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关键词： IL-6   sIL-6R   Long-COVID   Genetic variant   Seasonal variation   Misclassification bias  

摘要： This observational study focused on the impact of Interleukin-6 (IL-6)-related factors (notably the IL-6 receptor (IL-6R) gene's rs2228145 polymorphism) on long-COVID risk in individuals who had previously experienced COVID-19 infection(s). The purpose of the study was to better understand such factors' contribution to longCOVID risk, and thus possibly initiate future strategies for using IL-6-related factors as biomarkers predictive of risk (while also obtaining data that may influence long-COVID management and treatment more generally). DNA and blood samples, plus questionnaire responses regarding long-COVID symptoms (including chronic fatigue and cognitive impairment), were collected from 175 participants who had previously experienced COVID-19 infection(s). Potential associations between self-reported long-COVID symptoms and participants' rs2228145 genotypes (determined using TaqMan-based genotyping assays) and/or their circulating IL-6, sIL-6R and sgp130 levels (determined using ELISA) were evaluated. Univariate-regression analyses demonstrated that odds of exhibiting long-COVID symptoms increased with severity/number of previous COVID-19 infection(s) and with hypertension as a co-morbidity, while vaccination decreased the likelihood of developing long-COVID. While long-COVID sufferers exhibited higher IL-6 signalling activity than healthy control individuals, rs2228145 genotype was not associated with long-COVID odds-ratios in- the entire-study cohort. Following identification of significant seasonal variations within our dataset, the entire-study cohort was stratified depending on when samples/questionnaire responses were obtained. In the resulting 'summer' sub-cohort (but not the 'winter' sub-cohort), the rs2228145 AA genotype was significantly over-represented amongst those exhibiting long-COVID symptoms, and long-COVID odds-ratios were significantly reduced for the CC and AC genotypes. While interpretation is complicated by seasonal variations, these findi

关键词： Rabies virus   Single-chain antibodies   CD9   IL-16   Adeno-associated virus   Cell-penetrating peptide  

摘要： Rabies, caused by the rabies virus (RABV;scientific name Rabies lyssavirus), is invariably fatal, and currently, there is no specific drug for its treatment. Previous studies have demonstrated the relationship between CD9 and the RABV. However, it remains unclear whether CD9 and IL-16 affect the RABV life cycle. To verify the role of CD9 and IL-16 in the life cycle of the RABV and further explore drugs that can inhibit RABV replication. We examined the effects of overexpression or underexpression of CD9 and IL-16 on the RABV replication process. Subsequently, adeno-associated virus (AAV) vector-delivered single-chain antibodies against RABV glycoprotein (RABV-G) or IL-16, were utilized to specifically inhibit RABV replication and explore their therapeutic potential in a mouse model of rabies. Our study revealed that the CD9 protein significantly affected RABV replication in cells. Also, IL-16 could effectively inhibited the RABV replication in vitro and prolonged mouse survival in vivo. Single-chain antibodies against RABV and IL-16, delivered by AAV vectors carrying exocytotic peptides and membrane-penetrating peptides, inhibited RABV proliferation in vitro, and suppressed RABV replication in mice in vivo. The tetraspanin CD9 facilitates RABV infection, and like the RABV-G, it may also be a good therapeutic target for RABV infection. The CD9 ligand molecule IL-16 and single-chain antibodies against RABV carried by AAV delivery system are promising therapeutic approaches for RABV infection.

关键词： Methicillin-resistant staphylococcus aureus   Brazilin   SaeR   Hla  

摘要： Background: Methicillin-resistant Staphylococcus aureus (MRSA) is a super-resistant bacterium with strong pathogenicity, causing broad range of infections in various tissues. alpha-Hemolysin (Hla) is the main virulence factor of S. aureus. Brazilin (BN), is a homoisoflavonoid derivative, obtained from the wood of Caesalpinia echinata Lam (Brazil-wood), Caesalpinia sappan L (Leguminosae), and Caesalpinia violacea Standl, has been proven to exert excellent antibacterial and anti-virulence effects against S. aureus. However, the underlying mechanisms remain still unclear. Objective: This study aims to evaluate the inhibitory effect of BN on MRSA virulence and pathogenicity and elucidate its underlying mechanisms. Methods: Rabbit erythrocytes were used to evaluate the effect of BN on hemocytolysis. The potential target of BN was screened by transcriptomic sequencing and verified by qRT-PCR, western blot (WB), and molecular interaction experiments. The effects of BN on MRSA toxicity and pathogenicity were both validated using A549 cell and mouse skin abscess model caused by MRSA. Results: BN attenuated the hemolytic activity of MRSA by inhibiting Hla secretion. It was also found that BN blocks its binding to the P1 promoter of the sae operon, and then reduced its transcript level. Remarkably, Delta saeR strain exhibits significantly reduced hemolytic activity due to impaired regulation of Hla and no extra inhibitory effect was observed in the samples treated with BN. Moreover, BN relieved A549 cell damage and mouse skin abscess induced by MRSA by inhibiting SaeR. Conclusion: These findings reveal, for the first time, BN can alleviate MRSA virulence and pathogenicity by decreasing the secretion of the Hla via inhibiting SaeR. Overall, this study suggests that BN could be a candidate for being submitted to further studies with the aim of its development as a new antibiotic against MRSA.

关键词： HLA-E*01:152   next-generation sequencing   novel allele   variant  

摘要： E*01:152 differs from E*01:03:05:01 by a non-synonymous A>G substitution at gDNA position 958 (exon 3).

关键词： HLA   HLA-C*16:01:01:42Q   novel allele   sequencing-based typing  

摘要： HLA-C*16:01:01:42Q differs from HLA-C*16:01:01:01 by one nucleotide substitution in the splicing site between intron 2 and exon 3.

关键词： Incident atrial fibrillation   T cell   NKT-like cell  

摘要： Aims T cells are present in atrial tissue from atrial fibrillation (AF) patients. However, prospective studies of T cells and AF development are few. The current aim was to investigate if T-cell subsets are associated with the risk of developing *** and results T-cell subsets, measured by flow cytometry of cryopreserved mononuclear leucocytes isolated from blood at baseline, were analysed for associations of incident AF in 669 subjects from a population-based cohort. Subjects were followed for incidence of AF for 18.6 (11.5-21.7) years during which 145 subjects were diagnosed with AF. Incident AF cases had higher levels of CD3+CD56+ NKT-like cells. No differences in CD3+, CD3+CD4+, CD3+CD8, Th1, Th2, or regulatory T cells between incident AF cases and non-cases were observed. Women had higher levels of NKT-like cells than men. High numbers of NKT-like cells were associated with an increased risk of developing AF in women [HR (95% CI) 1.88 (1.10-3.23) above vs. below median], but not in men or in the total cohort. The majority of NKT-like cells were IFN gamma+ after stimulation. High numbers of IFN gamma+ NKT-like cells were associated with increased risk for developing AF in women. Median fluorescence intensity of IFN gamma for NKT-like cells was higher in cases of incident AF in women, but not in the total cohort or in *** High levels of IFN gamma+ NKT-like cells in blood are associated with increased risk of incident AF in women, supporting a role for T cells in development of AF and emphasizing sex differences in this context. Current treatments of AF are insufficient, and immunomodulatory and anti-inflammatory therapies are suggested as potential future therapies. T cells are present in atrial tissue of AF patients. However, there are few prospective studies of T cells and risk of AF *** presented data associate high levels of circulating IFN gamma-expressing NKT-like cells with increased risk of developing AF in women. Our data sup

关键词： Acute severe ulcerative colitis   Anti-TNF   Colectomy   Infliximab