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This study aims to explore the roles of phenylacetyl glutamine (PAGln) on myocardial infarction (MI) pathogenesis. Here, using targeted metabolomics analysis, it was found that the plasma metabolite PAGln was upregulated in coronary artery disease (CAD) patients and MI mice and could be an independent risk factor for CAD. In vivo and in vitro functional experiments revealed that PAGln pretreatment enhanced MI‐induced myocardial injury and cardiac fibrosis, as evident by the increased infarct size, cardiomyocyte death, and the upregulated expression of cardiac fibrosis markers (Col1a1 and α‐SMA). Combined with RNA‐sequencing analysis and G protein‐coupled receptor (GPCR) inhibitor, we found that the GPCR signaling activation is essential for PAGln‐mediated effects on cardiomyocyte death. Furthermore, drug affinity responsive target stability and cellular thermal shift assay demonstrated that PAGln could interact with β1‐adrenergic receptor (AR). Moreover, β1‐AR blocker treatment indeed extended the cardiac remodeling after PAGln‐enhanced MI. These results suggest that PAGln might be a potential therapeutic target for extending the cardiac remodeling window in MI patients that signals via β1‐AR. [ABSTRACT FROM AUTHOR]

The expression of major histocompatibility complex class I (MHC-I), a key antigen-presenting protein, can be induced in dopaminergic neurons in the substantia nigra, thus indicating its possible involvement in the occurrence and development of Parkinson's disease. However, it remains unclear whether oxidative stress induces Parkinson's disease through the MHC-I pathway. In the present study, polymerase chain reaction and western blot assays were used to determine the expression of MHC-I in 1-methyl-4-phenylpyridinium (MPP + )-treated SH-SY5Y cells and a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease mouse model. The findings revealed that MHC-I was expressed in both models. To detect whether the expression of MHC-I was able to trigger the infiltration of cytotoxic T cells, immunofluorescence staining was used to detect cytotoxic cluster of differentiation 8 (CD8) + T cell infiltration in the substantia nigra of MPTP-treated mice. The results indicated that the presentation of MHC-I in dopaminergic neurons was indeed accompanied by an increase in the number of CD8 + T cells. Moreover, in MPTP-induced Parkinson's disease model mice, the genetic knockdown of endogenous MHC-I, which was caused by injecting specific adenovirus into the substantia nigra, led to a significant reduction in CD8 + T cell infiltration and alleviated dopaminergic neuronal death. To further investigate the molecular mechanisms of oxidative stress-induced MHC-I presentation, the expression of PTEN-induced kinase 1 (PINK1) was silenced in MPP + -treated SH-SY5Y cells using specific small interfering RNA (siRNA), and there was more presentation of MHC-I in these cells compared with control siRNA-treated cells. Taken together, MPP + -/MPTP-induced oxidative stress can trigger MHC-I presentation and autoimmune activation, thus rendering dopaminergic neurons susceptible to immune cells and degeneration. This may be one of the mechanisms of oxidative stress-induced Parkinson's disease, and implies the potential neuroprotective role of PINK1 in oxidative stress-induced MHC-I presentation. All animal experiments were approved by the Southern Medical University Ethics Committee (No. 81802040, approved on February 25, 2018)., Competing Interests: None

Invasion and metastasis are both the main biological characteristics in malignant tumor which are influence tumor therapeutic effect and prognosis. The tumor cells interact with vascular endothelial cells and cell matrix, penetrate vascular endothelial and degrade the extracellular matrix, and metastasis to the local and distant by the interactions of a variety of signaling molecules. PTEN protein has protein phosphatase and lipid phosphatase dual activity which is produced by PTEN gene. As a tumor suppressor gene, regulates the cell signal pathways to sustain the normal physiological functions, negatively regulates of tumor cell growth and cell cycle, induces apoptosis, and inhibits invasion, infiltrating and metastasis of tumor cells. This article is reviewed about how PTEN participates in inhibiting tumor cell invasion and metastasis.

Recent studies have found that ABO blood group antigen is also closely related to the onset and development of many diseases. More and more attention is being paid to the decrease of A/B blood group antigen caused by some tumors. This study was purpose to investigate the correlation between DNA methylation of the ABO gene promoter CpG island and leukemia. The relative contents of ABH antigen on the surface of RBC from kinds of blood disease patients and healthy individuals were detected by using flow cytometry and confocal laser scanning microscopy. The DNA sequences and CpG methylation of ABO gene promoter in patients with hematopathy and healthy individuals, as well as the -102 site methylation of ABO gene promoter in patients with hematopathy and healthy individuals were detected by PCR and MSP-PCR respectively. The results showed that RBC from leukemia patients displayed different degree of A/B antigen decrease. The sequences of ABO gene promotor of patients with hematopathy were not different from healthy individuals indicating high conservation of promoter sequences. Comparison of sequences between patients with hematopathy and healthy individual indicated that CpG islands on ABO gene promoter either from blood disease patients or from healthy individual had no methylated site in AA patients, but C residues at position -102, -101, -100, -99 and -97 on the promoter of ABO gene in AML, CML, ALL and some MDS patients were methylated. It is concluded that methylation of CpG islands in promoter of ABO gene may result in AB antigen decrease in patients with leukemia. The methylation sites -102, -101, -100, -99 and -97 may be specific for leukemia. The methylation of site -102 can be used as a molecular marker in differential diagnosis for leukemias.