[Effect and mechanism of microRNA-155 in chronic obstructive pulmonary disease by targeting PIK3R1].

This study aimed to investigate the effect of microRNA-155 (miR-155) in chronic obstructive pulmonary disease (COPD) and cigarette smoke extract (CSE)-treated airway smooth muscle cells (ASMCs) by targeting phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1) to regulate the PTEN/PI3K/Akt signaling pathway. The COPD mouse model was induced by lipopolysaccharide (LPS) combined with passive smoking. After modeling, miR-155 mimics and miR-155 inhibitor were used for intervention treatment. The pulmonary function of each group was detected by an EMKA detector. Hematoxylin-eosin (HE) staining was used to observe the pathological changes and scores of lung tissues. The expression of TNF-α, IL-6, and IL-1ß in bronchial alveolar lavage fluid (BALF) was detected by ELISA. Primary ASMCs were isolated and cultured in adherent tissue culture. The proliferation activity was detected by CCK-8 and EdU assays. Transwell and wound healing assays were used to measure the migration of ASMCs. The targeting relationship between miR-155 and PIK3R1 was validated by a double luciferase reporter gene assay. The expression levels of miR-155 and PIK3R1 mRNA in lung tissues of mice in each group were detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Western blot was used to detect the expression levels of Ki67, PNCA, PTEN, p-PI3K, PI3K, p85α, p-Akt, and Akt in lung tissues and ASMCs. The results showed that lung function was significantly reduced in the miR-155 mimic group, and the levels of PIK3R1 were significantly increased; while lung function in the miR-155 inhibitor group was significantly improved. The results of HE staining showed that there was obvious inflammatory cell infiltration in the miR-155 mimics group compared to that of the model group. Lung histopathological injury was significantly reduced in the miR-155 inhibitor group, accompanied by decreased expression of Ki67, PNCA, PI3K, p-Akt, increased PTEN and p85α protein levels, and reduced levels of TNF-α, IL-6, and IL-1ß in BALF. The results of the double luciferase reporter gene assay showed that miRNA-155 could target bind to PIK3R1. Compared with those in the CSE+miR-155 NC group, the proliferation and migration of ASMCs were significantly increased in the CSE+miR-155 group. The proliferation and migration of ASMCs were significantly attenuated in the CSE+miR-155+pcDNA PIK3R1 group compared with those in the CSE+miR-155 group, accompanied by decreased expression of Ki67, PNCA, p-Akt and increased PTEN and p85α protein levels. These results suggest that miR-155 activates the PTEN/PI3K/Akt signaling pathway by targeting PIK3R1 to promote the occurrence and development of COPD, which provides new evidence for the use of miR-155 in the treatment of COPD.

[Effect of "Tongdu Tiaoshen" needling on cognitive dysfunction in patients with sepsis asso-ciated encephalopathy and its mechanism].

OBJECTIVE: To observe the efficacy of "Tongdu Tiaoshen" (dredging Governor Vessel and regula-ting mind,needling on the cognitive function of patients with sepsis associated encephalopathy (SAE). METHODS: A total of 64 patients with SAE were enrolled in the present study, and randomly and equally divided into a control group and a treatment group. Patients in the control group received conventional medicines and conventional needling treatment. The patients of the treatment group received conventional medicines and "Tongdu Tiaoshen" needling treatment. The treatment was conducted once daily for 10 days. The Montreal Cognitive Assessment (MoCA) scale was used to assess the therapeutic effect after the treatment. Serum interleukin-6 (IL-6) was detected by radioimmunoassay, serum C-reactive protein (CRP) was detected by immuno-scattering method, and arterial blood lactic acid (Lac) content was detected by blood gas analyzer. RESULTS: The effective rate in the treatment group was obviously higher than that in the control group (P<0.01). After the treatment, the MoCA scores were considerably increased in both groups compared with their own pre-treatment (P<0.01), and the MoCA scores in the treatment group were obviously higher than those of the control group in the visual space and executive function, attention and computational power, language, abstraction and delayed recall dimensions (P<0.01). The contents of IL-6, CRP and Lac in both groups were significantly decreased after the treatment relevant to those of their own pre-treatment (P<0.01), and were obviously lower in the treatment group than those in the control group (P<0.01). CONCLUSION: "Tongdu Tiaoshen" needling can significantly improve the cognitive function of SAE patients, which may be associated with its effect in reducing inflammatory reaction of sepsis.