Experimental Mouse Models and Human Lung Organoid Models for Studying Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD), a leading cause of morbidity and mortality throughout the world, is a highly complicated disease that includes chronic airway inflammation, airway remodeling, emphysema, and mucus hypersecretion. For respiratory function, an intact lung structure is required for efficient air flow through conducting airways and gas exchange in alveoli. Structural changes in small airways and inflammation are major features of COPD.

METTL3-STAT5B interaction facilitates the co-transcriptional mA modification of mRNA to promote breast tumorigenesis.

Enhanced expression of methyltransferase-like 3 (METTL3) promotes the mA modification of specific mRNAs, contributing to breast tumorigenesis. While the mRNA substrates targeted by METTL3 are well characterized, the factors dictating the selection of these specific mRNA remain elusive. This study aimed to examine the regulatory role of the transcription factor STAT5B in METTL3-induced mA modification.

TAZ is involved in breast cancer cell migration via regulating actin dynamics.

Background: Cancer metastasis is dependent on cell migration. Several mechanisms, including epithelial-to-mesenchymal transition (EMT) and actin fiber formation, could be involved in cancer cell migration. As a downstream effector of the Hippo signaling pathway, transcriptional coactivator with PDZ-binding motif (TAZ) is recognized as a key mediator of the metastatic ability of breast cancer cells.

Regulation of mA Methylome in Cancer: Mechanisms, Implications, and Therapeutic Strategies.

Reversible -adenosine methylation of mRNA, referred to as mA modification, has emerged as an important regulator of post-transcriptional RNA processing. Numerous studies have highlighted its crucial role in the pathogenesis of diverse diseases, particularly cancer. Post-translational modifications of mA-related proteins play a fundamental role in regulating the mA methylome, thereby influencing the fate of mA-methylated RNA.

The PIN1-YTHDF1 axis promotes breast tumorigenesis via the mA-dependent stabilization of AURKA mRNA.

The post-transcriptional processing of N-methyladenosine (mA)-modified mRNA by YTH domain-containing family protein 1 (YTHDF1) plays a crucial role in the regulation of gene expression. Although YTHDF1 expression is frequently upregulated in breast cancer, the regulatory mechanisms for this remain unclear. In this study, we examined the role of peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) in regulating YTHDF1 stability in breast cancer cells.

Sirtuin 5-mediated deacetylation of TAZ at K54 promotes melanoma development.

Purpose: Nuclear accumulation of YAP/TAZ promotes tumorigenesis in several cancers, including melanoma. Although the mechanisms underlying the nuclear retention of YAP are known, those underlying the retention of TAZ remain unclear. Our study investigates a novel acetylation/deacetylation switch in TAZ, governing its subcellular localization in melanoma tumorigenesis.

Clinicoradiological Features of Pulmonary Cryptococcosis in Immunocompetent Patients.

Purpose: To assess the clinicoradiological features of pulmonary cryptococcosis in immunocompetent patients.

Materials And Methods: This retrospective study included immunocompetent patients who had been diagnosed with pulmonary cryptococcosis on the histopathologic exam and underwent chest CT between January 2008 and November 2019. Imaging features were divided into major imaging patterns, distributions, and ancillary imaging findings.

METTL3 stabilization by PIN1 promotes breast tumorigenesis via enhanced mA-dependent translation.

Methyltransferase-like 3 (METTL3) is the catalytic subunit of the N-adenosine methyltransferase complex responsible for N-methyladenosine (mA) modification of mRNA in mammalian cells. Although METTL3 expression is increased in several cancers, the regulatory mechanisms are unclear. We explored the regulatory roles of peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) in METTL3 stability and mA modification of mRNA.

Modulation of Autophagy is a Potential Strategy for Enhancing the Anti-Tumor Effect of Mebendazole in Glioblastoma Cells.

Mebendazole (MBZ), a microtubule depolymerizing drug commonly used for the treatment of helminthic infections, has been suggested as a repositioning candidate for the treatment of brain tumors. However, the efficacy of MBZ needs further study to improve the beneficial effect on the survival of those patients. In this study, we explored a novel strategy to improve MBZ efficacy using a drug combination.

Regulation of Interleukin-36γ/IL-36R Signaling Axis by PIN1 in Epithelial Cell Transformation and Breast Tumorigenesis.

Given the increasing recognition of the relationship between IL-1 cytokines, inflammation, and cancer, the significance of distinct members of the IL-1 cytokine family in the etiology of cancer has been widely researched. In the present study, we investigated the underlying mechanism of the IL-36γ/IL-36R axis during breast cancer progression, which has not yet been elucidated. Initially, we determined the effects of IL-36γ on the proliferation and epithelial cell transformation of JB6 Cl41 mouse epidermal and MCF7 human breast cancer cells using BrdU incorporation and anchorage-independent growth assays.

Potent Imidazothiazole-based Inhibitor of BRAF V600E Overcomes Acquired Resistance Inhibition of RAF Dimerization in PLX4032-resistant Melanoma.

Background/aim: The B-raf proto-oncogene, serine/threonine kinase (BRAF) V600E mutation is frequent in patients with advanced melanoma. PLX4032, an inhibitor of BRAFV600E kinase, is effective for the treatment of melanoma in BRAF V600E-positive patients; however, resistance eventually develops due to paradoxical activation of the mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinases (ERK) pathway resulting from RAF dimerization. In this study, we investigated the inhibitory effects of a novel imidazothiazole-based compound, KS28, on RAF dimerization and resistance to PLX4032 in melanoma.

A multipathogen DNA vaccine elicits protective immune responses against two class A bioterrorism agents, anthrax and botulism.

The potential use of biological agents has become a major public health concern worldwide. According to the CDC classification, Bacillus anthracis and Clostridium botulinum, the bacterial pathogens that cause anthrax and botulism, respectively, are considered to be the most dangerous potential biological agents. Currently, there is no licensed vaccine that is well suited for mass immunization in the event of an anthrax or botulism epidemic.

Physiological Functions of Thiol Peroxidases (Gpx1 and Prdx2) during Embryonic Development.

Glutathione peroxidase 1 (Gpx1) and peroxiredoxin 2 (Prdx2) belong to the thiol peroxidase family of antioxidants, and have been studied for their antioxidant functions and roles in cancers. However, the physiological significance of Gpx1 and Prdx2 during vertebrate embryogenesis are lacking. Currently, we investigated the functional roles of Gpx1 and Prdx2 during vertebrate embryogenesis using as a vertebrate model.

METTL3 induces PLX4032 resistance in melanoma by promoting mA-dependent EGFR translation.

Acquired resistance often limits therapeutic efficacy of the BFAF (V600E) kinase inhibitor PLX4032 in patients with advanced melanoma. Epitranscriptomic modification of mRNAs by N-methyladenosine (mA) modification contributes to melanoma pathogenesis; however, its role in acquired PLX4032 resistance remains unexplored. Here, we showed that mA methyltransferase METTL3 expression is upregulated in A375R cells, a PLX4032-resistant subline of A375 melanoma cells, compared with the parental cells.

Discovery of New Imidazo[2,1-]thiazole Derivatives as Potent Pan-RAF Inhibitors with Promising and Anti-melanoma Activity.

BRAF is an important component of MAPK cascade. Mutation of BRAF, in particular V600E, leads to hyperactivation of the MAPK pathway and uncontrolled cellular growth. Resistance to selective inhibitors of mutated BRAF is a major obstacle against treatment of many cancer types.

IL-33-Induced Transcriptional Activation of LPIN1 Accelerates Breast Tumorigenesis.

Phospholipids are crucial materials that are not only required for cell membrane construction but also play significant roles as signaling molecules. LPIN1 is an enzyme that displays phosphatidate phosphatase activity in the triglyceride and phospholipid synthesis pathway. Recent studies have shown that overexpression of LPIN1 is involved in breast tumorigenesis, but the underlying mechanism regulating LPIN1 expression has not been elucidated yet.

Interleukin-34-CSF1R Signaling Axis Promotes Epithelial Cell Transformation and Breast Tumorigenesis.

IL-34 has been recently identified as a ligand for CSF1R that regulates various cellular processes including cell proliferation, survival, and differentiation. Although the binding of IL-34 to CSF1R modulates several cancer-driving signaling pathways, little is known about the role of IL-34/CSF1R signaling in breast cancer. Herein, we report that IL-34 induces epithelial cell transformation and breast tumorigenesis through activation of MEK/ERK and JNK/c-Jun pathways.

PIN1 facilitates ubiquitin-mediated degradation of serine/threonine kinase 3 and promotes melanoma development via TAZ activation.

The Hippo signaling pathway controls cellular processes including growth, homeostasis, and apoptosis. The kinase STK3 acts upstream in this pathway to activate LATS1/2 kinase, which phosphorylates and inactivates the transcriptional coactivators YAP/TAZ. The dysregulation of Hippo signaling leads to human diseases including cancer; however, the molecular mechanisms underlying its dysregulation in melanoma are unknown.

Novel Imidazo[2,1-b]oxazole Derivatives Inhibit Epithelial Cell Transformation and Triple Negative Breast Cancer Tumorigenesis.

Background/aim: Triple negative breast cancer (TNBC) is an aggressive type of breast cancer with limited targets for chemotherapy. This study evaluated the inhibitory effects of novel imidazo[2,1-b]oxazole-based rapidly accelerated fibrosarcoma (RAF) inhibitors, KIST0215-1 and KIST0215-2, on epithelial cell transformation and TNBC tumorigenesis.

Materials And Methods: Immunoblotting, BrdU incorporation assay, reporter gene assay, and soft agar assay analyses were performed.

Modification of imidazothiazole derivatives gives promising activity in B-Raf kinase enzyme inhibition; synthesis, in vitro studies and molecular docking.

B-Raf mutation was identified as a key target in cancer treatment. Based on structural features of dabrafenib (potent FDA approved B-Raf inhibitor), the design of new NH-based imidazothiazole derivatives was carried out affording new highly potent derivatives of imidazothiazole-based scaffold with amino substitution on the terminal phenyl ring as well as side chain with sulfonamide group and terminal substituted phenyl ring. In vitro enzyme assay was investigated against V600E B-Raf kinase.

Peroxidasin is essential for endothelial cell survival and growth signaling by sulfilimine crosslink-dependent matrix assembly.

Peroxidasin (PXDN) has been reported to crosslink the C-terminal non-collagenous domains of collagen IV (Col IV) by forming covalent sulfilimine bond. Here, we explored the physiological role of PXDN and its mechanism of action in endothelial cell survival and growth. Silencing of PXDN using siRNAs decreased cell proliferation without increase of the number of detached cells and decreased cell viability under serum-starved condition with increased fragmented nuclei and caspase 3/7 activity.

Skeletal stability after 2-jaw surgery via surgery-first approach in facial asymmetry patients using CBCT.

Background: The purpose of this study is to compare the skeletal stability of two-jaw surgery via surgery-first approach with conventional two-jaw surgery in facial asymmetry patients by measuring the skeletal changes after surgery from a three-dimensional analysis. From January 2010 to January 2014, 40 patients with facial asymmetry who underwent two-jaw surgery in Pusan National University Hospital were included in this study. They were classified into experimental group ( = 20) who underwent two-jaw surgery via surgery-first approach and control group ( = 20) who underwent conventional two-jaw surgery.

RhoA/ROCK Regulates Prion Pathogenesis by Controlling Connexin 43 Activity.

Scrapie infection, which converts cellular prion protein (PrP) into the pathological and infectious isoform (PrP), leads to neuronal cell death, glial cell activation and PrP accumulation. Previous studies reported that PrP regulates RhoA/Rho-associated kinase (ROCK) signaling and that connexin 43 (Cx43) expression is upregulated in and prion-infected models. However, whether there is a link between RhoA/ROCK and Cx43 in prion disease pathogenesis is uncertain.