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.

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).

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.

TRIOBP modulates β-catenin signaling by regulation of miR-29b in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a fatal and devastating lung disease of unknown etiology, described as the result of multiple cycles of epithelial cell injury and fibroblast activation. Despite this impressive increase in understanding, a therapy that reverses this form of fibrosis remains elusive. In our previous study, we found that miR-29b has a therapeutic effect on pulmonary fibrosis.

Tuftelin1 drives experimental pulmonary fibrosis progression by facilitating stress fiber assembly.

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease (ILD) with unknown etiology, characterized by sustained damage repair of epithelial cells and abnormal activation of fibroblasts, the underlying mechanism of the disease remains elusive.

Methods: To evaluate the role of Tuftelin1 (TUFT1) in IPF and elucidate its molecular mechanism. We investigated the level of TUFT1 in the IPF and bleomycin-induced mouse models and explored the influence of TUFT1 deficiency on pulmonary fibrosis.

ACSS3 regulates the metabolic homeostasis of epithelial cells and alleviates pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease of unknown etiology. The emerging evidence demonstrates that metabolic homeostatic imbalance caused by repetitive injuries of the alveolar epithelium is the potential pathogenesis of IPF. Proteomic analysis identified that Acetyl-CoA synthetase short chain family member 3 (ACSS3) expression was decreased in IPF patients and mice with bleomycin-induced fibrosis.

Single-Cell RNA Sequencing Provides New Insights into Therapeutic Roles of Thyroid Hormone in Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive fatal interstitial lung disease without an effective cure. Herein, we explore the role of 3,5,3'-triiodothyronine (T) administration on lung alveolar regeneration and fibrosis at the single-cell level. T supplementation significantly altered the gene expression in fibrotic lung tissues.

High-Fat Diet Related Lung Fibrosis-Epigenetic Regulation Matters.

Pulmonary fibrosis (PF) is an interstitial lung disease characterized by the destruction of the pulmonary parenchyma caused by excessive extracellular matrix deposition. Despite the well-known etiological factors such as senescence, aberrant epithelial cell and fibroblast activation, and chronic inflammation, PF has recently been recognized as a metabolic disease and abnormal lipid signature was observed both in serum and bronchoalveolar lavage fluid (BALF) of PF patients and mice PF model. Clinically, observational studies suggest a significant link between high-fat diet (HFD) and PF as manifested by high intake of saturated fatty acids (SFAs) and meat increases the risk of PF and mice lung fibrosis.

Serum Proteomics Identifies Biomarkers Associated With the Pathogenesis of Idiopathic Pulmonary Fibrosis.

The heterogeneity of idiopathic pulmonary fibrosis (IPF) limits its diagnosis and treatment. The association between the pathophysiological features and the serum protein signatures of IPF currently remains unclear. The present study analyzed the specific proteins and patterns associated with the clinical parameters of IPF based on a serum proteomic dataset by data-independent acquisition using MS.

Fenbendazole Attenuates Bleomycin-Induced Pulmonary Fibrosis in Mice via Suppression of Fibroblast-to-Myofibroblast Differentiation.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and fatal interstitial lung disease with unknown etiology. Despite substantial progress in understanding the pathogenesis of pulmonary fibrosis and drug development, there is still no cure for this devastating disease. Fenbendazole (FBZ) is a benzimidazole compound that is widely used as an anthelmintic agent and recent studies have expanded the scope of its pharmacological effects and application prospect.

Mechanical forces: The missing link between idiopathic pulmonary fibrosis and lung cancer.

Patients with idiopathic pulmonary fibrosis (IPF) have a high risk of developing lung cancer compared with the general population. The morbidity of lung cancer in IPF patient ranges from 3% to 22%, and in some cases exceeds 50%, and these patients have a reduced survival time. However, the mechanisms through which IPF increases the morbidity and mortality in lung cancer remain unclear.

Identification of SRY-box 30 as an age-related essential gatekeeper for male germ-cell meiosis and differentiation.

Although important factors governing the meiosis have been reported in the embryonic ovary, meiosis in postnatal testis remains poorly understood. Herein, we first report that SRY-box 30 (Sox30) is an age-related and essential regulator of meiosis in the postnatal testis. Sox30-null mice exhibited uniquely impaired testis, presenting the abnormal arrest of germ-cell differentiation and irregular Leydig cell proliferation.

Alveolar cells under mechanical stressed niche: critical contributors to pulmonary fibrosis.

Pulmonary fibrosis arises from the repeated epithelial mild injuries and insufficient repair lead to over activation of fibroblasts and excessive deposition of extracellular matrix, which result in a mechanical stretched niche. However, increasing mechanical stress likely exists before the establishment of fibrosis since early micro injuries increase local vascular permeability and prompt cytoskeletal remodeling which alter cellular mechanical forces. It is noteworthy that COVID-19 patients with severe hypoxemia will receive mechanical ventilation as supportive treatment and subsequent pathology studies indicate lung fibrosis pattern.

SOX30 is a prognostic biomarker and chemotherapeutic indicator for advanced-stage ovarian cancer.

The authors and journal apologize for errors in the above paper, which appeared in volume 26 part 3, pages 303–319. The errors relate to the legend of Fig. 1A on page 307 and the artwork of Fig.

Overexpression of microRNA-301b accelerates hippocampal microglia activation and cognitive impairment in mice with depressive-like behavior through the NF-κB signaling pathway.

Depression is a condition with a complex etiological pattern, whose effective treatments are highly limited. MicroRNAs (miRNAs) have been investigated in intensive studies owing to their involvement in pathophysiology of mood disorders. The current study aimed to elucidate the role of miR-301b in hippocampus in mouse models of depressive-like behavior.

SOX30 is a prognostic biomarker and chemotherapeutic indicator for advanced-stage ovarian cancer.

New potential biomarkers and therapeutic targets for ovarian cancer should be identified. The amplification in chromosomal region 5q31-5q35.3 exhibits the strongest correlation with overall survival (OS) of ovarian cancer.

Up-regulated miR-192-5p expression rescues cognitive impairment and restores neural function in mice with depression via the Fbln2-mediated TGF-β1 signaling pathway.

Depression represents a condition characterized by cognitive deficits and neural dysfunction and has recently been correlated with microRNAs (miRs) and their respective target genes. The present study was conducted with the goal of investigating the expression of miR-192-5p and its target gene fibulin (Fbln)-2 in an attempt to evaluate their roles in the occurrence and progression of cognitive impairment and neural function in mice with chronic unpredictable mild stress (CUMS)-induced depression through regulation of the TGF-β1 signal transduction pathway. Verification of the targeting relationship between miR-192-5p and Fbln2 was provided in the form of initial bioinformatics prediction, followed by a further verification in the form of a dual-luciferase reporter gene assay.

SOX30 Inhibits Tumor Metastasis through Attenuating Wnt-Signaling via Transcriptional and Posttranslational Regulation of β-Catenin in Lung Cancer.

Although high mortality of lung cancer is greatly due to distant metastasis, the mechanism of this metastasis remains unclear. Here, we investigate in lung cancer that SOX30 is sharply under-expressed in metastatic tumors compared with non-metastatic tumors, and suppresses plenty of metastasis related processes or pathways. SOX30 strongly inhibits tumor cell metastasis in vitro and in vivo.

ALX4, an epigenetically down regulated tumor suppressor, inhibits breast cancer progression by interfering Wnt/β-catenin pathway.

Background: ALX4 is a paired-like homedomain transcription factor mainly expressed in the mesenchymal compartment of variety of developing tissues, but its functions, regulation mechanisms and clinical values in breast cancer remains unclear.

Methods: The expression of ALX4 in breast cancer cell lines and patients' tissues were detected by RT-PCR, qPCR and western blot. Furthermore TCGA database was applied to confirm these results.

Copy number variations and expression of MPDZ are prognostic biomarkers for clear cell renal cell carcinoma.

The vital copy number variation (CNV) plays a crucial role in clear cell renal cell carcinoma (ccRCC). MPDZ inhibit cell polarity associate with osmotic pressure response and cancer-related biological processes. In order to clarify the role of the CNV of in the progression of ccRCC, we analyzed the CNV and expression of and prognosis in ccRCC patients from The Cancer Genome Atlas data portal.

LHX6, An Independent Prognostic Factor, Inhibits Lung Adenocarcinoma Progression through Transcriptional Silencing of β-catenin.

Our previous study identified LIM homeobox domain 6 (LHX6) as a frequently epigenetically silenced tumor-suppressor gene in lung cancer. However, its clinical value has never been evaluated, and the in-depth anti-tumor mechanism remains unclear. Public database was used for lung cancer, lung adenocarcinoma and lung squamous carcinoma patients and tissue microarray data was used for lung adenocarcinoma patients to study prognostic outcome of LHX6 expression by Kaplan-Meier and Cox-regression analysis.

Kinetic analysis of bypass of abasic site by the catalytic core of yeast DNA polymerase eta.

Abasic sites (Apurinic/apyrimidinic (AP) sites), produced ∼ 50,000 times/cell/day, are very blocking and miscoding. To better understand miscoding mechanisms of abasic site for yeast DNA polymerase η, pre-steady-state nucleotide incorporation and LC-MS/MS sequence analysis of extension product were studied using pol η(core) (catalytic core, residues 1-513), which can completely eliminate the potential effects of the C-terminal C2H2 motif of pol η on dNTP incorporation. The extension beyond the abasic site was very inefficient.