Pub Date : 2026-01-12DOI: 10.1152/physrev.00017.2025
Tessa A C Garrud,Daniel M Collier,Jonathan H Jaggar
Vascular smooth muscle cells express several types of potassium (K+) channel which control physiological functions including contractility, migration, proliferation, and differentiation. Five primary classes of K+ channel are present in vascular smooth muscle cells: large-conductance Ca2+-activated BK), voltage-dependent K+ (KV), inward rectifier K+ (Kir), adenosine triphosphate (ATP)-sensitive K+ KATP), and two-pore-domain (tandem pore domain) K+ (K2P) channels. Vascular smooth muscle cells express specific sub-members, splice variants, and auxiliary subunits of these five K+ channel classes to customize their properties. Expression patterns of K+ channels in smooth muscle cells can vary depending on vessel type, size, and anatomical origin. The expression, activity, trafficking, and surface abundance of K+ channels can be regulated by a wide variety of stimuli, including membrane voltage, ions, molecules, lipids, and proteins, including those generated by signal transduction pathways. K+ channel function can exhibit sexual dimorphism, change in conditions such as pregnancy aging, and alter in different diseases, including systemic and pulmonary hypertension, diabetes mellitus/metabolic syndrome, and brain disorders. Genetic mutations in genes which encode K+ channels are also associated with pathological alterations in vascular smooth muscle function. Here, provide a comprehensive summary of approximately 40 years of literature investigating the expression, regulation, function, and pathological modification of BK, KV, Kir, KATP, and K2P channels in vascular smooth muscle cells.
{"title":"Potassium channels in vascular smooth muscle cells.","authors":"Tessa A C Garrud,Daniel M Collier,Jonathan H Jaggar","doi":"10.1152/physrev.00017.2025","DOIUrl":"https://doi.org/10.1152/physrev.00017.2025","url":null,"abstract":"Vascular smooth muscle cells express several types of potassium (K+) channel which control physiological functions including contractility, migration, proliferation, and differentiation. Five primary classes of K+ channel are present in vascular smooth muscle cells: large-conductance Ca2+-activated BK), voltage-dependent K+ (KV), inward rectifier K+ (Kir), adenosine triphosphate (ATP)-sensitive K+ KATP), and two-pore-domain (tandem pore domain) K+ (K2P) channels. Vascular smooth muscle cells express specific sub-members, splice variants, and auxiliary subunits of these five K+ channel classes to customize their properties. Expression patterns of K+ channels in smooth muscle cells can vary depending on vessel type, size, and anatomical origin. The expression, activity, trafficking, and surface abundance of K+ channels can be regulated by a wide variety of stimuli, including membrane voltage, ions, molecules, lipids, and proteins, including those generated by signal transduction pathways. K+ channel function can exhibit sexual dimorphism, change in conditions such as pregnancy aging, and alter in different diseases, including systemic and pulmonary hypertension, diabetes mellitus/metabolic syndrome, and brain disorders. Genetic mutations in genes which encode K+ channels are also associated with pathological alterations in vascular smooth muscle function. Here, provide a comprehensive summary of approximately 40 years of literature investigating the expression, regulation, function, and pathological modification of BK, KV, Kir, KATP, and K2P channels in vascular smooth muscle cells.","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":"81 1","pages":""},"PeriodicalIF":33.6,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145956127","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}
Pub Date : 2025-12-29DOI: 10.1152/physrev.00049.2024
Marija Glisic,Adea Llane,Stevan Stojic,Erand Llanaj,Zayne Milena Roa-Díaz,Peter Francis Raguindin,Lum Kastrati,Lara Weed,Mintu P Turakhia,Euan Ashley,Taulant Muka,John P A Ioannidis
We conducted an umbrella review to synthesize the evidence on the effectiveness of interventions incorporating wrist-worn wearables* feedback on diverse health outcomes including health promotion (i.e., health behaviors and disease risk perception) morbidity, mortality, functioning, and other health-related metrics in humans. We searched in MEDLINE, Web of Science, Embase and Cochrane Library until 18th March 2025 for eligible systematic reviews. After screening 9 487 citations, we identified 39 systematic reviews, which included 98 original studies (one observational study, 95 randomized controlled trials, and two pre-post studies). The reviews primarily focused on adult populations, individuals with cardiometabolic conditions, and cancer survivors. The original interventional studies mainly included Fitbit (40.2%), Polar (12.4%), and ActiGraph (10.3%) devices. Over 80% of the clinical trials involved complex behavioral interventions with wearable-based feedback, and the control groups varied. Most systematic reviews were rated as low confidence, with common flaws including inadequate considerations for risk-of-bias and heterogeneity. Interventions incorporating wrist-worn activity trackers increased physical activity in diverse populations. The effect of interventions incorporating wrist-wearables' feedback on cardiometabolic risk markers, quality of life, depression/anxiety and pain was limited and remained inconsistent. Our findings rely on existing systematic reviews, which may vary in quality, review methodologies and comprehensiveness. There is also potential for missing more recent evidence not yet captured in these reviews. These limitations should be considered when interpreting our results. Acknowledging these caveats, wrist-worn wearables seem to increase physical activity, and may have also additional benefits that require further study.
我们进行了一项总括性综述，以综合有关干预措施有效性的证据，这些干预措施包括手腕可穿戴设备*对各种健康结果的反馈，包括人类健康促进（即健康行为和疾病风险感知）发病率、死亡率、功能和其他与健康相关的指标。我们在MEDLINE、Web of Science、Embase和Cochrane Library检索了符合条件的系统综述，检索截止日期为2025年3月18日。在筛选了9487篇引用后，我们确定了39篇系统综述，其中包括98项原始研究（1项观察性研究、95项随机对照试验和2项前后研究）。这些综述主要集中在成人人群、患有心脏代谢疾病的个体和癌症幸存者。最初的介入研究主要包括Fitbit（40.2%）、Polar（12.4%）和ActiGraph（10.3%）设备。超过80%的临床试验涉及复杂的行为干预和基于可穿戴设备的反馈，对照组各不相同。大多数系统评价被评为低置信度，常见的缺陷包括对偏倚风险和异质性考虑不足。结合手腕活动追踪器的干预措施增加了不同人群的身体活动。结合可穿戴腕带反馈的干预措施对心脏代谢风险指标、生活质量、抑郁/焦虑和疼痛的影响是有限的，并且仍然不一致。我们的研究结果依赖于现有的系统评价，这些评价在质量、评价方法和全面性上可能各不相同。在这些综述中还没有捕捉到的近期证据也有可能被遗漏。在解释我们的结果时应考虑到这些局限性。考虑到这些警告，腕戴式可穿戴设备似乎可以增加体力活动，而且可能还有其他好处，需要进一步研究。
{"title":"An umbrella review of systematic reviews of the impact of wrist-worn wearables on health outcomes.","authors":"Marija Glisic,Adea Llane,Stevan Stojic,Erand Llanaj,Zayne Milena Roa-Díaz,Peter Francis Raguindin,Lum Kastrati,Lara Weed,Mintu P Turakhia,Euan Ashley,Taulant Muka,John P A Ioannidis","doi":"10.1152/physrev.00049.2024","DOIUrl":"https://doi.org/10.1152/physrev.00049.2024","url":null,"abstract":"We conducted an umbrella review to synthesize the evidence on the effectiveness of interventions incorporating wrist-worn wearables* feedback on diverse health outcomes including health promotion (i.e., health behaviors and disease risk perception) morbidity, mortality, functioning, and other health-related metrics in humans. We searched in MEDLINE, Web of Science, Embase and Cochrane Library until 18th March 2025 for eligible systematic reviews. After screening 9 487 citations, we identified 39 systematic reviews, which included 98 original studies (one observational study, 95 randomized controlled trials, and two pre-post studies). The reviews primarily focused on adult populations, individuals with cardiometabolic conditions, and cancer survivors. The original interventional studies mainly included Fitbit (40.2%), Polar (12.4%), and ActiGraph (10.3%) devices. Over 80% of the clinical trials involved complex behavioral interventions with wearable-based feedback, and the control groups varied. Most systematic reviews were rated as low confidence, with common flaws including inadequate considerations for risk-of-bias and heterogeneity. Interventions incorporating wrist-worn activity trackers increased physical activity in diverse populations. The effect of interventions incorporating wrist-wearables' feedback on cardiometabolic risk markers, quality of life, depression/anxiety and pain was limited and remained inconsistent. Our findings rely on existing systematic reviews, which may vary in quality, review methodologies and comprehensiveness. There is also potential for missing more recent evidence not yet captured in these reviews. These limitations should be considered when interpreting our results. Acknowledging these caveats, wrist-worn wearables seem to increase physical activity, and may have also additional benefits that require further study.","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":"15 1","pages":""},"PeriodicalIF":33.6,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145847527","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}
Pub Date : 2025-12-23DOI: 10.1152/physrev.00010.2025
Kirsteen N Browning,R Alberto Travagli,Carolina Pellegrini
Thanks to its extensive intrinsic (enteric) neural networks spanning its entire length, the gastrointestinal (GI) tract has long been recognized for its ability to operate independently of the central nervous system (CNS). Despite that, the CNS provides both sympathetic and parasympathetic inputs to the GI tract, that confers an additional layer of regulation, modulation, and integration over GI functions. The sympathetic nervous system provides neurovascular control of GI blood flow in addition to its effects to decrease mucosal secretion, regulate sphincter tone, and modulate motility, principally via prejunctional and presynaptic actions. The parasympathetic nervous system, however, exerts both excitatory and inhibitory effects; the extent to which this influences gut functions varies throughout the length of the GI tract. Recent studies have also demonstrated that, in addition to regulation via the autonomic nervous system, 'higher' CNS nuclei also provide a significant degree of influence over GI functions under both physiological and pathophysiological conditions In addition to describing the anatomical neurocircuits and physiological functions of the extrinsic inputs to the GI tract, this review will also discuss the roles of brainstem, midbrain, and cortical nuclei that influence the gut within the context of relevant physiological and pathophysiological conditions.
{"title":"Central Control of Gastrointestinal Functions in Health and Disease.","authors":"Kirsteen N Browning,R Alberto Travagli,Carolina Pellegrini","doi":"10.1152/physrev.00010.2025","DOIUrl":"https://doi.org/10.1152/physrev.00010.2025","url":null,"abstract":"Thanks to its extensive intrinsic (enteric) neural networks spanning its entire length, the gastrointestinal (GI) tract has long been recognized for its ability to operate independently of the central nervous system (CNS). Despite that, the CNS provides both sympathetic and parasympathetic inputs to the GI tract, that confers an additional layer of regulation, modulation, and integration over GI functions. The sympathetic nervous system provides neurovascular control of GI blood flow in addition to its effects to decrease mucosal secretion, regulate sphincter tone, and modulate motility, principally via prejunctional and presynaptic actions. The parasympathetic nervous system, however, exerts both excitatory and inhibitory effects; the extent to which this influences gut functions varies throughout the length of the GI tract. Recent studies have also demonstrated that, in addition to regulation via the autonomic nervous system, 'higher' CNS nuclei also provide a significant degree of influence over GI functions under both physiological and pathophysiological conditions In addition to describing the anatomical neurocircuits and physiological functions of the extrinsic inputs to the GI tract, this review will also discuss the roles of brainstem, midbrain, and cortical nuclei that influence the gut within the context of relevant physiological and pathophysiological conditions.","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":"3 1","pages":""},"PeriodicalIF":33.6,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145807930","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}
Pub Date : 2025-12-22DOI: 10.1152/physrev.00012.2025
Ada Gjyrezi,Charalampos Skarlis,Clio Mavragani,Paraskevi Giannakakou
Autoimmune diseases arise from an aberrant immune response against self-antigens, whereas cancer often develops when the immune system fails to effectively detect and destroy malignant cells. Although historically viewed as distinct entities with opposing immune mechanisms, recent findings highlight significant overlaps in their immunological pathways. This review explores the intricate interplay between autoimmunity and cancer, focusing on immune surveillance, checkpoint regulation, cytokine signaling, and genetic susceptibility. In addition, we discuss epidemiological links, including the heightened risk of malignancy in patients with autoimmune disorders and the autoimmune manifestations often triggered by cancer immunotherapies. We place particular emphasis on shared molecular signatures, predictive biomarkers, and the bidirectional immune modulation that arises from checkpoint inhibitors and biologic agents. Finally, we address the major clinical challenges in managing patients who present with both conditions and propose future research directions aimed at refining immunotherapeutic strategies.
{"title":"Crossroads between autoimmunity and cancer: Underlying mechanisms and clinical implications.","authors":"Ada Gjyrezi,Charalampos Skarlis,Clio Mavragani,Paraskevi Giannakakou","doi":"10.1152/physrev.00012.2025","DOIUrl":"https://doi.org/10.1152/physrev.00012.2025","url":null,"abstract":"Autoimmune diseases arise from an aberrant immune response against self-antigens, whereas cancer often develops when the immune system fails to effectively detect and destroy malignant cells. Although historically viewed as distinct entities with opposing immune mechanisms, recent findings highlight significant overlaps in their immunological pathways. This review explores the intricate interplay between autoimmunity and cancer, focusing on immune surveillance, checkpoint regulation, cytokine signaling, and genetic susceptibility. In addition, we discuss epidemiological links, including the heightened risk of malignancy in patients with autoimmune disorders and the autoimmune manifestations often triggered by cancer immunotherapies. We place particular emphasis on shared molecular signatures, predictive biomarkers, and the bidirectional immune modulation that arises from checkpoint inhibitors and biologic agents. Finally, we address the major clinical challenges in managing patients who present with both conditions and propose future research directions aimed at refining immunotherapeutic strategies.","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":"21 1","pages":""},"PeriodicalIF":33.6,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145801011","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}
Pub Date : 2025-11-20DOI: 10.1152/physrev.00007.2025
Elena Krugliakova,Friederike Breuer,Nico Adelhöfer,Alejandra Alonso,Luciana Besedovsky,Keith Murphy,Emma Peters,Karolina Raczek,Björn Rasch,Leila Salvesen,Sophia Snipes,Sarah Schoch,Thomas Schreiner,Rick Wassing,Til Ole Bergmann,Martin Dresler
Sleep is essentially contributing to human health and wellbeing through multiple biological functions, including restoration and biosynthesis, brain clearance, energy metabolism, immunological and endocrine processing, synaptic plasticity, memory consolidation, and regulation of cognitive and emotional processes. Sleep disturbances are highly prevalent and are both a symptom and a contributing risk factor for psychiatric, neurological, and somatic disorders. Given the limitations of pharmacological interventions, non-invasive neuromodulation techniques ranging from non-invasive transcranial (TMS, tDCS, tACS, tRNS, tTIS, and TUS) to peripheral sensory (auditory, olfactory, visual, tactile, vestibular) and electrical nerve (galvanic vestibular, transcutaneous vagus nerve, and median nerve) stimulation have gained increasing attention as potential tools to modulate sleep physiology. These techniques offer promising avenues for both therapeutic applications and fundamental research into sleep-dependent neuroplasticity, interregional communication, and oscillatory activity. However, sleep is not a uniform state but a highly complex and dynamic phenomenon, with intricate macrostructural (e.g., NREM-REM sleep balance, sleep efficiency) and microstructural characteristics (e.g., hierarchically nested slow waves and spindles) that contribute to a variety of functions. This complexity necessitates precise targeting strategies, often employing real-time brain-state-de pendent stimulation, to modulate specific sleep-related processes effectively. In this review, we summarise the functions of sleep and the available non-invasive tools for its modulation, addressing key methodological challenges and providing recommendations for best practices in sleep neuromodulation.
{"title":"Hacking the functions of sleep: Non-invasive approaches to stimulate sleep neurophysiology.","authors":"Elena Krugliakova,Friederike Breuer,Nico Adelhöfer,Alejandra Alonso,Luciana Besedovsky,Keith Murphy,Emma Peters,Karolina Raczek,Björn Rasch,Leila Salvesen,Sophia Snipes,Sarah Schoch,Thomas Schreiner,Rick Wassing,Til Ole Bergmann,Martin Dresler","doi":"10.1152/physrev.00007.2025","DOIUrl":"https://doi.org/10.1152/physrev.00007.2025","url":null,"abstract":"Sleep is essentially contributing to human health and wellbeing through multiple biological functions, including restoration and biosynthesis, brain clearance, energy metabolism, immunological and endocrine processing, synaptic plasticity, memory consolidation, and regulation of cognitive and emotional processes. Sleep disturbances are highly prevalent and are both a symptom and a contributing risk factor for psychiatric, neurological, and somatic disorders. Given the limitations of pharmacological interventions, non-invasive neuromodulation techniques ranging from non-invasive transcranial (TMS, tDCS, tACS, tRNS, tTIS, and TUS) to peripheral sensory (auditory, olfactory, visual, tactile, vestibular) and electrical nerve (galvanic vestibular, transcutaneous vagus nerve, and median nerve) stimulation have gained increasing attention as potential tools to modulate sleep physiology. These techniques offer promising avenues for both therapeutic applications and fundamental research into sleep-dependent neuroplasticity, interregional communication, and oscillatory activity. However, sleep is not a uniform state but a highly complex and dynamic phenomenon, with intricate macrostructural (e.g., NREM-REM sleep balance, sleep efficiency) and microstructural characteristics (e.g., hierarchically nested slow waves and spindles) that contribute to a variety of functions. This complexity necessitates precise targeting strategies, often employing real-time brain-state-de pendent stimulation, to modulate specific sleep-related processes effectively. In this review, we summarise the functions of sleep and the available non-invasive tools for its modulation, addressing key methodological challenges and providing recommendations for best practices in sleep neuromodulation.","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":"8 1","pages":""},"PeriodicalIF":33.6,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145559009","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}
Episodic memory is a declarative long-term memory of a specific past experience. As such, it is multifaceted, encompassing both the objective and subjective components of that experience. These components can be flexibly represented at different levels of granularity, from precise, context-specific details to generalized, gist-like representations. In this review, we suggest that 1) multiple representations of an episodic memory at different levels of granularity are simultaneously encoded into a memory trace and 2) the relative weighting of these representations determines the extent to which a memory is reconstructed or reproduced at retrieval. We propose that this representational flexibility drives adaptive behavior by prioritizing reconstruction or reproduction depending on the age of the memory, its relationship to prior knowledge, current attentional goals, or task demands, and individual differences. Drawing on research in humans and non-human animals, we show a close correspondence between psychological and neural representations of a memory across encoding, consolidation, and retrieval. Specifically, we discuss how hippocampal activity in humans and engram formation and activation in rodents support the reproduction of detailed memory representations, while schema formation across species, mediated by the medial prefrontal cortex, facilitates reconstruction and generalization to guide behavior. Finally, we consider how species- and individual-level differences shape episodic memory representations. By integrating findings across species, we illustrate how the correspondence between neural and psychological representations enables multiple memory representations to balance stability and flexibility, ultimately driving adaptive behavior.
{"title":"Adaptive episodic memory: How multiple memory representations drive behaviour in humans and non-humans.","authors":"Hannah Tarder-Stoll,Melanie J Sekeres,Brian Levine,Morris Moscovitch","doi":"10.1152/physrev.00005.2025","DOIUrl":"https://doi.org/10.1152/physrev.00005.2025","url":null,"abstract":"Episodic memory is a declarative long-term memory of a specific past experience. As such, it is multifaceted, encompassing both the objective and subjective components of that experience. These components can be flexibly represented at different levels of granularity, from precise, context-specific details to generalized, gist-like representations. In this review, we suggest that 1) multiple representations of an episodic memory at different levels of granularity are simultaneously encoded into a memory trace and 2) the relative weighting of these representations determines the extent to which a memory is reconstructed or reproduced at retrieval. We propose that this representational flexibility drives adaptive behavior by prioritizing reconstruction or reproduction depending on the age of the memory, its relationship to prior knowledge, current attentional goals, or task demands, and individual differences. Drawing on research in humans and non-human animals, we show a close correspondence between psychological and neural representations of a memory across encoding, consolidation, and retrieval. Specifically, we discuss how hippocampal activity in humans and engram formation and activation in rodents support the reproduction of detailed memory representations, while schema formation across species, mediated by the medial prefrontal cortex, facilitates reconstruction and generalization to guide behavior. Finally, we consider how species- and individual-level differences shape episodic memory representations. By integrating findings across species, we illustrate how the correspondence between neural and psychological representations enables multiple memory representations to balance stability and flexibility, ultimately driving adaptive behavior.","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":"18 4 1","pages":""},"PeriodicalIF":33.6,"publicationDate":"2025-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145440772","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}
Pub Date : 2025-10-01DOI: 10.1152/physrev.00011.2024_cor
{"title":"Corrigendum for Lutsenko et al., volume 105, 2025, p. 441-491.","authors":"","doi":"10.1152/physrev.00011.2024_cor","DOIUrl":"https://doi.org/10.1152/physrev.00011.2024_cor","url":null,"abstract":"","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":"1 1","pages":"2231"},"PeriodicalIF":33.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144533289","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}
Pub Date : 2025-10-01Epub Date: 2025-06-11DOI: 10.1152/physrev.00039.2024
Irving L M H Aye, Stephen Tong, D Stephen Charnock-Jones, Gordon C S Smith
The placenta performs many key tasks that are essential for the healthy growth and development of the human fetus. Placental dysfunction has multiple manifestations, but they share the common property of lacking a mechanistic understanding of etiology. The clinical consequences of placental dysfunction are a major determinant of the global burden of disease. Currently, the primary clinical method for assessing placental function is ultrasonic Doppler flow velocimetry of the umbilical and uterine arteries. More recently, some biomarkers have emerged that can predict or diagnose placentally related complications of pregnancy. However, methods for identifying and characterizing placental dysfunction have developed relatively little over the last 20 years and perform poorly, and there remains an absence of disease-modifying therapies targeted at the placenta. Understanding disease mechanisms is made more difficult due to the profound differences in pregnancy and placentation comparing humans and the most commonly used laboratory animals, limiting the utility of animal models. The use of omics methods in human samples may yield progress: omics analyses of maternal blood show promise in identifying better predictors of disease, and single-cell analyses, including spatial omics of healthy and abnormal placentas, could identify therapeutic targets. Limitations in cellular models of the placenta have been significantly overcome in the last 5 to 10 years by the development of human cell models, including human trophoblast stem cells and organoids, and the use of these model systems may allow hypothesis testing experiments in a more clinically relevant context than animal models or immortalized cell lines.
{"title":"The human placenta and its role in reproductive outcomes revisited.","authors":"Irving L M H Aye, Stephen Tong, D Stephen Charnock-Jones, Gordon C S Smith","doi":"10.1152/physrev.00039.2024","DOIUrl":"10.1152/physrev.00039.2024","url":null,"abstract":"<p><p>The placenta performs many key tasks that are essential for the healthy growth and development of the human fetus. Placental dysfunction has multiple manifestations, but they share the common property of lacking a mechanistic understanding of etiology. The clinical consequences of placental dysfunction are a major determinant of the global burden of disease. Currently, the primary clinical method for assessing placental function is ultrasonic Doppler flow velocimetry of the umbilical and uterine arteries. More recently, some biomarkers have emerged that can predict or diagnose placentally related complications of pregnancy. However, methods for identifying and characterizing placental dysfunction have developed relatively little over the last 20 years and perform poorly, and there remains an absence of disease-modifying therapies targeted at the placenta. Understanding disease mechanisms is made more difficult due to the profound differences in pregnancy and placentation comparing humans and the most commonly used laboratory animals, limiting the utility of animal models. The use of omics methods in human samples may yield progress: omics analyses of maternal blood show promise in identifying better predictors of disease, and single-cell analyses, including spatial omics of healthy and abnormal placentas, could identify therapeutic targets. Limitations in cellular models of the placenta have been significantly overcome in the last 5 to 10 years by the development of human cell models, including human trophoblast stem cells and organoids, and the use of these model systems may allow hypothesis testing experiments in a more clinically relevant context than animal models or immortalized cell lines.</p>","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":" ","pages":"2305-2376"},"PeriodicalIF":28.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7617900/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144267132","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}
Pub Date : 2025-09-30DOI: 10.1152/physrev.00001.2024
Gergely Gyimesi,Susan Tweedie,Elspeth Bruford,Matthias A Hediger
Membrane transporters are essential for human health, mediating the movement of nutrients, electrolytes, metabolites and other molecules across cellular and organellar membranes. Genes encoding these proteins account for approximately 5.2% of the human protein coding genome. Nearly half of these belong to the solute carriers (SLC) supergroup, the largest class of membrane transport proteins, collectively termed the "SLC-ome." The current SLC-ome comprises 464 SLCs organized into 76 SLC families, of which 24% (111 SLCs) remain orphan transporters with unknown or incompletely characterized function. An additional 52 SLC-like proteins bring the total to 516 membrane transport proteins. SLCs function as molecular gatekeepers, and their dysfunction contributes to a wide spectrum of human diseases, including cancer, diabetes, and immunological, cardiovascular and neurodegenerative disorders. Pathological consequences of SLC defects include hypertension, hyperglycemia, hypercholesterolemia, nutritional deficiencies, metal ion imbalance, oxidative stress, and dysfunction of mitochondria, lysosomes, endoplasmic reticulum and Golgi apparatus. In addition, genetic defects in SLCs are the cause of many rare diseases. Several SLCs require additional subunits to form functional heteromeric complexes, while others exhibit additional or alternative roles, such as acting as transceptors. In this review, we provide updated physiological, structural, mechanistic, and pharmacological insights for each of the 516 human SLC and SLC-like proteins. We also summarize their classification, structural architecture, transport mechanisms and pharmaceutical relevance, and present the most recent SLC gene nomenclature assignments approved by the HUGO Gene Nomenclature Committee (HGNC).
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