Prevention of what

In addition to the roles of endothelial cells (ECs) in physiological processes, ECs actively participate in both innate and adaptive immune responses. We previously reported that, in comparison to macrophages, a prototypic innate immune cell type, ECs have many innate immune functions that macrophages carry out, including cytokine secretion, phagocytic function, antigen presentation, pathogen-associated molecular patterns-, and danger-associated molecular patterns-sensing, proinflammatory, immune-enhancing, anti-inflammatory, immunosuppression, migration, heterogeneity, and plasticity. In this highlight, we introduce recent advances published in both ATVB and many other journals: (1) several significant characters classify ECs as novel immune cells not only in infections and allograft transplantation but also in metabolic diseases; (2) several new receptor systems including conditional danger-associated molecular pattern receptors, nonpattern receptors, and homeostasis associated molecular patterns receptors contribute to innate immune functions of ECs; (3) immunometabolism and innate immune memory determine the innate immune functions of ECs; (4) a great induction of the immune checkpoint receptors in ECs during inflammations suggests the immune tolerogenic functions of ECs; and (5) association of immune checkpoint inhibitors with cardiovascular adverse events and cardio-oncology indicates the potential contributions of ECs as innate immune cells.

https://www.ahajournals.org/doi/pdf/10.1161/ATVBAHA.120.314330?download=true

Vascular Endothelial Cells and Innate Immunity.

Background Three different cell types constitute the glomerular filter: mesangial cells, endothelial cells, and podocytes. However, to what extent cellular heterogeneity exists within healthy glomerular cell populations remains unknown.Methods We used nanodroplet-based highly parallel transcriptional profiling to characterize the cellular content of purified wild-type mouse glomeruli.Results Unsupervised clustering of nearly 13,000 single-cell transcriptomes identified the three known glomerular cell types. We provide a comprehensive online atlas of gene expression in glomerular cells that can be queried and visualized using an interactive and freely available database. Novel marker genes for all glomerular cell types were identified and supported by immunohistochemistry images obtained from the Human Protein Atlas. Subclustering of endothelial cells revealed a subset of endothelium that expressed marker genes related to endothelial proliferation. By comparison, the podocyte population appeared more homogeneous but contained three smaller, previously unknown subpopulations.Conclusions Our study comprehensively characterized gene expression in individual glomerular cells and sets the stage for the dissection of glomerular function at the single-cell level in health and disease.

A Single-Cell Transcriptome Atlas of the Mouse Glomerulus.

In addition to being recognized as a chronic inflammatory disease that manifests in the skin, psoriasis is increasingly understood to be a systemic disease that causes immune dysregulation throughout the body. The systemic nature of psoriasis is evidenced by the higher burden of comorbidities and shorter life expectancies of patients with psoriasis, particularly those with early-onset and severe disease. Notably, psoriasis is associated with an increased risk for cardiovascular disease, which is the most common cause of morbidity and mortality in patients with psoriasis. In this review, we examine the association between psoriasis and cardiovascular disease and specifically focus on the role of interleukin 17–mediated inflammation as a potential mechanistic link between psoriasis and cardiovascular disease. Moreover, we describe potential treatment approaches to reduce the burden of cardiovascular disease in patients with psoriasis and discuss the clinical importance of the association of these 2 diseases with respect to patient management and education.

Interleukin 17, inflammation, and cardiovascular risk in patients with psoriasis.

A classical hallmark of acute inflammation is neutrophil infiltration of tissues, a multistep process that involves sequential cell–cell interactions of circulating leukocytes with IL-1– or TNF-activated microvascular endothelial cells (ECs) and pericytes (PCs) that form the wall of the postcapillary venules. The initial infiltrating cells accumulate perivascularly in close proximity to PCs. IL-17, a proinflammatory cytokine that acts on target cells via a heterodimeric receptor formed by IL-17RA and IL-17RC subunits, also promotes neutrophilic inflammation but its effects on vascular cells are less clear. We report that both cultured human ECs and PCs strongly express IL-17RC and, although neither cell type expresses much IL-17RA, PCs express significantly more than ECs. IL-17, alone or synergistically with TNF, significantly alters inflammatory gene expression in cultured human PCs but not ECs. RNA sequencing analysis identifies many IL-17–induced transcripts in PCs encoding proteins known to stimulate neutrophil-mediated immunity. Conditioned media from IL-17–activated PCs, but not ECs, induce pertussis toxin–sensitive neutrophil polarization, likely mediated by PC-secreted chemokines, and they also stimulate neutrophil production of proinflammatory molecules, including TNF, IL-1α, IL-1β, and IL-8. Furthermore, IL-17–activated PCs, but not ECs, can prolong neutrophil survival by producing G-CSF and GM-CSF, delaying the mitochondrial outer membrane permeabilization and caspase-9 activation. Importantly, neutrophils exhibit enhanced phagocytic capacity after activation by conditioned media from IL-17–treated PCs. We conclude that PCs, not ECs, are the major target of IL-17 within the microvessel wall and that IL-17–activated PCs can modulate neutrophil functions within the perivascular tissue space.

/pdf/il-17-promotes-neutrophil-mediated-immunity-by-activating-qw5cye9p7i.pdf

IL-17 Promotes Neutrophil-Mediated Immunity by Activating Microvascular Pericytes and Not Endothelium

Interleukin-17A Promotes Aortic Endothelial Cell Activation via Transcriptionally and Post-translationally Activating p38 Mitogen-activated Protein Kinase (MAPK) Pathway.

The biological and clinical features of chronic lymphocytic leukemia (CLL) exhibited profound heterogeneity across Chinese and patients of predominately European descent. However, the age-related peculiarities and risk assessment of Chinese CLL patients remained ill-defined. The present study demonstrated that CLL patients were characterized by the earlier age at onset in China (median age at diagnosis: 63 years old) than in the United States (median age at diagnosis: 69 years old). Young patients from Shandong Provincial Hospital CLL database displayed prolonged overall survival than the Surveillance, Epidemiology, and End Results cohort. Furthermore, among Chinese CLL patients, young patients showed an increased relapse rate compared with elderly patients. To optimize the risk assessment of CLL patients, novel risk score models named PR-Score and HBG-Score were developed for predicting the outcomes of young and elderly CLL patients respectively. The neonatal survival prediction systems were superior to international prognostic index for CLL (CLL-IPI) and Binet stage in assessing the overall survival and progression free survival of CLL patients. The analyses highlighted refinement of risk evaluation for CLL patients in different age groups, providing insights into individualized diagnosis and treatment of CLL.

Distinct Age-Related Clinical Features and Risk Assessment in Chinese With Chronic Lymphocytic Leukemia

Abstract The linking of ethacrynic acid with ethylenediamine and 1,4-butanediamine gave EDEA and BDEA, respectively, as membrane-permeable divalent pro-inhibitors of glutathione S-transferase (GST). Their divalent glutathione conjugates showed subnanomolar inhibition and divalence-binding to GSTmu (GSTM) (PDB: 5HWL) at ∼0.35 min−1. In cisplatin-resistant SK-OV-3, COC1, SGC7901 and A549 cells, GSTM activities probed by 15 nM BDEA or EDEA revealed 5-fold and 1.0-fold increases in cisplatin-resistant SK-OV-3 and COC1 cells, respectively, in comparison with the susceptible parental cells. Being tolerable by HEK293 and LO2 cells, BDEA at 0.2 μM sensitised resistant SK-OV-3 and COC1 cells by ∼3- and ∼5-folds, respectively, released cytochrome c and increased apoptosis; EDEA at 1.0 μM sensitised resistant SK-OV-3 and A549 cells by ∼5- and ∼7-fold, respectively. EDEA at 1.7 μg/g sensitised resistant SK-OV-3 cells to cisplatin at 3.3 μg/g in nude mouse xenograft model. BDEA and EDEA are promising leads for probing cellular GSTM and sensitising cisplatin-resistant ovarian cancers.

https://www.tandfonline.com/doi/pdf/10.1080/14756366.2022.2038591?needAccess=true

Short divalent ethacrynic amides as pro-inhibitors of glutathione S-transferase isozyme Mu and potent sensitisers of cisplatin-resistant ovarian cancers

This study aimed to evaluate the predictive value of systemic inflammation response index (SIRI) in primary gastrointestinal diffuse large B‐cell lymphoma (PGI‐DLBCL) patients and establish a highly discriminating risk prediction model.

Prognosis and complications of patients with primary gastrointestinal diffuse large B‐cell lymphoma: Development and validation of the systemic inflammation response index‐covered score


 
 Improving the accuracy of daily runoff in the lower Yellow River is important for flood control and reservoir scheduling in the lower Yellow River. Influenced by factors such as meteorology, climate change, and human activities, runoff series present non-stationary and non-linear characteristics. To weaken the non-linearity and non-smoothness of runoff time series and improve the accuracy of daily runoff prediction, a new combined runoff prediction model (VMD–HHO–KELM) based on the ensemble Variational Modal Decomposition (VMD) algorithm and Harris Hawk Optimisation (HHO) algorithm-optimised Kernel Extreme Learning Machine (KELM) is proposed and applied to Gaocun and Lijin hydrological stations. The VMD–HHO–KELM model has the highest prediction accuracy, with the prediction model R2 reaching 0.95, mean absolute error reaching 13.3, and root mean square error reaching 33.83 at the Gaocun hydrological station, and R2 reaching 0.96, mean absolute error reaching 8.03, and root mean square error reaching 38.45 at the Lijin hydrological station.

Fang Liu

Papers

Interleukin-17A Promotes Aortic Endothelial Cell Activation via Transcriptionally and Post-translationally Activating p38 Mitogen-activated Protein Kinase (MAPK) Pathway.

Distinct Age-Related Clinical Features and Risk Assessment in Chinese With Chronic Lymphocytic Leukemia

Short divalent ethacrynic amides as pro-inhibitors of glutathione S-transferase isozyme Mu and potent sensitisers of cisplatin-resistant ovarian cancers

Prognosis and complications of patients with primary gastrointestinal diffuse large B‐cell lymphoma: Development and validation of the systemic inflammation response index‐covered score

Daily runoff prediction during flood seasons based on the VMD–HHO–KELM model