Article
Multidisciplinary Sciences
Dmitry Chernyakov, Annika Fischer, Max Brandau, Federica Petrillo, Robert A. Fenton, Bayram Edemir
Summary: The osmotic gradient between renal cortex and medulla induces specific gene expression patterns, but the factors controlling these differences are not fully understood. This study demonstrates that NFAT5 plays a key role in adapting to a hypertonic environment. Loss of NFAT5 alters the expression of thousands of genes in the kidney, leading to renal inflammation and increased expression of kidney injury marker genes.
SCIENTIFIC REPORTS
(2022)
Article
Reproductive Biology
Ashitha Suresh, M. K. Shukla, Dharmendra Kumar, O. P. Shrivastava, Neeraj Verma
Summary: The study shows that the simulated physiological oocyte maturation system significantly enhances the developmental competence of goat oocytes and reduces the intensity of reactive oxygen species and embryonic apoptosis.
Article
Gastroenterology & Hepatology
Won-Mook Choi, Tom Ryu, Jun-Hee Lee, Young-Ri Shim, Myung-Ho Kim, Hee-Hoon Kim, Ye Eun Kim, Keungmo Yang, Kyurae Kim, Sung Eun Choi, Won Kim, Seok-Hwan Kim, Hyuk Soo Eun, Won-Il Jeong
Summary: mGluR5 activation in NK cells attenuates liver fibrosis by enhancing cytotoxicity, and insufficient mGluR5 expression in NK cells may lead to evasion of fibroblasts against NK cell cytotoxicity.
Article
Multidisciplinary Sciences
Brittany Epp-Ducharme, Michael Dunne, Linyu Fan, James C. Evans, Lubabah Ahmed, Pauric Bannigan, Christine Allen
Summary: The heat shock protein 90 inhibitor luminespib has shown promising preclinical activity against various cancers, with potential for even greater efficacy through reformulation using advanced drug delivery strategies. Specifically, the use of thermosensitive liposomes for drug delivery in combination with other chemotherapeutic agents has shown synergistic activity in lung cancer, offering hope for the resuscitation of this promising anticancer agent in clinical settings.
SCIENTIFIC REPORTS
(2021)
Article
Immunology
Sandra Hellberg, Johanna Raffetseder, Olof Rundquist, Rasmus Magnusson, Georgia Papapavlou, Maria C. Jenmalm, Jan Ernerudh, Mika Gustafsson
Summary: The changes in progesterone levels during and after pregnancy influence the course of autoimmune diseases such as multiple sclerosis and rheumatoid arthritis, possibly through immune-endocrine interactions. Study findings indicate that P4 significantly suppresses CD4(+) T cell activation, impacting gene and protein expression profiles and showing potential for regulating immune responses. These results suggest a role for P4 in immune modulation during pregnancy and highlight the importance of further research on its potential as a treatment option for pregnancy-induced diseases.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Cell Biology
Mirae Kim, Seon-Ung Hwang, Junchul David Yoon, Joohyeong Lee, Eunhye Kim, Lian Cai, Hyerin Choi, Dongjin Oh, Gabsang Lee, Sang-Hwan Hyun
Summary: This study explores the physiological role of neurotrophin-4 (NT-4) in porcine ovarian development and finds that NT-4 can promote the maturation of porcine oocytes by upregulating NFKB1 transcription via the neurotrophin/p75(NTR) signaling pathway. Additionally, NT-4 increases the phosphorylation levels of the mitogen-activated protein kinases ERK1/2 and improves embryonic development after in vitro fertilization and somatic cell nuclear transfer.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Medicine, Research & Experimental
Shangyi Wang, Mina Kozai, Hironobu Mita, Zimeng Cai, Md Abdul Masum, Osamu Ichii, Kensuke Takada, Mutsumi Inaba
Summary: Psoriasis is a chronic inflammatory skin disease characterized by epidermal hyperplasia and cellular infiltration. Recent research has highlighted the crucial role of gamma delta T17 cells in psoriasis pathogenesis, revealing their involvement in regulation through REV-ERBs. Synthetic REV-ERB agonists can suppress gamma delta T17 cells both in vitro and in vivo, providing a novel therapeutic approach for psoriasis targeting REV-ERBs in gamma delta T17 cells.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Fisheries
Yu Zhang, Kang Li, Cheng Li, Wei Liang, Kunming Li, Jiaqi Li, Xiumei Wei, Jialong Yang
Summary: The study revealed that the KLRG1-like molecule On-KLRG1-L in Nile tilapia plays a crucial role in lymphocyte activation and antibacterial adaptive immune response, serving as an activation marker of T lymphocytes.
FISH & SHELLFISH IMMUNOLOGY
(2021)
Article
Agriculture, Dairy & Animal Science
Muhammad Rosyid Ridlo, Eui Hyun Kim, Anukul Taweechaipaisankul, Byeong Chun Lee, Geon A. Kim
Summary: Successful attenuation of ER stress signaling benefits in vitro embryonal development, with adiponectin treatment enhancing the developmental capacity of porcine embryos by reducing ER stress and apoptosis, improving cleavage rates, blastocyst formation rates, and total cell numbers.
Article
Toxicology
Yaqian Qu, Lei Bao, Youliang Zhao, Yiping Li, Mingcui Ding, Changfu Hao, Wu Yao
Summary: Cimetidine enhances the maturity and T cell priming capacity of dendritic cells (DCs). It also interferes with DC-mediated T cell polarization, leading to enhanced pro-inflammatory T cell response and weakened immunosuppressive T cell response.
TOXICOLOGY IN VITRO
(2022)
Article
Biochemistry & Molecular Biology
Meredith J. Giblin, Taylor E. Smith, Garrett Winkler, Hannah A. Pendergrass, Minjae J. Kim, Megan E. Capozzi, Rong Yang, Gary W. McCollum, John S. Penn
Summary: Research indicates that the NFAT inhibitor INCA-6 can reduce the expression of IL-1 beta-induced inflammation in retinal cells and endothelial cells, thereby alleviating retinal inflammation secondary to diabetes.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2021)
Article
Biochemistry & Molecular Biology
Barbara Cisterna, Manuela Costanzo, Maria Assunta Lacavalla, Mirco Galie, Osvaldo Angelini, Gabriele Tabaracci, Manuela Malatesta
Summary: Oxygen-ozone therapy at low concentrations can induce different effects on fibroblasts depending on their activation state, stimulating proliferation and cytokine secretion in non-activated fibroblasts, while enhancing antioxidant response in already activated fibroblasts. This study provides insights into the potential activation-like responses induced by low O-3 concentrations in fibroblasts.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Immunology
Farid Ghorbaninezhad, Javad Masoumi, Mohammad Bakhshivand, Amir Baghbanzadeh, Ahad Mokhtarzadeh, Tohid Kazemi, Leili Aghebati-Maleki, Siamak Sandoghchian Shotorbani, Mahdi Jafarlou, Oronzo Brunetti, Mariacarmela Santarpia, Behzad Baradaran, Nicola Silvestris
Summary: DC-based immunotherapy has gained interest in anti-cancer immunotherapies. However, the immunosuppressive mechanisms in the tumor environment, such as inhibitory immune checkpoint molecules, can reduce the efficacy of DC-mediated anti-tumoral immune responses. In this study, we found that blocking CTLA-4 expression on DCs promoted their stimulatory properties and resulted in increased T cell proliferation and cytokine production.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Pharmacology & Pharmacy
Greylin Nielsen, Wendy J. Heiger-Bernays, Jennifer J. Schlezinger, Thomas F. Webster
Summary: The study highlights the potential impact of PFAS on human health, particularly the lack of data on the effects of PFAS mixtures on relevant molecular initiating events in the body. Experimental findings suggest that the GCA method is the most accurate in predicting the effects of PFAS mixtures on hPPARa activity, aiding in a more precise assessment of the potential risks posed by PFAS mixtures.
Article
Immunology
Yiqun Geng, Zhihao Lu, Jitian Guan, Nico van Rooijen, Ye Zhi
Summary: Inflammation after acute CNS injury involves a complex interaction between microglia/macrophages and CD4(+)CD25(+) T cells, with the former promoting neuroprotection by secreting cytokines to suppress T cell-mediated cytotoxicity on injured neurons.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Yusuke Kubo, Rainer Beckmann, Athanassios Fragoulis, Claudius Conrads, Prathyusha Pavanram, Sven Nebelung, Michael Wolf, Christoph Jan Wruck, Holger Jahr, Thomas Pufe
Summary: Oxidative stress is associated with osteoarthritis, and the Nrf2/ARE signaling pathway controls SOX9 expression. Nrf2 directly regulates SOX9 in articular cartilage, and the loss of Nrf2 may lead to mild osteoarthritis in old age.
Article
Biochemistry & Molecular Biology
Zeenath Unnisa, John K. Yoon, Jeffrey W. Schindler, Chris Mason, Niek P. van Til
Summary: Pompe disease is a genetic neuromuscular disorder caused by a deficiency of the enzyme acid alpha-glucosidase (GAA). While enzyme replacement therapy has limitations, gene therapies using adeno-associated virus (AAV) and lentiviral vector (LV) show potential in treating this disorder. Improved preclinical efficacy and safety data have been achieved by optimizing viral vector designs for tissue-specific expression and GAA protein modifications.
Article
Biochemistry & Molecular Biology
Holger Jahr, Anna E. van der Windt, Ufuk Tan Timur, Esther B. Baart, Wei-Shiung Lian, Bernd Rolauffs, Feng-Sheng Wang, Thomas Pufe
Summary: Increasing osmolarity to physiological levels promotes chondrogenic differentiation and marker expression in chondroprogenitor cells. The calcineurin inhibitor FK506 enhances this effect by modulating TGF-beta signaling at the type I receptor. Our findings provide insights into the mechanisms underlying cartilage repair strategies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Orthopedics
Ruurd J. A. Kuiper, Ralph J. B. Sakkers, Marijn van Stralen, Vahid Arbabi, Max A. Viergever, Harrie Weinans, Peter R. Seevinck
Summary: Semantic segmentation of bone from lower extremity CT scans has been shown to be beneficial for visualization, diagnosis, and surgical planning in orthopaedics. In this study, the researchers developed a cascaded deep learning approach with a multi-stage V-net, which achieved accurate and fast segmentation of lower extremity bones. The method outperformed the state-of-the-art nnU-net in terms of training time, inference time, and GPU memory requirements. Morphometric measurements performed on the automatic segmentations showed good correlation with the manual segmentations. Overall, this approach showed promise for clinical applications.
JOURNAL OF ORTHOPAEDIC RESEARCH
(2022)
Article
Biotechnology & Applied Microbiology
Robert N. Plasschaert, Mark P. DeAndrade, Fritz Hull, Quoc Nguyen, Tara Peterson, Aimin Yan, Mariana Loperfido, Cristina Baricordi, Luigi Barbarossa, John K. Yoon, Yildirim Dogan, Zeenath Unnisa, Jeffrey W. Schindler, Niek P. Van Til, Luca Biasco, Chris Mason
Summary: This study comprehensively investigated the engraftment dynamics and characteristics of genetically modified microglia-like cells (MLCs), and found that MLCs can effectively deliver therapeutic proteins to the brain, holding potential for the treatment of major neurological diseases.
Article
Medicine, Research & Experimental
Qiushi Liang, Eva C. Vlaar, Fabio Catalano, Joon M. Pijnenburg, Merel Stok, Yvette van Helsdingen, Arnold G. Vulto, Wendy W. J. Unger, Ans T. van der Ploeg, W. W. M. Pim Pijnappel, Niek P. van Til
Summary: This study found that lentiviral gene therapy induced robust and long-term immune tolerance to GAA in a murine model of Pompe disease, whether expressed by a transgene or supplied as ERT. These findings are important for the development of effective treatments for Pompe disease.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2022)
Review
Biochemistry & Molecular Biology
Wei-Shiung Lian, Feng-Sheng Wang, Yu-Shan Chen, Ming-Hsien Tsai, How-Ran Chao, Holger Jahr, Re-Wen Wu, Jih-Yang Ko
Summary: Osteoporosis and osteoarthritis are the leading causes of musculoskeletal dysfunction in older adults. Gut microbiota and metabolites play an important role in maintaining the homeostasis of cartilage and bone tissue. Modulating gut microbiota and supplementing microbiota-derived metabolites may help slow down the development of these skeletal disorders.
Article
Cell Biology
Maximilian Koblenzer, Marek Weiler, Athanassios Fragoulis, Stephan Ruetten, Thomas Pufe, Holger Jahr
Summary: This study aimed to develop a bone mineralization model for more physiological high-throughput screenings. MC3T3-E1 pre-osteoblasts were cultured to form 3D spheroids, and the mineralization process was evaluated through gene expression, enzyme activity, and calcium deposition analyses. The established biomimetic model provides a versatile and cost-efficient tool for improved pharmacological ex vivo screenings.
Article
Surgery
B. A. T. D. van der Gronde, T. P. C. Schlosser, J. H. J. van Erp, T. E. Snijders, R. M. Castelein, H. Weinans, A. de Gast
Summary: This systematic review examined the relationship between sagittal spinopelvic characteristics and implant dislocations after primary THA. The study found that several sagittal spinopelvic patient characteristics were related to THA dislocations, and the associated risks were greater than for other patient and surgery-related factors. Further research is needed to determine which characteristics and parameters should be considered in patients undergoing primary THA.
Review
Biochemistry & Molecular Biology
Athanassios Fragoulis, Mersedeh Tohidnezhad, Yusuke Kubo, Christoph Jan Wruck, Rogerio Bastos Craveiro, Anna Bock, Michael Wolf, Thomas Pufe, Holger Jahr, Frank Suhr
Summary: Mechanosensing is crucial for maintaining tissue functions. Mechanical loading is necessary for the physiological functions of various tissues, while mechanical unloading can lead to pathological remodeling and dysfunctions. At the cellular level, both loading and unloading regulate cellular pathways, especially those involving oxidants like reactive oxygen species (ROS), which are essential for tissue organization and function.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Clinical Neurology
Marianna Bugiani, Truus E. M. Abbink, Arthur W. D. Edridge, Lia van der Hoek, Anne E. J. Hillen, Niek P. van Til, Gino V. Hu-A-Ng, Marjolein Breur, Karen Aiach, Philippe Drevot, Michael Hocquemiller, Ralph Laufer, Frits A. Wijburg, Marjo S. van der Knaap
Summary: The AAVance gene therapy trial investigated the intracerebral injection of AAVrh.10 overexpressing human sulfamidase in children with MPSIIIA. Post-treatment MRI monitoring revealed lesions around injection sites. Investigations showed dysfunction of transduced cells close to the injection sites, leading to altered extracellular matrix composition and cystic white matter degeneration. The potential benefit-risk ratio of this therapy will be revealed by the trial results.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2023)
Article
Engineering, Biomedical
Y. Li, P. Pavanram, J. Buehring, S. Ruetten, K-U. Schroeder, J. Zhou, T. Pufe, L. N. Wang, A. A. Zadpoor, H. Jahr
Summary: This study investigates the performance of AM porous iron by comparing its biodegradation behavior and cytocompatibility under static and dynamic conditions. The research finds that the biodegradation rate of AM porous iron significantly increases under in situ-like conditions, and its compatibility with various cell types is enhanced.
ACTA BIOMATERIALIA
(2023)
Article
Orthopedics
M. C. Koper, R. W. A. Spek, M. Reijman, E. M. van Es, S. J. Baart, J. A. N. Verhaar, P. K. Bos
Summary: The study aims to determine the correlation between increasing serum cobalt and chromium levels and decreasing Harris Hip Score (HHS) and Hip disability and Osteoarthritis Outcome Score (HOOS) in patients who received the Articular Surface Replacement (ASR) hip resurfacing arthroplasty (HRA), as well as evaluate the ten-year revision rate and the influence of sex, inclination angle, and Co level.
BONE & JOINT JOURNAL
(2023)
Review
Pharmacology & Pharmacy
Fatima Aerts-Kaya, Niek P. van Til
Summary: Leukodystrophies are a group of genetic degenerative brain disorders that can be lethal if not treated. Gene therapy offers promising results for the treatment of leukodystrophies, and this article discusses the potential interventions of gene therapy in certain types of leukodystrophies, such as X-linked adrenoleukodystrophy and metachromatic leukodystrophy. The advantages and disadvantages of different gene therapy approaches are also discussed, along with the ongoing developments in the field of molecular technologies for treating leukodystrophies in the future.
Article
Medicine, Research & Experimental
Qiushi Liang, Fabio Catalano, Eva C. Vlaar, Joon M. Pijnenburg, Merel Stok, Yvette van Helsdingen, Arnold G. Vulto, Ans T. van der Ploeg, Niek P. van Til, W. W. M. Pim Pijnappel
Summary: Pompe disease is caused by the deficiency of acid a-glucosidase (GAA) and results in glycogen accumulation in various tissues. Enzyme replacement therapy can improve cardiac, motor, and respiratory functions, but its effectiveness is limited by poor cellular uptake and inability to cross the blood-brain barrier. Lentiviral gene therapy with codon-optimized GAA has shown glycogen reduction in previous studies, and fusing insulin-like growth factor 2 (IGF2) to codon-optimized GAA further enhances cellular uptake. This approach has been particularly effective in treating the CNS.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2022)