Respiratory diseases are major health concerns worldwide. Chronic respiratory diseases (CRDs) are the third leading cause of death worldwide and some of the most common are chronic obstructive pulmonary disease (COPD), asthma, occupational lung diseases, and pulmonary hypertension. Despite having different etiology and characteristics, these diseases share several features, such as a persistent inflammatory state, chronic oxidative stress, impaired mucociliary clearance, and increased alveolar surface tension. CRDs are not curable; however, various forms of treatment, that help restore airway patency and reduce shortness of breath, can improve daily life for people living with these conditions. In this regard myo-inositol may represent a valid therapeutic adjuvant approach due to its properties. Being a redox balancer, an inflammation modulator, and, most importantly, a component of pulmonary surfactant, it may improve lung function and counteract symptoms associated with respiratory diseases, as recently evidenced in patients with COPD, COVID-19, asthma, and bronchiectasis. The aim of this review is to evaluate the potential therapeutic role of myo-inositol supplementation in the management of patients with respiratory diseases.

Hypoxia-inducible factors (HIFs) are central regulators of gene expression in response to oxygen deprivation, a common feature in critical illnesses. The significant burden that critical illnesses place on global healthcare systems highlights the need for a deeper understanding of underlying mechanisms and the development of innovative treatment strategies. Among critical illnesses, impaired lung function is frequently linked to hypoxic conditions. This review focuses on the expression and regulation of HIF signalling in experimental models of acute lung injury (ALI) and clinical studies in critically ill patients with acute respiratory distress syndrome (ARDS). We explore the potential dual role of HIF signalling in acute lung inflammation. Furthermore, its role in key biological processes and its potential prognostic significance in clinical scenarios are discussed. Finally, we explore recent pharmacological advancements targeting HIF signalling, which have emerged as promising alternatives to existing therapeutic approaches, potentially enabling more effective management strategies.

Genetic association between SUMO-specific protease 1 (SENP1) and acute myeloid leukemia (AML) has been validated. However, the mechanism by which SENP1 affects AML proliferation, apoptosis, and autophagy remains unknown. The levels of SENP1 and polypyrimidine tract-binding protein 1 (PTBP1) were measured in patients with AML, AML cell lines, and xenograft tissues. The effects of SENP1 on AML proliferation, apoptosis, and beclin 1 (BECN1)-dependent autophagy were assessed through in vitro and in vivo loss- or gain-of-function experiments. SUMOylation analysis using immunoprecipitation (IP), RNA pull-down, RNA IP (RIP), and RNA stability assays were used to explore the molecular mechanism of SENP1 in AML development. The SENP1 level was elevated in AML samples. Silencing SENP1 impeded the development of AML, as evidenced by the inhibition of proliferation and promotion of G1-phase arrest and apoptosis resulting from SENP1 depletion in AML cells. Moreover, silencing of SENP1 restrained BECN1-depentent autophagy in AML cells. In addition, the overexpression of BECN1 or PTBP1 partially neutralized the effect of SENP1 knockdown on AML cell behavior. Mechanistically, SENP1 mediated PTBP1 deSUMOylation, which then directly interacted with BECN1 mRNA and enhanced its stability. In vivo experiments further confirmed the repressive effects of SENP1 suppression on AML development. Collectively, the SENP1/PTBP1/BECN1 signaling axis has been identified as a significant therapeutic target for enhancing AML treatment.

This review delves into the molecular complexities underpinning the epithelial-to-mesenchymal transition (EMT) induced by cigarette smoke (CS) in human bronchial epithelial cells (HBECs). The complex interplay of pathways, including those related to WNT//β-catenin, TGF-β/SMAD, hypoxia, oxidative stress, PI3K/Akt, and NF-κB, plays a central role in mediating this transition. While these findings significantly broaden our understanding of CS-induced EMT, the research reviewed herein leans heavily on 2D cell cultures, highlighting a research gap. Furthermore, the review identifies a stark omission of genetic and epigenetic factors in recent studies. Despite these shortcomings, the findings furnish a consolidated foundation not only for the academic community but also for the broader scientific and industrial sectors, including large tobacco companies and manufacturers of related products, both highlighting areas of current understanding and identifying areas for deeper exploration. The synthesis herein aims to propel further research, hoping to unravel the complexities of the EMT in the context of CS exposure. This review not only expands our understanding of CS-induced EMT but also reveals critical limitations in current methodologies, primarily the reliance on 2D cell cultures, which may not adequately simulate more complex biological interactions. Additionally, it highlights a significant gap in the literature concerning the genetic and epigenetic factors involved in CS-induced EMT, suggesting an urgent need for comprehensive studies that incorporate these types of experiments.

Sepsis-induced acute lung injury is associated with lung epithelial cell injury. This study analyzed the role of the antimicrobial peptide LL37 with mitochondrial DNA (LL37-mtDNA) and its potential mechanism of action in lipopolysaccharide (LPS)-treated rat type II alveolar epithelial cells (RLE-6TN cells). RLE-6TN cells were treated with LPS alone or with LL37-mtDNA, followed by transcriptome sequencing. Differentially expressed and pivotal genes were screened using bioinformatics tools. The effects of LL37-mtDNA on cell viability, inflammation, apoptosis, reactive oxygen species (ROS) production, and autophagy-related hallmark expression were evaluated in LPS-treated RLE-6TN cells. Additionally, the effects of Hsp90aa1 silencing following LL37-mtDNA treatment were investigated in vitro. LL37-mtDNA further suppressed cell viability, augmented apoptosis, promoted the release of inflammatory cytokines, increased ROS production, and elevated LC3B expression in LPS-treated RLE-6TN cells. Using transcriptome sequencing and bioinformatics, ten candidate genes were identified, of which three core genes were verified to be upregulated in the LPS + LL37-mtDNA group. Additionally, Hsp90aa1 downregulation attenuated the effects of LL37-mtDNA on LPS-treated RLE-6TN cells. Hsp90aa1 silencing possibly acted as a crucial target to counteract the effects of LL37-mtDNA on viability, apoptosis, inflammation, and autophagy activation in LPS-treated RLE-6TN cells.

Pulmonary fibrosis is one of the main reasons for the high mortality rate among acute respiratory distress syndrome (ARDS) patients. Mesenchymal stromal cell-derived microvesicles (MSC-MVs) have been shown to exert antifibrotic effects in lung diseases.

To investigate the effects and mechanisms of MSC-MVs on pulmonary fibrosis in ARDS mouse models.

MSC-MVs with low hepatocyte growth factor (HGF) expression (siHGF-MSC-MVs) were obtained via lentivirus transfection and used to establish the ARDS pulmonary fibrosis mouse model. Following intubation, respiratory mechanics-related indicators were measured via an experimental small animal lung function tester. Homing of MSC-MVs in lung tissues was investigated by near-infrared live imaging. Immunohistochemical, western blotting, ELISA and other methods were used to detect expression of pulmonary fibrosis-related proteins and to compare effects on pulmonary fibrosis and fibrosis-related indicators.

The MSC-MVs gradually migrated and homed to damaged lung tissues in the ARDS model mice. Treatment with MSC-MVs significantly reduced lung injury and pulmonary fibrosis scores. However, low expression of HGF (siHGF-MSC-MVs) significantly inhibited the effects of MSC-MVs (P < 0.05). Compared with the ARDS pulmonary fibrosis group, the MSC-MVs group exhibited suppressed expression of type I collagen antigen, type III collagen antigen, and the proteins transforming growth factor-β and α-smooth muscle actin, whereas the siHGF-MVs group exhibited significantly increased expression of these proteins. In addition, pulmonary compliance and the pressure of oxygen/oxygen inhalation ratio were significantly lower in the MSC-MVs group, and the effects of the MSC-MVs were significantly inhibited by low HGF expression (all P < 0.05).

MSC-MVs improved lung ventilation functions and inhibited pulmonary fibrosis in ARDS mice partly via HGF mRNA transfer.

Intervertebral disc degeneration (IVDD) is a main cause of low back pain (LBP), which can lead to disability and thus generate a heavy burden on society. IVDD is characterized by a decrease in nucleus pulposus cells (NPCs) and endogenous mesenchymal stem cells (MSCs), degradation of the extracellular matrix, macrophage infiltration, and blood vessel and nerve ingrowth. To date, the therapeutic approaches regarding IVDD mainly include conservative treatment and surgical intervention. However, both can only relieve symptoms rather than stop or revert the progression of IVDD, since the pathogenesis of IVDD is not yet clear. Pyroptosis, which is characterized by Caspase family dependence and conducted by the Gasdermin family, is a newly discovered mode of programmed cell death. Pyroptosis has been observed in NPCs, annulus fibrosus cells (AFCs), chondrocytes, MSCs, macrophages, vascular endothelial cells and neurons and may contribute to IVDD. MSCs are a kind of pluripotent stem cell that can be found in almost all tissues. MSCs have a strong ability to secrete extracellular vesicles (EVs), which contain exosomes, microvesicles and apoptotic bodies. EVs derived from MSCs play an important role in pyroptosis regulation and could be beneficial for alleviating IVDD. This review focuses on clarifying the regulation of pyroptosis to improve IVDD by MSCs and EVs derived from MSCs.

Alveolar epithelial cell injury is a key factor in the occurrence and development of pulmonary acute respiratory distress syndrome (ARDSp). Yet the gene expression profile of alveolar epithelial cells of patients with ARDSp remains unclear.

We analyzed single nuclear RNA sequencing (snRNA-Seq) data from autopsy lung tissues of both ARDSp patients and healthy donors. Sequence data for type 2 alveolar epithelizal cells (AT2) were extracted by the Seurat package. Differentially expressed genes (DEGs) in AT2 were identified by the criteria |log2FC| ≥ 0.25 and P < 0.05 with DESeq2. A protein interaction network was constructed using Search Tool for the Retrieval of Interacting Genes (STRING) and Cytoscape software to identify hub genes. We then constructed an ARDSp rat model through induction by lipopolysaccharide (LPS) airway instillation. Left lung RNA was extracted and sequenced via Illumina Hiseq platforms. Analysis of the rat RNA sequencing data was then used to verify hub genes. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed on the identified hub genes.

In AT2, a total of 289 genes were identified as differentially expressed between those from ARDSp patients and healthy donors, and these included 190 upregulated and 99 downregulated genes. Ten hub genes were further identified (RPS27A, ACTG1, CAV1, HSP90AA1, HSPA5, CCND1, ITGA3, B2M, NEDD4L, and SEMA5A). There was a similar expression trend of HSPA5 between rat RNA and snRNA sequencing data.

ARDSp altered the gene expression profile of AT2. The identified hub genes were enriched in biological processes mainly involved in cell growth and transformation. Relatedly, ferroptosis and autophagy are possibly involved in AT2 injury during ARDSp. These novel insights into ARDSp may aid the discovery of potential targets for the diagnosis and treatment of ARDSp.