The immunomodulatory of interleukin-33 in rheumatoid arthritis: A systematic review.

Rheumatoid arthritis (RA) is a systemic chronic autoimmune disease that primarily affects the joints and surrounding soft tissues, characterized by chronic inflammation and proliferation of the synovium. Various immune cells are involved in the pathophysiology of RA. The complex interplay of factors such as chronic inflammation, genetic susceptibility, dysregulation of serum antibody levels, among others, contribute to the complexity of the disease mechanism, disease activity, and treatment of RA. Recently, the cytokine storm leading to increased disease activity in RA has gained significant attention. Interleukin-33 (IL-33), a member of the IL-1 family, plays a crucial role in inflammation and immune regulation. ST2 (suppression of tumorigenicity 2 receptor), the receptor for IL-33, is widely expressed on the surface of various immune cells. When IL-33 binds to its receptor ST2, it activates downstream signaling pathways to exert immunoregulatory effects. In RA, IL-33 regulates the progression of the disease by modulating immune cells such as circulating monocytes, tissue-resident macrophages, synovial fibroblasts, mast cells, dendritic cells, neutrophils, T cells, B cells, endothelial cells, and others. We have summarized and analyzed these findings to elucidate the pathways through which IL-33 regulates RA. Furthermore, IL-33 has been detected in the synovium, serum, and synovial fluid of RA patients. Due to inconsistent research results, we conducted a meta-analysis on the association between serum IL-33, synovial fluid IL-33, and the risk of developing RA in patients. The pooled SMD was 1.29 (95% CI: 1.15-1.44), indicating that IL-33 promotes the onset and pathophysiological progression of RA. Therefore, IL-33 may serve as a biomarker for predicting the risk of developing RA and treatment outcomes. As existing drugs for RA still cannot address drug resistance in some patients, new therapeutic approaches are needed to alleviate the significant burden on RA patients and healthcare systems. In light of this, we analyzed the potential of targeting the IL-33/ST2-related signaling pathway to modulate immune cells associated with RA and alleviate inflammation. We also reviewed IL-33 and RA susceptibility-related single nucleotide polymorphisms, suggesting potential involvement of IL-33 and macrophage-related drug-resistant genes in RA resistance therapy. Our review elucidates the role of IL-33 in the pathophysiology of RA, offering new insights for the treatment of RA.

Nonlinear relationship between platelet count and 30-day in-hospital mortality in intensive care unit stroke patients: a multicenter retrospective cohort study.

Background: Evidence of the relationship between platelet count and 30-day in-hospital mortality in ICU stroke patients is still scarce. Therefore, the purpose of this study was to explore the relationship between platelet count and 30-day in-hospital mortality among ICU stroke patients. Methods: We conducted a multicenter retrospective cohort study using data from 8,029 ICU stroke patients in the US eICU-CRD v2.0 database from 2014 to 2015. Utilizing binary logistic regression, smooth curve fitting, and subgroup analyses, we examined the link between platelet count and 30-day in-hospital mortality. Results: The 30-day in-hospital mortality prevalence was 14.02%, and the mean platelet count of 223 × 109/L. Adjusting for covariates, our findings revealed an inverse association between platelet count and 30-day in-hospital mortality (OR = 0.975, 95% CI: 0.966, 0.984). Subgroup analyses supported the robustness of these results. Moreover, a nonlinear relationship was observed between platelet count and 30-day in-hospital mortality, with the inflection point at 163 × 109/L. On the left side of the inflection point, the effect size (OR) was 0.92 (0.89, 0.95), while on the right side, the relationship was not statistically significant. Conclusion: This study establishes an independent negative association between platelet count and 30-day in-hospital mortality in ICU stroke patients. Furthermore, a nonlinear relationship with a saturation effect was identified, suggesting that maintaining the platelet count around 163 × 109/L can reduce 30-day in-hospital mortality in these patients.

Blood urea nitrogen has a nonlinear association with 3-month outcomes with acute ischemic stroke: A second analysis based on a prospective cohort study.

BACKGROUND: Evidence regarding the relationship between blood urea nitrogen (BUN) and 3-month outcomes in acute ischemic stroke (AIS) patients is still scarce. Therefore, the present study was preformed to explore the link between the BUN and 3-month poor outcomes in patients with AIS. METHODS: A retrospective study of 1866 participants with AIS enrolled from January 2010 to December 2016 at a hospital in South Korea. Binary logistic regression, smooth curve fitting, and a set of sensitivity analyses were used to analyze the association between BUN and 3-month poor outcomes. RESULTS: After adjusting covariates, the results of the binary logistic regression model suggested that the relationship between the BUN and the risk of 3-month poor outcomes for AIS patients was not statistically significant. However, there was a special nonlinear relationship between them, and the inflection point of the BUN was 13 mg/dl. On the left side of the inflection point, every unit increase in the BUN reduces the risk of 3-month poor outcomes by 14.1 % (OR = 0.859, 95%CI: 0.780-0.945, p = 0.0019). On the right side of the inflection point, the relationship is not statistically significant. CONCLUSION: There is a nonlinear relationship with saturation effect between BUN level and 3-month poor outcomes in AIS patients. Maintaining the BUN at around 13 mg/dl can reduce the risk of 3-month poor outcome in AIS patients.

The role of IL-33 in depression: a systematic review and meta-analysis.

Depression has long been considered a disease involving immune hyperactivation. The impact of pro-inflammatory cytokines such as TNF-α, IL-1ß, IL-6, and IL-8 on depression has been widely studied. However, the effect of IL-33, another pro-inflammatory cytokine, has been less researched. Currently, research on the correlation between IL-33 and depression risk is inconsistent. In response to these divergent results, we conducted a review and meta-analysis aimed at resolving published research on the correlation between IL-33 and depression risk, and understanding the potential role of IL-33 in the development and treatment of depression. After searching different databases, we analyzed 8 studies. Our meta-analysis showed that IL-33 had a positive correlation with reduced risk of depression. The pooled standard mean differences (SMD) = 0.14, 95% confidence interval (CI): 0.05-0.24. Subgroup analysis results showed that IL-33 and ST2 levels in cerebrospinal fluid and serum is positive correlated with reduced risk of major depressive disorder (MDD) and bipolar disorder (BD). According to the characteristics of the included literature, the results mainly focuses on Caucasian. Furthermore, according to the subgroup analysis of depression-related data sources for disease or treatment, the correlation between IL-33 and depression risk is reflected throughout the entire process of depression development and treatment. Therefore, the change of IL-33 level in serum and cerebrospinal fluid can serve as useful indicators for assessing the risk of depression, and the biomarker provides potential treatment strategies for reducing the burden of the disease.

The role of IL-17 in lung cancer growth.

Interleukin 17 (IL-17) is an inflammatory cytokine with multiple roles in immune protection, immunopathology, and inflammation-related tumors. Lung cancer is inflammation-related cancer, and a large number of studies have shown that IL-17 contributes to the metastasis and progression of lung cancer. However, some studies have shown that IL17 inhibits the occurrence of lung cancer. At present, there is still some controversy about the role of IL17 in the occurrence and development of lung cancer. This review introduces the basic characteristics of IL-17 and focuses on its role in lung cancer, in order to provide a certain theoretical basis for the prevention, diagnosis, and treatment of lung cancer.

Electrochemical aptasensor based on exonuclease III-mediated signal amplification for sensitive detection of vomitoxin in cornmeal.

Vomitoxin (DON) residues in grains are of great concern to public health. Herein, a label-free aptasensor was constructed to detect DON distributed in grains. Cerium-based metal-organic framework composite gold nanoparticles (CeMOF@Au) were used as substrate materials to facilitate electron transfer and provided more binding sites for DNA. The separation of DON-aptamer (Apt) complex and cDNA was achieved by magnetic separation technique based on magnetic beads (MBs), ensuring the specificity of the aptasensor. Exonuclease III (Exo III)-assisted cDNA cycling process strategy would be triggered when cDNA was separated and introduced to the sensing interface for further signal amplification. Under optimal conditions, the constructed aptasensor presented a wide detection range from 1 × 10-8 mg·mL-1 to 5 × 10-4 mg·mL-1 for DON, and the detection limit was 1.79 × 10-9 mg·mL-1, including a satisfactory recovery in cornmeal sample spiked with DON. The results showed that the proposed aptasensor had high reliability and promising application potential in detecting DON.

Unraveling the impact of nitric oxide, almitrine, and their combination in COVID-19 (at the edge of sepsis) patients: a systematic review.

Introduction: During the coronavirus disease 2019 (COVID-19) pandemic, a large number of critically ill and severe COVID-19 patients meet the diagnostic criteria for sepsis and even septic shock. The treatments for COVID-19 patients with sepsis are still very limited. For sepsis, improving ventilation is one of the main treatments. Nitric oxide (NO) and almitrine have been reported to improve oxygenation in patients with "classical" sepsis. Here, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety of NO, almitrine, and the combination of both for COVID-19 (at the edge of sepsis) patients. Method: A systematic search was performed on Embase, PubMed, the Cochrane Library, the Web of Science, Wanfang Data, and China National Knowledge Infrastructure. Randomized clinical trials, cohort studies, cross-sectional studies, case-control studies, case series, and case reports in COVID-19 patients with suspected or confirmed sepsis were performed. Study characteristics, patient demographics, interventions, and outcomes were extracted from eligible articles. Results: A total of 35 studies representing 1,701 patients met eligibility criteria. Inhaled NO did not affect the mortality (OR 0.96, 95% CI 0.33-2.8, I2 = 81%, very low certainty), hospital length of stay (SMD 0.62, 95% CI 0.04-1.17, I2 = 83%, very low certainty), and intubation needs (OR 0.82, 95% CI 0.34-1.93, I2 = 56%, very low certainty) of patients with COVID-19 (at the edge of sepsis). Meanwhile, almitrine did not affect the mortality (OR 0.44, 95% CI 0.17-1.13, low certainty), hospital length of stay (SMD 0.00, 95% CI -0.29-0.29, low certainty), intubation needs (OR 0.94, 95% CI 0.5-1.79, low certainty), and SAEs (OR 1.16, 95% CI 0.63-2.15, low certainty). Compared with pre-administration, the PaO2/FiO2 of patients with NO (SMD-0.87, 95% CI -1.08-0.66, I2 = 0%, very low certainty), almitrine (SMD-0.73, 95% CI-1.06-0.4, I2 = 1%, very low certainty), and the combination of both (SMD-0.94, 95% CI-1.71-0.16, I2 = 47%, very low certainty) increased significantly. Conclusion: Inhaled NO, almitrine, and the combination of the two drugs improved oxygenation significantly, but did not affect the patients' mortality, hospitalization duration, and intubation needs. Almitrine did not significantly increase the patients' SAEs. Well-designed high-quality studies are needed for establishing a stronger quality of evidence. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=367667, identifier CRD42022367667.

IL-33/ST2 immunobiology in coronary artery disease: A systematic review and meta-analysis.

The IL-33/ST2 axis is reported to be controversially associated with coronary artery disease (CAD). A systematic review of the association between the IL-33/ST2 axis and CAD revealed that IL-33/ST2 plays a protective role in CAD and serum sST2 and IL-33 levels are increased in patients with cardiovascular disease. Therefore, the association of IL-33/ST2 single nucleotide polymorphisms (SNPs) with CAD prevalence, prognosis, and risk factors was assessed by performing a meta-analysis. Through a literature search of relevant articles in various databases using the relevant keywords, seven studies were included in the analysis. The meta-analysis showed that the IL-33/ST2 axis was associated with increased CAD risk [pooled odds ratio (OR) = 1.17, 95% confidence interval (CI): 1.13-1.20]. Gene subgroup analysis showed a close association of IL1RL1 (OR = 1.25, 95% CI: 1.20-1.30; I 2 = 85.9%; p = 0.000) and IL1RAcP (OR = 1.42, 95% CI: 1.26-1.60; I 2 = 27.1%; p = 0.203) with increased CAD risk. However, the association for the IL-33 gene was not statistically significant. SNPs rs7044343 (T), rs10435816 (G), rs11792633 (C) in IL-33 gene were associated with a protective effect in CAD. However, rs7025417 (T) in IL-33, rs11685424 (G) in IL1RL1, rs950880 (A) in sST2, and rs4624606 (A) in IL1RAcP were related to increased CAD risk. Overall, polymorphisms in IL-33/ST2 axis components were associated with increased CAD risk. These results may help identify key features of IL-33/ST2 immunobiology in CAD along with potential treatment strategies to lower disease burden.

Electrochemical aptasensor based on Ce3NbO7/CeO2@Au hollow nanospheres by using Nb.BbvCI-triggered and bipedal DNA walker amplification strategy for zearalenone detection.

Herein, an electrochemical aptasensor combining Nb.BbvCI-triggered bipedal DNA walking strategy was constructed for ultrasensitive assay of zearalenone (ZEN). The aptasensor used Ce3NbO7/CeO2 @Au hollow nanospheres as electrode modification material and PdNi@MnO2/MB as the signal label. Importantly, the Ce3NbO7/CeO2 synthesized by hydrothermal method were combined with Au nanoparticles and applied to the electrode surface. The as-prepared Ce3NbO7/CeO2 @Au possessed a large surface area, excellent electrical conductivity, stability and more binding sites. PdNi@MnO2 with high specific surface area and porosity combined with molecule methylene blue (MB) was introduced into electrodes as the signal label. The proposed aptasensor utilized the advantages of specific recognition of aptamers and target molecules to release bipedal DNA walker (w-DNA), and then the w-DNA was triggered by Nb.BbvCI and entered the cycle to release more signal probes. The feasibility of this strategy was recorded by the differential pulse voltammetry (DPV) method. Under the optimized conditions, the electrochemical aptasensor exhibited a wide linear dynamic range from 1 × 10-4 to 1 × 103 ng mL-1 with a low detection limit of 4.57 × 10-6 ng mL-1. Moreover, the aptasensor had high selectivity, good stability, excellent repeatability and provided an effective method for the trace detection of ZEN in real samples.

Association between the Phytochemical Index and Overweight/Obesity: A Meta-Analysis.

Some studies suggest that a higher phytochemical index (PI) is associated with a lower risk of overweight/obesity. This meta-analysis is performed to summarize published studies on the relationship of PI and the risk of overweight/obesity. We searched on PubMed, Cochrane Library and Web of Science from the inception dates to February 2022. The random-effect model was used based on heterogeneity. Meta-regression was used to explore potential sources of between-study heterogeneity. Publication bias was evaluated using Begg's and Egger's tests. The dose-response relationship was assessed using a restricted cubic spline model. Nine studies were included in the meta-analysis, with a total of 100,753 participants. The meta-analysis showed that the phytochemical index was associated with a decreased risk of overweight/obesity. The pooled OR (95% CI) was 0.81 (0.74-0.90). The findings from dose-response analysis showed a nonlinear association between the phytochemical index and the risk of overweight/obesity. The results of the meta-regression showed that gender and area were significant covariates influencing the heterogeneity between studies. There was no publication bias in the meta-analysis of this study. In conclusion, although this meta-analysis indicates that a high phytochemical index is associated with a reduced risk of overweight/obesity, all the studies included in this meta-analysis were cross-sectional studies with high heterogeneity. As such, more data from randomized controlled trials are required to confirm the efficacy of PI in evaluating the risk of overweight/obesity.

A label-free electrochemical immunosensing platform based on PEI-rGO/Pt@Au NRs for rapid and sensitive detection of zearalenone.

In this work, we design an immunosensor for zearalenone (ZEN) detection with PEI-rGO/Pt@Au NRs nanocomposite as the modification material. PEI-rGO/Pt@Au NRs nanocomposite have good stability, conductivity and a large specific surface area, so they are chosen as the substrate material for the modified electrode, which is beneficial in improving the detection performance of the sensor. When antibody binds to ZEN, the current signal decreases, and the response signal changes after ZEN incubation, recorded by differential pulse voltammetry (DPV) methods. Under the optimised conditions, the electrochemical response of the constructed immunosensor shows a linear relation to a wide concentration range from 1 pg/mL to 1 × 106 pg/mL with a detection limit of 0.02 pg/mL. Additionally, the proposed electrochemical immunosensor has high selectivity, good stability and great potential for the trace detection of ZEN in real samples.

Failure mechanism of TRSS mode in landslides induced by earthquake.

Investigation of the slopes in the Wenchuan earthquake shows that tension failures appear in the upper part in many landslides. The typical failure mode can be generalized as "tensile-rupture and sheared-sliding" (TRSS). In this paper, the distinct element method (DEM) is employed to simulate the gradual failure process of the Tangjiashan landslide under the excitation of the Wenchuan earthquake. It is found that the first failure is the appearance of deep tension cracks on the top, and then shearing slip along the bottom. The posterior fracture is deep, steep, and rough, and the bottom shear slip surface has a relatively gently dip. The simulation shows the failure mode of TRSS in the slope can be well reproduced, and the geological and mechanical mechanisms can be revealed in the DEM model.

IRGM promotes glioma M2 macrophage polarization through p62/TRAF6/NF-κB pathway mediated IL-8 production.

Alternatively activated (M2) macrophage promotes glioma progression and immune escape as the most immunocyte in glioma microenvironment. Finding out the key protein regulating M2 macrophage polarization is necessary for improving treatment. Whether immunity related GTPase M (IRGM) is involved in glioma development and M2 macrophage polarization is unknown. IRGM and M2 macrophage marker CD206 expression were examined using immunohistochemistry among 35 glioma and 11 non-cancerous brain specimens. We found IRGM scores were positively correlated with CD206 scores in glioma specimens and monocyte proportion in blood samples. A172 glioma cells transfected with either IRGM knock-down lentivirus (Lenti-IRGM) or control lentivirus (Lenti-HK) were subcutaneously injected into nude mice. In vivo, xenografted glioma size of the Lenti-IRGM group was smaller and had weaker fluorescence signal than Lenti-HK control group. Immunofluorescence results showed that there was obviously decreased IRGM, CD206, and IL-8 expression in the mice glioma of Lenti-IRGM group than Lenti-HK control group. In vitro, flow cytometry results showed that M2 polarization from THP-1 cocultured with Lenti-IRGM glioma cells decreased in contrast to that with Lenti-HK glioma cells; there were less interleukin-8 (IL-8) and macrophage inflammation protein 3-α (MIP-3α), but more interleukin-6 (IL-6) in the supernatant of Lenti-IRGM glioma cells than matched control. Western blot and immunofluorescence displayed that IRGM strongly promoted sequestosome-1 (p62/SQSTM1), necrosis factor receptor-activating factor 6 (TRAF6) expression and NF-κB transportation to the nucleus. Realtime PCR results demonstrated IRGM also promoted NF-κB downstream cytokines IL-8 and MIP-3α mRNA expression. These data suggested that IRGM could promote glioma development and M2 macrophage polarization by regulating p62/TRAF6/NF-κB pathway-mediated IL-8 production.

High expression of immunity-related GTPase family M protein in glioma promotes cell proliferation and autophagy protein expression.

Glioma is the commonest malignant tumor in the central nervous system (CNS), characterized by rapid growth. However, the molecular mechanism underlying the growth remains unclear. Immunity-related GTPase family M protein (IRGM) participates in immune response to pathogen and tumorigenesis. Proliferation and autophagy are two crucial functions contributing to aggressive growth. Therefore, our aims were to probe whether IRGM regulates glioma proliferation and autophagy. In this study, we found that 47 glioma specimens had more IRGM expression than 11 non-cancerous brain tissues with immunohistochemistry. IRGM was also up-regulated in human glioma cell lines U87, U251 and A172 and so on compared with immortalized astrocytes. Importantly, overexpression of IRGM significantly increased the cell colonies formation, cell proliferation and Akt activation (Thr308 and Ser473 sites) than matched control. On another hand, all of IRGM, autophagy marker LC3II and autophagy adaptor p62 gradually increased after starvation 2 and 4 h. Furthermore, western blot and immunofluorescence results showed that knockdown of IRGM inhibited the formation of LC3-II and the expression of p62. Our data uncovered that IRGM acted in glioma proliferation and autophagy, providing a new target with dual roles for the future translation research.

Earth surface deformation in the North China Plain detected by joint analysis of GRACE and GPS data.

Mass redistribution of the Earth causes variable loading that deforms the solid Earth. While most recent studies using geodetic techniques focus on regions (such as the Amazon basin and the Nepal Himalayas) with large seasonal deformation amplitudes on the order of 1-4 cm due to hydrologic loading, few such studies have been conducted on the regions where the seasonal deformation amplitude is half as large. Here, we use joint GPS and GRACE data to investigate the vertical deformation due to hydrologic loading in the North China Plain, where significant groundwater depletion has been reported. We found that the GPS- and GRACE-derived secular trends and seasonal signals are in good agreement, with an uplift magnitude of 1-2 mm/year and a correlation of 85.0%-98.5%, respectively. This uplift rate is consistent with groundwater depletion rate estimated from GRACE data and in-situ groundwater measurements from earlier report studies; whereas the seasonal hydrologic variation reflects human behavior of groundwater pumping for agriculture irrigation in spring, leading to less water storage in summer than that in the winter season. However, less than 20% of weighted root-mean-squared (WRMS) reductions were detected for all the selected GPS stations when GRACE-derived seasonal deformations were removed from detrended GPS height time series. This discrepancy is probably because the GRACE-derived seasonal signals are large-scale, while the GPS-derived signals are local point measurements.