Development of CRISPR/Cas9 system for targeted DNA modifications and recent improvements in modification efficiency and specificity.
Abstract The targeted nuclease clustered, regularly interspaced short palindromic repeats/CRISPR-associated proteins (CRISPR/Cas) system has recently emerged as a prominent gene manipulation method. Because of its ease in programming targeted DNA/protein binding through RNA in a vast range of organisms, this prokaryotic defense system is a versatile tool with many applications in the research field as well as high potential in agricultural and clinical improvements. This review will present a brief history that led to its discovery and adaptation. We also present some of its restrictions, and modifications that ha...
Source: BMB Reports - June 25, 2020 Category: Biochemistry Authors: Shin J, Oh JW Tags: BMB Rep Source Type: research

Organic matrix-free imaging mass spectrometry.
Abstract Mass spectrometry (MS) is an ideal tool for analyzing multiple types of (bio)molecular information simultaneously in complex biological systems. In addition, MS provides structural information on targets, and can easily discriminate between true analytes and background. Therefore, imaging mass spectrometry (IMS) enables not only visualization of tissues to give positional information on targets but also allows for molecular analysis of targets by affording the molecular weights. Matrixassisted laser desorption/ionization-time of flight (MALDI-TOF) MS is particularly effective and is generally used for IMS...
Source: BMB Reports - June 25, 2020 Category: Biochemistry Authors: Kim E, Kim J, Choi I, Lee J, Yeo WS Tags: BMB Rep Source Type: research

Synergistic antitumor activity of a DLL4/VEGF bispecific therapeutic antibody in combination with irinotecan in gastric cancer.
Abstract Notch signaling has been identified as a critical pathway in gastric cancer (GC) progression and metastasis, and inhibition of Delta-like ligand 4 (DLL4), a Notch ligand, is suggested as a potent therapeutic approach for GC. Expression of both DLL4 and vascular endothelial growth factor receptor 2 (VEGFR2) was similar in the malignant tissues of GC patients. We focused on vascular endothelial growth factor (VEGF), a known angiogenesis regulator and activator of DLL4. Here, we used ABL001, a DLL4/VEGF bispecific therapeutic antibody, and investigated its therapeutic effect in GC. Treatment with human DLL4 ...
Source: BMB Reports - June 25, 2020 Category: Biochemistry Authors: Kim DH, Lee S, Kang HG, Park HW, Lee HW, Kim D, Yoem DH, Ahn JH, Ha E, You WK, Lee SH, Kim SJ, Chun KH Tags: BMB Rep Source Type: research

Regulation of signal transducer and activator of transcription 3 activation by dual-specificity phosphatase 3.
This study demonstrated that DUSP3 inhibits interleukin 6 (IL-6)/STAT3 signaling and is expected to regulate cancer development. Novel functions of DUSP3 discovered in IL-6/STAT3 signaling regulation would help expand the understanding of cancer development mechanisms. PMID: 32475380 [PubMed - as supplied by publisher] (Source: BMB Reports)
Source: BMB Reports - June 1, 2020 Category: Biochemistry Authors: Kim BR, Ha J, Kang E, Cho S Tags: BMB Rep Source Type: research

The activation of NLRP3 inflammasome potentiates the immunomodulatory abilities of mesenchymal stem cells in a murine colitis model.
In conclusion, our findings suggest that the NLRP3 inflammasome components are expressed in hUCB-MSCs and its activation can regulate the differentiation capability and the immunomodulatory effects of hUCB-MSCs. PMID: 32475381 [PubMed - as supplied by publisher] (Source: BMB Reports)
Source: BMB Reports - June 1, 2020 Category: Biochemistry Authors: Ahn JS, Seo Y, Oh SJ, Yang JW, Shin YY, Lee BC, Kang KS, Sung ES, Lee BJ, Mohammadpour H, Hur J, Shin TH, Kim HS Tags: BMB Rep Source Type: research

Recent advances in intravital microscopy for investigation of dynamic cellular behavior in vivo.
Abstract Currently, most biological researches rely on conventional experimental techniques that only allow static analyses at certain time points in vitro or ex vivo. However, if one can visualize cellular dynamics in living organisms, it would provide a unique opportunity to study key biological phenomena in vivo. Intravital microscopy (IVM) encompasses diverse optical systems for direct visualization of objects including biological structures and individual cells in live animals. With the current development of devices and techniques, IVM addresses important questions in various fields of biological and biomedi...
Source: BMB Reports - June 1, 2020 Category: Biochemistry Authors: Choo YW, Jeong J, Jung K Tags: BMB Rep Source Type: research

From Genome Sequencing to the Discovery of Potential Biomarkers in Liver Disease.
Abstract Chronic liver disease progresses through several stages, fatty liver, steatohepatitis, cirrhosis, and eventually, it leads to hepatocellular carcinoma (HCC) over a long period of time. Since a large proportion of patients with HCC are accompanied by cirrhosis, it is considered to be an important factor in the diagnosis of liver cancer. This is because cirrhosis leads to an irreversible harmful effect, but the early stages of chronic liver disease could be reversed to a healthy state. Therefore, the discovery of biomarkers that could identify the early stages of chronic liver disease is important to preven...
Source: BMB Reports - June 1, 2020 Category: Biochemistry Authors: Oh S, Jo Y, Jung S, Yoon S, Yoo KH Tags: BMB Rep Source Type: research

TCP10L negatively regulates alpha-fetoprotein expression in hepatocellular carcinoma.
In this study, we found that TCP10L, a gene specifically expressed in the liver, is down-regulated in HCC and that its expression inversely correlates with AFP expression. Moreover, overexpression of TCP10L suppresses AFP expression whereas knockdown of TCP10L increases AFP expression, suggesting that TCP10L might be a negative regulator of AFP. We found that TCP10L is associated with the AFP promoter and inhibits AFP promoter-driven transcriptional activity. Taken together, these results indicate that TCP10L negatively regulates AFP expression in HCC and that it could be a potential prognostic marker and therapeutic targe...
Source: BMB Reports - May 22, 2020 Category: Biochemistry Authors: Shen S, Feng H, Liu L, Su W, Yu L, Wu J Tags: BMB Rep Source Type: research

miR-3074-3p promotes myoblast differentiation by targeting Cav1.
Abstract Muscle fibers are generally formed as multinucleated fibers that are differentiated from myoblasts. Several reports have identified transcription factors and proteins involved in the process of muscle differentiation, but the roles of microRNAs (miRNAs) in myogenesis remain unclear. Here, comparative analysis of the miRNA expression profiles in mouse myoblasts and gastrocnemius (GA) muscle uncovered miR-3074-3p as a novel miRNA showing markedly reduced expression in fully differentiated adult skeletal muscle. Interestingly, elevating miR-3074-3p promoted myogenesis in C2C12 cells, primary myoblasts, and H...
Source: BMB Reports - May 22, 2020 Category: Biochemistry Authors: Lee B, Shin YJ, Lee SM, Son YH, Yang YR, Lee KP Tags: BMB Rep Source Type: research

Antibody-secreting macrophages generated using CpG-free plasmid eliminate tumor cells through antibody-dependent cellular phagocytosis.
In this study, the microporation of a CpG-free and small plasmid (pCGfd-GFP) showed high transfection efficiency, sustainable transgene expression, and good cell viability in the transfections of Raw 264.7 and primary bone=marrow-derived macrophages. The non-viral method using the pCGfd vector encoding anti-EGFR single-chain Fv fused with Fc (scFv-Fc) generated the macrophages secreting anti-EGFR scFv-Fc. These macrophages effectively phagocytized tumor cells expressing EGFR through the antibody-dependent mechanism, as was proved by experiments using EGFR-knockout tumor cells. Finally, peri-tumoral injections of anti-EGFR ...
Source: BMB Reports - May 22, 2020 Category: Biochemistry Authors: Cha EB, Shin KK, Seo J, Oh DB Tags: BMB Rep Source Type: research

Angiogenesis and Vasculogenic Mimicry as Therapeutic Targets in Ovarian Cancer.
Abstract Tumor angiogenesis is an essential process for growth and metastasis of cancer cells as it supplies tumors with oxygen and nutrients. During tumor angiogenesis, many pro-angiogenic factors are secreted by tumor cells to induce their own vascularization via activation of pre-existing host endothelium. However, accumulating evidence suggests that vasculogenic mimicry (VM) is a key alternative mechanism for tumor vascularization when tumors are faced with insufficient supply of oxygen and nutrients. VM is a tumor vascularization mechanism in which tumors create a blood supply system, in contrast to tumor ang...
Source: BMB Reports - May 22, 2020 Category: Biochemistry Authors: Lim D, Do Y, Kim J, Cho JG Tags: BMB Rep Source Type: research

Improved Human Hematopoietic Reconstitution in HepaRG Co-transplanted Humanized NSG Mice.
Abstract Several humanized mouse models are being used to study human-specific immune responses and diseases. However, the pivotal needs of fetal tissues for the humanized mice model have been huddled because of the demand for ethical and medical approval. Thus, we have verified the hematopoietic and immunomodulatory function of HepaRG and developed a new and easy humanized mouse model to replace the use of fetal liver tissue. HepaRG co-transplanted Hu-NSG mice significantly increased CD45+ lymphocytes and CD19+ B cells and CD3+ T cells than normal Hu-NSG, suggesting enhanced reconstitution of the human immune sys...
Source: BMB Reports - April 29, 2020 Category: Biochemistry Authors: Kim J, Ryu B, Kim U, Kim CH, Hur GH, Kim CY, Park JH Tags: BMB Rep Source Type: research

Development and Evaluation of Next-generation Cardiotoxicity Assay Based on Embryonic Stem Cell-derived Cardiomyocytes.
In this study, in vitro high-efficiency CMs derived from human embryonic stem cells (hESC-CMs) were compared with Sprague-Dawley rats as in vivo experimental animals, and primary cultured in vitro rat-CMs for cardiotoxicity tests. In vivo rats were administrated with two consecutive injections of 100 mg/kg isoproterenol, 15 mg/kg doxorubicin, or 100 mg/kg nifedipine, while in vitro rat-CMs and hESC-CMs were treated with 5 μM isoproterenol, 5 μM doxorubicin, and 50 μM nifedipine. We have verified the equivalence of hESC-CMs assessments over various molecular biological markers, morphological analysis. Also, we have...
Source: BMB Reports - April 29, 2020 Category: Biochemistry Authors: Ryu B, Choi SW, Lee SG, Jeong YH, Kim U, Kim J, Jung CR, Chung HM, Park JH, Kim CY Tags: BMB Rep Source Type: research

Glycosyl flavones from Humulus japonicus suppress MMP-1 production via decreasing oxidative stress in UVB irradiated human dermal fibroblasts.
This study focused on the isolation of active compounds from H. japonicus and the evaluation of their effects on photoaging in UVB-irradiated human fibroblast (Hs68) cells. When the extract and four fractions of H. japonicus were treated respectively in UVB-irradiated Hs68 cells to investigate anti-photoaging effects, the ethyl acetate (EtOAc) fraction showed the strongest inhibitory effect on MMP-1 secretion. From EtOAc fraction, we isolated luteolin-8-C-glucoside (1), apigenin-8-C-glucoside (2), and luteolin-7-O-glucoside (3). These compounds suppressed UVB-induced MMP-1 production by inhibiting the phosphorylation of th...
Source: BMB Reports - April 22, 2020 Category: Biochemistry Authors: Nam EJ, Yoo G, Lee JY, Kim M, Jhin C, Son YJ, Kim SY, Jung SH, Nho CW Tags: BMB Rep Source Type: research

Tumor necrosis factor-inducible gene 6 interacts with CD44, which is involved in fate-change of hepatic stellate cells.
Abstract Tumor necrosis factor-inducible gene 6 protein (TSG-6) is a cytokine secreted by mesenchymal stem cells (MSCs) and regulates MSC stemness. We previously reported that TSG-6 changes primary human hepatic stellate cells (pHSCs) into stem-like cells by activating yes-associated protein-1 (YAP-1). However, the molecular mechanism behind the reprogramming action of TSG-6 in pHSCs remains unknown. Cluster of differentiation 44 (CD44) is a transmembrane protein that has multiple functions depending on the ligand it is binding, and it is involved in various signaling pathways, including the Wnt/β-catenin pat...
Source: BMB Reports - April 22, 2020 Category: Biochemistry Authors: Wang S, Kim J, Lee C, Jung Y Tags: BMB Rep Source Type: research

GPx7 ameliorates non-alcoholic steatohepatitis by regulating oxidative stress.
Abstract Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases. NAFLD can further progress to irreversible liver failure such as non-alcoholic steatohepatitis (NASH) fibrosis and cirrhosis. However, specific regulator of NASH-fibrosis has yet to be established. Here, we found that glutathione peroxidase 7 (GPx7) was markedly expressed in NASH fibrosis. Although GPx7 is an antioxidant enzyme protecting other organs, whether GPx7 plays a role in NASH fibrosis has yet to be studied. We found that knockdown of GPx7 in transforming growth factor-β (TGF-β) and free fatty acids (FFA...
Source: BMB Reports - April 22, 2020 Category: Biochemistry Authors: Kim HJ, Lee Y, Fang S, Kim W, Kim HJ, Kim JW Tags: BMB Rep Source Type: research

Transcription factor EGR-1 transactivates the MMP1 gene promoter in response to TNF α in HaCaT keratinocytes.
Transcription factor EGR-1 transactivates the MMP1 gene promoter in response to TNFα in HaCaT keratinocytes. BMB Rep. 2020 Apr 22;: Authors: Yeo H, Lee JY, Kim J, Lee YH, Shin SY Abstract Matrix metalloproteinase 1 (MMP-1), a calcium-dependent zinc-containing collagenase, is involved in the initial degradation of native fibrillar collagen. Tissue necrosis factor-alpha (TNFα) is a pro-inflammatory cytokine that is rapidly produced by dermal fibroblasts, monocytes/macrophages, and keratinocytes and regulates inflammation and damaged-tissue remodeling. MMP-1 is induced by TNFα and plays...
Source: BMB Reports - April 22, 2020 Category: Biochemistry Authors: Yeo H, Lee JY, Kim J, Lee YH, Shin SY Tags: BMB Rep Source Type: research

Cell cycle-related kinase is a crucial regulator for ciliogenesis and Hedgehog signaling in embryonic mouse lung development.
Abstract Cell cycle-related kinase (CCRK) has a conserved role in ciliogenesis, and Ccrk defects in mice lead to developmental defects, including exencephaly, preaxial polydactyly, skeletal abnormalities, retinal degeneration, and polycystic kidney. Here, we found that Ccrk is highly expressed in mouse trachea and bronchioles. Ccrk mutants exhibited pulmonary hypoplasia and abnormal branching morphogenesis in respiratory organ development. Furthermore, we demonstrated that Ccrk mutant lungs exhibit not only impaired branching morphogenesis but also a significant sacculation deficiency in alveoli associated with re...
Source: BMB Reports - April 22, 2020 Category: Biochemistry Authors: Lee H, Ko HW Tags: BMB Rep Source Type: research

Inhibition of LSD1 phosphorylation alleviates colitis symptoms induced by dextran sulfate sodium.
Abstract Inflammatory Bowel Disease is caused by an acute or chronic dysfunction of the mucosal inflammatory system in the intestinal tract. In line with the results of our previous study, wherein we found that the PKCα-LSD1-NF-κB signaling plays a critical role in the prolonged activation of the inflammatory response, we aimed to investigate the effect of signaling on colitis in the present study. Lsd1 S112A knock-in (Lsd1SA/SA) mice, harboring a deficiency in phosphorylation by PKCα, exhibited less severe colitis symptoms and a relatively intact colonic epithelial lining in dextran sulfate sodi...
Source: BMB Reports - April 22, 2020 Category: Biochemistry Authors: Oh C, Jeong J, Oh SK, Baek SH, Kim KI Tags: BMB Rep Source Type: research

Serine 389 phosphorylation of 3-phosphoinositide-dependent kinase 1 by UNC-51-like kinase 1 affects its ability to regulate Akt and p70 S6kinase.
Abstract Phosphorylation of the signaling component by protein kinase often leads to a kinase cascade or feedback loop. 3-Phosphoinositide-dependent kinase 1 (PDK1) signaling pathway diverges into various kinases including Akt and p70 S6 kinase (p70S6k). However, the PDK1 feedback mechanism remains elusive. Here, we demonstrated that UNC-51-like kinase (ULK1), an autophagy initiator kinase downstream of mechanistic target of rapamycin (mTOR), directly phosphorylated PDK1 on serine 389 at the linker region. Furthermore, our data showed that this phosphorylation affected the kinase activity of PDK1 toward downstream...
Source: BMB Reports - April 22, 2020 Category: Biochemistry Authors: Kim K, Park SG, Park BC, Kim JH, Kim S Tags: BMB Rep Source Type: research

Altered expression of parvalbumin immunoreactivity in rat main olfactory bulb following pilocarpine-induced status epilepticus.
Abstract Epilepsy is a chronic neurological disease characterized by spontaneous recurrent seizures and caused by various factors and mechanisms. Malfunction of the olfactory bulb is frequently observed in patients with epilepsy. However, the morphological changes in the olfactory bulb during epilepsy-induced neuropathology have not been elucidated. Therefore, in the present study, we investigated the expression of parvalbumin (PV), one of the calcium-binding proteins, and morphological changes in the rat main olfactory bulb (MOB) following pilocarpine-induced status epilepticus (SE). Pilocarpine-induced SE result...
Source: BMB Reports - April 22, 2020 Category: Biochemistry Authors: Yu YH, Park DK, Yoo DY, Kim DS Tags: BMB Rep Source Type: research

Bee venom inhibits the proliferation and migration of cervical-cancer cells in an HPV E6/E7-dependent manner.
In this study, we have shown the molecular mechanism underlying the therapeutic effect of BV on cancer. Treatment with BV reduced the proliferation of cervical-cancer cells in a dose- and time-dependent manner. Interestingly, the killing effect of BV was specific to HPV-positive cervical-cancer cell lines, such as Caski and HeLa cells, and not to HPV-negative cervical-cancer cells (C33A). BV reduced the expression of HPV E6 and E7 at RNA and protein levels, leading to an increase in the expression of p53 and Rb in Caski and HeLa cells. Further, BV decreased the levels of cell-cycle proteins, such as cyclin A and B, and inc...
Source: BMB Reports - April 22, 2020 Category: Biochemistry Authors: Kim DH, Lee HW, Park HW, Lee HW, Chun KH Tags: BMB Rep Source Type: research

Sulfasalazine Attenuates Tamoxifen-induced Toxicity in Human Retinal Pigment Epithelial Cells.
Abstract Tamoxifen, a nonsteroidal estrogen receptor (ER) antagonist, is used routinely as a chemotherapeutic agent for ER-positive breast cancer. However, it is also causes side effects, including retinotoxicity. The retinal pigment epithelium (RPE) has been recognized as the primary target of tamoxifen-induced retinotoxicity. The RPE plays an essential physiological role in the normal functioning of the retina. Nonetheless, potential therapeutic agents to prevent tamoxifen-induced retinotoxicity in breast cancer patients have not been investigated. Here, we evaluated the action mechanisms of sulfasalazine agains...
Source: BMB Reports - April 22, 2020 Category: Biochemistry Authors: Hwang N, Chung SW Tags: BMB Rep Source Type: research

Protein kinase CK2 activates Nrf2 via autophagic degradation of Keap1 and activation of AMPK in human cancer cells.
In this study, Nrf2 overexpression attenuated CK2 downregulation-induced ROS production and senescence markers including SA-β-gal staining and activation of p53-p21Cip1/WAF1 in human breast (MCF-7) and colon (HCT116) cancer cells. CK2 downregulation reduced the transcription of Nrf2 target genes, such as glutathione S-transferase, glutathione peroxidase 2, and glutathione reductase 1. Furthermore, CK2 downregulation destabilized Nrf2 protein via inhibiting autophagic degradation of Kelch-like ECH-associated protein 1 (Keap1). Finally, CK2 downregulation decreased the nuclear import of Nrf2 by deactivating AMP-activate...
Source: BMB Reports - April 22, 2020 Category: Biochemistry Authors: Jang DE, Song J, Park JW, Yoon SH, Bae YS Tags: BMB Rep Source Type: research

Analysis of Opposing Histone Modifications H3K4me3 and H3K27me3 Reveals Candidate Diagnostic Biomarkers for TNBC and Gene Set Prediction Combination.
Abstract Breast cancer encompasses a major portion of human cancers and must be carefully monitored for appropriate diagnoses and treatments. Among the many types of breast cancers, triple negative breast cancer (TNBC) has the worst prognosis and the least cases reported. To gain a better understanding and a more decisive precursor for TNBC, two major histone modifications, an activating modification H3K4me3 and a repressive modification H3K27me3, were analyzed using data from normal breast cell lines against TNBC cell lines. The combination of these two histone markers on the gene promoter regions showed a great ...
Source: BMB Reports - April 22, 2020 Category: Biochemistry Authors: Park HM, Kim H, Lee KH, Cho JY Tags: BMB Rep Source Type: research

Quantitative and qualitative analysis of autophagy flux using imaging.
Abstract As an intracellular degradation system, autophagy is an essential and defensive cellular program required for cell survival and cellular metabolic homeostasis in response to various stresses, such as nutrient deprivation and the accumulation of damaged organelles. In general, autophagy flux consists of four steps: (1) initiation (formation of phagophore), (2) maturation and completion of autophagosome, (3) fusion of autophagosomes with lysosomes (formation of autolysosome), and (4) degradation of intravesicular components within autolysosomes. The number of genes and reagents that modulate autophagy is in...
Source: BMB Reports - April 22, 2020 Category: Biochemistry Authors: Kim S, Choi S, Kang D Tags: BMB Rep Source Type: research

Functional Roles of Protein Phosphatase 4 in Multiple Aspects of Cellular Physiology: A Friend and A Foe.
Abstract Protein phosphatase 4 (PP4), one of serine/threonine phosphatases, is involved in many critical cellular pathways, including DNA damage response (DNA repair, cell cycle regulation, and apoptosis), tumorigenesis, cell migration, immune response, stem cell development, glucose metabolism, and diabetes. PP4 has been steadily studied over the past decade about wide spectrum of physiological activities in cells. Given the many vital functions in cells, PP4 has great potential to develop into the finding of key working mechanisms and effective treatments for related diseases such as cancer and diabetes. In this...
Source: BMB Reports - March 20, 2020 Category: Biochemistry Authors: Park J, Lee DH Tags: BMB Rep Source Type: research

Emerging Role of Transient Receptor Potential (TRP) channels in Cancer Progression.
Abstract Transient receptor potential (TRP) channels comprise a diverse family of ion channels, the majority of which are calcium permeable and show sophisticated regulatory patterns in response to various environmental cues. Early studies led to the recognition of TRP channels as environmental and chemical sensors. Later studies revealed that TRP channels mediated the regulation of intracellular calcium. Mutations in TRP channel genes result in abnormal regulation of TRP channel function or expression, and interfere with normal spatial and temporal patterns of intracellular local Ca2+ distribution. The resulting ...
Source: BMB Reports - March 16, 2020 Category: Biochemistry Authors: Yang D, Kim J Tags: BMB Rep Source Type: research

Mechanistic insights into differential requirement of receptor dimerization for oncogenic activation of mutant EGFR and its clinical perspective.
Abstract The epidermal growth factor receptor (EGFR), a member of the ErbB family (EGFR, ErbB2, ErbB3 and ErbB4), plays a crucial role in regulating various cellular responses such as proliferation, differentiation, and survival. As a result, aberrant activation of EGFR, mostly mediated through different classes of genomic alterations occurring within EGFR, is closely associated with the pathogenesis of numerous human cancers including lung adenocarcinoma, glioblastoma, and colorectal cancer. Thus, specific suppression of oncogenic activity of mutant EGFR with its targeted drugs has been routinely used in the clin...
Source: BMB Reports - March 16, 2020 Category: Biochemistry Authors: Cho J Tags: BMB Rep Source Type: research

Overexpression of three related root-cap outermost-cell-specific C2H2-type zinc-finger protein genes suppresses the growth of Arabidopsis in an EAR-motif-dependent manner.
Abstract The root meristem of Arabidopsis thaliana is protected by the root cap, the size of which is tightly regulated by the balance between the formative cell divisions and the dispersal of the outermost cells. We isolated an enhancer-tagged dominant mutant displaying the short and twisted root by the overexpression of ZINC-FINGER OF ARABIDOPSIS THALIANA1 (ZAT1) encoding an EAR motif-containing zinc-finger protein. The growth inhibition by ZAT1 was shared by ZAT4 and ZAT9, the ZAT1 homologues. The ZAT1 promoter was specifically active in the outermost cells of the root cap, in which ZAT1-GFP was localized when ...
Source: BMB Reports - March 16, 2020 Category: Biochemistry Authors: Song SK, Jang HU, Kim YH, Lee BH, Lee MM Tags: BMB Rep Source Type: research

Non-classical role of Galectin-3 in cancer progression: Translocation to nucleus by carbohydrate-recognition independent manner.
Abstract Galectin-3 is a carbohydrate-binding protein and regulates diverse functions, including cell proliferation and differentiation, mRNA splicing, apoptosis induction, immune surveillance and inflammation, cell adhesion, angiogenesis, and cancer-cell metastasis. Galectin-3 is also recommended as a diagnostic or prognostic biomarker of various diseases, including heart disease, kidney disease, and cancer. Galectin-3 exists as a cytosol, is secreted in extracellular spaces on cells, and is also detected in nuclei. It has been found that galectin-3 has different functions in cellular localization: (i) Extracellu...
Source: BMB Reports - March 16, 2020 Category: Biochemistry Authors: Kim SJ, Chun KH Tags: BMB Rep Source Type: research

MiR-449a attenuates autophagy of T-cell lymphoma cells by downregulating ATG4B expression.
In conclusion, our results demonstrated that the "miR-449a/ATG4B/autophagy" pathway played a vital role in the malignancy of T-cell lymphoma, suggesting a novel therapeutic target. PMID: 32172731 [PubMed - as supplied by publisher] (Source: BMB Reports)
Source: BMB Reports - March 16, 2020 Category: Biochemistry Authors: Zhang N, Qiu L, Li T, Wang X, Deng R, Yi H, Su Y, Fan FY Tags: BMB Rep Source Type: research

Solution structure and functional analysis of HelaTx1: the first toxin member of the к-KTx5 subfamily.
Abstract Scorpion venom comprises a cocktail of toxins that have proven to be useful molecular tools for studying the pharmacological properties of membrane ion channels. HelaTx1, a short peptide neurotoxin isolated recently from the venom of the scorpion Heterometrus laoticus, is a 25 amino acid peptide with two disulfide bonds that shares low sequence homology with other scorpion toxins. HelaTx1 effectively decreases the amplitude of the K+ currents of voltage-gated Kv1.1 and Kv1.6 channels expressed in Xenopus oocytes, and was identified as the first toxin member of the κ-KTx5 subfamily, based on a sequen...
Source: BMB Reports - March 16, 2020 Category: Biochemistry Authors: Park BG, Peigneur S, Esaki N, Yamaguchi Y, Ryu JH, Tytgat J, Kim JI, Sato K Tags: BMB Rep Source Type: research

Physalin D Inhibits RANKL-induced Osteoclastogenesis and Bone Loss via Regulating Calcium Signaling.
Abstract We investigated the effects of physalin A, B, D, and F on osteoclastogenesis induced by receptor activator of nuclear factor κB ligand (RANKL). The biological functions of different physalins were first predicted using an in silico bioinformatic tool (BATMAN-TCM). Afterwards, we tested cell viability and cell apoptosis rate to analyze the cytotoxicity of different physalins. We analyzed the inhibitory effects of physalins on RANKL-induced osteoclastogenesis from mouse bone-marrow macrophages (BMMs) using a tartrate-resistant acid phosphatase (TRAP) stain. We found that physalin D has the best select...
Source: BMB Reports - January 21, 2020 Category: Biochemistry Authors: Ding N, Lu Y, Cui H, Ma Q, Qiu D, Wei X, Dou C, Cao N Tags: BMB Rep Source Type: research

15d-PGJ2 inhibits NF- κB and AP-1-mediated MMP-9 expression and invasion of breast cancer cell by means of a heme oxygenase-1-dependent mechanism.
In this study, we investigated the effects of induction of HO-1 by PPARγ on TPA-induced MMP-9 expression and cell invasion using MCF-7 breast cancer cells. TPA treatment increased NF-κB /AP-1 DNA binding as well as MMP-9 expression. These effects were significantly blocked by 15d-PGJ2, a natural PPARγ ligand. 15d-PGJ2 induced HO-1 expression in a dose-dependent manner. Interestingly, HO-1 siRNA significantly attenuated the inhibition of TPA-induced MMP-9 protein expression and cell invasion by 15d-PGJ2. These results suggest that 15d-PGJ2 inhibits TPA-induced MMP-9 expression and invasion of MCF-7 cells b...
Source: BMB Reports - January 21, 2020 Category: Biochemistry Authors: Jang HY, Hong OY, Youn HJ, Kim MG, Kim CH, Jung SH, Kim JS Tags: BMB Rep Source Type: research

Antiviral activity of sertindole, raloxifene and ibutamoren against transcription and replication-competent Ebola virus-like particles.
Abstract A chemical library comprising 2,354 drug-like compounds was screened using a transcription and replication-competent virus-like particle (trVLP) system that implements the whole Ebola virus (EBOV) life cycle. Dose-dependent inhibition of Ebola trVLP replication was induced by 15 hit compounds, which target different kinds of G protein-coupled receptors (GPCRs) mainly. Based on the chemical structures, they were divided into three groups, diphenylmethane derivatives, promazine derivatives or without any core skeletons. Within the third group, sertindole, raloxifene, and ibutamoren showed prominent antivira...
Source: BMB Reports - January 21, 2020 Category: Biochemistry Authors: Yoon YS, Jang Y, Hoenen T, Shin H, Lee Y, Kim M Tags: BMB Rep Source Type: research

PEP-1-GLRX1 protein exhibits anti-inflammatory effects by inhibiting the activation of MAPK and NF- κB pathways in Raw 264.7 cells.
PEP-1-GLRX1 protein exhibits anti-inflammatory effects by inhibiting the activation of MAPK and NF-κB pathways in Raw 264.7 cells. BMB Rep. 2020 Jan 21;: Authors: Shin MJ, Kim DW, Choi YJ, Cha HJ, Lee SH, Lee S, Park J, Han KH, Eum WS, Choi SY Abstract Glutaredoxin 1 (GLRX1) has been recognized as an important regulator of redox signaling. Although GLRX1 plays an essential role in cell survival as an antioxidant protein, the function of GLRX1 protein in inflammatory response is still under investigation. Therefore, we wanted to know whether transduced PEP-1-GLRX1 protein inhibits lipopolysacchar...
Source: BMB Reports - January 21, 2020 Category: Biochemistry Authors: Shin MJ, Kim DW, Choi YJ, Cha HJ, Lee SH, Lee S, Park J, Han KH, Eum WS, Choi SY Tags: BMB Rep Source Type: research

MicroRNA-22 negatively regulates LPS-induced inflammatory responses by targeting HDAC6 in macrophages.
The objective of this study was to elucidate the regulatory role of microRNA-22 (miR-22) in HDAC6-mediated expression of pro-inflammatory cytokines in lipopolysaccharide (LPS)-stimulated macrophages. LPS stimulation induced HDAC6 expression, but suppressed miR-22 expression in macrophages, suggesting possible correlation between HDAC6 and miR-22. Luciferase reporter assays revealed that 3'UTR of HDAC6 was a bona fide target site of miR-22. Transfection of miR-22 mimic significantly inhibited LPS-induced HDAC6 expression, while miR-22 inhibitor further increased LPS-induced HDAC6 expression. LPS-induced activation of NF-&ka...
Source: BMB Reports - January 21, 2020 Category: Biochemistry Authors: Youn GS, Park JK, Lee CY, Jang JH, Yun SH, Kwon HY, Choi SY, Park J Tags: BMB Rep Source Type: research

Dehydrocostus lactone inhibits NFATc1 via regulation of IKK, JNK, and Nrf2, thereby attenuating osteoclastogenesis.
Abstract Excessive and hyperactive osteoclast activity causes bone diseases such as osteoporosis and periodontitis. Thus, the regulation of osteoclast differentiation has clinical implications. We recently reported that dehydrocostus lactone (DL) inhibits osteoclast differentiation by regulating a nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), but the underlying mechanism remains to be elucidated. Here we demonstrated that DL inhibits NFATc1 by regulating nuclear factor-κB (NF-κB), activator protein-1 (AP-1), and nuclear factor-erythroid 2-related factor 2 (Nrf2). DL attenuated IκB&...
Source: BMB Reports - January 21, 2020 Category: Biochemistry Authors: Lee HI, Lee GR, Lee J, Kim N, Kwon M, Kim HJ, Kim NY, Park JH, Jeong W Tags: BMB Rep Source Type: research

Characterization of human cardiac mesenchymal stromal cells and their extracellular vesicles comparing with human bone marrow derived mesenchymal stem cells.
Abstract Cardiac regeneration with adult stem-cell (ASC) therapy is a promising field to address advanced cardiovascular diseases. In addition, extracellular vesicles (EVs) from ASCs have been implicated in acting as paracrine factors to improve cardiac functions in ASC therapy. In our work, we isolated human cardiac mesenchymal stromal cells (h-CMSCs) by means of three-dimensional organ culture (3D culture) during ex vivo expansion of cardiac tissue, to compare the functional efficacy with human bone-marrow derived mesenchymal stem cells (h-BM-MSCs), one of the actively studied ASCs. We characterized the h-CMSCs ...
Source: BMB Reports - January 21, 2020 Category: Biochemistry Authors: Kang IS, Suh J, Lee MN, Lee C, Jin J, Lee C, Yang YI, Jang Y, Oh GT Tags: BMB Rep Source Type: research

Methylated-UHRF1 and PARP1 interaction is critical for homologous recombination.
Abstract A recent study suggested that methylation of ubiquitin-like with PHD and RING finger domain 1 (UHRF1) is regulated by SET7 and lysine-specific histone demethylase 1A (LSD1) and is essential for homologous recombination (HR). The study demonstrated that SET7-mediated methylation of UHRF1 promotes polyubiquitination of proliferating cell nuclear antigen (PCNA), inducing HR. However, studies on mediators that interact with and recruit UHRF1 to damaged lesions are needed to elucidate the mechanism of UHRF1 methylationinduced HR. Here, we identified that poly [ADP-ribose] polymerase 1 (PARP1) interacts with da...
Source: BMB Reports - January 21, 2020 Category: Biochemistry Authors: Hahm JY, Kang JY, Park JW, Jung H, Seo SB Tags: BMB Rep Source Type: research

Impact of mesenchymal stem cell senescence on inflammaging.
Abstract Life expectancy has dramatically increased around the world over the last few decades, and staying healthier longer, without chronic disease, has become an important issue. Although understanding aging is a grand challenge, our understanding of the mechanisms underlying the degeneration of cell and tissue functions with age and its contribution to chronic disease has greatly advanced during the past decade. As our immune system alters with aging, abnormal activation of immune cells leads to imbalance of innate and adaptive immunity and develops a persistent and mild systemic inflammation, inflammaging. Wi...
Source: BMB Reports - January 21, 2020 Category: Biochemistry Authors: Lee BC, Yu KR Tags: BMB Rep Source Type: research

Impact of mesenchymal stem cell senescence on inflammaging.
Abstract Under physiological and pathological conditions, mechanical forces generated from cells themselves or transmitted from extracellular matrix (ECM) through focal adhesions (FAs) and adherens junctions (AJs) are known to play a significant role in regulating various cell behaviors. Substantial progresses have been made in the field of mechanobiology towards novel methods to understand how cells are able to sense and adapt to these mechanical forces over the years. To address these issues, this review will discuss recent advancements of traction force microscopy (TFM), intracellular force microscopy (IFM), an...
Source: BMB Reports - January 21, 2020 Category: Biochemistry Authors: Hur SS, Jeong JH, Ban MJ, Park JH, Yoon JK, Hwang Y Tags: BMB Rep Source Type: research

Mitochondria and neurodegenerative diseases: Special issue of BMB Reports in 2020.
Abstract Mitochondria is essential to generate metabolic energy in eukaryotic cells as well as to regulate calcium buffering, cell signaling, the production of reactive oxygen species (ROS), and apoptosis. They mainly produce most of the cellular energy derived from the breakdown of carbohydrates and fatty acids, which is consequently converted to ATP via oxidative phosphorylation. Mitochondria are also distinctive among the cytoplasmic organelles in that they contain their own DNA, which encodes limited number of mitochondrial proteins, tRNAs, and rRNAs. Evidence has accumulated from many reports, indicating that...
Source: BMB Reports - December 23, 2019 Category: Biochemistry Authors: Chung KC Tags: BMB Rep Source Type: research

Peripheral inflammatory biomarkers in Alzheimer's disease: a brief review.
Abstract Alzheimer's disease (AD) is a chronic neurodegenerative disease characterized by the accumulation of amyloid plaques and neurofibrillary tangles in the brain. The AD pathophysiology entails chronic inflammation involving innate immune cells including microglia, astrocytes, and other peripheral blood cells. Inflammatory mediators such as cytokines and complements are also linked to AD pathogenesis. Despite increasing evidence supporting the association between abnormal inflammation and AD, no well-established inflammatory biomarkers are currently available for AD. Since many reports have shown that abnorma...
Source: BMB Reports - December 23, 2019 Category: Biochemistry Authors: Park JC, Han SH, Mook-Jung I Tags: BMB Rep Source Type: research

Hypoxia-induced miR-1260b regulates vascular smooth muscle cell proliferation by targeting GDF11.
Abstract Vascular smooth muscle cells (VSMCs) are a unique cell type that has unusual plasticity controlled by environmental stimuli. As an abnormal increase of VSMC proliferation is associated with various vascular diseases, tight regulation of VSMC phenotypes is essential for maintaining vascular homeostasis. Hypoxia is one environmental stress that stimulates VSMC proliferation. Emerging evidence has indicated that microRNAs (miRNAs) are critical regulators in the hypoxic responses of VSMCs. Therefore, we previously investigated miRNAs modulated by hypoxia in VSMCs and found that miR-1260b is one of the most up...
Source: BMB Reports - December 10, 2019 Category: Biochemistry Authors: Seong M, Kang H Tags: BMB Rep Source Type: research

Human transcription factor YY1 could upregulate the HIV-1 gene expression.
Abstract Gene expression in HIV-1 is regulated by the promoters in 5' long-terminal repeat (LTR) element, which contain multiple DNA regulatory elements that serve as binding sites for cellular transcription factors. YY1 could repress HIV-1 gene expression and latent infection (1-4). Here, however, we observed that virus production can be increased by YY1 over-expression and decreased under YY1 depleted condition by siRNA treatment. To identify functional domain(s) of YY1 activation, we constructed a number of YY1 truncated mutants. Our data show that full-length YY1 enhances the viral transcription both through U...
Source: BMB Reports - December 10, 2019 Category: Biochemistry Authors: Yu K, Jung YM, Park SH, Lee SD, You JC Tags: BMB Rep Source Type: research

Inhibition of p90RSK activation sensitizes triple-negative breast cancer cells to cisplatin by inhibiting proliferation, migration and EMT.
Abstract Cisplatin (Cis-DDP) is one of the most widely used anti-cancer drugs. It is applicable to many types of cancer, including lung, bladder, and breast cancer. However, its use is now limited because of drug resistance. p90 ribosomal S6 kinase (p90RSK) is one of the downstream effectors in the extracellular signalregulated protein kinases 1 and 2 (ERK1/2) pathway and high expression of p90RSK is observed in human breast cancer tissues. Therefore, we investigated the role of p90RSK in the Cis-DDP resistance-related signaling pathway and epithelialmesenchymal transition (EMT) in breast cancer cells. First, we d...
Source: BMB Reports - December 10, 2019 Category: Biochemistry Authors: Jin Y, Huynh DTN, Kang KW, Myung CS, Heo KS Tags: BMB Rep Source Type: research

TOMM20 as a Potential Therapeutic Target of Colorectal Cancer.
Abstract Translocase of outer mitochondrial membrane 20 (TOMM20) plays an essential role as a receptor for proteins targeted to mitochondria. TOMM20 was shown to be overexpressed in various cancers. However, the oncological function and therapeutic potential for TOMM20 in cancer remains largely unexplored. The purpose of this study was to elucidate the underlying molecular mechanism of TOMM20's contribution to tumorigenesis and to explore the possibility of its therapeutic potential using colorectal cancer as a model. The results show that TOMM20 overexpression resulted in an increase in cell proliferation, migrat...
Source: BMB Reports - December 10, 2019 Category: Biochemistry Authors: Park SH, Lee AR, Choi K, Joung S, Yoon JB, Kim S Tags: BMB Rep Source Type: research

Techniques for investigating mitochondrial gene expression.
Abstract The mitochondrial genome encodes 13 proteins that are components of the oxidative phosphorylation system (OXPHOS), suggesting that precise regulation of these genes is crucial for maintaining OXPHOS functions, including ATP production, calcium buffering, cell signaling, ROS production, and apoptosis. Furthermore, heteroplasmy or mis-regulation of gene expression in mitochondria frequently is associated with human mitochondrial diseases. Thus, various approaches have been developed to investigate the roles of genes encoded by the mitochondrial genome. In this review, we will discuss a wide range of techniq...
Source: BMB Reports - December 10, 2019 Category: Biochemistry Authors: Park D, Lee S, Min KT Tags: BMB Rep Source Type: research