Circulating myomiRs in Muscle Denervation: From Surgical to ALS Pathological Condition

ALS is a fatal neurodegenerative disease that is associated with muscle atrophy, motoneuron degeneration and denervation. Different mechanisms have been proposed to explain the pathogenesis of the disease; in this context, microRNAs have been described as biomarkers and potential pathogenetic factors for ALS. MyomiRs are microRNAs produced by skeletal muscle, and they play an important role in tissue homeostasis; moreover, they can be released in blood circulation in pathological conditions, including ALS. However, the functional role of myomiRs in muscle denervation has not yet been fully clarified. In this study, we analyze the levels of two myomiRs, namely miR-206 and miR-133a, in skeletal muscle and blood samples of denervated mice, and we demonstrate that surgical denervation reduces the expression of both miR-206 and miR-133a, while miR-206 but not miR-133a is upregulated during the re-innervation process. Furthermore, we quantify the levels of miR-206 and miR-133a in serum samples of two ALS mouse models, characterized by different disease velocities, and we demonstrate a different modulation of circulating myomiRs during ALS disease, according to the velocity of disease progression. Moreover, taking into account surgical and pathological denervation, we describe a different response to increasing amounts of circulating miR-206, suggesting a hormetic effect of miR-206 in relation to changes in neuromuscular communication.

Download Full-text

The Recent Understanding of the Neurotrophin's Role in Skeletal Muscle Adaptation

Journal of Biomedicine and Biotechnology ◽

10.1155/2011/201696 ◽

2011 ◽

Vol 2011 ◽

pp. 1-12 ◽

Cited By ~ 51

Author(s):

Kunihiro Sakuma ◽

Akihiko Yamaguchi

Keyword(s):

Skeletal Muscle ◽

Neuromuscular Disorders ◽

Muscle Fibers ◽

Brain Disorders ◽

Muscle Adaptation ◽

Bdnf Mrna ◽

Pathological Conditions ◽

Development And Differentiation ◽

And Function

This paper summarizes the various effects of neurotrophins in skeletal muscle and how these proteins act as potential regulators of the maintenance, function, and regeneration of skeletal muscle fibers. Increasing evidence suggests that this family of neurotrophic factors influence not only the survival and function of innervating motoneurons but also the development and differentiation of myoblasts and muscle fibers. Muscle contractions (e.g., exercise) produce BDNF mRNA and protein in skeletal muscle, and the BDNF seems to play a role in enhancing glucose metabolism and may act for myokine to improve various brain disorders (e.g., Alzheimer's disease and major depression). In adults with neuromuscular disorders, variations in neurotrophin expression are found, and the role of neurotrophins under such conditions is beginning to be elucidated. This paper provides a basis for a better understanding of the role of these factors under such pathological conditions and for treatment of human neuromuscular disease.

Download Full-text

Emerging role of extracellular vesicles in the regulation of skeletal muscle adaptation

Journal of Applied Physiology ◽

10.1152/japplphysiol.00914.2018 ◽

2019 ◽

Vol 127 (2) ◽

pp. 645-653 ◽

Cited By ~ 1

Author(s):

Ivan J. Vechetti

Keyword(s):

Skeletal Muscle ◽

Extracellular Vesicles ◽

Human Body ◽

Intercellular Communication ◽

Skeletal Muscle Mass ◽

Genetic Material ◽

Muscle Adaptation ◽

Pathological Conditions ◽

Isolation Methods

Extracellular vesicles (EVs) were initially characterized as “garbage bags” with the purpose of removing unwanted material from cells. It is now becoming clear that EVs mediate intercellular communication between distant cells through a transfer of genetic material, a process important to the systemic adaptation in physiological and pathological conditions. Although speculative, it has been suggested that the majority of EVs that make it into the bloodstream would be coming from skeletal muscle, since it is one of the largest organs in the human body. Although it is well established that skeletal muscle secretes peptides (currently known as myokines) into the bloodstream, the notion that skeletal muscle releases EVs is in its infancy. Besides intercellular communication and systemic adaptation, EV release could represent the mechanism by which muscle adapts to certain stimuli. This review summarizes the current understanding of EV biology and biogenesis and current isolation methods and briefly discusses the possible role EVs have in regulating skeletal muscle mass.

Download Full-text

Mechanisms of immune suppression by myeloid-derived suppressor cells: the role of interleukin-10 as a key immunoregulatory cytokine

Open Biology ◽

10.1098/rsob.200111 ◽

2020 ◽

Vol 10 (9) ◽

pp. 200111 ◽

Cited By ~ 2

Author(s):

Mahmoud Mohammad Yaseen ◽

Nizar Mohammad Abuharfeil ◽

Homa Darmani ◽

Ammar Daoud

Keyword(s):

Immune Responses ◽

Disease Progression ◽

Immune Activation ◽

Pathological Condition ◽

Suppressor Cells ◽

Interleukin 10 ◽

Myeloid Derived Suppressor Cells ◽

Chronic Infections ◽

Pathological Conditions

Chronic immune activation and inflammation are unwanted consequences of many pathological conditions, since they could lead to tissue damage and immune exhaustion, both of which can worsen the pathological condition status. In fact, the immune system is naturally equipped with immunoregulatory cells that can limit immune activation and inflammation. However, chronic activation of downregulatory immune responses is also associated with unwanted consequences that, in turn, could lead to disease progression as seen in the case of cancer and chronic infections. Myeloid-derived suppressor cells (MDSCs) are now considered to play a pivotal role in the pathogenesis of different inflammatory pathological conditions, including different types of cancer and chronic infections. As a potent immunosuppressor cell population, MDSCs can inhibit specific and non-specific immune responses via different mechanisms that, in turn, lead to disease persistence. One such mechanism by which MDSCs can activate their immunosuppressive effects is accomplished by secreting copious amounts of immunosuppressant molecules such as interleukin-10 (IL-10). In this article, we will focus on the pathological role of MDSC expansion in chronic inflammatory conditions including cancer, sepsis/infection, autoimmunity, asthma and ageing, as well as some of the mechanisms by which MDSCs/IL-10 contribute to the disease progression in such conditions.

Download Full-text

Effects of deoxynivalenol-feed contamination on circulating LPS in pigs

Innate Immunity ◽

10.1177/1753425919829552 ◽

2019 ◽

Vol 25 (3) ◽

pp. 168-175 ◽

Cited By ~ 1

Author(s):

Stefan Kahlert ◽

Lydia Renner ◽

Jeannette Kluess ◽

Jana Frahm ◽

Tanja Tesch ◽

...

Keyword(s):

Septic Shock ◽

Body Mass ◽

Systemic Inflammation ◽

Blood Circulation ◽

Liver Metabolism ◽

Additional Stress ◽

Serum Samples ◽

Low Concentration ◽

Feed Samples

Low concentration of LPS can be detected in healthy mammals without triggering systemic inflammation. Here we analysed the influence of the mycotoxin deoxynivalenol (DON) on very low LPS concentrations and the role of DON in the physiology of pigs challenged with high artificial LPS dosage mimicking septic shock. Pigs were fed for 29 d with DON-contaminated (4.59 mg/kg feed) or control feed. Samples of control animals showed 6.6 ± 13.5 pg/ml LPS in portal and 3.1 ± 7.6 pg/ml LPS in jugular serum samples. In the DON fed group, 3.4 ± 7.2 pg/ml and 0.6 ± 0.8 pg/ml were detected. The differences were statistically not significant, indicating that DON is not a trigger for enhanced LPS transfer into the blood circulation. Next, pigs were challenged with 7.5 µg LPS/kg body mass via portal or jugular route. The application route did not significantly influence the LPS concentration. We expected higher circulating LPS concentrations in the presence of DON due to the additional stress of liver metabolism and reduced liver capacity to remove LPS from circulation. This scenario is supported by tendency. In summary, we found that DON is unlikely to influence LPS transfer in the gut; DON likely reduces the capacity for LPS removal in septic shock conditions.

Download Full-text

The Hedgehog Signaling Pathway in the Ischemic Heart, Brain, and Skeletal Muscle

10.20944/preprints201808.0027.v1 ◽

2018 ◽

Author(s):

Igor Giarretta ◽

Eleonora Gaetani ◽

Paolo Tondi ◽

Takayuki Asahara ◽

Roberto Pola

Keyword(s):

Skeletal Muscle ◽

Signaling Pathway ◽

Tissue Regeneration ◽

Hedgehog Signaling ◽

Potential Role ◽

Pathological Conditions ◽

Ischemic Tissue ◽

Hh Signaling ◽

The Brain

Hedgehog (Hh) proteins are prototypical morphogens known to regulate epithelial/mesenchymal interactions during embryonic development. In addition to its pivotal role in embryogenesis, the Hh signaling pathway may be recapitulated in post-natal life in a number of physiological and pathological conditions, including ischemia. This review highlights the involvement of Hh signaling in ischemic tissue regeneration and angiogenesis, with particular attention to the heart, the brain, and the skeletal muscle. Updated information on the potential role of the Hh pathway as a therapeutic target in ischemic condition is also presented.

Download Full-text

Revealing histamine-sensible activity of Wood umbilical cord serum in experiments with ring segments of arteries and umbilical cord vein and with myometrium strips of pregnant women

Journal of obstetrics and women s diseases ◽

10.17816/jowd91123 ◽

2021 ◽

Vol 51 (4) ◽

pp. 55-60

Author(s):

V. I. Tsyrkin ◽

M. L. Sazanova ◽

S. A. Dvorianskiy ◽

S. V. Khlybova

Keyword(s):

Pregnant Women ◽

Umbilical Cord ◽

Blood Circulation ◽

Histamine Receptors ◽

Obstetric Complications ◽

Fetal Blood ◽

Pathological Conditions ◽

Cord Blood Serum ◽

Umbilical Cord Vein

In experiments with 60 segments of arteries and 46 segments of the umbilical cord vein of 24 newborns and 35 strips of myometrium of 12 pregnant women, the effect of 100-fold dilutions of cord blood serum (SPK-1: 100) on the contractile effects of histamine (0.01, 0.1 and 1 ϻg l ml). SPK-1: - 100 increased the vasoconstrictor and uterostimulating effects of histamine. H1-histaminosensitizing activity of SPK-1: 100 and the efficiency of activation of H1-histamine receptors of myocytes of the arteries and umbilical cord veins are increased in the presence of obstetric complications. A conclusion was made about the content of endogenous sensitizer H1-histamine receptors (ESGR) in the fetal blood, the level of which increases in the presence of obstetric complications, as well as the possible role of histamine and ESGR in the regulation of fetoplacental blood circulation in conditions of normal and pathological conditions.

Download Full-text

Emerging role for regulated in development and DNA damage 1 (REDD1) in the regulation of skeletal muscle metabolism

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00059.2016 ◽

2016 ◽

Vol 311 (1) ◽

pp. E157-E174 ◽

Cited By ~ 26

Author(s):

Bradley S. Gordon ◽

Jennifer L. Steiner ◽

David L. Williamson ◽

Charles H. Lang ◽

Scot R. Kimball

Keyword(s):

Skeletal Muscle ◽

Dna Damage ◽

Cellular Response ◽

Muscle Protein ◽

Muscle Metabolism ◽

Causative Role ◽

Skeletal Muscle Protein ◽

Skeletal Muscle Metabolism ◽

Pathological Conditions

Since its discovery, the protein regulated in development and DNA damage 1 (REDD1) has been implicated in the cellular response to various stressors. Most notably, its role as a repressor of signaling through the central metabolic regulator, the mechanistic target of rapamycin in complex 1 (mTORC1) has gained considerable attention. Not surprisingly, changes in REDD1 mRNA and protein have been observed in skeletal muscle under various physiological conditions (e.g., nutrient consumption and resistance exercise) and pathological conditions (e.g., sepsis, alcoholism, diabetes, obesity) suggesting a role for REDD1 in regulating mTORC1-dependent skeletal muscle protein metabolism. Our understanding of the causative role of REDD1 in skeletal muscle metabolism is increasing mostly due to the availability of genetically modified mice in which the REDD1 gene is disrupted. Results from such studies provide support for an important role for REDD1 in the regulation of mTORC1 as well as reveal unexplored functions of this protein in relation to other aspects of skeletal muscle metabolism. The goal of this work is to provide a comprehensive review of the role of REDD1 (and its paralog REDD2) in skeletal muscle during both physiological and pathological conditions.

Download Full-text

585 Increased expression of MafBx ubiquitin ligase mRNA in skeletal muscle after induction of heart failure: role of inflammatory cytokines

European Journal of Heart Failure Supplements ◽

10.1016/s1567-4215(05)80360-1 ◽

2005 ◽

Vol 4 (1) ◽

pp. 131-131

Keyword(s):

Heart Failure ◽

Skeletal Muscle ◽

Inflammatory Cytokines ◽

Ubiquitin Ligase

Download Full-text

TO DETERMINE THE ROLE OF CA125 IN THE DIAGNOSIS OF ACUTE APPENDICITIS

International Journal of Medical and Biomedical Studies ◽

10.32553/ijmbs.v4i7.1276 ◽

2020 ◽

Vol 4 (7) ◽

Author(s):

Vinod Kumar ◽

Bhupen Songra ◽

Richa Jain ◽

Deeksha Mehta

Keyword(s):

Acute Appendicitis ◽

Clinical Diagnosis ◽

Tertiary Care Hospital ◽

Tertiary Care ◽

Ca 125 ◽

Care Hospital ◽

Serum Samples ◽

Roc Curve Analysis ◽

Surgery Department

Background: the present study was under taken to determine the role of CA-125 in the diagnosis of acute appendicitis (AA), to prevent its complications and also in preventing negative appendicectomies in tertiary care hospital. Methods: The study was conducted at a tertiary care and research center between 01/03/2018 to 30/06/2019. Patients admitted to the surgery department with diagnosis of AA were considered for the study. After informed consent, a, standardized history was obtained as a case Performa. Serum samples from all the cases with clinical diagnosis of AA were obtained and stored. Only the cases with histopathologically approved AA were included in the study. Cases operated for clinical diagnosis of AA, but not histopathologically proven AA was not included in the study. CA125 levels in cases with definitive diagnosis of AA were measured. Results: In present study, ROC curve analysis revealed the sensitivity of 87.27 % and specificity of 90.91 % when the CA 125 cut-off value of > 16.8 was taken to diagnose acute appendicitis. AUC was 0.911 with a standard error of 0.0292. Conclusion: In this study we have observed that CA125 showed a positive correlation with acute appendicitis, that was statistically not significant (P>0.05). We didn’t evaluate the correlation with the disease severity. We consider that CA125 can be used as a marker in acute appendicitis cases although further research is still needed. Keywords: CA125, Acute Appendicitis, Surgery.

Download Full-text