Germinal center B-cell-like diffuse large B-cell lymphoma (GCB-DLBCL) is a common subtype of lymphoma in adults. Previously, we found that actin filament-associated protein 1-antisense RNA 1 (AFAP1-AS1) is among the most overexpressed lncRNAs in GCB-DLBCL. In this study, we explored its biological functions and molecular mechanisms in the progression of GCB-DLBCL. We discovered, via bioinformatics, that patients with a high expression of AFAP1-AS1 had significantly poor disease-free survival (DFS) and overall survival (OS). Subsequent assays demonstrated that AFAP1-AS1 knockdown inhibited cell proliferation and prompted arrest of the G0/G1 cell cycle and apoptosis in GCB-DLBCL cell lines. Proteomics analysis indicated that hundreds of proteins were deregulated after AFAP1-AS1 knockdown and KEGG pathway analysis revealed that the deregulated proteins belonged to multiple signaling pathways, such as "B-cell receptor signaling pathway". Moreover, in the comprehensive identification of proteins that bind to RNA (by ChIRP-MS), several proteins associated with RNA splicing were identified (e.g., SFPQ, NONO, SRSF2, SRSF6, and KHSRP) that could specifically bind to AFAP1-AS1, which was confirmed by parallel reaction monitoring assay (PRM). Conclusively, we demonstrated that AFAP1-AS1 is a possible prognostic marker of poor outcomes in GCB-DLBCL patients and could modulate gene expression through connecting to specific proteins to practice its oncogenic role in GCB-DLBCL.Acute Lymphoblastic Leukemia (ALL) is the most common type of cancer in children. Polymorphisms that alter the normal function of the microRNAs involved in the development of ALL have been widely investigated, although published data on these polymorphisms in admixed populations are scarce. We investigated the role of 10 polymorphisms in the microRNA and protein-coding genes of the microRNA synthesis complex in susceptibility to pediatric B-cell ALL. The study includes 100 pediatric ALL patients and 180 healthy individuals. The statistical analyses were run in SPSS v.25.0. In the case of the microRNA synthesizing genes, a significant pattern was found in only gene, that is, the rs3805500 polymorphism of DROSHA, in which the homozygous mutant (AA) genotype was associated with a threefold increase in the risk of developing ALL when compared to other genotypes (P=0.004, OR=2.913, CI=1.415-5.998). In the microRNA coding genes, the homozygous mutant rs3746444 genotype of the MIR499A gene was associated with a 17-fold increase in the risk of development of ALL (P less then 0.001, OR=17.797, CI=5.55-57.016). A protective effect against the development of ALL was also observed in the carriers of the wild homozygous rs2505901 genotype in the MIR938 gene. Our findings highlight the potential of these polymorphisms in the genes involving in the coding of microRNAs for the evaluation of the risk of contracting ALL in the population of the Brazilian Amazon region. These findings contribute to a more complete understanding of the complex etiology of ALL.Eosinophil cationic protein (ECP) is a cytotoxic protein released from eosinophils. https://www.selleckchem.com/products/crenolanib-cp-868596.html The level of ECP increases in some allergic diseases. Recently, vitamin D deficiency has been suggested to be a risk factor for childhood allergic disease. The first aim of the study is to measure the serum vitamin D levels and ECP in infants with ***'s milk protein allergy (CMPA) and compare them with controls. The second aim of this study is to investigate whether vitamin D levels are correlated with ECP or not. Sixty-two infants with CMPA were compared to 58 healthy, similar to distribution of age and sex normal infants as controls. The serum ECP levels were detected by an immunoassay system. Serum 25(OH)D levels were measured by using an enzyme-linked immunoassay kit. Vitamin D deficiency was defined as a serum 25(OH)D level of less then 10 ng/mL and sufficient 30 ng/mL. The median serum ECP level in the CMPA group was significantly higher than in the control group (51.45 and 17.55 ng/mL, respectively, P = 0.001). There were no significant differences between groups with regards to median 25(OH)D levels (29.31 ± 1.67 and 27.32 ± 1.41 ng/mL, respectively, P = 0.646). The serum 25(OH)D levels were under 30 ng/mL in 38 of infants with CMPA (61.2%) and in 32 of controls (55.1%). Correlation analysis between the serum 25(OH)D level and ECP of infants with CMPA have revealed no significant relation (P = 0.888). Our results do not support the hypothesis that vitamin D deficiency may be a risk factor for CMPA.This study aimed to investigate factors affecting coronavirus disease 2019 (COVID-19) progression, also to explore the clinical features and prognosis of nervous system symptom (NSS) involved COVID-19 patients. 417 COVID-19 patients were analyzed in this retrospective study, and they were clinically classified as severe patients and non-severe patients. According to NSS involved status, COVID-19 patients were further divided into NSS patients and non-NSS patients. Elderly cases, males, common comorbidities, NSS, respiratory/cardiovascular/gastrointestinal symptoms, bilateral lesion, multifocal lesion, bacterial infection, bacterial&fungal infection were more common in severe patients compared to non-severe patients. Meanwhile, severe COVID-19 patients showed increased baseline APTT, TT, D-dimer, CRP, ESR, CK-MB, creatine kinase, AST, ALT, creatinine, but decreased baseline platelet level, lymphocyte, albumin, GFR compared to non-severe patients. Notably, the continuous differences of lymphocyte, D-dimer, CRP, AST, ALT, albumin, GFR between severe patients and non-severe patients during treatment were observed. Age, NSS, bacterial & fungal infection, CRP and creatinine were further identified as independent risk factors for severe COVID-19, which could predict severe COVID-19 with area under curve of 0.861. Furthermore, severe patients presented with worse prognosis. Regrading NSS patients, they were related to older age, surgery history, diabetes comorbidities, respiratory/cardiovascular/gastrointestinal symptoms, bilateral lesion, multifocal lesion, bacterial infection, bacterial&fungal infection and more dysregulated laboratory indexes compared to non-NSS patients. Besides, NSS patients were correlated with poor prognosis to some extent. More intensive attention should be paid to COVID-19 patients with severe-disease risk factors and those with NSS involvement, in case of rapid deterioration.
Germinal center B-cell-like diffuse large B-cell lymphoma (GCB-DLBCL) is a common subtype of lymphoma in adults. Previously, we found that actin filament-associated protein 1-antisense RNA 1 (AFAP1-AS1) is among the most overexpressed lncRNAs in GCB-DLBCL. In this study, we explored its biological functions and molecular mechanisms in the progression of GCB-DLBCL. We discovered, via bioinformatics, that patients with a high expression of AFAP1-AS1 had significantly poor disease-free survival (DFS) and overall survival (OS). Subsequent assays demonstrated that AFAP1-AS1 knockdown inhibited cell proliferation and prompted arrest of the G0/G1 cell cycle and apoptosis in GCB-DLBCL cell lines. Proteomics analysis indicated that hundreds of proteins were deregulated after AFAP1-AS1 knockdown and KEGG pathway analysis revealed that the deregulated proteins belonged to multiple signaling pathways, such as "B-cell receptor signaling pathway". Moreover, in the comprehensive identification of proteins that bind to RNA (by ChIRP-MS), several proteins associated with RNA splicing were identified (e.g., SFPQ, NONO, SRSF2, SRSF6, and KHSRP) that could specifically bind to AFAP1-AS1, which was confirmed by parallel reaction monitoring assay (PRM). Conclusively, we demonstrated that AFAP1-AS1 is a possible prognostic marker of poor outcomes in GCB-DLBCL patients and could modulate gene expression through connecting to specific proteins to practice its oncogenic role in GCB-DLBCL.Acute Lymphoblastic Leukemia (ALL) is the most common type of cancer in children. Polymorphisms that alter the normal function of the microRNAs involved in the development of ALL have been widely investigated, although published data on these polymorphisms in admixed populations are scarce. We investigated the role of 10 polymorphisms in the microRNA and protein-coding genes of the microRNA synthesis complex in susceptibility to pediatric B-cell ALL. The study includes 100 pediatric ALL patients and 180 healthy individuals. The statistical analyses were run in SPSS v.25.0. In the case of the microRNA synthesizing genes, a significant pattern was found in only gene, that is, the rs3805500 polymorphism of DROSHA, in which the homozygous mutant (AA) genotype was associated with a threefold increase in the risk of developing ALL when compared to other genotypes (P=0.004, OR=2.913, CI=1.415-5.998). In the microRNA coding genes, the homozygous mutant rs3746444 genotype of the MIR499A gene was associated with a 17-fold increase in the risk of development of ALL (P less then 0.001, OR=17.797, CI=5.55-57.016). A protective effect against the development of ALL was also observed in the carriers of the wild homozygous rs2505901 genotype in the MIR938 gene. Our findings highlight the potential of these polymorphisms in the genes involving in the coding of microRNAs for the evaluation of the risk of contracting ALL in the population of the Brazilian Amazon region. These findings contribute to a more complete understanding of the complex etiology of ALL.Eosinophil cationic protein (ECP) is a cytotoxic protein released from eosinophils. https://www.selleckchem.com/products/crenolanib-cp-868596.html The level of ECP increases in some allergic diseases. Recently, vitamin D deficiency has been suggested to be a risk factor for childhood allergic disease. The first aim of the study is to measure the serum vitamin D levels and ECP in infants with cow's milk protein allergy (CMPA) and compare them with controls. The second aim of this study is to investigate whether vitamin D levels are correlated with ECP or not. Sixty-two infants with CMPA were compared to 58 healthy, similar to distribution of age and sex normal infants as controls. The serum ECP levels were detected by an immunoassay system. Serum 25(OH)D levels were measured by using an enzyme-linked immunoassay kit. Vitamin D deficiency was defined as a serum 25(OH)D level of less then 10 ng/mL and sufficient 30 ng/mL. The median serum ECP level in the CMPA group was significantly higher than in the control group (51.45 and 17.55 ng/mL, respectively, P = 0.001). There were no significant differences between groups with regards to median 25(OH)D levels (29.31 ± 1.67 and 27.32 ± 1.41 ng/mL, respectively, P = 0.646). The serum 25(OH)D levels were under 30 ng/mL in 38 of infants with CMPA (61.2%) and in 32 of controls (55.1%). Correlation analysis between the serum 25(OH)D level and ECP of infants with CMPA have revealed no significant relation (P = 0.888). Our results do not support the hypothesis that vitamin D deficiency may be a risk factor for CMPA.This study aimed to investigate factors affecting coronavirus disease 2019 (COVID-19) progression, also to explore the clinical features and prognosis of nervous system symptom (NSS) involved COVID-19 patients. 417 COVID-19 patients were analyzed in this retrospective study, and they were clinically classified as severe patients and non-severe patients. According to NSS involved status, COVID-19 patients were further divided into NSS patients and non-NSS patients. Elderly cases, males, common comorbidities, NSS, respiratory/cardiovascular/gastrointestinal symptoms, bilateral lesion, multifocal lesion, bacterial infection, bacterial&fungal infection were more common in severe patients compared to non-severe patients. Meanwhile, severe COVID-19 patients showed increased baseline APTT, TT, D-dimer, CRP, ESR, CK-MB, creatine kinase, AST, ALT, creatinine, but decreased baseline platelet level, lymphocyte, albumin, GFR compared to non-severe patients. Notably, the continuous differences of lymphocyte, D-dimer, CRP, AST, ALT, albumin, GFR between severe patients and non-severe patients during treatment were observed. Age, NSS, bacterial & fungal infection, CRP and creatinine were further identified as independent risk factors for severe COVID-19, which could predict severe COVID-19 with area under curve of 0.861. Furthermore, severe patients presented with worse prognosis. Regrading NSS patients, they were related to older age, surgery history, diabetes comorbidities, respiratory/cardiovascular/gastrointestinal symptoms, bilateral lesion, multifocal lesion, bacterial infection, bacterial&fungal infection and more dysregulated laboratory indexes compared to non-NSS patients. Besides, NSS patients were correlated with poor prognosis to some extent. More intensive attention should be paid to COVID-19 patients with severe-disease risk factors and those with NSS involvement, in case of rapid deterioration.
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