Physiological reviews最新文献

The origins and progression of pyloric metaplasia following gastric mucosal injury. 胃粘膜损伤后幽门化生的起源和进展。

IF 35.7 1区医学

Physiological reviews Pub Date : 2026-10-01 Epub Date: 2026-06-19 DOI: 10.1152/physrev.00042.2025

Sophia K Cornish, Eunyoung Choi, Jason C Mills, James R Goldenring

{"title":"The origins and progression of pyloric metaplasia following gastric mucosal injury.","authors":"Sophia K Cornish, Eunyoung Choi, Jason C Mills, James R Goldenring","doi":"10.1152/physrev.00042.2025","DOIUrl":"10.1152/physrev.00042.2025","url":null,"abstract":"The human gastric mucosa contends with insults throughout the course of its normal functions. Superficial injuries are rapidly resolved by the normal cellular lineages within the glandular epithelium. Deeper injuries often cause loss of acid-secreting cells, necessitating extensively coordinated repair mechanisms that significantly alter the cellular content of the gastric glands, culminating in pyloric metaplasia. Pyloric metaplasia is defined by the hyperplastic expansion of foveolar and mucous neck cell lineages as well as spasmolytic polypeptide-expressing metaplasia (SPEM) cells transdifferentiated from zymogenic chief cells. SPEM cells resemble mucus-secreting deep antral gland cells and possess proliferative qualities meant to aid in wound healing. Chief cell transdifferentiation into SPEM cells is regulated by an orderly process in which differentiated zymogenic cells reenter the cell cycle after downregulating mature transcriptional programs. The resolution of injury is followed by the restitution of normal cell lineages. However, metaplasia can persist when there is continuing inflammation and/or severe chronic injury. The aberrant persistence of proliferative SPEM cells can drive glandular intestinalization. The resulting intestinal metaplasia glands, particularly those with mixed gastric and intestinal lineages, are at increased risk for progression to dysplasia and ultimately gastric cancer. Understanding the dynamics of metaplastic cell lineage progression and uncovering lineage transition markers is critical to identifying targets suitable for therapeutic intervention. Here, we discuss the current knowledge, controversies, and remaining questions pertaining to the establishment and progression of metaplasia in response to deep gastric mucosal injury.","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":" ","pages":"2441-2471"},"PeriodicalIF":35.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13358225/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148278422","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}

引用次数: 0

Manganese transport, homeostasis, and neurotoxicity. 锰运输、体内平衡和神经毒性。

IF 35.7 1区医学

Physiological reviews Pub Date : 2026-10-01 Epub Date: 2026-08-08 DOI: 10.1152/physrev.00006.2026

Ashvini Melkote, Michael Aschner, Aaron B Bowman, Somshuvra Mukhopadhyay

引用次数: 0

Esophageal peristalsis in health and disease: mechanistic insights. 食道蠕动在健康和疾病：机制的见解。

IF 35.7 1区医学

Physiological reviews Pub Date : 2026-10-01 Epub Date: 2026-05-14 DOI: 10.1152/physrev.00016.2025

Ravinder K Mittal, Yifeng Bu, Nick J Spencer

{"title":"Esophageal peristalsis in health and disease: mechanistic insights.","authors":"Ravinder K Mittal, Yifeng Bu, Nick J Spencer","doi":"10.1152/physrev.00016.2025","DOIUrl":"10.1152/physrev.00016.2025","url":null,"abstract":"The mechanism of esophageal peristalsis or sequential contractions of the skeletal and smooth muscle esophagus resides at multiple levels, i.e., brain stem (central pattern generator), neurons within the wall of the esophagus (myenteric plexus), and smooth muscle (myogenic). Esophageal peristalsis consists of initial inhibition followed by excitation, for which there may be parallel pathways from the central pattern generator, traveling via the vagus nerve to communicate with the inhibitory and excitatory neurons of the myenteric plexus. Primary and secondary esophageal peristalsis are associated with concurrent contraction and relaxation of the circular and longitudinal muscle layers. The longitudinal muscle contraction in the contracted segment exerts mechanical stretch on the segment ahead of it, which likely activates the mechanosensitive inhibitory motor neurons in the myenteric plexus to induce descending relaxation, a peripheral mechanism of the peristaltic reflex. In achalasia esophagus, there is inflammation and fibrosis in the muscularis propria and myenteric plexus, resulting in loss of inhibitory nerves in the myenteric plexus. It also results in replacement of muscle with fibrous tissue in the muscularis propria of the lower esophageal sphincter (LES), impaired LES relaxation, and low distensibility of the esophagogastric junction in achalasia esophagus. The esophageal hiatus contains a pad of fat that is replaced with fibrosis in patients with achalasia esophagus. Whether hiatal fibrosis leads to impaired LES relaxation/low distensibility of the esophagogastric junction and changes in esophageal peristalsis are secondary to obstruction requires further study. Esophageal hypersensitivity is currently the favored mechanism of \"angina-like\" esophageal pain and refractory heartburn. Spastic or long-duration contractions of the longitudinal muscle of the esophagus may also play a role in the genesis of noncardiac esophageal pain and heartburn sensation.","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":" ","pages":"2149-2188"},"PeriodicalIF":35.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13355913/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147942554","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}

引用次数: 0

Impact of gastric emptying and small intestinal carbohydrate absorption on glycemia in health and diabetes: therapeutic implications. 胃排空和小肠碳水化合物吸收对健康和糖尿病患者血糖的影响：治疗意义

IF 35.7 1区医学

Physiological reviews Pub Date : 2026-10-01 Epub Date: 2026-05-11 DOI: 10.1152/physrev.00009.2025

Ryan J Jalleh, Tongzhi Wu, Mahesh M Umapathysivam, Richard L Young, Karen L Jones, Chinmay S Marathe, Christopher K Rayner, Mark P Plummer, Michael Horowitz

{"title":"Impact of gastric emptying and small intestinal carbohydrate absorption on glycemia in health and diabetes: therapeutic implications.","authors":"Ryan J Jalleh, Tongzhi Wu, Mahesh M Umapathysivam, Richard L Young, Karen L Jones, Chinmay S Marathe, Christopher K Rayner, Mark P Plummer, Michael Horowitz","doi":"10.1152/physrev.00009.2025","DOIUrl":"10.1152/physrev.00009.2025","url":null,"abstract":"Gastric emptying, which exhibits a substantial interindividual, but much lesser intraindividual, variation in health and is frequently disordered (particularly delayed) in diabetes, is now appreciated to be a major determinant of postprandial glycemia. The incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are secreted in the proximal and distal small intestine, respectively, in response to nutrients. GLP-1, together with peptide tyrosine-tyrosine (PYY), stimulates potent negative feedback on gastric emptying. Modulation of gastric emptying, through dietary, pharmacologic, and surgical therapies, has been utilized in current clinical practice for the treatment of hyperglycemia, particularly relating to type 2 diabetes. We review the complex, interdependent relationships between gastric emptying, small intestinal transit, glucose absorption, neurohormonal regulatory responses, and postprandial glycemia. We discuss how this has informed fundamental advances in the understanding and rational management of obesity, stress hyperglycemia, type 1 and 2 diabetes, and gestational diabetes, and we provide recommendations for research priorities that have the potential to impact practice. We also discuss the frequent complication of abnormally delayed gastric emptying (gastroparesis) in both type 1 and type 2 diabetes, the implications for management of diabetes, and the impact of treatment on gastric emptying. With the increasing recognition of the importance of gastric emptying in the management of conditions associated with disordered glucose metabolism, and the advent and increasing use of GLP-1 receptor agonists, an improved definition of the interactions between gastrointestinal motility (gastric emptying and small intestinal transit) and enteropancreatic hormonal responses is essential.","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":" ","pages":"2317-2382"},"PeriodicalIF":35.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147869411","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}

引用次数: 0

AKAP signaling: physiological and pathophysiological roles and opportunities for novel therapeutic concepts. AKAP信号：生理和病理生理的作用和新治疗概念的机会。

IF 35.7 1区医学

Physiological reviews Pub Date : 2026-10-01 Epub Date: 2026-05-19 DOI: 10.1152/physrev.00043.2025

Friedrich W Herberg, Ester Paolocci, Enno Klussmann

{"title":"AKAP signaling: physiological and pathophysiological roles and opportunities for novel therapeutic concepts.","authors":"Friedrich W Herberg, Ester Paolocci, Enno Klussmann","doi":"10.1152/physrev.00043.2025","DOIUrl":"10.1152/physrev.00043.2025","url":null,"abstract":"A-kinase anchoring proteins (AKAPs) received their name based on their ability to bind protein kinase A (PKA). Now, AKAPs have grown to a diverse family of more than 50 proteins, coordinating molecules far beyond PKA and the PKA signaling pathway. AKAPs are scaffolding proteins spanning in size between 15 and several hundred kilodaltons and can directly engage in protein interactions with other signaling proteins, their upstream regulators, and their downstream effectors. AKAPs possess unique targeting domains directing them to defined cellular compartments to coordinate cellular signaling spatially and temporally. A few AKAPs possess their own catalytic activity. AKAPs are crucial in directing cAMP signaling locally and in mediating cross talk with other second messenger systems. This review introduces individual AKAPs and their physiological functions in their respective cellular compartments and illustrates how they organize local signal transduction. The crucial role of AKAPs in coordinating cAMP responses to extracellular cues and how they facilitate specific responses to each stimulus will be exemplified. Dysregulation of AKAPs is associated with or causes disease. We will examine the pathophysiological roles of AKAPs in inherited and noninherited noncommunicable diseases, such as cardiovascular diseases and cancer. Due to the lack of understanding of molecular mechanisms underlying most of these diseases, the available therapeutic approaches often only slow progression and cause side effects. This review will discuss the unique opportunities AKAPs provide to address the medical need for novel therapeutic concepts. Finally, gaps in our knowledge about AKAPs will be outlined, and future directions in AKAP research will be suggested.","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":" ","pages":"2189-2266"},"PeriodicalIF":35.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147974857","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}

引用次数: 0

Mechanisms of transcranial magnetic brain stimulation. 经颅磁脑刺激的机制。

IF 35.7 1区医学

Physiological reviews Pub Date : 2026-10-01 Epub Date: 2026-05-19 DOI: 10.1152/physrev.00026.2025

Marcello Massimini, Angel V Peterchev, Andreas Vlachos, Ulf Ziemann

{"title":"Mechanisms of transcranial magnetic brain stimulation.","authors":"Marcello Massimini, Angel V Peterchev, Andreas Vlachos, Ulf Ziemann","doi":"10.1152/physrev.00026.2025","DOIUrl":"10.1152/physrev.00026.2025","url":null,"abstract":"Transcranial magnetic stimulation (TMS) noninvasively activates the human cortex through the intact skull and is now employed worldwide to interrogate physiological and pathological functions of the human brain and to treat a variety of neurological and psychiatric brain disorders. Yet the precise routes from the induced electric field to neuronal excitation including network effects remain not fully resolved, limiting the mechanistic basis of all TMS applications. This review deeply surveys how TMS activates the human cortex. We integrate evidence from physics, biophysics, computational modeling, neurophysiological studies in humans using electromyography, electroencephalography, and epidural spinal recordings, and converging nonhuman primate, rodent, and cortical slice studies. Collectively, the data suggest that TMS preferentially depolarizes superficial large-diameter myelinated axons, likely at bends, thereby triggering near-instantaneous synaptic activation of local cortical circuits and the emergence of long-range corticocortical and cortico-subcortical network activity. Through this cascade, axonal excitation, cell and circuit recruitment, and network propagation, TMS provides a versatile probe of excitability, function, and dysfunction across spatial scales, from single axons to distributed human brain networks.","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":" ","pages":"2267-2316"},"PeriodicalIF":35.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13340031/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147974872","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}

引用次数: 0

Glial cells in neuropathic pain. 神经性疼痛中的神经胶质细胞。

IF 35.7 1区医学

Physiological reviews Pub Date : 2026-10-01 Epub Date: 2026-05-11 DOI: 10.1152/physrev.00034.2025

Temugin Berta, Arkady Khoutorsky, Jing Xu, Ru-Rong Ji

{"title":"Glial cells in neuropathic pain.","authors":"Temugin Berta, Arkady Khoutorsky, Jing Xu, Ru-Rong Ji","doi":"10.1152/physrev.00034.2025","DOIUrl":"10.1152/physrev.00034.2025","url":null,"abstract":"Neuropathic pain is a chronic, debilitating condition that affects ∼7-8% of the global population and remains difficult to treat because of limited therapeutic options. Over the past two decades, mounting preclinical evidence has highlighted the crucial role of glial cells in the development, maintenance, and resolution of neuropathic pain. Conditions such as peripheral nerve injury are associated with reactive responses of glial cells, namely microglia and astrocytes in the central nervous system and satellite glial cells in the peripheral ganglia. Under physiological conditions, glial cells contribute to homeostatic regulation of spinal nociceptive circuits, preserving normal pain sensitivity. However, neuropathic pain is increasingly recognized as a form of gliopathy, wherein dysregulated glial activity contributes to pain hypersensitivity through enhanced excitability of primary sensory neurons (peripheral sensitization) and neuronal plasticity in the central pain circuits (central sensitization). In this review, we provide a comprehensive overview of glial cell research in neuropathic pain, with a specific focus on microglia, astrocytes, and satellite glial cells, the most extensively studied glial types in this context. We also highlight the critical involvement of glial cells in neuroinflammation and neuro-glial interactions and evaluate emerging therapeutic strategies targeting glial mechanisms of neuropathic pain.","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":" ","pages":"2079-2148"},"PeriodicalIF":35.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13276489/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147869350","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}

引用次数: 0

Magnetosensation: the unsolved mystery. 磁感应——未解之谜。

IF 35.7 1区医学

Physiological reviews Pub Date : 2026-10-01 Epub Date: 2026-03-28 DOI: 10.1152/physrev.00032.2025

Billy Y K Lam, E Pascal Malkemper

引用次数: 0

Understanding Physiological Adaptations of Pregnancy to the Chronic Hypoxia of High Altitude to Inform Obstetrical and Neonatal Care 了解妊娠对高原慢性缺氧的生理适应，为产科和新生儿护理提供信息

IF 33.6 1区医学

Physiological reviews Pub Date : 2026-08-15 DOI: 10.1152/physrev.00003.2026

Germán A. Arenas, Emilio A. Herrera, Bernardo J. Krause, Dino A. Giussani, Colleen G. Julian, Lorna G. Moore, Ramón A. Lorca

引用次数: 0

Extracellular Vesicles in Reproductive Physiology and Pathology 生殖生理病理中的细胞外囊泡