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关键词： Diacerein   Intestinal ischemia reperfusion   Interleukin-1 beta   Inflammasome  

摘要： Intestinal ischemia reperfusion (II/R) is an abdominal critical case especially in neonates and during childhood affecting not only the intestinal tissue but also it could damage other remote organs including cardiac tissue even following surgical intervention. Immune homeostasis during II/R has a major role in controlling its progression. Thus, finding additive medical treatment besides the surgical one becomes an urgent need to keep the tissue. So that, we aimed to evaluate the possible ameliorative effect of diacerein (DIA) on II/R-induced injury in juvenile rats. Forty juvenile rats of Wistar albino species were randomly allocated into four different groups: sham group, DIA given group, II/R group via clamping superior mesenteric artery, DIA-treated group (50 mg/kg) with induction of II/R. Data of current model revealed a significant elevation of the measured cardiac enzymes, cleaved caspase-3, and nuclear factor kappa beta (NF-kappa B) in the untreated ischemic group with disturbed oxidative stress parameters, accompanied with dysregulation of inflammasome/caspase-1/IL-1 beta and Wnt/beta-catenin signaling cascades. Fortunately, upon co-administration of DIA, there is a significant decrease of cardiac enzymes, cleaved caspase-3, and NF-kappa B with normalization of oxidative stress parameters and regulation of inflammasome/caspase-1/IL-1 beta and Wnt/beta-catenin pathways confirmed by marked mitigation of the histopathological changes. This effect of DIA is greatly attributed to its pharmacological properties including IL-1 beta antagonist effect, anti-oxidant, anti-apoptotic, and anti-inflammatory properties. Thus, DIA could be considered as an adjuvant future medical therapy for those cases of II/R.

关键词： Zearalenone   TNF   Ovary   Gut microbes   Inflammation  

摘要： As a widely encountered foodborne mycotoxin, Zearalenone (ZEN) has the potential to accumulate along the food chain, posing threats to public health and safety. However, the precise mechanisms by which ZEN causes tissue damage remain incompletely understood. Here, we established in vivo (40 mu g/kg) and in vitro (30 mu M) models to elucidate the underlying processes of ZEN-induced damage to the ovary and intestine. Our results demonstrated that, following ZEN exposure, pro-inflammatory signaling factors, including NLR family pyrin domain containing 3 (NLRP3) and Interleukin 6 (IL6), were significantly elevated in both ovarian and intestines. Metagenomic analysis revealed dysbiosis of the gut microbiota, which was closely associated with tumor necrosis factor (TNF)-alpha signaling pathway. Transcriptomic results further indicated that inflammatory response are intricately linked to TNF signaling pathway. Additionally, the Tnf-alpha knockout mouse model showed a marked resistance to ZEN-induced ovarian and intestinal injuries. In vitro, RNA interference targeting TNF-alpha attenuated the inflammatory response in IPEC-J2 cells. Moreover, dysregulated expression of the hormone synthesis genes, including KISS-1 metastasis suppressor (Kiss1) and gonadotropin releasing hormone 1 (Gnrh1), was observed, suggesting that ZEN-induced microbial dysbiosis and ovary damage may be interconnected through hormonal disruption. In summary, our results emphasize the role of TNF-alpha in causing ovarian and intestinal damage after ZEN exposure.

关键词： Schizophrenia   Interleukin-33   Aggression   Cytokine   Alarmin  

摘要： Aggression in schizophrenia (SCZ) poses a serious risk to others and complicates treatment. Inflammation has been confirmed to be associated with aggression in SCZ, but specific biomarkers remain unidentified. This study aimed to measure plasma interleukin-33 (IL-33) levels and explore their association with aggression in SCZ for the first time. The enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of IL-33 in SCZ with aggression (SCZ-Ag, n = 31) and non-aggression (NSCZ-Ag, n = 32), and healthy controls (HCs, n = 26). Aggression was measured using the Modified Overt Aggression Scale (MOAS), and clinical symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS). The results showed that the plasma IL-33 levels were elevated in SCZ-Ag compared with NSCZ-Ag and HCs, with no significant difference between NSCZ-Ag and HCs. In the patient group, partial correlation analysis indicated a positive correlation between IL-33 levels and PANSS total scores, positive symptom subscores, and MOAS total scores. Regression analysis showed that a higher likelihood of aggression in SCZ was associated with elevated plasma IL-33 levels (OR = 1.075, 95 % CI: 1.023-1.129). ROC curve analysis showed that IL-33 (AUC = 0.713, 95 % CI: 0.582-0.844) demonstrated moderate performance in distinguishing SCZ-Ag from NSCZ-Ag. These findings suggest that elevated plasma IL-33 levels are a potential risk factor for aggression in patients with SCZ and are implicated in the clinical symptoms of patients. Increased plasma IL-33 levels may serve as a potential marker for aggression in SCZ. These findings require further validation in future studies.

关键词： Colorectal Cancer   Immunotherapy   MHC class I-related chain A   T cell  

摘要： Background Distant metastasis and immune evasion are the major obstacles for successful colorectal cancer (CRC) treatment. The link between metastasis and immune evasion, as well as their therapeutic significance, remains *** Long non-coding RNAs from six paired CRC and normal tissues were screened by RNA sequencing (RNA-seq). LncRNA-CTD (CTD-2568A17.8) expression levels were determined using in situ hybridization and quantitative PCR analysis. In vitro and in vivo assays were performed to confirm the function of lncRNA-CTD. Flow cytometry was used to analyze the impact of lncRNA-CTD on immune cell infiltration and T-cell function. RNA-seq combined with RNA pull-down and RNA immunoprecipitation assay was used to identify the changes in downstream molecules induced by lncRNA-CTD. The therapeutic value of the combination of lncRNA-CTD and immune checkpoint inhibitors has been *** In this study, we identified a novel long non-coding RNA, lncRNA-CTD, which is downregulated in CRC and correlates with both metastasis and immunotherapy response. Mechanistically, the interaction of lncRNA and smad2 prevented the phosphorylation and nuclear translocation of smad2, which inhibited the expression of snail1, thereby inhibiting the metastasis of CRC. LncRNA-CTD enhances major histocompatibility complex class I (MHC-I) expression on the cancer cell membrane by interacting with STUB1 to disrupt the interaction of STUB1 with the MHC-I activator NLRC5 and subsequent NLRC5 ubiquitination-mediated degradation, increasing the susceptibility of CRC cells to being killed by CD8+ T cells. TFAP4 overexpression in CRC cells caused lncRNA-CTD downregulation. Moreover, the combination of lncRNA-CTD gene delivery therapy with immune checkpoint inhibitors exerted an additive effect on tumor growth *** Collectively, our study reveals the role and mechanism of lncRNA-CTD in CRC metastasis and immune evasion. Overexpression of lncRNA-CTD suppresses CRC

关键词： Interleukin-6   Molecularly imprinted polymer   Electrochemical sensor   Lipopolysaccharide   Point-of-care  

摘要： Interleukin-6 (IL-6) is a multifunctional cytokine that plays a key role in driving proinflammatory responses in a wide range of acute, chronic, and infectious diseases. Therefore, it is of practical importance to monitor the IL-6 level of individuals in disease diagnosis and healthcare. Currently, there is an urgent need for developing rapid, cost-effective diagnostic and prognostic sensing systems. Herein, we developed a molecularly imprinted polymer (MIP)-based electrochemical sensor for IL-6 detection. The results showed that the MIP sensor demonstrated high sensitivity in the trace of IL-6 concentration, with a limit of detection of 31.3 fM and a wide dynamic range of 100 fg/mL to 1 mu g/mL. Moreover, the MIP sensors are highly selective for IL-6, compared to other inflammatory cytokines (Interleukin-1 beta, transforming growth factor-beta 3, and tumor necrosis factor-alpha) and various interfering biomolecules (glucose, human serum albumin, fibrinogen, and lactic acid). We also confirmed that the MIP sensors maintained robust stability over three weeks without appreciable deterioration. The performance of the MIP sensors was validated using a lipopolysaccharide-induced cellular senescence model, emphasizing its potential as a point-of-care tool for IL-6 monitoring. The results suggest that our MIP-based IL-6 sensor could serve as an effective point-of-care tool in quantifying age-related physiological changes and monitoring low-grade systemic inflammation.

关键词： Chronic stress intensity   Depression severity   Behavior   Cortisol   Inflammatory factors  

摘要： Backgrounds: The etiology of depression involves chronic stress, a recognized determinant of onset and severity. This study adopts a translational approach, utilizing a mouse model and a clinical cohort to explore the relationship between chronic stress, molecular changes, and depression severity. Methods: In the mouse model, mice were exposed to varying frequencies of chronic stressors over several weeks, followed by behavioral assessments to confirm depressive-like behaviors and measurement of serum indicators to analyze their relationship with stress intensity. In the clinical cohort, we recruited 239 participants, including 137 patients with diagnosed depression and 102 healthy controls, and analyzed their plasma profiles for cortisol and inflammatory cytokines. The clinical cohort revealed distinctive plasma profiles, identifying cortisol and IL17 as potential markers. Machine learning models were developed using these markers to distinguish depression severity. Results: The study revealed subtle behavioral-molecular changes in mice subjected to varying chronic stress intensities, confirming dose-response relationships. It identified cortisol and IL-17 as potential biomarkers for distinguishing depression severity and developed machine learning models demonstrating robust diagnostic capabilities. Limitations: There is a substantial disparity in the number of individuals among different groups in the clinical participants. Conclusion: The study establishes a correlation between cortisol, IL-17, and chronic stress intensity, suggesting the latter accelerates depression progression. Cortisol and IL-17 exhibit diagnostic potential, providing insights into depression progression and guiding targeted interventions. This research advances our understanding of stress-induced molecular changes in depression, contributing to the comprehension of the intricate relationship between chronic stress, molecular alterations, and depression severity.

关键词： IL-2   IL-2 receptor alpha   IL-2 receptor beta &   gamma   Inclusion body   Refolding   Assay validation  

摘要： IL-2 is a potent cytokine that promotes multiple immune cells proliferation and activation. Accordingly, IL-2 based immunotherapies are emerging to treat cancers or AIDS by enhancing T cell growth and function. Besides, IL-2 is indispensable in in vitro cultivation of immune cells which is a critical step of CAR-T or CAR-NK immunotherapies. In bulk manufacturing of recombinant IL-2, E. coli expression system has several advantages such as low cost and rapid growth. However, high level protein expression in prokaryotic organisms often results in inactive insoluble aggregates, also known as inclusion bodies. It is crucial and most challenging work to solubilize and refold the protein of interest from inclusion bodies to generate its bioactive form. While multiple spectrum method had been applied to monitor the refolding process, the question of how to measure the refolding efficiency from the perspective of its biological function remained unaddressed. Here we present a receptor-based sandwich ELISA method to evaluate the bioactive product in samples and provide a guidance for manufacturing bioactive rhIL-2 (recombinant human IL-2) with prokaryotic expression system. Compared to traditional antibody-based ELISA method, this novel approach truly measures the presence of functional rhIL-2 and also potentially allows the detection of rhIL-2 variants with modifications like PEGylation as it doesn't rely on the exact amino acid sequence.

关键词： 侵袭性肺曲霉病   临床特征   预后不良   危险因素   淋巴细胞   重症医学科  

摘要： 目的 分析侵袭性肺曲霉病(IPA)患者的病原菌特点及临床特征,归纳影响预后不良的危险因素。方法 通过电子病例系统查询东南大学附属中大医院2022年8月-2024年7月通过痰或肺泡灌洗液培养微生物鉴定为曲霉菌,且结合诊断标准诊断为IPA患者的89例临床资料,回顾性分析IPA患者曲霉菌病原菌分布及患者临床特征,归纳影响患者预后不良的危险因素。结果 89例病例共检出107株曲霉,其中烟曲霉55株(51.40%)、黄曲霉30株(28.04%)、黑曲霉10株(9.34%)。男性63例(70.79%),不良预后34例。外周血基础淋巴细胞计数(<0.645×10～9)(OR=6.653,95%CI:2.013～21.990,P=0.002)及入住ICU(OR=8.303,95%CI:1.283～53.741,P=0.026)是IPA患者预后不良的危险因素。受试者工作特征曲线分析结果显示,IPA患者预后的外周血基础淋巴细胞计数折点为0.645×10～9/L,敏感度为85.22%,特异度为69.67%。结论 外周血基础淋巴细胞计数、入住ICU是IPA患者预后不良的危险因素,外周血基础淋巴细胞计数警戒值为0.645×10～9/L,对预后不良的发生有较好预测价值。