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Topic Review
Lymphatic Clearance of Immune Cells in Cardiovascular Disease
The lymphatic vasculature is a vital component of the cardiovascular system, consisting of a blind-ended, highly permeable vascular network, integral in maintaining tissue homeostasis, regulation of interstitial fluid, lipid absorption, fluid drainage, and immune cell trafficking. Its role in immune cell transport is critical in the initiation of the immune response, especially following injury. This is of particular importance in the heart, where the lymphatic vasculature plays a vital role in myocardial healing following cardiac injury. By promoting cell egress or exit from the heart, the lymphatic systems favour cell clearance by way of reduction of the immune cell load in damaged tissue.
  • 628
  • 13 Apr 2022
Topic Review
SLC9C1 (NHE10/sNHE) in Male Fertility
The SLC9C1 gene encodes the NHE10 protein (also known as sNHE). This protein has been shown to be essential for male fertility in both mice and humans and therefore there has been much interest in studying this protein. What is known about NHE10 and its role in male fertility is highlighted.
  • 624
  • 26 Oct 2023
Topic Review
SLC9B2 (NHA2/NHEDC2) in Male Fertility
The SLC9B2 gene encodes the NHA2 protein (also known as NHEDC2). While NHA2 has been shown to be important for regulating various aspects of physiology such as blood pressure, this protein has also been implicated as being important for male fertility in mice. What is known about NHA2 and its potentially important role in male fertility is emphasized.
  • 621
  • 26 Oct 2023
Topic Review
L-Arginine Metabolism in Cancer
L-Arginine plays a crucial role in detoxification of ammonia—a protein breakdown product acts as a secretagogue and serves as a substrate for the synthesis of NO, an important signaling molecule that regulates vascular tone and cytotoxic functions of macrophages. L-Arg is also a precursor in the synthesis of L-ornithine and agmatine, creatine and polyamines. Metabolism of L-Arg is involved in immune cell regulation. It is now clear that L-Arg metabolism is engaged in the pathogenesis of tumor growth, inflammation, infectious diseases, and fibrotic processes, as well as physiological immunodeficiencies in newborns and pregnant women. 
  • 617
  • 21 Sep 2023
Topic Review
Circadian Rhythms and Sleep, Metabolic and Cardiovascular Disorders
Circadian rhythms are generated by the circadian clock, a self-sustained internal timing system that exhibits 24-h rhythms in the body. Many metabolic, cellular, behavioral and physiological processes are regulated by the circadian clock in coordination with environmental cues. 
  • 614
  • 08 Feb 2024
Topic Review
Underpin Sarcopenia, Cardiovascular and Metabolic Diseases
Worldwide, the main reason for all-cause mortality is attributed to non-communicable diseases, namely, cardiovascular disease (CVD) and metabolic diseases (MDs). CVD refers to conditions affecting the heart and blood vessels, such as coronary artery disease, heart failure and hypertension. MDs refer to disorders of processing nutrients and the use of energy. These conditions can include diabetes, obesity and metabolic syndrome, among others. Both CVD and MDs can have serious consequences, including heart attacks, stroke and organ damage. CVD remains the leading cause of death worldwide. 
  • 609
  • 29 Jun 2023
Topic Review
The Anti-Epileptic Effects of Carbenoxolone
Gap junctions (GJs) are intercellular junctions that allow the direct transfer of ions and small molecules between neighboring cells, and GJs between astrocytes play an important role in the development of various pathologies of the brain, including regulation of the pathological neuronal synchronization underlying epileptic seizures. Recently, we found that a pathological change is observed in astrocytes during the ictal and interictal phases of 4-aminopyridin (4-AP)-elicited epileptic activity in vitro, which was correlated with neuronal synchronization and extracellular epileptic electrical activity. This finding raises the question: Does this signal depend on GJs between astrocytes?
  • 605
  • 25 Jan 2022
Topic Review
Nanoparticles for Brain Protection
Strokes rank as the second most common cause of mortality and disability in the human population across the world. Currently, available methods of treating or preventing strokes have significant limitations, primarily the need to use high doses of drugs due to the presence of the blood–brain barrier. In the last decade, increasing attention has been paid to the capabilities of nanotechnology. However, the vast majority of research in this area is focused on the mechanisms of anticancer and antiviral effects of nanoparticles.
  • 605
  • 29 Jan 2024
Topic Review
Neurological Disorders in Animals with NKA Mutations
Endogenous cardiotonic steroids are involved in the pathogenesis of affective disorders, including depression and bipolar disorder, which are linked to dopaminergic system dysfunction. Animal models have shown that the cardiotonic steroid ouabain induces mania-like behavior through dopamine-dependent intracellular signaling pathways. In addition, mutations in the alpha subunit of Na+,K+-ATPase lead to the development of neurological pathologies. Evidence from animal models confirms the neurological consequences of mutations in the Na+,K+-ATPase alpha subunit. 
  • 604
  • 06 Jul 2023
Topic Review
Airway Smooth Muscle Calcium Handling Mechanisms and Estrogens
Cell calcium (Ca2+) homeostasis is maintained by a finely tuned Ca2+ signaling system made-up of numerous Ca2+ transporters (channels, exchangers, and pumps) regulating the influx and efflux of this cation from the cytoplasm to preserve its balance. Ca2+ homeostasis is essential for the cell. As a second messenger, Ca2+ signaling regulates various cellular processes that depend on the Ca2+ concentration. It is well known that Ca2+ regulates exocytosis, contraction, protein phosphorylation, dephosphorylation, metabolism, gene transcription, fecundation, cell proliferation, and even apoptosis. In the ASM, Ca2+ homeostasis keeps intracellular basal Ca2+ concentrations (b[Ca2+]i) at around 100–150 nM, while Ca2+ concentrations in the intracellular stores and extracellular space are higher (5–10 mM and 2 mM, respectively) creating a large chemical gradient in favor of Ca2+ influx into the cytosol. In order to regulate [Ca2+]i, numerous proteins exist to facilitate the cellular influx and efflux of Ca2+. Among the calcium-handling proteins, the voltage-dependent Ca2+ channels (VDCCs), store-operated Ca2+ channels (SOCCs), receptor-operated Ca2+ channel (ROCCs), transient receptor potential channels (TRPs), and the Na+/Ca2+ exchanger in its reverse form (NCXREV) as influx mechanisms located in the cellular membrane can be included. On the other hand, the Na+/Ca2+ Exchanger (NCX) and the plasma membrane Ca2+ ATPase (PMCA) are efflux mechanisms located in the cellular membrane.
  • 603
  • 15 May 2023
Topic Review
Early Cell Signaling in Developing Lung Edema
The lung promptly responds to edemagenic conditions through functional adaptations that contrast the increase in microvascular filtration. In hypoxia, thinning of endothelial cells, a decrease in caveolae and AQP-1, and an increase in lipid rafts are observed. The interpretation of this response is that it favors oxygen diffusion and hinders trans-cellular water fluxes. In hydraulic edema, which generates greater capillary water leakages, an increase in cell volume and opposite changes in membrane rafts were observed; further, the remarkable increase in caveolae suggests a potential abluminal–luminal vesicular-dependent fluid reabsorption.
  • 602
  • 19 Jun 2023
Topic Review
Role of Dynamical Network Biomarkers Theory in Aging
Aging is the slowest process in a living organism. During this process, mortality rate increases exponentially due to the accumulation of damage at the cellular level. Cellular senescence is a well-established hallmark of aging, as well as a promising target for preventing aging and age-related diseases. Given that the appearance of senescent cells is considered to be a cell fate transition from the proliferative state to the non-proliferative state, similar to the critical transitions that occur during cell differentiation and symptom onset, it can be detectable by the dynamical network biomarkers (DNB) theory, which detects early warning signals just before bifurcation points, such as “the pre-disease state”.
  • 593
  • 27 Sep 2023
Topic Review
KCa and Regulation of the Uteroplacental Circulation
Adequate uteroplacental blood supply is essential for the development and growth of the placenta and fetus during pregnancy. Aberrant uteroplacental perfusion is associated with pregnancy complications such as preeclampsia, fetal growth restriction (FGR), and gestational diabetes. The regulation of uteroplacental blood flow is thus vital to the well-being of the mother and fetus. Ca2+-activated K+ (KCa) channels of small, intermediate, and large conductance participate in setting and regulating the resting membrane potential of vascular smooth muscle cells (VSMCs) and endothelial cells (ECs) and play a critical role in controlling vascular tone and blood pressure. KCa channels are important mediators of estrogen/pregnancy-induced adaptive changes in the uteroplacental circulation. Activation of the channels hyperpolarizes uteroplacental VSMCs/ECs, leading to attenuated vascular tone, blunted vasopressor responses, and increased uteroplacental blood flow. However, the regulation of uteroplacental vascular function by KCa channels is compromised in pregnancy complications.
  • 588
  • 02 Feb 2023
Topic Review
SITE for the Management of Neurological Disorders
Sub-scalp Implantable Telemetric EEG (SITE) devices are under development for the treatment of epilepsy. However, beyond epilepsy, continuous EEG analysis could revolutionize the management of patients suffering from all types of brain disorders.
  • 588
  • 17 Aug 2023
Topic Review
Mitochondrial Impairment Is Involved in RGC Degeneration
Dysfunctional mitochondria are implicated in the development and progression of retinal pathologies and are directly involved in retinal neuronal degeneration. Retinal ganglion cells (RGCs) are higher energy consumers susceptible to mitochondrial dysfunctions that ultimately cause RGC loss. Proper redox balance and mitochondrial homeostasis are essential for maintaining healthy retinal conditions and inducing neuroprotection.
  • 585
  • 28 Nov 2023
Topic Review
Mitochondrial Turnover and Aging
Aerobic organisms use molecular oxygen in several reactions, including those in which the oxidation of substrate molecules is coupled to oxygen reduction to produce large amounts of metabolic energy. The utilization of oxygen is associated with the production of ROS, which can damage biological macromolecules but also act as signaling molecules, regulating numerous cellular processes. Mitochondria are the cellular sites where most of the metabolic energy is produced and perform numerous physiological functions by acting as regulatory hubs of cellular metabolism. 
  • 573
  • 14 Aug 2023
Topic Review
Lipidome Fingerprint of Longevity
Lipids were determinants in the appearance and evolution of life. Studies disclose the existence of a link between lipids and animal longevity. Findings from both comparative studies and genetics and nutritional interventions in invertebrates, vertebrates, and exceptionally long-lived animal species—humans included—demonstrate that both the cell membrane fatty acid profile and lipidome are a species-specific optimized evolutionary adaptation and traits associated with longevity. All these emerging observations point to lipids as a key target to study the molecular mechanisms underlying differences in longevity and suggest the existence of a lipidome profile of long life.
  • 573
  • 15 Nov 2023
Topic Review
Oxidative Stress and Bio-Regulation
Reactive oxygen species (ROS) and free radicals work to maintain homeostasis in the body, but their excessive production causes damage to the organism. The human body is composed of a variety of cells totaling over 60 trillion cells. Each cell performs different functions and has a unique lifespan. The lifespan of cells is preprogrammed in their genes, and the death of cells that have reached the end of their lifespan is called apoptosis. This is contrary to necrosis, which is the premature death of cells brought about by physical or scientific forces. Each species has its own unique lifespan, which in humans is estimated to be up to 120 years. Elucidating the mechanism of the death of a single cell will lead to a better understanding of human death, and, conversely, the death of a single cell will lead to exploring the mechanisms of life. In this sense, research on active oxygen and free radicals, which are implicated in biological disorders and homeostasis, requires an understanding of both the physicochemical as well as the biochemical aspects. Based on the discussion above, it is clear to see that active oxygen and free radicals have dual functions of both injuring and facilitating homeostasis in living organisms.
  • 572
  • 27 Mar 2024
Topic Review
Bioactive Macronutrients from Chlorella and Physical Exercise
Chlorella is a marine microalga rich in proteins and containing all the essential amino acids. Chlorella also contains fiber and other polysaccharides, as well as polyunsaturated fatty acids such as linoleic acid and alpha-linolenic acid. The proportion of the different macronutrients in Chlorella can be modulated by altering the conditions in which it is cultured. Physical exercise represents a stressful activity for the body’s cells, tissues, and organs, which dysregulates whole-body homeostasis in a progressive and reversible way. However, as a consequence of its regular and systematic practice, different cellular signaling pathways become activated and generate systemic and local chronic adaptations.
  • 567
  • 10 May 2023
Topic Review
Genome Editing in Treating Cardiac Arrhythmias
Despite advances in screening and preventative treatments, the estimated lifetime risk for premature death due to arrhythmogenic sudden cardiac death remains high. A growing understanding of the genetics underlying cardiac arrhythmias has enabled new treatment possibilities including the use of cardiac genome editing.
  • 567
  • 03 Jul 2023
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