AimMyocardial infarction (MI) is a severe disease with increased mortality and disability rates, posing heavy economic burden for society. Exosomes were uncovered to mediate intercellular communication after MI. This study aims to explore the effect and mechanism of lncRNA KLF3-AS1 in exosomes secreted by human mesenchymal stem cells (hMSCs) on pyroptosis of cardiomyocytes and MI.MethodsExosomes from hMSCs were isolated and identified. Exosomes from hMSCs with transfection of KLF3-AS1 for overexpression were injected into MI rat model or incubated with hypoxia cardiomyocytes. Effect of KLF3-AS1 on MI area, cell viability, apoptosis, and pyroptosis was determined. The relationship among miR-138-5p, KLF3-AS1, and Sirt1 was verified by dual-luciferase reporter assay. Normal cardiomyocytes were transfected with miR-138-5p inhibitor or sh-Sirt1 to clarify whether alteration of miR-138-5p or sh-Sirt1 can regulate the effect of KLF3-AS1 on cardiomyocytes.ResultsExosomes from hMSCs were successfully extracted. Transfection of KLF3-AS1 exosome in rats and incubation with KLF3-AS1 exosome in hypoxia cardiomyocytes both verified that overexpression of KLF3-AS1 in exosomes leads to reduced MI area, decreased cell apoptosis and pyroptosis, and attenuated MI progression. KLF3-AS1 can sponge miR-138-5p to regulate Sirt1 expression. miR-138-5p inhibitor transfection and KLF3-AS1 exosome incubation contribute to attenuated pyroptosis and MI both in vivo and in vitro, while transfection of sh-Sirt1 could reverse the protective effect of exosomal KLF3-AS1 on hypoxia cardiomyocytes.ConclusionLncRNA KLF3-AS1 in exosomes secreted from hMSCs by acting as a ceRNA to sponge miR-138-5p can regulate Sirt1 so as to inhibit cell pyroptosis and attenuate MI progression.

Lung cancer is the most common and fatal malignant tumor in the world. The tumor microenvironment (TME) is closely related to the occurrence and development of lung cancer, in which the inflammatory microenvironment plays an important role. Inflammatory cells and inflammatory factors in the tumor inflammatory microenvironment promote the activation of the NF-κB and STAT3 inflammatory pathways and the occurrence, development, and metastasis of lung cancer by promoting immune escape, tumor angiogenesis, epithelial–mesenchymal transition, apoptosis, and other mechanisms. Clinical and epidemiological studies have also shown a strong relationship among chronic infection, inflammation, inflammatory microenvironment, and lung cancer. The relationship between inflammation and lung cancer can be better understood through the gradual understanding of the tumor inflammatory microenvironment, which is advantageous to find more therapeutic targets for lung cancer.

To solve the problem that analyte molecules cannot easily enter "hot spots" on a conventional solid SERS substrate, we developed a mixing-assisted "hot spots" occupying (MAHSO) SERS strategy to improve utilization of "hot spots". Compared with the conventional substrate, the MAHSO substrate enhances the sensitivity of SERS measurement by thousands of times. The MAHSO substrate possesses excellent properties of high enhancement, high uniformity, and long-term stability because the MAHSO substrate is integrated inside an ultrafast microfluidic mixer. The mixer makes analytes and metal colloid homogeneously mixed, and analytes are naturally located in "hot spots", the gaps between adjacent NPs, during the process that NPs deposit on the channel wall. As a multi-inlet device, the MAHSO chip offers a convenient in situ method to study environmental effects on analytes or molecular interactions by flexibly regulating fluid in microchannels and monitoring responses of analytes by SERS spectra. Because all experiments are conducted in aqueous environments, which is similar to the physiological conditions, the MAHSO chip is especially suitable to be applied to study biomolecules. Using this strategy, different conformational changes of the wild type and mutant G150D of protein PMP22-TM4 depending on environmental pH have been observed in situ and analyzed. As a lab-on-a-chip (LoC) device, the MAHSO SERS chip will benefit the field of molecular dynamics, as well as molecule-molecule or molecule-surface interactions in the future.

Toll‑like receptor 3 (TLR3) can react with double stranded RNA and is involved in the inflammatory response to respiratory syncytial virus (RSV) infection. Also, oxidative stress has been reported to be involved in RSV infection. However, the correlation between oxidative stress and TLR3 activation during RSV infection is unclear. Therefore, the present study investigated the association between TLR3 expression and oxidative stress modulation during RSV infection in A549 cells. For comparison, seven treatment groups were established, including RSV‑treated cells, N‑acetyl‑L‑cysteine (NAC)+RSV‑treated cells, oxidant hydrogen peroxide (H2O2)+RSV‑treated cells, normal cell control, inactivated RSV control, NAC control and H2O2 control. The mRNA expression changes of TLR3, interferon regulatory factor‑3 (IRF3), nuclear factor‑κB (NF‑κB) and superoxide dismutase 1 (SOD1) were measured using semi‑quantitative reverse transcription‑polymerase chain reaction, and the protein changes of TLR3 and phospho‑NF‑κB p65 were determined using western blot in A549 cells from the different treatment groups. The present study also evaluated the differences in hydroxyl free radical (·OH), nitric oxide (NO) and total SOD activity in the different treatment groups. The results demonstrated that RSV infection of A549 cells increased the levels of ·OH and NO, while decreasing the activity of total SOD. Pretreatment of A549 cells with H2O2 prior to RSV infection upregulated the mRNA and protein expression of TLR3 and NF‑κB, and downregulated the mRNA expression of IRF3 and SOD1, as well as the total SOD activity. When the infected cells were pretreated with NAC, the mRNA and protein expression of these genes were reversed. These variations in the TLR3‑mediated signaling pathway molecules suggested that oxidative stress may be a key regulator for TLR3 activation during RSV infection. RSV‑induced oxidative stress may potentially activate TLR3 and enhance TLR3‑mediated inflammation. These results may provide better understanding of the RSV‑induced inflammatory and immune pathways, and may also contribute to the drug development and prevention of human RSV diseases.