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关键词： depression   anxiety   cytokines   IL-6   TNF   vitamin D   cortisol   biomarkers   machine learning   random forest  

摘要： Depression and anxiety are mental health disorders that significantly impact global public health, affecting more than 280 million people with depression and 301 million with anxiety worldwide. These conditions impair individuals' ability to engage in economic and personal activities and can lead to severe outcomes, such as suicide. Current research suggests that inflammatory cytokines, such as interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and tumor necrosis factor (TNF), play crucial roles in the pathophysiology of these disorders, influencing neurotransmitters. Elevated cortisol levels, typically associated with anxiety, worsen these conditions through dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. Additionally, vitamin D deficiency has been linked to reduced production of dopamine and norepinephrine, hormones involved in depressive symptoms. This study utilized the Random Forest machine learning algorithm along with cross-validation to assess the importance of various biomarkers, including IL-1 beta, IL-6, IL-8, TNF, cortisol, vitamin D, NT-proBNP, CK-MB, troponin, myoglobin, and C-reactive protein (CRP), in volunteers of both sexes diagnosed with mental disorders. A single sample from each of the 96 participants was analyzed, consisting of 50 women and 46 men. The results revealed sex-specific differences in biomarker relevance, with vitamin D, CRP, and D-dimer being the most predictive for depression in men, while IL-6, CRP, and vitamin D were significant in women. For anxiety, vitamin D and myoglobin were important biomarkers in men, while IL-8 and vitamin D were key in women. The methodological strategy adopted, based on the use of Random Forest and cross-validation assessment, not only confirmed the robustness of the model but also reliably identified the most important biomarkers for the outcomes studied.

关键词： plaque stability   CD8(+) T cells   MAPK pathway   atherosclerosis  

摘要： Background and aims: CD8(+) T cell subpopulations participate in the formation of atherosclerotic plaques through activation or exhaustion. Yet, it is unclear which specific subset it critically involved. The SLC4A10(+) CD8(+) T cell possess atherogenic attributes and this study aimed to investigate the associated pathway involved in affecting plaque stability. Methods: Carotid plaques were collected from patients that underwent carotid endarterectomy in our institute and categorized into stable or unstable plaques. The SLC4A10(+) CD8(+) T cell subset were investigated. For in vivo analysis, carotid artery tangem ligation was performed in 8-week-old, AAV-6 overexpressed mice fed with high-fat diet to acquire unstable carotid plaques. Isolated CD8(+) T cells were cultivated and their immunopathological characteristics were examined in vitro. Results: SLC4A10(+) CD8(+) T cells were significantly enriched in unstable human carotid plaques and were correlated with the apoptosis of vascular smooth muscle cells (VSMCs). SLC4A10-overexpressed mice, serum IL-4, IL-17A, and IL-6 were increased, while the level of granzyme B (GZMB) decreased. The extent of atherosclerotic plaques was mitigated, the amount of collagen fibers were diminished, and the apoptosis of VSMCs were alleviated. Flow cytometry suggested that SLC4A10 decreased the levels of IFN-gamma and GZMB in CD8(+)T cells. The CCK8 demonstrated that IFN-gamma and GZMB lead to the decrease in MOVAS cell viability. KEGG analysis revealed that SLC4A10(+) CD8(+) T cells participated in the MAPK pathway, cytokine-cytokine receptor interaction, TNF signaling pathway, and cell adhesion molecule pathway. The differential expression of related genes MAPK2K6, ELK4, and MAP3K5 in the MAPK pathway were verified. Conclusions: These data demonstrate that SLC4A10 mitigates cytotoxicity by decreasing the levels of IFN-gamma/GZMB of SLC4A10(+) CD8(+) T cells via the MAPK pathway, which impedes plaque progression and aids stabilization

关键词： Gpr109A   Macrophages   Hepatocellular carcinoma   Immune microenvironment   MerTK   Proteases  

摘要： To delineate Gpr109A's role and mechanisms in modulating the immune microenvironment of hepatocellular carcinoma. Employing Gpr109A-knockout mice and in vitro co-cultures of hepatocellular carcinoma cells with macrophages, this study utilized a suite of techniques, including lentiviral vectors for stable cell line establishment, Western blotting, cell scratch, CCK-8, transwell assays, flow cytometry, immunohistochemistry and phagocytosis assay to assess various cellular behaviors and interactions. Gpr109A deletion markedly reduced the oncogenic potential of H22 cells, both in vivo and when co-cultured with knockout macrophages, impairing their growth, invasion, and migration. In Gpr109A-knockout macrophages, an upregulation of MerTK and a reduction in immunosuppressive cytokine release were observed, indicating a shift towards an M2c macrophage phenotype. This shift is linked to Gpr109A's role in promoting protease overexpression and inhibiting SHP2 phosphorylation, crucial for enhancing cancer cell proliferation and invasiveness. Gpr109A significantly influences macrophage polarization to the M2c type, augmenting hepatocellular carcinoma cell aggressiveness.

关键词： 牛冠状病毒   多克隆抗体   双抗体夹心ELISA   鉴定  

摘要： 不断发现的新型冠状病毒对人类的危害极其严重，牛冠状病毒（BCoV）具有致人畜共患病的潜力，而BCoV分离鉴定及病原检测均缺乏有效的方法。本研究制备与BCoV发生特异性反应的家兔多克隆抗体，为BCoV的检测和鉴定奠定技术基础。本研究将BCoV灭活后免疫家兔制备针对病毒的多克隆抗体。经3次免疫后检测血清中和效价，将纯化后的多克隆抗体用于间接免疫荧光（IFA）、免疫印迹（Western-blot）和夹心ELISA试验。结果显示，制备的家兔多克隆抗体与BCoV反应，血清中和效价可达到1∶28，与cpCoV反应，可达1∶29。经IFA鉴定，该多克隆抗体能够与不同毒株的BCoV和cpCoV发生特异性反应；Western-blot分析发现在约50 kDa处出现特异性条带；将家兔多克隆抗体作为夹心ELISA的包被抗体，只与BCoV和cpCoV发生特异性反应，而不与其他病毒发生交叉反应。该多克隆抗体与不同毒株的BCoV和cpCoV特异性结合，可用于分离鉴定BCoV和cpCoV的IFA和Western-blot分析，制备的多克隆抗体还可作为包被抗体用于检测BCoV与cpCoV的双抗夹心ELISA。本研究为BCoV与cpCoV的病原检测与流行病学调查奠定了基础。

关键词： prediction   inflammation   cytokines   outcome   IL-18  

摘要： Background Abdominal sepsis is a critical and high-risk condition in intensive care, characterized by diagnostic challenges, complex treatment, and high mortality. Non-specific symptoms and the difficulty of discriminating harmful bacteria from the normal flora complicate a timely diagnosis and treatment. Although timely interventions are crucial, the best timing of surgery remains uncertain, especially in unstable patients. Diagnostic markers like C-reactive protein, procalcitonin, and interleukins help guide diagnosis but often lack specificity of an abdominal focus. This study aims to identify possible additional markers for earlier detection of abdominal *** Plasma samples were collected from 47 sepsis patients at the day of sepsis diagnosis, and from 10 healthy controls. Patients were retrospectively categorized into those with abdominal (n=23) and those with non-abdominal (n=24) sepsis. Patient`s characteristics, clinical outcomes, physiological and laboratory parameters, and cytokine levels were assessed. Receiver operating characteristic curves and Spearman correlation analyses were *** Age and sex proportions were comparable across the sepsis groups, as were the chronic disease prevalence, the severity of illness and mortality rates. Patients with abdominal sepsis were more likely to undergo emergency surgeries. Pro-inflammatory cytokines like IL-6, MCP-1, and IL-18 were elevated, as was the anti-inflammatory IL-10 in both sepsis cohorts compared to healthy controls. IL-18 was particularly associated with a more severe inflammatory response in non-abdominal sepsis. IL-18 levels below 1892.00 pg/mL showed 82.6% sensitivity and 56.5% specificity for identifying patients with abdominal sepsis, with a significant diagnostic accuracy (AUC 0.68, p = 0.034). This suggests IL-18 as a useful additional moderate predictor for critical *** The results demonstrate that IL-18, IL-6, MCP-1, and IL-10 are increased in sepsis, while IL

摘要： The cytogenetic risk category retains a pivotal role in the prediction of prognosis in acute myeloid leukemia (AML) patients undergoing hematopoietic stem cell transplantation (HSCT), however, its impact on secondary AML (sAML) is less established. We assessed whether the ELN 2022 cytogenetic risk score predicts outcomes in sAML patients in remission undergoing HSCT from HLA-matched donors performed between 2010 and 2022. Among 1119 patients, 829 had intermediate and 284 had adverse cytogenetics (6 with favorable risk were excluded). Engraftment rates was 72.4% vs. 99.5%. Acute graft-versus-host disease (GVHD) incidence did not differ, but 2-years all grades and extensive chronic GVHD were higher in the intermediate vs. adverse cytogenetics risk groups, hazard ratio (HR) = 0.72;p = 0.034 and HR = 0.58;p = 0.027, respectively. Two-year non-relapse mortality (NRM) was similar. All other HSCT outcomes were inferior in the adverse risk vs. intermediate-risk patients: The HR for 2-year relapse incidence (RI) was 2.48 (95% CI 1.95-3.15, p < 0.001). The HRs for 2-year leukemia-free survival (LFS), overall survival (OS), and GVHD-free/relapse-free survival (GRFS) were 1.62 (95% CI 1.34-1.95, p < 0.001), 1.59 (95% CI 1.3-1.93, p < 0.001) and 1.38 (95% CI 1.15-1.65, p < 0.001), respectively. We conclude that cytogenetic risk score predicts HSCT outcomes in sAML patients.

关键词： WDFY1   transcription factor   miRNA   luciferase   IL-6  

摘要： WD40 repeat and FYVE containing protein 1 (WDFY1) functions in membrane trafficking and protein complex scaffolding. WDFY1 has been studied in the immune system and in different oncogenic conditions. Therefore, comprehensive understanding of WDFY1 regulation mechanisms is much desired. In this study, we analyzed the promoter and 5 '- and 3 '-untranslated regions (UTRs) of wdfy1 and identified critical sequence elements, transcription factors (TFs), and miRNAs that collaboratively regulate wdfy1 gene expression. A 3.5 kb segment of the mouse wdfy1 promoter and 5 '-UTR was cloned into a luciferase expression vector and transfected into HeLa cells. Luciferase assays of promoter deletion mutants revealed approximately four-fold increased activity attributed by a 500 bp distal fragment upstream of the wdfy1 5 '-UTR. Four TFs (Sp1, Ap-1, Hes1, and TCF7) were found to be critical for wdfy1 expression with binding sites spread throughout the promoter and 5 '-UTR regions. Cloning of a 3.2 kb fragment of wdfy1 3 '-UTR into the luciferase expression vector led to an similar to 3.5-fold decrease in luciferase activity. Complementary siRNA and luciferase assays mutually confirmed our findings. Most importantly, IL-6, a critical cytokine in organ inflammation, was found to promote WDFY1 expression through the upregulation of Sp1 in primary renal mesangial cells. We, therefore, identified a potential inflammation-driven WDFY1 upregulation in mice.

关键词： Fourier transform infrared spectroscopy  

摘要： The current study uses the ionic liquid (IL) 1-butyl-3-methylimidazolium hexafluorophosphate, also known as BMIM-PF6, as a stabilizing agent to synthesize a bismuth oxide/ionic liquid/reduced graphene oxide (Bi2O3/IL/rGO) hybrid nanomaterial. A range of techniques, including scanning electron microscopy (SEM), X-ray diffraction (XRD), energy dispersive X-ray spectroscopy (EDX), Fourier transform infrared spectroscopy (FTIR), and UV-visible spectroscopy, were used to characterize the synthesized Bi2O3/IL/rGO nanocomposite. XRD confirmed that the composite was crystalline, and FTIR analysis suggested the presence of certain functional groups. The main elements oxygen, carbon, and bismuth were confirmed by EDX analysis, and SEM imaging showed an exfoliated and detached morphology. The synthesized nanocomposite was used to modify a glassy carbon electrode to develop a sensor for the detection of lead (Pb2+). The fabricated sensor was characterized using electrochemical impendence spectroscopy (EIS) and cyclic voltammetry (CV). The results indicated that the Bi2O3/IL/rGO/GCE was more conductive, having a charge transfer resistance (Rct) of 428.5 Omega compared to 1870 Omega for the bare electrode. The sensor has a low detection limit of 0.001 mu M and a quantification limit of 0.003 mu M. When tested on water and soil samples, the sensor was confirmed to have acceptable recovery rates, ranging from 95% to 102%. In conclusion, our fabricated sensor has excellent performance in terms of ease, affordability, energy usage, and quick efficiency.

关键词： Diabetic nephropathy   IL-6   Polymorphisms  

摘要： Introduction: The pathogenesis of diabetes mellitus (DM) and its complications has been previously linked to elevated levels of interleukin-6 (IL-6);IL-6 triggers intracellular pathways through interaction with the IL-6 receptor (IL-6R). This study aimed to determine the association of single nucleotide polymorphisms (SNPs) IL-6 -597G/A (rs1800797), -572G/C (rs1800796), -174G/C (rs1800795), its receptor (IL-6R) Asp358Ala (+48892A/C, rs2228145) and DM or its complications in the Czech population. Materials and Methods: In total, 669 subjects participated in this case-control study, including 167 controls, 119 patients with type 1 DM (T1DM), and 383 patients with type 2 DM (T2DM). The subjects were monitored for glycemia, glycated hemoglobin, lipid profile, glomerular filtration rate (GFR), and common complications, such as diabetic nephropathy (DN), retinopathy (DR), (poly)neuropathy (DPN), and periodontitis (P). Results: Frequencies of the IL-6 and IL-6R alleles or genotypes, and IL-6 haplotypes were similar between the controls and the patients with T1DM or T2DM (P > 0.05). However, lower values of GFR were observed in diabetic patients with IL-6 -174CC homozygotes compared to other (CG and GG) genotypes (P <= 0.05). In addition, the IL-6R Asp358Ala variant was associated with DN (P = 0.031, OR = 1.74, 95% CI: 1.05-2.89). After subclassification according to the type of DM, the significant association of the IL-6R polymorphism with DN was only found in T1DM (P = 0.013, OR = 2.90, 95% CI: 1.25-6.71). Conclusions: This study implies a significant relationship between the IL-6R Asp358Ala polymorphism and DN in Czech T1DM patients.

关键词： 降钙素原   hs—CRP   白介素-6   血清淀粉样蛋白A   细菌感染  

摘要： 研究PCT、hs—CRP、IL-6及SAA在细菌感染诊断中的作用。方法 选取重症监护室住院患者采用随机法,从已经确诊的感染患者中抽取63例为观察组,从发热未细菌感染患者中抽取50例为对照组,入院后予以降钙素原、hs—CRP、白介素-6及血清淀粉样蛋白A检验,分析最终检验指标。结果 观察组检出PCT、hs—CRP的阳性率高于对照组(P<0.05);观察组检出的PCT、hs—CRP、IL-6及SAA水平均高于对照组(P<0.05);观察组PCT、hs—CRP的占比明显高于对照组(P<0.05)。结论 针对出现发热但不确定是否细菌感染患者,予以降钙素原、hs—CRP、白介素-6及血清淀粉样蛋白A等指标检测,通过获取准确数据有助于判断患者是否存在细菌感染,制定合理治疗方案对细菌进行抑制,提高疾病治疗效果。