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关键词： Peanut hypersensitivity   food hypersensitivity   anaphy   laxis   genetic association study   HLA antigens   MHC   racial groups  

摘要： Background: Peanut is a major cause of food allergy. HLA genes have been consistently associated with peanut allergy in association studies. To date, however, there have been very few genetic studies of peanut allergy in non-Hispanic Black (Black) individuals, a group disproportionately affected by food allergy. Objective: Our aim was to study the relationship between HLA alleles and peanut allergy among Black individuals. Methods: The analysis consisted of Black participants from the Study of Asthma-Related Phenotypes and Pharmacogenomic Interactions by Race-Ethnicity (SAPPHIRE), a large cohort of individuals from metropolitan Detroit. At the time of enrollment, participants provided detailed food allergy histories, including symptoms. Four-digit resolution HLA allele calls were made using whole genome sequence data. Results: The cases consisted of 119 individuals with reported peanut allergy and 59 individuals with peanut-related anaphylaxis;the comparison group consisted of 2640 individuals without reported food allergy. HLA-DRB1*13:02 was the most significant allele associated with peanut allergy (adjusted odds ratio = 1.94 [95% CI = 1.28-2.93]), and HLA-DQA1*01:02 was the top association with peanut-related anaphylaxis (aOR = 1.67 [95% CI = 1.14-2.44]). Amino acid polymorphisms at position 71 in the binding groove of HLADRB1 were associated with peanut allergy and estimated to affect peanut allergen binding affinity. Conclusions: In a cohort of Black individuals, this study independently identified the same associations of peanut allergy and HLA that were previously observed in non-Hispanic White individuals. Our findings suggest that specific HLA binding groove amino acid polymorphisms may confer similar peanut allergy risk across population groups and HLA alleles. Allergy Clin Immunol Global 2025;4:100485.)

摘要： Objective Human Leukocyte Antigen (HLA), specifically HLA-B*58:01, testing before allopurinol initiation in patients with gout in Thailand was previously shown to be cost-effective. However, several drugs are available in the treatment of gout in Thailand, so the updated cost-effectiveness analysis is warranted. This study aimed to update the cost-effectiveness of HLA-B*58:01 testing before allopurinol initiation in patients with gout in *** A hybrid model consisting of a decision tree and a Markov model with a lifetime horizon from a societal perspective was undertaken. The HLA-B*58:01 testing was compared to the standard of care as no testing. Total health care costs and quality-adjusted life years (QALYs) were assessed. A comprehensive literature review along with retrospective data analysis and prospective data collection were conducted to determine inputs to inform the model. The incremental cost-effectiveness ratio analysis was *** HLA-B*58:01 testing could avoid 1.554 Stevens-Johnson syndrome and toxic epidermal necrosis cases, resulting in a saving of 0.140 patients' lives per 1,000 patients. It could gain 0.002 life-years and 0.004 QALYs compared to no testing. However, it required a higher lifetime cost of 4,690 Thai baht (THB), resulting in an incremental cost-effectiveness ratio of 1,093,068 THB/QALY (31,404 US dollars per QALY).Conclusion HLA-B*58:01 testing was not cost-effective before allopurinol initiation in Thai patients with gout at the current price of 1,000 THB per test. However, HLA-B*58:01 testing would be cost-effective if only probenecid was the alternative treatment for patients with positive HLA-B*58:01 results. This result would be useful for health authorities, policy decision-makers, and physicians' organizations in providing the recommendation for HLA-B*58:01 testing before initiation of allopurinol.

摘要： Background and Aims: Atherosclerosis is one of the leading causes of myocardial infarction (MI). The immune system plays an important role in disease development and progression. We recently completed a randomised clinical trial (LILAC and IVORY) ...

关键词： MHC class II   Genetic diversity   Phylogroups   Pathogenic load   Natural selection   Population differentiation   Amplicon sequencing   Illumina  

摘要： The common hamster is listed in the IUCN Red Data Book as a species with a drastically decreasing population. At the same time, against the background of a general decline in nature, the species began to actively settle in cities. A consequence of the population decline is reduced genetic diversity, which in turn can lead to decreased resistance to pathogens, reproductive deterioration, etc. We analyzed the allelic diversity of exon 2 of the DRB gene in common hamsters belonging to phylogroups from the eastern part of the range ("Europe", "Caucasus", "Altai"), using amplicon sequencing on the Illumina platform. The results were compared to earlier known data from urban and rural populations in Crimea, and two populations from the western part of the range ("Pannonia", "North"). We found that the allelic diversity of the DRB gene in the eastern part of the range is three times greater than that of the western ones. Based on the number and diversity of alleles and corresponding amino acid sequences, the presence of unique alleles, the phylogroup "Europe" is the most diverse. The "Caucasus" is the least diverse of all the eastern populations. The urban Crimean population, belonging to "Europe", in contrast, exhibits the greatest diversity in alleles compared to all newly studied populations. Notably, positive selection for antigen-binding regions has only been shown for urban populations. This information can be used for conservation planning for common hamster.

关键词： Oyster polysaccharide   Muscle atrophy  

摘要： This study aimed to elucidate how Crassostrea hongkongensis polysaccharide (CHP) alleviates TNF-alpha-induced atrophy in C2C12 myotubes. CHP enhances MyHC expression while suppressing the muscle atrophy markers MuRF1 and MaFbx. Additionally, CHP significantly enhanced mitochondria biogenesis and ATP production. This effect may be attributed to CHP induced activation of glucagon and glycolysis/gluconeogenesis signalling pathways, as well as its modulation of insulin resistance. Transcriptomic analyses demonstrated that CHP attenuated the TNF-alpha mediated inhibition of C2C12 myoblast differentiation and multinucleated myotubes formation, potentially through modulation of calcium signalling pathways. Molecular docking, molecular dynamics, and quantum chemical assessments suggest that the branched structure of CHP molecules promotes flexible electron distribution. This stabilizes the binding of CHP to sarco/endoplasmic reticulum calcium ATPase (SERCA), which is crucial for calcium reuptake. Consequently, CHP upregulates energy metabolism pathways to improve mitochondrial function, increases the SERCA expression to promote calcium reuptake, thereby alleviating muscle waste.

关键词： TGEV   IFN   IFIT3   TBK1   STAT1  

摘要： TGEV mainly infects pig small intestinal epithelium, resulting in vomiting, diarrhea, dehydration, and death. IFIT3 is involved in resisting viral infection and is an innate immune regulator. In this study, we determined that TGEV infection could induce IFIT3 expression. The overexpression of IFIT3 inhibited TGEV infection, promoted the phosphorylation of TBK1 and STAT1, and upregulated the transcription of IFN-beta and interferon-stimulated genes (ISGs). Conversely, knockdown of IFIT3 decreased the activation of the interferon immune response. Blocking the JAK-STAT1 pathway inhibited the transmission of interferon signals and reversed the restriction of IFIT3 to TGEV infection. Immunoprecipitation revealed that IFIT3 interacted with TBK1 and STAT1, indicating that TBK1 and STAT1 are key molecules through which IFIT3 regulates the interferon immune response and inhibits TGEV infection. This study preliminarily revealed that IFIT3 regulated the innate immune response to inhibit TGEV infection, enriching the theoretical understanding of the interaction between TGEV and the host.