Eccentric strength training alters muscle architecture, but it is also an important factor for the prevention of hamstring injuries. The purpose was to determine the architectural adaptations of the ...biceps femoris long head (BFlh) after eccentric strength training with nordic hamstring exercise (NHE), followed by a subsequent detraining period. The participants in this intervention (n=23) completed a period of 13 weeks consisting of a first week of control and prior training, followed by 8 weeks of eccentric strength training with NHE, and concluding with a 4‐week period of detraining. The architectural characteristics of the BFlh were measured at rest using two‐dimensional ultrasound before (M1—week 1) and after (M2—week 9) the eccentric strength training, and at the end of the detraining period (M3—week 13). The muscle fascicle length significantly increased (t=−7.73, d=2.28, P<.001) in M2 compared to M1, as well as the muscle thickness (t=−5.23, d=1.54, P<.001), while the pennation angle presented a significant decrease (t=7.81, d=2.3, P<.001). The muscle fascicle length decreased significantly (t=6.07, d=1.79, P<.001) in M3 compared to M2, while the pennation angle showed a significant increase (t=−4.63, d=1.36, P<.001). The results provide evidence that NHE may cause alterations in the architectural conditions of the BFlh and may have practical implications for injury prevention and rehabilitation programs.
Neutrophil extracellular traps (NETs) are implicated in autoimmunity, but how they are generated and their roles in sterile inflammation remain unclear. Ribonucleoprotein immune complexes (RNP ICs), ...inducers of NETosis, require mitochondrial reactive oxygen species (ROS) for maximal NET stimulation. After RNP IC stimulation of neutrophils, mitochondria become hypopolarized and translocate to the cell surface. Extracellular release of oxidized mitochondrial DNA is proinflammatory in vitro, and when this DNA is injected into mice, it stimulates type I interferon (IFN) signaling through a pathway dependent on the DNA sensor STING. Mitochondrial ROS are also necessary for spontaneous NETosis of low-density granulocytes from individuals with systemic lupus erythematosus. This was also observed in individuals with chronic granulomatous disease, who lack NADPH oxidase activity but still develop autoimmunity and type I IFN signatures. Mitochondrial ROS inhibition in vivo reduces disease severity and type I IFN responses in a mouse model of lupus. Together, these findings highlight a role for mitochondria in the generation not only of NETs but also of pro-inflammatory oxidized mitochondrial DNA in autoimmune diseases.
Mitochondrial stress releases mitochondrial DNA (mtDNA) into the cytosol, thereby triggering the type Ι interferon (IFN) response. Mitochondrial outer membrane permeabilization, which is required for ...mtDNA release, has been extensively studied in apoptotic cells, but little is known about its role in live cells. We found that oxidatively stressed mitochondria release short mtDNA fragments via pores formed by the voltage-dependent anion channel (VDAC) oligomers in the mitochondrial outer membrane. Furthermore, the positively charged residues in the N-terminal domain of VDAC1 interact with mtDNA, promoting VDAC1 oligomerization. The VDAC oligomerization inhibitor VBIT-4 decreases mtDNA release, IFN signaling, neutrophil extracellular traps, and disease severity in a mouse model of systemic lupus erythematosus. Thus, inhibiting VDAC oligomerization is a potential therapeutic approach for diseases associated with mtDNA release.
Vascular cannulation is common practice in critical care, and is traditionally performed using the landmark technique - though failures and complications are not uncommon. In this regard, ultrasound ...guided vascular cannulation (USGVC) has been shown to improve the procedure success rate and reduce its associated complications. This review addresses the fundamental aspects of USGVC and discusses some training issues related to this technique which is currently regarded as essential for intensivists.
Upon antigen exposure, immune cells rely on cell-specific metabolic pathways to mount an efficient immune response. In autoimmunity, failure in critical metabolic checkpoints may lead to immune cell ...hyperactivation and tissue damage. Oxidative stress in autoimmune patients can also contribute to immune dysregulation and injury to the host. Recent insights into the immune cell metabolism signatures, specifically associated with systemic lupus erythematosus (SLE) and the consequences of heightened oxidative stress in patients, are discussed herein.
Glucose metabolism inhibitors, mechanistic target of rapamycin pathway modulators, and peroxisome proliferator-activated receptor gamma-activating compounds demonstrate therapeutic benefit in experimental models of lupus. Mitochondrial-derived reactive oxygen species (ROS) and molecular modifications induced by oxidative stress appear to be detrimental in lupus. Effective therapies tailored toward the reconfiguration of metabolic imbalances in lupus immune cells and the reduction of mitochondrial ROS production/availability are currently being tested.
A paucity of knowledge exists regarding the metabolic needs of a number of immune cells involved in the pathogenesis of SLE, including myeloid cells and B cells. Nonetheless, SLE-specific metabolic signatures have been identified and their specific targeting, along with mitochondrial ROS inhibitors/scavengers, could show therapeutic advantage in lupus patients.
The possibility of using magnesium based eutectic metal alloys as phase change material (PCM) for thermal energy storage (TES) in concentrated solar power (CSP) applications is analysed. An extensive ...thermophysical characterization of the Mg–51%Zn eutectic metal alloy between room temperature and melting temperature has been performed. The results are compared with some available data in the literature, and differences found are discussed. A comparison with pure, binary and ternary inorganic salts used as PCM is presented highlighting the advantages and disadvantages of the different systems. This alloy is proposed not only as a candidate for latent heat thermal energy storage for direct steam generation (DSG) in CSP applications but for high pressure and high energy steam processes as well. Reported data are essential for ensuing modelling and experimental reactor studies employing this alloy as a PCM for TES.
•Storage material for direct steam generation applications.•Metal alloy as PCM with high thermal conductivity.•Thermal energy storage for high pressure and high energy steam processes.
Systemic autoimmune diseases are characteristically associated with aberrant autoreactive innate and adaptive immune responses that lead to tissue damage and increased morbidity and mortality. ...Autoimmunity has been linked to alterations in the metabolic functions of immune cells (immunometabolism) and, more specifically, to mitochondrial dysfunction. Much has been written about immunometabolism in autoimmunity in general, so this Essay focuses on recent research into the role of mitochondrial dysfunction in the dysregulation of innate and adaptive immunity that is characteristic of systemic autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Enhancing the understanding of mitochondrial dysregulation in autoimmunity will hopefully contribute to accelerating the development of immunomodulatory treatments for these challenging diseases.
Type III IFN lambdas (IFN-λ) have recently been described as important mediators of immune responses at barrier surfaces. However, their role in autoimmune diseases such as systemic lupus ...erythematosus (SLE), a condition characterized by aberrant type I IFN signaling, has not been determined. Here, we identify a nonredundant role for IFN-λ in immune dysregulation and tissue inflammation in a model of TLR7-induced lupus. IFN-λ protein is increased in murine lupus and IFN-λ receptor (Ifnlr1) deficiency significantly reduces immune cell activation and associated organ damage in the skin and kidneys without effects on autoantibody production. Single-cell RNA sequencing in mouse spleen and human peripheral blood revealed that only mouse neutrophils and human B cells are directly responsive to this cytokine. Rather, IFN-λ activates keratinocytes and mesangial cells to produce chemokines that induce immune cell recruitment and promote tissue inflammation. These data provide insights into the immunobiology of SLE and identify type III IFNs as important factors for tissue-specific pathology in this disease.
Differences between female and male immunity may contribute to variations in response to infections and predisposition to autoimmunity. We previously reported that neutrophils from reproductive-age ...males are more immature and less activated than their female counterparts. To further characterize the mechanisms that drive differential neutrophil phenotypes, we performed RNA sequencing on circulating neutrophils from healthy adult females and males. Female neutrophils displayed significant up-regulation of type I IFN (IFN)-stimulated genes (ISGs). Single-cell RNA-sequencing analysis indicated that these differences are neutrophil specific, driven by a distinct neutrophil subset and related to maturation status. Neutrophil hyperresponsiveness to type I IFNs promoted enhanced responses to Toll-like receptor agonists. Neutrophils from young adult males had significantly increased mitochondrial metabolism compared to those from females and this was modulated by estradiol. Assessment of ISGs and neutrophil maturation genes in Klinefelter syndrome (47, XXY) males and in prepubescent children supported that differences in neutrophil phenotype between adult male and female neutrophils are hormonally driven and not explained by X chromosome gene dosage. Our results indicate that there are distinct sex differences in neutrophil biology related to responses to type I IFNs, immunometabolism, and maturation status that may have prominent functional and pathogenic implications.
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