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关键词： Danshensu   Autophagy   Pyroptosis   Macrophage polarization   TNF-alpha   Ischemic flaps  

摘要： Background: The significant distal necrosis of the random-pattern skin flaps greatly restricts their clinical applications in flap transplantation. Previous studies have demonstrated the potential of danshensu (DSS) to alleviate ischemic tissue injury. However, no research to date has confirmed whether DSS can improve the survival of ischemic flaps. This study employed DSS to examine its role and the mechanisms underlying its impact on flap survival. Methods: RNA sequencing was conducted to identify potential targets of DSS in ischemic flaps. The viability of random-pattern skin flaps was assessed by analyzing the survival area, tissue edema, laser Doppler blood flow, and histological examination. Western blot and immunofluorescence were used to determine the protein levels related to angiogenesis, pyroptosis, macrophage polarization, autophagy, and the TNF-alpha-mediated NF-kappa B signaling pathway. Results: Through RNA sequencing analysis, we observed differences in gene expression related to inflammation and cell death before and after flap injury. Based on the above, DSS, which possesses anti-inflammatory and antioxidant properties, came into our view and was confirmed to enhance the viability of ischemic flaps. The results showed that DSS promoted angiogenesis, induced macrophage polarization toward the M2 type, and reduced pyroptosis. We also demonstrated that enhancing autophagic flux promoted angiogenesis and reduced inflammation. In addition, DSS enhanced autophagy by suppressing the NF-kappa B signaling pathway through the downregulation of TNF-alpha. Overexpression of TNF-alpha activated the NF-kappa B signaling pathway, reduced autophagic flux, and eliminated the protective effect of DSS. Conclusion: DSS promoted autophagy and reduced inflammation by downregulating TNF-alpha to suppress the NF-kappa B signaling pathway, thereby improving the vitality of ischemic flaps and providing strong support for its clinical application.

关键词： Metabolic stress   Macrophages   Interleukin-6   Interleulin-1 beta   Macrophage polarization and inflammation  

摘要： Macrophages are highly variable immune cells that are important in controlling inflammation and maintaining tissue balance. The ability to polarize into two major types-M1, promoting inflammation, and M2, resolving inflammation and contributing to tissue repair-determines their specific roles in health and disease. M2 macrophages are particularly important for reducing inflammation and promoting tissue regeneration, but their function is shaped mainly by surrounding cells. This is evident in obesity, diabetes, and chronic inflammation. Although many cytokines regulate macrophage polarization, interleukin-6 (IL-6) and interleukin-1 beta (IL-1 beta) are major players, but their effects on M2 macrophage behavior under metabolic stress remain unclear. This study describes the intricacies within M2 macrophages concerning IL-6 and IL-1 beta signaling when under metabolic stress. Though, more frequently than not, IL-6 is labelled as pro-inflammatory, it can also behave as an antiinflammatory mediator. On the other hand, IL-1 beta is the main pro-inflammatory agent, particularly in metabolic disorders. The relationship between these cytokines and the macrophages is mediated through important pathways such as JAK/STAT and NF kappa B, which get perturbed by metabolic stress. Therefore, metabolic stress also alters the functional parameters of macrophages, including alterations in mitochondrial metabolism, glycolytic and oxidative metabolism. Phosphorylation alters the kinetics involved in energy consumption and affects their polarization and their function. However, it has been suggested that IL-6 and IL-1 beta may work in concert or competition when inducing M2 polarization and, importantly, implicate cytokine release, phagocytic activity, and tissue repair processes. In this review, we discuss the recent literature on the participation of IL-6 and IL-1 beta cytokines in macrophage polarization and how metabolic stress changes cytokine functions and synergistic relations. A

关键词： HLA-B*15:662   novel allele   sequencing-based typing  

摘要： HLA-B*15:662 differs from HLA-B*15:11:01 by one nucleotide in exon 5.

关键词： Osteoporosis   IL-6   TGF-beta1   Bone density   Bone turnover   Diagnostic value  

摘要： PurposeThis research is intended to evaluate the correlations of serum IL-6 and TGF-beta 1 concentrations with bone density and turnover markers as well as their diagnostic value in elderly male patients with osteoporosis (OP).MethodsA retrospective analysis was conducted on 335 elderly men (>= 60 years;90 with normal bone mass, 120 osteopenia cases, and 125 OP cases). Lumbar spine/femoral neck BMD values were measured using dual-energy X-ray absorptiometry. Correlations of serum IL-6 and TGF-beta 1 concentrations with bone density and bone turnover markers in OP patients were analyzed utilizing Pearson or Spearman correlation coefficients. Independent influencing factors for OP were identified by logistic multivariate regression analysis. The diagnostic value of serum IL-6 and TGF-beta 1 was assessed with ROC curves and MedCalc *** history, drinking history, lumbar spine BMD, femoral neck BMD, PINP, and beta-CTX markedly differed among the normal bone mass, osteopenia, and OP groups. Elevated IL-6 and reduced TGF-beta 1 concentrations were observed in serum samples of OP. Serum IL-6 concentrations was inversely associated with bone density markers but positively lined to bone turnover markers. Conversely, serum TGF-beta 1 was positively related to bone density markers but negatively associated with bone turnover markers. Smoking history, PINP, and IL-6, were identified as independent risk factors while lumbar spine BMD, femoral neck BMD, and TGF-beta 1 were independent protective markers for OP. The combined assessment of serum IL-6 and TGF-beta 1 showed superior diagnostic performance for *** IL-6 in combination with TGF-beta 1 exhibits good diagnostic performance for *** of evidenceDiagnostic: individual cross-sectional studies with consistently applied reference standard and blinding

关键词： HLA   HLA-DPB1*04:02:27   novel allele   sequencing-based typing  

摘要： HLA-DPB1*04:02:27 differs from HLA-DPB1*04:02:01:01 by one nucleotide substitution in codon 193 in exon 4.

关键词： HLA   HLA-B*44:417   novel allele   sequencing-based typing  

摘要： HLA-B*44:417 differs from HLA-B*44:02:01:01 by one nucleotide substitution in codon -6 in exon 1.

关键词： HLA   HLA-B*35:627   novel allele   sequencing-based typing  

摘要： HLA-B*35:627 differs from HLA-B*35:01:01:01 by one nucleotide substitution in codon 80 in exon 2.

关键词： t1081   ST45   Hemolytic activity   alpha-hemolysin   Hla   RNAIII-Independent  

摘要： Background: alpha-Hemolysin, encoded by hla, is a major virulence factor of Staphylococcus aureus. Sequence type (ST) 45 is a globally spread clone with increasing clinical prevalence in Taiwan. Our previous study showed that among the CC45 isolates, the spa type t1081 isolates presented greater hemolytic activity. Materials and methods: The hemolytic activity of 67 CC45 isolates (44 t1081 and 23 non-t1081) from clinical blood cultures was assessed using rabbit red blood cells. The sequences of hla and its upstream regulatory regions and RNAIII were compared between the two groups. The expression of hla and its regulators RNAIII, mgrA, and saeR was analyzed via qRT-PCR, while Hla protein levels were measured via Western blotting. Results: Compared with non-t1081 isolates, t1081 isolates presented increased hemolytic activity. No significant differences in hla sequences, upstream regulatory regions, or gene expression levels were detected between the two groups. The expression of the transcriptional regulators mgrA and saeR was also similar between the two groups. Western blotting revealed increased Hla protein in the t1081 isolates. However, neither the sequence or expression of RNAIII, a regulator of hla at both the transcriptional and posttranscriptional levels, differed between the groups. Conclusion: Our study revealed that, compared with other CC45 isolates, the t1081/ST45 isolates presented greater hemolytic activity. This heightened activity was due mainly to increased Hla protein levels. Moreover, the higher translation levels may be independent of the known regulator RNAIII, indicating a potential RNAIIIindependent mechanism for Hla regulation.

关键词： Droplet digital PCR   Immunogenicity   PBMCs   ELISpot   T -cell activation   SARS-CoV-2  

摘要： This study evaluated the effectiveness of the Reverse Transcription-droplet digital PCR (RT-ddPCR) method in measuring T-cell-mediated immunity by quantifying IFN-gamma mRNA expression. The results demonstrated that peak IFN-gamma expression occurred approximately 4 h after stimulation of whole blood and peripheral blood mononuclear cells (PBMCs) by stimulants. The fold activation of IFN-y mRNA expression in 100 mu L of blood challenged with CEF peptides was lower than that observed in PBMCs. Our findings highlighted the effectiveness of the RT-ddPCR assay in detecting IFN-gamma mRNA expression with the least number of cells and at the lowest stimulant concentration for varying numbers of PBMCs. Additionally, there was a strong and significant positive correlation between the number of SARS-CoV-2-specific spot-forming units (SFUs) and the fold activation of IFN-gamma gene expression (r = 0.78, p <0.02) in PBMC from 10 donors vaccinated with SARS-CoV-2, further supporting the usefulness of the RT-ddPCR method. Importantly, even with just 10,000 PBMCs, we detected SARS-CoV-2-specific IFN-y mRNA induction. The RTddPCR and ELISpot assays demonstrated similar sensitivities and measured IFN-y activation by low concentrations of stimulants. This study suggests that the RT-ddPCR method effectively assesses T-cell mediated immunity through IFN-gamma expression, offering a feasible alternative to the ELISpot assay. (c) 2024 American Pharmacists Association. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

关键词： cytokines   genes   IL-17   IL-23   peri-implantitis   periodontitis  

摘要： BackgroundThe objective of this systematic review was to identify genetic variants of the IL-23, IL-17, IL-23R and IL-17R genes and isoforms and its possible association with increased development of periodontitis and *** systematic review was prepared according to the guidelines, registered in the OSF database with the registration number: 10.17605/OSF. IO/X95ZC. The electronic search was performed in four databases: PubMed, Scopus, Web of Science, and Google Scholar from 1984 until March 15th, 2024. The JBI Critical Appraisal Checklist for Case-Control Studies was used to assess the quality of included *** papers with a case-control design were those that ultimately met the eligibility criteria. A total of 3904 individuals (2315 with periodontitis and 90 with peri-implantitis), and 1589 healthy subjects) were studied. The age range of the study population was 14-70 years, with a mean age +/- (SD) of 40.43 +/- 6.33 years. A total of 28 genetic variants corresponding to the IL-17A (rs 2275913, rs 3819024, rs 10484879) IL-17F (rs 763780), IL-17R (rs 879576) and IL-23R (rs 11209026) genes were analyzed in this study. Six (33.3%) studies found an association between the IL-17A 197 G/A (rs 2275913) genetic variant and peri-implantitis and periodontitis. One study (5.5%) found an association between the IL-17A rs10484879 variant and peri-implantitis and *** polymorphisms were evaluated, highlighting rs 2275913 of the cytokine IL-17A in patients with periodontitis or peri-implantitis. Only 50% of studies found an association despite having a small sample. This suggests that other factors such as the degree of disease, systemic diseases and ethnic groups studied may play a role.