Physiological reviewsPub Date : 2024-07-01Epub Date: 2024-03-22DOI: 10.1152/physrev.00041.2023
Leigh Peterson, Magdi H Yacoub, David Ayares, Kazuhiko Yamada, Daniel Eisenson, Bartley P Griffith, Muhammad M Mohiuddin, Willard Eyestone, J Craig Venter, Ryszard T Smolenski, Martine Rothblatt
{"title":"Physiological basis for xenotransplantation from genetically modified pigs to humans.","authors":"Leigh Peterson, Magdi H Yacoub, David Ayares, Kazuhiko Yamada, Daniel Eisenson, Bartley P Griffith, Muhammad M Mohiuddin, Willard Eyestone, J Craig Venter, Ryszard T Smolenski, Martine Rothblatt","doi":"10.1152/physrev.00041.2023","DOIUrl":"10.1152/physrev.00041.2023","url":null,"abstract":"<p><p>The collective efforts of scientists over multiple decades have led to advancements in molecular and cellular biology-based technologies including genetic engineering and animal cloning that are now being harnessed to enhance the suitability of pig organs for xenotransplantation into humans. Using organs sourced from pigs with multiple gene deletions and human transgene insertions, investigators have overcome formidable immunological and physiological barriers in pig-to-nonhuman primate (NHP) xenotransplantation and achieved prolonged pig xenograft survival. These studies informed the design of Revivicor's (Revivicor Inc, Blacksburg, VA) genetically engineered pigs with 10 genetic modifications (10 GE) (including the inactivation of 4 endogenous porcine genes and insertion of 6 human transgenes), whose hearts and kidneys have now been studied in preclinical human xenotransplantation models with brain-dead recipients. Additionally, the first two clinical cases of pig-to-human heart xenotransplantation were recently performed with hearts from this 10 GE pig at the University of Maryland. Although this review focuses on xenotransplantation of hearts and kidneys, multiple organs, tissues, and cell types from genetically engineered pigs will provide much-needed therapeutic interventions in the future.</p>","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":" ","pages":"1409-1459"},"PeriodicalIF":29.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11390123/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140185347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Physiological reviewsPub Date : 2024-07-01Epub Date: 2024-03-14DOI: 10.1152/physrev.00042.2023
Raffael Kalisch, Scott J Russo, Marianne B Müller
{"title":"Neurobiology and systems biology of stress resilience.","authors":"Raffael Kalisch, Scott J Russo, Marianne B Müller","doi":"10.1152/physrev.00042.2023","DOIUrl":"10.1152/physrev.00042.2023","url":null,"abstract":"<p><p>Stress resilience is the phenomenon that some people maintain their mental health despite exposure to adversity or show only temporary impairments followed by quick recovery. Resilience research attempts to unravel the factors and mechanisms that make resilience possible and to harness its insights for the development of preventative interventions in individuals at risk for acquiring stress-related dysfunctions. Biological resilience research has been lagging behind the psychological and social sciences but has seen a massive surge in recent years. At the same time, progress in this field has been hampered by methodological challenges related to finding suitable operationalizations and study designs, replicating findings, and modeling resilience in animals. We embed a review of behavioral, neuroimaging, neurobiological, and systems biological findings in adults in a critical methods discussion. We find preliminary evidence that hippocampus-based pattern separation and prefrontal-based cognitive control functions protect against the development of pathological fears in the aftermath of singular, event-type stressors [as found in fear-related disorders, including simpler forms of posttraumatic stress disorder (PTSD)] by facilitating the perception of safety. Reward system-based pursuit and savoring of positive reinforcers appear to protect against the development of more generalized dysfunctions of the anxious-depressive spectrum resulting from more severe or longer-lasting stressors (as in depression, generalized or comorbid anxiety, or severe PTSD). Links between preserved functioning of these neural systems under stress and neuroplasticity, immunoregulation, gut microbiome composition, and integrity of the gut barrier and the blood-brain barrier are beginning to emerge. On this basis, avenues for biological interventions are pointed out.</p>","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":" ","pages":"1205-1263"},"PeriodicalIF":29.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11381009/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140120382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Physiological reviewsPub Date : 2024-07-01Epub Date: 2024-03-07DOI: 10.1152/physrev.00043.2023
Teresa Cunha-Oliveira, John P A Ioannidis, Paulo J Oliveira
{"title":"Best practices for data management and sharing in experimental biomedical research.","authors":"Teresa Cunha-Oliveira, John P A Ioannidis, Paulo J Oliveira","doi":"10.1152/physrev.00043.2023","DOIUrl":"10.1152/physrev.00043.2023","url":null,"abstract":"<p><p>Effective data management is crucial for scientific integrity and reproducibility, a cornerstone of scientific progress. Well-organized and well-documented data enable validation and building on results. Data management encompasses activities including organization, documentation, storage, sharing, and preservation. Robust data management establishes credibility, fostering trust within the scientific community and benefiting researchers' careers. In experimental biomedicine, comprehensive data management is vital due to the typically intricate protocols, extensive metadata, and large datasets. Low-throughput experiments, in particular, require careful management to address variations and errors in protocols and raw data quality. Transparent and accountable research practices rely on accurate documentation of procedures, data collection, and analysis methods. Proper data management ensures long-term preservation and accessibility of valuable datasets. Well-managed data can be revisited, contributing to cumulative knowledge and potential new discoveries. Publicly funded research has an added responsibility for transparency, resource allocation, and avoiding redundancy. Meeting funding agency expectations increasingly requires rigorous methodologies, adherence to standards, comprehensive documentation, and widespread sharing of data, code, and other auxiliary resources. This review provides critical insights into raw and processed data, metadata, high-throughput versus low-throughput datasets, a common language for documentation, experimental and reporting guidelines, efficient data management systems, sharing practices, and relevant repositories. We systematically present available resources and optimal practices for wide use by experimental biomedical researchers.</p>","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":" ","pages":"1387-1408"},"PeriodicalIF":29.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11380994/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140050180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Physiological reviewsPub Date : 2024-07-01Epub Date: 2024-02-01DOI: 10.1152/physrev.00008.2023
Joseph L Wilkerson, Sean M Tatum, William L Holland, Scott A Summers
{"title":"Ceramides are fuel gauges on the drive to cardiometabolic disease.","authors":"Joseph L Wilkerson, Sean M Tatum, William L Holland, Scott A Summers","doi":"10.1152/physrev.00008.2023","DOIUrl":"10.1152/physrev.00008.2023","url":null,"abstract":"<p><p>Ceramides are signals of fatty acid excess that accumulate when a cell's energetic needs have been met and its nutrient storage has reached capacity. As these sphingolipids accrue, they alter the metabolism and survival of cells throughout the body including in the heart, liver, blood vessels, skeletal muscle, brain, and kidney. These ceramide actions elicit the tissue dysfunction that underlies cardiometabolic diseases such as diabetes, coronary artery disease, metabolic-associated steatohepatitis, and heart failure. Here, we review the biosynthesis and degradation pathways that maintain ceramide levels in normal physiology and discuss how the loss of ceramide homeostasis drives cardiometabolic pathologies. We highlight signaling nodes that sense small changes in ceramides and in turn reprogram cellular metabolism and stimulate apoptosis. Finally, we evaluate the emerging therapeutic utility of these unique lipids as biomarkers that forecast disease risk and as targets of ceramide-lowering interventions that ameliorate disease.</p>","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":" ","pages":"1061-1119"},"PeriodicalIF":29.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11381030/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139651524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Physiological reviewsPub Date : 2024-07-01Epub Date: 2024-01-11DOI: 10.1152/physrev.00024.2023
Shao-Nian Yang, Yue Shi, Per-Olof Berggren
{"title":"The anterior chamber of the eye technology and its anatomical, optical, and immunological bases.","authors":"Shao-Nian Yang, Yue Shi, Per-Olof Berggren","doi":"10.1152/physrev.00024.2023","DOIUrl":"10.1152/physrev.00024.2023","url":null,"abstract":"<p><p>The anterior chamber of the eye (ACE) is distinct in its anatomy, optics, and immunology. This guarantees that the eye perceives visual information in the context of physiology even when encountering adverse incidents like inflammation. In addition, this endows the ACE with the special nursery bed iris enriched in vasculatures and nerves. The ACE constitutes a confined space enclosing an oxygen/nutrient-rich, immune-privileged, and less stressful milieu as well as an optically transparent medium. Therefore, aside from visual perception, the ACE unexpectedly serves as an excellent transplantation site for different body parts and a unique platform for noninvasive, longitudinal, and intravital microimaging of different grafts. On the basis of these merits, the ACE technology has evolved from the prototypical through the conventional to the advanced version. Studies using this technology as a versatile biomedical research platform have led to a diverse range of basic knowledge and in-depth understanding of a variety of cells, tissues, and organs as well as artificial biomaterials, pharmaceuticals, and abiotic substances. Remarkably, the technology turns in vivo dynamic imaging of the morphological characteristics, organotypic features, developmental fates, and specific functions of intracameral grafts into reality under physiological and pathological conditions. Here we review the anatomical, optical, and immunological bases as well as technical details of the ACE technology. Moreover, we discuss major achievements obtained and potential prospective avenues for this technology.</p>","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":" ","pages":"881-929"},"PeriodicalIF":29.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11381035/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139417871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Physiological reviewsPub Date : 2024-07-01Epub Date: 2024-02-08DOI: 10.1152/physrev.00019.2023
Emily Hamburg-Shields, Sam Mesiano
{"title":"The hormonal control of parturition.","authors":"Emily Hamburg-Shields, Sam Mesiano","doi":"10.1152/physrev.00019.2023","DOIUrl":"10.1152/physrev.00019.2023","url":null,"abstract":"<p><p>Parturition is a complex physiological process that must occur in a reliable manner and at an appropriate gestation stage to ensure a healthy newborn and mother. To this end, hormones that affect the function of the gravid uterus, especially progesterone (P4), 17β-estradiol (E<sub>2</sub>), oxytocin (OT), and prostaglandins (PGs), play pivotal roles. P4 via the nuclear P4 receptor (PR) promotes uterine quiescence and for most of pregnancy exerts a dominant block to labor. Loss of the P4 block to parturition in association with a gain in prolabor actions of E<sub>2</sub> are key transitions in the hormonal cascade leading to parturition. P4 withdrawal can occur through various mechanisms depending on species and physiological context. Parturition in most species involves inflammation within the uterine tissues and especially at the maternal-fetal interface. Local PGs and other inflammatory mediators may initiate parturition by inducing P4 withdrawal. Withdrawal of the P4 block is coordinated with increased E<sub>2</sub> actions to enhance uterotonic signals mediated by OT and PGs to promote uterine contractions, cervix softening, and membrane rupture, i.e., labor. This review examines recent advances in research to understand the hormonal control of parturition, with focus on the roles of P4, E<sub>2</sub>, PGs, OT, inflammatory cytokines, and placental peptide hormones together with evolutionary biology of and implications for clinical management of human parturition.</p>","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":" ","pages":"1121-1145"},"PeriodicalIF":29.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11380996/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139703236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Degenerate Neuronal and Circuit Mechanisms Important for Generating Rhythmic Motor Patterns","authors":"Ronald L Calabrese, Eve Marder","doi":"10.1152/physrev.00003.2024","DOIUrl":"https://doi.org/10.1152/physrev.00003.2024","url":null,"abstract":"Physiological Reviews, Ahead of Print. <br/>","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":"33 1","pages":""},"PeriodicalIF":33.6,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141315569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kiran Kumar Adepu, Andriy Anishkin, Sean H. Adams, Sree V Chintapalli
{"title":"A versatile delivery vehicle for cellular oxygen and fuels, or metabolic sensor? - A review and perspective on the functions of myoglobin","authors":"Kiran Kumar Adepu, Andriy Anishkin, Sean H. Adams, Sree V Chintapalli","doi":"10.1152/physrev.00031.2023","DOIUrl":"https://doi.org/10.1152/physrev.00031.2023","url":null,"abstract":"Physiological Reviews, Ahead of Print. <br/>","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":"35 1","pages":""},"PeriodicalIF":33.6,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140821082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Neuronal glucose sensing mechanisms and circuits in the control of insulin and glucagon secretion","authors":"Bernard Thorens","doi":"10.1152/physrev.00038.2023","DOIUrl":"https://doi.org/10.1152/physrev.00038.2023","url":null,"abstract":"Glucose homeostasis is mainly under the control of the pancreatic islet hormones insulin and glucagon, which, respectively, stimulate glucose uptake and utilization by liver, fat, and muscle or glucose production by the liver. The balance between the secretion of these hormones is under the control of blood glucose concentrations. Indeed, pancreatic islet b-cells and a-cells can sense variations in glycemia and respond by an appropriate secretory response to restore euglycemia. However, the secretory activity of these cells is also under multiple additional metabolic, hormonal, and neuronal signals that combine to ensure the perfect control of glycemia over a lifetime. The central nervous system (CNS), which has an almost absolute requirement for glucose as a source of metabolic energy and, thus, a vital interest in ensuring that glycemic levels never fall below ~5mM, is equipped with populations of neurons responsive to changes in glucose concentrations. These neurons control pancreatic islet cells secretion activity in multiple ways: through both branches of the autonomic nervous system, through the hypothalamic-pituitary-adrenal axis, and by secreting vasopressin (AVP) in the blood at the level of the posterior pituitary. Here, we will present the autonomic innervation of the pancreatic islets; the mechanisms of neurons activation by a rise or a fall in glucose concentration; how current viral tracing, chemogenetic, and optogenetic techniques allow to integrate specific glucose sensing neurons in defined neuronal circuits that control endocrine pancreas function. Finally, how genetic screens in mice can untangle the diversity of the hypothalamic mechanisms controlling the response to hypoglycemia.","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":"23 1","pages":""},"PeriodicalIF":33.6,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140648916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Physiological reviewsPub Date : 2024-04-01Epub Date: 2023-10-19DOI: 10.1152/physrev.00032.2023
Alain R Thierry
{"title":"NETosis creates a link between diabetes and Long COVID.","authors":"Alain R Thierry","doi":"10.1152/physrev.00032.2023","DOIUrl":"10.1152/physrev.00032.2023","url":null,"abstract":"","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":" ","pages":"651-654"},"PeriodicalIF":33.6,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49681334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}