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1.
Curr Issues Mol Biol ; 46(5): 4609-4629, 2024 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-38785548

RESUMO

Ermp1 is a putative metalloprotease from Schizosaccharomyces pombe and a member of the Fxna peptidases. Although their function is unknown, orthologous proteins from rats and humans have been associated with the maturation of ovarian follicles and increased ER stress. This study focuses on proposing the first prediction of PPI by comparison of the interologues between humans and yeasts, as well as the molecular docking and dynamics of the M28 domain of Ermp1 with possible target proteins. As results, 45 proteins are proposed that could interact with the metalloprotease. Most of these proteins are related to the transport of Ca2+ and the metabolism of amino acids and proteins. Docking and molecular dynamics suggest that the M28 domain of Ermp1 could hydrolyze leucine and methionine residues of Amk2, Ypt5 and Pex12. These results could support future experimental investigations of other Fxna peptidases, such as human ERMP1.

2.
Viruses ; 16(2)2024 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-38400014

RESUMO

This review presents comparative information corresponding to the progress in knowledge of some aspects of infection by the porcine epidemic diarrhea virus (PEDV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) coronaviruses. PEDV is an alphacoronavirus of great economic importance due to the million-dollar losses it generates in the pig industry. PEDV has many similarities to the SARS-CoV-2 betacoronavirus that causes COVID-19 disease. This review presents possible scenarios for SARS-CoV-2 based on the collected literature on PEDV and the tools or strategies currently developed for SARS-CoV-2 that would be useful in PEDV research. The speed of the study of SARS-CoV-2 and the generation of strategies to control the pandemic was possible due to the knowledge derived from infections caused by other human coronaviruses such as severe acute respiratory syndrome (SARS) and middle east respiratory syndrome (MERS). Therefore, from the information obtained from several coronaviruses, the current and future behavior of SARS-CoV-2 could be inferred and, with the large amount of information on the virus that causes COVID-19, the study of PEDV could be improved and probably that of new emerging and re-emerging coronaviruses.


Assuntos
COVID-19 , Vírus da Diarreia Epidêmica Suína , Humanos , Animais , Suínos , SARS-CoV-2
3.
Viruses ; 16(2)2024 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-38400084

RESUMO

The characteristics of the whole PEDV genome that has circulated in Mexico from the first outbreak to the present are unknown. We chose samples obtained from 2013 to 2017 and sequenced them, which enabled us to identify the genetic variation and phylogeny in the virus during the first four years that it circulated in Mexico. A 99% identity was found among the analyzed pandemic strains; however, the 1% difference affected the structure of the S glycoprotein, which is essential for the binding of the virus to the cellular receptor. The S protein induces the most efficacious antibodies; hence, these changes in structure could be implicated in the clinical antecedents of the outbreaks. Antigenic changes could also help PEDV avoid neutralization, even in the presence of previous immunity. The characterization of the complete genome enabled the identification of three circulating strains that have a deletion in ORF1a, which is present in attenuated Asian vaccine strains. The phylogenetic analysis of the complete genome indicates that the first PEDV outbreaks in Mexico were caused by INDEL strains and pandemic strains related to USA strains; however, the possibility of the entry of European strains exists, which may have caused the 2015 and 2016 outbreaks.


Assuntos
Infecções por Coronavirus , Vírus da Diarreia Epidêmica Suína , Doenças dos Suínos , Animais , Suínos , Vírus da Diarreia Epidêmica Suína/genética , Filogenia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/veterinária , México/epidemiologia , Surtos de Doenças , Doenças dos Suínos/epidemiologia , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/química , Diarreia
4.
Viruses ; 15(6)2023 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-37376630

RESUMO

Hepatitis C virus (HCV), human immunodeficiency virus (HIV) and hepatitis B virus (HBV) can be transmitted by blood transfusion. Most transmission occurs during the acute viremic phase (AVP), before antibody development. To reduce transmission risk, individual donor nucleic acid testing (ID-NAT) is used. In Puebla, Mexico, serological tests and ID-NAT have been applied to screen blood donors and detect individuals in AVP. In the present study, 106,125 blood donors' data in two periods (2012-2015 and 2017-2019) were analyzed. The residual risk (RR) values were calculated considering ID-NAT results. The RR for HIV was 14 in 1 million donations or 1 in 71,428, the RR for HVC was 6.8 in 1 million donations or 1 in 147,058 and, for HBV, it was 156 in 1 million donations, or 1 in 6410. Previously, it was predicted that the transmission RR of these viruses would be reduced in Mexico through better screening with NAT. The use of ID-NAT has, indeed, increased the safety of blood reserves for HIV and HCV. However, more research is needed to determine why the residual risk of HBV did not decrease as much over the study period. ID-NAT is an important complementary tool for blood donor screening that should be implemented.


Assuntos
Infecções por HIV , HIV-1 , Hepatite B , Hepatite C , Humanos , Vírus da Hepatite B/genética , Hepacivirus/genética , Bancos de Sangue , México/epidemiologia , Centros de Atenção Terciária , HIV-1/genética , Hepatite C/diagnóstico , Hepatite C/epidemiologia , Doadores de Sangue , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Viremia/diagnóstico , Doença Iatrogênica , Hepatite B/diagnóstico , Hepatite B/epidemiologia , Técnicas de Amplificação de Ácido Nucleico/métodos
5.
Cell Signal ; 101: 110487, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36216165

RESUMO

Triple negative breast cancer (TNBC) is the breast cancer subtype with the worst prognosis and still lacks a targeted therapy. In this study, we found increased ERK phosphorylation in TNBC cell lines and an important role for ERK in sustaining the migration of TNBC cells. Although ROS have been suggested to have an important role in sustaining MAPK signaling, antioxidant treatment increased ERK phosphorylation, probably suggesting increased invasive potential. Interestingly, treatment with PD0325901 (PD), a MEK inhibitor, decreased ROS levels in TNBC cells and decreased mitochondrial fragmentation in the MDAMB231 cell line. Our data supports an important role for MEK/ERK in TNBC, sustaining cellular migration, regulating mitochondrial dynamics and ROS production in this breast cancer subtype.


Assuntos
Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Quinases de Proteína Quinase Ativadas por Mitógeno , Proliferação de Células
6.
PLoS One ; 17(2): e0263582, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35139120

RESUMO

The membrane protein M of the Porcine Epidemic Diarrhea Virus (PEDV) is the most abundant component of the viral envelope. The M protein plays a central role in the morphogenesis and assembly of the virus through protein interactions of the M-M, M-Spike (S) and M-nucleocapsid (N) type. The M protein is known to induce protective antibodies in pigs and to participate in the antagonistic response of the cellular antiviral system coordinated by the type I and type III interferon pathways. The 3D structure of the PEDV M protein is still unknown. The present work exposes a predicted 3D model of the M protein generated using the Robetta protocol. The M protein model is organized into a transmembrane and a globular region. The obtained 3D model of the PEDV M protein was compared with 3D models of the SARS-CoV-2 M protein created using neural networks and with initial machine learning-based models created using trRosetta. The 3D model of the present study predicted four linear B-cell epitopes (RSVNASSGTG and KHGDYSAVSNPSALT peptides are noteworthy), six discontinuous B-cell epitopes, forty weak binding and fourteen strong binding T-cell epitopes in the CV777 M protein. A high degree of conservation of the epitopes predicted in the PEDV M protein was observed among different PEDV strains isolated in different countries. The data suggest that the M protein could be a potential candidate for the development of new treatments or strategies that activate protective cellular mechanisms against viral diseases.


Assuntos
Infecções por Coronavirus/virologia , Proteínas M de Coronavírus/química , Vírus da Diarreia Epidêmica Suína/química , Doenças dos Suínos/virologia , Suínos/virologia , Sequência de Aminoácidos , Animais , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/veterinária , Proteínas M de Coronavírus/imunologia , Epitopos de Linfócito B/química , Epitopos de Linfócito B/imunologia , Epitopos de Linfócito T/química , Epitopos de Linfócito T/imunologia , Modelos Moleculares , Vírus da Diarreia Epidêmica Suína/imunologia , Conformação Proteica , Doenças dos Suínos/imunologia
7.
Life Sci ; 284: 119942, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34506835

RESUMO

Cancer is one of the major causes of death in the world and its global burden is expected to continue increasing. In several types of cancers, reactive oxygen species (ROS) have been extensively linked to carcinogenesis and cancer progression. However, studies have reported conflicting evidence regarding the role of ROS in cancer, mostly dependent on the cancer type or the step of the tumorigenic process. We review recent studies describing diverse aspects of the interplay of ROS with cancer in the different stages of cancer progression, with a special focus on their role in carcinogenesis, their importance for cancer cell signaling and their relationship to the most prevalent cancer risk factors.


Assuntos
Carcinogênese/metabolismo , Progressão da Doença , Neoplasias/metabolismo , Neoplasias/patologia , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Animais , Carcinogênese/patologia , Humanos , Fatores de Risco
8.
Expert Opin Ther Pat ; 31(1): 81-90, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32945223

RESUMO

INTRODUCTION: OX40 is an immune checkpoint in cancer and its presence in cancer is a good prognosis, making it a highly relevant target for the development of new immunotherapies. AREAS COVERED: The patent literature reveals vital information on new trends in cancer therapies. The authors used the patent databases of the six major patent offices in the world: United States Patent and Trademark Office, European Patent Office, World Intellectual Property Organization, Japan Patent Office, State Office of Intellectual Property of China and Korean Intellectual Property Office, to generate a panorama of patents related to OX40 agonists. Specific patents have been grouped into innovative patents and adoption patents. EXPERT OPINION: An increasing trend in the development of OX40 agonists in cancer, particularly in the years 2018 and 2019. United States was the leader in generating patents, followed by China and England. Major pharmaceutical companies have at least one anti-OX40 agonist, MEDI6469 and MEDI-0562 (AstraZeneca), PF-04518600 (Pfizer), GSK3174998 (GlaxoSmithKline), BMS-986,178 (Bristol-Myers Squibb) and MOXR0916 (Roche), which represent 68% of clinical trials conducted with OX40 agonists.


Assuntos
Antineoplásicos/farmacologia , Neoplasias/tratamento farmacológico , Receptores OX40/agonistas , Animais , Desenvolvimento de Medicamentos , Humanos , Imunoterapia , Neoplasias/imunologia , Neoplasias/patologia , Patentes como Assunto , Receptores OX40/imunologia
9.
PLoS One ; 15(9): e0239785, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32976525

RESUMO

Porcine rubulavirus (PRV), which belongs to the family Paramyxoviridae, causes blue eye disease in pigs, characterized by encephalitis and reproductive failure in newborn and adult pigs, respectively. There is no effective treatment against PRV and no information on the effectiveness of the available vaccines. Continuous outbreaks have occurred in Mexico since the early 1980s, which have caused serious economic losses to pig producers. Vaccination can be used to control this disease. Searching for effective antigen candidates against PRV, we first sequenced the PAC1 F protein, then we used various immunoinformatics tools to predict antigenic determinants of B-cells and T-cells against the two glycoproteins of the virus (HN and F proteins). Finally, we used AutoDock Vina to determine the binding energies. We obtained the F gene sequence of a PRV strain collected in the early 1990s in Mexico and compared its amino acid profile with previous and more recent strains, obtaining an identity similarity of 97.78 to 99.26%. For the F proteins, seven linear B-cell epitopes, six conformational B-cell epitopes and twenty-nine T-cell MHC class I epitopes were predicted. For the HN proteins, sixteen linear B-cell epitopes, seven conformational B-cell epitopes and thirty-four T-cell MHC class I epitopes were predicted. The ATRSETDYY and AAYTTTTCF epitopes of the HN protein might be important for neutralizing the viral infection. We determined the in silico binding energy between the predicted epitopes on the F and HN proteins and swine MHC-I molecules. The binding energy of these epitopes ranged from -5.8 to -7.8 kcal/mol. The present study aimed to assess the use of HN and F proteins as antigens, either as recombinant proteins or as a series of peptides that could activate different responses of the immune system. This may help identify relevant immunogens, saving time and costs in the development of new vaccines or diagnostic tools.


Assuntos
Epitopos/química , Proteína HN/imunologia , Rubulavirus/imunologia , Proteínas Virais de Fusão/imunologia , Animais , Antígenos Virais/química , Antígenos Virais/imunologia , Chlorocebus aethiops , Biologia Computacional/métodos , Epitopos/imunologia , Proteína HN/química , Antígenos de Histocompatibilidade/química , Antígenos de Histocompatibilidade/imunologia , Suínos , Células Vero , Proteínas Virais de Fusão/química
10.
Expert Opin Ther Pat ; 30(2): 83-86, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31874056

RESUMO

Introduction: TIGIT is an inhibitory receptor expressed by lymphocytes that suppresses the immune response against tumor cells. There is a great need to discover and develop new therapies focused on inhibiting the action of TIGIT and consequently improving the immune response in the various types of cancer. Authors of WO2018102536 patent propose a method to eradicate cancer utilizes anti-TIGIT antibody, etigilimab, in combination with anti-PD-1/PD-L1 antibody, nivolumab.Areas covered: WO2018102536 patent describes a method of cancer combinatorial treatment consisting of the utilization of either a pharmaceutical cocktail containing anti-TIGIT and an anti-PD-L1 antibody.Expert opinion: The results of the clinical trials only support trials regarding the tolerability of therapy with etigilimab, but does not show data related to the combined use of etigilimab and nivolumab.


Assuntos
Imunoterapia/métodos , Neoplasias/terapia , Nivolumabe/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Antígeno B7-H1/antagonistas & inibidores , Humanos , Neoplasias/imunologia , Patentes como Assunto , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptores Imunológicos/antagonistas & inibidores
11.
Expert Opin Ther Pat ; 29(12): 921-924, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31627712

RESUMO

Introduction: OX40 is a potent costimulatory receptor of the immune response in various types of cancer and has been used as a target for the generation of agonists of its function. Authors of WO2018202649 patent propose a method to eradicate cancer using a bispecific antibodies against OX40/CTLA-4.Areas covered: WO2018202649 patent describes several bispecific antibodies capable of specifically binding to OX40 and CTLA-4 that target regulatory T cells in the tumor microenvironment.Expert opinion: WO2018202649 patent demonstrates that bispecific antibodies against OX40/CTLA-4 have anti-tumor activity against colon, pancreatic and bladder cancer, and that there is a synergistic action with anti-PD-1 antibodies for the treatment of colon cancer. However, there is no evidence to conclude that bispecific antibodies can be used in cancers other than colon, pancreas and bladder. Likewise, the patent only describes the application in combinatorial therapy with anti-PD-1 antibodies, without presenting data relative to the combination with other immunotherapeutic agents against other checkpoint targets.


Assuntos
Anticorpos Biespecíficos/administração & dosagem , Imunoterapia/métodos , Neoplasias/tratamento farmacológico , Animais , Anticorpos Biespecíficos/imunologia , Antígeno CTLA-4/imunologia , Sinergismo Farmacológico , Quimioterapia Combinada , Humanos , Terapia de Alvo Molecular , Neoplasias/imunologia , Neoplasias/patologia , Patentes como Assunto , Receptores OX40/imunologia , Microambiente Tumoral/imunologia
12.
Int J Mol Sci ; 21(1)2019 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-31905601

RESUMO

The participation of proinflammatory cytokines in the progression of Multiple Sclerosis (MS) has been well documented. Cytokines activate the JAK-STAT pathway, in which the suppressors of cytokine signaling (SOCS) exert a negative feedback. This paper analyzes the levels of SOCS5 and SOCS7 transcripts, quantified by RT-qPCR, in MS patients, and the concentrations of proinflammatory cytokines, IFN-γ, IL17, and IL6, determined by ELISA. Samples of peripheral blood were obtained from MS patients in the relapsing-remitting phase, treated with IFN-ß or glatiramer acetate (GA), and from healthy individuals. SOCS7 mRNA was significantly higher in patients treated with GA (1.36 ± 0.23) than in those treated with IFN-ß (0.65 ± 0.1). Regarding gender, the level of SOCS5 and SOCS7 transcripts were similar between MS and healthy females; in MS males, the level of SOCS7 transcripts were significantly lower (0.59 ± 0.03) than in healthy males (1.008 ± 0.05). Plasmatic levels of IFN-γ were significantly higher in MS patients (60 pg/mL, range 0-160) than in healthy subjects (0 range, 0-106). The same pattern was observed in MS patients treated with IFN-ß (68 pg/mL, range 0-160) compared to patients treated with GA (51 pg/mL, range 0-114), and in MS females (64 pg/mL, range 0-161) compared to healthy females (0, range 0-99). We hypothesize that the increase in SOCS7 transcription in patients treated with GA could partially explain the action mechanism of this drug, while the increase in the concentration of IFN-γ in MS patients could help elucidate the immunopathology of the disease.


Assuntos
Acetato de Glatiramer/uso terapêutico , Interferon beta/uso terapêutico , Esclerose Múltipla Recidivante-Remitente/genética , Proteínas Supressoras da Sinalização de Citocina/genética , Adulto , Feminino , Humanos , Fatores Imunológicos/uso terapêutico , Imunossupressores/uso terapêutico , Interferon gama/sangue , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas Supressoras da Sinalização de Citocina/metabolismo
13.
PLoS One ; 13(10): e0205356, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30304056

RESUMO

BACKGROUND: Occult hepatitis B infection (OBI) is defined as the presence of hepatitis B virus (HVB) DNA in the liver of HBsAg negative individuals with or without detectable viral DNA in serum. OBI is a diagnostic challenge as it is characterized by a very low viral load, intermittently detectable through time. Individuals with OBI can develop chronic hepatic disease, including liver cirrhosis and hepatocellular carcinoma. The aim of this work was to produce tools to improve OBI detection of the HVB genotypes prevalent in Mexico. METHODS: We designed and tested primers to detect OBI in serum samples by nested and real-time PCR. Conserved sites in the viral genome were determined by alignment of the most frequent HBV genotypes in Mexico (H, G/H, F and D) and primers spanning the entire viral genome were designed for first round and nested PCR. Primers were tested in serum samples of 45 patients not co-infected with hepatitis C virus or with HIV, out of a group of 116 HBsAg (-)/anti-HBc (+) individuals. Primers were also tested in a control group with chronic HBV. Nested PCR products obtained from HBsAg (-)/anti-HBc (+) were sequenced and used to design primers for real-time PCR (SYBR Green). RESULTS: The most effective primer pairs to detect HBV products by nested PCR targeted ORF regions: PreS2/P, S/P, X/PreC, and C; while by real-time PCR they targeted ORF regions PreS2/P, S/P, X, and C. Out of the 45 HBsAg (-)/anti-HBc (+) patients tested, the viral genome was detected in 28 (62.2%) and 34 (75.5%), with nPCR and real-time PCR respectively. CONCLUSION: Primers designed for real-time PCR detected up to 75.5% of suspected OBI Mexican patients, with or without liver disease, which represents an improvement from previous PCR strategies.


Assuntos
DNA Viral/sangue , Vírus da Hepatite B/isolamento & purificação , Hepatite B/sangue , Fígado/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Genótipo , Hepatite B/epidemiologia , Hepatite B/genética , Hepatite B/virologia , Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B/genética , Vírus da Hepatite B/patogenicidade , Humanos , Fígado/patologia , Fígado/virologia , Masculino , México , Pessoa de Meia-Idade , Carga Viral
14.
Infect Drug Resist ; 11: 1751-1756, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30349332

RESUMO

BACKGROUND: Influenza causes high rates of morbidity and mortality. Genetic variability of influenza viruses generates resistance to antivirals, which are of two types, since they act on two different viral targets: adamantanes, which block the M2 ion channel, and the neuraminidase (NA) inhibitors. METHODS: In Mexico, the available studies on the antiviral resistance of circulating influenza strains are scarce, so this work undertook an analysis of the Mexican sequences reported in public gene banks to perform a systematic analysis of the antiviral resistance markers on both M2 and NA. In all, 284 M2 sequences and 423 NA sequences were retrieved from three genetic databases (sequences from 2000 to 2017 were considered). RESULTS: The resistance markers to M2 blockers were present in 100% of H1N1 pdm2009, 83.6% of H3N2, and 5.8% of seasonal H1N1 sequences. Two resistance markers conferring resistance to NA inhibitors were present in seasonal H1N1 sequences, H275Y (50.0%) and N70S (33.3%). None of these viruses had both resistance markers, which are associated with oseltamivir resistance. The more frequent resistance marker in H1N1 pdm2009 NA sequences was H275Y, present in 3.6%, while S247N was present in 0.30%. Only one of the resistance-associated markers (Q136K) in NA (1.5%) was present in the analyzed H3N2 sequences, while sequences of influenza B virus did not present resistance markers to NA inhibitors. Some influenza A H1N1 pdm2009 sequences (1.8%) presented resistance markers to both M2 and NA. CONCLUSION: Based on the present analysis, 7.1% of the all serotypes of influenza virus A sequences analyzed in Mexico from 2000 to 2017 have mutations conferring resistance to NA inhibitors. Because of this, and the limited availability of influenza drugs, it is necessary to increase the epidemiological surveillance, including molecular analysis, which will provide data such as the presence of changes associated with antiviral resistance.

15.
Mol Med Rep ; 18(1): 617-621, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29749491

RESUMO

ST3GAL4 gene expression is altered in different cancer types, including cervical cancer. Several mRNA transcripts have been reported for this gene; however, their expression levels in cervical cancer have not been analyzed. ST3GAL4 encodes for ß­galactosidase α­2,3­sialyltransferase 4, involved in the biosynthesis of the tumour antigens sLe(x) and sulfo­sLe(x). The present study evaluated the presence of three mRNA variants (V1, V2 and V3) in cervical cancer cell lines, detecting the three variants. Additionally, the expression level of the V1 transcript of the ST3GAL4 gene was determined by reverse transcription­quantitative polymerase chain reaction in cervical cell lines and in normal, premalignant and cervical cancer tissue. The V1 transcript of the ST3GAL4 demonstrated significant decreased expression in premalignant and malignant cervical tissues. The results suggested that deregulation of this gene could occur prior to the presence of cancer and demonstrated the importance of evaluating the expression level of V1, and its association with disease progression.


Assuntos
Regulação Neoplásica da Expressão Gênica , Isoformas de RNA/genética , Sialiltransferases/genética , Neoplasias do Colo do Útero/enzimologia , Adolescente , Adulto , Idoso , Progressão da Doença , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias do Colo do Útero/genética , Adulto Jovem
16.
BMC Complement Altern Med ; 18(1): 95, 2018 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-29548293

RESUMO

BACKGROUND: Urtica dioica, Taraxacum officinale, Calea integrifolia and Caesalpinia pulcherrima are widely used all over the world for treatment of different illnesses. In Mexico, these plants are traditionally used to alleviate or counteract rheumatism and inflammatory muscle diseases. In the present study we evaluated the activity of aqueous and methanolic extracts of these four plants, on the replication of dengue virus serotype 2 (DENV2). METHODS: Extraction process was carried out in a Soxtherm® system at 60, 85 and 120 °C; a chemical fractionation in silica gel chromatography was performed and compounds present in the active fractions were identified by HPLC-DAD-ESI/MSn. The cytotoxic concentration and the inhibitory effect of extracts or fractions on the DENV2 replication were analyzed in the BHK-21 cell line (plaque forming assay). The half maximal inhibitory concentration (IC50) and the selectivity index (SI) were calculated for the extracts and fractions. RESULTS: The methanolic extracts at 60 °C of T. officinale and U. dioica showed the higher inhibitory effects on DENV2 replication. After the chemical fractionation, the higher activity fraction was found for U. dioica and T. officinale, presenting IC50 values of 165.7 ± 3.85 and 126.1 ± 2.80 µg/ml, respectively; SI values were 5.59 and 6.01 for each fraction. The compounds present in T. officinale, were luteolin and caffeoylquinic acids derivatives and quercertin diclycosides. The compounds in the active fraction of U. dioica, were, chlorogenic acid, quercertin derivatives and flavonol glycosides (quercetin and kaempferol). CONCLUSIONS: Two fractions from U. dioica and T. officinale methanolic extracts with anti-dengue activity were found. The compounds present in both fractions were identified, several recognized molecules have demonstrated activity against other viral species. Subsequent biological analysis of the molecules, alone or in combination, contained in the extracts will be carried out to develop therapeutics against DENV2.


Assuntos
Antivirais/farmacologia , Vírus da Dengue/efeitos dos fármacos , Extratos Vegetais/farmacologia , Taraxacum/química , Urtica dioica/química , Replicação Viral/efeitos dos fármacos , Antivirais/química , Cromatografia Líquida de Alta Pressão , Dengue/virologia , Vírus da Dengue/classificação , Vírus da Dengue/fisiologia , Humanos , Espectrometria de Massas , Extratos Vegetais/química
17.
Int J Mol Sci ; 19(2)2018 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-29439487

RESUMO

Alternative splicing is a key mechanism determinant for gene expression in metazoan. During alternative splicing, non-coding sequences are removed to generate different mature messenger RNAs due to a combination of sequence elements and cellular factors that contribute to splicing regulation. A different combination of splicing sites, exonic or intronic sequences, mutually exclusive exons or retained introns could be selected during alternative splicing to generate different mature mRNAs that could in turn produce distinct protein products. Alternative splicing is the main source of protein diversity responsible for 90% of human gene expression, and it has recently become a hallmark for cancer with a full potential as a prognostic and therapeutic tool. Currently, more than 15,000 alternative splicing events have been associated to different aspects of cancer biology, including cell proliferation and invasion, apoptosis resistance and susceptibility to different chemotherapeutic drugs. Here, we present well established and newly discovered splicing events that occur in different cancer-related genes, their modification by several approaches and the current status of key tools developed to target alternative splicing with diagnostic and therapeutic purposes.


Assuntos
Processamento Alternativo , Antineoplásicos/uso terapêutico , Neoplasias/genética , Oligonucleotídeos Antissenso/uso terapêutico , Animais , Humanos , Neoplasias/tratamento farmacológico
18.
Hepat Mon ; 16(6): e36942, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27630726

RESUMO

BACKGROUND: The hepatitis B virus (HBV) causes chronic hepatitis, hepatic cirrhosis, and hepatocellular carcinoma. Surface antigen (HBsAg) detection is a definitive test that can confirm HBV infection, while the presence of antibodies against the core protein (anti-HBc) suggests either a previous or ongoing infection or occult hepatitis B infection (OBI). OBJECTIVES: The aim of the present study was to determine the prevalence of anti-HBc and HBsAg in blood donors. Further, the study aimed to estimate the anti-HBc level at which HBV DNA is detected in putative OBI cases, as well as to search for mutations in the "a" determinant associated with the non-detection of HBsAg in serum. PATIENTS AND METHODS: We conducted a cross-sectional study from 2003-2009. The study included 120,552 blood donors from the state of Puebla, Mexico. Different commercial systems based on microparticles (enzymatic (MEIA) or chemiluminescent (CMIA)) were used to determine the HBsAg and anti-HBc levels. For the detection of HBV DNA, a nested polymerase chain reaction (nested PCR) was used and the genotypes were determined using Sanger sequencing. RESULTS: Of the 120,552 blood donors, 1437 (1.19%, 95% CI: 1.12 - 1.26) were reactive to anti-HBc, while 82 (0.066%, 95% CI: 0.053 - 0.079) were reactive to HBsAg. Some 156 plasma samples collected in 2009 from anti-HBc-positive/HBsAg-negative blood donors were submitted for HBV DNA detection in a search for probable OBI. Viral DNA was detected in 27/156 (17.3%, 95% CI: 11.5 - 23.1). Our results show an association between HBV DNA or HBsAg and anti-HBc S/CO levels ≥ 4.0. All DNA samples were identified as genotype H and some "a" determinant mutations were identified, although none corresponded to mutations previously reported to hinder the detection of HBsAg by commercial immunoassays. CONCLUSIONS: We observed that as the anti-HBc levels increase, there is a higher prevalence of the viral protein HBsAg in blood donors. Samples testing positive for HBV-DNA were seen to exhibit a ten-fold higher presence of anti-HBc S/CO ≥ 4 than those with S/CO ≥ 1 and < 4.0, which highlights the relevance of anti-HBc determination in blood donor samples.

19.
Biomed Res Int ; 2016: 3681094, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27610372

RESUMO

In eukaryotes, genes are frequently interrupted with noncoding sequences named introns. Alternative splicing is a nuclear mechanism by which these introns are removed and flanking coding regions named exons are joined together to generate a message that will be translated in the cytoplasm. This mechanism is catalyzed by a complex machinery known as the spliceosome, which is conformed by more than 300 proteins and ribonucleoproteins that activate and regulate the precision of gene expression when assembled. It has been proposed that several genetic diseases are related to defects in the splicing process, including cancer. For this reason, natural products that show the ability to regulate splicing have attracted enormous attention due to its potential use for cancer treatment. Some microbial metabolites have shown the ability to inhibit gene splicing and the molecular mechanism responsible for this inhibition is being studied for future applications. Here, we summarize the main types of natural products that have been characterized as splicing inhibitors, the recent advances regarding molecular and cellular effects related to these molecules, and the applications reported so far in cancer therapeutics.


Assuntos
Processamento Alternativo/efeitos dos fármacos , Antineoplásicos/farmacologia , Neoplasias/tratamento farmacológico , Animais , Álcoois Graxos/farmacologia , Humanos , Camundongos , Piranos/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
20.
J Biotechnol ; 223: 52-61, 2016 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-26940828

RESUMO

Blue-eye disease (BED) of swine is a viral disease endemic in Mexico. The etiological agent is a paramyxovirus classified as Porcine rubulavirus (PoRV-LPMV), which exhibits in its envelope the hemagglutinin-neuraminidase (HN) glycoprotein, the most immunogenic and a major target for vaccine development. We report in this study the obtaining of ectodomain of PoRV HN (eHN) through the Pichia pastoris expression system. The expression vector (pPICZαB-HN) was integrated by displacement into the yeast chromosome and resulted in a Mut(+) phenotype. Expressed eHN in the P. pastoris X33 strain was recovered from cell-free medium, featuring up to 67 nmol/min/mg after 6 days of expression. eHN was recognized by the serum of infected pigs with strains currently circulating in the Mexican Bajio region. eHN induces antibodies in mice after 28 days of immunization with specific recognition in ELISA test. These antibodies were able to inhibit >80% replication by viral neutralization assays in cell culture. These studies show the obtaining of a protein with similar characteristics to the native HN and which may be a candidate to propose a vaccine or to use the antigen in a serologic diagnostic test.


Assuntos
Proteína HN/química , Pichia/crescimento & desenvolvimento , Proteínas Recombinantes/metabolismo , Rubulavirus/metabolismo , Animais , Anticorpos Antivirais/metabolismo , Sistema Livre de Células , Proteína HN/genética , Proteína HN/imunologia , Proteína HN/metabolismo , Imunização , Camundongos , Pichia/genética , Domínios Proteicos , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Rubulavirus/genética , Suínos
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