The role and mechanism of AMPK in pulmonary hypertension.

Pulmonary hypertension (PH) is a chronic progressive disease with high mortality. There has been more and more research focusing on the role of AMPK in PH. AMPK consists of three subunits-α, ß, and γ. The crosstalk among these subunits ultimately leads to a delicate balance to affect PH, which results in conflicting conclusions about the role of AMPK in PH. It is still unclear how these subunits interfere with each other and achieve balance to improve or deteriorate PH. Several signaling pathways are related to AMPK in the treatment of PH, including AMPK/eNOS/NO pathway, Nox4/mTORC2/AMPK pathway, AMPK/BMP/Smad pathway, and SIRT3-AMPK pathway. Among these pathways, the role and mechanism of AMPK/eNOS/NO and Nox4/mTORC2/AMPK pathways are clearer than others, while the SIRT3-AMPK pathway remains still unclear in the treatment of PH. There are drugs targeting AMPK to improve PH, such as metformin (MET), MET combination, and rhodiola extract. In addition, several novel factors target AMPK for improving PH, such as ADAMTS8, TUFM, and Salt-inducible kinases. However, more researches are needed to explore the specific AMPK signaling pathways involved in these novel factors in the future. In conclusion, AMPK plays an important role in PH.

NLRP3 Inflammasome Triggers Inflammation of Obstructive Sleep Apnea.

Obstructive sleep apnea [OSA] is widespread in the population and affects as many as one billion people worldwide. OSA is associated with dysfunction of the brain system that controls breathing, which leads to intermittent hypoxia [IH], hypercapnia, and oxidative stress [OS]. The number of NOD-like receptor family pyrin domain-containing [NLRP3] inflammasome was increased after IH, hypercapnia, and OS. NLRP3 inflammasome is closely related to inflammation. NLRP3 inflammasome causes a series of inflammatory diseases by activating IL-1ß and IL-18. Subsequently, NLRP3 inflammasome plays an important role in the complications of OSA, including Type 2 diabetes [T2DM], coronary heart disease [CHD], hypertension, neuroinflammation, and depression. This review will introduce the basic composition and structure of the NLRP3 inflammasome and focus on the relationship between the NLRP3 inflammasome and OSA and OSA complications. We can deeply understand how NLRP3 inflammasome is strongly associated with OSA and OSA complications.

MST1/2 in inflammation and immunity.

The mammalian Sterile 20-like kinase 1/2 (MST1/2) belongs to the serine/threonine (GC) protein kinase superfamily. Collective studies confirm the vital role MST1/2 in inflammation and immunity. MST1/2 is closely related to the progress of inflammation. Generally, MST1/2 aggravates the inflammatory injury through MST1-JNK, MST1-mROS, MST1-Foxo3, and NF-κB pathways, as well as several regulatory factors such as tumor necrosis factor-α (TNF-α), mitochondrial extension factor 1 (MIEF1), and lipopolysaccharide (LPS). Moreover, MST1/2 is also involved in the regulation of immunity to balance immune activation and tolerance by regulating MST1/2-Rac, MST1-Akt1/c-myc, MST1-Foxos, MST1-STAT, Btk pathways, and lymphocyte function-related antigen 1 (LFA-1), which subsequently prevents immunodeficiency syndrome and autoimmune diseases. This article reviews the effects of MST1/2 on inflammation and immunity.

Analysis of characteristics related to interstitial lung disease or pulmonary hypertension in patients with dermatomyositis.

INTRODUCTION: Dermatomyositis (DM) is often associated with interstitial lung disease (ILD) or pulmonary hypertension (PH). The aim of this study was to investigate the clinical characteristics of DM patients with ILD or PH. METHODS: This study retrospectively analysed the clinical characteristics of 372 patients with DM, including cytokines, lymphocyte subsets, immunoglobulin and complement. The DM patients were divided into different groups according to whether complicated with ILD, PH or anti-melanoma differentiation-associated gene 5 antibodies (MDA5). A qualitative and quantitative data analysis was performed. RESULTS: IgG, IgA and IgM in the DM-associated ILD (ILD-DM) were higher than that of the DM non-complicating ILD (Non-ILD-DM) (p = 0.022, 0.002 and 0.029, respectively). Meanwhile, IL-6 (p = 0.008) and IL-10 (p = 0.001) were increased in the DM-associated PH (PH-DM) than in the DM non-complicating PH (Non-PH-DM), while IL-17 (p = 0.004), double positive (DP) cell ratio and B lymphocyte ratio were reduced in the PH-DM. Moreover, the incidence of ILD and levels of C4 were higher in the DM with MDA5 (MDA5+ DM) than that of the DM without MDA5. CONCLUSION: ILD-DM has higher IgG, IgA and IgM than that of Non-ILD-DM. PH-DM has higher IL-6, IL-10 and lower IL-17, DP cell ratio and B lymphocyte ratio than that of Non-PH-DM.