The clinical success of immune checkpoint inhibitors is compromised by the fact of immune-related adverse events (irAEs), especially for older patients. To identify predictive biomarkers for older patients with irAEs, we used multiplex immunoassay and flow cytometry and liquid chromatography-tandem mass spectrometry to test immune factors and plasma protein and metabolites levels in non-small cell lung cancer (NSCLC) patients. The results showed that older patients with irAEs displayed lower CD28, CD4+ T cell, and B cell and higher interleukin (IL)-10 and CCL2 levels at baseline. Besides, lower aldolase, fructose-bisphosphate B (ALDOB), higher ST6GAL1, and lower lactate/pyruvate ratio at baseline were found in older patients with irAEs. Based on metabolomic markers, predictive models were developed to distinguish patients with grade 2-4 irAEs from grade 0-1 (Area under curve, AUC = 0.831) and to distinguish patients with grade 3-4 irAEs from grade 2 (AUC = 1). Our results confirmed the predictive value of plasma metabolites for irAEs in older patients with NSCLC.© 2024 Published by Elsevier Inc.

Helicobacter pylori is planted in the human stomach and is the most common cause of chronic gastritis, which produced specific local and systemic humoral immunity, while the associations of these immune responses and H. pylori in the development of chronic gastritis remain unclear.
This study analyzed histology, the number of Th22 and regulatory T (Treg) cells, and the levels of inflammation- and gastritis-related indicators between 22 H. pylori-infected and 24 non-H. pylori-infected chronic gastritis patients by hematoxylin-eosin staining, enzyme-linked immunosorbent assay, quantitative reverse transcription PCR, and flow cytometry analysis.
This study found that the pathological damage degree of gastric mucosa in H. pylori infection patients was more serious. In the H. pylori-infected patient serum, the gastrin, G-17, interleukins (IL)-22, transforming growth factor (TGF)-β, tumor necrosis factor (TNF)-α, IL-4, and IL-17A levels were notably raised, while the interferon (IFN)-γ level was inhibited, and in gastric mucosa, and except IFN-γ, the IL-22, forkhead box P3 (Foxp3), TNF-α, IL-4, and IL-17A mRNA levels were raised too. The receiver operating characteristic curve analysis indicates serum IL-22, TGF-β, TNF-α, IL-4, and IL-17A are suitable for differential diagnosis of H. pylori infection. In addition, in the peripheral blood, the percentages of the IL-22+ CD4+ and Foxp3+ CD4+ T cells were raised with H. pylori infection. The positive correlation between IL-22 and Foxp3 mRNA levels and the degree of H. pylori colonization and gastric mucositis by Pearson's correlation analysis.
Treg and Th22 cells were positively associated with the degree of H. pylori infection and the severity of gastritis. In summary, this study provides an experimental basis for the study of the eradication of H. pylori and the biological mechanism of chronic gastritis.
© 2023 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.

Mechanisms of hippocampus-related memory formation are time-of-day-dependent. While the circadian system and clock genes are related to timing of hippocampal mnemonic processes (acquisition, consolidation, and retrieval of long-term memory [LTM]) and long-term potentiation (LTP), little is known about temporal gating mechanisms. Here, the role of the neurohormone melatonin as a circadian time cue for hippocampal signaling and memory formation was investigated in C3H/He wildtype (WT) and melatonin receptor-knockout ( MT 1 / 2 - / - ) mice. Immunohistochemical and immunoblot analyses revealed the presence of melatonin receptors on mouse hippocampal neurons. Temporal patterns of time-of-day-dependent clock gene protein levels were profoundly altered in MT 1 / 2 - / - mice compared to WT animals. On the behavioral level, WT mice displayed better spatial learning efficiency during daytime as compared to nighttime. In contrast, high error scores were observed in MT 1 / 2 - / - mice during both, daytime and nighttime acquisition. Day-night difference in LTP, as observed in WT mice, was absent in MT 1 / 2 - / - mice and in WT animals, in which the sympathetic innervation of the pineal gland was surgically removed to erase rhythmic melatonin synthesis. In addition, treatment of melatonin-deficient C57BL/6 mice with melatonin at nighttime significantly improved their working memory performance at daytime. These results illustrate that melatonin shapes time-of-day-dependent learning efficiency in parallel to consolidating expression patterns of clock genes in the mouse hippocampus. Our data suggest that melatonin imprints a time cue on mouse hippocampal signaling and gene expression to foster better learning during daytime.
© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

We describe the production and properties of a permanent cell line, CEM.NKR-CCR5-Luc. This line is a derivative of the CEM.NKR-CCR5 line, stably transfected to express the luciferase reporter gene under the transcriptional control of the HIV-2 LTR. Thus the cells respond to Tat expression during HIV-1 infection by producing luciferase, a protein that can be readily and accurately quantitated in a luminometer. The CEM.NKR-CCR5-Luc line expresses both the CCR5 and CXCR4 coreceptors and can therefore be infected with a range of HIV-1 isolates, irrespective of their tropism properties. This is true of HIV-1 isolates from several genetic subtypes and also of a group O isolate. Furthermore, luciferase expression is also activated by infection of the cells with SIVmac239 or SIVmac251. We show that the CEM.NKR-CCR5-Luc cells can be used in assays of HIV-1 neutralization and also for identifying inhibitors of HIV-1 entry targeted at the CCR5 and CXCR4 coreceptors. The luciferase end point simplifies the performance of neutralization and inhibitor-screening assays compared to the use of more conventional end points such as the detection of extracellular p24 antigen.
Copyright 2001 Academic Press.