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BACKGROUND: Inborn Errors of Immunity (IEI) significantly affect patients' health-related quality of life (HRQOL), presenting greater challenges than those faced by the healthy population and other chronic disease sufferers. Current research lacks comprehensive integration of this critical issue. OBJECTIVE: This study explores HRQOL in IEI patients, identifies impacting factors, and advocates for increased research focus on their quality of life. METHODS: Following systematic review and meta-analysis guidelines, a search of Scopus and PubMed until November 15, 2023, yielded 1633 publications. We evaluated the literature, assessed study quality, and compared the HRQOL of IEI patients to that of healthy individuals and other chronic disease patients. RESULTS: Of 90 articles and 10,971 IEI patients analyzed, study quality varied (nine good, 63 moderate, and 18 poor). The Short Form-36 (SF-36) and Pediatric Quality of Life Inventory generic core scales (PedsQL) were the primary generic instruments used among adults and children, respectively, with 12 studies each using the disease-specific instruments. Meta-analysis showed IEI patients have significantly lower scores in general health, physical and mental health, and social and emotional roles compared to healthy populations. We noted significant differences between self and proxy reports, indicating caregiver anxiety and perception disparities. CONCLUSION: Despite limitations like small sample sizes and reliance on generic instruments, this research underscores the substantially lower HRQOL among IEI patients, emphasizing the need for a patient-centered, multidisciplinary approach to improve their life quality and calling for more focused attention on IEI patients and their caregivers' HRQOL.
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Hennekam Lymphangiectasia-Lymphedema Syndrome 3 (HKLLS3) is a rare genetical disorder caused by mutations in a few genes including ADAMTS3. It is characterized by lymphatic dysplasia, intestinal lymphangiectasia, severe lymphedema and distinctive facial appearance. Up till now, no extensive studies have been conducted to elucidate the mechanism of the disease caused by various mutations. As a preliminary investigation of HKLLS3, we sorted out the most deleterious nonsynonymous single nucleotide polymorphisms (nsSNPs) that might affect the structure and function of ADAMTS3 protein by using a variety of in silico tools. A total of 919 nsSNPs in the ADAMTS3 gene were identified. 50 nsSNPs were predicted to be deleterious by multiple computational tools. 5 nsSNPs (G298R, C567Y, A370T, C567R and G374S) were found to be the most dangerous and can be associated with the disease as predicted by different bioinformatics tools. Modelling of the protein shows it can be divided into segments 1, 2 and 3, which are connected by short loops. Segment 3 mainly consists of loops without substantial secondary structures. With prediction tools and molecular dynamics simulation, some SNPs were found to significantly destabilize the protein structure and disrupt the secondary structures, especially in segment 2. The deleterious effects of mutations in segment 1 are possibly not from destabilization but from other factors such as the change in phosphorylation as suggested by post-translational modification (PTM) studies. This is the first-ever study of ADAMTS3 gene polymorphism, and the predicted nsSNPs in ADAMST3, some of which have not been reported yet in patients, will serve for diagnostic purposes and further therapeutic implications in Hennekam syndrome, contributing to better diagnosis and treatment.
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Linfedema , Polimorfismo de Nucleotídeo Único , Humanos , Simulação de Dinâmica Molecular , Linfedema/genética , Estabilidade Proteica , Biologia ComputacionalRESUMO
Single-nucleotide polymorphisms in the ELANE (Elastase, Neutrophil Expressed) gene are associated with severe congenital neutropenia, while the ELANE gene provides instructions for making a protein called neutrophil elastase. We identified disease susceptibility single-nucleotide polymorphisms (SNPs) in the ELANE gene using several computational tools. We used cutting-edge computational techniques to investigate the effects of ELANE mutations on the sequence and structure of the protein. Our study suggested that eight nsSNPs (rs28931611, rs57246956, rs137854448, rs193141883, rs201723157, rs201139487, rs137854451, and rs200384291) are the most deleterious in ELANE gene and disturb protein structure and function. The mutants F218L, R34W, G203S, R193W, and T175M have not yet been identified in patients suffering from SCN and cyclic hematopoiesis, while C71Y, P139R, C151Y, G214R, and G203C reported in our study are already associated with both of the disorders. These mutations are shown to destabilize structure and disrupt ELANE protein activation, splicing, and folding and might diminish trypsin-like serine protease efficiency. Prediction of posttranslation modifications highlighted the significance of deleterious nsSNPs because some of nsSNPs affect potential phosphorylation sites. Gene-gene interactions showed the relation of ELANE with other genes depicting its importance in numerous pathways and coexpressions. We identified the deleterious nsSNPs, constructed mutant protein structures, and evaluated the impact of mutation by employing molecular docking. This research sheds light on how ELANE failure upon mutation results in disease progression, including congenital neutropenia, and validation of these novel predicted nsSNPs is required through the wet lab.
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Polimorfismo de Nucleotídeo Único , Humanos , Síndrome Congênita de Insuficiência da Medula Óssea , Simulação de Acoplamento Molecular , Mutação , Neutropenia/congênito , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
BACKGROUND: Immunotherapies including PD-1/PD-L1 antibodies have been approved for the treatment of Muscle-invasive Bladder Cancer (MIBC) patients. However, immunotherapies could only be beneficial for about 20% MIBC patients. Thus, identification of the immune subtype is becoming increasingly important. This study aimed to explore the immune subtype by analyzing the gene expression profiles. METHODS: A total of 6 datasets including (GSE13507, GSE31684, GSE32548, GSE32894, GSE69795, and TCGA-BLCA) were downloaded. The gene expression profiles from different datasets were combined since the batch effects were removed. We performed unsupervised clustering analysis to identify the immune subtype by the combined gene expression profiles. The tumor-infiltration levels of 22 immune cells, immune scores, and tumor purity were calculated, and the survival analysis was performed to investigate the prognosis difference between immune subtypes. The enriched pathways for each immune subtype were obtained. RESULTS: We identified four novel immune subtypes (referred to S1, S2, S3, and S4) among MIBC patients. We found that S1 was enriched in immune scores had the best prognosis. In contrast, S3 was poor in immune scores and had the worst prognosis. Subtype S1, S2, S3, and S4 were enriched in immune-related pathways, extracellular matrix-related pathways, metabolism-related pathways, and cancer-related pathways, respectively. CONCLUSION: The current study suggests that the immune subtypes based on gene expression profiles could contribute to select the appropriate MIBC patient for immunotherapies.
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Neoplasias da Bexiga Urinária , Análise por Conglomerados , Humanos , Músculos/patologia , Prognóstico , Transcriptoma , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/terapiaRESUMO
Immunotherapy, especially anti-PD-1, is becoming a pillar of modern muscle-invasive bladder cancer (MIBC) treatment. However, the objective response rates (ORR) are relatively low due to the lack of precise biomarkers to select patients. Herein, the molecular subtype, tumor mutation burden (TMB), and CD8+ T cells were calculated by the gene expression and mutation profiles of MIBC patients. MIBC immunotypes were constructed using clustering analysis based on tumor mutation burden, CD8+ T cells, and molecular subtypes. Mutated genes, enriched functional KEGG pathways and GO terms, and co-expressed network-specific hub genes have been identified. We demonstrated that ORR of immunotype A patients identified by molecular subtype, CD8+ T cells, and TMB is about 36% predictable. PIK3CA, RB1, FGFR3, KMT2C, MACF1, RYR2, and EP300 are differentially mutated among three immunotypes. Pathways such as ECM-receptor interaction, PI3K-Akt signaling pathway, and TGF-beta signaling pathway are top-ranked in enrichment analysis. Low expression of ACTA2 was associated with the MIBC survival benefit. The current study constructs a model that could identify suitable MIBC patients for immunotherapy, and it is an important step forward to the personalized treatment of bladder cancers.
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Biomarcadores Tumorais/genética , Linfócitos T CD8-Positivos/citologia , Neoplasias da Bexiga Urinária/classificação , Humanos , Músculos/patologia , Mutação , Fenótipo , Transdução de Sinais , Neoplasias da Bexiga Urinária/genéticaRESUMO
Hennekam lymphangiectasia-lymphedema syndrome has been linked to single-nucleotide polymorphisms in the CCBE1 (collagen and calcium-binding EGF domains 1) gene. Several bioinformatics methods were used to find the most dangerous nsSNPs that could affect CCBE1 structure and function. Using state-of-the-art in silico tools, this study examined the most pathogenic nonsynonymous single-nucleotide polymorphisms (nsSNPs) that disrupt the CCBE1 protein and extracellular matrix remodeling and migration. Our results indicate that seven nsSNPs, rs115982879, rs149792489, rs374941368, rs121908254, rs149531418, rs121908251, and rs372499913, are deleterious in the CCBE1 gene, four (G330E, C102S, C174R, and G107D) of which are the highly deleterious, two of them (G330E and G107D) have never been seen reported in the context of Hennekam syndrome. Twelve missense SNPs, rs199902030, rs267605221, rs37517418, rs80008675, rs116596858, rs116675104, rs121908252, rs147974432, rs147681552, rs192224843, rs139059968, and rs148498685, are found to revert into stop codons. Structural homology-based methods and sequence homology-based tools revealed that 8.8% of the nsSNPs are pathogenic. SIFT, PolyPhen2, M-CAP, CADD, FATHMM-MKL, DANN, PANTHER, Mutation Taster, LRT, and SNAP2 had a significant score for identifying deleterious nsSNPs. The importance of rs374941368 and rs200149541 in the prediction of post-translation changes was highlighted because it impacts a possible phosphorylation site. Gene-gene interactions revealed CCBE1's association with other genes, showing its role in a number of pathways and coexpressions. The top 16 deleterious nsSNPs found in this research should be investigated further in the future while researching diseases caused CCBE1 gene specifically HS. The FT web server predicted amino acid residues involved in the ligand-binding site of the CCBE1 protein, and two of the substitutions (R167W and T153N) were found to be involved. These highly deleterious nsSNPs can be used as marker pathogenic variants in the mutational diagnosis of the HS syndrome, and this research also offers potential insights that will aid in the development of precision medicines. CCBE1 proteins from Hennekam syndrome patients should be tested in animal models for this purpose.
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Proteínas de Ligação ao Cálcio/genética , Anormalidades Craniofaciais/genética , Linfangiectasia Intestinal/genética , Linfedema/genética , Mutação de Sentido Incorreto/genética , Polimorfismo de Nucleotídeo Único/genética , Proteínas Supressoras de Tumor/genética , Biologia Computacional , Previsões , HumanosRESUMO
BACKGROUND: The life cycle of human immunodeficiency virus type-1 (HIV-1) makes possible the realization of regulatory strategies that can lead to complex dynamical behavior of the system. We analyze the strategy which is based on two feedback mechanisms, one mediating a positive regulation of the virus replication by Tat protein via the antitermination of the genomic RNAs transcription on TAR (transactivation responsive) element of the proviral DNA and the second mechanism providing a negative regulation of the splicing of the full-length (9 kb) RNAs and incompletely spliced (4 kb) RNAs via their transport from the nucleus to the cytoplasm. Although the existence of these two regulatory feedback loops has been considered in other mathematical models, none of them examined the conditions for the emergence of complex oscillatory patterns in the intracellular dynamics of viral components. RESULTS: We developed a mechanistic mathematical model for the Tat-Rev mediated regulation of HIV-1 replication, which considers the activation of proviral DNA transcription, the Tat-specific antitermination of transcription on TAR-element, resulting in the synthesis of the full-length 9 kb RNA, the splicing of the 9 kb RNA down to the 4 kb RNA and the 4 kb RNA to 2 kb RNA, the transport of 2 kb mRNAs from the nucleus to the cytoplasm by the intracellular mechanisms, the multiple binding of the Rev protein to RRE (Rev Response Element) sites on 9 kb and 4 kb RNA resulting in their export to the cytoplasm and the synthesis of Tat and Rev proteins in the cytoplasm followed by their transport into the nucleus. The degradation of all viral proteins and RNAs both in the cytoplasm and the nucleus is described. The model parameters values were derived from the published literature data. The model was used to examine the dynamics of the synthesis of the viral proteins Tat and Rev, the mRNAs under the intracellular conditions specific for activated HIV-1 infected macrophages. In addition, we analyzed alternative hypotheses for the re-cycling of the Rev proteins both in the cytoplasm and the nuclear pore complex. CONCLUSIONS: The quantitative mathematical model of the Tat-Rev regulation of HIV-1 replication predicts the existence of oscillatory dynamics which depends on the efficacy of the Tat and TAR interaction as well as on the Rev-mediated transport processes. The biological relevance of the oscillatory regimes for the HIV-1 life cycle is discussed.
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Regulação Viral da Expressão Gênica , HIV-1/genética , Modelos Genéticos , Replicação Viral , Produtos do Gene rev do Vírus da Imunodeficiência Humana/metabolismo , Produtos do Gene tat do Vírus da Imunodeficiência Humana/metabolismo , Transporte Ativo do Núcleo Celular , Núcleo Celular/metabolismo , Repetição Terminal Longa de HIV , HIV-1/metabolismo , HIV-1/fisiologia , Íntrons , Iniciação Traducional da Cadeia Peptídica , Periodicidade , Provírus/genética , Splicing de RNA , Estabilidade de RNA , RNA Mensageiro/metabolismo , RNA Viral/biossíntese , Transcrição Gênica , Proteínas Virais/biossíntese , Produtos do Gene rev do Vírus da Imunodeficiência Humana/genéticaRESUMO
The mechanisms regulating clonal expansion and contraction of T cells in response to immunization remain to be identified. A recent study established that there was a log-linear relation between CD4 T-cell precursor number (PN) and factor of expansion (FE), with a slope of â¼-0.5 over a range of 3-30,000 precursors per mouse. The results suggested inhibition of precursor expansion either by competition for specific antigen-presenting cells or by the action of other antigen-specific cells in the same microenvironment as the most likely explanation. Several molecular mechanisms potentially accounting for such inhibition were examined and rejected. Here we adopt a previously proposed concept, "feedback-regulated balance of growth and differentiation," and show that it can explain the observed findings. We assume that the most differentiated effectors (or memory cells) limit the growth of less differentiated effectors, locally, by increasing the rate of differentiation of the latter cells in a dose-dependent manner. Consequently, expansion is blocked and reversed after a delay that depends on initial PN, accounting for the dependence of the peak of the response on that number. We present a parsimonious mathematical model capable of reproducing immunization response kinetics. Model definition is achieved in part by requiring consistency with available BrdU-labeling and carboxyfluorescein diacetate succinimidyl ester (CFSE)-dilution data. The calibrated model correctly predicts FE as a function of PN. We conclude that feedback-regulated balance of growth and differentiation, although awaiting definite experimental characterization of the hypothetical cells and molecules involved in regulation, can explain the kinetics of CD4 T-cell responses to antigenic stimulation.
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Linfócitos T CD4-Positivos/citologia , Diferenciação Celular , Proliferação de Células , Retroalimentação Fisiológica , Modelos Biológicos , Células Precursoras de Linfócitos T/citologia , Animais , Linfócitos T CD4-Positivos/imunologia , Diferenciação Celular/imunologia , Cinética , Ativação Linfocitária , Contagem de Linfócitos , CamundongosRESUMO
UNLABELLED: 2-butoxyethanol (C6H14O2) is widely used in many industrial reagents; according to the in vitro data it was established that 2-butoxyethanol metabolites are strong haemolytic poisons. Ghanayem B.I., Sullivan Ch.A. (1993) investigated in vitro the effect of BE on the red blood cells of 10 species of mammals, including humans. In this study, the authors established the species specificity with regard to the development of hemolytic anemia under the effect of butoxyethanol. In the context of the available data, creation of experimental model based on the introduction of animal butoxyethanol is taking place. Since the drug-induced hemolytic anemia is formed at the adjacency of toxic and autoimmune forms, the study of immunology of any toxic anemia is of great interest. OBJECTIVE: to develop a new experimental model of hemolytic anemia after butoxyethanol and to study its immunology. In conclusion, the proposed model of hemolytic anemia after butoxyethanol may be used in the experimental and preclinical studies. The intraperitoneal administration of butoxyethanol provokes an autoimmune response directed against own red blood cells. The intraperitoneal administration of butoxyethanol to experimental animals is accompanied by a reduction of the lymphoid tissue that corresponds to the appropriate response to stress in the central and peripheral organs of immunogenesis.
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Background: Inborn Errors of Immunity (IEI) are characterized by a heightened susceptibility to infections, allergies, and various other health complications. Health-Related Quality of Life (HRQOL) in patients with IEI is a critical area of research that demands attention due to the impact of IEI on patients' lives. This study utilized bibliometric methods, aiming to comprehensively explore the research content and hotspots in the field of HRQOL in patients with IEI. Methods: This bibliometric analysis utilized data from the Science Citation Index Expanded (SCIE) and Social Sciences Citation Index (SSCI) within the Web of Science core datasets up to January 1, 2024. The study focused on literature that addressed HRQOL in IEI patients, involving a total of 1,807 authors and 309 articles published across 112 journals. The analysis included publication volume and growth trends, country and institutional contributions, authorship, and journal analysis. Results: The research found that despite the importance of HRQOL in IEI, the volume of publications in this field remains consistently low, with no significant increase in trend. The USA leads in publication and citation volumes, reflecting a geographical imbalance in research contributions. Key journals in this field include the Journal of Clinical Immunology, Frontiers in Immunology, and the Journal of Allergy and Clinical Immunology. The study highlights that while treatments like hematopoietic stem cell transplants and gene therapy have improved patient IEI survival rates, they still often come with significant side effects impacting HRQOL. The analysis underlines the need for comprehensive HRQOL assessments in IEI, considering the physical and psychological impacts of treatments. Conclusions: This study represents a bibliometric analysis focusing on HRQOL in patients with. It underscores the need for more extensive and systematic research in this area, emphasizing the importance of a multidisciplinary approach. Despite advancements in medical treatments for IEI, there is a crucial need to focus on HRQOL to enhance patient satisfaction and overall well-being. The findings advocate for more personalized treatment plans and a better understanding of the psychosocial needs of patients with IEI to improve their quality of life.
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Bibliometria , Qualidade de Vida , HumanosRESUMO
Background: Given the rising interest in complementary therapeutic strategies for autism spectrum disorder (ASD), this research aims to provide a comprehensive analysis of the impact of animal-assisted activities and therapies (AAAT) on various ASD symptoms. Methods: A meticulous search of databases, including Scopus and PubMed, was conducted to gather relevant research on AAAT for ASD. This process led to the selection of 45 studies encompassing 1,212 participants. The chosen studies were then subjected to a meta-analysis to evaluate the efficacy of AAAT in alleviating core ASD symptoms. Results: The meta-analysis revealed significant improvements in several core ASD symptoms due to AAAT. Notably, there were improvements in social communication (MD = -4.96, 95% CI [-7.49, -2.44]), irritability (MD = -2.38, 95% CI [-4.06, -0.71]), hyperactivity (MD = -4.03, 95% CI [-6.17, -1.89]), and different word usage skills (MD = 20.48, 95% CI [7.41, 33.55]). However, social awareness (MD = -1.63, 95% CI [-4.07, 0.81]), social cognition (MD = -3.60, 95% CI [-9.36, 2.17]), social mannerisms (MD = -0.73, 95% CI [-2.55, 1.09]), social motivation (MD = -1.21, 95% CI [-2.56, 0.13]), lethargy (MD = -1.12, 95% CI [-3.92, 1.68]), and stereotypical behaviors (MD = -0.23, 95% CI [-1.27, 0.80]) did not significantly improve. Conclusion: The study demonstrates the potential of AAAT in improving certain core symptoms of ASD, such as social communication, irritability, hyperactivity, and word usage skills. However, the effectiveness of AAAT in other ASD symptom domains remains uncertain. The research is limited by the absence of long-term follow-up data and a high risk of bias in existing studies. Therefore, while the findings indicate the promise of AAAT in specific areas, caution is advised in generalizing its efficacy across all ASD symptoms.
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Plasmacytoid dendritic cell (pDC)-mediated protection against cytopathic virus infection involves various molecular, cellular, tissue-scale, and organism-scale events. In order to better understand such multiscale interactions, we have implemented a systems immunology approach focusing on the analysis of the structure, dynamics and operating principles of virus-host interactions which constrain the initial spread of the pathogen. Using high-resolution experimental data sets coming from the well-described mouse hepatitis virus (MHV) model, we first calibrated basic modules including MHV infection of its primary target cells, i.e. pDCs and macrophages (Mphis). These basic building blocks were used to generate and validate an integrative mathematical model for in vivo infection dynamics. Parameter estimation for the system indicated that on a per capita basis, one infected pDC secretes sufficient type I IFN to protect 10(3) to 10(4) Mphis from cytopathic viral infection. This extremely high protective capacity of pDCs secures the spleen's capability to function as a 'sink' for the virus produced in peripheral organs such as the liver. Furthermore, our results suggest that the pDC population in spleen ensures a robust protection against virus variants which substantially down-modulate IFN secretion. However, the ability of pDCs to protect against severe disease caused by virus variants exhibiting an enhanced liver tropism and higher replication rates appears to be rather limited. Taken together, this systems immunology analysis suggests that antiviral therapy against cytopathic viruses should primarily limit viral replication within peripheral target organs.
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Alergia e Imunologia , Células Dendríticas/imunologia , Biologia de Sistemas/métodos , Viroses/imunologia , Antivirais , Sistemas de Liberação de Medicamentos , Interações Hospedeiro-Patógeno/imunologia , Fígado/virologia , Macrófagos/imunologia , Macrófagos/virologia , Modelos Biológicos , Modelos Teóricos , Viroses/tratamento farmacológicoRESUMO
T Cell Immune Regulator 1, ATPase H + Transporting V0 Subunit A3 (TCIRG1 gene provides instructions for making one part, the a3 subunit, of a large protein complex known as a vacuolar H + -ATPase (V-ATPase). V-ATPases are a group of similar complexes that act as pumps to move positively charged hydrogen atoms (protons) across membranes. Single amino acid changes in highly conserved areas of the TCIRG1 protein have been linked to autosomal recessive osteopetrosis and severe congenital neutropenia. We used multiple computational approaches to classify disease-prone single nucleotide polymorphisms (SNPs) in TCIRG1. We used molecular dynamics analysis to identify the deleterious nsSNPs, build mutant protein structures, and assess the impact of mutation. Our results show that fifteen nsSNPs (rs199902030, rs200149541, rs372499913, rs267605221, rs374941368, rs375717418, rs80008675, rs149792489, rs116675104, rs121908250, rs121908251, rs121908251, rs149792489 and rs116675104) variants are likely to be highly deleterious mutations as by incorporating them into wild protein they destabilize the wild protein structure and function. They are also located in the V-ATPase I domain, which may destabilize the structure and impair TCIRG1 protein activation, as well as reduce its ATPase effectiveness. These mutants have not yet been identified in patients suffering from CN and osteopetrosis while (G405R, R444L, and D517N) reported in our study are already associated with osteopetrosis. Mutation V52L reported in our study was identified in a patient suspected for CN. Finally, these mutants can help to further understand the broad pool of illness susceptibilities associated with TCIRG1 catalytic kinase domain activation and aid in the development of an effective treatment for associated diseases.
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INTRODUCTION: Newborn screening (NBS) by quantifying T cell receptor excision circles (TRECs) and Kappa receptor excision circles in neonatal dried blood spots (DBS) enables early diagnosis of different types of primary immune deficiencies. Global newborn screening for PID, using an assay to detect T-cell receptor excision circles (TREC) in dried blood spots (DBS), is now being performed in all states in the United States. In this review, we discuss the development and outcomes of TREC, TREC/KREC combines screening, and continued challenges to implementation. OBJECTIVE: To review the diagnostic performance of published articles for TREC and TREC/ KREC based NBS for PID and its different types. METHODS: Different research resources were used to get an approach for the published data of TREС and KREC based NBS for PID like PubMed, Scopus, Google Scholar, Research gate EMBASE. We extracted TREC and KREC screening Publisher with years of publication, content and cut-off values, and a number of retests, repeat DBS, and referrals from the different published pilot, pilot cohort, Case series, and cohort studies. RESULTS: We included the results of TREC, combined TREC/KREC system based NBS screening from different research articles, and divided these results between the Pilot studies, case series, and cohort. For each of these studies, different parameter data are excluded from different articles. Thirteen studies were included, re-confirming 89 known SCID cases in case series and reporting 53 new SCID cases in 3.15 million newborns. Individual TREC contents in all SCID patients were <25 TRECs/µl (except in those evaluated with the New York State assay). CONCLUSION: TREC and KREC sensitivity for typical SCID and other types of PID was 100 %. It shows its importance and anticipating the significance of implementation in different undeveloped and developed countries in the NBS program in upcoming years. Data adapting the screening algorithm for pre-term/ill infants reduce the amount of false-positive test results.
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Triagem Neonatal/métodos , Doenças da Imunodeficiência Primária/diagnóstico , Linfócitos T/metabolismo , Humanos , Recém-NascidoRESUMO
We present here the complete genome sequence of Streptococcus pyogenes type emm111 strain GUR, a throat isolate from a scarlet fever patient, which has been used to treat cancer patients in the former Soviet Union. We also present the complete genome sequence of its derivative strain GURSA1 with an inactivated emm gene.
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Actinobacteria of the genus Rhodococcus produce trehalolipid biosurfactants with versatile biochemical properties and low toxicity. In recent years, these biosurfactants are increasingly studied as possible biomedical agents with expressed immunological activities. Applications of trehalolipids from Rhodococcus, predominantly cell-bound, in biomedicine are also attractive because their cost drawback could be less significant for high-value products. The review summarizes recent findings in immunomodulatory activities of trehalolipid biosurfactants from nonpathogenic Rhodococcus and related actinobacteria and compares their biomedical potential with well-known immunomodifying properties of trehalose dimycolates from Mycobacterium tuberculosis. Molecular mechanisms of trehalolipid interactions with immunocompetent cells are also discussed.
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Fatores Imunológicos/biossíntese , Fatores Imunológicos/imunologia , Lipídeos/imunologia , Rhodococcus/classificação , Rhodococcus/metabolismo , Tensoativos/metabolismo , Animais , Camundongos , Rhodococcus/imunologia , Especificidade da EspécieRESUMO
Glycolipid biosurfactant (GLB) from Rhodococcus ruber IEGM 231 was found to stimulate tumor necrosis factor-α (TNF-α), interleukin (IL) -1ß and IL-6 production when applied as an ultrasonic emulsion to the adherent human peripheral blood monocyte culture. However, a lack of cytokine-stimulating activity was registered with the GLB applied as a hydrophobic film coating in 24-well culture plates, indicating that it may have been due to its inhibitory effect on monocyte adhesion. The mode of GLB application may therefore play an important role in in vitro assay of immunostimulatory activity of this compound as well as other bacterial glycolipids. Additionally, GLB from R. ruber displayed no cytotoxicity against human lymphocytes and therefore could be proposed as a potential immunomodulating and antitumor agent.
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In the experiments on male Wistar rats a study was made on the effect of acute 6-h immobilization stress on antibody formation, delayed type hypersensitivity (DTH), functional activity of phagocytes in the case of a local form of immune response to sheep red blood cells at the background of beta-adrenergic receptor blockade. It was established that immobilization stress resulted in substantial inhibition of the expressibility of immune inflammation in the case of DTH, cancellation of an increase of the phagocytic activity of macrophages of the regional lymph node and the level of antibodies. The blockade of the beta-adrenergic receptors with propranolol antagonized with these effects of stress. After termination of the immobilization, activation of neutrophil phagocytosis was detected, this being related to an increase of neutrophil immigration from the bone marrow. Eosinophilic phagocytosis at the early period of stress was inhibited, the blockade of beta-adrenergic receptors canceled this effect.
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The purpose of present paper is the investigation of polyoxidonium effects on the functions of circulating pool of phagocytic cells and the estimation of its potential inclusion in complex therapy in penetrating eye injuries. On experimental model of eye injuring in rats there has been established that polyoxidonium attenuated some negative glucocorticoid effects on phagocytic cells. Inclusion of polyoxidonium in complex therapy optimized the course of injuring process according to parameters of the least infiltration of damage area with immunocompetent and effector cells, scar structure and other parameters. The stimulation of neutrophil, and in a less degree of eosinophil phagocytosis, was demonstrated at concentration range from 10(-11) to 10 &mgr;g/ml under conditions of 1 h drug preincubation in vitro with blood cells of healthy people. At concentrations 10(-11)-10(-8) &mgr;g/ml polyoxidonium caused a slightly stimulated effect on the parameters of monocyte phagocytosis. As a whole the results obtained show that further studies are promising for potential use of polyoxidonium in complex therapy for penetrating eye injuries.