Integrative analysis of gene expression and chromatin dynamics multi-omics data in mouse models of bleomycin-induced lung fibrosis.

Background: Pulmonary fibrosis is a relentless and ultimately fatal lung disorder. Despite a wealth of research, the intricate molecular pathways that contribute to the onset of PF, especially the aspects related to epigenetic modifications and chromatin dynamics, continue to be elusive and not fully understood.

Methods: Utilizing a bleomycin-induced pulmonary fibrosis model, we conducted a comprehensive analysis of the interplay between chromatin structure, chromatin accessibility, gene expression patterns, and cellular heterogeneity.

Inhibition of macrophage inflammasome assembly and pyroptosis with GC-1 ameliorates acute lung injury.

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a critical syndrome with a mortality rate of up to 40%, and it is characterized by a prominent inflammatory cascade. The inflammasome and pyroptosis play crucial regulatory roles in regulating various inflammatory-related diseases by serving as pivotal signaling platforms for inflammatory responses and mediating the release of substantial quantities of inflammatory factors. Our previous studies confirmed that GC-1, a clinical-stage thyroid hormone analog, effectively mitigated pulmonary fibrosis by restoring mitochondrial function in epithelial cells.

YAP/TAZ as master regulators in liver regeneration and disease: insights into mechanisms and therapeutic targets.

Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) are key downstream effectors of the Hippo pathway that regulate organ size, tissue homeostasis, and cancer development. YAP/TAZ play crucial regulatory roles in organ growth, cell proliferation, cell renewal, and regeneration. Mechanistically, YAP/TAZ influence the occurrence and progression of liver regeneration (LR) through various signaling pathways, including Notch, Wnt/β-catenin, TGF-β/Smad.

Fatty acid synthase inhibition alleviates lung fibrosis via β-catenin signal in fibroblasts.

Idiopathic pulmonary fibrosis is a progressive and lethal interstitial lung disease with an unclear etiology and limited treatment options. Fatty acid synthase (FASN) plays various roles in metabolic-related diseases. This study demonstrates that FASN expression is increased in fibroblasts from the lung tissues of patients with idiopathic pulmonary fibrosis and in bleomycin-treated mice.

Lactate activates ER stress to promote alveolar epithelial cells apoptosis in pulmonary fibrosis.

Pulmonary fibrosis (PF) is a chronic, progressive lung disease characterized by fibroblast proliferation, extensive extracellular matrix and collagen deposition, accompanied by inflammatory damage, ultimately leading to death due to respiratory failure. Endoplasmic reticulum (ER) stress in pulmonary fibrotic tissue is indeed recognized as a significant factor exacerbating PF development. Emerging evidences indicated a potential association between ER stress induced by lactate and cellular apoptosis in PF.

The role of the cytoskeleton in fibrotic diseases.

Fibrosis is the process whereby cells at a damaged site are transformed into fibrotic tissue, comprising fibroblasts and an extracellular matrix rich in collagen and fibronectin, following damage to organs or tissues that exceeds their repair capacity. Depending on the affected organs or tissues, fibrosis can be classified into types such as pulmonary fibrosis, hepatic fibrosis, renal fibrosis, and cardiac fibrosis. The primary pathological features of fibrotic diseases include recurrent damage to normal cells and the abnormal activation of fibroblasts, leading to excessive deposition of extracellular matrix and collagen in the intercellular spaces.

RegⅢγ promotes the proliferation, and inhibits inflammation response of macrophages by Akt, STAT3 and NF-κB pathways.

As an inflammatory regulator, intestinal regenerating islet-derived 3 gamma (RegⅢγ) contributes to alleviating liver injury in liver diseases and colitis. However, it is unclear whether hepatic RegⅢγ exerts a vital impact on liver regeneration (LR). In this study, the expression profile and localization of RegⅢγ in LR were demonstrated by microarray analysis, qRT-PCR and immunofluorescence staining.

Comparative plastome analysis of Arundinelleae (Poaceae, Panicoideae), with implications for phylogenetic relationships and plastome evolution.

Background: Arundinelleae is a small tribe within the Poaceae (grass family) possessing a widespread distribution that includes Asia, the Americas, and Africa. Several species of Arundinelleae are used as natural forage, feed, and raw materials for paper. The tribe is taxonomically cumbersome due to a paucity of clear diagnostic morphological characters.

TRβ activation confers AT2-to-AT1 cell differentiation and anti-fibrosis during lung repair via KLF2 and CEBPA.

Aberrant repair underlies the pathogenesis of pulmonary fibrosis while effective strategies to convert fibrosis to normal regeneration are scarce. Here, we found that thyroid hormone is decreased in multiple models of lung injury but is essential for lung regeneration. Moreover, thyroid hormone receptor α (TRα) promotes cell proliferation, while TRβ fuels cell maturation in lung regeneration.

The Thyroid Hormone Analog GC-1 Mitigates Acute Lung Injury by Inhibiting M1 Macrophage Polarization.

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a life-threatening condition with a high mortality rate of ≈40%. Thyroid hormones (THs) play crucial roles in maintaining homeostasis of the cellular microenvironment under stress. The previous studies confirmed that the clinical-stage TH analog GC-1 significantly alleviates pulmonary fibrosis by improving the function of mitochondria in epithelial cells.

Triiodothyronine acts on DAO to regulate pulmonary fibrosis progression by facilitating cell senescence through the p53/p21 signaling pathway.

Background: Idiopathic pulmonary fibrosis (IPF) is the result of multiple cycles of epithelial cell injury and fibroblast activation; currently, there is no clear etiology. Increasing evidence suggests that protein metabolism and amino acids play a crucial role in IPF, but the role of D-amino acids is not yet clear. The aim of this study was to identify novel mediators in order to test the hypothesis that D-amino acid oxidase (DAO) plays a significant role in the pathogenesis of IPF.

Assessing the impact of triiodothyronine treatment on the lung microbiome of mice with pulmonary fibrosis.

Background: Idiopathic pulmonary fibrosis (IPF), an interstitial lung disease, is characterized by the exacerbation of progressive pulmonary fibrosis (PF). IPF primarily affects older individuals and can lead to respiratory failure. This study aimed to assess the effects of triiodothyronine (T) treatment on the lung microbiome of mice with PF.

Induction of hepatic fibrosis in mice with schistosomiasis by extracellular microRNA-30 derived from eggs.

Background: Schistosomiasis is a zoonotic parasitic disorder induced by the infestation of schistosomes, a genus of trematodes. MicroRNAs (miRNAs) in egg-derived exosomes are crucial for modulating the host's immune responses and orchestrating the pathophysiological mechanisms. Although the exosomes secreted by contain abundant miRNAs, the specific roles of these miRNAs in the pathogenesis of schistosomiasis-induced hepatic fibrosis are yet to be comprehensively elucidated.

Comprehensive proteomic characterization of urethral stricture disease in the Chinese population.

Background: Male urethral stricture disease (USD) is predominantly characterized by scar formation. There are few effective therapeutic drugs, and comprehensive molecular characterizations of USD formation remain undefined.

Methods: The proteomic profiling of twelve scar tissues and five matched normal adjacent tissues (NATs).

Proteomic Profiling of Serum Extracellular Vesicles Identifies Diagnostic Signatures and Therapeutic Targets in Breast Cancer.

Analysis of extracellular vesicles (EV) is a promising noninvasive liquid biopsy approach for breast cancer detection, prognosis, and therapeutic monitoring. A comprehensive understanding of the characteristics and proteomic composition of breast cancer-specific EVs from human samples is required to realize the potential of this strategy. In this study, we applied a mass spectrometry-based, data-independent acquisition proteomic approach to characterize human serum EVs derived from patients with breast cancer (n = 126) and healthy donors (n = 70) in a discovery cohort and validated the findings in five independent cohorts.

Aging-Associated Metabolite Methylmalonic Acid Increases Susceptibility to Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease characterized by pulmonary fibroblast overactivation, resulting in the accumulation of abnormal extracellular matrix and lung parenchymal damage. Although the pathogenesis of IPF remains unclear, aging was proposed as the most prominent nongenetic risk factor. Propionate metabolism undergoes reprogramming in the aging population, leading to the accumulation of the by-product methylmalonic acid (MMA).

Lactate facilitated mitochondrial fission-derived ROS to promote pulmonary fibrosis via ERK/DRP-1 signaling.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrotic interstitial lung diseases, which mainly existed in middle-aged and elderly people. The accumulation of reactive oxygen species (ROS) is a common characteristic of IPF. Previous research also shown that lactate levels can be abnormally elevated in IPF patients.

Effect of LRRC15 on autophagy in A549 cells.

Idiopathic pulmonary fibrosis (IPF) is a progressive, chronic, and irreversible interstitial lung disease with unknown cause. To explore the role and regulatory mechanism of leucine-rich repeat-containing protein 15 (LRRC15) in IPF, bleomycin (BLM)-induced pulmonary fibrosis in mouse and A549 cells were constructed, and the expression of LRRC15 were detected. Then, MTT, GFP-RFP-LC3 dual fluorescent labeling system and Western blotting were used to investigate the effects of LRRC15 on cell activity and autophagy after transfection of siLRRC15, respectively.

CCT6A alleviates pulmonary fibrosis by inhibiting HIF-1α-mediated lactate production.

Idiopathic pulmonary fibrosis (IPF) is a lethal progressive fibrotic lung disease. The development of IPF involves different molecular and cellular processes, and recent studies indicate that lactate plays a significant role in promoting the progression of the disease. Nevertheless, the mechanism by which lactate metabolism is regulated and the downstream effects remain unclear.

Downregulation of HMGCS2 mediated AECIIs lipid metabolic alteration promotes pulmonary fibrosis by activating fibroblasts.

Background: Abnormal lipid metabolism has recently been reported as a crucial signature of idiopathic pulmonary fibrosis (IPF). However, the origin and biological function of the lipid and possible mechanisms of increased lipid content in the pathogenesis of IPF remains undetermined.

Methods: Oil-red staining and immunofluorescence analysis were used to detect lipid accumulation in mouse lung fibrosis frozen sections, Bleomycin-treated human type II alveolar epithelial cells (AECIIs) and lung fibroblast.

Repair and regeneration of the alveolar epithelium in lung injury.

Considerable progress has been made in understanding the function of alveolar epithelial cells in a quiescent state and regeneration mechanism after lung injury. Lung injury occurs commonly from severe viral and bacterial infections, inhalation lung injury, and indirect injury sepsis. A series of pathological mechanisms caused by excessive injury, such as apoptosis, autophagy, senescence, and ferroptosis, have been studied.

Hibiscus manihot L. flower extract induces anticancer activity through modulation of apoptosis and autophagy in A549 cells.

Lung cancer is a major public health issue and heavy burden in China and worldwide due to its high incidence and mortality without effective treatment. It's imperative to develop new treatments to overcome drug resistance. Natural products from food source, given their wide-ranging and long-term benefits, have been increasingly used in tumor prevention and treatment.

NR2F2 alleviates pulmonary fibrosis by inhibition of epithelial cell senescence.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fatal, and aging-associated interstitial lung disease with a poor prognosis and limited treatment options, while the pathogenesis remains elusive. In this study, we found that the expression of nuclear receptor subfamily 2 group F member 2 (NR2F2), a member of the steroid thyroid hormone superfamily of nuclear receptors, was reduced in both IPF and bleomycin-induced fibrotic lungs, markedly in bleomycin-induced senescent epithelial cells. Inhibition of NR2F2 expression increased the expression of senescence markers such as p21 and p16 in lung epithelial cells, and activated fibroblasts through epithelial-mesenchymal crosstalk, inversely overexpression of NR2F2 alleviated bleomycin-induced epithelial cell senescence and inhibited fibroblast activation.

Differential DNA methylation landscape of miRNAs genes in mice liver fibrosis.

Background: Patients with chronic liver disease were found nearly all to have liver fibrosis, which is characterized by excess accumulation of extracellular matrix (ECM) proteins. While ECM accumulation can prevent liver infection and injury, it can destroy normal liver function and architecture. miRNA's own regulation was involved in DNA methylation change.