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Regulation of protein metabolism by a physiological concentration of insulin in mouse soleus and extensor digitorum longus muscles. Effects of starvation and scald injury.

1. Although high concentrations of insulin affect both synthesis and degradation of skeletal-muscle protein, it is not known to what extent these effects occur with physiological concentrations. The effects of a physiological concentration of insulin (100 mu units/ml) on muscle protein synthesis, measured with [3H]tyrosine, and on muscle protein degradation, measured by tyrosine release in the presence of cycloheximide, were studied in mouse soleus and extensor digitorum longus muscles in vitro. 2. Insulin significantly stimualated protein synthesis in both muscles, but an inhibition of degrad

Correction of metabolic acidosis by the kidney during isometric expansion of extracellular fluid volume.

In dogs with chronic hypochloremic metabolic alkalosis associated with ECFV contraction, plasma [HCO-3] ([HCO-3]p) normalizes during expansion of ECFV with a solution containing Cl- and HCO-3 in concentrations duplicating those in the plasma before expansion (isometric expansion). The kidney selectively rejects administered HCO-3 and retains Cl-. If this preferential Cl- less than HCO-3 reabsorptive selectivity were a characteristic renal response to ECFV expansion, isometric expansion during hyperchloremic acidosis would exacerbate the acid-base disturbance rather than correct it as it does i

Explanation of timing of botulinum neurotoxin effects, onset and duration, and clinical ways of influencing them.

While the steps in the action of botulinum neurotoxin (BoNT) are well known, the factors underlying the timing of these steps are not fully understood. After toxin is injected into a muscle, it resides in the extracellular space and must be taken up into the nerve terminals. More toxin will be taken up if near the endplate. Toxin is distributed mainly by convection and there is likely little diffusion. Toxin that is not taken up will go into the general circulation where it may have a slight systemic effect. The uptake is activity and temperature dependent. Encouraging the unwanted muscle cont…

Mitochondrial DNA released by senescent tumor cells enhances PMN-MDSC-driven immunosuppression through the cGAS-STING pathway.

Mitochondrial dysfunction is a hallmark of cellular senescence. Here, we investigated whether senescent cells release mitochondrial (mt)DNA into the extracellular space and its impact on innate immunity. We found that both primary senescent cells and tumor cells undergoing therapy-induced senescence actively released mtDNA into the extracellular environment. mtDNA released by senescent cells was packaged within extracellular vesicles and selectively transferred to polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) in the tumor microenvironment. Upon uptake, extracellular mtDNA enha…

Endogenous H+ modulation of NMDA receptor-mediated EPSCs revealed by carbonic anhydrase inhibition in rat hippocampus.

1. The occurrence of extracellular alkaline transients during excitatory synaptic transmission suggests that the NMDA receptor H(+)-modulato … se data demonstrate that NMDA receptor activity is dependent on the buffering kinetics of the brain extracellular space. The results suggest that endogenous pH shifts can modulate NMDA receptor function in a physiologically relevant time frame.

A Single-Chain Variable Fragment Antibody Alleviates Inflammation and Apoptosis of Neurons by Inhibiting Tau Aggregation.

Tau pathology is one of the main pathological features of Alzheimer's disease (AD). Intracellular Tau may be released to the extracellular space upon neuron degeneration, where it has the potential to be toxic to other neurons. The propagation of Tau pathology, mediated by extracellular Tau aggregates, may underlie the pathogenesis of AD. Antibody therapies targeting Tau proteins are, therefore, considered highly promising. In this study, the cytotoxicity of extracellular Tau aggregates on SH-SY5Y cells was examined. The effect of extracellular Tau aggregates on intracellular Tau aggregation w…

Extracellular vesicles from keratinocytes and other skin-related cells in psoriasis: A review.

Psoriasis is a highly prevalent chronic inflammatory skin condition involving abnormal proliferation and differentiation of keratinocytes, together with substantial infiltration of immune cells. Extracellular vesicles (EVs), which are released spontaneously into the extracellular space by virtually all cell types, play a crucial role in cell-to-cell communication by delivering bioactive cargos such as mRNA nucleic acids and proteins to recipient cells. Numerous studies have highlighted the significant contributions of EVs to both the pathogenesis and treatment of psoriasis. This review provide…

Exosome-derived microRNAs: emerging players in vitiligo.

Exosome-derived microRNAs (miRNAs) are biomacromolecules and nanoscale extracellular vesicles originating from intracellular compartments that are secreted by most cells into the extracellular space. This review examines the formation and function of exosomal miRNAs in biological information transfer, explores the pathogenesis of vitiligo, and highlights the relationship between exosomal miRNAs and vitiligo. The aim is to deepen the understanding of how exosomal miRNAs influence immune imbalance, oxidative stress damage, melanocyte-keratinocyte interactions, and melanogenesis disorders in the …

Neutrophil Extracellular Traps in Airway Diseases: Pathological Roles and Therapeutic Implications.

Neutrophils are important effector cells of the innate immune response that fight pathogens by phagocytosis and degranulation. Neutrophil extracellular traps (NETs) are released into the extracellular space to defend against invading pathogens. Although NETs play a defensive role against pathogens, excessive NETs can contribute to the pathogenesis of airway diseases. NETs are known to be directly cytotoxic to the lung epithelium and endothelium, highly involved in acute lung injury, and implicated in disease severity and exacerbation. This review describes the role of NET formation in airway d…

Extracellular Redox Balance as a Determinant of Immune Regulation and Tissue Inflammation.

Reactive oxygen species (ROS) are widely recognized as intracellular signaling mediators and contributors to oxidative damage. Increasing evidence indicates that redox processes in the extracellular space constitute a distinct and functionally relevant layer of immune regulation. Extracellular ROS are generated in a spatially and temporally controlled manner by immune and non-immune cells and are shaped by local antioxidant buffering, redox-active metabolites, and tissue architecture. Rather than acting as diffuse by-products of inflammation, extracellular redox conditions modulate immune cell…

Overexpression of extracellular-SOD in islets of nonobese diabetic mice and development of diabetes.

Mice of the nonobese diabetic strain develop a progressive insulitis resulting in beta-cell destruction and diabetes. Superoxide radicals ar … genic mice was, however, not modified. The results suggest that superoxide radicals secreted to the extracellular space do not contribute to the beta cell destruction in the nonobese diabetic mouse model.

Development of cataractous macrophthalmia in mice expressing an active MEK1 in the lens.

PURPOSE: To characterize the extracellular signal-regulated kinase (ERK) pathway in the lens and to try to understand how this pathway contr … thalmia. Distinct morphologic alterations, such as lens enlargement, swelling fiber cells, enlarged extracellular space, and vacuole formation, were observed in the lenses of these transgenic mice. A significant increase in the glucose transporter 1 (GLUT1) level, as well as in the glucose level, was detected in the lens. CONCLUSIONS: The MAP kinase pathway is invol …

Церебральная глимфатическая система: структура, регулирование, старение и механизмы энцефалопатии.

Глимфатическая система первоначально рассматривалась в качестве периваскулярного канала, отвечающего за удаление веществ в мозге. В связи с углублением понимания функций внеклеточного пространства (ЭКС) и открытием менинговых лимфатических сосудов и субарахноидной лимфатической мембраны предлагается, чтобы глимфатическая система представляла собой сложную систему, охватывающую периваскулярное пространство, ЭКС и лимфатические структуры, и она играет решающую роль в передаче веществ, удалении отходов и нейроиммунных функций в мозгу. Недавние исследования показали, что ECS мозга в основном регул

Совпадение в аннотации оригинала
The glymphatic system was initially considered as a perivascular channel, responsible for the clearance of substances within the brain. With the deepening comprehension of the functions of the extracellular space (ECS) and the discovery of meningeal lymphatic vessels and subarachnoid lymphatic-like membrane, it is proposed that the glymphatic system should b…

Extracellular vesicles in coronary artery disease.

Membrane vesicles released in the extracellular space are composed of a lipid bilayer enclosing soluble cytosolic material and nuclear components. Extracellular vesicles include apoptotic bodies, exosomes, and microvesicles (also known previously as microparticles). Originating from different subcellular compartments, the role of extracellular vesicles as regulators of transfer of biological information, acting locally and remotely, is now acknowledged. Circulating vesicles released from platelets, erythrocytes, leukocytes, and endothelial cells contain potential valuable biological informatio…

The Role of Extracellular Matrix Components in the Spreading of Pathological Protein Aggregates.

Several neurodegenerative diseases are characterized by the accumulation of aggregated misfolded proteins. These pathological agents have be … n cells and this event occurs, at least partially, via secretion of these protein aggregates in the extracellular space followed by re-uptake. Conversely, Aβ aggregates are found mainly extracellularly, and their spreading occurs in the extracellular space between brain regions. Due to the inherent nature of their spreading modalities, these proteins are exposed to c …

Intra- and extracellular electrolytes and sarcolemmal ATPase in the failing heart due to pressure overload in dogs.

An investigation of changes in the Mg2+ -dependent, Na+ -K+ -stimulated sarcolemmal ATPase and of intracellular electrolytes in the left failing heart due to pressure overload (aortic banding) was carried out in dogs. There was no change in the sarcolemmal Mg2+ -ATPase of the left or right ventricle for the whole duration (3 to 9 months) of left ventricular pressure overload. In the early phase (3 months) of aortic banding, when there was no haemodynamic evidence of left ventricular failure, there was also no significant change in the sarcolemmal Na+ -K+ -ATPase, extracellular space, or intra-…