Article
Pharmacology & Pharmacy
Cai Qing, Zhao Xinyi, Yu Xuefei, Xue Xindong, Fu Jianhua
Summary: Bronchopulmonary dysplasia (BPD) is a common devastating pulmonary complication in preterm infants, characterized by alveolar maldevelopment associated with oxidative stress and excessive apoptosis. Gap26, a connexin 43-inhibiting peptide, has been shown to improve alveolar development by inhibiting intercellular communication in BPD.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Reproductive Biology
Yuxi Li, Hsun-Ming Chang, Yu-Wen Sung, Hua Zhu, Peter C. K. Leung, Ying-Pu Sun
Summary: In this study, it was found that the phosphorylation of connexin 43 (Cx43) is mediated by protein kinase C (PKC) signaling pathway, leading to a decline in gap junction intercellular communication (GJIC) and subsequent effects on oocyte meiotic resumption. This finding is crucial for understanding the molecular mechanisms of oocyte meiotic resumption.
JOURNAL OF OVARIAN RESEARCH
(2023)
Review
Biochemistry & Molecular Biology
Daniel Rodjakovic, Lilian Salm, Guido Beldi
Summary: Recent studies have shown that Connexin-43 plays important roles in macrophages, including migration, antigen-presentation, intercellular communication, electrochemical support, and immunomodulation. Dysregulation of Cx43 has been described in diseases such as inflammatory bowel disease, tumors, and HIV. However, its involvement in other macrophage functions and inflammatory processes requires further research.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Neurosciences
Xinyu Wang, Chuan Jiang, Chunli Lu, Longbing Ma, Yuxin Feng, Shengyu Cui, Qian Li, Kang Li, Xiang Wang, Fengzeng Jian
Summary: In this study, changes in the number and morphology of ependymal cilia in a syringomyelia rat model were investigated. The results showed a decline in cilia during the early stage of the disease, leading to disrupted intercellular communication. In the later stage, cilia were further reduced due to shear stress exposure, causing a potential mechanism of ependymal cilia decline in syringomyelia development.
EXPERIMENTAL NEUROLOGY
(2023)
Article
Endocrinology & Metabolism
Wen Shi, Zhishang Meng, Jing Luo
Summary: This study identified Cx43 as a key molecule in the development of diabetic retinopathy, and showed that Cx43 knockdown improved DR in a mouse model.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Medicine, General & Internal
Xiaoping Li, Yunshuo Xiao, Xiaoqi Wang, Ruihao Huang, Rui Wang, Yi Deng, Jun Rao, Qiangguo Gao, Shijie Yang, Xi Zhang
Summary: In this study, it was found that Cx43 deficiency exists in CML patients, and its expression is negatively correlated with HIF-1 alpha. Further experiments revealed that overexpression of Cx43 in BMSCs can increase apoptosis rate and block cell cycle in CML cells, while the opposite was observed in the absence of Cx43. Cx43 mediates gap junction intercellular communication (GJIC) through direct contact, and Ca2+ is the key factor mediating the downstream apoptotic pathway. Animal experiments confirmed the findings in vitro, suggesting that enhancing Cx43 expression and GJIC function in the HM may be a novel strategy to reverse drug resistance and promote IM efficacy.
CHINESE MEDICAL JOURNAL
(2023)
Article
Biochemistry & Molecular Biology
Shreyas B. Rao, Nadia Skauli, Nenad Jovanovic, Shirin Katoozi, Antonio Frigeri, Stanley C. Froehner, Marvin E. Adams, Ole Petter Ottersen, Mahmood Amiry-Moghaddam
Summary: The study reveals the interdependence between astrocytic AQP4 and gap junctions, with limited impact on AQP4 isoform expression from deletion of beta 1-syntrophin, but with increased astrocytic gap junctions from double knockout of alpha 1- and beta 1-syntrophin. It highlights the importance of syntrophins in organizing specialized functional domains of brain astrocytes.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2021)
Review
Biochemistry & Molecular Biology
Meng Zhang, Zhen-Zhen Wang, Nai-Hong Chen
Summary: Connexin 43 (Cx43) is widely distributed in mammals, especially in the cardiovascular and nervous systems. Its phosphorylation status is regulated by multiple kinases and phosphatases. Phosphorylation of Cx43 affects the permeability, electrical conductivity, and gating properties of gap junctions, influencing intercellular communication and physiological/pathological processes.
Article
Cell Biology
Weiqi Zeng, Zhizhao Deng, Yingxin Gao, Guoliang Sun, Xianlong Li, Dongdong Yuan
Summary: Long-term exposure to Ang II significantly enhances the expression and function of Cx43-GJs in HUASMCs, leading to the accumulation of intracellular Ca2+ and the activation of downstream signaling pathways. However, propofol inhibits the function of Cx43-GJs in Ang II-pretreated HUASMCs, resulting in the inhibition of intracellular Ca2+ and its downstream signaling pathways and ultimately excessive relaxation of HUASMCs. This explains why patients with chronic hypertension experience more severe blood pressure fluctuations after propofol induction.
CELL COMMUNICATION AND SIGNALING
(2023)
Article
Biology
Filippo Torrisi, Cristiana Alberghina, Debora Lo Furno, Agata Zappala, Samuel Valable, Giovanni Li Volti, Daniele Tibullo, Nunzio Vicario, Rosalba Parenti
Summary: Manipulating the sonic hedgehog pathway to affect connexin 43 expression can regulate cell migration and proliferation in glioblastoma, potentially offering a new therapeutic strategy.
Article
Reproductive Biology
Bongki Kim, Sylvie Breton
Summary: This study aimed to clarify the role of the MAPK/ERK signaling pathway in regulating the expression and localization of Cx43 in the mouse proximal epididymis. The results showed that PD325901 treatment significantly increased the localization of Cx43 on tight junctions, where it colocalized with ZO-1.
BIOLOGY OF REPRODUCTION
(2022)
Article
Medicine, Research & Experimental
Huiqin Wang, Xueying Yang, Huaqing Lai, Yang Sun, Xu Yan, Qidi Ai, Meiyu Lin, Songwei Yang, Yantao Yang, Shifeng Chu, Zhenzhen Wang, Naihong Chen
Summary: Hypericin repaired the dysfunction of gap junctions in the chronic unpredictable stress (CUS) rat model of depression. While hypericin showed potential for treating depression in in vivo experiments, it failed to demonstrate antidepressant benefits in cell experiments. This study suggests that gap junctional function may be a novel therapeutic target for hypericin in the treatment of depression.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Review
Chemistry, Medicinal
Yagya P. Subedi, Guillermo A. Altenberg, Cheng-Wei T. Chang
Summary: Gap-junction channels formed by connexin hemichannels are crucial for intercellular communication, but abnormal activity can lead to diseases. Amphiphilic kanamycins, especially towards connexin 43 inhibition, show promising potential with low cytotoxicity.
FUTURE MEDICINAL CHEMISTRY
(2021)
Article
Environmental Sciences
Jeremy Gingrich, Yong Pu, Brad L. Upham, Madeline Hulse, Sarah Pearl, Denny Martin, Anita Avery, Almudena Veiga-Lopez
Summary: Gap junction intercellular communication (GJIC) is crucial for ovarian function and can be modulated by chemicals like bisphenol S, which may enhance GJIC in ovine and human theca cells through signal pathway regulation. Upregulation of GJIC could lead to the hyperplasia of the theca cell layer or hinder ovulation by maintaining the oocyte in meiotic arrest.
Article
Physiology
Aya Yamada, Keigo Yoshizaki, Masaki Ishikawa, Kan Saito, Yuta Chiba, Emiko Fukumoto, Ryoko Hino, Seira Hoshikawa, Mitsuki Chiba, Takashi Nakamura, Tsutomu Iwamoto, Satoshi Fukumoto
Summary: Connexin 43 (Cx43) is an integral membrane protein that plays a crucial role in tooth development, regulating intercellular communication through gap junction activity by modulating TGF-beta 1-mediated ERK signaling and enamel formation.
FRONTIERS IN PHYSIOLOGY
(2021)
Article
Oncology
Tiemo S. Gerber, Benjamin Goeppert, Anne Hausen, Hagen R. Witzel, Fabian Bartsch, Mario Schindeldecker, Lisa-Katharina Groeger, Dirk A. Ridder, Oscar Cahyadi, Irene Esposito, Matthias M. Gaida, Peter Schirmacher, Peter R. Galle, Hauke Lang, Wilfried Roth, Beate K. Straub
Summary: This study focuses on the differential expression and localization of cell-cell contact proteins E-cadherin and N-cadherin in primary liver cancer and liver metastases of ductal adenocarcinoma of the pancreas. The study demonstrates that N-cadherin positivity can distinguish intrahepatic cholangiocarcinoma from liver metastases of ductal adenocarcinoma of the pancreas, improving the accuracy of the diagnosis. The findings suggest that N-cadherin can be a helpful marker for differential diagnosis between these two types of cancers.
Article
Oncology
Tiemo S. Gerber, Lukas Mueller, Fabian Bartsch, Lisa-Katharina Groger, Mario Schindeldecker, Dirk A. Ridder, Benjamin Goeppert, Markus Moehler, Christoph Dueber, Hauke Lang, Wilfried Roth, Roman Kloeckner, Beate K. Straub
Summary: Accurate diagnosis is crucial for individual patients with liver cancer subtypes. This study identified relevant clinical, radiological, and histological parameters for improved subtype diagnosis of intrahepatic cholangiocarcinoma. Factors such as growth pattern, location, and contrast agent behavior should be considered by radiologists, while pathologists should focus on precursor lesions, mucin secretion, and periductal-infiltrating growth.
Article
Medicine, Research & Experimental
Elena Catanzaro, Eleonora Turrini, Tessa Kerre, Simon Sioen, Ans Baeyens, Alessandra Guerrini, Mohamed Lamin Abdi Bellau, Gianni Sacchetti, Guglielmo Paganetto, Dmitri V. Krysko, Carmela Fimognari
Summary: This study investigates the potential of the monoterpene compound perillaldehyde to induce ferroptosis in leukemia cells. Perillaldehyde induces lipid peroxidation, decreases the expression of a specific protein, and reduces intracellular glutathione. Additionally, it stimulates the secretion of ATP.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Immunology
Olga Krysko, Joshua H. Bourne, Elena Kondakova, Elena A. Galova, Katharine Whitworth, Maddy L. Newby, Claus Bachert, Harriet Hill, Max Crispin, Zania Stamataki, Adam F. Cunningham, Matthew Pugh, Abdullah O. Khan, Julie Rayes, Maria Vedunova, Dmitri V. Krysko, Alexander Brill
Summary: This study found a strong association between SARS-CoV-2 infection and activation of mast cells (MC), which is likely driven by the inflammatory response. The levels of MC proteases were increased in the serum of COVID-19 patients and correlated with disease severity. The results suggest that MC protease levels could predict the course of the disease and that including MC-stabilizing drugs in the treatment scheme might be beneficial for severe COVID-19 patients.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Cell Biology
Maria Vedunova, Victoria Turubanova, Olga Vershinina, Maria Savyuk, Iuliia Efimova, Tatiana Mishchenko, Robrecht Raedt, Anne Vral, Christian Vanhove, Daria Korsakova, Claus Bachert, Frauke Coppieters, Patrizia Agostinis, Abhishek D. D. Garg, Mikhail Ivanchenko, Olga Krysko, Dmitri V. V. Krysko
Summary: This study aimed to develop novel patient-adjusted immunotherapies to improve glioma therapy by inducing Th17 immunity using DC vaccines and predicting the overall survival of glioma patients with a prognostic model.
CELL DEATH & DISEASE
(2022)
Article
Oncology
Lea Penzkofer, Lisa-Katharina Groeger, Maria Hoppe-Lotichius, Janine Baumgart, Stefan Heinrich, Jens Mittler, Tiemo S. Gerber, Beate K. Straub, Arndt Weinmann, Fabian Bartsch, Hauke Lang
Summary: Mixed hepatocellular cholangiocarcinoma (mHC-CC) is a rare tumor with limited data on its prognosis. This study compared the recurrence and survival of mHC-CC with pure hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). The cholangiocarcinoma component of mHC-CC appears to be the defining factor for prognosis. Liver transplant within the Milan criteria may offer a good long-term outcome for mHC-CC.
Review
Biochemistry & Molecular Biology
Ilio Vitale, Federico Pietrocola, Emma Guilbaud, Stuart A. Aaronson, John M. Abrams, Dieter Adam, Massimiliano Agostini, Patrizia Agostinis, Emad S. Alnemri, Lucia Altucci, Ivano Amelio, David W. Andrews, Rami Aqeilan, Eli Arama, Eric H. Baehrecke, Siddharth Balachandran, Daniele Bano, Nickolai A. Barlev, Jiri Bartek, Nicolas G. Bazan, Christoph Becker, Francesca Bernassola, Mathieu J. M. Bertrand, Marco E. Bianchi, Mikhail V. Blagosklonny, J. Magarian Blander, Giovanni Blandino, Klas Blomgren, Christoph Borner, Carl D. Bortner, Pierluigi Bove, Patricia Boya, Catherine Brenner, Petr Broz, Thomas Brunner, Rune Busk Damgaard, George A. Calin, Michelangelo Campanella, Eleonora Candi, Michele Carbone, Didac Carmona-Gutierrez, Francesco Cecconi, Francis K-M Chan, Guo-Qiang Chen, Quan Chen, Youhai H. Chen, Emily H. Cheng, Jerry E. Chipuk, John A. Cidlowski, Aaron Ciechanover, Gennaro Ciliberto, Marcus Conrad, Juan R. Cubillos-Ruiz, Peter E. Czabotar, Vincenzo D'Angiolella, Mads Daugaard, Ted M. Dawson, Valina L. Dawson, Ruggero De Maria, Bart De Strooper, Klaus-Michael Debatin, Ralph J. Deberardinis, Alexei Degterev, Giannino Del Sal, Mohanish Deshmukh, Francesco Di Virgilio, Marc Diederich, Scott J. Dixon, Brian D. Dynlacht, Wafik S. El-Deiry, John W. Elrod, Kurt Engeland, Gian Maria Fimia, Claudia Galassi, Carlo Ganini, Ana J. Garcia-Saez, Abhishek D. Garg, Carmen Garrido, Evripidis Gavathiotis, Motti Gerlic, Sourav Ghosh, Douglas R. Green, Lloyd A. Greene, Hinrich Gronemeyer, Georg Haecker, Gyorgy Hajnoczky, J. Marie Hardwick, Ygal Haupt, Sudan He, David M. Heery, Michael O. Hengartner, Claudio Hetz, David A. Hildeman, Hidenori Ichijo, Satoshi Inoue, Marja Jaeaettelae, Ana Janic, Bertrand Joseph, Philipp J. Jost, Thirumala-Devi Kanneganti, Michael Karin, Hamid Kashkar, Thomas Kaufmann, Gemma L. Kelly, Oliver Kepp, Adi Kimchi, Richard N. Kitsis, Daniel J. Klionsky, Ruth Kluck, Dmitri Krysko, Dagmar Kulms, Sharad Kumar, Sergio Lavandero, Inna N. Lavrik, John J. Lemasters, Gianmaria Liccardi, Andreas Linkermann, Stuart A. Lipton, Richard A. Lockshin, Carlos Lopez-Otin, Tom Luedde, Marion MacFarlane, Frank Madeo, Walter Malorni, Gwenola Manic, Roberto Mantovani, Saverio Marchi, Jean-Christophe Marine, Seamus J. Martin, Jean-Claude Martinou, Pier G. Mastroberardino, Jan Paul Medema, Patrick Mehlen, Pascal Meier, Gerry Melino, Sonia Melino, Edward A. Miao, Ute M. Moll, Cristina Munoz-Pinedo, Daniel J. Murphy, Maria Victoria Niklison-Chirou, Flavia Novelli, Gabriel Nunez, Andrew Oberst, Dimitry Ofengeim, Joseph T. Opferman, Moshe Oren, Michele Pagano, Theocharis Panaretakis, Manolis Pasparakis, Josef M. Penninger, Francesca Pentimalli, David M. Pereira, Shazib Pervaiz, Marcus E. Peter, Paolo Pinton, Giovanni Porta, Jochen H. M. Prehn, Hamsa Puthalakath, Gabriel A. Rabinovich, Krishnaraj Rajalingam, Kodi S. Ravichandran, Markus Rehm, Jean-Ehrland Ricci, Rosario Rizzuto, Nirmal Robinson, Cecilia M. P. Rodrigues, Barak Rotblat, Carla Rothlin, David C. Rubinsztein, Thomas Rudel, Alessandro Rufini, Kevin M. Ryan, Kristopher A. Sarosiek, Akira Sawa, Emre Sayan, Kate Schroder, Luca Scorrano, Federico Sesti, Feng Shao, Yufang Shi, Giuseppe S. Sica, John Silke, Hans-Uwe Simon, Antonella Sistigu, Anastasis Stephanou, Brent R. Stockwell, Flavie Strapazzon, Andreas Strasser, Liming Sun, Erwei Sun, Qiang Sun, Gyorgy Szabadkai, Stephen W. G. Tait, Daolin Tang, Nektarios Tavernarakis, Carol M. Troy, Boris Turk, Nicoletta Urbano, Peter Vandenabeele, Tom Vanden Berghe, Matthew G. Vander Heiden, Jacqueline L. Vanderluit, Alexei Verkhratsky, Andreas Villunger, Silvia von Karstedt, Anne K. Voss, Karen H. Vousden, Domagoj Vucic, Daniela Vuri, Erwin F. Wagner, Henning Walczak, David Wallach, Ruoning Wang, Ying Wang, Achim Weber, Will Wood, Takahiro Yamazaki, Huang-Tian Yang, Zahra Zakeri, Joanna E. Zawacka-Pankau, Lin Zhang, Haibing Zhang, Boris Zhivotovsky, Wenzhao Zhou, Mauro Piacentini, Guido Kroemer, Lorenzo Galluzzi
Summary: Apoptosis is a regulated cell death process involving caspase family proteases. Inhibiting or delaying apoptosis experimentally through pharmacological and genetic strategies has demonstrated its importance in embryonic development, tissue homeostasis, and the pathogenesis of various human disorders. Defects in apoptotic cell death machinery impair development and promote oncogenesis, while inappropriate activation of apoptosis contributes to cell loss and tissue damage in neurological, cardiovascular, renal, hepatic, infectious, neoplastic, and inflammatory conditions.
CELL DEATH AND DIFFERENTIATION
(2023)
Article
Cell Biology
Louis Van der Meeren, Joost Verduijn, Dmitri V. Krysko, Andre G. Skirtach
Summary: The investigation of regulated cell death (RCD) has gained increasing importance in recent years. A microfluidics-based technique called shear flow deformability cytometry (sDC) is used to distinguish dying cells from viable cells based on their mechanical properties. Analysis of the deformation and morphological characteristics of cells indicates significant differences in RCD-induced cells compared to control cells. These results highlight the importance of mechanical properties during RCD and the significance of label-free techniques like sDC for the detection and sorting of live and dead cells.
CELL PROLIFERATION
(2023)
Article
Engineering, Biomedical
Louis van der Meeren, Iuliia Efimova, Robin Demuynck, Bogdan Parakhonskiy, Dmitri V. Krysko, Andre G. Skirtach
Summary: The clearance of dead cells is important for tissue homeostasis and immune responses, but the impact of the mechanobiological properties of dead cells on efferocytosis is not well understood. This study found that cancer cells undergoing ferroptosis have reduced Young's modulus. A nano-coating was developed to modulate their Young's modulus. The coating increased the Young's modulus of the dead cells and enhanced their efferocytosis by macrophages. This research highlights the crucial role of mechanobiology in regulating efferocytosis and its potential for therapeutic strategies and drug delivery systems.
ADVANCED HEALTHCARE MATERIALS
(2023)
Editorial Material
Oncology
Robin Demuynck, Iuliia Efimova, Elena Catanzaro, Dmitri Krysko
Summary: Ferroptosis has attracted attention due to its immunogenicity and higher sensitivity of cancer cells to it. However, recent studies have shown that ferroptosis in tumor-associated neutrophils leads to immunosuppression and negatively impacts therapy. Here, we discuss the potential implications of both the friend and foe roles of ferroptosis in cancer immunotherapy.
Review
Oncology
Jenny Sprooten, Raquel S. Laureano, Isaure Vanmeerbeek, Jannes Govaerts, Stefan Naulaerts, Daniel M. Borras, Lisa Kinget, Jitka Fucikova, Radek Spisek, Lenka Palova Jelinkova, Oliver Kepp, Guido Kroemer, Dmitri V. Krysko, An Coosemans, Rianne D. W. Vaes, Dirk De Ruysscher, Steven De Vleeschouwer, Els Wauters, Evelien Smits, Sabine Tejpar, Benoit Beuselinck, Sigrid Hatse, Hans Wildiers, Paul M. Clement, Peter Vandenabeele, Laurence Zitvogel, Abhishek D. Garg
Summary: Immunogenic cell death (ICD) is a unique process of regulated cell death that activates the immune system. The effectiveness of ICD relies on the antigenicity of dying cells and their ability to expose immunostimulatory molecules. Certain chemotherapies, such as anthracyclines, paclitaxels, and oxaliplatin, have been validated as potent ICD inducers and can be used in combination with immunotherapies against resistant tumors. This article discusses the integration of ICD-inducing chemotherapy in immuno-oncological paradigms.
Article
Biology
Simon Sioen, Louise D'Hondt, Fien Van Houte, Robin Demuynck, Klaus Bacher, Carlos De Wagter, Anne Vral, Barbara Vanderstraeten, Dmitri V. Krysko, Ans Baeyens
Summary: This study compared the DNA damage response in peripheral blood lymphocytes exposed to X-rays with varying beam quality, mean photon energy, and dose rate. The results showed that different beam qualities and mean photon energies of X-rays had varying effects on chromosomal damage and DNA double-stranded breaks, while cell death induction was similar. Additional copper filtration reduced chromosomal damage and double-stranded breaks, but dose rate variation did not have a significant effect on cell response.
INTERNATIONAL JOURNAL OF RADIATION BIOLOGY
(2023)
Article
Pharmacology & Pharmacy
Tikhon S. Redkin, Ekaterina E. Sleptsova, Victoria D. Turubanova, Mariia O. Saviuk, Svetlana A. Lermontova, Larisa G. Klapshina, Nina N. Peskova, Irina V. Balalaeva, Olga Krysko, Tatiana A. Mishchenko, Maria V. Vedunova, Dmitri V. Krysko
Summary: Research in the past decade has shown that the immunogenicity of dying tumor cells is crucial for effective anticancer therapy. In this study, we characterized the abilities of two photoactive dyes to induce immunogenic cell death (ICD) in glioma cells. We demonstrated that these dyes can efficiently induce ICD and stimulate anti-tumor immune responses, leading to the elimination of tumor cells and the formation of long-term immunological memory.
Review
Immunology
Alexey D. Perenkov, Alena D. Sergeeva, Maria V. Vedunova, Dmitri V. Krysko
Summary: mRNA vaccine technology has gained significant momentum in recent years and holds promise as an effective platform for treating cancer and viral diseases. In addition to traditional mRNA vaccines, more modern platforms such as self-amplifying mRNA, trans-amplifying mRNA, and circular RNA are being studied and discussed.
Article
Biochemistry & Molecular Biology
Tiemo Sven Gerber, Hagen Roland Witzel, Arndt Weinmann, Fabian Bartsch, Mario Schindeldecker, Peter R. Galle, Hauke Lang, Wilfried Roth, Dirk Andreas Ridder, Beate Katharina Straub
Summary: This study investigated the levels of 4-hydroxy-nonenal (4-HNE) in liver carcinomas and analyzed their correlation with clinical data and survival outcomes. The results showed that lower levels of 4-HNE were associated with unfavorable survival outcomes and aggressive tumor behavior in hepatocellular carcinoma (HCC). However, in intrahepatic cholangiocarcinoma (iCCA), 4-HNE levels were not correlated with prognostic parameters or survival outcomes.
