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关键词： Interleukin-6   D-dimer   White blood cell   Severe pneumonia   Independent factor   Predictive value  

摘要： Introduction: This paper aimed to unravel the value of interleukin-6 (IL-6), D-dimer (D-D), and white blood cell (WBC) tests in the diagnosis of severe pneumonia. Methods: Sixty cases of pneumonia patients were selected as the observation group, which were divided into the non-severe group (35 cases) and the severe group (25 cases) following the severity of the disease, and 50 health check-up participants in the same time period were chosen as the control group. The general information of the control and the observation groups was compared;IL-6, D-D, and WBC levels were observed in the non-severe and the severe groups. Logistic multivariate regression analysis was implemented to analyze the independent factors predicting severe pneumonia, and the receiver operating characteristic (ROC) curve was adopted to observe the diagnostic value of IL-6, D-D, and WBC for severe pneumonia. Results: There was no difference in general information between the observation and the control groups, and between the severe and the non-severe groups (p > 0.05);IL-6, D-D, and WBC levels in the severe group were markedly higher relative to the non-severe group;the multivariate logistic regression analysis showed that IL-6 (p < 0.05, 95% CI: 1.076-1.443) and D-D (p < 0.05, 95% CI: 1.367-66.079) were independent factors predicting severe pneumonia;the ROC curve analysis revealed that the area under the curves (AUCs) of IL-6, D-D, and WBC were 0.957, 0.874, and 0.639, respectively;the combined AUC of the three was 0.978, demonstrating that the predictive value of the combined test was higher than that of the single test. Conclusion: IL-6, D-D, and WBC are significantly elevated in severe pneumonia and have predictive value in severe pneumonia.

摘要： Parasitic helminths induce the production of interleukin-4 (IL-4), which causes the expansion of virtual memory CD8+ T cells (TVM cells), a cell subset that contributes to the control of coinfection with intracellular pathogens. However, the mechanisms regulating IL-4-dependent TVM cell activation and expansion remain ill defined. Here, we used single-cell RNA sequencing of CD8+ T cells to identify pathways that control IL-4-dependent TVM cell responses. Gene signature analysis of CD8+ T cells identified a cell cluster marked by CD22, a canonical regulator of B cell activation, as a selective surface marker of IL-4-induced TVM cells. CD22+ TVM cells were enriched for interferon-gamma and granzyme A and retained a diverse TCR repertoire while enriched in self-reactive CDR3 sequences. CD22 intrinsically regulated the IL-4-induced CD8+ T cell effector program, resulting in reduced responsiveness of CD22+ TVM cells and regulatory functions to infection and inflammation. Thus, helminth-induced IL-4 drives the expansion and activation of TVM cells that is counterinhibited by CD22.

关键词： Acute anterior uveitis   Ethiopia   HLA-B27 allele  

摘要： Purpose: We compared the distribution of the HLA-B27 allele among Ethiopian patients with acute anterior uveitis (AAU) and controls without that disease. Methods: The clinical features of patients were collected from their medical records. HLA-B27 genotyping was performed for 64 patients, with AAU using the real-time polymerase chain reaction (RT-PCR), and the results were compared to those from a panel of 192 healthy, unrelated volunteer control participants (refraction patients and volunteers) free of signs of anterior uveitis. Other outcomes were assessed comparing HLA-B27 positive vs. negative patients. Results: The histocompatibility antigen HLA-B27 was identified in 6 out of 64 (9.4%) AAU patients, compared with 1.0% in controls (Odds Ratio = 9.8, 95% CI (1.93, 50.01)). Sub-group analysis of the cases revealed that patients with HLA-B27 positivity had a higher incidence of ocular hypertension (Odds Ratio = 5.93, 95% CI (1.29, 27.2)). Conclusion: The antigen HLA-B27 was represented similar to 10-fold more frequently in the patient group than in the control group. HLA-B27 allele distribution in both cases and controls is lower than in reports from Caucasian and Asian populations, but similar to South Africa.

关键词： Silicosis   crystalline silica (alpha-quartz)   LPS   IL-1 beta   TNF-alpha   IL-10   Type I IFN   granulomas   M1   M2  

摘要： Occupational exposure to crystalline silica (CS) is known to induce silicosis, a chronic lung disease characterized by the formation of granulomas and severe lung fibrosis. Specifically, individuals exposed to low doses of CS may develop silicosis after a decade or more of exposure. Similarly, in rat silicosis models exposed to occupationally relevant doses of alpha-quartz, there is an initial phase characterized by minimal and well-controlled pulmonary inflammation, followed by the development of robust and persistent inflammation. During the initial phase, the inflammation provoked by alpha-quartz is subdued by two mechanisms. Firstly, alpha-quartz particles are engulfed by alveolar macrophages (AMs) of the alternatively activated (M2) subtype and interstitial macrophages (IMs), limiting their interaction with other lung cells. Secondly, the anti-inflammatory cytokine, interleukin (IL)-10, is constitutively expressed by these macrophages, further dampening the inflammatory response. In the later inflammatory phase, IL-10-dependent anti-inflammatory state is disrupted by Type I interferons (IFNs), leading to the production of pro-inflammatory cytokines in response to alpha-quartz, aided by lipopolysaccharides (LPS). This review delves into the complex pathways involving IL-10, LPS, and Type I IFNs in alpha-quartz-induced pulmonary inflammation, offering a detailed analysis of the underlying mechanisms and identifying areas for future research.

关键词： Alarmin   Thrombosis   Cytokine   Immune Checkpoint Inhibitor  

关键词： pyrethroids   proinflammatory cytokines   CD56   caspase-3   mRNA expression   anemia   ROS   MDA  

摘要： Introduction Conflict reports exist on the impact of pyrethroid insecticides on immune function and the probable underlying *** This study evaluated the effect of an extensively used pyrethroid insecticide, fenpropathrin (FTN) (15 mg/kg ***), on the innate and humoral immune components, blood cells, splenic oxidative status, and mRNA expression of CD3, CD20, CD56, CD8, CD4, IL-6, TNF-alpha, and Caspase3 in a 60-day trial in rats. Besides, the possible defensive effect of curcumin-loaded chitosan nanoparticle (CML-CNP) (50 mg/kg ***) was *** FTN exposure resulted in hypochromic normocytic anemia, thrombocytosis, leukocytosis, and lymphopenia. Besides, a significant reduction in IgG, not IgM, but increased C3 serum levels was evident in the FTN-exposed rats. Moreover, their splenic tissues displayed a substantial increase in the ROS, MDA, IL-6, and IL-1 beta content, altered splenic histology, and reduced GPX, GSH, and GSH/GSSG. Furthermore, a substantial upregulation of mRNA expression of splenic CD20, CD56, CD8, CD4, CD3, IL-6, and TNF-alpha, but downregulation of CD8 was detected in FTN-exposed rats. FTN exposure significantly upregulated splenic Caspase-3 and increased its immunohistochemical expression, along with elevated TNF-alpha immunoexpression. However, the alterations in immune function, splenic antioxidant status, blood cell populations, and immune-related gene expression were notably restored in the FTN + CML-CNP-treated *** The findings of this study highlighted the immunosuppressive effects of FTN and suggested the involvement of many CD cell markers as a potential underlying mechanism. Additionally, the results demonstrated the effectiveness of CML-CNP in mitigating pollutant-induced immune disorders.

关键词： Psoriasis   Protocatechuic aldehyde   Inflammation   STAT3   Ttranscription   Keratinocyte  

摘要： Psoriasis is a chronic inflammatory skin disease. Consistent activation of Signal Transducer and Activator of Transcription 3 (STAT3) in epidermal keratinocyte transactivates various keratinocyte-derived pro-inflammatory cytokines and elicits spontaneous psoriasis-like skin inflammation. In the current study, we first report that topical application of protocatechuic aldehyde (PA), the bioactive compound from Salvia miltiorrhiza (Danshen), significantly improved psoriasis-like skin symptoms and reduced immune cell infiltration in psoriatic lesions. Further molecular mechanism studies demonstrated that PA inactivated STAT3 and inhibited STAT3-mediated transactivation of interleukin-1 alpha (IL-1 alpha) and C-X-C motif chemokine ligand 9 (CXCL9) in epidermal keratinocyte both in vivo and in vitro. Knockdown of STAT3 attenuated the repression effect on IL-1 alpha and CXCL9 by PA. Our results suggested that PA repressed the transactivation of IL-1 alpha and CXCL9 through inhibiting STAT3 in keratinocyte. PA could be potentially used for psoriasis topical treatment or be as a lead compound for drug development.

关键词： IL-33   Intercellular interaction   Periodontal ligament fibroblasts   Immunomodulation   Macrophages   Diabetes-associated periodontitis  

摘要： Tissue-resident fibroblasts with immunomodulatory properties have recently been identified as key players in inflammation. However, their roles within the periodontal niche in diabetes-associated periodontitis remain unclear. Interleukin (IL)-33, known as an "alarmin" in inflammatory responses, has recently emerged as a potential contributor to periodontitis. Herein, we show that IL-33 levels are reduced in periodontal ligament fibroblasts (PDLFs) in the in vivo models of diabetes-associated periodontitis and in vitro models of diabetic inflammation. In the in vitro co-culture model, overexpression of IL-33 in PDLFs promotes M2 macrophage polarization, while knockdown of IL-33 in PDLFs instigates M1 macrophage polarization. Notably, supplementation with IL-33 in vivo significantly alleviates periodontal tissue destruction and enhances M2 macrophage infiltration, whereas targeting the IL-33/ST2 axis exacerbates tissue damage and promotes M1 macrophage polarization in diabetes-associated periodontitis. Additionally, the CUT&RUN assay confirms the direct regulation of IL-33 by Yes-associated protein (YAP). These findings demonstrate that IL-33 deficiency in PDLFs favors M1 macrophage polarization, thereby exacerbating the pathogenesis of diabetes-associated periodontitis. Our study underscores the essential immunomodulatory role of PDLFs in creating an inflammatory niche and unveils a novel interaction axis between PDLFs and macrophages in diabetes-associated periodontitis.

关键词： copolymer/ionic liquid membrane   morphology   nanoconfinement   mesoscopic dynamics simulation   grand canonical Monte Carlo-molecular dynamics simulation   gas transport   gas separation  

摘要： The phenomenon of ionic liquid (IL) nanoconfinement within a copolymer/IL membrane reportedly enhances membrane selectivity, solubility, and transport in gas separations. Also, the copolymer/IL membrane morphology has been found to affect IL stability at high transmembrane pressures. In this work, a combined mesoscopic dynamics simulation and hybrid grand canonical Monte Carlo/molecular dynamics (GCMC-MD) simulations were carried out to investigate the morphologies, as well as CO2/CH4 gas diffusivities, solubilities, and selectivities of polystyrene-b-poly(ethylene oxide) (PS-b-PEO)/1-Ethyl-3-methylimidazolium thiocyanate ([EMIM][SCN]) and PS-b-PEO/1-Ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([EMIM][Tf2N]) membranes. The latter simulations focused on nanoconfined ILs in the copolymer/IL phase boundaries at 2.5 and 5 nm confinement lengths. The investigated systems were four nanoconfined ILs, i.e., PS/[EMIM][SCN]/PEO (the IL forming a separate microphase, denoted IL-Micro), PS/[EMIM][Tf2N]/PEO, PS/[EMIM][SCN]-PEO/PS (the IL distributed in the PEO phase, denoted IL-PEO), and PS/[EMIM][Tf2N]-PEO/PS, and five control systems, i.e., PS/PEO/PS, bulk PS, bulk PEO, bulk [EMIM][SCN], and bulk [EMIM][Tf2N]. Based on the mesoscopic dynamics simulation results, the dominant membrane morphologies at IL loadings of <50 vol % were lamellar or cylindrical (favorable for both IL stability at high transmembrane pressures if the bedding planes are horizontal, i.e. at 90 degrees to the nominal direction of the transmembrane pressure gradient) with the IL-PEO or IL-Micro phases. Also, there was an overall 50% match between the observed PS-b-PEO/[EMIM][SCN] and PS-b-PEO/[EMIM][Tf2N] membrane morphologies. Based on the MD simulation results, both CO2 and CH4 diffusivities were the smallest in the bulk PS (control) and highest in the PS/[EMIM][Tf2N]/PEO system (IL-Micro between the PS and PEO phases) at both confinement lengths. The CO2 diffusivities were, on average, lar