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关键词： Antibody avidity   Interleukin-21   Interleukin-27   Severe acute respiratory syndrome coronavirus 2  

摘要： The quantity and quality of anti-Spike (anti-S) antibodies, rapidly elicited by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are necessary for understanding the immune response induced by infection. Antibody avidity is a good indicator of the quality of antibody response. Interleukin (IL)-21 and IL-27 are two cytokines that play vital roles in the affinity maturation process. Therefore, we decided to investigate whether there are any relationships between the avidities of antibodies against spike and nucleocapsid (N) antigens of SARS-CoV-2 and serum levels of these cytokines in symptomatic and asymptomatic coronavirus disease 2019 (COVID-19) patients. Forty symptomatic COVID-19 patients and 40 asymptomatic carriers were enrolled. Anti-S and anti-N IgG avidity indices (AIs) were determined using a modified enzyme-linked immunosorbent assay (ELISA). Serum levels of IL-21 and IL-27 were quantified by specific ELISA kits. AI values of both anti-S and anti-N IgG were lower in the symptomatic group compared to asymptomatic cases, while only that of anti-N IgG was statistically significant. For IL-21 and IL-27 serum levels, no significant difference between the two groups was shown. Also, we could not find any correlations between cytokine levels and antibody AI values. However, an inverse correlation between anti-S AI value and IL-27 serum level was found in asymptomatic patients. Our study suggests that serum levels of IL-21 and IL-27 cannot predict differences in anti-S and anti-N IgG avidity between symptomatic and asymptomatic COVID-19 patients.

关键词： Public health   Observational studies/registry   Epidemiology  

摘要： Background: Spondyloarthritis (SpA) comprises a family of inflammatory disorders including axial and peripheral spondyloarthritis. This group includes patients with radiographic axial SpA (r-axSpA, also termed ankylosing spondylitis) who typically has symptoms of inflammatory back pain, asymmetrical oligoarthritis, enthesitis and dactylitis. The prevalence of r-axSpA closely parallels the frequency of HLA-B27 and it remains one of the strongest observed associations for any HLA gene with immune mediated disease. In general, r-axSpA occurs in all parts of the world, but there are race-related differences in prevalence, what reflects the difference in the distribution of HLA-B27 among races. Objectives: Establish a robust statistical correlation between the frequency of HLA-B27 and the prevalence of r-axSpA in different populations around the world, where there are no prevalence studies of r-axSpA but the HLA-B27 frequency data is known through other genetic studies in different contexts. Methods: A systematic search of the literature from 1970 onwards evaluating frequency of positivity for HLA-B27 and prevalence of r-axSpA in general populations from different countries around the world was conducted. The selection of publications adhered the following eligibility criteria: complete articles or abstracts available electronically, whose titles and abstracts are congruent with the purpose of the literature review. The protocol was registered in International Prospective Register of Systematic Reviews (PROSPERO) (CRD42024561795). We used a generalized linear mixed model (GLMM) with a logit link function to model the relationship between r-axSpA prevalence and HLA- B27 frequency, featuring fixed country effects and study random effects. Another regression model was fitted combining both analyses to r-axSpA prevalence adjusted for HLA-B27. The average estimate of the regression line was determined using a parametric bootstrap method. Results: Data collected were analyzed

关键词： Interferon-gamma   Tumor necrosis factor-alpha   Endothelial barrier   Synergism   Proinflammatory cytokine  

摘要： Crosstalk and synergy between interferon-gamma (IFN-Y) and tumor necrosis factor-alpha (TNF-alpha) in endothelial cells have previously been documented, however, there is an absence of articles reviewing the synergistic effect of IFN-Y and TNF-alpha in regulating the endothelial barrier function. This review discusses the regulatory mechanisms and recent evidence of the synergism of IFN-gamma and TNF-alpha in causing destabilization of endothelial junctions in various clinical studies and preclinical models. Articles were retrieved from electronic databases such as Web of Science, PubMed, Google Scholar, and Scopus. The search terms used were "interferon", "interferon-gamma", "tumor necrosis factor-alpha", "vascular inflammation", "endothelial barrier", "endothelial permeability" and "synergism". We selected articles published between 2004 and 2024. Through the Rho-associated protein kinase (ROCK) and p38 mitogen-activated protein (MAP) kinase pathways, our results showed that IFN-gamma controls the remodeling of actin and the stability of junctions. In comparison to IFN-gamma, the signaling cascades triggered by TNF-alpha involve a variety of pathways such as nuclear factor-kappa B (NF-kappa B), small GTPases, tyrosine kinases, integrin receptors, and barrier-stabilizing molecules such as Ras-related proteins 1A (Rap1A) and Rac family small GTPase 1 (Rac1). In the context of IFN-gamma and TNF-alpha synergism, combined IFN-gamma and TNF-alpha alter adherens and tight junctions. It is deduced that c-Jun N-terminal kinase (JNK), signal transducers and activators of transcription (STAT1), and caspase signaling pathways regulate endothelial barrier disruption caused by IFN-gamma and TNF-alpha. Collectively, the mechanism underlying the synergistic action of IFN-gamma and TNF-alpha is still lacking. Future work is needed to explore the crosstalk pathways of IFN-gamma and TNF-alpha involved in the regulation of endothelial barrier function such as modulation of extracellu

关键词： interleukin-22   pancreas   liver   metabolism   steatohepatitis   obesity   diabetes   IL-22RA1  

摘要： Primarily perceived as an anti-inflammatory and antimicrobial mediator in mucosa and skin, interleukin-22 (IL-22) has emerged as a pivotal metabolic regulator. Central to IL-22 signaling is its receptor, IL-22RA1. Through IL-22RA1, IL-22 or-chestrates glucose homeostasis by modulating insulin secretion, reducing cellu-lar stress in pancreatic islets, promoting beta-cell regeneration, and influencing hepatic glucose and lipid metabolism. These actions suggest its potential as a therapeutic for metabolic dysfunctions like diabetes, obesity, and steatohepatitis. However, clinical applications of IL-22 face challenges related to off-target effects and safety concerns. This review explores IL-22's physiological roles, regulatory mechanisms, and profound influence on metabolic tissues. It also underscores IL-22's dual role in metabolic health and disease, advocating further research to harness its therapeutic potential.

关键词： Idiopathic facial pain   Perception   Pharmacotherapy   Behavioural therapy   Treatment   Saudi Arabia  

摘要： Background: Persistent idiopathic facial pain (PIFP) is a complex condition characterized by chronic, unexplained facial pain that significantly impacts patients' quality of life and remains poorly understood by the general public. This research aimed to assess the knowledge and understanding of PIFP among the general population of Ha'il, Saudi Arabia. Methods: This cross-sectional study examined Ha'il residents' attitudes and levels of knowledge regarding PIFP and investigated the associated factors. Anonymised surveys were distributed to 350 respondents between November 2023 and March 2024. The original survey draft was based on a combination of previously published research, the Facial Pain Association, and previously validated questionnaires addressing similar objectives. A standardised survey scheme was designed, pre-coded and validated. The refined survey instrument was then transformed into an online questionnaire using Google Survey (c) 2023 and distributed. Results: In total, 254 respondents filled out the survey. The chi-square test was utilised to assess knowledge and attitudes in relation to participants' sociodemographic characteristics. Spearman's rank correlation coefficient (p < 0.05), odds ratios and confidence intervals were calculated to assess the relationship between attitudes and knowledge. Binary logistic regression analysis was performed to identify predictors of high knowledge levels and positive attitudes. The participants showed moderate knowledge of PIFP, with 51.24% correct responses. Notably, 96.90% identified dental issues, infections and nerve abnormalities as key factors. Gender influenced perceptions, with 30.9% of women and 45.9% of men downplaying PIFP's significance, while age, education and occupation had minimal impact (p > 0.05). Conclusions: This study emphasises the critical need for targeted educational programs to address misconceptions and information gaps around PIFP. The information gained highlights the need for an adv

关键词： Paclitaxel   H1.0   HDAC5   NF-kappa B   IL-6   Ovarian cancer  

摘要： Chemoresistance is a significant challenge and major obstacle to achieving cancer remission during chemotherapy, primarily due to the risk of recurrence and metastasis. This study reveals that linker histone H1.0 plays a crucial role in paclitaxel resistance (TXR) in ovarian cancer cells by regulating Histone deacetylase 5 (HDAC5), which deacetylates core histones and represses gene transactivation. Transcriptomic profile analysis revealed that cytokine signaling networks are enriched pathways that correlate with H1.0 expression. Advanced clustering analysis identified interleukin 6 (IL-6) as a key molecule connecting these enriched H1.0-related pathways. Furthermore, gain- and loss-of-H1.0 expression experiments showed that H1.0 controls IL-6 mRNA and protein expression in ovarian cancer cells. Additionally, our findings indicate that HDAC5 expression is downregulated in SKOV3/Txr cells compared with parental cells. H1.0 silencing in TXR cells increases HDAC5 levels, suggesting an antagonistic effect between H1.0 and HDAC5. Cell viability assays showed that HDAC5 overexpression markedly inhibited cell survival. Furthermore, ectopic HDAC5 overexpression reduced IL-6 mRNA and protein expression, which was increased by H1.0. This effect was associated with reduced H3K9Ac core histone acetylation and decreased NF-kappa B binding on the IL-6 promoter, as demonstrated by chromatin immunoprecipitation assays. Further analysis revealed that HDAC5 is downregulated in several tumor types. Furthermore, high H1.0 and IL-6 expression, coupled with low HDAC5 levels, was exclusively observed in ovarian carcinoma. Together, our results demonstrate an interplay between H1.0, HDAC5, and IL-6 in modulating paclitaxel resistance in ovarian cancer cells, highlighting new therapeutic targets to overcome chemoresistance.

关键词： dibutyltin   human immune cells   IL-1 beta   IL-6   inflammation   pentachlorophenol   TLR  

摘要： Pentachlorophenol (PCP) and dibutyltin dichloride (DBT) contaminate the environment due to their diverse applications. PCP has been found from 0.26 to 5 mu M in the serum of exposed individuals and at an average of 0.15 mu M in the unexposed. DBT has been detected in human blood at levels up to 0.3 mu M. Exposure to these contaminants is linked to pathological conditions including cancer. Interleukin-1 beta (IL-1 beta) and IL-6 are pro-inflammatory cytokines that when produced inappropriately can cause chronic inflammation, which is linked to pathologies including autoimmune diseases and cancer. PCP and DBT have been shown to increase the production of IL-1 beta and IL-6 by immune cells in a MAP kinase (MAPK) dependent process. Toll-like receptors (TLRs) activate the signaling pathways linked to MAPK that lead to production of these cytokines. This study demonstrates that PCP-induced production of IL-1 beta and IL-6 is dependent on TLR4 and TLR8, and independent of TLR1/2, TLR2, and TLR3. Additionally, DBT-induced IL-6 production depends on TLR1/2, whereas IL-1 beta production does not. Blocking the TLR-linked adapter protein, MyD88, lead to a loss of both PCP and DBT stimulation of IL-1 beta and IL-6. These findings indicate that both PCP and DBT interact with selected TLRs as part of their mechanisms of elevating the levels of critical pro-inflammatory cytokines, which may contribute to chronic inflammation and its related pathologies.

关键词： biological DMARD   Biosimilar Pharmaceuticals   Descriptive Studies   Patient Reported Outcome Measures