Article
Clinical Neurology
Jessie De Ridder, Birgit Verhelle, Jan Vervisch, Katrien Lemmens, Katarzyna Kotulska, Romina Moavero, Paolo Curatolo, Bernhard Weschke, Kate Riney, Martha Feucht, Pavel Krsek, Rima Nabbout, Anna C. Jansen, Konrad Wojdan, Dorota Domanska-Pakiela, Magdalena Kaczorowska-Frontczak, Christoph Hertzberg, Cyrille H. Ferrier, Sharon Samueli, Barbora Benova, Eleonora Aronica, David J. Kwiatkowski, Floor E. Jansen, Sergiusz Jozwiak, Lieven Lagae
Summary: The timing and characteristics of the first electroencephalography (EEG) with epileptiform discharges (ED-EEG) are associated with epilepsy and neurodevelopment at 24 months in infants with tuberous sclerosis complex (TSC). Early recording of ED-EEG can help identify TSC infants at risk of severe epilepsy and those who may benefit from preventive treatment with vigabatrin.
Article
Pharmacology & Pharmacy
Hong Zhang, Zongwei Guo, Yafei Guo, Ziqian Wang, Yao Tang, Ting Song, Zhichao Zhang
Summary: The research showed that the transfer of Bim between Bcl-2-like protein and Hsp70 underlies the crosstalk in mitochondrial apoptosis pathway, leading to apoptosis in cancer cell lines by inhibiting free Bim and facilitating oncogenic client AKT folding and activation.
BIOCHEMICAL PHARMACOLOGY
(2021)
Review
Pharmacology & Pharmacy
Alakananda Basu
Summary: The interplay between apoptosis and senescence is crucial in cancer development, and targeting the Bcl-2 family proteins could be a promising strategy for cancer therapy. Therapy-induced senescence (TIS), induced by chemotherapeutic agents, has been controversial in its effect on therapeutic outcome. Clearance of senescent cells and overcoming their pro-survival mechanisms are important challenges in cancer treatment. This review article discusses recent literature on the role of the Bcl-2 family proteins in apoptosis and senescence, and the progress and limitations in targeting them for cancer therapy.
PHARMACOLOGY & THERAPEUTICS
(2022)
Review
Clinical Neurology
Guihua Chen, Zheyu Zhang, Meiping Wang, Yu Geng, Bo Jin, Thandar Aung
Summary: Epilepsy is a common neurological disorder that lacks effective prevention methods for epileptogenesis, making the identification of reliable biomarkers crucial for predicting the development of epilepsy following a potential brain insult. Various neuroimaging and EEG techniques show promise in identifying biomarkers, but further validation in larger clinical trials is needed.
FRONTIERS IN NEUROLOGY
(2021)
Article
Oncology
Carter K. Fairchild, Konstantinos V. Floros, Sheeba Jacob, Colin M. Coon, Madhavi Puchalapalli, Bin Hu, Hisashi Harada, Mikhail G. Dozmorov, Jennifer E. Koblinski, Steven C. Smith, Gregory Domson, Joel D. Leverson, Andrew J. Souers, Naoko Takebe, Hiromichi Ebi, Anthony C. Faber, Sosipatros A. Boikos
Summary: Synovial sarcoma is a type of soft-tissue sarcoma with limited treatment options and poor prognosis. Research has shown that targeting both the pro-survival proteins BCL-2 and MCL-1 in combination therapy has proven to be effective in cell culture and animal models, suggesting potential for clinical trials.
Article
Medicine, Research & Experimental
Elisabetta Valentini, Simona D'Aguanno, Marta Di Martile, Camilla Montesano, Virginia Ferraresi, Alexandros Patsilinakos, Manuela Sabatino, Lorenzo Antonini, Martina Chiacchiarini, Sergio Valente, Antonello Mai, Gianni Colotti, Rino Ragno, Daniela Trisciuoglio, Donatella Del Bufalo
Summary: Bcl-2 family anti-apoptotic proteins play a significant role in cancer, and finding new molecules targeting these proteins has therapeutic potential. Through virtual screening and experimental validation, IS20 and IS21 were identified as compounds that can inhibit the activity of Bcl-2 family proteins and have anti-proliferative and pro-apoptotic effects on various tumors.
Review
Biochemistry & Molecular Biology
Lisenn Lalier, Francois Vallette, Stephen Manon
Summary: This review examines the role of mitochondrial import machineries in the localization of Bcl-2 family members and how these machineries regulate the function of pro- and anti-apoptotic proteins in resting and apoptotic cells.
Article
Clinical Neurology
Amanda M. McGann, Grace C. Westerkamp, Alisha Chalasani, Cole S. K. Danzer, Emma V. Parkins, Valerine Rajathi, Paul S. Horn, Ernest V. Pedapati, Durgesh Tiwari, Steve C. Danzer, Christina Gross
Summary: This study investigated whether antagonism of miR-324-5p during epileptogenesis inhibits the development of epilepsy using an intrahippocampal kainic acid model in male wild type C57BL/6 J mice. The results suggest that miR-324-5p inhibition during epileptogenesis induced by status epilepticus does not convey anti-epileptogenic effects, but has subtle effects on EEG frequency bands. This highlights the importance of timing of intervention in epilepsy development and suggests that miR-324-5p may primarily act as a proconvulsant rather than a pro-epileptogenic regulator.
FRONTIERS IN NEUROLOGY
(2023)
Review
Oncology
Shanna Qian, Zhong Wei, Wanting Yang, Jinling Huang, Yinfeng Yang, Jinghui Wang
Summary: Apoptosis, a crucial biological process, plays a central role in cancer development and traditional cytotoxic therapies. The study of BCL-2 family proteins in regulating apoptosis and the development of anticancer drugs targeting BCL-2 anti-apoptotic proteins has gained increasing attention, showing great potential in cancer therapy.
FRONTIERS IN ONCOLOGY
(2022)
Article
Genetics & Heredity
Xuming Hu, Huan Luo, Chunfeng Dou, Xujing Chen, Yi Huang, Liping Wang, Songlei Xue, Zhen Sun, Shihao Chen, Qi Xu, Tuoyu Geng, Xin Zhao, Hengmi Cui
Summary: Metformin induces apoptosis in macrophages, especially M1 macrophages, via G0S2 induction, providing a novel anti-inflammatory mechanism.
Article
Endocrinology & Metabolism
Jung Hoon Park, Yeonggwang Hwang, Yen Nhi Doan Nguyen, Hyoung-Chun Kim, Eun-Joo Shin
Summary: The neuroprotective effects of ramelteon, a selective agonist of melatonin receptors, were investigated in a mouse model of KA-induced neurotoxicity. Ramelteon attenuated oxidative stress, restored glutathione homeostasis, and inhibited neuroinflammatory changes in the hippocampus after KA treatment. The activation of melatonin receptors by ramelteon provided neuroprotection by activating Nrf2 signaling and inhibiting NF kappa B signaling.
JOURNAL OF PINEAL RESEARCH
(2023)
Review
Biochemistry & Molecular Biology
Linlin Zhang, Zaiming Lu, Xiangxuan Zhao
Summary: Apoptosis deficiency is a crucial feature in neoplastic diseases, with the Bcl-2 family of proteins playing a decisive role in regulating apoptosis. Studies have shown that hyperactivation of Bcl-2 anti-apoptotic effects is associated with cancer occurrence and resistance to therapy, making targeting Bcl-2 inactivation a promising route for cancer treatment.
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER
(2021)
Article
Plant Sciences
Jiazhe Liu, Yongzhi Liu, Hongchang Li, Chuangchao Wei, Anwei Mao, Weiyan Liu, Gaofeng Pan
Summary: The study found that Polyphyllin D (PD) can induce autophagy in breast cancer cells through activation of the JNK1/Bcl-2 pathway, and increase PD-induced cell apoptosis by inhibiting autophagy, thus achieving anti-tumor effects.
JOURNAL OF ETHNOPHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Anna Geueke, Giada Mantellato, Florian Kuester, Peter Schettina, Melanie Nelles, Jens Michael Seeger, Hamid Kashkar, Catherin Niemann
Summary: This study reveals the impact of Bcl-2 on the function of hair follicle stem cells, maintaining the homeostasis and regeneration of stem cells by controlling the apoptosis response, which may also suppress carcinogenesis.
Review
Biochemistry & Molecular Biology
Daniel Barriuso, Lucia Alvarez-Frutos, Lucia Gonzalez-Gutierrez, Omar Motino, Guido Kroemer, Roberto Palacios-Ramirez, Laura Senovilla
Summary: The Bcl-2 family of proteins, known for regulating apoptosis, is also involved in cellular senescence. These proteins play a role in determining the entry into senescence and the expression levels are modulated during senescence, promoting cell survival. Manipulation of Bax and Bcl-2 expression affects the appearance and survival of tetraploid cells. Understanding the role of Bcl-2 family proteins in senescence can lead to new therapeutic strategies for targeting cancer cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Gastroenterology & Hepatology
Manuela Salvucci, Nyree Crawford, Katie Stott, Susan Bullman, Daniel B. Longley, Jochen H. M. Prehn
Summary: The study identifies CMS4/CRIS-B patients with high Fn/Fusobacteriales prevalence as a high-risk subpopulation that may benefit from therapeutics targeting mesenchymal biology.
Article
Biochemical Research Methods
John Graf, Sanghee Cho, Elizabeth McDonough, Alex Corwin, Anup Sood, Andreas Lindner, Manuela Salvucci, Xanthi Stachtea, Sandra Van Schaeybroeck, Philip D. Dunne, Pierre Laurent-Puig, Daniel Longley, Jochen H. M. Prehn, Fiona Ginty
Summary: The study presented a new immunoFLuorescence Image NOrmalization method and evaluated it against alternative methods using multiround immunofluorescence staining with DAPI. Comparison of multiple normalization methods showed that upper quartile normalization of grid objects in log space had nearly equivalent performance to normalizing segmented cell objects by the middle quantile.
Article
Biochemistry & Molecular Biology
Andreas Ulrich Lindner, Manuela Salvucci, Elizabeth McDonough, Sanghee Cho, Xanthi Stachtea, Emer P. O'Connell, Alex D. Corwin, Alberto Santamaria-Pang, Steven Carberry, Michael Fichtner, Sandra Van Schaeybroeck, Pierre Laurent-Puig, John P. Burke, Deborah A. McNamara, Mark Lawler, Anup Sood, John F. Graf, Markus Rehm, Philip D. Dunne, Daniel B. Longley, Fiona Ginty, Jochen H. M. Prehn
Summary: The study utilized multiplexed immunofluorescence analysis to quantify 18 cell lineage and apoptosis proteins in different cells, revealing differences in apoptosis sensitivity. Single-cell resolution systems modeling identified enhanced sensitivity of cancer cells to mitochondrial permeabilization and executioner caspase activation compared to immune and stromal cells, with significant inter- and intra-tumor heterogeneity.
CELL DEATH AND DIFFERENTIATION
(2022)
Article
Pathology
Xanthi Stachtea, Maurice B. Loughrey, Manuela Salvucci, Andreas U. Lindner, Sanghee Cho, Elizabeth McDonough, Anup Sood, John Graf, Alberto Santamaria-Pang, Alex Corwin, Pierre Laurent-Puig, Sonali Dasgupta, Jinru Shia, Jonathan R. Owens, Samantha Abate, Sandra Van Schaeybroeck, Mark Lawler, Jochen H. M. Prehn, Fiona Ginty, Daniel B. Longley
Summary: In this study, immune signatures in the tumor and tumor microenvironment were assessed using a multiplexed immunofluorescence imaging technology, revealing a significant association between regulatory T cells (Tregs) and survival rates in colorectal cancer patients. Multi-marker classification provided more accurate quantitation of immune cell types with stronger correlations with patient outcomes compared to single markers.
Article
Oncology
Vera Grinkevitch, Mark Wappett, Nyree Crawford, Stacey Price, Andrea Lees, Christopher McCann, Katherine McAllister, Jochen Prehn, Jamie Young, Jess Bateson, Lewis Gallagher, Magali Michaut, Vivek Iyer, Aikaterini Chatzipli, Syd Barthorpe, Daniel Ciznadija, Ido Sloma, Amy Wesa, David A. Tice, Lodewyk Wessels, Mathew Garnett, Daniel B. Longley, Ultan McDermott, Simon S. McDade
Summary: Second-generation TRAIL-R2 agonists face two major clinical challenges: lack of predictive biomarkers and development of resistance. This study identifies caspase-8:FLIP(L) and caspase-8:MCL-1 ratios as potential predictive biomarkers for second-generation TRAIL-R2 agonists, and loss of key effectors like FADD and caspase-8 as likely drivers of clinical resistance in solid tumors.
MOLECULAR CANCER THERAPEUTICS
(2022)
Review
Cell Biology
Sandeep Chenna, Werner J. H. Koopman, Jochen H. M. Prehn, Niamh M. C. Connolly
Summary: This article discusses the mechanistic models and minimal models of mitochondrial reactive oxygen species (ROS) homeostasis. Mechanistic models provide valuable insights but are complex, while minimal models use a smaller set of equations to describe empirical relationships and generate hypotheses. Finally, the article illustrates the application of minimal models in studying the pathophysiology of ROS.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2022)
Review
Cell Biology
William P. Duggan, Emer O'Connell, Jochen H. M. Prehn, John P. Burke
Summary: Alternative splicing, regulated by SRPK1, is implicated in cancer progression and poor survival. Increased SRPK1 expression is associated with proliferation, invasion, migration, and apoptosis in vitro, as well as tumor growth, tumorigenicity, and metastasis in vivo. Aberrant SRPK1 expression is involved in multiple signaling pathways associated with oncogenesis. SRPK1-targeting microRNAs play a role in regulating SRPK1 activity. SRPK1 expression is closely related to the response of tumors to platinum-based chemotherapy.
MOLECULAR AND CELLULAR BIOCHEMISTRY
(2022)
Article
Oncology
Hajrah Khawaja, Rebecca Briggs, Cheryl H. Latimer, Mustasin Rassel, Dary Griffin, Lyndsey Hanson, Alberto Bardelli, Frederica Di Nicolantonio, Simon S. McDade, Christopher J. Scott, Shauna Lambe, Manisha Maurya, Andreas U. Lindner, Jochen H. M. Prehn, Jose Sousa, Chris Winnington, Melissa J. LaBonte, Sarah Ross, Sandra Van Schaeybroeck
Summary: Novel covalent inhibitors of KRASG12C have shown limited response rates in patients with KRASG12C-mutant colorectal cancer. In this study, researchers found that the combination of AZ'1569 and a Bcl-xL inhibitor led to a dramatic and universal apoptosis, suggesting a potential therapeutic strategy for patients with KRAS G12C-mutant colorectal cancer.
MOLECULAR CANCER THERAPEUTICS
(2023)
Article
Cell Biology
Angelo Iannielli, Mirko Luoni, Serena Gea Giannelli, Rosangela Ferese, Gabriele Ordazzo, Matteo Fossati, Andrea Raimondi, Felipe Opazo, Olga Corti, Jochen H. M. Prehn, Stefano Gambardella, Ronald Melki, Vania Broccoli
Summary: In this study, researchers generated a panel of isogenic iPSCs with SNCA gene triplication using gene editing technology. Through this cellular model, they found that loss of growth factor may contribute to mitochondrial dysfunction, increased levels of oxidized dopamine, and alpha-Synuclein aggregation in early DA neurons. Additionally, they observed that exposing neurons to structurally well-characterized synthetic alpha-Synuclein fibrils can accelerate the aggregation process and form deposits resembling Lewy bodies commonly observed in PD patient brain tissues.
CELL DEATH & DISEASE
(2022)
Article
Cell Biology
James Kealey, Heiko Dussmann, Irene Llorente-Folch, Natalia Niewidok, Manuela Salvucci, Jochen H. M. Prehn, Beatrice D'Orsi
Summary: The study reveals that activating KRAS mutations and loss of TP53 remodel cancer metabolism and lead to alterations in bioenergetics under metabolic stress conditions by modulating cellular ATP production, NADH oxidation, mitochondrial respiration and function.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Editorial Material
Cell Biology
Tobias Engel, Eva Maria Jimenez-Mateos, Miguel Diaz-Hernandez
Article
Biochemistry & Molecular Biology
Florian Pichot, Marion C. Hogg, Virginie Marchand, Valerie Bourguignon, Elisabeth Jirstrom, Cliona Farrell, Hesham A. Gibriel, Jochen H. M. Prehn, Yuri Motorin, Mark Helm
Summary: Modification of tRNA is crucial for generating RNA expression diversity. In this study, the stoichiometry of incompletely modified sites in human tRNAs was investigated, and it was found that up to 75% of sites can be incompletely modified. The modification patterns of tRNA populations can provide information to differentiate different cell lines.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2023)
Review
Biochemistry & Molecular Biology
Tobias Engel
Summary: Epilepsy is a brain disease affecting over 70 million people worldwide, characterized by recurrent spontaneous seizures. Challenges in epilepsy management include diagnosis and treatment. Current research aims to identify new drugs with different mechanisms of action for patients not responding to current medications. The P2X7 receptor (P2X7R) has attracted attention as a potential therapeutic and diagnostic target due to its involvement in epilepsy and altered expression in experimental models and patients. This review discusses the latest findings and the potential of P2X7R-based treatments for epilepsy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Endocrinology & Metabolism
N. Ng, H. A. Y. Gibriel, L. Halang, E. Jirstrom, J. A. Ioana, M. Burke, M. M. Byrne, J. H. M. Prehn
Summary: This study investigated the levels of tiRNA 5'ValCAC (alone and in combination with miR-23b-3p) in serum samples from healthy controls, type 1 diabetes, type 2 diabetes, and MIDD subjects. The results showed reduced levels of 5'ValCAC in MIDD and type 2 diabetes subjects compared to controls, and higher levels of miR-23b-3p in type 2 diabetes subjects. Receiver Operating Characteristic analysis demonstrated the potential of 5'ValCAC and miR-23b-3p as MIDD biomarkers, with the combination showing excellent separation from type 2 diabetes subjects.
Meeting Abstract
Oncology
Hajrah Khawaja, Rebecca Briggs, Cheryl Latimer, Md A. M. B. Rassel, Daryl Griffin, Lyndsey Hanson, Alberto Bardelli, Federica Di Nicolantonio, Simon McDade, Christopher Scott, Shauna Lambe, Manisha Maurya, Andreas Ulrich Lindner, Jochen H. M. Prehn, Jose Sousa, Chris Winnington, Melissa J. LaBonte, Sarah Ross, Sandra Van Schaeybroeck
JOURNAL OF CLINICAL ONCOLOGY
(2022)