Omaveloxolone ameliorates isoproterenol-induced pathological cardiac hypertrophy in mice.

Nuclear factor erythroid 2-related factor 2 (Nrf2) is an important transcriptional regulator that plays a protective role against various cardiovascular diseases. Omaveloxolone is a newly discovered potent activator of Nrf2 that has a variety of cytoprotective functions. However, the potential role of omaveloxolone in the process of pathological cardiac hypertrophy and heart failure are still unknown. In this study, an isoproterenol (ISO)-induced pathological cardiac hypertrophy model was established to investigate the protective effect of omaveloxolone in vivo and in vitro. Our study first confirmed that omaveloxolone administration improved ISO-induced pathological cardiac hypertrophy in mice and neonatal cardiomyocytes. Omaveloxolone administration also diminished ISO-induced cardiac oxidative stress, inflammation and cardiomyocyte apoptosis. In addition, omaveloxolone administration activated the Nrf2 signaling pathway, and Nrf2 knockdown almost completely abolished the cardioprotective effect of omaveloxolone, indicated that the cardioprotective effect of omaveloxolone was directly related to the activation of the Nrf2 signaling. In summary, our study identified that omaveloxolone may be a promising therapeutic agent to mitigate pathological cardiac hypertrophy.

Single-Cell Sequencing Informs That Mesenchymal Stem Cell Alleviates Renal Injury Through Regulating Kidney Regional Immunity in Lupus Nephritis.

Lupus nephritis (LN) is the common complication of systemic lupus erythematosus. The pathogenesis of LN kidney injury is unclear. In addition to systemic (extrarenal) immune cells, local (intrarenal) immune cells residing in "kidney regional immunity" are momentous in LN. Mesenchymal stem cell (MSC) therapy is effective for LN. However, mechanisms of MSC therapy remains unclear. In this study, we first systematically investigated the effects of MSC on immune cells in kidney regional immunity in LN using single-cell sequencing. We found that MSC reduced proinflammatory central memory CD4+ T cells, cytotoxic tissue-resident memory CD8+ T cells and exhausted CD8+ T cells, increased anti-inflammatory Naive/Effector CD8+ T cells and type 1 regulatory T cells; reduced infiltrating proinflammatory Ly6c hi/inter/lo era2+ macrophages, increased anti-inflammatory resident macrophage and Ly6c lo ear2- macrophage; and reduced long-lived plasma cells and proinflammatory neutrophils and dendritic cells. This study laid a foundation for clinical applications of MSC.

The effect of spraying bacterial and fungal solutions on Korean pine Pinus koraiensis Sieb. et Zucc. cone development and seed quality when sprayed during the flowering phase.

Korean pine is an economically essential afforestation species limited by the unreasonable collection of cones, indiscriminate use of chemical pesticides and pest damage. This study aimed to determine whether spraying bacterial or fungal solutions affected insect pests, cone development, and the seed quality of Korean pine Pinus koraiensis Sieb. et Zucc. The experiment was conducted in a forest plantation in Linkou County (Heilongjiang, China) in 2019. Four fungal strains and one bacterial strain were applied during the flowering phase of Korean pine. The results after a year and a half of study indicated that a high concentration of Bacillus thuringiensis 223176 promoted cone development, increased seed weight, and reduced the proportion of damaged cones. Under this treatment, there were 15.873% damaged cones; the seed weight reached 0.829 g, and there were 82.738% fully developed cones. Trees treated with the second most effective strain, Beauveria bassiana 122077, had 30.556% damaged cones and an average seed weight of 0.810 g. Leucanicillium antillanum 01 performed the worst in this study. The seed weight was only 0.775 g, and the damaged and fully developed cones were 52.444 and 41.773%, respectively. In summary, spraying bacterial or fungal solutions during the flowering stage of Korean pine positively impacted seed quality and effectively decreased damage by the lepidopteran species that feed on the cones and seeds in this study.

Ciprofol attenuates the isoproterenol-induced oxidative damage, inflammatory response and cardiomyocyte apoptosis.

Background and Purpose: Ciprofol (HSK3486), a novel 2,6-disubstituted phenol derivative, is a new intravenous anesthetic compound with a similar chemical structure to propofol. Animal studies have also shown that propofol plays a protective role in a variety of cardiovascular diseases, including myocardial infarction, myocardial ischemia-reperfusion injury and takotsubo syndrome. However, whether ciprofol exerts cardioprotective effects on myocardial infarction remains unclear. Thus, the aim of this work was to explore the potential cardioprotective mechanism of ciprofol on isoproterenol (ISO)-induced myocardial infarction. Experimental Approach: In the present study, male C57BL/6 mice were subjected to subcutaneous injection of ISO (100 mg/kg) for 2 consecutive days to induce experimental myocardial infarction. Herein, we found that ciprofol could inhibit the abnormal increase in myocardial injury enzymes, the area of myocardial infarction and cardiac dysfunction in ISO-treated mice. Ciprofol administration increased the activity of superoxide dismutase and reduced the levels of NADPH oxidase and malondialdehyde in ISO-treated hearts. Additionally, ciprofol administration markedly reduced the expression of pro-inflammatory cytokines and cardiomyocyte apoptosis. In an in vitro model, the results also confirmed that ciprofol could inhibit ISO-induced oxidative damage, the inflammatory response and cardiomyocyte apoptosis. Moreover, ciprofol can activate the sirtuin1 (Sirt1)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway and Sirt1 and Nrf2 inhibition almost abolished ciprofol-mediated cardioprotective effects. Interpretation: Ciprofol protects the heart against ISO-induced myocardial infarction by reducing cardiac oxidative stress, the inflammatory response and cardiomyocyte apoptosis.

Establishment of PLAFMCi007-A, an induced pluripotent stem cell line, from peripheral blood mononuclear cells (PBMCs) of a healthy adult woman.

Induced pluripotent stem cell (iPSC) lines for studies investigating many diseases can be established from peripheral blood mononuclear cells; here, an iPSC line was established from CD34+ cells isolated from the peripheral blood of a healthy woman. The cells were electrotransfected with three different recombinant plasmids to generate a normal-karyotype iPSC line that expresses characteristic surface markers and other pluripotent stem cell genes and can differentiate into all three germ layers in vivo. These newly established iPSC lines, a normal human cell line, can serve as a control line in studies investigating the pathogenesis of various diseases and meet the conditions for organoid studies.

Establishment of the induced pluripotent stem cell line PLAFMCi006-A from peripheral blood mononuclear cells of polycystic kidney disease patients with PKD2 gene mutation.

Polycystic kidney disease (PKD) caused by PKD2 mutation is an important type of autosomal dominant PKD. In this study, peripheral blood mononuclear cells from a patient with PKD2 polycystic kidney disease were reprogrammed to obtain induced pluripotent stem cells (iPSCs). After stable amplification, the pluripotency of the iPSCs was determined by identifying their cell-surface markers, their expression of pluripotency-related genes, and their ability to form teratomas with three germ layers in vivo. The establishment of the iPSC line could provide a basis for a kidney-like organ model of human PKD caused by PKD2 mutation for use in studying the pathogenesis of PKD along with relevant screening and testing intervention drugs.

Corrigendum to "Interleukin-9 Deletion Relieves Vascular Dysfunction and Decreases Blood Pressure via the STAT3 Pathway in Angiotensin II-Treated Mice".

[This corrects the article DOI: 10.1155/2020/5741047.].

Interleukin-9 Aggravates Isoproterenol-Induced Heart Failure by Activating Signal Transducer and Activator of Transcription 3 Signalling.

BACKGROUND: Previous studies have demonstrated that inflammation is closely related to the occurrence and development of heart failure (HF). As an inflammation-related cytokine, interleukin (IL)-9 has been reported to be involved in the development of cardiovascular diseases. However, the role of IL-9 in HF in response to isoproterenol (ISO) stimulation has barely been explored. Thus, this study aimed to investigate whether IL-9 participates in HF and the possible associated mechanisms. METHODS: Chronic ISO infusion was used to establish an HF model, and the IL-9 levels in mice and isolated cardiomyocytes were measured. In addition, ISO-treated mice received an injection of recombinant mouse IL-9 (rIL-9) or an antimouse IL-9 neutralizing monoclonal antibody (mAb) to investigate the effects of IL-9 on cardiac function, hypertrophy, and fibrosis. RESULTS: IL-9 levels were significantly increased in mice and isolated cardiomyocytes after ISO treatment. Treatment with rIL-9 resulted in aggravated cardiac dysfunction and amplified cardiac hypertrophy and fibrosis, whereas treatment with the anti-IL-9 neutralizing mAb ameliorated cardiac dysfunction and reduced cardiac hypertrophy and fibrosis in ISO-treated mice. In addition, ISO infusion-induced cardiac inflammation and cardiomyocyte apoptosis was aggravated by rIL-9 but prevented by the anti-IL-9 mAb. IL-9 did not activate signal transducer and activator of transcription (STAT)1 or STAT5 but induced STAT3 phosphorylation in ISO-induced HF. Moreover, S31-201, a specific STAT3 inhibitor, nearly abolished rIL-9-induced increases in cardiac dysfunction, hypertrophy, and fibrosis in response to ISO stimulation. CONCLUSIONS: IL-9 aggravated cardiac dysfunction and amplified cardiac hypertrophy and fibrosis in the ISO-induced HF model by activating STAT3 signalling. These data indicate that blocking IL-9 may be an attractive pharmacotherapeutic strategy for the treatment of cardiac hypertrophy and fibrosis induced by chronic ß-adrenergic receptor activation to limit the progression of HF.

Interleukin-9 Deletion Relieves Vascular Dysfunction and Decreases Blood Pressure via the STAT3 Pathway in Angiotensin II-Treated Mice.

BACKGROUND: Multiple interleukin (IL) family members were reported to be closely related to hypertension. We aimed to investigate whether IL-9 affects angiotensin II- (Ang II-) induced hypertension in mice. METHODS: Mice were treated with Ang II, and IL-9 expression was determined. In addition, effects of IL-9 knockout (KO) on blood pressure were observed in Ang II-infused mice. To determine whether the effects of IL-9 on blood pressure was mediated by the signal transducer and activator of the transcription 3 (STAT3) pathway, Ang II-treated mice were given S31-201. Furthermore, circulating IL-9 levels in patients with hypertension were measured. RESULTS: Ang II treatment increased serum and aortic IL-9 expression in a dose-dependent manner; IL-9 levels were the highest in the second week and continued to remain high into the fourth week after the treatment. IL-9 KO downregulated proinflammatory cytokine expression, whereas it upregulated anti-inflammatory cytokine levels, relieved vascular dysfunction, and decreased blood pressure in Ang II-infused mice. IL-9 also reduced smooth muscle 22α (SM22α (SM22. CONCLUSIONS: IL-9 KO alleviates inflammatory response, prevents phenotypic transformation of smooth muscle, reduces vascular dysfunction, and lowers blood pressure via the STAT3 pathway in Ang II-infused mice. IL-9 might be a novel target for the treatment and prevention of clinical hypertension.

Function of SOD1, SOD2, and PI3K/AKT signaling pathways in the protection of propofol on spinal cord ischemic reperfusion injury in a rabbit model.

AIMS: To verify that co-application of propofol preconditioning and postconditioning protects spinal cord from ischemia/reperfusion injury by enhancing the different subtypes of SOD activity, which is related to PI3K/AKT signal pathway. MATERIALS AND METHODS: 60 rabbits were randomly equally assigned to 3 groups: Group S, sham-operation group; Group I/R., ischemia/reperfusion group; Group P, ischemia/reperfusion group with propofol treatment. Four rabbits per group were randomly executed at the time-points: days 1, 2, 3, 5, and 7 post-surgery. Spinal cord tissues at L3 to L4 levels were harvested. The bioactivities of SOD1 and SOD2, and the mRNA expression levels of SOD1, SOD2, PI3K, and AKT were detected. KEY FINDINGS: On day 1, the bioactivity of SOD1 increased significantly in Group I/R or Group P compared with Group S (P<0.05). On day 2, compared with Group S, the bioactivity of SOD1 increased significantly in Group P (P<0.05). On days 3, 5, and 7, the bioactivity of SOD1 decreased significantly respectively in Group I/R compared with Group S (P<0.05). On all timepoints, the bioactivity of SOD2 decreased significantly in Group I/R compared with Group S (P<0.05). There was a positive correlation between the SOD1 activity and the respective mRNA expression of SOD1, PI3K, and AKT. SIGNIFICANCE: Co-application of propofol preconditioning and postconditioning resulted in potent protective effects against spinal cord ischemia/reperfusion injury, which was associated with the increased expression of SOD1 in spinal cord tissues by activating PI3K/AKT signal pathway.