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关键词： crp: c-reactive protein   diagnosis of neonatal sepsis   interleukin-6 (il-6)   maternal mental health   neonatal sepsis  

摘要： Neonatal sepsis (NS) remains a significant cause of morbidity and mortality in newborns, particularly in preterm and low-birthweight infants. It has been shown previously that interleukin-6 (IL-6) can predict sepsis, and its non-invasive determination can be performed quickly, leading to the diagnosis and appropriate treatment for each case. Elevated IL-6 levels have been associated with early and late-onset NS, showing potential as an early indicator of infection before the onset of clinical symptoms. IL-6, in conjunction with other biomarkers such as C-reactive protein (CRP) and procalcitonin, may improve the accuracy of sepsis diagnosis and help guide antibiotic therapy.  We conducted a retrospective study to assess the validity of IL-6 in predicting NS. The optimal IL-6 cutoff was 181 pg/ml, yielding a sensitivity of 80.1%, a specificity of 85.7%, a positive predictive value of 84.6%, and a negative predictive value of 81.8%. Among culture-positive cases, IL-6 sensitivity was 90%, while in culture-negative cases, sensitivity was 71.4%. Our study showed that IL-6 is a new biomarker with high sensitivity and good specificity for identifying sepsis, and it has been linked with a better diagnostic value than CRP.

关键词： allogeneic   haplobank   histocompatibility   HLA   iPSC   registry  

摘要： Background: Several countries have either developed or are developing national induced pluripotent stem cell (iPSC) banks of cell lines derived from donors with HLA homozygous genotypes (two identical haplotypes) prevalent in their local populations to provide immune matched tissues and cells to support regenerative medicine therapies. This 'haplobank' approach relies on knowledge of the HLA genotypes of the population to identify the most beneficial haplotypes for patient coverage, and ultimately identify donors or cord blood units carrying two copies of the target haplotype. Aims: A potentially more efficient alternative to a national bank approach is to assess the haplotypes required to provide global patient coverage and to produce a single, global haplobank. Toward that end, we have developed an algorithm to prioritize HLA haplotypes that optimize coverage across the global population. Methods: We analyzed data from eighteen countries participating in the Global Alliance for iPS Therapy (GAiT). A representative pool of HLA genotypes, reflecting the HLA of patients, was derived by sampling from each country's WMDA hematopoietic stem cell donor registry, or surrogate population. An algorithm was created based on HLA-A, -B and -DRB1 haplotype homozygous types with population HLA matching coverage defined by the absence of Host versus Graft (HvG) mismatches at these loci. HLA matching coverage was determined by iteratively selecting HLA haplotypes that provide the largest coverage against patient HLA genotypes sampled from the same population, excluding genotypes compatible with previous iterations. Results: The top 10 haplotypes for each of the 18 countries were identified with patient coverage ranging from 19.5% in Brazil to 63.8% in Japan, with a mean coverage of 33.3%. In a 'global' model, utilizing the 180 most frequent haplotypes across all 18 populations (equivalent to 10 lines per country), the patient coverage ranged from 54.6% in India to 81.7% in Sweden,

关键词： plaque psoriasis   FOXP3 variants   Tregs   IL-10   TGF-beta 1  

摘要： Plaque psoriasis (PP) is a chronic immune-mediated skin disorder with a genetic basis, characterized by abnormal T-cell responses. This study investigated the role of FOXP3 gene variants rs2280883 and rs3761548 in T-cell regulation through their effects on IL-10 and TGF-beta 1 cytokine levels and their association with PP risk. A case-control study was conducted, including 101 individuals with PP and 106 healthy controls from the Mexican population. Genotyping of FOXP3 variants was performed using PCR-RFLP, and cytokine levels were measured with ELISA kits. Significant differences in allele and genotype frequencies of the rs2280883 variant were observed between PP patients and controls, suggesting an association with an increased risk of PP. IL-10 levels were found to be elevated in PP patients, regardless of FOXP3 gene variants, indicating that cytokine dysregulation in PP may involve alternative pathways independent of FOXP3-mediated regulatory T-cell (Treg) function. No significant differences were detected in TGF-beta 1 levels or rs3761548 genotype frequencies across the study groups. In conclusion, the rs2280883 variant in the FOXP3 gene is significantly associated with a higher risk of developing PP in the Mexican population, while dysregulated IL-10 levels suggest a complex cytokine interaction beyond Treg activity.

关键词： Erythema Nodosum Leprosum (ENL)   Thalidomide   Immune response   Polymorphisms   Cytokines  

摘要： Erythema nodosum leprosum (ENL), an inflammatory reaction in leprosy, causes painful nodules, fever, and malaise due to immune system activation. Thalidomide is an effective treatment, although associated with important adverse effects. We aimed to evaluate the association of genetic variants in genes encoding tumor necrosis factor alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) with the response to treatment of ENL with thalidomide. 148 patients from the South and Northeast regions of Brazil were included. Genomic DNA was isolated from blood and/or saliva samples using commercial kits, and genetic variants in TNF, IL6, IL1/3, and IFN gamma genes were genotyped by TaqMan system. We identified an association between polymorphisms in TNF (rs1799964C, rs1800630A, rs1799724T and rs1800629A) IL1/3 (rs4848306G, rs1143623G, rs16944A, and rs1143627A), IL6 (rs2069840C and rs2069845G) and IFN gamma (rs2430561T) with thalidomide dose variation in a time-dependent manner. Associations of IL6 and TNF haplotypes with thalidomide dosage variation over the time of treatment were also observed. Polymorphisms in TNF, IL6, IL1/3, and IFN gamma genes may modulate their expression levels, potentially impacting the required dosage of thalidomide in the treatment of ENL. Our findings should be confirmed in further studies to estimate the size effect of these polymorphisms on ENL treatment with thalidomide.

关键词： HLA   HLA-DRB5*01:02:05   next-generation sequencing   novel allele  

摘要： HLA-DRB5*01:02:05 differs from the HLA-DRB5*01:02:01 by one synonymous nucleotide in codon 14 in exon 2.

关键词： anti-HLA antibodies   donor selection   engraftment   desensitization strategy  

摘要： Background-Antibodies directed against donor-specific HLA allele(s)/antigen(s) (DSAs) representa known risk factor for hematopoietic stem cell transplantation (HSCT) engraftment. Still, the overall management needs to be standardized. Material and methods-GITMO and AIBT ran a survey on DSAs in Italian Transplant Programs including mismatched HSCT performed between January 2014 and June 2017. Results-One-thousand-thirty-three patients were proposed for the study, 804 were evaluable. Overall, 355 (44%) were screened: 91/355 (25.6%) showed anti-HLA antibodies, 23 DSAs (6.5%). Female gender and at least 4 previous pregnancies showed an impact on alloimmunization. Eleven patients with DSAs underwent desensitization. In seven cases no desensitization was employed. An alternative donor was selected for five patients. Neutrophil and platelet engraftment were obtained in 93.6% and 86.6% of the whole population, respectively, and were statistically associated with the absence of anti-HLA antibodies, ABO match, a higher number of infused nucleated cells and lack of a-GvHD. In addition, significant factors for platelet engraftment were the use of leuco-depleted transfusions, HLA match, younger age of the patient. Graft failure (GF) was associated with bone marrow stem cell source, and a lower number of infused CD34+. The detection of antibodies directed against both HLA classes, donor and patient age, the hematologic and molecular remission at HSCT, HLA match, ANC and PLTS engraftment, full donor engraftment within 28 days after HSCT, early and late GF, grade>II a-GVHD showed an impact on OS. Discussion-Anti-HLA antibodies and DSAs were confirmed as risk factors affecting OS. DSAs were managed with various approaches resulting in stable engraftment in 81.9% of patients. Our study supports the clinical relevance of DSAs detection and management in mmHSCT. A standardized approach of DS is warranted.

关键词： Immune system development   Embryonic immunity   Avian   Evolutionary relic   Poultry  

摘要： Chickens are renowned as a model for embryogenesis but have also been responsible for crucial advances in virology, cancer research and immunology. However, chickens are best known as a major source of animal protein for human nutrition, with roughly 80 billion chickens alive each year supplying meat and eggs, the vast majority part of a global poultry industry. As a result, avian immunology been studied intensively for over 60 years, and it has become clear that a major genetic locus in chickens determining resistance to infectious disease and response to vaccines is the major histocompatibility complex (MHC). Compared to typical mammals, the chicken MHC is compact and simple, with only two classical class I genes. A dominantly-expressed class I gene, BF2, is the major ligand for cytotoxic T lymphocytes (CTLs), while the other locus, BF1, is much less wellexpressed, lacking in some MHC haplotypes, and is a ligand for natural killer (NK) cells. Cell surface class I expression in neonatal chicks is far less than in adults, and one possibility is that BF2 is not well-expressed early in ontogeny. A precedent is found for amphibians: the single classical class I molecule is not expressed in tadpoles of Xenopus frogs, although non-polymorphic (and thus non-classical) class I molecules from the XNC locus are expressed, which are recognised for immune defence by non-canonical NKT lymphocytes. Indeed, three waves of different T cells are produced by the Xenopus thymus: in tadpoles, during metamorphosis and finally as adults. Three waves of thymic emigrants are also found for chickens, and reasoning by analogy, it may be that the waves of thymocytes and the expression of class I molecules during ontogeny of chickens are evolutionary relics. As well as scientific interest in the ontogeny of MHC class I expression and appearance of peripheral T cells, there are potential practical implications, given the importance of vaccination in ovo and in day-old chicks for the poultry in

关键词： Extracorporeal shock wave   Temporomandibular joint disorder syndrome   IGF-1   TNF-alpha   IL-1 beta  

摘要： As a new therapeutic method, extracorporeal shock wave (ESW) has shown remarkable efficacy in the treatment of temporomandibular joint disorder syndrome. Numerous studies have shown that it has the advantages of noninvasiveness, short treatment time, etc. It can effectively relieve pain and improve symptoms such as joint mobility and opening degree. In clinical practice, through accurate diagnosis and positioning of different patients, appropriate treatment parameters such as therapeutic transducer, frequency and pressure can be selected to significantly improve the efficacy. At the same time, follow-up evaluation after treatment, including temporomandibular joint disorder index and visual analogue score, is also helpful to fully understand the rehabilitation of patients. Extracorporeal shock wave therapy (ESWT) brings new hope to patients with temporomandibular joint disorder syndrome and has a broad application prospect.

关键词： TNF   immunotherapy   CD137L   CD137   monomer   dimer   trimer   MD simulation   binding affinity   structural stability  

摘要： CD137 is a prominent costimulatory molecule of the tumor necrosis factor (TNF) receptor superfamily that activates T cells through a complex bidirectional signaling process involving CD137L. The clinical value of immunotherapies underscores the potential of CD137L/CD137 as an effective target for boosting antitumor immune responses;however, the intricate mechanisms governing these interactions have not been fully elucidated. Herein, we constructed various oligomeric states of CD137L (monomeric, dimeric, and trimeric CD137L) and explored their interactions with CD137 using molecular dynamics simulations. Our findings revealed that trimeric CD137L exhibits higher thermal stability but reduced binding affinity for CD137 compared with the dimer form, with the A'B' loop of CD137L playing a critical role in both structural stability and promoting CD137 interactions. Notably, the formation of hexameric structures enhanced the binding affinity and stability. This study provides valuable insights into the CD137L/CD137 bidirectional signaling mechanisms, which may inform the design of next-generation CD137 agonists. Ultimately, these advancements may improve cancer immunotherapy strategies, aiming to enhance therapeutic outcomes for patients through more effective and targeted therapies.