Expression and clinical significance of NRLP1 in patients with ST-segment elevation myocardial infarction combined with malignant ventricular arrhythmia.

Objective: To investigate the clinical effects of NRLP1 expression in patients with ST-segment elevation myocardial infarction (STEMI) combined with arrhythmia. Methods: We enrolled 231 patients with STEMI in the first hospital of Quanzhou affiliated to Fujian Medical University from January 2019 to December 2020 to the observational group and 230 healthy individuals as the control group. We divided patients with STEMI into a malignant ventricular arrhythmia (MVA) group (n=36) and non-MVA(NMVA) group (n=195) depending on whether the individuals had experienced an episode of MVA within 48 hours after PCI. We recorded general variables such as age, gender, history of smoking, hypertension, of diabetes, hyperlipidemia, left ventricular ejection fraction (LVEF), Gensini score, and mortality. Moreover, we determined NLRP1, IL-1ß, TNF-α, high-sensitivity C-reactive protein (hs-CRP), N-terminal pro-brain natriuretic peptide (NT-pro-BNP), cardiac troponin-1 (cTnI), and creatine kinase isoenzyme (CK-MB) in peripheral blood by ELISA. Results: We found significant differences in LVEF, Gensini scores, smoking history, and mortality between the MVA and NMVA groups. The mean NLRP1 expression was highest in the MVA group, which was positively correlated with the levels of IL-1ß, TNF-α, hs-CRP, NT-pro-BNP, cTnI and CK-MB. The expression of NLRP1 was associated with the smoking history, the LVEF value, the Gensini score, the MVA incidence and the mortality. Patients with higher NLRP1 expression levels had a higher MACE incidence and worse overall survivals within one year. Conclusion: The NLRP1 pathway is associated with the presence of arrhythmias after PCI treatments, and the NLRP1 expression level may be useful as a predictor of arrhythmia in patients with STEMI.

Promoting the healing of methicillin-resistant Staphylococcus aureus-infected wound by a multi-target antimicrobial AIEgen of 6-Aza-2-thiothymine-decorated gold nanoclusters.

The use of conventional antibiotic therapies is in question owing to the emergence of drug-resistant pathogenic bacteria. Therefore, novel, highly efficient antibacterial agents to effectively overcome resistant bacteria are urgently needed. Accordingly, in this work, we described a novel class luminogen of 6-Aza-2-thiothymine-decorated gold nanoclusters (ATT-AuNCs) with aggregation-induced emission property that possessed potent antimicrobial activity against methicillin-resistant Staphylococcus aureus (MRSA). Scanning electron microscopy was performed to investigate the interactions between ATT-AuNCs and MRSA. In addition, ATT-AuNCs exhibited excellent ROS generation efficiency and could effectively ablate MRSA via their internalization to the cells. Finally, tandem mass tag-labeling proteome analysis was carried out to investigate the differential expression proteins in MRSA strains. The results suggested that ATT-AuNCs killed MRSA cells through altering the expression of multiple target proteins involved in DNA replication, aminoacyl-tRNA synthesis, peptidoglycan and arginine biosynthesis metabolism. Parallel reaction monitoring technique was further used for the validation of these proteome results. ATT-AuNCs could also be served as a wound-healing agent and accelerate the healing process. Overall, we proposed ATT-AuNCs could serve as a robust antimicrobial aggregation-induced emission luminogen (AIEgen) that shows the ability to alter the activities of multiple targets for the elimination of drug-resistant bacteria.

6-Aza-2-Thiothymine-Capped Gold Nanoclusters as Robust Antimicrobial Nanoagents for Eradicating Multidrug-Resistant Escherichia coli Infection.

Multidrug-resistant bacterial infections, especially those caused by multidrug-resistant Escherichia coli (E. coli) bacteria, are an ever-growing threat because of the shrinking arsenal of efficacious antibiotics. Therefore, it is urgently needed to develop a kind of novel, long-term antibacterial agent effectively overcome resistant bacteria. Herein, we present a novel designed antibacterial agent-6-Aza-2-thiothymine-capped gold nanoclusters (ATT-AuNCs), which show excellent antibacterial activity against multidrug-resistant E. coli bacteria. The prepared AuNCs could permeabilize into the bacterial cell membrane via binding with a bivalent cation (e.g., Ca2+), followed by the generation of reactive oxygen species (e.g., •OH and •O2-), ultimately resulting in protein leakage from compromised cell membranes, inducing DNA damage and upregulating pro-oxidative genes intracellular. The AuNCs also speed up the wound healing process without noticeable hemolytic activity or cytotoxicity to erythrocytes and mammalian tissue. Altogether, the results indicate the great promise of ATT-AuNCs for treating multidrug-resistant E. coli bacterial infection.

MicroRNA-301a-3p increases oxidative stress, inflammation and apoptosis in ox-LDL-induced HUVECs by targeting KLF7.

Arteriosclerotic cardiovascular disease is an inflammatory disease of ischemia or endothelial dysfunction caused by atherosclerosis, thereby causing high mortality. The viability and apoptosis of human umbilical vein endothelial cells (HUVECs) following oxidized low-density lipoprotein (ox-LDL) induction or transfection was detected by Cell Counting Kit-8 (CCK-8) assay and flow cytometry analysis. MicroRNA (miR)-301a-3p and Krueppel-like factor 7 (KLF7) mRNA expression was determined by reverse transcription-quantitative PCR (RT-qPCR). The levels of monocyte chemoattractant protein-1 (MCP-1) and IL-6, activities of reactive oxygen species and superoxide dismutase and lactate dehydrogenase leakage were analyzed by respective commercial assay kits. The protein expression of IL-6, MCP-1, Bcl2, Bax, poly (ADP-ribose) polymerase (PARP), cleaved PARP, pro-caspase3 and cleaved caspase-3 was detected by western blotting. miR-301a-3p expression is highly expressed in ox-LDL-induced HUVECs. miR-301a-3p is also a target of KLF7. Inhibition of miR-301a-3p suppressed oxidative stress, inflammation and apoptosis in ox-LDL-induced HUVECs, which was reversed by KLF7 inhibition. In conclusion, miR-301a-3p promotes oxidative stress, inflammation and apoptosis in ox-LDL-induced HUVECs via decreasing KLF7 expression.