Samples
    (2023-03-01) de Oliveira, Luciana Bonome Zeminian [UNESP]; Della Coletta, Amanda Manoel [UNESP]; Gardizani, Taiane Priscila [UNESP]; Garces, Hans Garcia [UNESP]; Bagagli, Eduardo [UNESP]; Trilles, Luciana; Barrozo, Ligia Vizeu; Marques, Sílvio de Alencar [UNESP]; Faveri, Julio De [UNESP]; Dias-Melicio, Luciane Alarcão [UNESP]; Universidade Estadual Paulista (UNESP); Oswaldo Cruz Foundation (FIOCRUZ); Universidade de São Paulo (USP)
    Paracoccidioidomycosis (PCM) is the main and most prevalent systemic mycosis in Latin America, that until recently, it was believed to be caused only by Paracoccidioides brasiliensis (P. brasiliensis). In 2006, researchers described three cryptic species: S1, PS2, PS3, and later, another one, PS4. In 2009, Paracoccidioides lutzii (Pb01-like) was described, and in 2017, a new nomenclature was proposed for the different agents: P. brasiliensis (S1), P. americana (PS2), P. restrepiensis (PS3), and P. venezuelensis (PS4). These species are not uniformly distributed throughout Latin America and, knowing that more than one cryptic species could coexist in some regions, we aimed to identify those species in patients’ biopsy samples for a better understanding of the distribution and occurrence of these recently described species in Botucatu region. The Hospital of Medical School of Botucatu—UNESP, which is a PCM study pole, is located in São Paulo State mid-west region and is classified as a PCM endemic area. Genotyping analyses of clinical specimens from these patients that have been diagnosed and treated in our Hospital could favor a possible correlation between genetic groups and mycological and clinical characteristics. For this, molecular techniques to differentiate Paracoccidioides species in these biopsies, such as DNA extraction, PCR, and sequencing of three target genes (ITS, CHS2, and ARF) were conducted. All the sequences were analyzed at BLAST to testify the presence of P. brasiliensis. The phylogenetic trees were constructed using Mega 7.0 software and showed that 100% of our positive samples were from S1 cryptic species, therefore P. brasiliensis. This is important data, demonstrating the predominance of this species in the São Paulo State region.
  • ItemCarta
    Discrepancy in transcriptomic profiling between CD34 + stem cells and primary bone marrow cells in myelodysplastic neoplasm
    (2023-06-01) Ribeiro Junior, Howard Lopes; Gonçalves, Paola Gyuliane [UNESP]; Moreno, Daniel Antunes; Goes, João Vitor Caetano; de Oliveira, Roberta Taiane Germano; Montefusco-Pereira, Carlos Victor; Komoto, Tatiana Takahasi; Pinheiro, Ronald Feitosa; Federal University of Ceara; Barretos Cancer Hospital; Universidade Estadual Paulista (UNESP)
    Differentially expressed genes (DEGs) biomarkers can be used to help diagnose and monitor the disease, as well as to determine which treatments are most effective. So, given the complexity of Myelodysplastic neoplasm (MDS), it is difficult to determine the impact and disparities of DEGs between CD34+ HSC (hematopoietic stem cells) or primary bone marrow cells (PBMC) in MDS pathogenesis, and therefore it remains largely unknown. Here, we performed an in-silico transcriptome analysis on CD34+ HSC and PBMC from 1092 MDS patients analyzing the divergences between differential gene expression patterns in these two cell types as potential pathogenic biomarkers for MDS. Initially, we observed a difference of 7117 expressed transcripts between PBMC (n = 40,165) and CD34 +HSC (n = 33,048). Also, we identified that CD34+ HSC and PBMC samples showed 240 and 2948 DEGs, respectively. In summary, we identified DEGs disparities in CD34+ HSC and PBMC cell types. However, there was a certain similarity of the activated pathways in both cellular samples based on Gene Ontology and KEGG pathways enrichment analyses. Our results provide novel insights into novel DEGs biomarkers to MDS pathogenesis with clinical significance. Availability of data and materials: All microarray databases were obtained from Gene Expression Omnibus (https://www.ncbi.nlm.nih.gov/geo/). To evaluate the biological function of differentially expressed genes, the DAVID (Database for Annotation, Visualization and Integrated Discovery tool was used) (https://david.ncifcrf.gov/).
  • ItemArtigo
    LncRNA JHDM1D-AS1 Is a Key Biomarker for Progression and Modulation of Gemcitabine Sensitivity in Bladder Cancer Cells
    (2023-03-01) Pereira, Isadora Oliveira Ansaloni; da Silva, Glenda Nicioli; Almeida, Tamires Cunha; Lima, Ana Paula Braga; Sávio, André Luiz Ventura; Leite, Katia Ramos Moreira; Salvadori, Daisy Maria Fávero [UNESP]; UFOP—Federal University of Ouro Preto; Butantan Institute; Faculdade do Centro Oeste Paulista—FACOP; Universidade do Oeste Paulista—UNOESTE; Universidade de São Paulo (USP); Universidade Estadual Paulista (UNESP)
    Long non-coding RNAs are frequently found to be dysregulated and are linked to carcinogenesis, aggressiveness, and chemoresistance in a variety of tumors. As expression levels of the JHDM1D gene and lncRNA JHDM1D-AS1 are altered in bladder tumors, we sought to use their combined expression to distinguish between low-and high-grade bladder tumors by RTq-PCR. In addition, we evaluated the functional role of JHDM1D-AS1 and its association with the modulation of gemcitabine sensitivity in high-grade bladder-tumor cells. J82 and UM-UC-3 cells were treated with siRNA-JHDM1D-AS1 and/or three concentrations of gemcitabine (0.39, 0.78, and 1.56 µM), and then submitted to cytotoxicity testing (XTT), clonogenic survival, cell cycle progression, cell morphology, and cell migration assays. When JHDM1D and JHDM1D-AS1 expression levels were used in combination, our findings indicated favorable prognostic value. Furthermore, the combined treatment resulted in greater cytotoxicity, a decrease in clone formation, G0/G1 cell cycle arrest, morphological alterations, and a reduction in cell migration capacity in both lineages compared to the treatments alone. Thus, silencing of JHDM1D-AS1 reduced the growth and proliferation of high-grade bladder-tumor cells and increased their sensitivity to gemcitabine treatment. In addition, the expression of JHDM1D/JHDM1D-AS1 indicated potential prognostic value in the progression of bladder tumors.
  • ItemArtigo
    Unraveling Hepatic Metabolomic Profiles and Morphological Outcomes in a Hybrid Model of NASH in Different Mouse Strains
    (2023-02-01) Bacil, Gabriel P. [UNESP]; Romualdo, Guilherme R. [UNESP]; Piagge, Priscila M. F. D.; Cardoso, Daniel R.; Vinken, Mathieu; Cogliati, Bruno; Barbisan, Luís F. [UNESP]; Universidade Estadual Paulista (UNESP); Universidade de São Paulo (USP); University of Vrije
    Nonalcoholic fatty liver disease (NAFLD) encompasses nonalcoholic steatohepatitis (NASH) and affects 25% of the global population. Although a plethora of experimental models for studying NASH have been proposed, still scarce findings regarding the hepatic metabolomic/molecular profile. In the present study, we sought to unravel the hepatic metabolomic profile of mice subjected to a hybrid model of NASH, by combining a Western diet and carbon tetrachloride administration, for 8 weeks, in male C57BL/6J and BALB/c mice. In both mouse strains, the main traits of NASH—metabolic (glucose intolerance profile), morphologic (extensive microvesicular steatosis and fibrosis, lobular inflammation, and adipose tissue-related inflammation/hypertrophy), and molecular (impaired Nrf2/NF-κB pathway dynamics and altered metabolomic profile)—were observed. The hepatic metabolomic profile revealed that the hybrid protocol impaired, in both strains, the abundance of branched chain-aromatic amino acids, carboxylic acids, and glycosyl compounds, that might be linked to the Nrf2 pathway activation. Moreover, we observed a strain-dependent hepatic metabolomic signature, in which the tricarboxylic acid metabolites and pyruvate metabolism were dissimilarly modulated in C57BL/6J and BALB/c mice. Thus, we provide evidence that the strain-dependent hepatic metabolomic profile might be linked to the distinct underlying mechanisms of NASH, also prospecting potential mechanistic insights into the corresponding disease.
  • ItemCapítulo de livro
    Type I interferons: History and perspectives as immunotherapeutic agents against cancer
    (2020-09-24) Gorgulho, Carolina Mendonça [UNESP]; Romagnoli, Graziela Gorete [UNESP]; Kaneno, Ramon; Universidade Estadual Paulista (UNESP); UNOESTE; BRA
    Interferons (IFNs) were first described in the context of viral infection as macromolecules capable of interfering with the ability of a viral particle to infect a host cell. Besides viral interference, since their discovery, IFNs have been further implicated in different processes linked to immunity and cancer. The family of IFNs has been divided into three categories according to biological properties and signaling pathways: type I IFNs (consisting of IFN-α and β), type II IFNs (IFN-γ, also known as the immune IFN), and type III IFNs (consisting of IFN-λ). This chapter focuses on type I IFNs, which are closely linked to key processes in cancer, such as malignant transformation, differentiation, tumor cell growth, and death. Within the immune system, type I IFNs communicate with several populations involved in the antitumor immune response, such as NK (natural killer) and dendritic cells, contributing to cancer immunoediting. Type I IFNs are approved for the treatment of a number of cancers, including melanoma, renal cell carcinoma, and Kaposi's sarcoma. However, currently the biggest challenge in the therapeutic use of type I IFNs, as well as other cytokines, is the toxic side effects, which can compromise the efficacy of the treatment and reduce patient's quality of life. In this chapter, we review the biology of type I IFNs along with many therapeutic approaches being currently explored in order to reduce toxicity and fully harness the antitumor potential of type I IFNs.
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    Dendritic cell vaccines for cancer therapy: Fundamentals and clinical trials
    (2020-09-24) Romagnoli, Graziela Gorete [UNESP]; Kaneno, Ramon [UNESP]; Universidade Estadual Paulista (UNESP); Oeste Paulista University - UNOESTE
    Since conventional chemo- and radiotherapy and surgery are not completely satisfactory to fight cancer, active and passive immunotherapeutic approaches have figured as effective agents of customized medicine. Dendritic cells (DCs) are key cells to trigger an effective antitumor response, being the only antigen-presenting cells (APCs) able to prime naïve T lymphocytes for tumor antigens. Therefore, several approaches have been proposed to use these cells as therapeutic antitumor vaccines. Different strategies of tumor antigen delivery, as well as the use of the best DC activators, are in constant search for the development of more immunogenic DC-based vaccines. In the present chapter, we reviewed the strategies for developing clinical-grade DC vaccines and the data of clinical trials with patients with selected types of cancer. Current studies show positive but not definitive results, indicating that the association with other immunotherapeutic agents, such as checkpoint blockers, or even chemotherapeutic agents may contribute to achieve the clinical regression of cancer.