Physiological reviews最新文献

Circadian rhythms, governed by the body's endogenous clock mechanism, regulate daily fluctuations in cardiovascular function, optimizing physiological processes like blood pressure regulation, cardiac metabolism, and myocardial repair. Rhythms also align cardiovascular reactivity with predictable environmental and behavioral cycles, enabling normal function and affecting disease susceptibility. Major adverse cardiovascular events, including myocardial infarction, ventricular arrhythmias, and stroke, exhibit a distinct morning peak, with evidence for circadian regulation in cardiovascular health. Indeed, controlled human laboratory studies demonstrate that beyond the influences of sleep and other behaviors, endogenous circadian rhythms independently regulate blood pressure, autonomic nervous system activity, blood clotting, vascular tone, and metabolic function. Additionally, the kidney plays a critical role in circadian sodium handling, fluid balance, and blood pressure control, with disruptions in renal circadian rhythms contributing to hypertension and progression to heart failure. Chronic circadian misalignment resulting from shift work, irregular sleep-wake cycles, or misaligned lifestyle habits is strongly associated with increased cardiovascular risk and disease progression. The emerging field of Circadian Medicine applies circadian principles to clinical care, leveraging interventions such as optimizing light exposure, meal timing, and physical activity to restore biological alignment. Chronotherapy, the strategic timing of medications or procedures to align with a patient's diurnal or circadian rhythms, offers further potential for enhancing treatments and reducing adverse effects. By integrating circadian biology into cardiovascular medicine, novel strategies are emerging to help prevent disease, improve patient outcomes, and enhance therapeutic precision. Understanding the interplay between circadian regulation and cardiovascular physiology provides a foundation for advancing cardiovascular prevention and treatment strategies.

Oligodendrocytes are highly specialized neural cells that produce myelin, essential for rapid electrical conduction of neural signals in the central nervous system (CNS). The emergence of oligodendrocytes and myelin was a critical step in the evolution of vertebrates, fundamental for the development of the mammalian connectome, and indispensable for miniaturization and enhanced computing power of the brain. The advance in cognitive capacity is paralleled by increasing eminence of white matter, composed of interconnected bundles of myelinated axons; white matter volume increases from 6% of the brain in shrews, considered related to the most primitive mammals, up to 50% in Homo sapiens. Myelinating oligodendrocytes together with smaller populations of oligodendrocyte precursor cells (OPCs) and satellite or perineuronal oligodendrocytes account for more than half of the glial cells in the human brain. Together, these three cell types make up the oligodendroglial cell lineage that express common lineage-specific proteins and transcription factors and display a degree of molecular and functional diversity. OPCs are the most numerous oligodendroglial cells during developmental axonal myelination, which extends postnatally for many years in humans. The generation of myelinating oligodendrocytes from OPCs throughout life continues to be important for adaptive plasticity of neural circuits and myelination of new axons required for learning. Myelination decreases in the aging brain and correlates with natural or physiological age-related cognitive decline. Like all neural cells, oligodendroglia express a wide assortment of ion channels, transporters, and neurotransmitter receptors that are essential for maintaining neuronal signaling, principally myelination, axonal metabolic support, and homeostatic regulation of the periaxonal microenvironment. Notably, OPCs are unique among neuroglia in that, like neurons, they are electrically excitable and form synapses with neurons. Oligodendroglial cells also contribute to neuroplasticity through multiple mechanisms including axon guidance, synapse formation, and adaptive myelination. In short, oligodendroglia are essential for normal CNS integrity, cognitive function, and behavior.

The alpha rhythm, first identified by Hans Berger 100 years ago, is the dominant noninvasive electrophysiological signature of the healthy human brain in the awake state. For decades, it was believed that the alpha rhythm reflected rest or idling; however, this perspective changed in the 2000s when researchers found that alpha oscillations increase with cognitive demands. This discovery led to a paradigm shift, demonstrating that alpha oscillations reflect the functional inhibition of brain regions that are not needed for a specific task, thereby directing information to task-specific areas. We have reviewed the physiological mechanisms involved in generating alpha oscillations, which have informed computational models explaining how these oscillations emerge within physiologically realistic networks. At the behavioral level, alpha oscillations are strongly modulated across nearly all cognitive paradigms tested in humans, reflecting the allocation of computational resources within the active brain network. Research in individuals with attention-related issues has highlighted their impaired ability to modulate alpha oscillations, which is associated with performance deficits. Therefore, further exploration of alpha oscillations has the potential to uncover causal mechanisms underlying attention problems, such as those related to attention deficit hyperactivity disorder (ADHD) and aging. Finally, advancements in technology are opening new avenues for characterizing alpha oscillations in ecologically valid settings and across the lifespan. This progress sets the stage for exploring the role of alpha oscillations in cognitive development and their functioning in natural environments.

The stomach is home to numerous nuclear receptor transcription factors (NRs) that can respond to food, toxins, and other ingested agents. Conversely, signals secreted from other organs (e.g., hormones) can engage gastric NRs to modulate gastric physiology. Thus, there is a rich potential interface between external and internal signals that gastric NRs might respond to and interpret. Here, we seek to comprehensively review the role of NRs in gastric homeostasis and disease pathogenesis. NRs are evolutionarily conserved proteins that regulate gene transcription by interpreting hormonal and environmental signals. We explore NR roles in normal stomach development, cell fate determination, and responses to dietary compounds and xenobiotics. The last topic is of particular recent importance 1) because NRs stimulated by ingested agents might directly regulate gastric physiology like the relative activity of acid-secreting and stem cells and 2) because the stomach is one of the first organs to encounter dietary compounds and pollutants. Additionally, we review the emerging yet understudied field of gastro-endocrinology, exploring how systemic endocrine circuits influence the stomach's function. We also discuss how NRs contribute to pathological conditions like precancerous lesions and cancer. Additionally, we summarize known agonists, antagonists, and coregulatory proteins, highlighting potential therapeutic targets. Understanding NR roles could pave the way for a better understanding of dietary and environmental toxin exposure and also lead to innovative treatments for gastric disorders, including gastritis, gastric intestinal metaplasia, and gastric cancer.

From its early genesis, cancer is integrated with the surrounding tissue. Its very existence depends on surrounding normal tissue cells engaging with cancer cells to create an alternative tissue environment. This emerging abnormal structure becomes connected with the host organism via blood, lymphatic vessels, and neural connections. Through those connections, the cancer mass communicates and perturbs the entire organism altering various aspects of the steady-state body physiology. At early, asymptomatic stages, the induced changes within distant organs that harbor the potential to facilitate the spread of cancer are termed "premetastatic niche." Many processes involved with premetastatic changes hijack processes typical in other contexts such as development, injury, or infections, but their co-occurrence creates a new alternative physiology. The cancer to body connections not only have important consequences for the efficacy of cancer therapy but also enable cancer to evolve and adapt under the very pressure of those treatments. Furthermore, as cancer-induced changes are closely related to other physiological challenges, extrinsic perturbations such as diet, injury, and other inflammatory events have a strong impact on the tumor disease. As the disease progresses, the complex intersection of inflammatory, metabolic, and regenerative changes creates an escalating cascade of events causing cancer-related syndrome, such as cachexia, that threatens the homeostasis of the entire body and can, per se, be deadly. In this article, we will review the recent advances in the understanding of cancer as a systemic malady.