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During the summer of 2022, a cluster of Madagascar periwinkle plants with white and mauve flowers were observed with foliar mild yellow mosaic symptoms on a private property in Harlingen, Cameron County, Texas. The symptoms were reproduced on mechanically inoculated periwinkle and Nicotiana benthamiana plants. Virions of 776 to 849 nm in length and 11.7 to 14.8 nm in width were observed in transmission electron microscopy of leaf dip preparations made from symptomatic periwinkle leaves. High-throughput sequencing (HTS) analysis of total RNA extracts from symptomatic leaves revealed the occurrence of two highly divergent variants of a novel Potyvirus species as the only virus-like sequences present in the sample. The complete genomes of both variants were independently amplified via reverse transcriptase PCR, cloned, and Sanger sequenced. The 5' and 3' of the genomes were acquired using random amplification of cDNA ends methodology. The assembled virus genomes were 9,936 and 9,944 nucleotides (nt) long, and they shared 99.9 to 100% identities with the respective HTS-derived genomes. Each genome encoded hypothetical polyprotein of 3,171 amino acids (aa) (362.6 kilodaltons [kDa]) and 3,173 aa (362.7 kDa), respectively, and they shared 77.3/84.4% nt/aa polyprotein identities, indicating that they represent highly divergent variants of the same Potyvirus species. Both genomes also shared below-species-threshold polyprotein identity levels with the most closely phylogenetically related known potyviruses, thus indicating that they belong to a novel species. The name periwinkle mild yellow mosaic virus (PwMYMV) is given to the potyvirus with complete genomes of 9,936 nt for variant 1 (PwMYMV-1) and 9,944 nt for variant 2 (PwMYMV-2). We propose that PwMYMV be assigned into the genus Potyvirus (family Potyviridae).
Assuntos
Catharanthus , Genoma Viral , Filogenia , Doenças das Plantas , Potyvirus , Potyvirus/genética , Potyvirus/classificação , Potyvirus/isolamento & purificação , Doenças das Plantas/virologia , Genoma Viral/genética , Catharanthus/virologia , Folhas de Planta/virologia , Sequenciamento de Nucleotídeos em Larga Escala , RNA Viral/genética , Variação Genética , Nicotiana/virologia , TexasRESUMO
The generation of anti-tumor immunity in the draining lymph nodes is known as the cancer immunity cycle. Accumulating evidence supports the occurrence of such a cycle at tumor sites in the context of chronic inflammation. Here, we review the role of tertiary lymphoid structures (TLS) in the generation of T and B cell immunities, focusing on the impact of B cells that undergo full maturation, resulting in the generation of plasma cells (PCs) producing high-affinity IgG and IgA antibodies. In this context, we propose that antibodies binding to tumor cells induce macrophage or natural killer (NK)-cell-dependent apoptosis. Subsequently, released antigen-antibody complexes are internalized and processed by dendritic cells (DCs), amplifying antigen presentation to T cells. Immune complexes may also be fixed by follicular DCs (FDCs) in TLS, thereby increasing memory B cell responses. This amplification loop creates an intra-tumoral immunity cycle, capable of increasing sensitivity of tumors to immunotherapy even in cancers with low mutational burden.
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Background: The identification of genetic risk factors for Acute Lymphoblastic Leukemia (ALL), are increasingly urgent and necessary. Objective: The purpose of this study is to determine the association of the genetic polymorphisms ABCC1 rs3743527, NCF4 rs1883112 and CBR3 rs1056892 with ALL. Methods: DNA samples were obtained in 71 children with ALL (from 2 to 18 years) and in 71 controls without ALL, to determine the polymorphisms by real-time polymerase chain reaction (qPCR), using specific TaqMan probes in a StepOne® thermal cycler (Applied Biosystems, United States). Results: The results of the Odds Ratio analysis show that in the rs1883112 polymorphism of the NCF4 gene, the heterozygous allele has a risk effect for ALL (OR = 3.1870, CI = 1.8880-7.9383 and p = 0.0002), in turn the mutated genotype (AA) is associated with a protective effect (OR = 0.26, 0.1248 to 0.5434 and p = 0.0003). On the other hand, the CBR3 rs1056892 polymorphism shows a significant association of risk to ALL, in the presence of the HT genotype (OR = 2.77, IC = 1.3837 to 5.5651 and p = 0.004) and the mutated genotype of this polymorphism has a significant association with protection to ALL in the HM genotype (OR = 0.52, IC = 0.2639 to 1.0304 and p = 0.05). While the inheritance models of the polymorphisms let us see that of the rs1883112 polymorphism of the NCF4 polymorphism; the HT genotype of the codominant model shows a protective effect against ALL (OR = 0.4117, IC = 0.1718 to 0.9866 and p = 0.04), the recessive model shows us and confirms what we already saw in table number 3, being that there is an association with protective effect in the HM genotype (OR = 0.2604, IC = 0.1248 to 0.5434 and p = 0.0003). In the polymorphism rs1056892 of the CBR3 gene, a protection association was found in the heterozygous allele of the codominant model (OR = 0.3448, IC = 0.1375 to 0.8896 and p = 0.0274). In addition, the recessive inheritance model for the HM genotype shows a protective effect to ALL, (OR = 0.52, CI = 0.9919 to 3.8638 and p = 0.05). Conclusion: There is an evident impact of the NCF4 rs1883112 and CBR3 rs1056892 polymorphisms with an increased risk of susceptibility to ALL; Likewise, through the codominant inheritance model, the effect of the variation of the CBR3 rs1056892 gene as a protective factor against ALL was evaluated.
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BACKGROUND: Folate metabolism plays an essential role in the processes of DNA synthesis and methylation. Deviations in the folate flux resulting from single-nucleotide polymorphisms in genes encoding folate-dependent enzymes may affect the susceptibility to leukemia. This case-control study aimed to assess associations among MTHFR (C677T, A1298C) and TPMT (*2, *3A) mutations as well as to evaluate the synergistic effects of combined genotypes for both genes. Therefore, these genetic variants may lead to childhood acute lymphoblastic leukemia (ALL) susceptibility, in a Mexican population study. METHODS: DNA samples obtained from 70 children with ALL and 152 age-matched controls (range, 1-15 years) were analyzed by real-time reverse transcription polymerase chain reaction (RT-qPCR) to detect MTHFR C677T and A1298C and TPMT*2 and TPMT*3A genotypes. RESULTS: The frequency of the MTHFR A1298C CC genotype was statistically significant (odds ratio [OR], 6.48; 95% 95% confidence intervals [CI], 1.26-33.2; p=0.025). In addition, the combined 677CC+1298AC genotype exhibited a statistically significant result (OR, 0.23; 95% CI, 0.06-0.82; p=0.023). No significant results were obtained from the MTHFR (C677T CT, C677T TT) or TPMT (*2, *3A) genotypes. More importantly, no association between the synergistic effects of either gene (MTHFR and/or TPMT) and susceptibility to ALL was found. CONCLUSIONS: The MTHFR A1298C CC genotype was associated with an increased risk of developing childhood ALL. However, a decreased risk to ALL with the combination of MTHFR 677CC+1298AC genotypes was found.
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Predisposição Genética para Doença , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Metiltransferases/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Genótipo , Humanos , Lactente , Masculino , México , Mutação , Polimorfismo de Nucleotídeo Único , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
BACKGROUND: Acute lymphoblastic leukemia (ALL) is one of the most frequent oncological disorders in pediatric populations. To date, the drug of choice for the treatment of ALL is methotrexate, a drug associated with a high risk of adverse reactions (ADRs). The xanthine oxidase (XO) polymorphisms, 1936A>G and 2107A>G, as well as the polymorphic variants derived from ATP-binding cassette transporter gene subfamilies, ABCB1 and ABCC5, of drug resistant codifying genes, are implicated as precursors of drug-related neurologic, hepatic, and renal toxicities. Our aim was to determine whether the mentioned polymorphisms are risk or protective factors for the development of adverse reactions by methotrexate in our pediatric population with ALL. METHODS: A total of 35 Mexican children from Centro Estatal de Cancerología-Durango, Mexico, with ALL and the previously noted polymorphisms as determined qPCR were studied. At the same time, a 12-month drug monitoring program was conducted in accordance with WHO-PAHO guidelines for pharmacovigilance. RESULTS: The ABCB11936A>G and 2107A>G and ABCC5 3414+434A>C polymorphisms were not associated with methotrexate ADRs. Single nucleotide polymorphisms (SNPs) of ABCB1 1236C>T (OR 0.19, 95% CI: 0.03-0.9, p<0.05) and ABCC5 3933+313T>C (OR 0.12, 95% CI: 0.027-0.58, p<0.05) were associated with methotrexate ADRs. CONCLUSIONS: SNPs 1236C>T of ABCB1 and ABCC5 3933+313T>C are not associated with the development of typical ADRs by methotrexate, rather, they showed a protective factor for myelosuppression in the studied sick population.
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Antimetabólitos Antineoplásicos/efeitos adversos , Metotrexato/efeitos adversos , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Polimorfismo de Nucleotídeo Único , Xantina Oxidase/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Adolescente , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/uso terapêutico , Institutos de Câncer , Criança , Pré-Escolar , Feminino , Estudos de Associação Genética , Humanos , Quimioterapia de Manutenção/efeitos adversos , Masculino , Metotrexato/administração & dosagem , Metotrexato/uso terapêutico , México , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Mielopoese/efeitos dos fármacos , Farmacovigilância , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/enzimologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Estudos Prospectivos , Xantina Oxidase/metabolismoRESUMO
OBJECTIVE: The aim of the present work was to look at differences in the placental tissue expression of KiSS-1 and REN genes from preeclamptic and healthy pregnant women, that could account for a possible synergistic function for both genes in the pathogenesis of preeclampsia. STUDY DESIGN: This case-control study involved 27 preeclamptic women and 27 normoevolutive pregnant women. cDNA was obtained from placental tissue to carry out qPCR for both KiSS-1 and REN genes in order to compare mRNA expression levels in the studied groups. Statistical analysis showed expression differences that correlate with clinical and/or biochemical variables. RESULTS: Higher expression for KiSS-1 in PEE vs. control woman (p=0.001) was observed, whereas no difference was observed for REN expression (p=0.300) when all the subjects were included. However, REN expression was significant higher when the samples were stratified according to preeclampsia severity. For 18 mild preeclamptic patients the p-value was p=0.001 compared to their controls, while for the remaining nine with severe preeclampsia the expression became significant (p=0.001). CONCLUSION: Our results suggest that the high KiSS-1 expression seen in preeclamptic patients is in accordance with its role as an inhibitor of trophoblast invasiveness and maintained until the end of gestation. On the other hand, aggressive therapeutic management and/or severity status of patients have a direct effect on placental REN expression levels, masking the natural high expression of this gene on preeclamptic placental tissue. Therefore it was not possible to establish a real concordant expression profile for KiSS-1 and REN genes.
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Kisspeptinas/metabolismo , Placenta/metabolismo , Pré-Eclâmpsia/metabolismo , Proteínas da Gravidez/metabolismo , Renina/metabolismo , Regulação para Cima , Adolescente , Adulto , Anti-Hipertensivos/uso terapêutico , Estudos de Casos e Controles , Análise por Conglomerados , Feminino , Estudos de Associação Genética , Humanos , Hipertensão/etiologia , Kisspeptinas/genética , Pré-Eclâmpsia/tratamento farmacológico , Pré-Eclâmpsia/fisiopatologia , Pré-Eclâmpsia/urina , Gravidez , Proteínas da Gravidez/genética , Proteinúria/etiologia , RNA Mensageiro/metabolismo , Renina/genética , Índice de Gravidade de Doença , Regulação para Cima/efeitos dos fármacos , Adulto JovemRESUMO
En el Hospital General "Dr. Darío Fernández", en el período de 1993-1994, se estudiaron 50 pacientes con una edad media de 20-30 años y síntomas de enfermedad acidopéptica. A todos se les practicó endoscopía y toma de biopsia del antro gástrico en la cual se realizó detección de ureasa y estudio morfológico de la mucosa gástrica. La ureasa fue positiva en 14 de las 20 biopsias obtenidas. Morfológicamente, el 40 por ciento se diagnosticaron como gastritis crónica activa; el 30 por ciento como gastritis crónica atrófica; el 18 por ciento como gastritis crónica superficial y el 1 por ciento como gastritis crónica con metaplasia intestinal. El H. pylori se observó con más frecuencia en las biopsias de los pacientes con gastritis crónica activa. Hacemos énfasis en la necesidad de tomar biopsia, durante la endoscopia, a todos los pacientes con síntomas de enfermedad ácido péptica y hacer una correlación con los estudios histoquímicos e inmunológicos