Review
Immunology
Jiale Li, Qinbao Peng, Ronghua Yang, Kunsheng Li, Peng Zhu, Yufeng Zhu, Pengyu Zhou, Gabor Szabo, Shaoyi Zheng
Summary: This review discusses the use of machine perfusion and mesenchymal stem cells to improve the quality and outcomes of marginal organs in transplantation. By continuously perfusing the organs to mimic physiological conditions, evaluating pre-transplant organ function, and treating the organs with pharmacological, gene, and stem cell therapy, the quality and adaptability of the organs can be enhanced. Promising preclinical results indicate the potential clinical translation of this innovative strategy to improve the quality of marginal grafts.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Surgery
Dinesh Jaishankar, Kristen M. Quinn, Jes Sanders, Leah Plumblee, Thomas A. Morinelli, Satish N. Nadig
Summary: This article discusses the regulatory influence of connexin proteins in maintaining endothelial cell barrier integrity and their role in ischemia-reperfusion injury in organ transplantation. Certain isoforms of connexin proteins play a crucial role in preserving organ function, but more research is needed to understand their roles in transplant immunology and their application in targeted therapeutics.
AMERICAN JOURNAL OF TRANSPLANTATION
(2022)
Review
Pharmacology & Pharmacy
Min Cao, Guoqing Wang, Hongli He, Ruiming Yue, Yong Zhao, Lingai Pan, Weiwei Huang, Yang Guo, Tao Yin, Lina Ma, Dingding Zhang, Xiaobo Huang
Summary: The transplant community is still striving to improve graft quality and recipient prognosis, with a focus on enhancing oxygenation during organ preservation. The addition of HBOCs to traditional preservation protocols has shown promise in providing more oxygen to organs, reducing ischemia-reperfusion injury, and increasing the pool of transplantable donors.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Cardiac & Cardiovascular Systems
Etienne Abdelnour-Berchtold, Aadil Ali, Cristina Baciu, Erika L. Beroncal, Aizhou Wang, Olivia Hough, Mitsuaki Kawashima, Manyin Chen, Yu Zhang, Mingyao Liu, Tom Waddell, Ana C. Andreazza, Shaf Keshavjee, Marcelo Cypel
Summary: Injured donor lungs stored at 10℃ demonstrated superior oxygenation and protective effects compared to the current clinical standard of 4℃ storage.
JOURNAL OF HEART AND LUNG TRANSPLANTATION
(2022)
Review
Biochemistry & Molecular Biology
Maria Irene Bellini, Francesco Tortorici, Maria Ida Amabile, Vito D'Andrea
Summary: Kidney transplantation is the preferred treatment for end-stage renal disease, with static cold storage being the standard preservation method. However, dynamic techniques like machine perfusion have shown potential to improve graft function and quality assessment, particularly in kidneys from extended criteria donors.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Immunology
Jiao Lu, Xiaoying Wang, Zhihao Feng, Yucheng Chen, Diguang Wen, Zuojin Liu
Summary: Isoflurane pretreatment significantly alleviates liver IRI in mice and LPS-induced inflammation in liver macrophages. Furthermore, isoflurane pretreatment inhibits caspase-11 expression and production of noncanonical pyroptosis-related cytokines. Interestingly, isoflurane preconditioning reduces intracellular Ca2+ levels, NF-kappa B translocation, and NLRP3 inflammasome activation in LPS-induced macrophages.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2021)
Review
Cell Biology
Marc Mico-Carnero, Mohamed Amine Zaouali, Carlos Rojano-Alfonso, Cristina Maroto-Serrat, Hassen Ben Abdennebi, Carmen Peralta
Summary: Ischemia and reperfusion injury (IRI), an inevitable step in organ transplantation, can cause serious organ damage. Most organs used for transplantation today come from extended criteria donors (ECDs), which are more sensitive to IRI. The main objective of organ preservation solutions is to protect against IRI through specific components.
Review
Biochemistry & Molecular Biology
George Clarke, Hynek Mergental, Angus Hann, M. Thamara P. R. Perera, Simon C. Afford, Darius F. Mirza
Summary: The increasing use of extended criteria donors (ECDs) is a result of the growing disparity between the number of patients listed for transplantation and the availability of suitable organs. ECDs are at higher risk of developing ischaemia reperfusion injury, but the utilization of machine perfusion has proven to be a significant advancement in organ preservation and transplantation success. This review focuses on exploring how machine perfusion can improve the graft's response to ischaemia reperfusion injury.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Surgery
Kai Nishime, Chika Miyagi-Shiohira, Kazuho Kuwae, Yoshihito Tamaki, Tasuku Yonaha, Mayuko Sakai-Yonaha, Issei Saitoh, Masami Watanabe, Hirofumi Noguchi
Summary: Hydrogen sulfide can protect organ grafts against ischemia-reperfusion injury, leading to improved success rates of islet transplantation. Preservation of pancreas in UW solution supplemented with AP39 can protect pancreatic islets against IRI and enhance islet transplantation outcomes.
AMERICAN JOURNAL OF TRANSPLANTATION
(2021)
Article
Biochemistry & Molecular Biology
Csaba Revesz, Anita A. Wasik, Maria Godo, Pal Tod, Sanna Lehtonen, Gabor Szenasi, Peter Hamar
Summary: The study reveals that perfusion with ice-cold saline can cause more severe injury than ischemia-reperfusion at body temperature. Saline independently causes serious injury, while preservation solutions are more beneficial especially at 4 degrees Celsius. Therefore, using preservation solutions in kidney transplantation can help improve ischemic recovery.
Article
Surgery
Isabel M. A. Brueggenwirth, Matteo Mueller, Veerle A. Lantinga, Stefania Camagni, Riccardo De Carlis, Luciano De Carlis, Michele Colledan, Daniele Dondossola, Moritz Drefs, Janina Eden, Davide Ghinolfi, Dionysios Koliogiannis, Georg Lurje, Tommaso M. Manzia, Diethard Monbaliu, Paolo Muiesan, Damiano Patrono, Johann Pratschke, Renato Romagnoli, Michel Rayar, Federico Roma, Andrea Schlegel, Philipp Dutkowski, Robert J. Porte, Vincent E. de Meijer
Summary: Prolonged hypothermic oxygenated machine perfusion (HOPE) preservation of donor livers is safe and can lead to good outcomes in liver transplantation, with low incidence of complications and high survival rates. It can also reduce ischemia-reperfusion injury-related complications.
AMERICAN JOURNAL OF TRANSPLANTATION
(2022)
Article
Biochemistry & Molecular Biology
Hanno Maassen, Leonie H. Venema, Marc G. Weiss, Tobias M. Huijink, H. Sijbrand Hofker, Anna K. Keller, Tom E. Mollnes, Marco Eijken, Soren E. Pischke, Bente Jespersen, Harry van Goor, Henri G. D. Leuvenink
Summary: Kidney extraction time has a detrimental effect on post-transplantation outcome. This study aimed to improve the flush-out and decrease ischemic injury by adding hydrogen sulphide (H2S) to the flush medium. The addition of H2S during flush out and static cold storage resulted in a reduction in pro-inflammatory cytokines without affecting renal function or injury markers.
Review
Medicine, General & Internal
Sara Akalay, Sarah A. Hosgood
Summary: Although machine perfusion is gradually being applied in clinical practice, the improvement of organ reconditioning therapies is still at the experimental stage, showing a translational gap. This review discusses the biological processes and current strategies and interventions for preventing ischemia-reperfusion injury, treating its deleterious consequences, or supporting the reparative response of the kidney, and explores prospects to improve the clinical translation of these therapies by addressing multiple aspects of ischemia-reperfusion injury to achieve robust and long-lasting protective effects on the kidney graft.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Surgery
Ola Ahmed, Min Xu, Fangyu Zhou, Alexander N. Wein, Gundumi A. Upadhya, Li Ye, Brian W. Wong, Yiing Lin, Cliona O'Farrelly, William C. Chapman
Summary: Antioxidant defense mechanisms, particularly the NRF2 axis, play a crucial role in oxidative stress responses and ischemic injury. High NRF2 expression in donor livers is associated with improved liver function, suggesting that targeting this axis may be a rational supplemental treatment strategy for rescuing marginal donor livers.
AMERICAN JOURNAL OF TRANSPLANTATION
(2022)
Article
Biochemistry & Molecular Biology
Joris Blondeel, Nicholas Gilbo, Veerle Heedfeld, Tine Wylin, Louis Libbrecht, Ina Jochmans, Jacques Pirenne, Hannelie Korf, Diethard Monbaliu
Summary: During normothermic machine perfusion (NMP), livers procured after warm ischemia (WI) exhibit a distinct innate immune response compared to directly procured (DP) livers. The cytokine profile in WI livers shifts towards an anti-inflammatory phenotype during NMP and whole blood (WB) reperfusion, while pro-apoptotic signaling is stronger during NMP. WB reperfusion results in a blunted cytokine release in livers, suggesting a reconditioning effect of NMP, regardless of ischemic damage.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Endocrinology & Metabolism
Ming Yang, Frank Reimann, Fiona M. Gribble
Summary: The review discusses the role of enteroendocrine cells in intestinal function, food intake, and glucose homeostasis, as well as the importance of understanding their chemosensory mechanisms for therapeutic development. Recent research has shown similarities in the function and mechanisms of EECs between human cells and mouse models, providing new strategies for treating metabolic and gastrointestinal diseases.
CURRENT OPINION IN ENDOCRINOLOGY DIABETES AND OBESITY
(2021)
Article
Endocrinology & Metabolism
Emma Roth, Simon Benoit, Baptiste Quentin, Brian Lam, Sarah Will, Marcella Ma, Nick Heeley, Tamana Darwish, Yashaswi Shrestha, Fiona Gribble, Frank Reimann, Irina Pshenichnaya, Giles Yeo, David J. Baker, James L. Trevaskis, Clemence Blouet
Summary: Combinatorial therapy of GLP-1R and CCK1R agonists in the brain was found to enhance rapid and sustained appetite suppression and weight loss by engaging specific neuronal populations, such as NTS/AP Calcrlthorn neurons, in discrete brain nuclei including the NTS.
MOLECULAR METABOLISM
(2021)
Review
Neurosciences
Orla R. M. Woodward, Fiona M. Gribble, Frank Reimann, Jo E. Lewis
Summary: Obesity has tripled worldwide since 1975, posing serious implications for public health due to its association with metabolic syndrome, type 2 diabetes, cardiovascular disease, and cancer. Gastrointestinal peptides play a key role in regulating food intake through homeostatic control centers and hedonic mechanisms, offering potential therapeutic strategies for the treatment of obesity and its comorbidities.
JOURNAL OF PHYSIOLOGY-LONDON
(2022)
Review
Biology
Sandra Petrus-Reurer, Marco Romano, Sarah Howlett, Joanne Louise Jones, Giovanna Lombardi, Kourosh Saeb-Parsy
Summary: The article discusses the roles of both innate and adaptive immune responses in allogeneic graft rejection, as well as how these responses are determined by the cellular therapy being studied. It also describes the range of in vitro and in vivo approaches used to examine the immunogenicity of cellular therapies and considers potential confounders and strategies that can be employed to ameliorate immune rejection.
COMMUNICATIONS BIOLOGY
(2021)
Article
Endocrinology & Metabolism
Jonathan E. Campbell, Jacqueline L. Beaudry, Berit Svendsen, Laurie L. Baggio, Andrew N. Gordon, John R. Ussher, Chi Kin Wong, Fiona M. Gribble, David A. D'Alessio, Frank Reimann, Daniel J. Drucker
Summary: This study reveals that GIP receptors are predominantly expressed in pericytes and mesothelial cells, rather than adipocytes, in white adipose tissue. This finding has mechanistic implications for understanding the role of GIP and GIP-based co-agonists in controlling adipose tissue biology.
Article
Emergency Medicine
Neeral R. Patel, Aia S. Mehdi, Amandeep Sandhu, Dermot Mallon, Elizabeth Dick, Nicola Batrick, Elika Kashef
Summary: Hepatic pseudoaneurysm is a rare but potentially life-threatening complication of blunt or penetrating liver trauma. This study found that using an early trauma imaging pathway can effectively detect hepatic pseudoaneurysms.
Article
Biology
Anna Veprik, Geoffrey Denwood, Dong Liu, Rula Bany Bakar, Valentin Morfin, Kara McHugh, Nchimunya N. Tebeka, Laurene Vetterli, Ekaterina Yonova-Doing, Fiona Gribble, Frank Reimann, Kyle L. Hoehn, Piers A. Hemsley, Jonas Ahnfelt-Ronne, Patrik Rorsman, Quan Zhang, Heidi de Wet, James Cantley
Summary: Acetyl-CoA-carboxylase 1 (ACC1) is involved in the regulation of glucagon secretion and the S-acylation of glucose-sensing proteins. Loss of ACC1 in alpha-cells impairs glucagon secretion and function, and also affects pancreatic and gastrointestinal endocrine cells.
COMMUNICATIONS BIOLOGY
(2022)
Article
Radiology, Nuclear Medicine & Medical Imaging
D. H. Mallon, C. D. McNamara, G. S. Rahmani, D. P. O'Regan, D. G. Amiras
Summary: This study developed and tested a model based on a convolutional neural network that accurately identifies the position of enteric tube on chest radiography. The model achieved high accuracy and sensitivity on an external test data set, which can help reduce the risk of feeding through a misplaced enteric tube.
CLINICAL RADIOLOGY
(2022)
Article
Neurosciences
Dermot H. Mallon, Eleanor J. R. Taylor, Orsolya Vittay, Alexander Sheeka, David Doig, Kyriakos Lobotesis
Summary: The study found a high correlation between the CTP outputs from Brainomix and RapidAI, but there were differences in mechanical thrombectomy eligibility. Decisions regarding mechanical thrombectomy should not be based solely on imaging parameters.
JOURNAL OF STROKE & CEREBROVASCULAR DISEASES
(2022)
Article
Multidisciplinary Sciences
Akimichi Inaba, Zewen Kelvin Tuong, Tian X. X. Zhao, Andrew P. P. Stewart, Rebeccah Mathews, Lucy Truman, Rouchelle Sriranjan, Jane Kennet, Kourosh Saeb-Parsy, Linda Wicker, Frank Waldron-Lynch, Joseph Cheriyan, John A. A. Todd, Ziad Mallat, Menna R. R. Clatworthy
Summary: Activation of B cells expressing CD25 can be enhanced by low-dose recombinant IL-2, leading to increased secretion of IL-10. Administration of low dose IL-2 to patients results in an increase in IL-10-producing B cells. Single-cell RNA sequencing reveals enrichment of regulatory B cell gene signature in plasma cell populations from IL-2-treated patients, with significant down-regulation of the transcriptional repressor BACH2. BACH2 suppression leads to increased B cell IL-10, suggesting its role in promoting an immunoregulatory phenotype in B cells through IL-2 modulation.
NATURE COMMUNICATIONS
(2023)
Article
Biology
Marito Hayashi, Judith A. Kaye, Ella R. Douglas, Narendra R. Joshi, Fiona M. Gribble, Frank Reimann, Stephen D. Liberles
Summary: Enteroendocrine cells, which are found in the gut and play a role in the gut-brain axis, produce multiple gut hormones with potentially opposing effects. In this study, the researchers developed a method to selectively study enteroendocrine cells in mice using genetic techniques. They were able to target specific enteroendocrine cell lineages that produce different hormones and found that activating different types of enteroendocrine cells had varying effects on feeding behavior and gut motility. Understanding the physiological roles of different enteroendocrine cell types is important for the study of sensory biology in the intestine.
Article
Biochemical Research Methods
Rachel E. Foreman, Emily L. Miedzybrodzka, Finnur Freyr Eiriksson, Margret Thorsteinsdottir, Christopher Bannon, Robert Wheller, Frank Reimann, Fiona M. Gribble, Richard G. Kay
Summary: The hormone cholecystokinin (CCK) is released by duodenal enteroendocrine cells after a meal and circulates in the low picomolar range. Current methods for detecting CCK suffer from sensitivity issues and cross-reactivity problems. Therefore, a new liquid chromatography and mass spectrometry-based method was developed to measure CCK-derived peptides in cell culture supernatants. This method proved effective in detecting the peptide ppCCK(21-44) in human plasma and secretion buffer solutions.
JOURNAL OF PROTEOME RESEARCH
(2023)
Article
Surgery
F. Georgiades, A. N. S. Silva, K. Purohit, S. King, N. Torpey, K. Saeb-Parsy, G. J. Pettigrew, F. J. Rouhani
Summary: This study compared the removal of a kidney transplant stent using a new type of camera in the operating theatre and in clinic. The results showed that it is safe and cost-effective to perform this procedure in clinic, despite the risk of infection in transplanted patients.
BRITISH JOURNAL OF SURGERY
(2022)
Article
Surgery
M. O. Hamed, A. D. Barlow, N. Dolezalova, S. Khosla, A. Sagar, F. M. Gribble, S. Davies, M. P. Murphy, S. A. Hosgood, M. L. Nicholson, K. Saeb-Parsy
Summary: This study presents a reliable and effective technique for ex vivo perfusion of porcine small intestine segments. The experiments demonstrated well-perfused bowel segments with intact intestinal functions during the perfusion. There were no significant differences between control and leucocyte-depleted animals regarding various parameters at the end of the 4-hour perfusion.
Article
Endocrinology & Metabolism
Daniel I. Brierley, Marie K. Holt, Arashdeep Singh, Alan de Araujo, Molly McDougle, Macarena Vergara, Majd H. Afaghani, Shin Jae Lee, Karen Scott, Calyn Maske, Wolfgang Langhans, Eric Krause, Annette de Kloet, Fiona M. Gribble, Frank Reimann, Linda Rinaman, Guillaume de Lartigue, Stefan Trapp
Summary: GLP-1 suppresses eating through independent gut-brain circuits, with PPG(NTS) neurons not being necessary for the eating suppression effects of GLP-1 receptor agonists. Concurrent activation of PPG(NTS) neurons can more effectively suppress eating than using semaglutide alone.