Article
Biochemistry & Molecular Biology
Chakrabhavi Dhananjaya Mohan, Chulwon Kim, Kodappully Sivaraman Siveen, Kanjoormana Aryan Manu, Shobith Rangappa, Arunachalam Chinnathambi, Sulaiman Ali Alharbi, Kanchugarakoppal S. Rangappa, Alan Prem Kumar, Kwang Seok Ahn
Summary: Crocetin inhibits STAT3 activation in HCC cells and affects the expression of multiple genes associated with cancer, thereby suppressing cell proliferation and invasive capacity.
Article
Biochemistry & Molecular Biology
Hanna Mannell, Petra Kameritsch, Heike Beck, Alexander Pfeifer, Ulrich Pohl, Kristin Pogoda
Summary: The gap junction protein Cx43 is involved in endothelial cell migration and angiogenesis through its interaction with the phosphatase SHP-2, enhancing its activity and regulating migration.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Ye-Rin Park, Wona Jee, So-Mi Park, Seok Woo Kim, Hanbit Bae, Ji Hoon Jung, Hyungsuk Kim, Sangki Kim, Jong Sup Chung, Hyeung-Jin Jang
Summary: In this study, we investigated the potential anticancer effects of Viscum album, a parasitic plant that grows on Malus domestica (VaM) on breast cancer cells, and explored the underlying mechanisms. VaM significantly inhibited cell viability and proliferation and induced apoptosis in a dose-dependent manner. VaM also regulated cell cycle progression and effectively inhibited activation of the STAT3 signaling pathway through SHP-1. Combining VaM with low-dose doxorubicin produced a synergistic effect, highlighting its potential as a promising therapeutic. In vivo, VaM administration inhibited tumor growth and modulated key molecular markers associated with breast cancer progression. Overall, our findings provide strong evidence for the therapeutic potential of VaM in breast cancer treatment and support further studies exploring clinical applications.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Zhenjiang Pan, Jing Bao, Liujun Zhang, Shepeng Wei
Summary: Our study revealed that UBE2D3 is highly expressed in glioma, promoting cell proliferation, glycolysis, and STAT3 pathway activation. Additionally, UBE2D3 interacts with SHP-2, facilitating its ubiquitination and subsequent activation of the STAT3 pathway. These findings suggest that UBE2D3 could be a potential therapeutic target for glioma treatment.
FRONTIERS IN ONCOLOGY
(2021)
Article
Endocrinology & Metabolism
Adrienn Markovics, Sydney Lupo, Niyati Patel, Katalin Mikecz, D. Rick Sumner, Ryan D. Ross
Summary: This study found that Shp1 overexpression leads to increased bone mass and improved mechanical properties in mice, but only in 28-day-old mice. Female SHP1-Tg mice showed higher trabecular bone volume, trabecular number, and connectivity density compared to wildtype mice.
CALCIFIED TISSUE INTERNATIONAL
(2023)
Article
Immunology
QinLei Gu, Kenneth S. Tung, Ulrike M. Lorenz
Summary: To achieve a healthy and functional immune system, there is a delicate balance between the activation of Tcon cells and the suppression by Treg cells. SHP-1 plays a role in modulating this balance by regulating Tcon cell resistance to Treg-mediated suppression. However, the role of SHP-1 in Treg function is still not fully understood.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Hematology
Cedric Garcia, Sebastien Dejean, Nicolas Savy, Jean-Claude Bordet, Jennifer Series, Sarah Cadot, Agnes Ribes, Sophie Voisin, Lucia Rugeri, Bernard Payrastre, Pierre Sie
Summary: In this study, a new approach using multicolor flow cytometry with fluorescent barcoding technique was introduced for rapid platelet signaling profiling in clinical practice.
RESEARCH AND PRACTICE IN THROMBOSIS AND HAEMOSTASIS
(2022)
Article
Oncology
Fang Yuan, Qian Gao, Hailin Tang, Jun Shi, Yiqun Zhou
Summary: This study revealed the inhibitory effect of OP-B on hepatocellular carcinoma (HCC) and its mechanism. OP-B inhibited HCC progression by downregulating PTP1B expression, thus inactivating the PI3K/AKT pathway and activating the AMPK pathway, leading to the suppression of HCC growth, proliferation, invasion, and angiogenesis.
MOLECULAR MEDICINE REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Federica Bono, Zaira Tomasoni, Veronica Mutti, Giulia Sbrini, Rajesh Kumar, Francesca Longhena, Chiara Fiorentini, Cristina Missale
Summary: The heteromer composed of dopamine D1 and D3 receptors can activate Erk1/2 and Akt signaling in a G protein-independent, beta-arrestin 1-dependent way. Abnormal levels of D1R-D3R heteromer in Parkinson's disease patients with L-DOPA-induced dyskinesia (LID) suggest its involvement in the abnormal PKA-Shp-2-Erk1/2 pathway. The signaling pathway induced by the D1R/D3R heteromer involves D1R molecular effectors, Gs protein, PKA, phosphatase Shp-2, and beta-arrestins.
Article
Biochemistry & Molecular Biology
Amanguli Tuohongerbieke, Liu Liu, Jun Li, Xuelei Xin, Haji Akber Aisa
Summary: Phytochemical study of Limonium gmelinii roots led to the isolation of five lignanamides (1-5). Among them, limoniumins J, K, and M (1, 2, and 4) are new compounds, limoniumin L (3) is a new naturally occurring lignanamide, and limoniumin B (5) is a known compound that showed PTP1B inhibition activity. The compounds showed potent PTP1B inhibition and also increased glucose consumption and uptake in muscle cells.
BIOORGANIC CHEMISTRY
(2023)
Article
Cell Biology
Pardis Mohammadzadeh, Mina Roueinfar, Gregory C. Amberg
Summary: This study reveals a novel role for AXL as a modulator of GnRH receptor signaling. Gas6 enhances GnRH-dependent ERK phosphorylation and Egr-1 transcript abundance, and promotes LH beta production and pro-MMP9 protein generation, as well as cell migration.
CELL COMMUNICATION AND SIGNALING
(2023)
Article
Neurosciences
Jiang-Lin Wang, Yan Wang, Wei Sun, Yang Yu, Na Wei, Rui Du, Yan Yang, Ting Liang, Xiao-Liang Wang, Ce-Hua Ou, Jun Chen
Summary: The study demonstrates the natural existence of a SPN-protein phosphatase 1Rac1 complex in spinal neurons, and shows that SPN may regulate dendritic spine morphogenesis and spinal pain sensitivity by negatively controlling GTP-bound Rac1-ERK activities.
NEUROBIOLOGY OF DISEASE
(2021)
Article
Cell Biology
Delia I. Fernandez, Marijke J. E. Kuijpers, Johan W. M. Heemskerk
Summary: Platelets are stimulated to increase Ca2+ levels through G-protein coupled receptors or ITAM-linked receptors. There are significant differences in Ca2+ signaling between different receptor types, and simultaneous stimulation of both types of receptors can lead to a highly enforced Ca2+ rise.
Article
Plant Sciences
Xinkai Jin, Xingxing Li, Zizhao Xie, Ying Sun, Liang Jin, Tingzhang Hu, Junli Huang
Summary: The nuclear factor OsNF-YC5 integrates abscisic acid (ABA) and jasmonic acid (JA) signaling to regulate rice seed germination. OsNF-YC5 regulates seed germination by controlling ABA synthesis and catabolism genes, as well as activating a K+ transporter gene. OsNF-YC5 also enhances seed germination under salt stress.
Article
Multidisciplinary Sciences
Jae Sung Ko, Dongjin Jeong, Jaemoon Koh, Hyeryeon Jung, Kyeong Cheon Jung, Yoon Kyung Jeon, Hye Young Kim, Eugene C. Yi, Ho Lee, Chang-Woo Lee, Doo Hyun Chung
Summary: Ssu72 regulates the fine-tuning of TCR signaling by acting as a tyrosine phosphatase for ZAP-70. Ssu72 deficiency leads to hyperresponsiveness in T cells upon TCR stimulation due to increased ZAP-70 phosphorylation, which can be restored by reducing ZAP-70 phosphorylation levels. Additionally, Cd4-CreSsu72fl/fl mice show defects in thymic development and alterations in peripheral T cell populations, with a predisposition for spontaneous inflammation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
S. A. Misek, K. M. Appleton, T. S. Dexheimer, E. M. Lisabeth, R. S. Lo, S. D. Larsen, K. A. Gallo, R. R. Neubig
Article
Pharmacology & Pharmacy
Casandra L. Larrivee, Huijie Feng, Josiah A. Quinn, Vincent S. Shaw, Jeffrey R. Leipprandt, Elena Y. Demireva, Huirong Xie, Richard R. Neubig
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
(2020)
Review
Cell Biology
Maurizio Tomaiuolo, Rustem I. Litvinov, John W. Weisel, Timothy J. Stalker
Article
Biophysics
Marek Brzezinski, Marta Socka, Tomasz Makowski, Bartlomiej Kost, Marcin Cieslak, Karolina Krolewska-Golinska
Summary: This study developed a novel microfluidic approach for preparing (co)polymeric and hybrid nanoparticles, which showed great potential in drug release and inhibition of breast cancer cells. The composition of PCL/TA NPs demonstrated the most efficient antitumor activity among all formulations, surpassing the efficacy of free DOX.
COLLOIDS AND SURFACES B-BIOINTERFACES
(2021)
Article
Biochemistry & Molecular Biology
Marcin Cieslak, Mariola Napiorkowska, Julia Kazmierczak-Baranska, Karolina Krolewska-Golinska, Anna Hawryl, Iwona Wybranska, Barbara Nawrot
Summary: In this study, a series of 26 new dicarboximide derivatives were designed and synthesized, showing high to moderate cytotoxicity in cancer cells and upregulation of apoptotic genes. The derivatives also activated MAPKs signaling pathway, indicating potential as novel anticancer drugs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Kathryn M. Appleton, Charuta C. Palsuledesai, Sean A. Misek, Maja Blake, Joseph Zagorski, Kathleen A. Gallo, Thomas S. Dexheimer, Richard R. Neubig
Summary: In NRAS mutant melanoma cells, activation of the Rho pathway is associated with high intrinsic resistance to the MEK inhibitor trametinib. Combining a Rho/MRTF pathway inhibitor with trametinib can synergistically reduce cell viability and induce apoptosis in resistant melanoma cells. Targeting both the Rho/MRTF pathway and MEK shows therapeutic potential in NRAS mutant melanomas.
Article
Hematology
Tanya T. Marar, Chelsea N. Matzko, Jie Wu, Charles T. Esmon, Talid Sinno, Lawrence F. Brass, Timothy J. Stalker, Maurizio Tomaiuolo
Summary: Researchers found that the spatial distribution of thrombin plays a crucial role in the activation of protein C during hemostasis and thrombosis. This study utilized pharmacological, genetic, imaging, and computational approaches to investigate the relationship between thrombin distribution, protein C activation, and anticoagulant function.
Article
Biochemistry & Molecular Biology
Sandra Gorska-Jakubowska, Marzenna Klimaszewska, Piotr Podsadni, Beata Kaleta, Radoslaw Zagozdzon, Sabina Gorska, Andrzej Gamian, Tomasz Straczek, Czeslaw Kapusta, Marcin Cieslak, Julia Kazmierczak-Baranska, Barbara Nawrot, Jadwiga Turlo
Summary: The selenium-enriched polysaccharides from fungal sources exhibit immunomodulatory and antioxidant activities, enhancing cell viability and inhibiting the proliferation of human peripheral blood mononuclear cells, but with lower activity compared to selenium-containing mycelial isolates.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Neurosciences
Huijie Feng, Yukun Yuan, Michael R. Williams, Alex J. Roy, Jeffery R. Leipprandt, Richard R. Neubig
Summary: This study investigates the electrophysiological mechanisms of a movement disorder animal model with monoallelic Gnao1 loss. It reveals the role of G alpha(o) protein in regulating GABA release in the mouse cerebellum. The findings could lead to the discovery of new drugs or the repurposing of existing drugs for GNAO1-associated disorders. Additionally, targeting GNAO1 could have implications for the treatment of other monogenic movement disorders.
JOURNAL OF NEUROPHYSIOLOGY
(2022)
Article
Engineering, Chemical
Monika Richert, Renata Mikstacka, Mariusz Walczyk, Marcin Janusz Cieslak, Julia Kazmierczak-Baranska, Karolina Krolewska-Golinska, Tadeusz Mikolaj Muziol, Stanislaw Biniak
Summary: Gold(I) complexes with phosphine ligands were investigated as bioactive gold metallodrugs, with complex (2) showing the most promising biological properties including high stability, selectivity towards cancer cells, and the highest inhibitory effect on cytosolic NADPH-dependent reductases.
Article
Oncology
Iga Stukan, Marek Gryzik, Grazyna Hoser, Andrew Want, Wioleta Grabowska-Pyrzewicz, Mikolaj Zdioruk, Mariola Napiorkowska, Marcin Cieslak, Karolina Krolewska-Golinska, Barbara Nawrot, Grzegorz Basak, Urszula Wojda
Summary: Chemotherapy is widely used for cancer treatment but often leads to therapy resistance. This study discovered that the novel compound BK124.1 can overcome chemotherapy resistance in chronic myeloid leukemia. BK124.1 showed efficacy in animal and cellular models, targeting multidrug resistant leukemia blasts and cancer stem cells. Future development of BK124.1 could offer a cure for chronic myeloid leukemia and other chemotherapy-resistant cancers.
Article
Biochemistry & Molecular Biology
Mohamed Abdelgied, Katie Uhl, Oliver G. Chen, Chad Schultz, Kaylie Tripp, Angela M. Peraino, Shreya Paithankar, Bin Chen, Maximiliano Tamae Kakazu, Alicia Castillo Bahena, Tara E. Jager, Cameron Lawson, Dave W. Chesla, Nikolay Pestov, Nikolai N. Modyanov, Jeremy Prokop, Richard R. Neubig, Bruce D. Uhal, Reda E. Girgis, Xiaopeng Li
Summary: Idiopathic pulmonary fibrosis (IPF) is a pathological condition with unknown cause that leads to lung injury and fibrotic response, resulting in thickening of alveolar walls and obliteration of alveolar space. Small airway disease and mucus accumulation are prominent in IPF lungs, similar to cystic fibrosis lung disease. Overexpression of the ATP12A protein in distal small airways of IPF patients and in mouse lungs exacerbates pulmonary fibrosis, which can be prevented by vonoprazan, a potassium competitive proton pump blocker. Inhibiting ATP12A protein may serve as a novel therapeutic strategy for IPF.
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2023)
Article
Hematology
Stephanie A. Renna, Xuefei Zhao, Satya P. Kunapuli, Peisong Ma, Michael Holinstat, Matthew B. Boxer, David J. Maloney, James V. Michael, Steven E. Mckenzie
Summary: This study investigated the cooperativity of PARs (protease-activated receptors) and Fc & gamma;RIIA in HIT using human and mouse model systems. It was found that pharmacological inhibition of 12-LOX can decrease platelet procoagulant phenotype and reduce thrombocytopenia and thrombosis in a mouse model of HIT.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2023)
Review
Pharmacology & Pharmacy
Marcin Cieslak, Marta Slowianek
Summary: The traditional low-molecular-weight drugs target specific biological targets with receptor or enzymatic activity to inhibit their function. However, there are disease proteins that cannot be targeted using this approach. PROTACs, on the other hand, can bind both the protein of interest and the E3 ubiquitin ligase complex, leading to degradation. This review focuses on PROTACs recruiting CRBN E3 ubiquitin ligase and targeting various proteins involved in tumorigenesis.
Article
Chemistry, Multidisciplinary
Sophia D. Staerz, Erika M. Lisabeth, Evert Njomen, Thomas S. Dexheimer, Richard R. Neubig, Jetze J. Tepe
Summary: The balance between protein degradation and synthesis, proteostasis, is key for proper cellular function. The majority of intracellular protein degradation occurs through the ubiquitin-proteasome system, with pathways targeting unfolded proteins playing an important role. Dysregulation of proteolysis can lead to the accumulation of intrinsically disordered proteins (IDPs), contributing to various diseases. Enhancing the activity of the 20S proteasome using small molecules, such as erlotinib, has shown potential in combating IDP accumulation.