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关键词： Renal ischemia/reperfusion   Remote ischemic pre-conditioning   Apelin   Inflammation   Oxidative stress  

摘要： Background Remote limb ischemic pre-conditioning (RIPreC) can invoke potent renal protection. The involvement of oxidative stress and inflammatory pathways in renal ischemia/reperfusion injury (I/RI) was also confirmed. This study was designed to investigate the RIPreC effects on IRI-induced kidney dysfunction in rats through NF kappa B/TNF-alpha/TGF-beta/apelin signaling *** Renal I/RI was induced by occluding the kidney arteries for 45 min, then reperfusion for 24 h. Four similar cycles of left femoral artery ischemia (2 min)/reperfusion (3 min) before the onset of kidney ischemia were performed to create RIPreC. Animals were randomly divided into three groups: sham, I/R, and RIPreC + I/R. Following the reperfusion phase, urine and blood samples were taken, and the kidney was removed for functional, molecular, and histological *** When compared to sham rats, renal IRI resulted in decreased creatinine clearance and increased sodium fractional excretion, lower antioxidant enzyme activities, higher malondialdehyde content and higher nuclear factor-kappa B (NF-kappa B), tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-betta (TGF-beta), and Apelin expression levels, and histologically damaged kidney tissue. All of the alterations, as mentioned earlier, were alleviated using the RIPreC *** Thus, RIPreC can protect against renal dysfunction after renal I/RI via modulation of the TNF-alpha/NF-kappa B/TGF-beta Apelin signaling pathway and strengthening the antioxidant defense system.

关键词： COVID-19   HIV infections   Polymorphism   Single nucleotide   Interleukin   Cytokine storm  

摘要： Introduction The people living with HIV with abnormal immune responses have been identified as a population that is particularly susceptibility to contracting COVID-19. We explored the correlation between gene polymorphisms of IL-17A, IL-17F, and IL-6, and the susceptibility to COVID-19 in individuals with HIV infection. Methods In this cross-sectional study, 337 HIV-positive patients were included. Serological and molecular tests were done using ELISA and PCR-RFLP methods. Allelic frequency, haplotype analyses, linkage disequilibrium were calculated. A linear regression model was used to analyze the interleukin SNP genotypes in HIV patients with and without COVID-19. Results A total of 337 PLWH were recruited for this study, with 170 having COVID-19 and 167 not having it. The mean age and laboratory indicators showed no significant differences between the two groups (P > 0.05). The allele frequency analysis found no significant difference in the IL-17A rs2275913 polymorphism between case and control groups. However, the IL-17F rs763780 and IL-6 rs1800795 had significantly greater frequencies of specific alleles in the case group compared to the control group. The A-A haplotype of IL-17 in SNPs-rs 2,275,913 and rs763780 rising the risk of COVID-19 infection in PLWH by up to 2.398 times compared with the other haplotypes, and the A-G and G-A haplotypes have a protective role against the incidence of COVID-19 infection. Conclusion This study is the first to show a significant correlation between the prevalence of COVID-19 and variety polymorphism at IL-17 and IL-6, which suggests that genetic changes in interleukin genes may relate to COVID-19 distribution.

关键词： Pyroptosis   Glucocorticoid resistance   IL-8   Epithelial cells  

摘要： ObjectiveThis study seeks to elucidate the role and molecular mechanisms of IL-8 in nasal epithelial cell pyroptosis and its impact on glucocorticoid (GC) *** assessed the expression of pyroptosis-related biomarkers and IL-8 in tissues and human nasal epithelial cells (hNECs) from both control and nasal polyp patients using western blot. Their localization was determined through immunohistochemistry and immunofluorescence. Cell death and cytotoxicity assay, electron microscopy, ELISA, and immunofluorescence were utilized to investigate IL-8-induced pyroptosis and GC resistance in hNECs, alongside the examination of the involved signaling pathways via western blot and immunofluorescence. In a murine model, hematoxylin-eosin staining and immunohistochemistry clarified relationship between pyroptosis and GC ***-8 and pyroptotic biomarker expression were significantly higher in nasal polyp-derived tissues and hNECs compared to controls. IL-8 showed a positive correlation and co-localized with the pyroptotic biomarkers. IL-8 triggered pyroptosis in hNECs by activating the ERK signaling pathway, leading to increased IL-1 beta and IL-18 secretion. Moreover, IL-8-induced pyroptosis was found to contribute to GC resistance by affecting phosphorylation of GC receptor Ser211. Inhibition of pyroptotic proteins mitigated IL-8-induced GC resistance both in vitro and in *** IL-8 facilitates pyroptosis via the ERK signaling pathway and plays a significant role in GC resistance in nasal polyps.

关键词： Conservation genomics   Immune genes   Bellinger River turtle   Major histocompatibility complex   Whole-genome re-sequencing  

摘要： Small, isolated populations are often vulnerable to increased inbreeding and genetic drift, both of which elevate the risk of extinction. The Bellinger River turtle (Myuchelys georgesi) is a critically endangered species endemic to a single river catchment in New South Wales, Australia. The only extant wild population, along with the breeding program, face significant threats from viral outbreaks, most notably a nidovirus outbreak in 2015 that led to a 90% population decline. To enhance our understanding of genomic characteristics in the species, including genome-wide and functional gene diversity, we re-sequenced, assembled, and analysed 31 re-sequenced genomes for pure M. georgesi (N = 31). We manually annotated the major histocompatibility complex (MHC), identifying five MHC class I and ten MHC class II genes and investigated genetic diversity across both classes in M. georgesi. Our results showed that genome-wide diversity is critically low in pure M. georgesi, contexualised through comparison with opportunistically sampled backcross animals-offspring of F1 hybrids (M. georgesi x Emydura macquarii) backcrossed to pure M. georgesi (N = 4). However, the variation observed within the core MHC region of pure M. georgesi, extending across scaffold 10, exceeded that of all other macrochromosomes. Additionally, no significant short-term changes in either genome-wide or immunogenetic diversity were detected following the 2015 nidovirus outbreak (before;N = 19, after;N = 12). Demographic history reconstructions indicated a sustained, long-term decline in effective population size since the last interglacial period, accompanied by more recent steep declines. These patterns suggested that prolonged isolation and reduced population size have significantly influenced the dynamics of genome-wide diversity. It is likely that contemporary stressors, including the recent nidovirus outbreak, are acting on an already genetically depleted population. This study offers new insights

关键词： Sepsis   Macrophage   ILC2   IL-9   Lung injury  

摘要： BackgroundGroup 2 innate lymphoid cells (ILC2) are the main group of tissue-resident ILCs in the lungs, which protect airway barrier integrity following infection. Macrophages are integral to the regulation of immune homeostasis in sepsis. However, the relationship between ILC2 and macrophages in the context of sepsis induced acute lung injury remains *** sepsis was conducted by cecal ligation and puncture (CLP) model in Wild Type (WT) mice and ILC2 depleted mice. Septic mice were injected intratracheally IL-9, and the frequency and markers expression of ILC2 and macrophage were measured by Flow cytometry and CyTOF. The lung injury was conducted with pathological analysis. In vitro studies, MH-S cells were exposed to LPS with/without interleukin-9 (IL-9), and mTOR level and MH-S cells death were measured with western bloting or Flow *** induced the accumulation of ILCs and pulmonary macrophages in lungs. Furtherly, we revealed that ILC2 and CD45+F4/80+CD11c+ macrophages expanded during sepsis induced acute lung injury. Meanwhile, ILC2 depletion significantly enhanced macrophages expansion. In vivo and in vitro studies determined that pulmonary macrophage death followed by sepsis were protedced by IL-9, which was main secreted by ILC2 in lung. Furthermore, IL-9 significantly declined the expression of mTOR, and the presence of ILC2 or IL-9 reduced the expression of M1 markers (CD86 or MHC II).ConclusionsIL-9 secreted by ILC2 has a protective role in sepsis induced lung injury by reducing macrophage apoptosis and M1 polarization via mTOR.

关键词： Hepatitis C   HCV   Cellular immune response   CD8(+ )T response   HLA-A*02:01   Peptide microarray  

摘要： Several barriers for the development of an HCV vaccine still exist, including the genetic diversity of the virus, and the shortage of assessable models for in vitro and in vivo assays. Therefore, in this study, HCV epitope mapping was performed for 59 polyprotein sequences from 7 HCV genotypes. Around 2,880 peptides were considered epitopes for CD8+ T cells. The peptide induction of cytokines from Th1 and/or Th2 axes of the cellular immune response was assessed, indicating a tendency for Th2 axis. In vitro evaluation was performed using peptide microarray and a recombinant HLA-A*02:01 molecule. A total of 615 peptides of high reactivity to HLA-A*02:01 were identified, with predominance of leucine and tryptophan residues, highlighting their importance for TCR-epitope binding and CD8+ T activation. Finally, HCV-derived peptide patterns restricted to HLA-A2*02:01 observed in this study provide important information for the development of a multi-epitope-based pan-genotypic vaccine against the virus.

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.