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摘要： Several theoretical studies have concluded that heterozygote advantage makes at most a minor contribution to MHC diversity. Siljestam and Rueffler (2024) recently presented models in which heterozygote advantage alone can lead to realistically high diversity. Here I argue that heterozygote advantage cannot by itself explain MHC diversity, and that its contribution to diversity is unlikely to be large in most species. I first show that the high diversity reported by Siljestam and Rueffler is so sensitive to parameter values that the underlying phenomenon cannot explain the widespread diversity of MHC genes. I then consider a fundamental problem with explaining MHC diversity by heterozygote advantage alone: selective forces that favored heterozygotes would lead to the evolution of haplotypes having much higher fitness when homozygous, diminishing or eliminating heterozygote advantage. Diversity maintained by another force, however, might bring about adaptation to the more common heterozygous state at the expense of homozygous fitness. Thus, substantial heterozygote advantage may arise as a consequence of MHC diversity.

关键词： Breast Cancer   B cell   Tumor microenvironment - TME  

摘要： Background Breast cancer is the leading cause of cancer-related deaths among women globally. Tumor-secreted proteins foster an immunosuppressive environment, enabling immune evasion and reducing the effectiveness of antitumor immunity. Interleukin (IL)-10, an immune-regulatory cytokine, is upregulated in breast cancer (BRCA), but the underlying mechanism remains *** In silico analysis was used to identify candidate genes associated with IL-10 expression. Mouse model of BRCA and in vitro co-culture assays were conducted to identify immune cells responsible for IL-10 upregulation. The efficacy of galectin-3 (Gal-3) inhibition combined with chemotherapy was also *** Tumor-secreted Gal-3 served as a key immunosuppressive factor in BRCA. Gal-3 promoted IL-10 production in B cells, thus impairing antitumor immunity. Mechanistically, Gal-3 triggered CD45 polymerization, reducing its phosphatase activity and subsequently activating STAT3 to promote IL-10 production. Knockdown of STAT3 or its blockade abrogated Gal-3-induced IL-10 upregulation. Furthermore, Gal-3 inhibition combined with chemotherapy significantly reduced tumor growth and enhanced antitumor *** Gal-3 is a crucial regulator of immune evasion in BRCA. Targeting Gal-3 may improve the efficacy of BRCA therapies.

关键词： Coronary heart disease   IL-29   Diagnosis   ROC   Logistic regression   SYNTAX score  

摘要： BackgroundCoronary heart disease (CHD) is a chronic inflammatory disease carrying high morbidity and mortality. Interleukin (IL)-29 may be used as a biomarker for autoimmune diseases. This paper investigates the diagnostic value of serum IL-29 in CHD *** total of 90 CHD patients (39 mild and 51 severe patients) and 90 controls were included. Serum IL-29 levels were detected by ELISA, and the diagnostic value of IL-29 in CHD was analyzed by ROC curve. According to the median value of serum IL-29 level, CHD patients were categorized into IL-29 low-level group and high-level group. The correlation between IL-29 and pathological indexes of CHD patients was analyzed by chi-square test. SYNTAX score was used to classify CHD patients into mild CHD and moderate/severe CHD. Pearson coefficient analyzed the correlation between IL-29 and CHD severity. Multivariate logistic regression analyzed the risk factors for CHD ***-29 serum levels were elevated in CHD patients. The AUC for CHD diagnosis by serum IL-29 was 0.789 (65.6% sensitivity and 76.7% specificity). IL-29 was correlated with BMI, PHASE score, and CRP. IL-29 serum level was positively correlated with CHD severity. The AUC for differentiating mild and moderate/severe CHD patients by IL-29 level was 0.739 (70.6% sensitivity and 66.7% specificity). IL-29 was an independent risk factor for CHD exacerbation, and each one-unit increase in IL-29 increased the risk of exacerbation in CHD patients by ***-29 is highly expressed in CHD patients and has auxiliary diagnostic value for CHD.

关键词： Sepsis   cognitive impairment   S100B   GFAP   IL-6  

摘要： Objective The main purpose of this study was to comprehensively investigate the combined utility of S100B, GFAP, and IL-6 as predictors of long-term cognitive impairment in sepsis survivors. Specifically, we aimed to determine whether these biomarkers, either individually or in combination, could effectively predict the occurrence of long-term cognitive impairment in this patient population, and to explore their potential as valuable clinical tools for early detection and intervention. Methods This retrospective study enrolled 114 sepsis patients. Patients were divided into non-cognitive impairment and cognitive impairment groups. Serum biomarker levels were compared, and correlations between biomarkers and cognitive impairment were explored. ROC analysis evaluated the predictive value of S100B, GFAP, and IL-6 levels, and the combined diagnosis of the three biomarkers was studied. Results The non-cognitive impairment group had a younger age, higher education level, employment rate, married rate, and presence of family members (p < 0.05). Correlation analysis showed positive correlations between cognitive impairment and CRP, IL-10, S100B, GFAP, and IL-6 (p < 0.05). AUC values of S100B, GFAP, and IL-6 were 0.792, 0.752, and 0.732, respectively, indicating significant predictive value for cognitive impairment. Combined prediction using the three biomarkers had an AUC value of 0.887, with a specificity of 88% and sensitivity of 89%. Conclusion Long-term cognitive impairment in sepsis survivors is influenced by various cytokines. Significant differences were found in biomarker levels between non-cognitive impairment and cognitive impairment groups. The combined utility of S100B, GFAP, and IL-6 showed significant predictive value for cognitive impairment in survivors of sepsis.

关键词： dry eye disease (DED)   definition   diagnosis   differential diagnosis   subtypes   subclassification   blepharitis, meibomian gland dysfunction (MGD)   DED   Dry eye disease   DEWS   Dry eye workshop   IL   Interleukin   LIPCOF   Lid-parallel conjunctival folds   MGD   Meibomian gland dysfunction   MMP   Matrix metalloproteinase(s)   OCT   Optical coherence tomography imaging   OR   Odds ratio   OSDI   Ocular Surface Disease Index   TFOS   Tear Film & Ocular Surface Society  

摘要： A standard approach to the diagnosis of dry eye disease across eye care practitioners is critical to reassuring the patient, providing consistency between practitioners and informing governments as to the true prevalence and resulting healthcare needs. The Tear Film & Ocular Surface Society (TFOS) Dry Eye Workshop (DEWS) III has reviewed the evidence-base since their previous reports published in 2017 and revised the definition to “Dry eye is a multifactorial, symptomatic disease characterized by a loss of homeostasis of the tear film and/or ocular surface, in which tear film instability and hyperosmolarity, ocular surface inflammation and damage, and neurosensory abnormalities are etiological factors.” Key features from the definition include that dry eye disease is multifactorial, is a disease and not a syndrome and is always symptomatic. Differential diagnosis and ocular examination guidance is given along with the risk factors that should be discussed with the patient. The recommended screening questionnaire is the OSDI-6 with a cut-off score ≥4. A positive result together with a non-invasive breakup time <10s or alternatively tear film hyperosmolarity (≥308mOsm/L in higher eye or an interocular difference >8mOsm/L) gives a diagnosis of dry eye. In addition, the ocular surface should be stained and positive symptomology together with >5 corneal fluorescein and/or >9 conjunctival lissamine green punctate spots and/or lid margin lissamine green staining of ≥2mm length & ≥25 %width also gives a diagnosis of dry eye. Subclassification was separated into tear film (lipid, aqueous and mucin/glycocalyx) and ocular surface and adnexa (anatomical misalignment, blink/lid closure, lid margin, neural dysfunction, ocular surface cell damage/disruption and primary inflammation/oxidative stress) components, with appropriate clinical tests and cut-offs provided to identify these etiological drivers in an individual, to inform appropriate management and therapy.

关键词： diabetic foot   prognosis   interleukin-6   intercellular adhesion molecule-1   soluble suppression of tumorigenicity 2  

摘要： Diabetes foot (DF) is one of the most serious chronic complications of diabetes. This study explored the relationship between serum interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1) and soluble suppression of tumorigenicity 2 (sST2) and wound prognosis in 210 DF patients between January 2019 and January 2024. 210 DF patients were divided into the good prognosis (n = 147) and poor prognosis (n = 63) group according to the prognosis. Comparative analysis revealed that levels of serum IL-6, ICAM-1 and sST2 in the poor prognosis group were all higher than those in the good prognosis group significantly (P < .05). Multivariate logistic regression identified these 3 biomarkers as independent risk factors for poor wound healing (P < .05). Positive correlations between serum IL-6 (r = 0.269), ICAM-1 (r = 0.302), sST2 (r = 0.289) levels and poor prognosis were confirmed through Pearson's correlation analysis. A prediction model was established to analyse their predictive value. The training and validation sets ROC curves had AUCs of 0.79 (0.71-0.87) and 0.75 (0.59-0.91) respectively. Calibration curves were plotted to evaluate the consistency of the model, and the results showed that the predictive value of the nomogram model was similar to that of the actual one. Decision curves were plotted, which showed that the nomogram had higher positive net benefit in the range of 20% to 60%. This study suggest that serum IL-6, ICAM-1, and sST2 levels may serve as valuable prognostic indicators for wound healing progression in DF patients, with combined biomarker assessment showing potential clinical utility for outcome prediction. The total sample size (n = 210), with validation set (n = 63) of this study are relatively limited and the representativeness is restricted, which may affect the universality of the research conclusions.

摘要： Interleukin-2 (IL-2) is a pivotal cytokine that plays a crucial role in the activation, proliferation, and functional regulation of multiple immune cells. High-dose IL-2 has been approved for antitumor therapy but may cause toxicity. IL-2 levels within the body are also associated with various pathological states, making it a potential diagnostic and prognostic biomarker. Consequently, the development of efficient tools for the rapid detection and real-time quantification of IL-2 is of great significance. In this study, we identified two human IL-2-binding aptamers, Apt24 and Apt35, through the systematic evolution of ligands by exponential enrichment (SELEX). On this basis, we constructed two aptamer beacons to detect IL-2 proteins in solution. Further, we successfully developed a membrane-anchored aptamer sensor, Chol-Apt35, to realize in situ detection of IL-2 secretion in living cells. The sensor exhibits good membrane-insertion ability and performs comparably with fluorescent antibodies. In conclusion, this study provides simple yet effective tools for IL-2 detection, which may facilitate dose optimization in immunotherapy and assessment of immunological status.

关键词： selenomethionine   zearalenone   hepatic injury   inflammatory cytokines   IL-6/STAT3 signaling axis  

摘要： Zearalenone (ZEA), a mycotoxin primarily generated by the Fusarium species, constitutes a prevalent contaminant in both human and animal feedstuffs. Chronic exposure to this mycotoxin induces hepatic inflammatory responses in livestock species including rabbits, ultimately leading to organ damage. Selenomethionine (SeMet), an organic selenium source recognized for its antioxidant properties and anti-inflammatory bioactivity, demonstrates protective benefits in animals through its detoxification mechanism and growth promotion. The present study investigated the protective effect of SeMet against ZEA-induced hepatic inflammation and elucidated its underlying mechanisms. Fifty healthy 90-day-old rabbits were randomly divided into five groups: control, ZEA-exposed and three SeMet-supplemented groups receiving 0.2, 0.35 or 0.5 mg/kg via dietary inclusion. After two weeks of SeMet pretreatment, ZEA administration (1.2 mg/kg B.W.) was imitated via oral gavage daily for one week in both the ZEA group and three SeMet-treated groups. As a result, ZEA exposure induced the significant structural disruption of the hepatic lobules, accompanied by increased collagen deposition, elevated pro-inflammatory cytokine profiles (IL-6, IL-1 beta, TNF-alpha) and reduced anti-inflammatory mediator levels (IL-10, TGF-beta). SeMet supplementation alleviated ZEA-induced histological alterations, including inflammatory cell infiltration and collagen accumulation. Biochemical analysis indicated the restoration of inflammatory markers to near-normal levels when treated with SeMet. Notably, immunohistochemical results showed that SeMet significantly reduced the protein levels of IL-6 and its downstream target STAT3 under ZEA exposure. These findings indicated that SeMet attenuated ZEA-induced hepatic inflammation by modulating the IL-6/STAT3 signaling axis, with dietary supplementation of 0.35 mg/kg SeMet exhibiting the most significant effect on alleviating ZEA-induced hepatic inflammatory injury

关键词： A1AT   Alpha-1 antitrypsin   cfDNA   Cell free DNA   C-GSF   Granulocyte colony-stimulating factor   DBD   Donation after brain death   DCD   Donation after circulatory death   EVLP   Ex vivo lung perfusion   ET-1   Endothelin-1   GAGs   Glycosaminoglycans   GM-CSF   Granulocyte macrophage colony-stimulating factor   GRO-α   Growth-regulated oncogene-α   HMGB-1   High mobility group box-1   ICAM-1   Intercellular cell adhesion molecule 1   IL   Interleukin   IRI   Ischemia reperfusion injury   LTx   Lung transplantation   MCP-1   Monocyte chemoattractant protein-1   MMPs   Matrix metalloproteinases   mtDNA   Mitochondrial DNA   NETs   Neutrophil extracellular traps   NOx   Nitric oxide metabolites   nuDNA   Nuclear DNA   PCD   Programed cell death   PGD   Primary graft dysfunction   SCGF-β   Stem cell growth factor-β   TNF-α   Tumor Necrosis Factor-α   TLS   2   Toronto Lung Score (2-plex)   VCAM-1   Vascular cell adhesion molecule-1   Biomarkers   lung transplant   EVLP   donor lung assessment  

摘要： Lung transplantation remains the only curative treatment option for patients with end-stage lung disease, yet limited donor lung availability and utilization remains a significant obstacle. The ex vivo lung perfusion (EVLP) system allows for the extension of the donor assessment, providing the opportunity to perform advanced assessment on the isolated donor lung under near-physiological conditions. Measuring biomarkers in EVLP perfusate can provide valuable information on the condition of the donor lungs. This review examines biomarkers measured in EVLP perfusate and their ability to predict donor lung utilization and outcomes. Biomarkers in this review can be classified as cytokines, cell death, and endothelial-related molecules, showing potential for clinical application. Some of these biomarkers have also been used to monitor the effects of various therapeutics for donor lung repair or for modification of the EVLP technique. Yet, many limitations persist throughout these studies, which provides the opportunity for extensive future research. The integration of biomarkers with other data collected during EVLP through machine learning and artificial intelligence will lead to automated organ assessment to improve lung transplantation.