RESUMO
Salivary glands' neoplasms are hard to diagnose and present a complex etiology. However, several viruses have been detected in these neoplasms, such as HCMV, which can play a role in certain cancers through oncomodulation. The co-infections between HCMV with betaherpesviruses (HHV-6 and HHV-7) and polyomaviruses (JCV and BKV) has been investigated. The aim of the current study is to describe the frequency of HCMV and co-infections in patients presenting neoplastic and non-neoplastic lesions, including in the salivary gland. Multiplex quantitative polymerase chain reaction was used for betaherpesvirus and polyomavirus quantification purposes after DNA extraction. In total, 50.7% of the 67 analyzed samples were mucocele, 40.3% were adenoma pleomorphic, and 8.9% were mucoepidermoid carcinoma. Overall, 20.9% of samples presented triple-infections with HCMV/HHV-6/HHV-7, whereas 9.0% were co-infections with HCMV/HHV-6 and HCMV/HHV-7. The largest number of co-infections was detected in pleomorphic adenoma cases. All samples tested negative for polyomaviruses, such as BKV and JCV. It was possible to conclude that HCMV can be abundant in salivary gland lesions. A high viral load can be useful to help better understand the etiological role played by viruses in these lesions. A lack of JCV and BKV in the samples analyzed herein does not rule out the involvement of these viruses in one or more salivary gland lesion subtypes.
Assuntos
Coinfecção , Infecções por Citomegalovirus , Citomegalovirus , Neoplasias das Glândulas Salivares , Glândulas Salivares , Humanos , Coinfecção/virologia , Infecções por Citomegalovirus/virologia , Infecções por Citomegalovirus/diagnóstico , Citomegalovirus/genética , Citomegalovirus/isolamento & purificação , Masculino , Feminino , Neoplasias das Glândulas Salivares/virologia , Pessoa de Meia-Idade , Adulto , Idoso , Glândulas Salivares/virologia , Glândulas Salivares/patologia , Adenoma/virologia , Idoso de 80 Anos ou mais , Carcinoma/virologia , DNA Viral/genética , DNA Viral/análise , Adulto Jovem , AdolescenteRESUMO
BACKGROUND: The indigenous population located in the central region of Brazil, is the second largest in terms of population size in the country. The Indigenous Reserve of Dourados has risk factors that increase the vulnerability of the indigenous population to infectious diseases, especially Human alphaherpesvirus (HSV-1), a neglected disease with high prevalence in priority populations in developing countries. The virus can also cause many more severe diseases, including widespread neonatal infections, herpetic keratitis, and herpes encephalitis, which can be fatal if left untreated. We estimated the prevalence of anti-HSV-1 antibodies and correlated it with the demographic and behavioral characteristics of the Indigenous population of the Jaguapirú and Bororó villages (Dourados, Mato Grosso do Sul (MS), Brazil). METHODS: Our approach was cross-sectional. From March 2017 to November 2018. Using anti-HSV-1 (Gg1) IgM and anti-HSV-1 (gG1) IgG Euroimmun and the detection and quantification of HSV-1 viral load in plasma samples, through real-time PCR. The maps were constructed using QGIS and the statistical analyses using R Studio software. RESULTS: A total of 1138 individuals (> 18 years old) were enrolled. The prevalence of anti-HSV-1 IgM and IgG were 20% and 97.5%, respectively. The prevalence of anti-HSV-1 antibodies for IgG was higher in both sexes. Anti-HSV-1 IgM antibodies were present in 17.1%, 21.2%, 12.5%, and 22% of the participants with urinary problems, genital wounds, genital warts, and urethral discharge, respectively. Real-time PCR was used for confirmatory testing; HSV-1 DNA was detected in 25.6% (54/211) of anti-HSV1 IgM-positive samples. Viral loads ranged from 5.99E + 02 to 3.36E + 13. CONCLUSIONS: The seroprevalence of HSV-1 IgM and detection of HSV-1 DNA in the Indigenous population confirmed high silent prevalence. Furthermore, the seroprevalence of HSV-1 in the Indigenous population was higher than that reported in the general adult Brazilian population. Various socioeconomic factors, drug use, and health and sexual behaviors could contribute to the facilitation of HSV-1 transmission in the Indigenous population. Our results may help develop culturally appropriate intervention programs that eliminate health access barriers and improve the implementation of public health policies aimed at promoting information regarding the prevention, treatment, and control of HSV-1 infection in Brazilian Indigenous populations.
Assuntos
Anticorpos Antivirais , Herpes Simples , Adolescente , Adulto , Idoso , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Anticorpos Antivirais/sangue , Brasil/epidemiologia , Estudos Transversais , Herpes Simples/epidemiologia , Herpes Simples/virologia , Herpesvirus Humano 1/imunologia , Herpesvirus Humano 1/genética , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Indígenas Sul-Americanos/estatística & dados numéricos , Prevalência , Carga ViralRESUMO
This study aimed to identify factors associated with colonization by community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) in adult patients admitted to a Brazilian hospital. This is a cross-sectional study, in which patients underwent a nasal swab and were asked about hygiene behavior, habits, and clinical history. Among the 702 patients, 180 (25.6%) had S. aureus and 21 (2.9%) MRSA. The factors associated with MRSA colonization were attending a gym (OR 4.71; 95% CI; 1.42 - 15.06), smoking habit in the last year (OR 2.37; 95% CI; 0.88 - 6.38), previous hospitalization (OR 2.18; CI 95%; 0.89 - 5.25), and shared personal hygiene items (OR 1.99; 95% CI; 0.71 - 5.55). At the time of admission, colonization by CA-MRSA isolates was higher than that found in the general population. This can be an important public health problem, already endemic in hospitals, whose factors such as those associated with habits (smoking cigarettes) and behaviors (team sports practice and activities in gyms) have been strongly highlighted. These findings may help developing infection control policies, allowing targeting patients on higher-risk populations for MRSA colonization.
Assuntos
Infecções Comunitárias Adquiridas , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Humanos , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Estudos Transversais , Masculino , Feminino , Infecções Estafilocócicas/microbiologia , Infecções Comunitárias Adquiridas/microbiologia , Pessoa de Meia-Idade , Adulto , Fatores de Risco , Brasil/epidemiologia , Adulto Jovem , Idoso , Fatores Socioeconômicos , Portador Sadio/microbiologia , AdolescenteRESUMO
INTRODUCTION: Severe acute hepatitis (SAH) is defined by a severe inflammation of hepatocytes in the liver parenchyma which can lead to an acute liver failure, a clinical condition with high mortality rate that can be triggered by several factors but is usually associated to hepatotropic viruses' infection. In 2022, cases of children with severe acute hepatitis of unknown origin hospitalized in Glasgow, Scotland, were reported. Possible causes of this condition include, but are not limited to, undiagnosed viral (and non-viral) infections, autoimmune hepatitis, drug and/or chemical toxicity, mitochondrial chain respiratory and metabolic disorders. AREAS COVERED: Herpesviruses can cause severe acute hepatitis, but little is known about the role and the mechanisms of herpesviruses as a causative agent of this type of hepatitis. We review the role of herpesviruses as causative agent of SAH in children and other possible mechanisms involved in this disease. EXPERT OPINION: Differential diagnosis for herpesvirus in SAH should be implemented in all settings. Alternative fluids, such as saliva and dried blood, could be used in the diagnosis to overwhelm the availability of biological specimens at sufficient volume. In the future, genetic studies could also be added to increase the knowledge about severe acute hepatitis in children.
Assuntos
Hepatite , Herpesviridae , Viroses , Criança , Humanos , Diagnóstico Diferencial , Doença AgudaRESUMO
Breast cancer is one of the leading causes of death among women worldwide and can be classified into four major distinct molecular subtypes based on the expression of specific receptors. Despite significant advances, the lack of biomarkers for detailed diagnosis and prognosis remains a major challenge in the field of oncology. This study aimed to identify short single-stranded oligonucleotides known as aptamers to improve breast cancer diagnosis. The Cell-SELEX technique was used to select aptamers specific to the MDA-MB-231 tumor cell line. After selection, five aptamers demonstrated specific recognition for tumor breast cell lines and no binding to non-tumor breast cells. Validation of aptamer specificity revealed recognition of primary and metastatic tumors of all subtypes. In particular, AptaB4 and AptaB5 showed greater recognition of primary tumors and metastatic tissue, respectively. Finally, a computational biology approach was used to identify potential aptamer targets, which indicated that CSKP could interact with AptaB4. These results suggest that aptamers are promising in breast cancer diagnosis and treatment due to their specificity and selectivity.
Assuntos
Neoplasias da Mama , Neoplasias Mamárias Animais , Feminino , Humanos , Animais , Neoplasias da Mama/diagnóstico , Mama , Linhagem Celular Tumoral , OligonucleotídeosRESUMO
ABSTRACT This study aimed to identify factors associated with colonization by community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) in adult patients admitted to a Brazilian hospital. This is a cross-sectional study, in which patients underwent a nasal swab and were asked about hygiene behavior, habits, and clinical history. Among the 702 patients, 180 (25.6%) had S. aureus and 21 (2.9%) MRSA. The factors associated with MRSA colonization were attending a gym (OR 4.71; 95% CI; 1.42 - 15.06), smoking habit in the last year (OR 2.37; 95% CI; 0.88 - 6.38), previous hospitalization (OR 2.18; CI 95%; 0.89 - 5.25), and shared personal hygiene items (OR 1.99; 95% CI; 0.71 - 5.55). At the time of admission, colonization by CA-MRSA isolates was higher than that found in the general population. This can be an important public health problem, already endemic in hospitals, whose factors such as those associated with habits (smoking cigarettes) and behaviors (team sports practice and activities in gyms) have been strongly highlighted. These findings may help developing infection control policies, allowing targeting patients on higher-risk populations for MRSA colonization.
RESUMO
Ovarian cancer is among the seven most common types of cancer in women, being the most fatal gynecological tumor, due to the difficulty of detection in early stages. Aptamers are important tools to improve tumor diagnosis through the recognition of specific molecules produced by tumors. Here, aptamers and their potential targets in ovarian cancer cells were analyzed by in silico approaches. Specific aptamers were selected by the Cell-SELEX method using Caov-3 and OvCar-3 cells. The five most frequent aptamers obtained from the last round of selection were computationally modeled. The potential targets for those aptamers in cells were proposed by analyzing proteomic data available for the Caov-3 and OvCar-3 cell lines. Overexpressed proteins for each cell were characterized as to their three-dimensional model, cell location, and electrostatic potential. As a result, four specific aptamers for ovarian tumors were selected: AptaC2, AptaC4, AptaO1, and AptaO2. Potential targets were identified for each aptamer through Molecular Docking, and the best complexes were AptaC2-FXYD3, AptaC4-ALPP, AptaO1-TSPAN15, and AptaO2-TSPAN15. In addition, AptaC2 and AptaO1 could detect different stages and subtypes of ovarian cancer tissue samples. The application of this technology makes it possible to propose new molecular biomarkers for the differential diagnosis of epithelial ovarian cancer.
Assuntos
Aptâmeros de Nucleotídeos , Neoplasias Ovarianas , Feminino , Humanos , Neoplasias Ovarianas/metabolismo , Linhagem Celular Tumoral , Apoptose , Simulação de Acoplamento Molecular , Proteômica , Aptâmeros de Nucleotídeos/metabolismo , Técnica de Seleção de Aptâmeros/métodos , Proteínas de Membrana , Proteínas de NeoplasiasRESUMO
Chagas disease is an enduring public health issue in many Latin American countries, receiving insufficient investment in research and development. Strategies for disease control and management currently lack efficient pharmaceuticals, commercial diagnostic kits with improved sensitivity, and vaccines. Genetic heterogeneity of Trypanosoma cruzi is a key aspect for novel drug design since pharmacological technologies rely on the degree of conservation of parasite target proteins. Therefore, there is a need to expand the knowledge regarding parasite genetics which, if fulfilled, could leverage Chagas disease research and development, and improve disease control strategies. The growing capacity of whole-genome sequencing technology and its adoption as disease surveillance routine may be key for solving this long-lasting problem.
Assuntos
Doença de Chagas , Trypanosoma cruzi , Humanos , Doença de Chagas/epidemiologia , Trypanosoma cruzi/genética , Genômica , Gerenciamento ClínicoRESUMO
Leishmania tarentolae is a non-pathogenic trypanosomatid isolated from lizards widely used for heterologous protein expression and extensively studied to understand the pathogenic mechanisms of leishmaniasis. The repertoire of leishmanolysin genes was reported to be expanded in L. tarentolae genome, but no proteolytic activity was detected. Here, we analyzed L. tarentolae leishmanolysin proteins from the genome to the structural levels and evaluated the enzymatic activity of the wild-type and overexpressing mutants of leishmanolysin. A total of 61 leishmanolysin sequences were retrieved from the L. tarentolae genome. Five of them were selected for phylogenetic analysis, and for three of them, we built 3D models based on the crystallographic structure of L. major ortholog. Molecular dynamics simulations of these models disclosed a less negative electrostatic potential compared to the template. Subsequently, L. major LmjF.10.0460 and L. tarentolae LtaP10.0650 leishmanolysins were cloned in a pLEXSY expression system into L. tarentolae. Proteins from the wild-type and the overexpressing parasites were submitted to enzymatic analysis. Our results revealed that L. tarentolae leishmanolysins harbor a weak enzymatic activity about three times less abundant than L. major leishmanolysin. Our findings strongly suggest that the less negative electrostatic potential of L. tarentolae leishmanolysin can be the reason for the reduced proteolytic activity detected in this parasite.
Assuntos
Leishmania , Leishmaniose , Parasitos , Animais , Leishmania/genética , Leishmania/metabolismo , Leishmaniose/parasitologia , Metaloendopeptidases/metabolismo , FilogeniaRESUMO
The spread of antibiotic-resistant bacteria represents a substantial health threat. Current antibiotics act on a few metabolic pathways, facilitating resistance. Consequently, novel regulatory inhibition mechanisms are necessary. Riboswitches represent promising targets for antibacterial drugs. Purine riboswitches are interesting, since they play essential roles in the genetic regulation of bacterial metabolism. Among these, class I (2'-dG-I) and class II (2'-dG-II) are two different 2'-deoxyguanosine (2'-dG) riboswitches involved in the control of deoxyguanosine metabolism. However, high affinity for nucleosides involves local or distal modifications around the ligand-binding pocket, depending on the class. Therefore, it is crucial to understand these riboswitches' recognition mechanisms as antibiotic targets. In this work, we used a combination of computational biophysics approaches to investigate the structure, dynamics, and energy landscape of both 2'-dG classes bound to the nucleoside ligands, 2'-deoxyguanosine, and riboguanosine. Our results suggest that the stability and increased interactions in the three-way junction of 2'-dG riboswitches were associated with a higher nucleoside ligand affinity. Also, structural changes in the 2'-dG-II aptamers enable enhanced intramolecular communication. Overall, the 2'-dG-II riboswitch might be a promising drug design target due to its ability to recognize both cognate and noncognate ligands.