LY86 facilitates ox-LDL-induced lipid accumulation in macrophages by upregulating SREBP2/HMGCR expression.

LY86, also known as MD1, has been implicated in various pathophysiological processes including inflammation, obesity, insulin resistance, and immunoregulation. However, the role of LY86 in cholesterol metabolism remains incompletely understood. Several studies have reported significant up-regulation of LY86 mRNA in atherosclerosis; nevertheless, the regulatory mechanism by which LY86 is involved in this disease remains unclear. In this study, we aimed to investigate whether LY86 affects ox-LDL-induced lipid accumulation in macrophages. Firstly, we confirmed that LY86 is indeed involved in the process of atherosclerosis and found high expression levels of LY86 in human atherosclerotic plaque tissue. Furthermore, our findings suggest that LY86 may mediate intracellular lipid accumulation induced by ox-LDL through the SREBP2/HMGCR pathway. This mechanism could be associated with increased cholesterol synthesis resulting from enhanced endoplasmic reticulum stress response.

Cyclosporine A-resistant CAR-T cells mediate antitumour immunity in the presence of allogeneic cells.

Chimeric antigen receptor (CAR)-T therapy requires autologous T lymphocytes from cancer patients, a process that is both costly and complex. Universal CAR-T cell treatment from allogeneic sources can overcome this limitation but is impeded by graft-versus-host disease (GvHD) and host versus-graft rejection (HvGR). Here, we introduce a mutated calcineurin subunit A (CNA) and a CD19-specific CAR into the T cell receptor α constant (TRAC) locus to generate cells that are resistant to the widely used immunosuppressant, cyclosporine A (CsA). These immunosuppressant-resistant universal (IRU) CAR-T cells display improved effector function in vitro and anti-tumour efficacy in a leukemia xenograft mouse model in the presence of CsA, compared with CAR-T cells carrying wild-type CNA. Moreover, IRU CAR-T cells retain effector function in vitro and in vivo in the presence of both allogeneic T cells and CsA. Lastly, CsA withdrawal restores HvGR, acting as a safety switch that can eliminate IRU CAR-T cells. These findings demonstrate the efficacy of CsA-resistant CAR-T cells as a universal, 'off-the-shelf' treatment option.

Novel immune cell infiltration-related biomarkers in atherosclerosis diagnosis.

Background: Immune cell infiltration (ICI) has a close relationship with the progression of atherosclerosis (AS). Therefore, the current study was aimed to explore the role of genes related to ICI and to investigate potential mechanisms in AS. Methods: Single-sample gene set enrichment analysis (ssGSEA) was applied to explore immune infiltration in AS and controls. Genes related to immune infitration were mined by weighted gene co-expression network analysis (WGCNA). The function of those genes were analyzed by enrichment analyses of the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO). The interactions among those genes were visualized in the protein-protein interaction (PPI) network, followed by identification of hub genes through Cytoscape software. A receiver operating characteristic (ROC) plot was generated to assess the performance of hub genes in AS diagnosis. The expressions of hub genes were measured by reverse transcription quantitative real-time PCR (RT-qPCR) in human leukemia monocyticcell line (THP-1) derived foam cells and macrophages, which mimic AS and control, respectively. Results: We observed that the proportions of 27 immune cells were significantly elevated in AS. Subsequent integrative analyses of differential expression and WGCNA identified 99 immune cell-related differentially expressed genes (DEGs) between AS and control. Those DEGs were associated with tryptophan metabolism and extracellular matrix (ECM)-related functions. Moreover, by constructing the PPI network, we found 11 hub immune cell-related genes in AS. The expression pattern and receiver ROC analyses in two independent datasets showed that calsequestrin 2 (CASQ2), nexilin F-Actin binding protein (NEXN), matrix metallopeptidase 12 (MMP12), C-X-C motif chemokine ligand 10 (CXCL10), phospholamban (PLN), heme oxygenase 1 (HMOX1), ryanodine receptor 2 (RYR2), chitinase 3 like 1 (CHI3L1), matrix metallopeptidase 9 (MMP9), actin alpha cardiac muscle 1 (ACTC1) had good performance in distinguishing AS from control samples. Furthermore, those biomarkers were shown to be correlated with angiogenesis and immune checkpoints. In addition, we found 239 miRNAs and 47 transcription factor s (TFs), which may target those biomarkers and regulate their expressions. Finally, we found that RT-qPCR results were consistent with sequencing results.

Identification of immune-related biomarkers and construction of regulatory network in patients with atherosclerosis.

BACKGROUND: More and more evidence has established the crucial roles of the innate and adaptive immune systems in driving atherosclerosis-associated chronic inflammation in arterial blood vessels. Thus, the goal of this research was to determine immune-related biomarkers in atherosclerosis. METHODS: In this study, we conducted analysis on the mRNA expression profile of atherosclerosis obtained from Gene Expression Omnibus. Differentially expressed genes (DEGs) between atherosclerosis and control samples and immune-related genes (IRGs) were intersected to obtain differentially expressed immune-related genes (DEIRGs). The protein-protein interaction (PPI) network was created by STRING database and hub genes were identified by the MCODE plug-in. Furthermore, the receiver operating characteristic (ROC) curve was executed to verify the diagnostic value of the hub genes, and microRNA (miRNA)-gene-transcription factor (TF) regulatory networks were used to explain the regulatory mechanism of hub genes in atherosclerosis. Finally, qRT-PCR was performed to identify the mRNA levels of the target genes. RESULTS: A total of 199 overlapping genes were screened out as DEIRGs by intersecting the DEGs and IRGs. Then, 6 hub genes with high diagnostic value (IFIH1, IFIT1, IFIT2, IFIT3, ISG15 and OAS3) were identified via PPI network and ROC curve. Finally, miRNA-gene-TF networks revealed the regulatory mechanism of diagnostic genes.We used the carotid artery of AS patients and normal human carotid artery plaque samples for qRT-PCR verification, and the results showed that the hub gene had the same trend. CONCLUSION: Our study identified IFIH1, IFIT1, IFIT2, IFIT3, ISG15 and OAS3 as immune-related hub genes of atherosclerosis. These genes may serve as potential therapeutic targets for atherosclerosis patients.

Engineering γδ T Cells: Recognizing and Activating on Their Own Way.

Adoptive cell therapy (ACT) with engineered T cells has emerged as a promising strategy for the treatment of malignant tumors. Among them, there is great interest in engineered γδ T cells for ACT. With both adaptive and innate immune characteristics, γδ T cells can be activated by γδ TCRs to recognize antigens in a MHC-independent manner, or by NK receptors to recognize stress-induced molecules. The dual recognition system enables γδ T cells with unique activation and cytotoxicity profiles, which should be considered for the design of engineered γδ T cells. However, the current designs of engineered γδ T cells mostly follow the strategies that used in αß T cells, but not making good use of the specific characteristics of γδ T cells. Therefore, it is no surprising that current engineered γδ T cells in preclinical or clinical trials have limited efficacy. In this review, we summarized the patterns of antigen recognition of γδ T cells and the features of signaling pathways for the functions of γδ T cells. This review will additionally discuss current progress in engineered γδ T cells and provide insights in the design of engineered γδ T cells based on their specific characteristics.

Renal Artery Reconstruction for Refractory Hypertension Caused by Congenital Renal Artery Deficiency.

Renovascular hypertension is a common cause of secondary hypertension. According to the epidemiological survey, the prevalence of renovascular hypertension accounts for 1-5% of the population with hypertension. Most of the cases are associated with atherosclerosis and Fibromuscular Dysplasia (FMD). Owing to the lack of standard treatment, they will eventually develop into chronic kidney disease, which significantly affects the patient's quality of life. Hypertension is considered a prerequisite for renal artery surgery; renal function research is used to guide the treatment of unilateral lesions because endovascular intervention can only slightly improve hypertension and renal function. We advocate open surgery for patients with congenital dysplasia of renal vascular hypertension, in which the most common surgical operations are aortorenal artery bypass, renal artery endarterectomy, and renal artery replantation. This paper reports a rare case of renovascular hypertension. The patient was a 13-year-old female, and the operation was risky and complicated. He was diagnosed with a congenital absence of the right renal artery. The right renal function was recovered, and the blood pressure was well controlled after the Aorta-Right Renal Artery Bypass.

An Efficient Catalyst Derived from Carboxylated Lignin-Anchored Iron Nanoparticle Compounds for Carbon Monoxide Hydrogenation Application.

Catalytic activity and target product selectivity are strongly correlated to the size, crystallographic phase, and morphology of nanoparticles. In this study, waste lignin from paper pulp industry is employed as the carbon source, which is modified with carboxyl groups at the molecular level to facilitate anchoring of metals, and a new type of carbon-based catalyst was obtained after carbonization. As a result, the size of the metal particles is effectively controlled by the chelation between -COO- and Fe3+. Furthermore, Fe/CM-CL with a particle size of 1.5-2.5 nm shows excellent catalytic performance, the conversion of carbon monoxide reaches 82.3%, and the selectivity of methane reaches 73.2%.