Macrophage microvesicle-derived circ_YTHDF2 in methamphetamine-induced chronic lung injury.

Long-term abuse of methamphetamine (MA) can cause lung toxicity. Intercellular communication between macrophages and alveolar epithelial cells (AECs) is critical for maintaining lung homeostasis. Microvesicles (MVs) are an important medium of intercellular communication. However, the mechanism of macrophage MVs (MMVs) in MA-induced chronic lung injury remains unclear. This study aimed to investigate if MA can augment the activity of MMVs and if circ_YTHDF2 is a key factor in MMV-mediated macrophage-AEC communication, and to explore the mechanism of MMV-derived circ_YTHDF2 in MA-induced chronic lung injury. MA elevated peak velocity of the pulmonary artery and pulmonary artery accelerate time, reduced the number of alveolar sacs, thickened the alveolar septum, and accelerated the release of MMVs and the uptake of MMVs by AECs. Circ_YTHDF2 was downregulated in lung and MMVs induced by MA. The immune factors in MMVs were increased by si-circ_YTHDF. Circ_YTHDF2 knockdown in MMVs induced inflammation and remodelling in the internalised AECs by MMVs, which was reversed by circ_YTHDF2 overexpression in MMVs. Circ_YTHDF2 bound specifically to and sponged miRNA-145-5p. Runt-related transcription factor 3 (RUNX3) was identified as potential target of miR-145-5p. RUNX3 targeted zinc finger E-box-binding homeobox 1 (ZEB1)-related inflammation and EMT of AECs. In vivo, circ_YTHDF2 overexpression-MMVs attenuated MA-induced lung inflammation and remodelling by the circ_YTHDF2-miRNA-145-5p-RUNX3 axis. Therefore, MA abuse can induce pulmonary dysfunction and alveolus injury. The immunoactivity of MMVs is regulated by circ_YTHDF2. Circ_YTHDF2 in MMVs is the key to communication between macrophages and AECs. Circ_YTHDF2 sponges miR-145-5p targeting RUNX3 to participate in ZEB1-related inflammation and remodelling of AECs. MMV-derived circ_YTHDF2 would be an important therapeutic target for MA-induced chronic lung injury. KEY POINTS: Methamphetamine (MA) abuse induces pulmonary dysfunction and alveoli injury. The immunoactivity of macrophage microvesicles (MMVs) is regulated by circ_YTHDF2. Circ_YTHDF2 in MMVs is the key to MMV-mediated intercellular communication between macrophages and alveolar epithelial cells. Circ_YTHDF2 sponges miR-145-5p targeting runt-related transcription factor 3 (RUNX3) to participate in zinc finger E-box-binding homeobox 1 (ZEB1)-related inflammation and remodelling. MMV-derived circ_YTHDF2 would be an important therapeutic target for MA-induced chronic lung injury.

ZEB1: New advances in fibrosis and cancer.

Zinc finger E-box binding homeobox 1 (ZEB1) is an important transcription factor in epithelial mesenchymal transition (EMT) which participates in the numerous life processes, such as embryonic development, fibrosis and tumor progression. ZEB1 has multiple functions in human body and plays a crucial part in some life processes. ZEB1 is vital for the formation and development of the organs in the embryonic period. The abnormal expression of ZEB1 is a predictor for the poor prognosis or the poor survival in several cancers. ZEB1 contributes to the occurrence of fibrosis, cancer and even chemoresistance. Some research is indicated that fibrosis is finally developed into the cancers. Therefore, ZEB1 is probably taken as a biomarker in fibrosis or cancer. In this review, it is predicted of the structure of ZEB1 and the protein binding sites of ZEB1 with some protein, and it is discussed about the roles of ZEB1 in fibrosis and cancer progression to elaborate the potential applications of ZEB1 in clinic.

Non-coding RNA: insights into the mechanism of methamphetamine neurotoxicity.

Chronic exposure of the methamphetamine has been shown to lead to neurotoxicity in rodents and humans. The manifestations of methamphetamine neurotoxicity include methamphetamine use disorder, methamphetamine abuse, methamphetamine addiction and methamphetamine behavioral sensitization. Repeated use of methamphetamine can cause methamphetamine use disorder. The abuse and addiction of methamphetamine are growing epidemic worldwide. Repeated intermittent exposure to methamphetamine can cause behavioral sensitization. In addition, many studies have shown that changes in the expression of non-coding RNA in the ventral tegmental area and nucleus accumbens will affect the behavioral effects of methamphetamine. Non-coding RNA plays an important role in the behavioral effects of methamphetamine. Therefore, it is important to study the relationship between methamphetamine and non-coding RNA. The purpose of this review is to study the non-coding RNA associated with methamphetamine neurotoxicity to search for the possible therapeutic target of the methamphetamine neurotoxicity.

Calcium-sensing receptor in the development and treatment of pulmonary hypertension.

Calcium-sensing receptor (CaSR) is widely involved in the cell proliferation, differentiation, migration, adhesion and apoptosis, which can affect the vascular remodeling in the humanbody. The main ligand of CaSR is extracellular Ca2+. CaSR has the physiological significance in Ca2+ homeostasis. Pulmonary vascular remodeling is one of the main histopathological changes of pulmonary hypertension (PH). The abnormal proliferation of pulmonary artery smooth muscle cells (PASMCs) results in the pulmonary vascular remodeling. CaSR is an important regulator of [Ca2+]i. [Ca2+]i is the main cause of the excessive pulmonary vascular remodeling in patients with PH. In this review, it was conclued that the structure of CaSR was prone to explore the devolopment or the treatment of PH. It was found that the regulation of CaSR with some miRNA could inhibit the proliferation of PASMCs, and that CaSR could affect the occurrence of autophagy in PH. Therefore, CaSR would become a new therapeutic target to PH.

[Progress of researches on acupuncture treatment of allergic rhinitis].

Acupuncture therapy has been widely used in clinical treatment of allergic rhinitis (AR), and can induce a positive therapeutic effect through multi-targets and multi-aspects. In recent 10 years, the research on the mechanisms of acupuncture in treating AR mainly focused on humoral immunity, cellular immunity, cell apoptosis, inflammatory mediators and factors, neuropeptides, etc. By regulating the level of immunoglobulin in the blood, acupuncture intervention can restore the relative balance of cellular immune response, reduce the accumulation of eosinophils and promote apoptosis, down-regulate the expression of related inflammatory mediators and factors, regulate the excitability of related nerves, modulate the release of neuropeptides and other ways to diminish the inflammatory reaction of nasal mucosa, and enhance the repair and protection of nasal mucosa, relieve the nasal symptoms at last. On the basis of the existing studies, the follow-up research should make use of the advantages of acupuncture intervention, refine the treatment process, and deeply explore the feasibility of acupuncture treatment of AR, further promote the combination of mechanism study and clinical practice, provide references for clinical application. Moreover, some shortcomings exist, for example, the unknown correlation between the therapeutic effect and duration of treatment, the unknown correlation between the effect of acupuncture and various targets, and disconnection between experimental research achievements and clinical application, etc.

Microvesicles-mediated Cell Communication in Pulmonary Arterial Hypertension.

BACKGROUND: Pulmonary arterial hypertension is one of the chronic diseases that affect human health. Microvesicles participate in the communication between cells by fusing with the recipient cells to transfer the bioactive molecules, such as lipids, proteins, RNA, etc., to the target cells. Microvesicles are involved in various biological processes and have the functions of regulating immunity, promoting angiogenesis, and so on. Microvesicles derived from various cells may become the diagnostic biomarkers or therapeutic targets for the diseases. Therefore, exploring the role of microvesicles-mediated cell communication has become a potential therapeutic target for pulmonary arterial hypertension. OBJECTIVE: It is to clarify the classification, features, and mechanism of microvesicles in cell communication and to discuss the potentially important roles of microvesicles-mediated cell communication in pulmonary arterial hypertension. RESULTS: Inflammation is an important pathogenesis of pulmonary arterial hypertension. Many studies have shown that microvesicles from different cells can participate in the pathological process of pulmonary arterial hypertension by transferring the inflammatory factors contained in them. CONCLUSION: Microvesicles-mediated cell communication may become the therapeutic target for pulmonary arterial hypertension.

RUNX3-dependent oxidative epithelial-to-mesenchymal transition in methamphetamine-induced chronic lung injury.

Lung toxicity is the main cause of the death from methamphetamine (MA) abuse, but its mechanism has remained unclear. The purpose of our study was to investigate if MA can induce epithelial-to-mesenchymal transition (EMT) and if RUNX3 is involved in oxidative EMT in MA-induced chronic lung injury. The rats were divided into the control group and MA group. Extracted lungs were used for morphological measurements and Western blot. The alveolar epithelial cells were cultured or transfected and then treated with MA or/and N-acetyl cysteine (NAC) followed by flow cytometry, Western blot, and immunohistochemistry. Chronic exposure to MA resulted in the lower growth ratio of weight, increased right ventricular index, thickened alveolar walls, and reduced number of alveolar sacs. Long-term administration with MA caused oxidative stress and pulmonary EMT. NAC increased RUNX3 and alleviated EMT. However, after knockdown of RUNX3, reactive oxygen species (ROS) levels were significantly upregulated, indicating that RUNX3 was closely related to oxidative stress. Knockdown of RUNX3 aggravated MA-induced EMT by activating RUNX3-dependent TGF-ß signaling. Therefore, RUNX3 may be the key to oxidative EMT in methamphetamine-induced chronic lung injury.

Resveratrol protects the integrity of alveolar epithelial barrier via SIRT1/PTEN/p-Akt pathway in methamphetamine-induced chronic lung injury.

OBJECTIVES: SIRT1 is an antioxidative factor, but its mechanism in methamphetamine (MA)-induced lung injury remains unclear. The purpose of this study is to determine whether MA can disrupt the integrity of alveolar epithelial barrier, whether SIRT1 is involved in MA-induced chronic lung injury and whether Resveratrol (Res) can protect the integrity of alveolar epithelial cells by regulating ROS to activate SIRT1/PTEN/p-Akt pathway. MATERIALS AND METHODS: The rats were randomly divided into control group and MA group. Extracted lungs were detected by Western blot, HE staining and immunohistochemistry. The alveolar epithelial cells were treated with MA or/and Res, following by Western blot, LDH leakage assay and flow cytometry. MOE is used for bio-informatics prediction. RESULTS: Chronic exposure to MA can cause slower growth ratio of weight, increased RVI and induced lung injury including the reduced number of alveolar sacs and the thickened alveolar walls. MA-induced apoptosis was associated with SIRT1-related oxidative stress. Res suppressed ROS levels, activated SIRT1, negatively regulated PTEN, phosphorylated Akt, reduced LDH leakage, increased the expression of ZO-1 and E-cadherin and inhibited the apoptosis of alveolar epithelial cells to attenuate MA-induced higher permeability of alveolar epithelium. CONCLUSIONS: MA disrupted the integrity of alveolar epithelial barrier. Res inhibited oxidative stress and reversed MA-induced higher permeability and apoptosis of alveolar epithelium by the activation of SIRT1/PTEN/p-Akt pathway.