journal
https://read.qxmd.com/read/38413820/cost-and-time-efficient-construction-of-a-3-end-mrna-library-from-unpurified-bulk-rna-in-a-single-tube
#21
JOURNAL ARTICLE
Jungwon Choi, Jungheun Hyun, Jieun Hyun, Jae-Hee Kim, Ji Hyun Lee, Duhee Bang
The major drawbacks of RNA sequencing (RNA-seq), a remarkably accurate transcriptome profiling method, is its high cost and poor scalability. Here, we report a highly scalable and cost-effective method for transcriptomics profiling called Bulk transcriptOme profiling of cell Lysate in a single poT (BOLT-seq), which is performed using unpurified bulk 3'-end mRNA in crude cell lysates. During BOLT-seq, RNA/DNA hybrids are directly subjected to tagmentation, and second-strand cDNA synthesis and RNA purification are omitted, allowing libraries to be constructed in 2 h of hands-on time...
February 27, 2024: Experimental & Molecular Medicine
https://read.qxmd.com/read/38409448/notch-localizes-to-mitochondria-through-the-tbc1d15-fis1-interaction-and-is-stabilized-via-blockade-of-e3-ligase-and-cdk8-recruitment-to-reprogram-tumor-initiating-cells
#22
JOURNAL ARTICLE
Hye Yeon Choi, Yicheng Zhu, Xuyao Zhao, Simran Mehta, Juan Carlos Hernandez, Jae-Jin Lee, Yi Kou, Risa Machida, Mauro Giacca, Giannino Del Sal, Ratna Ray, Hyungjin Eoh, Stanley M Tahara, Lin Chen, Hidekazu Tsukamoto, Keigo Machida
The P53-destabilizing TBC1D15-NOTCH protein interaction promotes self-renewal of tumor-initiating stem-like cells (TICs); however, the mechanisms governing the regulation of this pathway have not been fully elucidated. Here, we show that TBC1D15 stabilizes NOTCH and c-JUN through blockade of E3 ligase and CDK8 recruitment to phosphodegron sequences. Chromatin immunoprecipitation (ChIP-seq) analysis was performed to determine whether TBC1D15-dependent NOTCH1 binding occurs in TICs or non-TICs. The TIC population was isolated to evaluate TBC1D15-dependent NOTCH1 stabilization mechanisms...
February 27, 2024: Experimental & Molecular Medicine
https://read.qxmd.com/read/38383581/helicobacter-pylori-caga-mediated-ether-lipid-biosynthesis-promotes-ferroptosis-susceptibility-in-gastric-cancer
#23
JOURNAL ARTICLE
Yanmei Peng, Xuetao Lei, Qingbin Yang, Guofan Zhang, Sixiao He, Minghao Wang, Ruoyu Ling, Boyang Zheng, Jiayong He, Xinhua Chen, Fengping Li, Qiming Zhou, Liying Zhao, Gengtai Ye, Guoxin Li
Helicobacter pylori, particularly cytotoxin-associated gene A (CagA)-positive strains, plays a key role in the progression of gastric cancer (GC). Ferroptosis, associated with lethal lipid peroxidation, has emerged to play an important role in malignant and infectious diseases, but the role of CagA in ferroptosis in cancer cells has not been determined. Here, we report that CagA confers GC cells sensitivity to ferroptosis both in vitro and in vivo. Mechanistically, CagA promotes the synthesis of polyunsaturated ether phospholipids (PUFA-ePLs), which is mediated by increased expression of alkylglycerone phosphate synthase (AGPS) and 1-acylglycerol-3-phosphate O-acyltransferase 3 (AGPAT3), leading to susceptibility to ferroptosis...
February 21, 2024: Experimental & Molecular Medicine
https://read.qxmd.com/read/38374207/baf-mediated-transcriptional-regulation-of-teashirt-is-essential-for-the-development-of-neural-progenitor-cell-lineages
#24
JOURNAL ARTICLE
Byung Su Ko, Myeong Hoon Han, Min Jee Kwon, Dong Gon Cha, Yuri Ji, Eun Seo Park, Min Jae Jeon, Somi Kim, Kyeongho Lee, Yoon Ha Choi, Jusung Lee, Monica Torras-Llort, Ki-Jun Yoon, Hyosang Lee, Jong Kyoung Kim, Sung Bae Lee
Accumulating evidence hints heterochromatin anchoring to the inner nuclear membrane as an upstream regulatory process of gene expression. Given that the formation of neural progenitor cell lineages and the subsequent maintenance of postmitotic neuronal cell identity critically rely on transcriptional regulation, it seems possible that the development of neuronal cells is influenced by cell type-specific and/or context-dependent programmed regulation of heterochromatin anchoring. Here, we explored this possibility by genetically disrupting the evolutionarily conserved barrier-to-autointegration factor (Baf) in the Drosophila nervous system...
February 19, 2024: Experimental & Molecular Medicine
https://read.qxmd.com/read/38355825/distinct-characteristics-of-the-dna-damage-response-in-mammalian-oocytes
#25
REVIEW
Jiyeon Leem, Crystal Lee, Da Yi Choi, Jeong Su Oh
DNA damage is a critical threat that poses significant challenges to all cells. To address this issue, cells have evolved a sophisticated molecular and cellular process known as the DNA damage response (DDR). Among the various cell types, mammalian oocytes, which remain dormant in the ovary for extended periods, are particularly susceptible to DNA damage. The occurrence of DNA damage in oocytes can result in genetic abnormalities, potentially leading to infertility, birth defects, and even abortion. Therefore, understanding how oocytes detect and repair DNA damage is of paramount importance in maintaining oocyte quality and preserving fertility...
February 14, 2024: Experimental & Molecular Medicine
https://read.qxmd.com/read/38351315/author-correction-inhibition-of-ripk1-dependent-regulated-acinar-cell-necrosis-provides-protection-against-acute-pancreatitis-via-the-ripk1-nf-%C3%AE%C2%BAb-aqp8-pathway
#26
Peng-Yu Duan, Yuan Ma, Xi-Na Li, Feng-Zhi Qu, Liang Ji, Xiao-Yu Guo, Wang-Jun Zhang, Fan Xiao, Le Li, Ji-Sheng Hu, Bei Sun, Gang Wang
No abstract text is available yet for this article.
February 13, 2024: Experimental & Molecular Medicine
https://read.qxmd.com/read/38351314/emerging-roles-of-mitf-as-a-crucial-regulator-of-immunity
#27
REVIEW
Aram Lee, Jihyun Lim, Jong-Seok Lim
Microphthalmia-associated transcription factor (MITF), a basic helix-loop-helix leucine zipper transcription factor (bHLH-Zip), has been identified as a melanocyte-specific transcription factor and plays a critical role in melanocyte survival, differentiation, function, proliferation and pigmentation. Although numerous studies have explained the roles of MITF in melanocytes and in melanoma development, the function of MITF in the hematopoietic or immune system-beyond its function in melanin-producing cells-is not yet fully understood...
February 13, 2024: Experimental & Molecular Medicine
https://read.qxmd.com/read/38337058/acid-sphingomyelinase-as-a-pathological-and-therapeutic-target-in-neurological-disorders-focus-on-alzheimer-s-disease
#28
REVIEW
Byung Jo Choi, Min Hee Park, Hee Kyung Jin, Jae-Sung Bae
Over the past decade, numerous studies have highlighted the importance of acid sphingomyelinase (ASM) in disease treatment in humans. This enzyme functions primarily to generate ceramide, maintain the cellular membrane, and regulate cellular function. However, in the blood and brain of patients with neurological disorders, including major depression, ischemic stroke, amyotrophic lateral sclerosis, multiple sclerosis, and Alzheimer's disease (AD), elevated ASM levels significantly suggest disease onset or progression...
February 9, 2024: Experimental & Molecular Medicine
https://read.qxmd.com/read/38316963/nucleus-pulposus-cells-regulate-macrophages-in-degenerated-intervertebral-discs-via-the-integrated-stress-response-mediated-ccl2-7-ccr2-signaling-pathway
#29
JOURNAL ARTICLE
Shuo Tian, Xuanzuo Chen, Wei Wu, Hui Lin, Xiangcheng Qing, Sheng Liu, BaiChuan Wang, Yan Xiao, Zengwu Shao, Yizhong Peng
Lower back pain (LBP), which is a primary cause of disability, is largely attributed to intervertebral disc degeneration (IDD). Macrophages (MΦs) in degenerated intervertebral discs (IVDs) form a chronic inflammatory microenvironment, but how MΦs are recruited to degenerative segments and transform into a proinflammatory phenotype remains unclear. We evaluated chemokine expression in degenerated nucleus pulposus cells (NPCs) to clarify the role of NPCs in the establishment of an inflammatory microenvironment in IDD and explored the mechanisms...
February 5, 2024: Experimental & Molecular Medicine
https://read.qxmd.com/read/38307937/the-deubiquitinase-usp40-preserves-endothelial-integrity-by-targeting-the-heat-shock-protein-hsp90%C3%AE
#30
JOURNAL ARTICLE
Jiaxing Miao, Lian Li, Nargis Shaheen, Jianxin Wei, Anastasia M Jacko, Prithu Sundd, Sarah J Taleb, Rama K Mallampalli, Yutong Zhao, Jing Zhao
Endothelial cell (EC) barrier disruption and inflammation are the pathological hallmarks of vascular disorders and acute infectious diseases and related conditions, including the coronavirus disease 2019 (COVID-19) and sepsis. Ubiquitination plays a critical role in regulating the stability, intracellular trafficking, and enzymatic activity of proteins and is reversed by deubiquitinating enzymes (DUBs). The role of DUBs in endothelial biology is largely unknown. In this study, we report that USP40, a poorly characterized DUB, prevents EC barrier disruption through reductions in the activation of RhoA and phosphorylation of myosin light chain (MLC) and cofilin...
February 2, 2024: Experimental & Molecular Medicine
https://read.qxmd.com/read/38297165/regulation-of-autophagy-by-perilysosomal-calcium-a-new-player-in-%C3%AE-cell-lipotoxicity
#31
REVIEW
Ha Thu Nguyen, Andreas Wiederkehr, Claes B Wollheim, Kyu-Sang Park
Autophagy is an essential quality control mechanism for maintaining organellar functions in eukaryotic cells. Defective autophagy in pancreatic beta cells has been shown to be involved in the progression of diabetes through impaired insulin secretion under glucolipotoxic stress. The underlying mechanism reveals the pathologic role of the hyperactivation of mechanistic target of rapamycin (mTOR), which inhibits lysosomal biogenesis and autophagic processes. Moreover, accumulating evidence suggests that oxidative stress induces Ca2+ depletion in the endoplasmic reticulum (ER) and cytosolic Ca2+ overload, which may contribute to mTOR activation in perilysosomal microdomains, leading to autophagic defects and β-cell failure due to lipotoxicity...
February 1, 2024: Experimental & Molecular Medicine
https://read.qxmd.com/read/38297164/exploring-the-potential-of-toxoplasma-gondii-in-drug-development-and-as-a-delivery-system
#32
REVIEW
Chanjin Yoon, Yu Seong Ham, Woo Jin Gil, Chul-Su Yang
Immune-mediated inflammatory diseases are various groups of conditions that result in immune system disorders and increased cancer risk. Despite the identification of causative cytokines and pathways, current clinical treatment for immune-mediated inflammatory diseases is limited. In addition, immune-mediated inflammatory disease treatment can increase the risk of cancer. Several previous studies have demonstrated that Toxoplasma gondii manipulates the immune response by inhibiting or stimulating cytokines, suggesting the potential for controlling and maintaining a balanced immune system...
February 1, 2024: Experimental & Molecular Medicine
https://read.qxmd.com/read/38297163/targeting-the-m-6-a-rna-methyltransferase-mettl3-attenuates-the-development-of-kidney-fibrosis
#33
JOURNAL ARTICLE
Hae Rim Jung, Jeonghwan Lee, Seung-Pyo Hong, Nayeon Shin, Ara Cho, Dong-Jin Shin, Jin Woo Choi, Jong-Il Kim, Jung Pyo Lee, Sung-Yup Cho
Kidney fibrosis is a major mechanism underlying chronic kidney disease (CKD). N6 -methyladenosine (m6 A) RNA methylation is associated with organ fibrosis. We investigated m6 A profile alterations and the inhibitory effect of RNA methylation in kidney fibrosis in vitro (TGF-β-treated HK-2 cells) and in vivo (unilateral ureteral obstruction [UUO] mouse model). METTL3-mediated signaling was inhibited using siRNA in vitro or the METTL3-specific inhibitor STM2457 in vivo and in vitro. In HK-2 cells, METTL3 protein levels increased in a dose- and time-dependent manner along with an increase in the cellular m6 A levels...
February 1, 2024: Experimental & Molecular Medicine
https://read.qxmd.com/read/38297162/deficiency-of-circadian-clock-gene-bmal1-exacerbates-noncanonical-inflammasome-mediated-pyroptosis-and-lethality-via-rev-erb%C3%AE-c-ebp%C3%AE-saa1-axis
#34
JOURNAL ARTICLE
Do-Wan Shim, Jun-Cheol Eo, Saeyoung Kim, Inhwa Hwang, BoYoung Nam, Jae-Eun Shin, Seung Hyeok Han, Je-Wook Yu
Circadian arrhythmia has been linked to increased susceptibility to multiple inflammatory diseases, such as sepsis. However, it remains unclear how disruption of the circadian clock modulates molecular aspects of innate immune responses, including inflammasome signaling. Here, we examined the potential role of the circadian clock in inflammasome-mediated responses through myeloid-specific deletion of BMAL1, a master circadian clock regulator. Intriguingly, Bmal1 deficiency significantly enhanced pyroptosis of macrophages and lethality of mice under noncanonical inflammasome-activating conditions but did not alter canonical inflammasome responses...
February 1, 2024: Experimental & Molecular Medicine
https://read.qxmd.com/read/38297161/cathepsin-d-promotes-polarization-of-tumor-associated-macrophages-and-metastasis-through-tgfbi-ccl20-signaling
#35
JOURNAL ARTICLE
Seul Gi Lee, Seon Min Woo, Seung Un Seo, Chan-Hyeong Lee, Moon-Chang Baek, Se Hwan Jang, Zee Yong Park, Simmyung Yook, Ju-Ock Nam, Taeg Kyu Kwon
M2-like tumor-associated macrophages (TAMs) are risk factors for cancer progression and metastasis. However, the mechanisms underlying their polarization are still not fully understood. Although cathepsin D (Cat D) has been reported as a procarcinogenic factor, little is known about the functional role of Cat D in the tumor microenvironment (TME). This study aimed to explore the effect and molecular mechanisms of Cat D in the TME. Cat D knockout (KO) altered the cytokine secretion pattern and induced TAM reprogramming from the M2 to M1 subtype, thereby preventing epithelial-mesenchymal transition and tumor metastasis...
February 1, 2024: Experimental & Molecular Medicine
https://read.qxmd.com/read/38297160/role-of-upf1-in-lncrna-heih-regulation-for-hepatocellular-carcinoma-therapy
#36
JOURNAL ARTICLE
Hyunho Cha, Minwoo Kim, Narae Ahn, Seong Dong Jeong, Elizaveta Ignatova, Sung Wook Chi, Hyeon Ho Kim, Jungwook Hwang
UPF1, a novel posttranscriptional regulator, regulates the abundance of transcripts, including long noncoding RNAs (lncRNAs), and thus plays an important role in cell homeostasis. In this study, we revealed that UPF1 regulates the abundance of hepatocellular carcinoma upregulated EZH2-associated lncRNA (lncRNA-HEIH) by binding the CG-rich motif, thereby regulating hepatocellular carcinoma (HCC) tumorigenesis. UPF1-bound lncRNA-HEIH was susceptible to degradation mediated by UPF1 phosphorylation via SMG1 and SMG5...
February 1, 2024: Experimental & Molecular Medicine
https://read.qxmd.com/read/38297159/hira-vs-daxx-the-two-axes-shaping-the-histone-h3-3-landscape
#37
REVIEW
Jinmi Choi, Taewan Kim, Eun-Jung Cho
H3.3, the most common replacement variant for histone H3, has emerged as an important player in chromatin dynamics for controlling gene expression and genome integrity. While replicative variants H3.1 and H3.2 are primarily incorporated into nucleosomes during DNA synthesis, H3.3 is under the control of H3.3-specific histone chaperones for spatiotemporal incorporation throughout the cell cycle. Over the years, there has been progress in understanding the mechanisms by which H3.3 affects domain structure and function...
February 1, 2024: Experimental & Molecular Medicine
https://read.qxmd.com/read/38297158/unraveling-the-intricacies-of-osteoclast-differentiation-and-maturation-insight-into-novel-therapeutic-strategies-for-bone-destructive-diseases
#38
REVIEW
Noriko Takegahara, Hyunsoo Kim, Yongwon Choi
Osteoclasts are the principal cells that efficiently resorb bone. Numerous studies have attempted to reveal the molecular pathways leading to the differentiation and activation of osteoclasts to improve the treatment and prevention of osteoporosis and other bone-destructive diseases. While the cumulative knowledge of osteoclast regulatory molecules, such as receptor activator of nuclear factor-kB ligand (RANKL) and nuclear factor of activated T cells 1 (NFATc1), contributes to the understanding of the developmental progression of osteoclasts, little is known about how the discrete steps of osteoclastogenesis modify osteoclast status but not the absolute number of osteoclasts...
February 1, 2024: Experimental & Molecular Medicine
https://read.qxmd.com/read/38297157/synaptotagmin-4-induces-anhedonic-responses-to-chronic-stress-via-bdnf-signaling-in-the-medial-prefrontal-cortex
#39
JOURNAL ARTICLE
Jeongseop Kim, Sihwan Seol, Tae-Eun Kim, Joonhee Lee, Ja Wook Koo, Hyo Jung Kang
Stressful circumstances are significant contributors to mental illnesses such as major depressive disorder. Anhedonia, defined as loss of the ability to enjoy pleasure in pleasurable situations, including rewarding activities or social contexts, is considered a key symptom of depression. Although stress-induced depression is associated with anhedonia in humans and animals, the underlying molecular mechanisms of anhedonic responses remain poorly understood. In this study, we demonstrated that synaptotagmin-4 (SYT4), which is involved in the release of neurotransmitters and neurotrophic factors, is implicated in chronic stress-induced anhedonia...
February 1, 2024: Experimental & Molecular Medicine
https://read.qxmd.com/read/38253797/cyb5r3-functions-as-a-tumor-suppressor-by-inducing-er-stress-mediated-apoptosis-in-lung-cancer-cells-via-the-perk-atf4-and-ire1%C3%AE-jnk-pathways
#40
JOURNAL ARTICLE
Joo-Young Im, Soo Jin Kim, Jong-Lyul Park, Tae-Hee Han, Woo-Il Kim, Inhyub Kim, Bomin Ko, So-Young Chun, Mi-Jung Kang, Bo-Kyung Kim, Sol A Jeon, Seon-Kyu Kim, Incheol Ryu, Seon-Young Kim, Ki-Hoan Nam, Inah Hwang, Hyun Seung Ban, Misun Won
Cytochrome b5 reductase 3 (CYB5R3) is involved in various cellular metabolic processes, including fatty acid synthesis and drug metabolism. However, the role of CYB5R3 in cancer development remains poorly understood. Here, we show that CYB5R3 expression is downregulated in human lung cancer cell lines and tissues. Adenoviral overexpression of CYB5R3 suppresses lung cancer cell growth in vitro and in vivo. However, CYB5R3 deficiency promotes tumorigenesis and metastasis in mouse models. Transcriptome analysis revealed that apoptosis- and endoplasmic reticulum (ER) stress-related genes are upregulated in CYB5R3-overexpressing lung cancer cells...
January 22, 2024: Experimental & Molecular Medicine
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