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Repurposing Drugs for Senotherapeutic Effect: Potential Senomorphic Effects of Female Synthetic Hormones Cells (IF 6.0) Pub Date : 2024-03-15 Laura R. Bramwell, Ryan Frankum, Lorna W. Harries
Repurposing previously approved drugs may fast track the route to the clinic for potential senotherapeutics and improves the inefficiency of the clinical drug development pipeline. We performed a repurposing screen of 240 clinically approved molecules in human primary dermal fibroblasts for their effects on CDKN2A expression. Molecules demonstrating effects on CDKN2A expression underwent secondary
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Unique Spatial Transcriptomic Profiling of the Murine Femoral Fracture Callus: A Preliminary Report Cells (IF 6.0) Pub Date : 2024-03-16 Will Jiang, Dennis L. Caruana, Jungho Back, Francis Y. Lee
Fracture callus formation is a dynamic stage of bone activity and repair with precise, spatially localized gene expression. Metastatic breast cancer impairs fracture healing by disrupting bone homeostasis and imparting an altered genomic profile. Previous sequencing techniques such as single-cell RNA and in situ hybridization are limited by missing spatial context and low throughput, respectively.
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Potential Utility of Urinary Follistatin as a Non-Invasive Indicator of Acute Tubular Damage in Patients with Acute Kidney Injury Cells (IF 6.0) Pub Date : 2024-03-16 Izumi Nagayama, Kaori Takayanagi, Daisuke Nagata, Hajime Hasegawa, Akito Maeshima
Activin A is known to impede tubular repair following renal ischemia, whereas exogenous follistatin, an activin A antagonist, has been shown to ameliorate kidney damage in rats. Despite these findings, the precise role of endogenous follistatin in the kidney has yet to be elucidated. In this study, we investigated the localization of follistatin in the normal human kidney and its potential utility
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Effects of Diabetes Mellitus on Corneal Immune Cell Activation and the Development of Keratopathy Cells (IF 6.0) Pub Date : 2024-03-18 Pier Luigi Surico, Akitomo Narimatsu, Katayoon Forouzanfar, Rohan Bir Singh, Sara Shoushtari, Reza Dana, Tomas Blanco
Diabetes mellitus (DM) is one of the most prevalent diseases globally, and its prevalence is rapidly increasing. Most patients with a long-term history of DM present with some degree of keratopathy (DK). Despite its high incidence, the underlying inflammatory mechanism of DK has not been elucidated yet. For further insights into the underlying immunopathologic processes, we utilized streptozotocin-induced
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Deep Learning Powered Identification of Differentiated Early Mesoderm Cells from Pluripotent Stem Cells Cells (IF 6.0) Pub Date : 2024-03-18 Sakib Mohammad, Arpan Roy, Andreas Karatzas, Sydney L. Sarver, Iraklis Anagnostopoulos, Farhan Chowdhury
Pluripotent stem cells can be differentiated into all three germ-layers including ecto-, endo-, and mesoderm in vitro. However, the early identification and rapid characterization of each germ-layer in response to chemical and physical induction of differentiation is limited. This is a long-standing issue for rapid and high-throughput screening to determine lineage specification efficiency. Here, we
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Disulfiram Inhibits Opsonin-Independent Phagocytosis and Migration of Human Long-Lived In Vitro Cultured Phagocytes from Multiple Inflammatory Diseases Cells (IF 6.0) Pub Date : 2024-03-18 Chen Li, Julian M. Schneider, E. Marion Schneider
Disulfiram (DSF), an anti-alcoholism medicine, exerts treatment effects in patients suffering from persistent Borreliosis and also exhibits anti-cancer effects through its copper chelating derivatives and induction of oxidative stress in mitochondria. Since chronic/persistent borreliosis is characterized by increased amounts of pro-inflammatory macrophages, this study investigated opsonin-independent
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Fluvastatin Converts Human Macrophages into Foam Cells with Increased Inflammatory Response to Inactivated Mycobacterium tuberculosis H37Ra Cells (IF 6.0) Pub Date : 2024-03-18 María Teresa Montero-Vega, Joaquín Matilla, Eulalia Bazán, Diana Reimers, Ana De Andrés-Martín, Rafael Gonzalo-Gobernado, Carlos Correa, Francisco Urbano, Diego Gómez-Coronado
Cholesterol biosynthesis inhibitors (statins) protect hypercholesterolemic patients against developing active tuberculosis, suggesting that these drugs could help the host to control the pathogen at the initial stages of the disease. This work studies the effect of fluvastatin on the early response of healthy peripheral blood mononuclear cells (PBMCs) to inactivated Mycobacterium tuberculosis (Mtb)
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Protein Stability Regulation in Osteosarcoma: The Ubiquitin-like Modifications and Glycosylation as Mediators of Tumor Growth and as Targets for Therapy Cells (IF 6.0) Pub Date : 2024-03-18 Jacopo Di Gregorio, Laura Di Giuseppe, Sara Terreri, Michela Rossi, Giulia Battafarano, Olivia Pagliarosi, Vincenzo Flati, Andrea Del Fattore
The identification of new therapeutic targets and the development of innovative therapeutic approaches are the most important challenges for osteosarcoma treatment. In fact, despite being relatively rare, recurrence and metastatic potential, particularly to the lungs, make osteosarcoma a deadly form of cancer. In fact, although current treatments, including surgery and chemotherapy, have improved survival
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The Exon Junction Complex Factor RBM8A in Glial Fibrillary Acid Protein-Expressing Astrocytes Modulates Locomotion Behaviors Cells (IF 6.0) Pub Date : 2024-03-13 Shravan Asthana, Jennifer Mott, Mabel Tong, Zifei Pei, Yingwei Mao
The role of RNA Binding Motif Protein 8a (RBM8A), an exon junction complex (EJC) component, in neurodevelopmental disorders has been increasingly studied for its crucial role in regulating multiple levels of gene expression. It regulates mRNA splicing, translation, and mRNA degradation and influences embryonic development. RBM8A protein is expressed in both neurons and astrocytes, but little is known
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Leucine Supplementation Prevents the Development of Skeletal Muscle Dysfunction in a Rat Model of HFpEF Cells (IF 6.0) Pub Date : 2024-03-13 Paula Ketilly Nascimento Alves, Antje Schauer, Antje Augstein, Maria-Elisa Prieto Jarabo, Anita Männel, Peggy Barthel, Beatrice Vahle, Anselmo S. Moriscot, Axel Linke, Volker Adams
Heart failure with preserved ejection fraction (HFpEF) is associated with exercise intolerance due to alterations in the skeletal muscle (SKM). Leucine supplementation is known to alter the anabolic/catabolic balance and to improve mitochondrial function. Thus, we investigated the effect of leucine supplementation in both a primary and a secondary prevention approach on SKM function and factors modulating
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The Effect of Leukocyte Removal and Matrix Metalloproteinase Inhibition on Platelet Storage Lesions Cells (IF 6.0) Pub Date : 2024-03-13 Alina Rak-Pasikowska, Kornela Hałucha, Agnieszka Sapa-Wojciechowska, Aneta Wrzyszcz, Wioletta Gałuszka, Anna Pęcak-Solińska, Iwona Bil-Lula
The reasons for unfavorable changes in platelet concentrate (PC) quality during storage are not fully understood yet. We aimed to evaluate whether leukocytes and matrix metalloproteinases (MMPs) lead to a decrease in the quality of PCs and examine whether MMP inhibition will slow down the platelets’ aging. Nine PCs were divided into three parts: (1) leukocyte-depleted (F) PCs, (2) PCs with no additional
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Recombinant Acetylcholine Receptor Immunization Induces a Robust Model of Experimental Autoimmune Myasthenia Gravis in Mice Cells (IF 6.0) Pub Date : 2024-03-14 Lukas Theissen, Christina B. Schroeter, Niklas Huntemann, Saskia Räuber, Vera Dobelmann, Derya Cengiz, Alexander Herrmann, Kathrin Koch-Hölsken, Norbert Gerdes, Hao Hu, Philipp Mourikis, Amin Polzin, Malte Kelm, Hans-Peter Hartung, Sven G. Meuth, Christopher Nelke, Tobias Ruck
Myasthenia gravis (MG) is a prototypical autoimmune disease of the neuromuscular junction (NMJ). The study of the underlying pathophysiology has provided novel insights into the interplay of autoantibodies and complement-mediated tissue damage. Experimental autoimmune myasthenia gravis (EAMG) emerged as a valuable animal model, designed to gain further insight and to test novel therapeutic approaches
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Vibration Rather than Microgravity Affects Bone Metabolism in Adult Zebrafish Scale Model Cells (IF 6.0) Pub Date : 2024-03-14 Marta Carnovali, Stefania Zava, Giuseppe Banfi, Angela Maria Rizzo, Massimo Mariotti
Gravity and mechanical forces cause important alterations in the human skeletal system, as demonstrated by space flights. Innovative animal models like zebrafish embryos and medaka have been introduced to study bone response in ground-based microgravity simulators. We used, for the first time, adult zebrafish in simulated microgravity, with a random positioning machine (RPM) to study bone remodeling
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Hypoxic Conditions Modulate Chondrogenesis through the Circadian Clock: The Role of Hypoxia-Inducible Factor-1α Cells (IF 6.0) Pub Date : 2024-03-14 Krisztián Zoltán Juhász, Tibor Hajdú, Patrik Kovács, Judit Vágó, Csaba Matta, Roland Takács
Hypoxia-inducible factor-1 (HIF-1) is a heterodimer transcription factor composed of an alpha and a beta subunit. HIF-1α is a master regulator of cellular response to hypoxia by activating the transcription of genes that facilitate metabolic adaptation to hypoxia. Since chondrocytes in mature articular cartilage reside in a hypoxic environment, HIF-1α plays an important role in chondrogenesis and in
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The Roles of Fibrinolytic Factors in Bone Destruction Caused by Inflammation Cells (IF 6.0) Pub Date : 2024-03-15 Yosuke Kanno
Chronic inflammatory diseases, such as rheumatoid arthritis, spondyloarthritis, systemic lupus erythematosus, Crohn’s disease, periodontitis, and carcinoma metastasis frequently result in bone destruction. Pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, and IL-17 are known to influence bone loss by promoting the differentiation and activation of osteoclasts
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Brain-Derived Neurotrophic Factor (BDNF) Enhances Osteogenesis and May Improve Bone Microarchitecture in an Ovariectomized Rat Model Cells (IF 6.0) Pub Date : 2024-03-15 Eugene J. Park, Van-Long Truong, Woo-Sik Jeong, Woo-Kie Min
Background: Brain-derived neurotrophic factor (BDNF) has gained attention as a therapeutic agent due to its potential biological activities, including osteogenesis. However, the molecular mechanisms involved in the osteogenic activity of BDNF have not been fully understood. This study aimed to investigate the action of BDNF on the osteoblast differentiation in bone marrow stromal cells, and its influence
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Neonatal Brains Exhibit Higher Neural Reparative Activities than Adult Brains in a Mouse Model of Ischemic Stroke Cells (IF 6.0) Pub Date : 2024-03-15 Ryo Nishiyama, Takayuki Nakagomi, Akiko Nakano-Doi, Yoji Kuramoto, Masahiro Tsuji, Shinichi Yoshimura
The neonatal brain is substantially more resistant to various forms of injury than the mature brain. For instance, the prognosis following ischemic stroke is generally poor in the elderly but favorable in neonates. Identifying the cellular and molecular mechanisms underlying reparative activities in the neonatal brain after ischemic injury may provide feasible targets for therapeutic interventions
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Characterization of Lysophospholipase D Activity in Mammalian Cell Membranes Cells (IF 6.0) Pub Date : 2024-03-16 Yuhuan Xie, Krishna M. Ella, Terra C. Gibbs, Marianne E. Yohannan, Stewart M. Knoepp, Pravita Balijepalli, G. Patrick Meier, Kathryn E. Meier
Lysophosphatidic acid (LPA) is a lipid mediator that binds to G-protein-coupled receptors, eliciting a wide variety of responses in mammalian cells. Lyso-phospholipids generated via phospholipase A2 (PLA2) can be converted to LPA by a lysophospholipase D (lyso-PLD). Secreted lyso-PLDs have been studied in more detail than membrane-localized lyso-PLDs. This study utilized in vitro enzyme assays with
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TNF-Related Apoptosis-Inducing Ligand: Non-Apoptotic Signalling Cells (IF 6.0) Pub Date : 2024-03-16 Abderrahmane Guerrache, Olivier Micheau
TNF-related apoptosis-inducing ligand (TRAIL or Apo2 or TNFSF10) belongs to the TNF superfamily. When bound to its agonistic receptors, TRAIL can induce apoptosis in tumour cells, while sparing healthy cells. Over the last three decades, this tumour selectivity has prompted many studies aiming at evaluating the anti-tumoral potential of TRAIL or its derivatives. Although most of these attempts have
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Primary Ciliary Dyskinesia and Retinitis Pigmentosa: Novel RPGR Variant and Possible Modifier Gene Cells (IF 6.0) Pub Date : 2024-03-16 Noelia Baz-Redón, Laura Sánchez-Bellver, Mónica Fernández-Cancio, Sandra Rovira-Amigo, Thomas Burgoyne, Rai Ranjit, Virginia Aquino, Noemí Toro-Barrios, Rosario Carmona, Eva Polverino, Maria Cols, Antonio Moreno-Galdó, Núria Camats-Tarruella, Gemma Marfany
We report a novel RPGR missense variant co-segregated with a familial X-linked retinitis pigmentosa (XLRP) case. The brothers were hemizygous for this variant, but only the proband presented with primary ciliary dyskinesia (PCD). Thus, we aimed to elucidate the role of the RPGR variant and other modifier genes in the phenotypic variability observed in the family and its impact on motile cilia. The
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Immune Cells, Gut Microbiota, and Vaccines: A Gender Perspective Cells (IF 6.0) Pub Date : 2024-03-17 Pierluigi Rio, Mario Caldarelli, Monica Chiantore, Francesca Ocarino, Marcello Candelli, Antonio Gasbarrini, Giovanni Gambassi, Rossella Cianci
The development of preventive and therapeutic vaccines has played a crucial role in preventing infections and treating chronic and non-communicable diseases, respectively. For a long time, the influence of sex differences on modifying health and disease has not been addressed in clinical and preclinical studies. The interaction of genetic, epigenetic, and hormonal factors plays a role in the sex-related
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PROTAC-Mediated Dual Degradation of BCL-xL and BCL-2 Is a Highly Effective Therapeutic Strategy in Small-Cell Lung Cancer Cells (IF 6.0) Pub Date : 2024-03-17 Sajid Khan, Lin Cao, Janet Wiegand, Peiyi Zhang, Maria Zajac-Kaye, Frederic J. Kaye, Guangrong Zheng, Daohong Zhou
BCL-xL and BCL-2 are validated therapeutic targets in small-cell lung cancer (SCLC). Targeting these proteins with navitoclax (formerly ABT263, a dual BCL-xL/2 inhibitor) induces dose-limiting thrombocytopenia through on-target BCL-xL inhibition in platelets. Therefore, platelet toxicity poses a barrier in advancing the clinical translation of navitoclax. We have developed a strategy to selectively
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HSP47 Increases the Expression of Type I Collagen in Fibroblasts through IRE1α Activation, XBP1 Splicing, and Nuclear Translocation of β-Catenin Cells (IF 6.0) Pub Date : 2024-03-17 So Young Ham, Min Ju Pyo, Moonkyung Kang, Yeon-Soo Kim, Dong Hun Lee, Jin Ho Chung, Seung-Taek Lee
Heat shock protein 47 (HSP47), also known as SERPINH1, functions as a collagen-specific molecular chaperone protein essential for the formation and stabilization of the collagen triple helix. Here, we delved into the regulatory pathways governed by HSP47, shedding light on collagen homeostasis. Our investigation revealed a significant reduction in HSP47 mRNA levels in the skin tissue of older mice
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Approaching Thrombospondin-1 as a Potential Target for Mesenchymal Stromal Cells to Support Liver Regeneration after Partial Hepatectomy in Mouse and Humans Cells (IF 6.0) Pub Date : 2024-03-17 Lysann Tietze, Madlen Christ, Jiyeon Yu, Peggy Stock, Sandra Nickel, Annelie Schulze, Michael Bartels, Hans-Michael Tautenhahn, Bruno Christ
Extended liver resection carries the risk of post-surgery liver failure involving thrombospondin-1-mediated aggravation of hepatic epithelial plasticity and function. Mesenchymal stromal cells (MSCs), by interfering with thrombospondin-1 (THBS1), counteract hepatic dysfunction, though the mechanisms involved remain unknown. Herein, two-thirds partial hepatectomy in mice increased hepatic THBS1, downstream
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Autologous T-Cell-Free Antigen Presentation System Unveils hCMV-Specific NK Cell Response Cells (IF 6.0) Pub Date : 2024-03-17 Maria O. Ustiuzhanina, Maria A. Streltsova, Nikita D. Timofeev, Maxim Kryukov, Dmitriy M. Chudakov, Elena I. Kovalenko
NK cells play a decisive role in controlling hCMV infection by combining innate and adaptive-like immune reactions. The hCMV-derived VMAPRTLFL (LFL) peptide is a potent activator of NKG2C+ NK cells. Proposed here is an autologous system of LFL stimulation without T lymphocytes and exogenous cytokines that allows us to evaluate NK-cell hCMV-specific responses in more native settings. In this model,
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Bitter Taste Receptor T2R14 and Autophagy Flux in Gingival Epithelial Cells Cells (IF 6.0) Pub Date : 2024-03-17 Nisha Singh, Ben Ulmer, Manoj Reddy Medapati, Christine Zhang, Robert J. Schroth, Saeid Ghavami, Prashen Chelikani
Macroautophagy (hereafter autophagy) is a lysosomal degradation pathway that functions in nutrient recycling and as a mechanism of innate immunity. Previously, we reported a novel host–bacteria interaction between cariogenic S. mutans and bitter taste receptor (T2R14) in gingival epithelial cells (GECs), leading to an innate immune response. Further, S. mutans might be using the host immune system
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Intrauterine Growth Restriction: Need to Improve Diagnostic Accuracy and Evidence for a Key Role of Oxidative Stress in Neonatal and Long-Term Sequelae Cells (IF 6.0) Pub Date : 2024-03-13 Eva Nüsken, Sarah Appel, Leon Saschin, Celien Kuiper-Makris, Laura Oberholz, Charlotte Schömig, Anne Tauscher, Jörg Dötsch, Angela Kribs, Miguel A. Alejandre Alcazar, Kai-Dietrich Nüsken
Intrauterine growth restriction (IUGR) and being small for gestational age (SGA) are two distinct conditions with different implications for short- and long-term child development. SGA is present if the estimated fetal or birth weight is below the tenth percentile. IUGR can be identified by additional abnormalities (pathological Doppler sonography, oligohydramnion, lack of growth in the interval, estimated
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Vitamin D in Cutaneous T-Cell Lymphoma Cells (IF 6.0) Pub Date : 2024-03-13 August-Witte Feentved Ødum, Carsten Geisler
Cutaneous T-cell lymphoma (CTCL) is characterized by the proliferation of malignant T cells in inflamed skin lesions. Mycosis fungoides (MF)—the most common variant of CTCL—often presents with skin lesions around the abdomen and buttocks (“bathing suit” distribution), i.e., in skin areas devoid of sun-induced vitamin D. For decades, sunlight and vitamin D have been connected to CTCL. Thus, vitamin
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Optical Genome Mapping Reveals Genomic Alterations upon Gene Editing in hiPSCs: Implications for Neural Tissue Differentiation and Brain Organoid Research Cells (IF 6.0) Pub Date : 2024-03-14 Lucia Gallego Villarejo, Wanda M. Gerding, Lisa Bachmann, Luzie H. I. Hardt, Stefan Bormann, Huu Phuc Nguyen, Thorsten Müller
Genome editing, notably CRISPR (cluster regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated protein 9), has revolutionized genetic engineering allowing for precise targeted modifications. This technique’s combination with human induced pluripotent stem cells (hiPSCs) is a particularly valuable tool in cerebral organoid (CO) research. In this study, CRISPR/Cas9-generated fluorescently
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The Potential of Mushroom Extracts to Improve Chemotherapy Efficacy in Cancer Cells: A Systematic Review Cells (IF 6.0) Pub Date : 2024-03-14 Jéssica Fonseca, Josiana A. Vaz, Sara Ricardo
Chemoresistance is a challenge in cancer treatment, limiting the effectiveness of chemotherapy. Mushroom extracts have shown potential as treatments for cancer therapies, offering a possible solution to overcome chemoresistance. This systematic review aimed to explore the role of mushroom extracts in enhancing chemotherapy and reversing chemoresistance in cancer cells. We searched the PubMed, Web of
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Recent Research Trends in Neuroinflammatory and Neurodegenerative Disorders Cells (IF 6.0) Pub Date : 2024-03-14 Jessica Cohen, Annette Mathew, Kirk D. Dourvetakis, Estella Sanchez-Guerrero, Rajendra P. Pangeni, Narasimman Gurusamy, Kristina K. Aenlle, Geeta Ravindran, Assma Twahir, Dylan Isler, Sara Rukmini Sosa-Garcia, Axel Llizo, Alison C. Bested, Theoharis C. Theoharides, Nancy G. Klimas, Duraisamy Kempuraj
Neuroinflammatory and neurodegenerative disorders including Alzheimer’s disease (AD), Parkinson’s disease (PD), traumatic brain injury (TBI) and Amyotrophic lateral sclerosis (ALS) are chronic major health disorders. The exact mechanism of the neuroimmune dysfunctions of these disease pathogeneses is currently not clearly understood. These disorders show dysregulated neuroimmune and inflammatory responses
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Differentiation of Adipose Tissue Mesenchymal Stem Cells into Endothelial Cells Depends on Fat Depot Conditions: Regulation by miRNA Cells (IF 6.0) Pub Date : 2024-03-14 Gemma Arderiu, Anna Civit-Urgell, Alberto Díez-Caballero, Fabrizio Moscatiello, Carlos Ballesta, Lina Badimon
The development of obesity is associated with substantial modulation of adipose tissue (AT) structure. The plasticity of the AT is reflected by its remarkable ability to expand or reduce in size throughout the adult lifespan, which is linked to the development of its vasculature. This increase in AT vasculature could be mediated by the differentiation of adipose tissue-derived stem cells (ASCs) into
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Wound Repair and Ca2+ Signalling Interplay: The Role of Ca2+ Channels in Skin Cells (IF 6.0) Pub Date : 2024-03-11 Gregorio Bonsignore, Simona Martinotti, Elia Ranzato
The process of wound healing is intricate and tightly controlled, involving a number of different cellular and molecular processes. Numerous cellular functions, especially those related to wound healing, depend critically on calcium ions (Ca2+). Ca2+ channels are proteins involved in signal transduction and communication inside cells that allow calcium ions to pass through cell membranes. Key Ca2+
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Phosphorylations and Acetylations of Cytochrome c Control Mitochondrial Respiration, Mitochondrial Membrane Potential, Energy, ROS, and Apoptosis Cells (IF 6.0) Pub Date : 2024-03-12 Paul T. Morse, Tasnim Arroum, Junmei Wan, Lucynda Pham, Asmita Vaishnav, Jamie Bell, Lauren Pavelich, Moh H. Malek, Thomas H. Sanderson, Brian F.P. Edwards, Maik Hüttemann
Cytochrome c (Cytc) has both life-sustaining and cellular death-related functions, depending on subcellular localization. Within mitochondria, Cytc acts as a single electron carrier as part of the electron transport chain (ETC). When released into the cytosol after cellular insult, Cytc triggers the assembly of the apoptosome, committing the cell to intrinsic apoptosis. Due to these dual natures, Cytc
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Mechanical Stress Induces Sodium Entry and Osmoprotective Responses in Murine Synovial Fibroblasts Cells (IF 6.0) Pub Date : 2024-03-13 Annemarie Proff, Ute Nazet, Agnes Schröder, Jonathan Jantsch
Osteoarthritis (OA) is a multifactorial disease depending on molecular, genetic, and environmental factors like mechanical strain. Next to the cartilage and the subchondral bone, OA also affects the synovium, which is critically involved in the maintenance of joint homeostasis. As there is a correlation between the extracellular sodium content in the knee joint and OA, this study investigates the impact
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Gut–Brain Interactions and Their Impact on Astrocytes in the Context of Multiple Sclerosis and Beyond Cells (IF 6.0) Pub Date : 2024-03-13 Julia Zißler, Veit Rothhammer, Mathias Linnerbauer
Multiple Sclerosis (MS) is a chronic autoimmune inflammatory disease of the central nervous system (CNS) that leads to physical and cognitive impairment in young adults. The increasing prevalence of MS underscores the critical need for innovative therapeutic approaches. Recent advances in neuroimmunology have highlighted the significant role of the gut microbiome in MS pathology, unveiling distinct
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A Recombinant Peptide Device Combined with Adipose Tissue-Derived Stem Cells Enhances Subcutaneous Islet Engraftment Cells (IF 6.0) Pub Date : 2024-03-13 Takahiro Mizui, Akiko Inagaki, Yasuhiro Nakamura, Takehiro Imura, Satomi Suzuki Uematsu, Shigehito Miyagi, Takashi Kamei, Michiaki Unno, Kimiko Watanabe, Masafumi Goto
Subcutaneous space has been considered an attractive site for islet graft transplantation; however, the oxygen tension and vascularization are insufficient for islet graft survival. We investigated whether subcutaneous pre-implantation of a recombinant peptide (RCP) device with adipose tissue-derived stem cells (ADSCs) enhanced subcutaneous islet engraftment. RCP devices with/without syngeneic ADSCs
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Molecular Mechanism of Autophagosome–Lysosome Fusion in Mammalian Cells Cells (IF 6.0) Pub Date : 2024-03-13 Po-Yuan Ke
In eukaryotes, targeting intracellular components for lysosomal degradation by autophagy represents a catabolic process that evolutionarily regulates cellular homeostasis. The successful completion of autophagy initiates the engulfment of cytoplasmic materials within double-membrane autophagosomes and subsequent delivery to autolysosomes for degradation by acidic proteases. The formation of autolysosomes
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Implementing Whole Genome Sequencing (WGS) in Clinical Practice: Advantages, Challenges, and Future Perspectives Cells (IF 6.0) Pub Date : 2024-03-13 Petar Brlek, Luka Bulić, Matea Bračić, Petar Projić, Vedrana Škaro, Nidhi Shah, Parth Shah, Dragan Primorac
The integration of whole genome sequencing (WGS) into all aspects of modern medicine represents the next step in the evolution of healthcare. Using this technology, scientists and physicians can observe the entire human genome comprehensively, generating a plethora of new sequencing data. Modern computational analysis entails advanced algorithms for variant detection, as well as complex models for
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Inflammatory Skin Diseases: Focus on the Role of Suppressors of Cytokine Signaling (SOCS) Proteins Cells (IF 6.0) Pub Date : 2024-03-13 Antonia Cianciulli, Rosa Calvello, Chiara Porro, Dario Domenico Lofrumento, Maria Antonietta Panaro
Inflammatory skin diseases include a series of disorders characterized by a strong activation of the innate and adaptive immune system in which proinflammatory cytokines play a fundamental role in supporting inflammation. Skin inflammation is a complex process influenced by various factors, including genetic and environmental factors, characterized by the dysfunction of both immune and non-immune cells
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Exploring Regorafenib Responsiveness and Uncovering Molecular Mechanisms in Recurrent Glioblastoma Tumors through Longitudinal In Vitro Sampling Cells (IF 6.0) Pub Date : 2024-03-11 Mariangela Morelli, Francesca Lessi, Sara Franceschi, Gianmarco Ferri, Manuel Giacomarra, Michele Menicagli, Carlo Gambacciani, Francesco Pieri, Francesco Pasqualetti, Nicola Montemurro, Paolo Aretini, Orazio Santo Santonocito, Anna Luisa Di Stefano, Chiara Maria Mazzanti
Glioblastoma, a deadly brain tumor, shows limited response to standard therapies like temozolomide (TMZ). Recent findings from the REGOMA trial underscore a significant survival improvement offered by Regorafenib (REGO) in recurrent glioblastoma. Our study aimed to propose a 3D ex vivo drug response precision medicine approach to investigate recurrent glioblastoma sensitivity to REGO and elucidate
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HDAC6 Enhances Endoglin Expression through Deacetylation of Transcription Factor SP1, Potentiating BMP9-Induced Angiogenesis Cells (IF 6.0) Pub Date : 2024-03-11 Chen Sun, Kuifang Xie, Lejie Yang, Shengyang Cai, Mingjie Wang, Yizhun Zhu, Beibei Tao, Yichun Zhu
Histone deacetylase 6 (HDAC6) plays a crucial role in the acetylation of non-histone proteins and is notably implicated in angiogenesis, though its underlying mechanisms were previously not fully understood. This study conducted transcriptomic and proteomic analyses on vascular endothelial cells with HDAC6 knockdown, identifying endoglin (ENG) as a key downstream protein regulated by HDAC6. This protein
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Progressive Irreversible Proprioceptive Piezo2 Channelopathy-Induced Lost Forced Peripheral Oscillatory Synchronization to the Hippocampal Oscillator May Explain the Onset of Amyotrophic Lateral Sclerosis Pathomechanism Cells (IF 6.0) Pub Date : 2024-03-12 Balázs Sonkodi
Amyotrophic lateral sclerosis (ALS) is a mysterious lethal multisystem neurodegenerative disease that gradually leads to the progressive loss of motor neurons. A recent non-contact dying-back injury mechanism theory for ALS proposed that the primary damage is an acquired irreversible intrafusal proprioceptive terminal Piezo2 channelopathy with underlying genetic and environmental risk factors. Underpinning
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Drosophila Importin Alpha 1 (Dα1) Is Required to Maintain Germline Stem Cells in the Testis Niche Cells (IF 6.0) Pub Date : 2024-03-12 James Heaney, Jiamin Zhao, Franca Casagranda, Kate L. Loveland, Nicole A. Siddall, Gary R. Hime
Stem cell maintenance and differentiation can be regulated via the differential activity of transcription factors within stem cells and their progeny. For these factors to be active, they need to be transported from their site of synthesis in the cytoplasm into the nucleus. A tissue-specific requirement for factors involved in nuclear importation is a potential mechanism to regulate stem cell differentiation
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Diversity of Intercellular Communication Modes: A Cancer Biology Perspective Cells (IF 6.0) Pub Date : 2024-03-12 Thanzeela Ebrahim, Abdul Shukkur Ebrahim, Mustapha Kandouz
From the moment a cell is on the path to malignant transformation, its interaction with other cells from the microenvironment becomes altered. The flow of molecular information is at the heart of the cellular and systemic fate in tumors, and various processes participate in conveying key molecular information from or to certain cancer cells. For instance, the loss of tight junction molecules is part
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Modification of Mesenchymal Stem/Stromal Cell-Derived Small Extracellular Vesicles by Calcitonin Gene Related Peptide (CGRP) Antagonist: Potential Implications for Inflammation and Pain Reversal Cells (IF 6.0) Pub Date : 2024-03-10 Kevin Liebmann, Mario A. Castillo, Stanislava Jergova, Thomas M. Best, Jacqueline Sagen, Dimitrios Kouroupis
During the progression of knee osteoarthritis (OA), the synovium and infrapatellar fat pad (IFP) can serve as source for Substance P (SP) and calcitonin gene-related peptide (CGRP), two important pain-transmitting, immune, and inflammation modulating neuropeptides. Our previous studies showed that infrapatellar fat pad-derived mesenchymal stem/stromal cells (MSC) acquire a potent immunomodulatory phenotype
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NF-κB as an Inducible Regulator of Inflammation in the Central Nervous System Cells (IF 6.0) Pub Date : 2024-03-11 Sudha Anilkumar, Elizabeth Wright-Jin
The NF-κB (nuclear factor K-light-chain-enhancer of activated B cells) transcription factor family is critical for modulating the immune proinflammatory response throughout the body. During the resting state, inactive NF-κB is sequestered by IκB in the cytoplasm. The proteasomal degradation of IκB activates NF-κB, mediating its translocation into the nucleus to act as a nuclear transcription factor
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Cannabidiol Disrupts Mitochondrial Respiration and Metabolism and Dysregulates Trophoblast Cell Differentiation Cells (IF 6.0) Pub Date : 2024-03-11 Tina Podinic, Louise Limoges, Cristina Monaco, Andie MacAndrew, Mahek Minhas, Joshua Nederveen, Sandeep Raha
Trophoblast differentiation is a crucial process in the formation of the placenta where cytotrophoblasts (CTs) differentiate and fuse to form the syncytiotrophoblast (ST). The bioactive components of cannabis, such as Δ9-THC, are known to disrupt trophoblast differentiation and fusion, as well as mitochondrial dynamics and respiration. However, less is known about the impact of cannabidiol (CBD) on
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Low Density Lipoprotein Cholesterol Decreases the Expression of Adenosine A2A Receptor and Lipid Rafts-Protein Flotillin-1: Insights on Cardiovascular Risk of Hypercholesterolemia Cells (IF 6.0) Pub Date : 2024-03-11 Marie-Charlotte Chaptal, Marie Maraninchi, Giorgia Musto, Julien Mancini, Hedi Chtioui, Janine Dupont-Roussel, Marion Marlinge, Julien Fromonot, Nathalie Lalevee, Florian Mourre, Sophie Beliard, Régis Guieu, René Valero, Giovanna Mottola
High blood levels of low-density lipoprotein (LDL)-cholesterol (LDL-C) are associated with atherosclerosis, mainly by promoting foam cell accumulation in vessels. As cholesterol is an essential component of cell plasma membranes and a regulator of several signaling pathways, LDL-C excess may have wider cardiovascular toxicity. We examined, in untreated hypercholesterolemia (HC) patients, selected regardless
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CD74 Promotes Cyst Growth and Renal Fibrosis in Autosomal Dominant Polycystic Kidney Disease Cells (IF 6.0) Pub Date : 2024-03-11 Julie Xia Zhou, Alice Shasha Cheng, Li Chen, Linda Xiaoyan Li, Ewud Agborbesong, Vicente E. Torres, Peter C. Harris, Xiaogang Li
The progression of autosomal dominant polycystic kidney disease (ADPKD), an inherited kidney disease, is associated with renal interstitial inflammation and fibrosis. CD74 has been known not only as a receptor of macrophage migration inhibitory factor (MIF) it can also have MIF independent functions. In this study, we report unknown roles and function of CD74 in ADPKD. We show that knockout of CD74
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Phosphodiesterases 4B and 4D Differentially Regulate cAMP Signaling in Calcium Handling Microdomains of Mouse Hearts Cells (IF 6.0) Pub Date : 2024-03-08 Axel E. Kraft, Nadja I. Bork, Hariharan Subramanian, Nikoleta Pavlaki, Antonio V. Failla, Bernd Zobiak, Marco Conti, Viacheslav O. Nikolaev
The ubiquitous second messenger 3′,5′-cyclic adenosine monophosphate (cAMP) regulates cardiac excitation-contraction coupling (ECC) by signaling in discrete subcellular microdomains. Phosphodiesterase subfamilies 4B and 4D are critically involved in the regulation of cAMP signaling in mammalian cardiomyocytes. Alterations of PDE4 activity in human hearts has been shown to result in arrhythmias and
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Piezo1 and Its Function in Different Blood Cell Lineages Cells (IF 6.0) Pub Date : 2024-03-09 Anastasia Iris Karkempetzaki, Katya Ravid
Mechanosensation is a fundamental function through which cells sense mechanical stimuli by initiating intracellular ion currents. Ion channels play a pivotal role in this process by orchestrating a cascade of events leading to the activation of downstream signaling pathways in response to particular stimuli. Piezo1 is a cation channel that reacts with Ca2+ influx in response to pressure sensation evoked
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Isolevuglandins Promote Mitochondrial Dysfunction and Electrophysiologic Abnormalities in Atrial Cardiomyocytes Cells (IF 6.0) Pub Date : 2024-03-09 Tuerdi Subati, Zhenjiang Yang, Matthew B. Murphy, Joshua M. Stark, David Z. Trykall, Sean S. Davies, Joey V. Barnett, Katherine T. Murray
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, yet the cellular and molecular mechanisms underlying the AF substrate remain unclear. Isolevuglandins (IsoLGs) are highly reactive lipid dicarbonyl products that mediate oxidative stress-related injury. In murine hypertension, the lipid dicarbonyl scavenger 2-hydroxybenzylamine (2-HOBA) reduced IsoLGs and AF susceptibility. We
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Emerging Roles and Mechanisms of RNA Modifications in Neurodegenerative Diseases and Glioma Cells (IF 6.0) Pub Date : 2024-03-05 Ami Kobayashi, Yosuke Kitagawa, Ali Nasser, Hiroaki Wakimoto, Keisuke Yamada, Shota Tanaka
Despite a long history of research, neurodegenerative diseases and malignant brain tumor gliomas are both considered incurable, facing challenges in the development of treatments. Recent evidence suggests that RNA modifications, previously considered as static components of intracellular RNAs, are in fact dynamically regulated across various RNA species in cells and play a critical role in major biological
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Neutral Sphingomyelinase 2 Inhibition Limits Hepatic Steatosis and Inflammation Cells (IF 6.0) Pub Date : 2024-03-06 Fatema Al-Rashed, Hossein Arefanian, Ashraf Al Madhoun, Fatemah Bahman, Sardar Sindhu, Halemah AlSaeed, Texy Jacob, Reeby Thomas, Areej Al-Roub, Fawaz Alzaid, MD Zubbair Malik, Rasheeba Nizam, Thangavel Alphonse Thanaraj, Fahd Al-Mulla, Yusuf A. Hannun, Rasheed Ahmad
Non-alcoholic fatty liver disease (NAFLD) is manifested by hepatic steatosis, insulin resistance, hepatocyte death, and systemic inflammation. Obesity induces steatosis and chronic inflammation in the liver. However, the precise mechanism underlying hepatic steatosis in the setting of obesity remains unclear. Here, we report studies that address this question. After 14 weeks on a high-fat diet (HFD)
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High-Resolution Microscopic Characterization of Tunneling Nanotubes in Living U87 MG and LN229 Glioblastoma Cells Cells (IF 6.0) Pub Date : 2024-03-06 Nicole Matejka, Asieh Amarlou, Jessica Neubauer, Sarah Rudigkeit, Judith Reindl
Tunneling nanotubes (TNTs) are fine, nanometer-sized membrane connections between distant cells that provide an efficient communication tool for cellular organization. TNTs are thought to play a critical role in cellular behavior, particularly in cancer cells. The treatment of aggressive cancers such as glioblastoma remains challenging due to their high potential for developing therapy resistance,
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Intravenous MSC-Treatment Improves Impaired Brain Functions in the R6/2 Mouse Model of Huntington’s Disease via Recovered Hepatic Pathological Changes Cells (IF 6.0) Pub Date : 2024-03-07 Libo Yu-Taeger, Ali El-Ayoubi, Pengfei Qi, Lusine Danielyan, Hoa Huu Phuc Nguyen
Huntington’s disease (HD), a congenital neurodegenerative disorder, extends its pathological damages beyond the nervous system. The systematic manifestation of HD has been extensively described in numerous studies, including dysfunction in peripheral organs and peripheral inflammation. Gut dysbiosis and the gut–liver–brain axis have garnered greater emphasis in neurodegenerative research, and increased
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Cisplatin and Starvation Differently Sensitize Autophagy in Renal Carcinoma: A Potential Therapeutic Pathway to Target Variegated Drugs Resistant Cancerous Cells Cells (IF 6.0) Pub Date : 2024-03-07 Ankita Dutta, Subarna Thakur, Debasish Kumar Dey, Anoop Kumar
Cisplatin, a powerful chemotherapy medication, has long been a cornerstone in the fight against cancer due to chemotherapeutic failure. The mechanism of cisplatin resistance/failure is a multifaceted and complex issue that consists mainly of apoptosis inhibition through autophagy sensitization. Currently, researchers are exploring ways to regulate autophagy in order to tip the balance in favor of effective
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Nicotinic Acetylcholine Receptors in Glial Cells as Molecular Target for Parkinson’s Disease Cells (IF 6.0) Pub Date : 2024-03-07 Érica Novaes Soares, Ana Carla dos Santos Costa, Gabriel de Jesus Ferrolho, Rodrigo Portes Ureshino, Bruk Getachew, Silvia Lima Costa, Victor Diogenes Amaral da Silva, Yousef Tizabi
Parkinson’s disease (PD) is a progressive neurodegenerative disease characterized by resting tremor, bradykinesia, rigidity, and postural instability that also includes non-motor symptoms such as mood dysregulation. Dopamine (DA) is the primary neurotransmitter involved in this disease, but cholinergic imbalance has also been implicated. Current intervention in PD is focused on replenishing central
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Border Control: The Role of the Microbiome in Regulating Epithelial Barrier Function Cells (IF 6.0) Pub Date : 2024-03-08 Fernanda Schreiber, Iulia Balas, Matthew J. Robinson, Ghaith Bakdash
The gut mucosal epithelium is one of the largest organs in the body and plays a critical role in regulating the crosstalk between the resident microbiome and the host. To this effect, the tight control of what is permitted through this barrier is of high importance. There should be restricted passage of harmful microorganisms and antigens while at the same time allowing the absorption of nutrients