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Despite promising advancements in leishmaniasis treatment, existing therapies often face limitations and significant side effects, stimulating the search for novel therapeutic alternatives. In this context, lectins, such as DVL extracted from Dioclea violacea seeds, have emerged as potential candidates due to their diverse biological activities. This study represents the first investigation of the leishmanicidal potential of DVL in vitro against Leishmania infantum. Our results demonstrate that DVL exhibits a leishmanicidal effect (IC50/24 h = 49.37 µg/mL or 2 µM), binding to glycans on L. infantum. Fluorescence assays revealed that DVL can induce the production of reactive oxygen species (ROS) and cause damage to the parasite's membrane. DVL demonstrated a modulating effect when combined with amphotericin B and glucantime, enhancing the activity of these drugs by 40 % and 80 %, respectively. It also showed no cytotoxicity in Raw 264.7 cells and was able to override the toxic effect of amphotericin B on cells and reduce the survival rate of macrophages infected with amastigote forms, as well as their percentage of infection by 31 %. Therefore, DVL shows promise as a treatment for visceral leishmaniasis caused by L. infantum. Our findings provide valuable insights for future therapeutic development targeting leishmania glycans.
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OBJECTIVE: This study aimed to evaluate the presence of human papillomavirus (HPV) and Epstein-Barr virus (EBV) and the expression of p53, p16, E-cadherin, COX-2, MLH1, and MYC in oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: One hundred OSCC specimens were submitted to in situ hybridization for HPV and EBV, and immunohistochemistry for detection of the human proteins. RESULTS: Thirty-one cases showed HPV in tumor tissue. EBV was not detected in any case investigated. The HPV(+) group demonstrated an increase of staining scores for nuclear p16 (p = .047), cytoplasmic MYC (p = .002), while a decrease for nuclear MLH1 (p = .048), suggesting that HPV may upregulate the expression of the first two proteins and down-regulate the latter. CONCLUSION: Our findings reinforce the hypothesis of the HPV-related oral carcinogenesis involving the expression of p16 and MYC, and MLH1 suppression. Exclusively cytoplasmic stainings for p16, MLH1, and MYC were also associated with more advanced tumors. Finally, in view of the lack of studies correlating the HPV or EBV infection to the expression of oncoproteins, more researches assessing a broader panel of markers and employing different approaches are still necessary in order to understand the role of these viruses as well as the molecular mechanisms involved in the development and progression of oral carcinomas.
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Alphapapillomavirus , Carcinoma de Células Escamosas , Infecciones por Virus de Epstein-Barr , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Infecciones por Papillomavirus , Alphapapillomavirus/metabolismo , Cadherinas/metabolismo , Carcinoma de Células Escamosas/patología , Inhibidor p16 de la Quinasa Dependiente de Ciclina/metabolismo , Ciclooxigenasa 2/metabolismo , Infecciones por Virus de Epstein-Barr/complicaciones , Herpesvirus Humano 4/genética , Humanos , Neoplasias de la Boca/metabolismo , Homólogo 1 de la Proteína MutL/genética , Homólogo 1 de la Proteína MutL/metabolismo , Papillomaviridae , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/diagnóstico , Carcinoma de Células Escamosas de Cabeza y Cuello , Proteína p53 Supresora de TumorRESUMEN
Over the past few decades, several publications have investigated the role of Epstein-Barr virus (EBV) in head and neck squamous cell carcinomas, and an increasing number of them have shown its presence in laryngeal tumors. The purpose of this meta-analysis was to evaluate the association of EBV with laryngeal carcinoma. The search was carried out in two databases, Scopus and PubMed, using the following terms: "Epstein-Barr virus" and "laryngeal carcinoma". A total of 187 records were found, of which 31 were selected for meeting the inclusion and exclusion criteria. The meta-analysis yielded an overall pooled prevalence of 43.72% (95% confidence interval (CI): 34.35-53.08). Studies carried out in Europe and Eurasia had slightly higher pooled prevalence than other subgroups, while the prevalence of studies performed in developed countries was higher than in developing countries (46.37% vs. 34.02%). Furthermore, laryngeal carcinoma occurred almost three times as often among EBV-infected individuals compared to those without EBV infection (odds ratio = 2.86 (95% CI: 1.18-6.90); Begg's test, p = 0.843 and Egger's test, p = 0.866). Our findings support the idea that EBV is related to laryngeal carcinoma. However, further studies are needed before recognizing a definitive etiological role of EBV in the development and/or progression of laryngeal carcinomas.
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Despite the recent announcement of the new pathogenic coronavirus to man, SARS-CoV2, a large number of publications are presented to the scientific community. An organized and systematic review of the epidemiological, etiological, and pathogenic factors of COVID-19 is presented. This is a systematic review using the databases MEDLINE, EMBASE, Web of Science, SCIELO; the descriptors coronavirus, SARS-CoV-2, etiology, epidemiology, pathophysiology, pathogenesis, COVID-19, with publications from December 2019 to January 2021, resulting in more than 800 publications and 210 selected. The data suggest that COVID-19 is associated with SAR-CoV-2 infection, with the transmission of contagion by fomites, salivary droplets, and other forms, such as vertical and fecal-oral. The bat and other vertebrates appear to be reservoirs and part of the transmission chain. The virus uses cell receptors to infect human cells, especially ACE2, like other coronaviruses. Heat shock proteins have different roles in the infection, sometimes facilitating it, sometimes participating in more severe conditions, when not serving as a therapeutic target. The available data allow us to conclude that COVID-19 is a pandemic viral disease, behaving as a challenge for public health worldwide, determining aggressive conditions with a high mortality rate in patients with risk factors, without treatment, but with the recent availability of the first vaccines.
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COVID-19 , Animales , Humanos , Masculino , Pandemias , ARN Viral , SARS-CoV-2RESUMEN
Leishmaniases are a complex of sand fly-borne diseases that are considered a public health issue in several countries. Brazil presents high leishmaniases rates. The South of Ceará State, known as Cariri region, shows worrying statistics mainly on American tegumentary leishmaniasis. In Barbalha, which is one of the municipalities in this region, there is still a lack of studies regarding the local phlebotomine (Diptera: Psychodidae) fauna in order to help clarify the high rates. This study aimed to characterize such fauna by capturing sand flies with light traps during a four-year period. A total of 3730 sand flies were captured, of which 37.8% were females. Fourteen species were found: 13 of the Lutzomyia genus and one of the Brumptomyia genus. Of the Lutzomyia species, four were proven and five had potential involvement in leishmaniasis transmission. Lutzomyia longipalpis was the most common species (66.97%). This predominance, especially in the urban area, indicates its epidemiological importance and adaptation to environmental conditions modified by human activity. In fact, further studies are still required to accurately determine the behavioral features of these vectors in order to guide public health measurements towards its control and prevention.
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Leishmania/aislamiento & purificación , Leishmaniasis Cutánea/transmisión , Psychodidae/parasitología , Animales , Biota , Brasil , Ciudades , Femenino , Masculino , Psychodidae/clasificaciónRESUMEN
The purpose of this meta-analysis is to evaluate the association of Epstein-Barr virus (EBV) with oral squamous cell carcinoma (OSCC). We searched the electronic scientific databases of PubMed and Scopus and included a total of 53 studies that were published from 1990 to 2019. The analysis yielded a 45.37% (95% confidence interval [CI]: 38.90-51.84; p < 0.001) overall pooled prevalence of EBV. Studies that used the applied methods of in situ hybridization, polymerase chain reaction, immunology, or RNA microarray showed the following pooled prevalence: 46.08%, 40.32, 54.97%, and 74.89%, respectively. EBV-infected individuals have a 2.5 higher risk for developing OSCC (odds ratio: 2.57; 95% CI: 1.23% to 5.36%; p < 0.001). The present meta-analysis supports the hypothesis of EBV association with OSCC, pointing to this virus as a risk factor for neoplasia. Our findings also suggest that EBV latent transcripts (latent membrane protein 1, EBV nuclear antigen 1 and 2, and EBV-encoded small RNAs) have an important role in this process. Furthermore, novel advancements could arise from large and standardized studies that are constructed to probe for other latent gene expression, eliminate confounding factors (tobacco, alcohol, and high-risk human papillomavirus infection), and define the relationship between EBV and oral carcinomas.
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Carcinoma de Células Escamosas/fisiopatología , Infecciones por Virus de Epstein-Barr/fisiopatología , Herpesvirus Humano 4/fisiología , Neoplasias de la Boca/fisiopatología , Consumo de Bebidas Alcohólicas/efectos adversos , Consumo de Bebidas Alcohólicas/epidemiología , Consumo de Bebidas Alcohólicas/fisiopatología , Carcinoma de Células Escamosas/epidemiología , Carcinoma de Células Escamosas/virología , Infecciones por Virus de Epstein-Barr/epidemiología , Humanos , Neoplasias de la Boca/epidemiología , Neoplasias de la Boca/virología , Fumar/efectos adversos , Fumar/epidemiología , Fumar/fisiopatologíaRESUMEN
Epstein-Barr virus (EBV) and human papillomavirus (HPV) have been implicated in 38% of all virus-related cancers. Over the past three decades, both have been detected in anogenital and head-and-neck squamous cell carcinomas (HNSCC), with evidence of involvement in tumor genesis and progression. Very little has been published on HPV/EBV coinfection. In this chapter, we review the literature on the role of these viruses in oral carcinoma and draw parallels with other HNSCCs and anogenital carcinomas, with emphasis on their interplay and potential signaling pathways. EBV infection seems to create an environment that favors HPV latency, supporting the claim that EBV is a cofactor in HPV-related carcinomas. In turn, under certain circumstances, HPV appears to be able to induce EBV to switch to the latent or replicative state. The main viral oncogenes expressed in these malignancies are EBNA1, EBNA2, LMP1, EBERs, and the high-risk HPV oncogenes E6 and E7. The most well-documented human proteins involved are p53, pRb, p16INK4a, p19ARF, Myc, E-cadherin, ß-catenin, EGFR, MLH1, and COX-2. These proteins are directly associated not only with viral products but also with one another in the development of malignancy. Knowledge of the molecular machinery behind carcinomas coinfected with HPV and EBV may help understand how these viruses trigger carcinogenesis and subsidize the development of new biomarkers of tumor aggressiveness and prognosis, alternative surrogate virus markers, and possible therapeutic targets.
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Neoplasias del Ano/fisiopatología , Infecciones por Virus de Epstein-Barr/fisiopatología , Herpesvirus Humano 4/fisiología , Neoplasias de la Boca/fisiopatología , Papillomaviridae/fisiología , Neoplasias Urogenitales/fisiopatología , Neoplasias del Ano/epidemiología , Carcinogénesis , Infecciones por Virus de Epstein-Barr/epidemiología , Femenino , Humanos , Masculino , Neoplasias de la Boca/epidemiología , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/fisiopatología , Neoplasias Urogenitales/epidemiologíaRESUMEN
Cutaneous Leishmaniasis (CL) is endemic in 88 countries, showing relevant prevalences. The aim of this study was to perform a systematic review on atypical lesions of CL around the world, addressing clinico-epidemiological, immunological and therapeutic aspects. A search of the literature was conducted via electronic databases Scopus and PubMed for articles published between 2010 and 2015. The search terms browsed were "cutaneous leishmaniasis", "atypical" and "unusual". Based on the eligibility criteria, 34 out of 122 articles were included in the final sample. Atypical lesions may include the following forms: erythematous volcanic ulcer, lupoid, eczematous, erysipeloid, verrucous, dry, zosteriform, paronychial, sporotrichoid, chancriform and annular. In any cases, they seem to be another disease like subcutaneous and deep mycosis, cutaneous lymphoma, pseudolymphoma, basal and squamous cell carcinoma. The lesions have been reported in the face, cheeks, ears, nose, eyelid, limbs, trunk, buttocks, as well as in palmoplantar and genital regions; sometimes occurring in more than one area. The reason for clinical cutaneous leishmaniasis pleomorphism is unclear but immunosuppression seems to play an important role in some cases. There are no established guidelines for the treatment of atypical cutaneous leishmaniasis. However, pentavalent antimonials remain as first line treatment for all forms of leishmaniasis even for HIV-infected patients and atpical forms. Finally, to diagnose an atypical lesion properly, the focus has to be on the medical history and the origin of the patient, comparing them to the natural history of leishmaniasis and always reminding of possible atypical presentations, to then start searching for the best diagnostic method and treatment, reducing the misdiagnosis rate and, subsequently, controlling the disease progression. Thereby, contributing for breaking the transmission chain of the parasite, due to early correct diagnosis which, in turn, contributes to reduce the prevalence.
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Leishmaniasis Cutánea/patología , Leishmaniasis Cutánea/parasitología , Antiprotozoarios/uso terapéutico , Coinfección , Infecciones por VIH/complicaciones , Humanos , Leishmaniasis Cutánea/complicaciones , Leishmaniasis Cutánea/tratamiento farmacológico , Piel/patologíaRESUMEN
Epstein-Barr virus (EBV) has been associated with 10% of gastric carcinomas. The aim of this study was to determine the frequency of EBV in gastric carcinomas in Brazil assessed by in situ hybridization (ISH) and PCR, which would contribute to the characterization of the clinical and pathological aspects of EBV-associated gastric carcinomas. One hundred and ninety-two gastric carcinoma cases were collected at hospitals in two Brazilian states. Seventy-three out of 151 cases were PCR(+), while 11/160 cases were ISH(+). Nine out of eleven ISH(+) cases displayed a diffuse staining pattern and 2 out of 11 a focal pattern. Both techniques showed that the EBV(+) cases were characterized by their association with males, older patients, lower gastric region, intestinal type, advanced stage and poorly to moderately differentiated tumors. The concordance between the two techniques was 55.8% (Cohen's kappa index = 0.034). Four cases were ISH(+)/PCR(-), while 49 cases were PCR(+)/ISH(-). Only two cases showed stained lymphocytes by ISH and one of them was PCR(-). The observed discrepancy between the two techniques could not be explained just by the elevated accuracy of PCR. ISH(+)/PCR(-) carcinomas may be encountered if EBV is not present in the whole tumor tissue or if there are polymorphisms in the sequences of the viral genome amplified. On the other hand, the high frequency of PCR(+) results associated with the absence of ISH staining in lymphocytes and/or tumors cells suggests that the virus may be present in tumor cells or other cell types without expressing EBER1, the target of the ISH technique.
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Evidence suggests that the carcinogenic process guided by Helicobacter pylori is related to the expression of cell cycle and apoptosis proteins as BCL-2, BAX, and MYC. However, the literature is conflicting regarding the expression frequency in the histological subtypes and did not consider cagA gene presence. To investigate the expression of these proteins considering the histological subtypes of gastric cancer associated with H. pylori (cagA), a total of 89 cases were used. H. pylori infection and cagA status were determined by PCR. Immunodetection was performed for MYC, BCL-2, and BAX proteins. H. pylori was found in 95.5% of the patients, among them, 65.8% were cagA(+). Nuclear MYC was detected in 36.4%, BAX in 55.7%, while BCl-2 in just 5%. Nuclear MYC staining was significantly lower in the intestinal than diffuse subtype (p = 0.008) and was related with the presence of H. pylori cagA(+). Additionally, most of the few cases cytoplasmic MYC positive were in the intestinal subtype. In diffuse tumors, although most nuclear MYC positive cases were cagA(+), it was not significant. No difference was observed between BCL-2 or BAX expression considering the presence of cagA gene in the histological subtypes. It seems that MYC could be relevant for the diffuse tumorigenic pathway associated with H. pylori and possibly influenced by the presence of cagA gene, while in intestinal tumors, the tumorigenic pathway does not occur through the MYC expression.
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Adenocarcinoma/metabolismo , Helicobacter pylori/aislamiento & purificación , Neoplasias Intestinales/metabolismo , Proteínas Proto-Oncogénicas c-myc/metabolismo , Neoplasias Gástricas/metabolismo , Adenocarcinoma/microbiología , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/metabolismo , Femenino , Genotipo , Helicobacter pylori/genética , Humanos , Neoplasias Intestinales/microbiología , Neoplasias Intestinales/patología , Masculino , Persona de Mediana Edad , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Estudios Retrospectivos , Neoplasias Gástricas/microbiología , Neoplasias Gástricas/patología , Proteína X Asociada a bcl-2/metabolismoRESUMEN
BACKGROUND: The association between Helicobacter pylori gene diversity and gastric cancer has been poorly reported, although it is one of the important ways to explain the gastric pathogenesis. The aim of this study was to investigate the frequency of cagE and virB11 genes in H. pylori isolated from patients with gastric cancer and to analyze the histology profiles. MATERIALS AND METHODS: The presence of H. pylori and subtypes (cagE and virB11) was detected by PCR from the genomic DNA of 101 patients who had been diagnosed with gastric cancer. The cases were grouped according to the presence/absence of the genes studied and were analyzed in relation to histopathological parameters. RESULTS: H. pylori infection was detected in 94 out of 101 (93.1%) gastric carcinomas. The cases were categorized into the following groups: cagE+/virB11+, cagE+/virB11-, cagE-/virB11+, and cagE-/virB11-. Frequencies were: 50% (47/94) cagE+/virB11+, 3.2% (3/94) cagE+/virB11-, 10.6% (10/94) cagE-/virB11+, and 36.2% (34/94) cagE-/virB11-. Tumors in the gastric antrum were predominant. An exception was the cagE-/virB11- group, in which tumors had a tendency to be located in the gastric cardia; the majority of the cardia tumors (56% (14/25)) were in this group. Intestinal histology type was the most frequent, but the cagE+/virB11- group only had diffuse tumors. H. pyloricagE+/virB11+ occurred most frequently (except at stage III), and was present at all gastric cancer stages. CONCLUSIONS: This study is the first to include a relevant number of gastric cancer cases with H. pylori infection, reporting the frequency and relationship of cagE and virB11 genes and the genesis of this tumor. The presence of these cag pathogenicity island genes shows that they are important factors for the pathogenesis and malignancy of gastric cancer related to H. pylori.
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Antígenos Bacterianos/genética , Proteínas Bacterianas/genética , Helicobacter pylori/genética , Neoplasias Gástricas/virología , Adulto , Anciano , Anciano de 80 o más Años , ADN Bacteriano/análisis , ADN Bacteriano/aislamiento & purificación , Femenino , Infecciones por Helicobacter/genética , Infecciones por Helicobacter/patología , Infecciones por Helicobacter/virología , Helicobacter pylori/metabolismo , Helicobacter pylori/patogenicidad , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa/métodos , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Virulencia/genética , Adulto JovenRESUMEN
AIM: To investigate the interrelationship between H pylori and Epstein-Barr virus (EBV) infection in the gastric carcinogenesis having in focus the p53 mutation and the c-Myc, Bcl-2 and Bax expression. METHODS: seventy-one gastric carcinoma tissues were assessed by polymerase chain reaction (PCR) for H pylori and in situ hybridization for EBV. c-Myc, Bcl-2 and Bax expression were detected by immunohistochemistry and single-stranded conformational polymorphism (SSCP) for p53 mutation. RESULTS: The positivity rates for H pylori and EBV were 94.4% and 8.45%, respectively. The majority of the cases displayed only the H pylori presence. All EBV positive cases were also H pylori positive. None infectious agent was observed in 5.55% of the cases. The intestinal type tumor was more frequent in the co-infected and non-infected groups. The female predominated in the non-infected group showing statistical significance (70.4% vs 29.6%, P = 0.039). The Bcl-2 was only detected in the group exclusively infected by H pylori. However, c-Myc and Bax were detected in the three groups but with a low frequency in the co-infected group. Mutation of p53 was present in all groups, with the highest frequencies in the H pylori positive groups. CONCLUSION: The frequency of H pylori infection in gastric carcinomas was high. The presented data indicated that gastric carcinogenesis has different pathways depending of the presence of the two investigated infectious agents, suggesting a possible involvement of H pylori with apoptotic process. The low expression of c-Myc and Bax in the EBV-positive groups suggests that EBV may inhibit the expression of these proteins. Nevertheless, p53 mutation shows to be a relevant alteration, independent of both infectious agents.