Runx1 Deficiency Promotes M2 Macrophage Polarization Through Enhancing STAT6 Phosphorylation.

Our previous study had demonstrated that Runx1 promoted LPS-induced macrophage inflammatory response, however, the role of Runx1 in M2 macrophage polarization still remains largely unknown. This study was conducted to investigate the role of Runx1 in IL-4/IL-13-induced M2 macrophage polarization and its potential regulatory mechanism. We found that exposure of macrophages to IL-4/IL-13 induced a remarkable increasement in Runx1 expression level. Specifically, we established genetically modified mice lacking Runx1 in myeloid cells, including macrophages. RNA-Seq was performed to identify differentially expressed genes (DEGs) between Runx1 knockout and WT control bone marrow-derived macrophages (BMDMs). We identified 686 DEGs, including many genes which were highly expressed in M2 macrophage. In addition, bioinformatics analysis indicated that these DEGs were significantly enriched in extracellular matrix-related processes. Moreover, RT-qPCR analysis showed that there was an obvious upregulation in the relative expression levels of M2 marker genes, including Arg1, Ym1, Fizz1, CD71, Mmp9, and Tgm2, in Runx1 knockout macrophages, as compared to WT controls. Consistently, similar results were obtained in the protein and enzymatic activity levels of Arg1. Finally, we found that the STAT6 phosphorylation level was significantly enhanced in Runx1 knockout macrophages, and the STAT6 inhibitor AS1517499 partly reduced the upregulated effect of Runx1 deficiency on the M2 macrophage polarization. Taken together, Runx1 deficiency facilitates IL-4/IL-13-induced M2 macrophage polarization through enhancing STAT6 phosphorylation.

Association Between the Frailty and Cognitive Impairment Among Patients With Hypertension-A Post Hoc Analysis of the SPRINT Trial.

Background Frailty and cognitive impairment are common in the elderly, with various shared risk factors like hypertension. Frailty is a marker for future cognitive function. Moreover, whether intensive blood pressure interacted with frailty and cognitive impairment is unknown. Methods and Results We performed a post hoc analysis of data from SPRINT (Systolic Blood Pressure Intervention Trial). The relationship between frailty and a composite of probable dementia (PD) and mild cognitive impairment (MCI) was analyzed. Also, we evaluated the interaction of intensive blood pressure lowering in the relationship between frailty and cognitive impairment. A total of 8537 patients were included in our study, and 35.1% were women. The mean age of these participants was 67.9±9.3 years. According to the baseline frailty index, 1670, 4637, and 2230 patients were in fit, less fit, and frail statuses, respectively. During a mean follow-up of 4.61 years, 871 cases of PD or MCI occurred. Compared with those in fit status, those with less fit (hazard ratio [HR], 2.14 [95% CI, 1.65-2.77]) and frailty (HR, 4.28 [95% CI, 3.26-5.61]) status had a higher incidence of a composite of PD and MCI. Blood pressure control strategy interacted with the correlation between frailty and cognitive impairment. Intensive blood pressure control (HR, 2.4 [95% CI, 2.0-2.8]) accelerated the relationship between frailty and incidence of PD and MCI compared with the standard treatment group (HR, 1.8 [95% CI, 1.5-2.1]; P for interaction=0.009). Conclusions This study found that the baseline frailty status was a possible marker for the incidence of a composite of PD and MCI. Intensive blood pressure control may strengthen this correlation. Registration URL: https://clinicaltrials.gov/; Unique identifier: NCT01206062.

A Study of the Mechanism and Separation of Structurally Similar Phenolic Acids by Commercial Polymeric Ultrafiltration Membranes.

This study examined the behavior and penetration mechanisms of typical phenolic (benzoic) acids, which determine their observed penetration rates during membrane separation, focusing on the influence of electrostatic and hydrophobic solute/membrane interactions. To understand the effects of hydrophobicity and electrostatic interaction on membrane filtration, the observed penetration of five structurally similar phenolic acids was compared with regenerated cellulose (RC) and polyamide (PA) membranes at different solute concentrations and solution pHs. Variation partitioning analysis (VPA) was performed to calculate the relative contributions of electrostatic and hydrophobic effects. The penetration of phenolic acids was mainly influenced by the electrostatic interaction, with salicylic acid having the highest penetration. Penetration of phenolic acids through the PA membrane decreased from 98% at pH 3.0 to 30-50% at pH 7.4, indicating the dominance of the electrostatic interaction. Moreover, based on its hydrophobicity and greater surface charge, the PA membrane could separate binary mixtures of protocatechuic/salicylic acid and 4-hydroxybenzoic/salicylic acid at pH 9.0, with separation factors of 1.81 and 1.78, respectively. These results provide a greater understanding of solute/membrane interactions and their effect on the penetration of phenolic acids through polymeric ultrafiltration membranes.

The role of exosomal lncRNAs in cancer biology and clinical management.

Exosomes play a vital role in cell-cell communication within the cancer microenvironment. Exosomal long noncoding RNAs (lncRNAs) are important regulators in cancer development and are involved in multiple processes, including cancer cell proliferation, angiogenesis, metastasis, drug resistance, and immunomodulation. Changes in the levels of exosomal lncRNAs often appear with the occurrence and development of cancer. Therefore, exosomal lncRNAs can be used as biomarkers for cancer diagnosis and prognosis. Exosomal lncRNAs can also indicate the treatment response of patients receiving chemotherapy. Moreover, exosomal lncRNAs are potential therapeutic targets for cancer treatment. In this review, we summarize the role of exosomal lncRNAs in cancer biology as well as in clinical management. A more comprehensive and in-depth understanding of the role of exosomal lncRNAs in cancer may help us better understand the mechanism of cancer development and clinically manage cancer patients.