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关键词： Chicken   Selenium deficiency   Bisphenol A   Nitrification stress   Apoptosis and necroptosis  

摘要： With the increasing production and demand of plastic products in life, inescapable bisphenol A (BPA) exposure results in a threat to the health of organisms. Selenium (Se) is an essential trace element for living organisms. The insufficient Se intake can cause multi-tissue organ damage. In the process of production and life, the exposure of BPA is usually accompanied by Se deficiency. In this study, the models of chicken with BPA exposure and/or Se deficiency was duplicated, the status of nitrification stress, apoptosis, necroptosis, and changes in TNF-alpha/FADD signaling pathways in chicken spleen were examined. At the same time, nitrification stress inhibitor and TNF-alpha inhibitor were introduced into MSB-1 cell model tests in vitro, , indicating that BPA exposure and Se deficiency up- regulated TNF-alpha/FADD signaling pathway through nitrification stress, inducing necroptosis and apoptosis, and heat shock protein was also involved in this process. This study provides a new control idea for healthy poultry breeding based on Se, and also provides a new reference for toxicity control of environmental pollutants.

关键词： Immunodeficiency   Infection   Major Histocompatibility Complex   Pneumonia  

摘要： Major Histocompatibility Complex (MHC) Class II deficiency is a rare autosomal recessive primary immunodeficiency caused by mutations in regulatory genes of MHC Class II proteins. Clinical manifestations include respiratory/gastrointestinal infections, failure-to-thrive, septicemia and early death. A 9-mo-old-girl presented with repeated episodes of pneumonia requiring hospitalization and ventilator support since the last 5 mo. Examination revealed absent tonsils, sparse scalp-hair, seborrhea and firm hepato-splenomegaly. Radiograph showed absence of thymic shadow with diffuse pulmonary infiltrates. CT scan showed multiple bilateral ground glass pulmonary opacities with patchy consolidation. Primary immunodeficiency disorder was suspected in view of repeated pulmonary infections, failure to thrive and suggestive family history. Lymphocyte subset assay revealed lymphocytopenia and HLA typing showed absence of HLA-DR expression on B cells suggestive of MHC Class II deficiency. Targeted gene panel detected a homozygous mutation in the RFX-5 gene (RFX5: c.848_849del:p.R283Tfs*6;Homozygous). Though this patient succumbed, parents have been counseled regarding need for prenatal diagnosis.

关键词： escin   bromelain   ginkgo biloba   sage miltiorrhiza   EBGS   tumor necrosis factor alpha   endothelial cells   platelet adhesion  

摘要： Thrombosis is a key process that determines acute coronary syndrome and ischemic stroke and is the leading cause of morbidity and mortality in the world, together with cancer. Platelet adhesion and subsequent activation and aggregation are critical processes that cause thrombus formation after endothelial damage. To date, high hopes are associated with compounds of natural origin, which show anticoagulant action without undesirable effects and can be proposed as supportive therapies. We investigated the effect of the new combination of four natural compounds, escin-bromelain-ginkgo biloba-sage miltiorrhiza (EBGS), on the initial process of the coagulation cascade, which is the adhesion of platelets to activated vascular endothelium. Our results demonstrated that EBGS pretreatment of endothelial cells reduces platelet adhesion even in the presence of the monocyte-lymphocyte population. Our data indicate that EBGS exerts its effects by inhibiting the transcription of adhesion molecules, including P-selectin, platelet membrane glycoprotein GP1b, integrins alpha V and beta 3, and reducing the secretion of the pro-inflammatory cytokines interleukin 6, interleukin 8, and the metalloproteinases MMP-2 and MMP-9. Furthermore, we demonstrated that EBGS inhibited the expression of focal adhesion kinase (FAK), strictly involved in platelet adhesion, and whose activity is correlated with that of integrin beta 3. The results shown in this manuscript suggest a possible inhibitory role of the new combination EBGS in the reduction in platelet adhesion to activated endothelium, thus possibly preventing coagulation cascade initiation.

关键词： HLA-A   HLA-B   HLA-C   HLA-DQB1   NGS  

摘要： Identification of seven new HLA alleles by next-generation sequencing.

关键词： Brazilian population   Illumina Miniseq   NGS   novel HLA allele  

摘要： The HLA-A*23:140 allele differs from HLA-A*23:01:01 by one nucleotide substitution (G > A), position 1968 in exon 5.

关键词： Lead   Rosmarinus officinalis   Cerebellum   Neurotoxicity   Neuroprotection  

摘要： Lead (Pb) toxicity is a worldwide significant public health challenge causing several neurological disorders. Reports indicate that plants rich in antioxidants, such as Rosmarinus officinalis (RO), can counteract Pb accumulation and its toxicity in the brain. Due to a dearth of literature evidence demonstrating the protective activity of RO against Pb toxicity, this study investigated such activity in Wistar rats. Thirty-six Wistar rats were allocated into six groups (n=6), namely I (control), II (lead acetate [Pb];100 mg/kg b.w.), III (100 mg/kg of RO and 100 mg/kg of Pb), IV (200 mg/kg of RO and 100 mg/kg of Pb), V (100 mg/kg b.w. of RO) and VI (200 mg/kg b.w. of RO). After 28 days, neurobehavioural, antioxidant, lipid peroxidation, apoptotic and inflammatory activities as well as the histology of the cerebellum were evaluated. Body weight, locomotion and exploration as well as antioxidant enzymes were significantly (p < 0.05) decreased in Pb-exposed rats when compared to control. Conversely, lipid peroxidation, nitric oxide, tumour necrosis factor-alpha and caspase-3 activities were significantly (p < 0.05) upregulated in the Pb-exposed rats when compared to control. These parameters were, however, significantly (p<0.05) attenuated in the RO-pretreated rats when compared to Pb-exposed rats. Cerebellar histology of the Pb-exposed rats showed severe degeneration of the Purkinje cells whereas the RO-pretreated rats showed better cerebellar architecture. These findings demonstrate that the neuroprotective activity of RO is facilitated via its effective antioxidant, anti-inflammatory and anti-apoptotic effects.

关键词： Directionality   Permissive mismatches   HLA-DP   Core T -cell epitope groups   Immunopeptidome   Unrelated HCT   GvHD   NRM   Relapse  

摘要： Mismatching at the HLA-DPB1 locus occurs frequently in hematopoietic cell transplantation with unrelated donors. Despite this, HLA-DPB1 allelic mismatches have traditionally not been considered in patient-donor matching. A T-cell epitope (TCE) model for the functional assessment of permissive mismatches at this locus has nevertheless been adopted in clinical practice. While initially based on a hierarchical immunogenicity elucidated from allorecognition by T-cell clones isolated from a patient, newer developments in the understanding of this model's biological basis, including a central role for immunopeptidome divergence between mismatched allotypes, have prompted changes in the assignment of permissiveness, providing the opportunity for a more granular evaluation of graft- versus-host disease and relapse risks according to the nature and directionality of permissive mismatches. How these advances impact the assessment of permissiveness at HLA-DPB1 and potentially the intelligent selection of donors according to the main clinical goal for different patients is the subject of the present review.

关键词： Glaucoma   IL-17A   IL-17A neutralizing antibody   NF-kappa B  

摘要： Objectives: To investigate the possible roles of Interleukin 17A (IL-17A) and IL-17A neutralizing antibodies (IL17Ab) in glaucoma and the potential mechanisms. Methods: The two glaucoma animal models, chronic ocular hypertension (COH) and N-methyl-D-aspartate (NMDA)-induced retinal ganglion cell (RGC) damage, were established and treated with intravitreal injection of IL-17A or IL-17Ab. Intraocular pressure (IOP) was measured by a rebound tonometer. The retina and RGC injury were evaluated by HE staining, TUNLE assay and Brn3a immunofluorescence staining. The frequency of IL17A+CD4+T cells in peripheral blood was detected by flow cytometry. The expression of glial fibrillary acidic protein (GFAP) was detected by immunofluorescence staining, Western Blot and qPCR in retina. The RNA and protein expression of Act1/TRAF6/NF-kappa B were detected by Western Blot and qPCR in retina. Results: The expression of IL-17A increased in glaucoma models. After intravitreal injection of IL-17A, in the retina, the number of RGCs decreased, the apoptosis of RGCs increased, the M & uuml;ller cell gliosis was more obvious. In addition, peripheral inflammation aggravated. Whereas the intravitreal injection of IL-17Ab alleviated the relevant manifestations and peripheral inflammation, reduced the gliosis of M & uuml;ller cells. In the COH model, IOP increased after the injection of IL-17A, while the intravitreal injection of IL-17Ab led to a decrease in IOP. Furthermore, IL-17A promotes the apoptosis of RGCs by binding to IL-17A receptor, activating Act1/TRAF6/NF kappa B pathways. Conclusion: IL-17A plays a role in and aggravates RGC damage in glaucoma. IL-17Ab can neutralize the proinflammatory effect of IL-17A and have a protective function in glaucoma. These findings reveal the importance of IL-17A in the pathogenesis of glaucoma, which will shed light on a novel direction for the prevention and treatment of glaucoma, and also provide a reference for further research on other retinal

关键词： Saudi Arabia   HLA   Virus   Risk   COVID-19   SARS CoV-2  

摘要： Background: the human leukocyte antigen (HLA) loci have been widely characterized to be associated with viral infectious diseases. Several studies including various ethnic groups and populations suggested associations between certain HLA alleles and SARS-CoV-2 infection. Despite the numerous associations identified, the role of HLA polymorphisms in determining the individual response to SARS-CoV-2 infection is controversial among different Saudi populations. Method: Here, we performed HLA typing by next-generation sequencing to investigate if variations in polymorphic HLA genes are linked to COVID-19 severity in the Saudi population. Namely, we analyzed HLA loci at allele level in 575 Saudi patients with SARS-CoV-2 infection. HLA class I and class II frequencies in patients were compared with allele frequency data from healthy Saudi population. Results: in our cohort HLA-A* 02:01:01 G was associated with mild disease but was not associated with moderate and severe disease. HLA-B* 51:01:01 G was protective from severe disease while HLAB* 50:01:01 G, HLA-C* 06:02:01 G and HLA-DRB1 * 07:01:01 G were associated with risk to severe disease as well as the total COVID-19 cohort. HLA-DRB1 * 15:01:01 G was associated with risk to all severity groups. Conclusion: in conclusion, we found significant associations between HLA alleles and COVID-19 disease severity in Saudis. Further studies are warranted to include HLA typing in the workup for any new COVID-19 patients. (c) 2024 Published by Elsevier Ltd on behalf of King Saud Bin Abdulaziz University for Health Sciences. This is an open access article under the CC BY-NC-ND license (http://***/licenses/by-nc-nd/4.0/).

关键词： telomere length   HLA   longevity   aging  

摘要： Aging is an exceptionally complex process that depends on genetic, environmental, and lifestyle factors. Previous studies within the International HLA and Immunogenetics Workshop (IHIWS) component "Immunogenetics of Ageing" showed that longevity is associated with positive selection of HLA-DRB1*11- and DRB1*16-associated haplotypes, shown to be protective against diseases. Within the 18th IHIWS, we aimed to investigate the relevance of telomere length for successful aging and its association with classical HLAs. In total 957 individuals from Bulgaria, Turkey, Romania, and Poland in two age groups, elderly individuals (age 65-99 years) and ethnically matched young group (age 18-64 years), were investigated. The obtained results confirmed interpopulation differences in the distribution of HLA alleles, documented the lengths of telomeres in analyzed populations, and demonstrated significant associations of telomere length with aging as well as with the presence of some HLA class I or class II alleles. They suggest that telomere length assessment combined with HLA genotyping may help identify immunogenetic profiles associated with longevity. The associations between HLA and telomeres support the theory that HLA genes influence the aging process. However, further research is needed to clarify the biological basis of the observed relationships.