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关键词： rs641153   Complement   Evolution   Factor B   HLA   Primates   Complotype   MHC   Bf   C2   C4   Disease   Orangutan   Immunity   Chimpanzee auroimmunity  

摘要： BackgroundMajor Human Histocompatibility complex (MHC or HLA in humans) has been associated to autoimmune diseases. However, only statistical phenomenological and no pathogenetic description has been reached after decades. This shows that MHC single locus association studies are probably useless for HLA/diseases association. Extended HLA (class I and class II genes) haplotypes should also be studied conjointly with class III or complement alleles (complotypes). Complotypes in humans are defined as alleles belonging to C2, C4 and Bf (Factor B) genes/proteins (class III). Also, the placing of MHC class I and class II genes close together with complement genes from at least birds to humans shows existence of a strong selection to gather conjointly these loci that fight microbes, help self-maintenance and avoid autoimmunity. In this paper we aim to study Bf alleles in primates in order to rise again interest to study the role of Bf alleles together with other MHC genes in their physiopathology and *** (Pongo pygmaeus, Popy) cell lines RNA from 6 different individuals were retrotranscribed, PCR amplified, cloned and DNA sequenced in order to study Bf *** Bf allele identical to that found in chimpanzee (Patr-Bf*A01) and human (rs641153) was found in two of the six studied orangutans: Popy-Bf*A01 and Popy-Bf*A02. This polymorphism is placed in Factor B codon 32 that defines BF*S and Bf*F proteins in man and produce Leu instead of Arg (Bf*S) or Gln (Bf*F). In addition, each new orangutan allele present synonymous differences with each other at codon 25: Popy-Bf*A01 shows ACG while Popy-Bf*A02 bears ACA, both codifying for *** selection for about 15 million years (time gap of evolutionary appearance between orangutan and hominids) shows the importance of this particular allele conservation in immune and self defense in primates. The complotypes (Bf,C2 and C4 loci) alleles together with other MHC class I and Cass II loci alle

关键词： Acute myeloid leukemia   FLT3   FLT3 ligand   TIM-3   HIF-1 alpha   TNF-alpha  

摘要： BackgroundAcute Myeloid Leukemia (AML) pathogenesis is driven by the dysregulation of various cell signaling pathways, including the FMS-Like Tyrosine Kinase 3 (FLT3) pathway and its ligand (FLT3L). These pathways play a critical role in promoting cell survival, proliferation, and resistance to apoptosis, contributing to leukemogenesis. In this study, we investigated the effects of FLT3L on the expression of key genes associated with immune regulation, hypoxia, and inflammation-TIM-3, HIF-1 alpha, and TNF-alpha-in the THP-1 cell line, a well-established model for AML ***-1 cells were cultured under standard conditions and treated with varying concentrations of FLT3L, alongside PMA as a positive control. Quantitative RT-PCR was employed to measure the expression levels of TIM-3, HIF-1 alpha, and TNF-alpha genes after 48 h of *** findings demonstrated that specific concentrations of FLT3L significantly upregulated the expression of TIM-3, HIF-1 alpha, and TNF-alpha in THP-1 cells. This suggests that FLT3L not only influences cell proliferation and survival but also modulates pathways related to immune evasion, hypoxia adaptation, and inflammatory responses, which are hallmarks of leukemia *** results highlight the pivotal role of FLT3L in regulating the expression of genes associated with AML pathogenesis, particularly those involved in hypoxia (HIF-1 alpha), immune checkpoint regulation (TIM-3), and inflammation (TNF-alpha). The findings underscore the potential of targeting the FLT3 pathway as a therapeutic strategy in AML. Further studies are warranted to elucidate the underlying molecular mechanisms and explore their clinical implications for improving patient outcomes.

关键词： APML   Cryptic PML::RARA fusion   HLA-DR  

摘要： We report the case of a 42-year-old female presented with cytopenia and abnormal promyelocytes on blood film. The promyelocytes were HLA-DR positive by flow cytometry. The rapid FISH for PML::RARA was negative. Myeloid NGS identified PML::RARA fusion, which was confirmed by molecular karyotyping and PCR. She was treated with ATRA and ATO to complete molecular remission. This case highlighted the importance of using rapid RNA sequencing to identify cryptic fusion and rare fusions and combining morphologic, immunophenotypic, cytogenetic and molecular analyses to ensure correct diagnosis and optimal management.

关键词： IL-33   Endometriosis   Pain   Macrophages   Inflammation  

摘要： Endometriosis, a persistent inflammatory disease, is associated with pelvic or abdominal pain. The immune system and sensory nervous system show a synergistic effect on regulation of pain. In particular, Interleukin-33 (IL-33) is released as a danger signal and drives key hallmarks of severe endometriosis. To explore the mechanistic involvement of IL-33 in pain associated with endometriosis, both an in vivo murine endometriosis model and in vitro experiments with RAW 264.7 cells and dorsal root ganglion (DRG) neurons were utilized. In vivo, we demonstrated that IL-33 significantly exacerbated endometriosis and induced hyperalgesia in mice. By interacting with the ST2 receptor in macrophages, IL-33 enhanced the release of tumor necrosis factor alpha (TNF-alpha) and Interleukin 1 beta (IL-1 beta). This process set off an inflammatory cascade, which further facilitated macrophages recruitment and neurogenesis in ectopic lesions. As an ion channel expressed by nociceptors, transient receptor potential vanilloid 1 (TRPV1) expression was significantly increased in DRG in the presence of IL-33. In vitro, we confirmed that IL-33 elevated the release of TNF-alpha in macrophages. Ultimately, macrophage-derived TNF-alpha increased TRPV1 protein level in DRG neuronal cells through the TNFR1/p38 MAPK signaling pathway. Overall, these results revealed an inductive role of IL-33 in pain associated with endometriosis, and highlighted the interaction between macrophages and sensory neurons.

关键词： IL-6   Post-transplantation cyclophosphamide   Anti-thymocyte globulin   GVHD   Hematopoietic stem cell transplantation  

摘要： BackgroundPost-transplantation cyclophosphamide (PTCy) and anti-thymocyte globulin (ATG) are common prophylactic strategies for graft-versus-host disease (GVHD) after haploidentical hematopoietic stem cell transplantation (haplo-HSCT). Interleukin (IL)-6 is a surrogate marker for cytokine release syndrome (CRS) and acute GVHD. MethodThe clinical outcomes and complications of haplo-HSCT with PTCy plus ATG versus PTCy monotherapy were compared according to serum IL-6 levels at Chungnam National University Hospital (Daejeon, South Korea) from January 2019 to February 2023. ResultsForty patients who underwent haplo-HSCT were analyzed. A significant difference in IL-6 levels was observed between the PTCy plus ATG and PTCy alone groups (7.47 +/- 10.55 vs. 117.65 +/- 127.67;p = 0.003). More patients in the PTCy plus ATG group had a CRS grade of 0 than in the PTCy alone group (p < 0.001). Serum IL-6 levels were associated with grades II-IV acute GVHD (r = 0.547, p < 0.001). The cumulative incidence (CI) of grades II-IV acute GVHD was significantly higher in the PTCy alone group (67.9% vs. 4.8%;p < 0.001). No significant difference in the CI for chronic GVHD was detected between the PTCy plus ATG and PTCy alone groups (72.1% vs. 82.0%;p = 0.730). The CI of 1-year non-relapse mortality was significantly higher in the PTCy alone group than in the PTCy plus ATG group (42.2% vs. 15.9%;p = 0.022). The 1-year overall survival (OS) was significantly better in the PTCy plus ATG group (75.9% vs. 35.3%;p = 0.011). The 1-year GVHD-free, relapse-free survival rate was 29.4% in the PTCy alone group and 54.0% in the PTCy plus ATG group (p = 0.038). ConclusionSerum IL-6 levels were higher in the PTCy alone group than in the PTCy plus ATG group. The addition of ATG before stem cell infusion affected IL-6 levels and reduced the incidences of CRS and grade II-IV acute GVHD in haplo-HSCT patients. This study suggests that PTCy plus ATG as GVHD prophylaxis in haplo-HSCT is beneficial in terms o

关键词： Sepsis   Acute respiratory distress syndrome (ARDS)   IL-27   Nrf2/HO1   Ferroptosis  

摘要： ObjectivesAcute respiratory distress syndrome (ARDS) is a clinical syndrome characterized by high morbidity and mortality rates. Sepsis-induced ARDS involves excessive inflammatory responses, which are modulated by macrophages. This study aimed to elucidate the effect of Recombinant Mouse IL-27 Protein on macrophage ferroptosis and polarization, as well as its impact on sepsis-induced *** cecal ligation and puncture (CLP)-induced sepsis model was established using wild-type (WT) or IL27R-/- mice. Then, the mice were randomly divided into 4 groups: a control group, a CLP group, an IL-27 + CLP combination group, and an IL-27, CLP, and Oltipraz combination group. RAW 264.7 cells and BMDMs were used to further determine the role and mechanism of IL-27 in *** vitro, IL-27 alone did not alter the expression of proteins linked to the ferroptosis pathway or macrophage polarization. Contrastingly, the combination of IL-27 with LPS further amplified LPS-induced alterations in the ferroptosis pathway, thereby promoting macrophage M1 polarization and inhibiting M2 polarization. Additionally, IL-27 + LPS increased ROS levels in macrophages. A sepsis-induced ARDS mouse model was then established via CLP. In vivo, IL-27 exacerbated CLP-induced lung injury in WT mice. Additionally, it decreased the expression levels of ferroptosis-related proteins (Nrf2, HO-1, GPX4) and increased those of Ptgs2 in the lung tissue of septic mice. Besides, GSH and SOD levels in lung tissue were also reduced. Moreover, IL-27 also promoted M1 polarization and inhibited M2 polarization in macrophages. In IL27R-/- mice, the effects of IL-27 were abrogated. Oltipraz inhibited IL-27-induced changes by up-regulating Nrf2 expression. Overall, this present study demonstrated that the combination of IL-27 and LPS-induced macrophage ferroptosis, promoted macrophage M1 polarization, and inhibited M2 polarization by inhibiting the Nrf2/HO-1 *** may alleviate ARDS-relat

关键词： Autoimmune   Biomarkers   Psychosis   Schizophrenia  

关键词： Psoriasis   Plaque psoriasis   Genetics   Pathogenesis   PASI index   Topical therapy   Phototherapy   Biological drugs   Combination of therapy   A3AR   A3 adenosine receptor   AhR   Aryl hydrocarbon receptor   BDs   Biological drugs   BSA   Body surface area   Cal/BD   Calcipotriol/Betamethasone   cAMP   Cyclic adenosine monophosphate   CBC   Complete blood count   CNVs   Copy number variations   CpG   Cytosine phosphate guanine   CsA   Cyclosporine A   DCs   Dendritic cells   DLQI   Dermatology Life Quality Index   EMA   European Medicines Agency   FDA   Food and Drug Administration   GM-CSF   Granulocyte-Macrophage Colony-Stimulating Factor   GM-CSFRα   GM-CSF receptor alpha   HIV   Human immunodeficiency virus   HLAs   Human leukocyte antigens   ICAMs   Intracellular adhesion molecules   IFN-γ   Interferon-γ   IgG   Immunoglobulin   IgG   Immunoglobulin G   IgG1   Immunoglobulin G1   IgG1λ   Immunoglobulin G1λ   IL   Interleukin   ITK   IL-2-inducible T-cell kinase   JAK   Janus Kinase   LFA-1   Lymphocyte-function-associated antigen-1 (1)   lncRNA   Long non-coding RNA   MHC   Major histocompatibility complex   miRNA   microRNA   MTX   Methotrexate   NB-UVB   Narrow-band UVB radiation   NF-Kβ   Nuclear factor kappa b   NK1R   Neurokinin-1 receptor   PASI   Psoriasis Area and Severity Index   PDE4   Phosphodiesterase-4   PKA   Protein kinase A   PP   Plaque psoriasis   PT   Phototherapy   PUVA   Photochemotherapy   PV   Psoriasis vulgaris   RORC   Retinoic acid-related orphan receptor C   RORγt   Retinoic acid-related orphan receptor gamma t   S1PR1   Sphingosine-1-phosphate receptor 1   SP   Substance P   T CD8   CD8+ T cells   TGF-I   Transforming growth factor I   Th-1   T-helper 1   Th-17   T-helper 17   Th-22   T-helper 22   TNF   Tumor necrosis factor   TNF-α   Tumor necrosis factor α   Treg   Regulatory T cells   TYK2   Tyrosine kinase 2   UV   Ultraviolet   UVA   Ultraviolet A   UVB   Ultraviolet B   WI-NRS   Worst Itch Numeric Rating Scale  

摘要： Psoriasis is a chronic, immune-mediated skin disease, with Plaque Psoriasis being its most common form. It is characterized by well-defined red plaques with raised white crusts. While its pathogenesis remains complex, involving keratinocytes, inflammatory cells and both adaptive and innate immunity, studies have highlighted an association with genetic predisposition. However, the absence of disease in subsequent generations suggests that environmental factors, such as sun exposure, also play a role in the pathology. Beyond skin manifestations, Plaque Psoriasis is linked to several comorbidities, and reduced quality of life, thus requiring an effective treatment. The Psoriasis Area and Severity Index and the Dermatology Quality of Life Index are used to assess the degree of the disease and guide therapy selection. Available therapies are suppressive rather than curative and include topical drugs, phototherapy, systemic oral agents and biological drugs. However, current and most widely used treatments present some drawbacks. Considering these disadvantages and combining the fact that more is known about the pathogenesis of the disease, research focuses on optimizing existing treatments and developing new drugs. In the context of innovations in the Psoriasis treatment, this review highlights biological drugs that have recently entered the market, those in the final phase of development, bisomilars and changes to topical formulations, aimed at improving therapeutic efficacy. These advances contribute to more informed treatment choices and sustained clinical outcomes.

关键词： Autophagy   Cell death   Dental cementum   Lysosomal membrane protein   Periapical periodontitis   Signal transduction  

摘要： Apical periodontitis (AP) is globally prevalent and characterized by inflammatory infiltration and periapical bone loss. The systemic RNA interference deficient-1 transmembrane family member 2 (Sidt2) is a nucleic acid transporter that plays essential roles in apoptosis and inflammatory response. However, the effect of Sidt2 on AP remains unknown. In this study, we established an AP mouse model and treated MC3T3-E1 cells and OCCM-30 cells with tumor necrosis factor-alpha (TNF-α). Compared to the control groups, the results of Western blot and quantitative real-time polymerase chain reaction (qRT-PCR) analysis confirmed that Sidt2 expression was downregulated in the AP mouse model and TNF-α-treated cells, in parallel with increased apoptosis and the production of inflammatory molecules, as evaluated by hematoxylin and eosin staining and immunohistochemistry staining. Furthermore, knockdown of Sidt2 reduced autophagic flux, aggravated TNF-α-induced apoptosis and inflammation in vitro, as detected by flow cytometry, Western blot, enzyme-linked immunosorbent assay, and qRT-PCR, and overexpression of Sidt2 yielded the opposite results. In addition, the autophagy inhibitors Chloroquine or 3-Methyladenine could reverse TNF-α-induced effects after overexpression of Sidt2. Moreover, knockdown of Sidt2 activated the TNF-α-induced p65 signaling, while blocking it with Pyrrolidinedithiocarbamate ammonium suppressed TNF-α-induced effects and autophagy. Taken together, our results suggest that Sidt2 ameliorates TNF-α-induced apoptosis and inflammation by enhancing autophagic flux via the downregulation of p65 signaling. These results demonstrate that Sidt2 functions as a negative regulator in the apoptosis and inflammatory response of AP, and it may contribute to the development of novel diagnostic and therapeutic approaches for the disease.