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关键词： anti-HLA antibodies   panel reactive antigens   thalassemia major   transplantation  

摘要： AimTo investigate the effects of anti-human Leucocyte Antigen (HLA) antibody positivity on early hematopoietic stem cell transplantation (HSCT) results in patients with thalassemia major (TM).MethodsOne hundred and twenty-four HLA-matched HSCTs were performed in patients with TM between 2015 and 2022. Ninety-one patients were screened for anti-HLA antibodies by testing panel reactive antigens (PRA). Demographic and transplantation characteristics of patients were recorded. The presence of PRA was tested with the Antibody Testing Assay (Luminex LIFECODES HLA Antibody Identification System).ResultsThe number of PRA-positive patients was 54. There was no relationship between acute graft versus host disease (GVHD), chronic GVHD, grade of GVHD, and viral reactivation of the patients. However, platelet engraftment took around 3 days longer in the PRA-positive group (p = 0.05). The median number of erythrocyte transfusions was significantly higher in PRA-positive patients in the post-transplant period (p = 0.003), as was the median number of platelet transfusions (p = 0.003). Treosulfan conditioning increased the stable mixed chimerism (MC) rate by 3.8-fold (p = 0.011). In contrast, reduced rates of MC were found in patients who received matched unrelated donor cells or peripherally derived stem cells (p = 0.011 and p = 0.039, respectively) in the posttransplantation period in TM patients. PRA-positivity did not affect MC (p = 0.478). However, 80% of patients who had primary graft failure (n = 5;p = 0.59) and 75% of patients who died (n = 4) were PRA positive (p = 0.64), but these results were statistically insignificant due to the low number of ***-HLA antibodies primarily delayed platelet engraftment in TM patients and increased the erythrocyte and thrombocyte transfusion requirements. Although PRA positivity was more common in patients with primary graft failure or who died, there was no statistically significant impact of PRA positivity on chimerism

关键词： Social stress   IFN-gamma   Oxytocin   Prefrontal cortex   Hippocampus  

摘要： The co-evolution of social behavior and the immune system plays a critical role in individuals' adaptation to their environment. However, also need for further research on the key molecules that co-regulate social behavior and immunity. This study focused on neonatal mice that were separated from their mothers for 4 hours per day between the 6th and 16th day after birth. The results showed that these mice had lower plasma levels of IFN-gamma and oxytocin, but higher levels of plasma glucocorticoids (GC), then impacting their social abilities. Additionally, maternal separation led to decreased levels of BDNF, IGF2, and CREB mRNAs in the hippocampus, while levels in the prefrontal cortex (PFC) remained unaffected. Maternal separation also resulted in increased levels of oxytocin and CRH mRNA in the hypothalamus, as well as an increase in CD45+ lymphocyte subsets in the meninges and choroid plexus (CP), with CD8+ lymphocytes in meninges and CD4+ lymphocytes in CP showing an increase. In IFN-gamma-/- mice, a decrease in social preference was observed alongside lower plasma oxytocin levels. Moreover, IFN-gamma-/- mice exhibited reduced numbers of oxytocin neurons in the paraventricular nucleus of the paraventricular nucleus of hypothalamus (PVN), decreased BDNF levels in the PFC and hippocampus, and alterations in CD45+ lymphocytes in CP and meninges, with an increase in CD8+ lymphocytes in meninges and CD4+ lymphocytes in CP. These findings highlight the immunological impact of social stress on IFN-gamma regulation, suggesting that the immunomodulatory molecule IFN-gamma may influence social behavior by affecting synaptic efficiency in brain regions such as the hippocampus and PFC, which are linked to oxytocin in the PVN.

关键词： HLA-G   Cervical cancer   Breast cancer   Ovarian cancer   Endometrial cancer  

摘要： Human leukocyte antigen G (HLA-G) is known as a non-classical molecule of the major histocompatibility complex class Ib and downregulates the mother's immune response against the fetus during pregnancy, thereby generating immune tolerance. Due to the latter effect, HLA-G is also referred to as an immune checkpoint molecule. Originally identified on extravillous trophoblasts, HLA-G is already known to induce immune tolerance at various stages of the immune response, for example through cell differentiation and proliferation, cytolysis and cytokine secretion. Because of these functions, HLA-G is involved in various processes of cancer progression, but a comprehensive review of the role of HLA-G in gynecologic cancers is lacking. Therefore, this review focuses on the existing knowledge of HLA-G in ovarian cancer, endometrial cancer, cervical cancer and breast cancer. HLA-G is predominantly expressed in cancer tissues adjacent to the extravillous trophoblast. Therefore, modulating its expression in the cancer target tissues of cancer patients could be a potential therapeutic approach to treat these diseases.

关键词： hepatocarcinogenesis   insulin resistance   metabolic inflammation   metabolic dysfunction-associated steatohepatitis (MASH)  

摘要： Background:An increasing number of HCC develops in the context of metabolic dysfunction-associated steatotic liver disease and its inflammatory form, metabolic dysfunction-associated steatohepatitis, even in the absence of cirrhosis. Chronic metabolic inflammation is the driving force of metabolic dysfunction-associated steatotic liver disease progression and a key factor in hepatocarcinogenesis. Given the prominent role of IL-1 signaling in inflammation and metabolic diseases, we investigated the relevance of the hepatocyte-specific IL-1 receptor type 1 knockout in metabolic dysfunction-associated steatohepatitis-related noncirrhotic ***:For HCC induction, Il1r1 Hep-/- mice received a single i.p. injection of diethylnitrosamine at 2 weeks and were fed with high-fat plus high-carbohydrate diet, starting from 4 weeks. After 18 weeks of diet intervention, mice were sacrificed, and macroscopic and microscopic tumor loads were ***:Knockout of the hepatic IL-1 receptor type 1 pathway significantly reduced liver tumor growth. Il1r1 Hep-/- mice were also less susceptible to hepatic steatosis, insulin resistance, and associated hepatic c-Jun N-terminal kinase activation than their wild-type (WT) littermates. Reduced Ki-67 and cyclin D1 levels, as well as decreased phosphorylation of signal transducer and activator of transcription 3, occur in Il1r1 Hep-/- livers, lowering cancer cell proliferation and growth. Additionally, in Il1r1 Hep-/- livers, the chemokine (C-X-C motif) ligand 1/2-driven accumulation of myeloid-derived suppressor cells and CD8+ T-cell infiltration were reduced compared to the wild ***:Metabolic inflammation mediated by the hepatocytic IL-1 receptor type 1 is a cofactor in mutagenic hepatocarcinogenesis. Targeting IL-1 signaling could be an adjunct strategy to the current immunomodulatory HCC treatments.

关键词： Amino acids   Postoperative cognitive dysfunction   TNF-alpha/HMGB1   Microglial polarization   Pyroptosis  

摘要： Peripheral surgery-induced neural inflammation is a key pathogenic mechanism of postoperative cognitive dysfunction (POCD). However, the mechanism underlying neuroinflammation and associated neural injury remains elusive. Surgery itself can lead to gut damage, and the occurrence of POCD is accompanied by high levels of TNF-alpha in the serum and blood-brain barrier (BBB) damage. Reductions in stress, inflammation and protein loss have been emphasized as strategies for enhanced recovery after surgery (ERAS). We designed an amino acids and dipeptide (AAD) formula for injection that could provide intestinal protection during surgery. Through the intraoperative infusion of AAD based on the ERAS concept, we aimed to explore the effect of AAD injection on POCD and its underlying mechanism from the gut to the brain. Here, we observed that AAD injection ameliorated neural injury in POCD, in addition to restoring the function of the intestinal barrier and BBB. We also found that TNF-alpha levels decreased in the ileum, blood and hippocampus. Intestinal barrier protectors and TNF-alpha inhibitors also alleviated neural damage. AAD injection treatment decreased HMGB1 production, pyroptosis, and M1 microglial polarization and increased M2 polarization. In vitro, AAD injection protected the impaired gut barrier and decreased TNF-alpha production, alleviating damage to the BBB by stimulating cytokine transport in the body. HMGB1 and Caspase-1 inhibitors decreased pyroptosis and M1 microglial polarization and increased M2 polarization to protect TNF-alpha-stimulated microglia in vitro. Collectively, these findings suggest that the gut barrier-TNF-alpha-BBB-HMGB1-Caspase-1 inflammasome-pyroptosis-M1 microglia pathway is a novel mechanism of POCD related to the gut-brain axis and that intraoperative AAD infusion is a potential treatment for *** AbstractAccording to our findings, AAD injection, which is based on the ERAS concept, alleviates POCD by decreasing the activity

关键词： Birds   Genotype methods   MHC   Polymorphism  

摘要： The Major Histocompatibility Complex (MHC) has attracted attention to use in ecological and evolutionary studies in the last decades. Its high polymorphism has been associated with selection pressures, as sexual and/or balancing selection. Thus, MHC has become an excellent marker to provide information about evolutionary forces that shape the evolutionary history of populations. However, the high polymorphism in the MHC also brings some methodological challenges, such as isolating and sequencing only one gene, one time that it is a superfamily gene. Thus, this review aims to consolidate the knowledge about MHC in birds, searching to understand its applications, mainly theory, and some methodological difficulties. Only 5% of bird species were studied by MHC, probably due to the cost and complexity of the methodological procedures. However, both markers (MHC Class I and MHC Class II) have been used, and their simultaneous use have increase due to NGS thecnique. Since 2011, the number of studies that used next-generation sequencing (NGS) has increased (32.8%). A great part of the studies related mate choice and MHC diversity (31.82%), followed by papers that describe MHC diversity in bird species (27.27%), and evaluation evolutionary processes in this superfamily (22.73%), and the relation of genetic diversity and parasites (12.1%), remaining of the other studies approach different thematics. The MHC genes appear to be a good candidate gene for evolutionary, sexual selection, and immunology studies in birds. The number of studies of each theme yet is low, but some hypothesed have been became clearer, as different selective process act in this gene, and relation of MHC and mate choice. As many studies have shown strength influence of MHC diversity in female selection specific males, dissimilar increase the genetic diversity or with specific genotype. However, the selection processes that act in different groups is directly associated to pathogens pressures, so their evo

关键词： Type 2 diabetes mellitus   Ginger   ZnO-NPs   Antioxidants   Pancreatic tissue  

摘要： Background Diabetes is a life-threatening health condition that requires expensive treatment and places a significant financial burden on society. Consequently, this study aimed to explore the potential of low and high concentrations of ginger extract, ZnO-NPs, and a combination of both to help manage diabetes and reduce high levels of lipids in diabetic *** and results The research focused on agglomerated nanoparticles under 100 nm, specifically ZnO nanoparticles. The size of the nanoparticles was determined using X-ray diffraction analysis and scanning electron microscopy analysis, with a monodisperse particle size distribution of 20 to 48 nm and an average size of 38 nm, as shown by dynamic light scattering. Fourier transform infrared spectroscopy revealed the presence of typical peaks of ginger extract and ZnO-NPs in the nanocomposite structure. The pancreatic tissue histopathological study indicated that a concentration of 10 mg/kg of the composite had the most significant antidiabetic effect compared to other treatments. Lower concentrations could significantly reduce and balance fasting blood sugar and triglycerides levels while also increasing the high-density lipoproteins levels. However, all treatments induced a significant decrease in total cholesterol and low-density lipoproteins levels. Only metformin and ZnO-NPs in lower concentrations could decrease very low-density lipoproteins levels. The molecular technique showed that a low concentration of the composite led to the most significant decrease in Tnf-alpha gene expression compared to the diabetic group. The expression of the glutathione peroxidase 1 (Gpx1) gene in treated groups had no significant difference with the level of Gpx1 expression in the control *** In general, this study demonstrated that lower concentrations of the treatments, especially composite, were more effective for treating diabetic rats due to reduced pancreatic tissue damage.

关键词： heart failure   heart failure with preserved ejection fraction   heart failure with reduced ejection fraction   high sensitive CRP   interleukin-6  

摘要： AimsInflammation accompanies heart failure (HF) and elevated levels of inflammatory biomarkers are linked to new onset of HF. However, whether the prognostic relevance of inflammatory biomarkers is different in HF with reduced (HFrEF) and preserved ejection fraction (HFpEF) is unclear. The aim of the current study is to explore the role of inflammation on the mortality risk in patients with *** analysed interleukin-6 and hsCRP levels by ELISA and immunonephelometry, respectively, in HFpEF and HFrEF patients referred for coronary angiography and assessed the prognostic value in the Ludwigshafen Risk and Cardiovascular Health (LURIC) *** was present in 1086 patients (N = 506 HFpEF;N = 580 HFrEF;mean age 65 +/- 10 years;28% female). Increasing IL-6 levels were significantly associated with increased CV mortality in HFpEF [1.5 (95% CI: 1.1-2.2), P = 0.018] but not HFrEF [HR 1.3 (95% CI: 1.0-1.7), P = 0.06] patients. High-sensitive CRP followed a similar pattern but failed to reach statistical significance after full-adjustment (HFpEF: HR 1.4 95%C I: 1.0-2.0;P = 0.065;HFrEF HR: 1.0 95% CI: 0.7-1.3;P = 0.800). Interaction analysis in patients stratified by IL-6 and N terminal pro brain natriuretic peptide (NT-proBNP) above and below the median revealed a stepwise increase in CV-mortality in HFpEF (P = 0.036) but not HFrEF patients (P = 0.220). To investigate the relationship between IL-6 and NT-proBNP, we assessed the genetic IL6-Receptor variant ***358Ala (rs2228145) which is linked to impaired IL-6 receptor signalling. Homozygous carriers with HFpEF but not HFrEF exhibited significantly lower NT-pro-BNP levels compared with wildtype carriers (HFpEF 779 pg/mL +/- 787 vs. 1180 pg/ mL +/- 1532;P = 0.008;HFrEF 2289 pg/ mL +/- 3439 vs. 2326 pg/ mL +/- 3386;P = 0.94), raising the hypothesis that IL-6 signalling may play a pathophysiological role in *** data suggest a predictive value of elevated IL-6 for CV-mortality in HFpEF but not