Publications by authors named "Young Yang"

383 Publications

Anoctamin1 Induces Hyperproliferation of HaCaT Keratinocytes and Triggers Imiquimod-Induced Psoriasis-Like Skin Injury in Mice.

Int J Mol Sci 2021 Jul 1;22(13). Epub 2021 Jul 1.

Department of Pharmacy, College of Pharmacy and Institute of Pharmaceutical Sciences, CHA University, 120 Haeryong-ro, Pocheon 11160, Korea.

Psoriasis, a long-lasting and multifactorial skin disease, is related to comorbidities such as metabolic disease, depression, and psoriatic arthritis. Psoriasis occurs due to a variety of factors including keratinocyte hyperproliferation, inflammation, and abnormal differentiation. Proinflammatory cytokines upregulated by increased activation of keratinocytes and immune cells in the skin trigger progression of psoriasis. This study aimed to investigate the effects of anoctamin1 (ANO1) on psoriasis development in vitro and in vivo. We analyzed the proliferation of HaCaT keratinocytes and ANO1-related ERK and AKT signaling pathways after ANO1 inhibitor (T16Ainh-A01 and Ani9) treatment and knock-down of . Furthermore, after applying imiquimod (IMQ) cream or coapplying IMQ cream and T16Ainh-A01 on mouse ears, we not only observed psoriatic symptoms, including ear thickening, but also quantified the effects of treatment on ERK and AKT signaling-involved proteins and proinflammatory cytokines. Inhibition of ANO1 attenuated the proliferation of HaCaT cells and induced reduction of pERK1/2. Coapplication of IMQ and T16Ainh-A01 on ears of mice reduced not only symptoms of IMQ-induced psoriasis such as thickening and erythema, but also expression of ANO1 and pERK1/2 compared to that of application of IMQ alone. In addition, the expression levels of , , , , , , and increased after applying IMQ and were significantly reduced by coapplying IMQ and T16Ainh-A01. These results aid in understanding the underlying mechanisms of ANO1 in epidermal layer keratinocyte hyperproliferation and suggest the potential of ANO1 as a target to treat psoriasis.
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http://dx.doi.org/10.3390/ijms22137145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268182PMC
July 2021

[Corrigendum] Cryptotanshinone inhibits IgE‑mediated degranulation through inhibition of spleen tyrosine kinase and tyrosine‑protein kinase phosphorylation in mast cells.

Mol Med Rep 2021 Sep 19;24(3). Epub 2021 Jul 19.

Department of Biological Science, Sookmyung Women's University, Seoul 04310, Republic of Korea.

Following the publication of the above article, an interested reader drew to the authors' attention that they had mentioned that activated PKCδ phosphorylates IKKβ in order that IKKβ is relocated to the plasma membrane, resulting in the induction of mast cell degranulation; however, four references the authors had included did not seem to support this statement. The authors have re-examined their paper, and realized that the four references the reader mentioned were indeed cited incorrectly, and wish to rectify this error through revising the third paragraph in the Discussion section, the References section, and an associated figure (Fig. 6C) in order to avoid any further misunderstandings on the part of the readership. First, the authors wish to revise the wording of the third and fourth paragraphs of the Discussion, as featured on pp. 1101-1102, to the following (changed text is indicated in bold): 'We showed that CRT exerts anti-AD effect through inhibition of the mast cell degranulation in mast cells. Upon IgE/antigen stimulation, the immunoreceptor tyrosine-based activation motif (ITAM) region of FcεRI receptor which is on the mast cell surface is phosphorylated and the initial signalling protein kinases Lyn and Syk are recruited to the ITAM (28,29). Then, the activated Lyn and Syk leads to phosphorylation of the transmembrane adaptor linker for activation of T cells (LAT). Phosphorylated LAT which is a scaffold for multimolecular signalling complexes and activates PLCγ through phosphorylation. The activated PLCγ hydrolyses phosphatidylinositol biphosphate (PIP2) to generate second signalling molecules IP3 and DAG, which activate PKCs including PKCδ to induce the mast cell degranulation (30,31). On the other hand, cross-linking of FcεRI also activates IKKβ, which moves to the lipid raft fractions and phosphorylates synaptosomal-associated protein 23 (SNAP-23) leading to degranulation (7). Since PKCδ phosphorylates IKKα, but not IKKβ (32), it is not likely that two signalling pathways are directly connected. In this study, novel function of CRT on phosphorylations of Lyn/Syk kinases in mast cells is elucidated for the first time. Furthermore, it is likely that this inhibitory effect of CRT on Lyn/Syk kinases negatively affected activities of their downstream signalling molecules including PLCγ, PKCδ, and IKKβ, which leads to decrease in mast cell degranulation by CRT treatment. Besides the inhibitory effect of CRT on mast cell degranulation, here we provide additional evidence that CRT exerts anti-AD effects through inactivation of MAPK and NF‑κB. It has been reported that CRT regulates the activities of MAPK and NF‑κB in various cell types. In rhabdomyosarcoma, hepatoma, and breast carcinoma, CRT activates MAPK p38/JNK and suppresses ERK1/2, followed by caspase-independent apoptosis (10,33,34). In chronic myeloid leukaemia cells, CRT enhances TNF‑α-induced apoptosis through the activation of MAPK p38 (35). In smooth muscle cells, CRT exerts anti-migration/invasion effect as it inhibits TNF‑α/NF‑κB signalling pathway (36).' Secondly, the authors wish to make the following changes to the Reference list: New references 30-32 have been inserted to the list, as follows: 30. Ozawa K, Szallasi Z, Kazanietz MG, Blumberg PM, Mischak H, Mushinski JF and Beaven MA: Ca-dependent and Ca-independent isozymes of protein kinase C mediate exocytosis in antigen-stimulated rat basophilic RBL-2H3 cell. J Biol Chem 268: 1749-1756, 1993. 31. Cho SH, Woo CH, Yoon SB and Kim JH: Protein kinase Cδ functions downstream of Ca mobilization in FcεRI signaling to degranulation in mast cells. J Allergy Clin Immunol 114: 1085-1092, 2004. 32. Yamaguchi T, Miki Y and Yoshida K: Protein kinase Cδ activates IκB-kinase α to induce the p53 tumor suppressor in response to oxidative stress. Cell Signal 19: 2088-2097, 2007. The addition of these new references means that the former references 30-33 have been accordingly renumbered to references 33-36. Finally, the authors have revised Fig. 6C, as it appeared on p. 1102, in order to assist the understanding of the readers, and the corrected version of Fig. 6 appears on the next page. All these corrections have been approved by all the authors, with the exception of the first author, Sumiyasuren Buyanravjikh, who is no longer uncontactable. The authors regret that these errors were included in the paper, even though they did not substantially alter any of the major conclusions reported in the study, are grateful to the Editor for allowing them this opportunity to publish a Corrigendum, and apologize to the readership for any inconvenience caused. [the original article was published in 18: 1095‑1193, 2018; DOI: 10.3892/mmr.2018.9042].
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http://dx.doi.org/10.3892/mmr.2021.12283DOI Listing
September 2021

Intramyocardial delivery of human cardiac stem cell spheroids with enhanced cell engraftment ability and cardiomyogenic potential for myocardial infarct repair.

J Control Release 2021 Jul 2;336:499-509. Epub 2021 Jul 2.

Department of Pharmacy, Ewha Womans University, 52, Ewhayeodae-gil, Seodaemun-gu, Seoul 03760, Republic of Korea. Electronic address:

Strategies for stem cell-based cardiac regeneration and repair are key issues for the ischemic heart disease (IHD) patients with chronic complications related to ischemic necrosis. Cardiac stem cells (CSCs) have demonstrated high therapeutic efficacy for IHD treatment owing to their specific cardiac-lineage commitment. The therapeutic potential of CSCs could be further enhanced by designing a cellular spheroid formulation. The spheroid culture condition of CSCs was optimized to ensure regulated size and minimal core necrosis in the spheroids. The CSC spheroids revealed mRNA profiles of the factors related to cardiac regeneration, angiogenesis, anti-inflammatory, and cardiomyocyte differentiation with a higher expression level than the CSCs. Intramyocardially delivered CSC spheroids in the rat IHD model resulted in a significant increase in retention rate by 1.82-fold (day 3) and 1.98-fold (day 14) compared to CSCs. Endothelial cell differentiation and neovascularization of the engrafted CSC spheroids were noted in the infarcted myocardium. CSC spheroids significantly promoted cardiac regeneration: i.e., decreased infarction and fibrotic area (11.22% and 4.18%) and increased left ventricle thickness (0.62 mm) compared to the untreated group. Cardiac performance was also improved by 2.04-fold and 1.44-fold increase in the ejection fraction and fractional shortening, respectively. Intramyocardial administration of CSC spheroids might serve as an advanced therapeutic modality with enhanced cell engraftment and regenerative abilities for cardiac repair after myocardial infarction.
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http://dx.doi.org/10.1016/j.jconrel.2021.06.040DOI Listing
July 2021

Epigenetic Upregulation of MAGE-A Isoforms Promotes Breast Cancer Cell Aggressiveness.

Cancers (Basel) 2021 Jun 25;13(13). Epub 2021 Jun 25.

Laboratory of Biomedical Genomics, Department of Biological Sciences, Sookmyung Women's University, Seoul 04310, Korea.

After decades-long efforts to diagnose and treat breast cancer, the management strategy that has proved most successful to date is molecular-subtype-specific inhibition of the hormone receptors and HER2 that are expressed by individual cancers. Melanoma-associated antigen (MAGE) proteins comprise >40 highly conserved members that contain the MAGE homology domain. They are often overexpressed in multiple cancers and contribute to cancer progression and metastasis. However, it remains unclear whether the biological activity arising from MAGE gene expression is associated with breast cancer subtypes. In this study, we analyzed the RNA-sequencing (RNA-seq) data of 70 breast cancer cell lines and found that MAGEA12 and MAGEA3 were highly expressed in a subset of these lines. Significantly, MAGEA12 and MAGEA3 expression levels were independent of hormone receptor expression levels but were closely associated with markers of active histone modifications. This indicates that overexpression of these genes is attributable to epigenetic deregulation. RNA-seq of MAGEA12-depleted cells was then used to identify 382 candidate targets of MAGEA12 that were downregulated by MAGEA12 depletion. Furthermore, our gain-of-function experiments showed that MAGEA12 overexpression promoted aggressive behaviors of malignant breast cancer cells, including enhancing their cell migration and invasion. These changes were associated with increased epigenetic deregulation of the MAGEA12 signature genes. Thus, MAGEA12 may play an important role in breast cancer malignancy. Taken together, our findings suggest that MAGEA12 could be a promising therapeutic target in breast cancer, and its overexpression and epigenetic changes could serve as subtype classification biomarkers.
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http://dx.doi.org/10.3390/cancers13133176DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268034PMC
June 2021

Non-toxic sulfur inhibits LPS-induced inflammation by regulating TLR-4 and JAK2/STAT3 through IL-6 signaling.

Mol Med Rep 2021 07 28;24(1). Epub 2021 Apr 28.

Department of Pathology, School of Medicine, Institute of Biomedical Science and Technology, Konkuk University, Chungju, North Chungcheong 27478, Republic of Korea.

Janus kinase 2 (JAK2) and STAT3 signaling is considered a major pathway in lipopolysaccharide (LPS)‑induced inflammation. Toll‑like receptor 4 (TLR‑4) is an inflammatory response receptor that activates JAK2 during inflammation. STAT3 is a transcription factor for the pro‑inflammatory cytokine IL‑6 in inflammation. Sulfur is an essential element in the amino acids and is required for growth and development. Non‑toxic sulfur (NTS) can be used in livestock feeds as it lacks toxicity. The present study aimed to inhibit LPS‑induced inflammation in C2C12 myoblasts using NTS by regulating TLR‑4 and JAK2/STAT3 signaling via the modulation of IL‑6. The 3‑(4,5‑dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazolium bromide assay was conducted to analyze cell viability and reverse transcription polymerase chain reaction and western blotting performed to measure mRNA and protein expression levels. Chromatin immunoprecipitation and enzyme‑linked immunosorbent assays were used to determine the binding activity of proteins. The results indicated that NTS demonstrated a protective effect against LPS‑induced cell death and inhibited LPS‑induced expression of TLR‑4, JAK2, STAT3 and IL‑6. In addition, NTS inhibited the expression of nuclear phosphorylated‑STAT3 and its binding to the IL‑6 promoter. Therefore, NTS may be a potential candidate drug for the treatment of inflammation.
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http://dx.doi.org/10.3892/mmr.2021.12124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8127030PMC
July 2021

Increased Melanoma-Associated Antigen C2 Expression Affords Resistance to Apoptotic Deathin Suspension-Cultured Tumor Cells.

J Breast Cancer 2021 Apr 5;24(2):138-152. Epub 2021 Feb 5.

Department of Biological Sciences, Sookmyung Women's University, Seoul, Korea.

Purpose: Melanoma-associated antigen C2 (MAGEC2) is an oncogene associated with various types of cancers. However, the biological function of MAGEC2 in circulating tumor cells remains unclear. In this study, we investigated the role of MAGEC2 using adapted suspension cells (ASCs), which were previously developed to study circulating tumor cells (CTCs).

Methods: Differential gene expression in adherent cells (ADs) and ASCs was examined using RNA-seq analysis. MAGEC2 expression was assessed using reverse transcription quantitative polymerase chain reaction (RT-qPCR), immunoblotting, and ChIP-seq analysis. Depletion of MAGEC2 expression was performed using siRNA. MAGEC2-depleted ADs and ASCs were used to investigate changes in the proliferation rate and cell cycle. Then, the protein levels of signal transducer and activator of transcription 3 (STAT3), phosphorylated STAT3, and downstream of STAT3 were measured using control and MAGEC2-depleted ADs and ASCs. In ASCs, the direct effect of active STAT3 inhibition with Stattic, a STAT3 inhibitor, was assessed in terms of proliferation and apoptosis. Finally, an Annexin V/7-AAD assay was performed to determine the percentage of apoptotic cells in the Stattic-treated cells.

Results: MAGEC2 was highly expressed in ASCs when compared with ADs. Depletion of MAGEC2 reduced the proliferation rate and viability of ASCs. To elucidate the underlying mechanism, the level of STAT3 was examined owing to its oncogenic properties. Tyrosine-phosphorylated active STAT3 was highly expressed in ASCs and decreased in MAGEC2-depleted ASCs. Furthermore, on treating ASCs with Stattic, an active STAT3 inhibitor, the cells were markedly sensitive to intrinsic pathway-mediated apoptosis.

Conclusions: High MAGEC2 expression may play an important role in the survival of ASCs by maintaining the expression of activated STAT3 to prevent apoptotic cell death.
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http://dx.doi.org/10.4048/jbc.2021.24.e6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8090803PMC
April 2021

An Overview of the Molecular Mechanisms Contributing to Musculoskeletal Disorders in Chronic Liver Disease: Osteoporosis, Sarcopenia, and Osteoporotic Sarcopenia.

Int J Mol Sci 2021 Mar 5;22(5). Epub 2021 Mar 5.

Department of Internal Medicine, Hallym University College of Medicine, Gangwon-do, Chuncheon 24252, Korea.

The prevalence of osteoporosis and sarcopenia is significantly higher in patients with liver disease than in those without liver disease and osteoporosis and sarcopenia negatively influence morbidity and mortality in liver disease, yet these musculoskeletal disorders are frequently overlooked in clinical practice for patients with chronic liver disease. The objective of this review is to provide a comprehensive understanding of the molecular mechanisms of musculoskeletal disorders accompanying the pathogenesis of liver disease. The increased bone resorption through the receptor activator of nuclear factor kappa (RANK)-RANK ligand (RANKL)-osteoprotegerin (OPG) system and upregulation of inflammatory cytokines and decreased bone formation through increased bilirubin and sclerostin and lower insulin-like growth factor-1 are important mechanisms for osteoporosis in patients with liver disease. Sarcopenia is associated with insulin resistance and obesity in non-alcoholic fatty liver disease, whereas hyperammonemia, low amount of branched chain amino acids, and hypogonadism contributes to sarcopenia in liver cirrhosis. The bidirectional crosstalk between muscle and bone through myostatin, irisin, β-aminoisobutyric acid (BAIBA), osteocalcin, as well as the activation of the RANK and the Wnt/β-catenin pathways are associated with osteosarcopenia. The increased understandings for these musculoskeletal disorders would be contributes to the development of effective therapies targeting the pathophysiological mechanism involved.
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http://dx.doi.org/10.3390/ijms22052604DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961345PMC
March 2021

Loss of splicing factor IK impairs normal skeletal muscle development.

BMC Biol 2021 04 1;19(1):44. Epub 2021 Apr 1.

Department of Biological Sciences, Sookmyung Women's University, Seoul, 04310, Republic of Korea.

Background: IK is a splicing factor that promotes spliceosome activation and contributes to pre-mRNA splicing. Although the molecular mechanism of IK has been previously reported in vitro, the physiological role of IK has not been fully understood in any animal model. Here, we generate an ik knock-out (KO) zebrafish using the CRISPR/Cas9 system to investigate the physiological roles of IK in vivo.

Results: The ik KO embryos display severe pleiotropic phenotypes, implying an essential role of IK in embryonic development in vertebrates. RNA-seq analysis reveals downregulation of genes involved in skeletal muscle differentiation in ik KO embryos, and there exist genes having improper pre-mRNA splicing among downregulated genes. The ik KO embryos display impaired neuromuscular junction (NMJ) and fast-twitch muscle development. Depletion of ik reduces myod1 expression and upregulates pax7a, preventing normal fast muscle development in a non-cell-autonomous manner. Moreover, when differentiation is induced in IK-depleted C2C12 myoblasts, myoblasts show a reduced ability to form myotubes. However, inhibition of IK does not influence either muscle cell proliferation or apoptosis in zebrafish and C2C12 cells.

Conclusion: This study provides that the splicing factor IK contributes to normal skeletal muscle development in vivo and myogenic differentiation in vitro.
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http://dx.doi.org/10.1186/s12915-021-00980-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8015194PMC
April 2021

Retropharyngeal chordoma extending to the spinal cord, mimicking a neurogenic tumor: a case report and literature review.

J Int Med Res 2021 Mar;49(3):300060521999566

Department of Pathology, Inje University School of Medicine, Busan Paik Hospital, Busan, Republic of Korea.

Chordomas are rare, locally aggressive bone malignancies with poor prognoses. However, those with minimal or no bone involvement are more easily resectable because of their well-delineated margins and thus have better prognoses. Such extraosseous chordomas of the spine are localized both intradurally and extradurally. Only a few case reports have focused on extraosseous, extradural spinal chordomas. Radiologically, this type of chordoma has a dumbbell shape; however, dumbbell-shaped spinal tumors are traditionally thought to be neurogenic tumors (i.e., schwannomas or neurofibromas). We herein report a unique case involving a woman with a dumbbell-shaped extraosseous chordoma protruding predominantly into the retropharyngeal space. A 44-year-old woman presented for evaluation of a left submandibular mass. A T2-hyperintense, gadolinium-enhancing mass was found in her cervical spinal canal, protruding through the C2/3 neural foramen into the retropharyngeal space with minimal vertebral involvement. The initial diagnosis was a neurogenic tumor, most likely a schwannoma. After subtotal removal, the pathologic diagnosis was a chordoma. Because chordomas and schwannomas have significantly different prognoses, caution is warranted when a dumbbell-shaped tumor is identified in the spine with minimal or no vertebral deterioration on radiology. This report also provides the first thorough review of extraosseous dumbbell-shaped intraspinal-extraspinal chordomas.
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http://dx.doi.org/10.1177/0300060521999566DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166386PMC
March 2021

MiR-146a Regulates Migration and Invasion by Targeting NRP2 in Circulating-Tumor Cell Mimicking Suspension Cells.

Genes (Basel) 2020 12 30;12(1). Epub 2020 Dec 30.

Research Institute for Women's Health, Sookmyung Women's University, Seoul 04310, Korea.

Cancer metastasis is the primary cause of cancer-related death and metastatic cancer has circulating-tumor cells (CTCs), which circulate in the bloodstream before invading other organs. Thus, understanding the precise role of CTCs may provide new insights into the metastasis process and reduce cancer mortality. However, the molecular characteristics of CTCs are not well understood due to a lack of number of CTCs. Therefore, suspension cells were generated from MDA-MB-468 cells to mimic CTCs, and we investigate the microRNA (miRNA)-dependent molecular networks and their role in suspension cells. Here, we present an integrated analysis of mRNA and miRNA sequencing data for suspension cell lines, through comparison with adherent cells. Among the differentially regulated miRNA-mRNAs axes, we focus on the miR-146a-Neuropilin2 (NRP2) axis, which is known to influence tumor aggressiveness. We show that miR-146a directly regulates NRP2 expression and inhibits Semaphorin3C (SEMA3C) signaling. Functional studies reveal that miR-146a represses SEMA3C-induced invasion and proliferation by targeting NRP2. Finally, high-NRP2 is shown to be associated with poor outcomes in breast cancer patients. This study identifies the key role of the miR-146a-NRP2 signaling axis that is critical for the regulation of migration and invasion in CTC-mimicking cells.
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http://dx.doi.org/10.3390/genes12010045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7824086PMC
December 2020

Applications and Functions of γ-Poly-Glutamic Acid and its Derivatives in Medicine.

Curr Pharm Biotechnol 2020 Nov 18. Epub 2020 Nov 18.

College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083. China.

Background: γ-Poly-glutamic acid (γ-PGA) is a naturally occurring homo-polyamide produced by various strains of Bacillus. It is made from repeating units of L-glutamic acid, D-glutamic acid, or both connected through amide linkages between α-amino and γ-carboxylic acid groups. As a biopolymer substance, the attractive properties of γ-PGA are that it is water-soluble, biodegradable, biocompatible, non-toxic, non-immunogenic, and edible. Therefore, it can be used as a green and environmentally friendly biological material.

Methods: The review concentrates on the reports revealing the functions and potential use of γ-PGA and its derivatives in medicine.

Results & Discussion: γ-PGA is described to possess several properties which may be exploited in medicine. The biopolymer reportedly has been successfully applied not only as metal chelator, drug carrier/deliverer, and gene vector, but also used safely as vaccine adjuvant, tissue engineering material, and contrast agent.

Conclusion: γ-PGA could be potentially considered as a potential biomedical material in the field of medicine.
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http://dx.doi.org/10.2174/1389201021999201118161155DOI Listing
November 2020

Design of Anticancer 2,4-Diaminopyrimidines as Novel Anoctamin 1 (ANO1) Ion Channel Blockers.

Molecules 2020 Nov 6;25(21). Epub 2020 Nov 6.

Department of Pharmacy, College of Pharmacy and Institute of Pharmaceutical Sciences, CHA University, 120 Haeryong-ro, Pocheon 11160, Korea.

Pyrimidine is a privileged scaffold in many synthetic compounds exhibiting diverse pharmacological activities, and is used for therapeutic applications in a broad spectrum of human diseases. In this study, we prepared a small set of pyrimidine libraries based on the structure of two hit compounds that were identified through the screening of an in-house library in order to identify an inhibitor of anoctamin 1 (ANO1). ANO1 is amplified in various types of human malignant tumors, such as head and neck, parathyroid, and gastrointestinal stromal tumors, as well as in breast, lung, and prostate cancers. After initial screening and further structure optimization, we identified as a dose-dependent ANO1 blocker. This compound exhibited more potent anti-cancer activity in the NCI-H460 cell line, expressing high levels of ANO1 compared with that in A549 cells that express low levels of ANO1. Our results open a new direction for the development of small-molecule ANO1 blockers composed of a pyrimidine scaffold and a nitrogen-containing heterocyclic moiety, with drug-like properties.
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http://dx.doi.org/10.3390/molecules25215180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7664333PMC
November 2020

Real-World Clinical Data of Palbociclib in Asian Metastatic Breast Cancer Patients: Experiences from Eight Institutions.

Cancer Res Treat 2021 Apr 28;53(2):409-423. Epub 2020 Oct 28.

Division of Medical Oncology, Department of Internal Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.

Purpose: Use of cyclin-dependent kinase 4/6 inhibitors improved survival outcome of hormone receptor (HR) positive metastatic breast cancer (MBC) patients, including Asian population. However, Asian real-world data of palbociclib is limited. We analyzed the real-world clinical practice patterns and outcome in HR-positive, MBC Asian patients treated with palbociclib.

Materials And Methods: Between April 2017 to November 2019, 169 HR-positive, human epidermal growth factor-2-negative MBC patients treated with letrozole or fulvestrant plus palbocilib were enrolled from eight institutions. Survival outcome (progression-free survival [PFS]), treatment response and toxicity profiles were analyzed.

Results: Median age of letrozole plus palbociclib (145 patients, 85.8%) and fulvestrant plus palbociclib (24 patients, 14.2%) was 58 and 53.5 years, with median follow-up duration of 14.63 months (range 0.2 to 33.9 months). Median PFS (mPFS) of letrozole plus palbociclib and fulvestrant plus palbociclib was 25.6 (95% confidence interval [CI], 19.1 to not reached) and 6.37 months (95% CI, 5.33 to not reached), comparable to previous phase 3 trials. In letrozole plus palbociclib arm, luminal A (hazard ratio, 2.86; 95% CI, 1.20 to 6.80; p=0.017) and patients with good performance (Eastern Cooperative Oncology Group 0-1 [hazard ratio, 3.68; 95% CI, 1.70 to 7.96]) showed better mPFS. In fulvestrant plus palbociclib group, chemotherapy naïve patients showed better mPFS (hazard ratio, 12.51, 95% CI, 1.59 to 99.17; p=0.017). The most common grade 3 or 4 adverse event was neutropenia (letrozole 86.3%, fulvestrant 88.3%).

Conclusion: To our knowledge, this is the first real-world data of palbociclib reported in Asia. Palbociclib showed comparable benefit to previous phase 3 trials in Asian patients during daily clinical practice.
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http://dx.doi.org/10.4143/crt.2020.451DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8053880PMC
April 2021

Wake-sleep cycles are severely disrupted by diseases affecting cytoplasmic homeostasis.

Proc Natl Acad Sci U S A 2020 11 26;117(45):28402-28411. Epub 2020 Oct 26.

Department of Biomedical Sciences, College of Medicine, Florida State University, Tallahassee, FL 32306;

The circadian clock is based on a transcriptional feedback loop with an essential time delay before feedback inhibition. Previous work has shown that PERIOD (PER) proteins generate circadian time cues through rhythmic nuclear accumulation of the inhibitor complex and subsequent interaction with the activator complex in the feedback loop. Although this temporal manifestation of the feedback inhibition is the direct consequence of PER's cytoplasmic trafficking before nuclear entry, how this spatial regulation of the pacemaker affects circadian timing has been largely unexplored. Here we show that circadian rhythms, including wake-sleep cycles, are lengthened and severely unstable if the cytoplasmic trafficking of PER is disrupted by any disease condition that leads to increased congestion in the cytoplasm. Furthermore, we found that the time delay and robustness in the circadian clock are seamlessly generated by delayed and collective phosphorylation of PER molecules, followed by synchronous nuclear entry. These results provide clear mechanistic insight into why circadian and sleep disorders arise in such clinical conditions as metabolic and neurodegenerative diseases and aging, in which the cytoplasm is congested.
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http://dx.doi.org/10.1073/pnas.2003524117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7668169PMC
November 2020

Molecular Mechanisms and Emerging Therapeutics for Osteoporosis.

Int J Mol Sci 2020 Oct 15;21(20). Epub 2020 Oct 15.

Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon 34141, Korea.

Osteoporosis is the most common chronic metabolic bone disease. It has been estimated that more than 10 million people in the United States and 200 million men and women worldwide have osteoporosis. Given that the aging population is rapidly increasing in many countries, osteoporosis could become a global challenge with an impact on the quality of life of the affected individuals. Osteoporosis can be defined as a condition characterized by low bone density and increased risk of fractures due to the deterioration of the bone architecture. Thus, the major goal of treatment is to reduce the risk for fractures. There are several treatment options, mostly medications that can control disease progression in risk groups, such as postmenopausal women and elderly men. Recent studies on the basic molecular mechanisms and clinical implications of osteoporosis have identified novel therapeutic targets. Emerging therapies targeting novel disease mechanisms could provide powerful approaches for osteoporosis management in the future. Here, we review the etiology of osteoporosis and the molecular mechanism of bone remodeling, present current pharmacological options, and discuss emerging therapies targeting novel mechanisms, investigational treatments, and new promising therapeutic approaches.
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http://dx.doi.org/10.3390/ijms21207623DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7589419PMC
October 2020

NO-Reduction Performance Test for TiO Paint.

Molecules 2020 Sep 7;25(18). Epub 2020 Sep 7.

School of Architecture and Building Science, Chung-Ang University, Seoul 06974, Korea.

In South Korea, the gradual increase in particulate matter generation has received significant attention from central and local governments. Exhaust gas, which contains nitrogen oxides (NO), is one of the main sources of particulate matter. In this study, the reduction of NO using a coating material mixed with a titanium dioxide (TiO) photocatalyst was demonstrated. The NO reduction performance of the TiO photocatalyst-infused coating was evaluated by applying the ISO 22197-1: 2007 standard. Subsequently, the performance was evaluated by changing the NO gas concentration and ultraviolet (UV)-A irradiance under standard experimental conditions. It was determined that NO reduction can be achieved even if the NO gas concentration and UV-A irradiance are lower than those under the standard conditions when the TiO photocatalyst-infused coating was used. This study revealed that NO reduction can be realized through TiO photocatalyst-infused coating in winter or cloudy days with a low solar altitude. It was also confirmed that compared with the UV-A irradiance, the NO gas concentration has a greater effect on the NO reduction performance of the TiO photocatalyst-infused coating. These findings can be used to evaluate a variety of construction materials with TiO photocatalysts in the future.
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http://dx.doi.org/10.3390/molecules25184087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7571102PMC
September 2020

Effect of methylsulfonylmethane on oxidative stress and CYP3A93 expression in fetal horse liver cells.

Anim Biosci 2021 Feb 24;34(2):312-319. Epub 2020 Aug 24.

Department of Animal Science, College of Natural Resources and Life Sciences, Pusan National University, Miryang 50463, Korea.

Objective: Stress-induced cytotoxicity caused by xenobiotics and endogenous metabolites induces the production of reactive oxygen species and often results in damage to cellular components such as DNA, proteins, and lipids. The cytochrome P450 (CYP) family of enzymes are most abundant in hepatocytes, where they play key roles in regulating cellular stress responses. We aimed to determine the effects of the antioxidant compound, methylsulfonylmethane (MSM), on oxidative stress response, and study the cytochrome P450 family 3 subfamily A (CYP3A) gene expression in fetal horse hepatocytes.

Methods: The expression of hepatocyte markers and CYP3A family genes (CYP3A89, CYP3A93, CYP3A94, CYP3A95, CYP3A96, and CYP3A97) were assessed in different organ tissues of the horse and fetal horse liver-derived cells (FHLCs) using quantitative reverse transcription polymerase chain reaction. To elucidate the antioxidant effects of MSM on FHLCs, cell viability, levels of oxidative markers, and gene expression of CYP3A were investigated in H2O2-induced oxidative stress in the presence and absence of MSM.

Results: FHLCs exhibited features of liver cells and simultaneously maintained the typical genetic characteristics of normal liver tissue; however, the expression profiles of some liver markers and CYP3A genes, except that of CYP3A93, were different. The expression of CYP3A93 specifically increased after the addition of H2O2 to the culture medium. MSM treatment reduced oxidative stress as well as the expression of CYP3A93 and heme oxygenase 1, an oxidative marker in FHLCs.

Conclusion: MSM could reduce oxidative stress and hepatotoxicity in FHLCs by altering CYP3A93 expression and related signaling pathways.
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http://dx.doi.org/10.5713/ajas.20.0061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876717PMC
February 2021

Methylsulfonylmethane Induces Cell Cycle Arrest and Apoptosis, and Suppresses the Stemness Potential of HT-29 Cells.

Anticancer Res 2020 Sep;40(9):5191-5200

Department of Pathology, School of Medicine, Institute of Biomedical Science and Technology, Konkuk University, Chungju, Republic of Korea

Background/aim: Colorectal cancer is one of the most common malignancies worldwide. Small molecule-based chemotherapy is an attractive approach for the chemoprevention and treatment of colorectal cancer. Methylsulfonylmethane (MSM) is a natural organosulfur compound with anticancer properties, as revealed by studies on in vitro models of gingival, prostate, lung, hepatic, and breast cancer. However, the molecular mechanisms underlying the effects of MSM in colon cancer cells remain unclear.

Materials And Methods: Here, we investigated the effects of MSM, especially on the cell cycle arrest and apoptosis, in HT-29 cells.

Results: MSM suppressed the viability of HT-29 cells by inducing apoptosis and cell cycle arrest at the G/G phase. MSM suppressed the sphere-forming ability and expression of stemness markers in HT-29 cells.

Conclusion: MSM has anti-cancer effects on HT-29 cells, and induces cell cycle arrest and apoptosis, while suppressing the stemness potential.
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http://dx.doi.org/10.21873/anticanres.14522DOI Listing
September 2020

Chyle Leakage after Esophageal Cancer Surgery.

Korean J Thorac Cardiovasc Surg 2020 Aug;53(4):191-199

Department of Thoracic and Cardiovascular Surgery, Yonsei University College of Medicine, Seoul, Korea.

Surgeons recommend dissecting lymph nodes in the thorax, abdomen, and neck during surgery for esophageal cancer because of the possibility of metastasis to the lymph nodes in those areas through the lymphatic plexus of the esophageal submucosal layer. Extensive lymph node dissection is essential for accurate staging and is thought to improve survival. However, it can result in several complications, including chyle leakage, which refers to continuous lymphatic fluid leakage and can occur in the thorax, abdomen, and neck. Malnutrition, fluid imbalance, and immune compromise may result from chyle leakage, which can be potentially life-threatening if it persists. Therefore, various treatment methods, including conservative treatment, pharmacological treatment such as octreotide infusion, and interventions such as thoracic duct embolization and surgical thoracic duct ligation, have been applied. In this article, the risk factors, diagnosis, and treatment methods of chyle leakage after esophagectomy are reviewed.
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http://dx.doi.org/10.5090/kjtcs.2020.53.4.191DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7409880PMC
August 2020

Double-Blind, Randomized, Placebo-Controlled Trial of DA-9701 in Parkinson's Disease: PASS-GI Study.

Mov Disord 2020 11 6;35(11):1966-1976. Epub 2020 Aug 6.

Department of Neurology, Hanyang University Medical Center, Seoul, South Korea.

Objectives: This study aimed to assess the efficacy of DA-9701 on gastrointestinal symptom-related quality of life in patients with Parkinson's disease on stable dopaminergic medications.

Methods: This multicenter, double-blind, placebo-controlled, phase 4 trial included a total of 144 patients with Parkinson's disease with gastrointestinal dysfunctions based on predefined criteria. Participants were randomized to take either DA-9701 or placebo for 4 weeks, and then both groups were administered DA-9701 for an additional 8 weeks while antiparkinsonian medications were unchanged. The primary outcome measure was gastrointestinal symptoms and related quality-of-life changes assessed on the Korean Nepean dyspepsia index after 4 and 12 weeks of therapy. We also evaluated the impact of DA-9701 therapy on parkinsonian motor symptoms at each time point.

Results: The gastrointestinal symptom-related quality-of-life score significantly improved in the DA-9701-treated group compared with the placebo-treated group after 4weeks (adjusted P = 0.012 by linear mixed effect model analysis). The overall gastrointestinal symptom and dyspepsia sum scores improved at 12 weeks after intervention in the DA-9701-first treated group (adjusted P = 0.002 and 0.014, respectively) and also in the placebo-first treated group (adjusted P = 0.019 and 0.039) compared with the baseline. Parkinsonian motor severity was not significantly affected by DA-9701 treatment in both groups at 4 and 12 weeks after intervention. There were no drug-related serious adverse events throughout the trial.

Conclusions: DA-9701 therapy improved gastrointestinal symptom-related quality of life, and 12 weeks of daily administration can relieve the overall severity of gastrointestinal symptoms in patients with Parkinson's disease without affecting motor symptoms. (Clinical trial identifier: NCT02775591.) © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.28219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7754502PMC
November 2020

The Future of Capsule Endoscopy: The Role of Artificial Intelligence and Other Technical Advancements.

Authors:
Young Joo Yang

Clin Endosc 2020 Jul 16;53(4):387-394. Epub 2020 Jul 16.

Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea.

Capsule endoscopy has revolutionized the management of small-bowel diseases owing to its convenience and noninvasiveness. Capsule endoscopy is a common method for the evaluation of obscure gastrointestinal bleeding, Crohn's disease, small-bowel tumors, and polyposis syndrome. However, the laborious reading process, oversight of small-bowel lesions, and lack of locomotion are major obstacles to expanding its application. Along with recent advances in artificial intelligence, several studies have reported the promising performance of convolutional neural network systems for the diagnosis of various small-bowel lesions including erosion/ulcers, angioectasias, polyps, and bleeding lesions, which have reduced the time needed for capsule endoscopy interpretation. Furthermore, colon capsule endoscopy and capsule endoscopy locomotion driven by magnetic force have been investigated for clinical application, and various capsule endoscopy prototypes for active locomotion, biopsy, or therapeutic approaches have been introduced. In this review, we will discuss the recent advancements in artificial intelligence in the field of capsule endoscopy, as well as studies on other technological improvements in capsule endoscopy.
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http://dx.doi.org/10.5946/ce.2020.133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7403015PMC
July 2020

Tannic Acid Inhibits Non-small Cell Lung Cancer (NSCLC) Stemness by Inducing G/G Cell Cycle Arrest and Intrinsic Apoptosis.

Anticancer Res 2020 Jun;40(6):3209-3220

Department of Pathology, School of Medicine, Institute of Biomedical Science and Technology, Konkuk University, Seoul, Republic of Korea

Background/aim: Non-small cell lung cancer (NSCLC) is one among the most common cancers worldwide. Recently, dietary phytochemicals have been reported as an attractive approach to improve the symptoms of NSCLC patients. Tannic acid is a natural polyphenol, which is known to have anticancer effects on in vitro models of breast, gingival and colon cancer. However, the molecular mechanisms associated with the actions of tannic acid on A549 human lung cancer cells have not been elucidated.

Materials And Methods: In this study, we analyzed the effect of tannic acid on A549 cells and their underlying mechanisms using western blotting, flow cytometry, invasion assay and tumorsphere formation assay.

Results: Tannic acid treatment suppressed the viability of A549 cells through cell cycle arrest and induction of the intrinsic pathways of apoptosis. In addition, the various malignant phenotypes of A549 cells including invasion, migration, and stemness were inhibited by tannic acid treatment.

Conclusion: Tannic acid could be used as an effective inhibitor of lung cancer progression.
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http://dx.doi.org/10.21873/anticanres.14302DOI Listing
June 2020

Automated Classification of Colorectal Neoplasms in White-Light Colonoscopy Images via Deep Learning.

J Clin Med 2020 May 24;9(5). Epub 2020 May 24.

Department of Internal Medicine, Hallym University College of Medicine, Chuncheon 24252, Korea.

Classification of colorectal neoplasms during colonoscopic examination is important to avoid unnecessary endoscopic biopsy or resection. This study aimed to develop and validate deep learning models that automatically classify colorectal lesions histologically on white-light colonoscopy images. White-light colonoscopy images of colorectal lesions exhibiting pathological results were collected and classified into seven categories: stages T1-4 colorectal cancer (CRC), high-grade dysplasia (HGD), tubular adenoma (TA), and non-neoplasms. The images were then re-classified into four categories including advanced CRC, early CRC/HGD, TA, and non-neoplasms. Two convolutional neural network models were trained, and the performances were evaluated in an internal test dataset and an external validation dataset. In total, 3828 images were collected from 1339 patients. The mean accuracies of ResNet-152 model for the seven-category and four-category classification were 60.2% and 67.3% in the internal test dataset, and 74.7% and 79.2% in the external validation dataset, respectively, including 240 images. In the external validation, ResNet-152 outperformed two endoscopists for four-category classification, and showed a higher mean area under the curve (AUC) for detecting TA+ lesions (0.818) compared to the worst-performing endoscopist. The mean AUC for detecting HGD+ lesions reached 0.876 by Inception-ResNet-v2. A deep learning model presented promising performance in classifying colorectal lesions on white-light colonoscopy images; this model could help endoscopists build optimal treatment strategies.
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http://dx.doi.org/10.3390/jcm9051593DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7291169PMC
May 2020

Sulfur Compounds Inhibit High Glucose-Induced Inflammation by Regulating NF-κB Signaling in Human Monocytes.

Molecules 2020 May 17;25(10). Epub 2020 May 17.

Department of Pathology, School of Medicine, Institute of Biomedical Science and Technology, Konkuk University, Chungju 27478, Korea.

High glucose-induced inflammation leads to atherosclerosis, which is considered a major cause of death in type 1 and type 2 diabetic patients. Nuclear factor-kappa B (NF-κB) plays a central role in high glucose-induced inflammation and is activated through toll-like receptors (TLRs) as well as canonical and protein kinase C-dependent (PKC) pathways. Non-toxic sulfur (NTS) and methylsulfonylmethane (MSM) are two sulfur-containing natural compounds that can induce anti-inflammation. Using Western blotting, real-time polymerase chain reaction, and flow cytometry, we found that high glucose-induced inflammation occurs through activation of TLRs. An effect of NTS and MSM on canonical and PKC-dependent NF-κB pathways was also demonstrated by western blotting. The effects of proinflammatory cytokines were investigated using a chromatin immunoprecipitation assay and enzyme-linked immunosorbent assay. Our results showed inhibition of the glucose-induced expression of TLR2 and TLR4 by NTS and MSM. These sulfur compounds also inhibited NF-κB activity through reactive oxygen species (ROS)-mediated canonical and PKC-dependent pathways. Finally, NTS and MSM inhibited the high glucose-induced expression of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α and binding of NF-κB protein to the DNA of proinflammatory cytokines. Together, these results suggest that NTS and MSM may be potential drug candidates for anti-inflammation therapy.
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http://dx.doi.org/10.3390/molecules25102342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7287819PMC
May 2020

Deubiquitinase USP47-stabilized splicing factor IK regulates the splicing of pre-mRNA.

Cell Death Discov 2020 4;6:34. Epub 2020 May 4.

1Department of Biological Sciences, Sookmyung Women's University, Seoul, 04310 Korea.

IK depletion leads to an aberrant mitotic entry because of chromosomal misalignment through the enhancement of Aurora B activity at the interphase. Here, we demonstrate that IK, a spliceosomal component, plays a crucial role in the proper splicing of the pre-mRNA among other genes related with the DNA Damage Response (DDR). Intron 1 in the pre-mRNA, having lengths <200 bp, was not spliced in the IK-depleted cells and led to a deficiency of the ATM protein. Subsequently, the IK depletion-induced ATM protein deficiency impaired the ability to repair the damaged DNA. Because the absence of SMU1 results in IK degradation, the mechanism underlying IK degradation was exploited. IK was ubiquitinated in the absence of SMU1 and then subjected to proteolysis through the 26S proteasome. To prevent the proteolytic degradation of IK, a deubiquitinating enzyme, USP47, directly interacted with IK and stabilized it through deubiquitination. Collectively, our results suggest that IK is required for proper splicing of the pre-mRNA and USP47 contributes toward the stabilization of IK.
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http://dx.doi.org/10.1038/s41420-020-0268-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7198525PMC
May 2020

Amoxicillin or tetracycline in bismuth-containing quadruple therapy as first-line treatment for infection.

Gut Microbes 2020 09 2;11(5):1314-1323. Epub 2020 May 2.

Department of Internal Medicine, Hallym University College of Medicine , Chuncheon, Korea.

Aim: To compare the efficacy and safety between modified quadruple- and bismuth-containing quadruple therapy as first-line eradication regimen for infection.

Methods: This study was a multicenter, randomized-controlled, non-inferiority trial. Subjects endoscopically diagnosed with infection were randomly allocated to receive modified quadruple- (rabeprazole 20 mg bid, amoxicillin 1 g bid, metronidazole 500 mg tid, bismuth subcitrate 300 mg qid [elemental bismuth 480 mg]; PAMB) or bismuth-containing quadruple therapy (rabeprazole 20 mg bid, bismuth subcitrate 300 mg qid, metronidazole 500 mg tid, tetracycline 500 mg qid; PBMT) for 14 days. Rates of eradication success and adverse events were investigated. Antibiotic resistance was determined using the agar dilution and DNA sequencing of the clarithromycin resistance point mutations in the 23 S rRNA gene of .

Results: In total, 233 participants were randomized, 27 were lost to follow-up, and four violated the protocol. Both regimens showed an acceptable eradication rate in the intention-to-treat (PAMB: 87.2% vs. PBMT: 82.8%, = .37), modified intention-to-treat (96.2% vs. 96%, > .99), and per-protocol (96.2% vs. 96.9%, > .99) analyses. Non-inferiority in the eradication success between PAMB and PBMT was confirmed. The amoxicillin-, metronidazole-, tetracycline-, clarithromycin-, and levofloxacin-resistance rates were 8.3, 40, 9.4, 23.5, and 42.2%, respectively. Antimicrobial resistance did not significantly affect the efficacy of either therapy. Overall compliance was 98.1%. Adverse events were not significantly different between the two therapies.

Conclusion: Modified quadruple therapy comprising rabeprazole, amoxicillin, metronidazole, and bismuth is an effective first-line treatment for the infection in regions with high clarithromycin and metronidazole resistance.
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http://dx.doi.org/10.1080/19490976.2020.1754118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7524369PMC
September 2020

Factors Affecting the Number of Stapler Cartridges in Complete Video-Assisted Thoracoscopic Surgery Lobectomy for Non-small Cell Lung Cancer.

Korean J Thorac Cardiovasc Surg 2020 Apr;53(2):53-57

Department of Thoracic and Cardiovascular Surgery, Yonsei University College of Medicine, Seoul, Korea.

Background: Video-assisted thoracoscopic surgery (VATS) lobectomy has become the major surgical option for the treatment of non-small cell lung cancer (NSCLC). Endoscopic instruments such as stapler cartridges are essential for VATS procedures. In this study, we investigated the factors that affect the number of stapler cartridges used in VATS lobectomy.

Methods: A retrospective analysis was conducted of patients who underwent complete VATS lobectomy for NSCLC from January 2013 to December 2015.

Results: In total, 596 patients underwent complete VATS lobectomy. The average number of stapler cartridges used for VATS lobectomy was 5.3±1.9. The number of stapler cartridges used for VATS lobectomy was higher in men (5.5±1.9 vs. 5.0±18, p=0.006), those aged older than 70 years (5.5±2.1 vs. 5.1±1.7, p=0.038), those who underwent upper or middle lobectomy procedures (5.7±1.9 vs. 4.1±1.2, p<0.001), those with a higher fissure sum average (p<0.001), and those in whom surgery was performed by a surgeon with a preference for staplers (5.6±2.0 vs. 4.9±1.6, p<0.001).

Conclusion: The number of stapler cartridges required to perform VATS lobectomy in NSCLC patients appears to be influenced by sex, age, the location of the tumor, the degree of fissure development, and the surgeon's preference.
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http://dx.doi.org/10.5090/kjtcs.2020.53.2.53DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7155176PMC
April 2020

Effect of Methylsulfonylmethane on Proliferation and Apoptosis of A549 Lung Cancer Cells Through G/M Cell-cycle Arrest and Intrinsic Cell Death Pathway.

Anticancer Res 2020 Apr;40(4):1905-1913

Department of Pathology, School of Medicine, Institute of Biomedical Science and Technology, Konkuk University, Seoul, Republic of Korea

Background/aim: Methylsulfonylmethane (MSM) is a natural organic compound that displays anti-inflammatory as well as antioxidant properties. MSM reportedly has potential in inhibition of tumor cells. However, molecular mechanisms underlying the effects of MSM on lung cancer remain unclear.

Materials And Methods: In this study, the effect of MSM on A549 cells was examined. We focused on the mode of apoptosis induced by MSM and investigated alterations in the integrity of the outer membrane of mitochondria.

Results: Our results showed that MSM inhibited viability of A549 cells and changed the shape and permeability of nuclei. In addition, MSM induced G/M arrest. MSM reduced the mitochondrial membrane potential and contributed to release of cytochrome c from mitochondria to cytoplasm.

Conclusion: MSM is a potential anticancer agent for the treatment of lung cancer.
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http://dx.doi.org/10.21873/anticanres.14145DOI Listing
April 2020

The Inhibitory Mechanisms of Tumor PD-L1 Expression by Natural Bioactive Gallic Acid in Non-Small-Cell Lung Cancer (NSCLC) Cells.

Cancers (Basel) 2020 Mar 19;12(3). Epub 2020 Mar 19.

Department of Pathology, School of Medicine, Institute of Biomedical Science and Technology, Konkuk University, Seoul 05029, Korea.

Non-small-cell lung cancer (NSCLC) is the most common lung cancer subtype and accounts for more than 80% of all lung cancer cases. Epidermal growth factor receptor (EGFR) phosphorylation by binding growth factors such as EGF activates downstream prooncogenic signaling pathways including KRAS-ERK, JAK-STAT, and PI3K-AKT. These pathways promote the tumor progression of NSCLC by inducing uncontrolled cell cycle, proliferation, migration, and programmed death-ligand 1 (PD-L1) expression. New cytotoxic drugs have facilitated considerable progress in NSCLC treatment, but side effects are still a significant cause of mortality. Gallic acid (3,4,5-trihydroxybenzoic acid; GA) is a phenolic natural compound, isolated from plant derivatives, that has been reported to show anticancer effects. We demonstrated the tumor-suppressive effect of GA, which induced the decrease of PD-L1 expression through binding to EGFR in NSCLC. This binding inhibited the phosphorylation of EGFR, subsequently inducing the inhibition of PI3K and AKT phosphorylation, which triggered the activation of p53. The p53-dependent upregulation of miR-34a induced PD-L1 downregulation. Further, we revealed the combination effect of GA and anti-PD-1 monoclonal antibody in an NSCLC-cell and peripheral blood mononuclear-cell coculture system. We propose a novel therapeutic application of GA for immunotherapy and chemotherapy in NSCLC.
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http://dx.doi.org/10.3390/cancers12030727DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7140102PMC
March 2020