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REVIEW
Anand Kumar Yadav, Ramina Maharjan Shrestha, Paras Nath Yadav
The structural motif of coumarins is related with various biological activities and pharmacological properties. Both natural coumarin extracted from various plants or a new coumarin derivative synthesized by modification of the basic structure of coumarin, in vitro experiments showed that coumarins are a promising class of anti-tumor agents with high selectivity. Cancer is a complex and multifaceted group of diseases characterized by the uncontrolled and abnormal growth of cells in the body. This review focuses on the anticancer mechanism of various coumarins synthesized and isolated in more than a decade...
March 5, 2024: European Journal of Medicinal Chemistry
#22
Qingyu Luo, Evangeline G Raulston, Miguel A Prado, Xiaowei Wu, Kira Gritsman, Kezhi Yan, Christopher A G Booth, Ran Xu, Peter van Galen, John G Doench, Shai Shimony, Henry W Long, Donna S Neuberg, Joao A Paulo, Andrew A Lane
Phosphoinositide 3-kinase gamma (PI3Kγ) is implicated as a target to repolarize tumor-associated macrophages and promote anti-tumor immune responses in solid cancers. However, cancer cell-intrinsic roles of PI3Kγ are unclear. Here, by integrating unbiased genome-wide CRISPR interference screening with functional analyses across acute leukemias, we define a selective dependency on the PI3Kγ complex in a high-risk subset that includes myeloid, lymphoid, and dendritic lineages. This dependency is characterized by innate inflammatory signaling and activation of phosphoinositide 3-kinase regulatory subunit 5 ( PIK3R5 ), which encodes a regulatory subunit of PI3Kγ and stabilizes the active enzymatic complex...
December 15, 2023: bioRxiv
#23
JOURNAL ARTICLE
Kazuhiro Okumura, Takao Morinaga, Megumi Saito, Yurika Tokunaga, Keisuke Otoyama, Sora Tanaka, Eriko Isogai, Masahito Kawazu, Yosuke Togashi, Kimi Araki, Yuichi Wakabayashi
No abstract text is available yet for this article.
February 5, 2024: Journal of Investigative Dermatology
#24
JOURNAL ARTICLE
Xiaofang Zou, Yiwen Lin, Hongzheng Ren, Yuhua Meng, Shuanglong Chen, Yinhui Jiang, Weiheng Cui, Yinfang Gu, Longhua Guo, Lilan Yi, Dianzheng Zhang, Hao Zhang, Guowu Wu
BACKGROUND/AIM: Protein arginine methyltransferase 5 (PRMT5), a member of the arginine methyltransferases, is an enzyme catalyzing the methylation of arginine residuals of histones and non-histone proteins to serve as one of many critical posttranslational modifications (PTMs). Phosphorylated P21-activated kinase 1 (p-PAK1), a serine/threonine protein kinase family member, is a cytoskeletal protein that plays a critical role in metastasis. We examined the expression of PRMT5 and PAK1 in esophageal squamous cell carcinoma (ESCC) and evaluated the correlation between PRMT5/p-PAK1 and both clinicopathological parameters and prognosis of ESCC patients...
February 2024: Anticancer Research
#25
JOURNAL ARTICLE
Jia-Hua Qu, Khalid Chakir, Kirill V Tarasov, Daniel R Riordon, Maria Grazia Perino, Allwin Jennifa Silvester, Edward G Lakatta
Our prior study (Tarasov et al., 2022) discovered that numerous adaptive mechanisms emerge in response to cardiac-specific overexpression of adenylyl cyclase type 8 (TGAC8) which included overexpression of a large number of proteins. Here, we conducted an unbiased phosphoproteomics analysis in order to determine the role of altered protein phosphorylation in the adaptive heart performance and protection profile of adult TGAC8 left ventricle (LV) at 3-4 months of age, and integrated the phosphoproteome with transcriptome and proteome...
January 22, 2024: ELife
#26
JOURNAL ARTICLE
Lara J Bou Malhab, Vidhya A Nair, Rizwan Qaisar, Gianfranco Pintus, Wael M Abdel-Rahman
Obesity is a growing pandemic with an increasing risk of inducing different cancer types, including breast cancer. Adipose tissue is proposed to be a major player in the initiation and progression of breast cancer in obese people. However, the mechanistic link between adipogenicity and tumorigenicity in breast tissues is poorly understood. We used in vitro and in vivo approaches to investigate the mechanistic relationship between obesity and the onset and progression of breast cancer. In obesity, adipose tissue expansion and remodeling are associated with increased inflammatory mediator's release and anti-inflammatory mediators' reduction...
January 17, 2024: Cells
#27
JOURNAL ARTICLE
Hui Tian, Gaofeng Liang, Qi Qin, Chaoqun Yu, Jinxian He
Circular RNAs are emerging players in human cancers, including esophageal squamous cell carcinoma (ESCC). Herein, we assessed the expression level of circ_0023990 and explored the molecular mechanisms of circ_0023990 in ESCC. circ_0023990, miR-6884-5p, and PAK1 expressions in ESCC tissues and cells were detected by quantitative real-time polymerase chain reaction and western blot. ESCC cells were transfected with different constructs to alter the expression of circ_0023990, miR-6884-5p, and PAK1. The effect of circ_0023990 on the proliferation, invasion, and glycolysis of ESCC cells was observed...
January 19, 2024: Biochemical Genetics
#28
JOURNAL ARTICLE
Xiaokai Huang, Chengwu Xu, Haipeng Dai, Jianchun Yang, Tingting Huang, Shuan Chen, Lingxin Qi, Jichen Ruan, Juxiang Wang
Background: Glioblastoma (GBM) is a type of central nervous system malignancy. In our study, we determined the effect of NCDN in GBM patients through The Cancer Genome Atlas (TCGA) data analysis, and studied the effects of NCDN on GBM cell function to estimate its potential as a therapeutic target. Methods: Gene expression profiles of glioblastoma cohort were acquired from TCGA database and analyzed to look for central genes that may serve as GBM therapeutic targets. Then the cell function of NCDN in glioblastoma cell was explored through in vitro cell experiments...
2024: Journal of Cancer
#29
JOURNAL ARTICLE
Agnes Donkó, Svetlana O Sharapova, Juraj Kabat, Sundar Ganesan, Fabian Hauck, Louis Marois, Jordan Abbott, Despina Moshous, Kelli W Williams, Nicholas Campbell, Paul L Martin, Chantal Lagresle-Peyrou, Timothy David Trojan, Natalia Kuzmenko, Ekaterina Deordieva, Elena Raykina, Michael S Abers, Hassan Abolhassani, Vincent Barlogis, Carlos Carlos Milla Milla, Geoffrey Hall, Talal Mousallem, Joseph A Church, Neena Kapoor, Guilhem Cros, Hugo Chapdelaine, Clara Franco-Jarava, Ingrid Lopez-Lerma, Maurizio Miano, Jennifer W Leiding, Christoph Klein, Marie José Stasia, Alain Fischer, Kuang-Chih Hsiao, Timi Martelius, Mikko R J Seppänen, Sara Barmettler, Jolan E Walter, Tania Nicole Masmas, Anna Mukhina, Emilia Liana Falcone, Sven Kracker, Anna Shcherbina, Steven M Holland, Thomas L Leto, Amy P Hsu
Mutations in the small Rho-family GTPase, RAC2, critical for actin cytoskeleton remodeling and intracellular signal transduction, are associated with neonatal severe combined immunodeficiency (SCID), infantile neutrophilic disorder resembling leukocyte adhesion deficiency (LAD), and later-onset combined immune deficiency (CID). We investigated 54 RAC2 patients (23 previously reported) from 37 families. Data were collected from referring physicians and literature reports with updated clinical information. Patients were grouped by presentation: neonatal SCID (n=5), infantile LAD-like disease (n=5), or CID (n=44)...
January 9, 2024: Blood
#30
JOURNAL ARTICLE
Tian Su, Yue He, Yan Huang, Mingsheng Ye, Qi Guo, Ye Xiao, Guangping Cai, Linyun Chen, Changjun Li, Haiyan Zhou, Xianghang Luo
The crosstalk between the bone and adipose tissue is known to orchestrate metabolic homeostasis, but the underlying mechanisms are largely unknown. Herein, we find that GCA + (grancalcin) immune cells accumulate in the bone marrow and release a considerable amount of GCA into circulation during obesity. Genetic deletion of Gca in myeloid cells attenuates metabolic dysfunction in obese male mice, whereas injection of recombinant GCA into male mice causes adipose tissue inflammation and insulin resistance...
January 2, 2024: Nature Communications
#31
JOURNAL ARTICLE
Sofía Ibáñez-Molero, Joannes T M Pruijs, Alisha Atmopawiro, Fujia Wang, Alexandra M Terry, Maarten Altelaar, Daniel S Peeper, Kelly E Stecker
Functional interactions between cytotoxic T cells and tumor cells are central to anti-cancer immunity. However, our understanding of the proteins involved is limited. Here, we present HySic (hybrid quantification of stable isotope labeling by amino acids in cell culture [SILAC]-labeled interacting cells) as a method to quantify protein and phosphorylation dynamics between and within physically interacting cells. Using co-cultured T cells and tumor cells, we directly measure the proteome and phosphoproteome of engaged cells without the need for physical separation...
December 26, 2023: Cell Reports
#32
JOURNAL ARTICLE
Shiran Gerassy-Vainberg, Elina Starosvetsky, Renaud Gaujoux, Alexandra Blatt, Naama Maimon, Yuri Gorelik, Sigal Pressman, Ayelet Alpert, Haggai Bar-Yoseph, Tania Dubovik, Benny Perets, Adir Katz, Neta Milman, Meital Segev, Yehuda Chowers, Shai S Shen-Orr
Personalized treatment of complex diseases has been mostly predicated on biomarker identification of one drug-disease combination at a time. Here, we use a computational approach termed Disruption Networks to generate a data type, contextualized by cell-centered individual-level networks, that captures biology otherwise overlooked when performing standard statistics. This data type extends beyond the "feature level space", to the "relations space", by quantifying individual-level breaking or rewiring of cross-feature relations...
December 12, 2023: Cell reports medicine
#33
JOURNAL ARTICLE
Antje Schaefer, Richard G Hodge, Haisheng Zhang, G Aaron Hobbs, Julien Dilly, Minh V Huynh, Craig M Goodwin, Feifei Zhang, J Nathaniel Diehl, Mariaelena Pierobon, Elisa Baldelli, Sehrish Javaid, Karson Guthrie, Naim U Rashid, Emanuel F Petricoin, Adrienne D Cox, William C Hahn, Andrew J Aguirre, Adam J Bass, Channing J Der
Cancer-associated mutations in the guanosine triphosphatase (GTPase) RHOA are found at different locations from the mutational hotspots in the structurally and biochemically related RAS. Tyr42 -to-Cys (Y42C) and Leu57 -to-Val (L57V) substitutions are the two most prevalent RHOA mutations in diffuse gastric cancer (DGC). RHOAY42C exhibits a gain-of-function phenotype and is an oncogenic driver in DGC. Here, we determined how RHOAL57V promotes DGC growth. In mouse gastric organoids with deletion of Cdh1 , which encodes the cell adhesion protein E-cadherin, the expression of RHOAL57V , but not of wild-type RHOA, induced an abnormal morphology similar to that of patient-derived DGC organoids...
December 19, 2023: Science Signaling
#34
Marcus Harrell, Ziyi Liu, Bethany F Campbell, Olivia Chinsen, Tian Hong, Maitreyi Das
The conserved GTPase Cdc42 is a major regulator of polarized growth in most eukaryotes. Cdc42 periodically cycles between active and inactive states at sites of polarized growth. These periodic cycles are caused by positive feedback and time-delayed negative feedback loops. In the bipolar yeast S. pombe , both growing ends must regulate Cdc42 activity. At each cell end, Cdc42 activity recruits the Pak1 kinase which prevents further Cdc42 activation thus establishing negative feedback. It is unclear how Cdc42 activation returns to the end after Pak1-dependent negative feedback...
November 9, 2023: bioRxiv
#35
JOURNAL ARTICLE
Cheng-Jun Liu, Hong-Xin Li, Yong-Ming Zhang, Wei Shi, Feng-Xiang Zhang
RATIONALE: Tetrandrine, the Q-marker in Stephaniae Tetrandrae Radix, was proven to present an obvious antitumor effect. Until now, the metabolism and antitumor mechanism of tetrandrine have not been fully elucidated. METHODS: The metabolites of tetrandrine in rats were profiled using ultra-high-performance liquid chromatography coupled with time-of-flight mass spectrometry. The potential antitumor mechanism of tetrandrine in vivo was predicted using network pharmacology...
January 15, 2024: Rapid Communications in Mass Spectrometry: RCM
#36
JOURNAL ARTICLE
Julian Gonzalez-Rubio, Vu Thuy Khanh Le-Trilling, Lea Baumann, Maria Cheremkhina, Hannah Kubiza, Anja E Luengen, Sebastian Reuter, Christian Taube, Stephan Ruetten, Daniela Duarte Campos, Christian G Cornelissen, Mirko Trilling, Anja Lena Thiebes
Introduction: The Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), which caused the coronavirus disease 2019 (COVID-19) pandemic, enters the human body via the epithelial cells of the airway tract. To trap and eject pathogens, the airway epithelium is composed of ciliated and secretory cells that produce mucus which is expelled through a process called mucociliary clearance. Methods: This study examines the early stages of contact between SARS-CoV-2 particles and the respiratory epithelium, utilizing 3D airway tri-culture models exposed to ultraviolet light-irradiated virus particles...
2023: Frontiers in Bioengineering and Biotechnology
#37
JOURNAL ARTICLE
Elliot Jokl, Aoibheann F Mullan, Kara Simpson, Lindsay Birchall, Laurence Pearmain, Katherine Martin, James Pritchett, Sayyid Raza, Rajesh Shah, Nigel W Hodson, Craig J Williams, Elizabeth Camacho, Leo Zeef, Ian Donaldson, Varinder S Athwal, Neil A Hanley, Karen Piper Hanley
Myofibroblasts are responsible for scarring during fibrosis. The scar propagates mechanical signals inducing a radical transformation in myofibroblast cell state and increasing profibrotic phenotype. Here, we show mechanical stress from progressive scarring induces nuclear softening and de-repression of heterochromatin. The parallel loss of H3K9Me3 enables a permissive state for distinct chromatin accessibility and profibrotic gene regulation. Integrating chromatin accessibility profiles with RNA expression provides insight into the transcription network underlying the switch in profibrotic myofibroblast states, emphasizing mechanoadaptive regulation of PAK1 as key drivers...
November 13, 2023: Cell Reports
#38
JOURNAL ARTICLE
Ning Su, Yu Fang, Xu Chen, Xiaoqin Chen, Zhongjun Xia, Huiqiang Huang, Yi Xia, Panpan Liu, Xiaopeng Tian, Qingqing Cai
T-cell lymphoblastic lymphoma (T-LBL) is a highly aggressive non-Hodgkin lymphoma with a poor prognosis. P21-activated kinase (PAK) is a component of the gene expression-based classifier that can predict the prognosis of T-LBL. However, the role of PAK in T-LBL progression and survival remains poorly understood. Herein, we found that the expression of PAK1 was significantly higher in T-LBL cell lines (Jurkat, SUP-T1, and CCRF-CEM) compared to the human T-lymphoid cell line. Moreover, PAK2 mRNA level of 32 relapsed T-LBL patients was significantly higher than that of 37 cases without relapse ( P = ...
October 2023: Blood Sci
#39
EDITORIAL
Wei Yang, Kavita Shah, Rong Yang
No abstract text is available yet for this article.
2023: Frontiers in Cell and Developmental Biology
#40
JOURNAL ARTICLE
Fan Bu, Jia-Wei Min, Md Abdur Razzaque, Ahmad El Hamamy, Anthony Patrizz, Li Qi, Akihiko Urayama, Jun Li
Brain functional impairment after stroke is common; however, the molecular mechanisms of post-stroke recovery remain unclear. It is well-recognized that age is the most important independent predictor of poor outcomes after stroke as older patients show poorer functional outcomes following stroke. Mounting evidence suggests that axonal regeneration and angiogenesis, the major forms of brain plasticity responsible for post-stroke recovery, diminished with advanced age. Previous studies suggest that Ras-related C3 botulinum toxin substrate (Rac) 1 enhances stroke recovery as activation of Rac1 improved behavior recovery in a young mice stroke model...
April 2024: Neural Regeneration Research
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