- Zebrafish FGFR3 is a negative regulator of RLR pathway to decrease IFN expression. [Journal Article]
- FSFish Shellfish Immunol 2019 Jun 11
- Fibroblast growth factor receptor (FGFR) 3 is one of the four distinct membrane-spanning tyrosine kinases required for proper skeletal development. In fish, the role of FGFR3 is still unclear. In thi…
Fibroblast growth factor receptor (FGFR) 3 is one of the four distinct membrane-spanning tyrosine kinases required for proper skeletal development. In fish, the role of FGFR3 is still unclear. In this article, we reveal that zebrafish FGFR3 is a negative regulator of interferon (IFN) production in the innate immune response by suppressing the activity of TANK-binding kinase 1 (TBK1) in the process of virus infection. qPCR experiments demonstrate that the transcriptional level of cellular FGFR3 was upregulated by infection with spring viremia of carp virus (SVCV), indicating that FGFR3 might be involved in the process of host cell response to viral infection. Then, overexpression of FGFR3 significantly impeded the IFN promoter activity induced by a stimulator. In addition, the capabilities of a retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) system to activate IFN promoter were decreased during the overexpression of FGFR3. Subsequently, FGFR3 decreased the phosphorylation of interferon regulatory factor 3 (IRF3) and mediator of IRF3 activation (MITA) by TBK1. These findings suggest that zebrafish FGFR3 is a negative regulator of IFN by attenuating the kinase activity of TBK1, leading to the suppression of IFN expression.
- Obesity and aging affects skeletal muscle renin-angiotensin system and myosin heavy chain proportions in pre-diabetic Zucker rats. [Journal Article]
- JPJ Physiol Biochem 2019 Jun 13
- There is a gap in the knowledge regarding regulation of local renin-angiotensin system (RAS) in skeletal muscle during development of obesity and insulin resistance in vivo. This study evaluates the …
There is a gap in the knowledge regarding regulation of local renin-angiotensin system (RAS) in skeletal muscle during development of obesity and insulin resistance in vivo. This study evaluates the obesity- and age-related changes in the expression of local RAS components. Since RAS affects skeletal muscle remodelling, we also evaluated the muscle fibre type composition, defined by myosin heavy chain (MyHC) mRNAs and protein content. Gene expressions were determined by qPCR and/or Western blot analysis in musculus quadriceps of 3- and 8-month-old male obese Zucker rats and their lean controls. The enzymatic activity of aminopeptidase A (APA) was determined flourometrically. Activation of renin receptor (ReR)/promyelocytic leukaemia zinc finger (PLZF) negative feedback mechanism was observed in obesity. The expression of angiotensinogen and AT1 was downregulated by obesity, while neutral endopeptidase and AT2 expressions were upregulated in obese rats with aging. Skeletal muscle APA activity was decreased by obesity, which negatively correlated with the increased plasma APA activity and plasma cholesterol. The expression of angiotensin-converting enzyme (ACE) positively correlated with MyHC mRNAs characteristic for fast-twitch muscle fibres. The obesity- and age-related alterations in the expression of both classical and alternative RAS components suggest an onset of a new equilibrium between ACE/AngII/AT1 and ACE2/Ang1-7/Mas at lower level accompanied by increased renin/ReR/PLZF activation. Increased APA release from the skeletal muscle in obesity might contribute to increased plasma APA activity. There is a link between reduced ACE expression and altered muscle MyHC proportion in obesity and aging.
- StatPearls: Trigger Point Injection [BOOK]
- BOOKStatPearls Publishing: Treasure Island (FL)
- Myofascial trigger points are focal "knots" located in a taut band of skeletal muscle. These points are usually palpable and produce a characteristic referred pain upon palpation, along with pain loc…
Myofascial trigger points are focal "knots" located in a taut band of skeletal muscle. These points are usually palpable and produce a characteristic referred pain upon palpation, along with pain locally and occasionally a local twitch response, they can sometimes be associated with chronic disorders of the musculoskeletal system. Trigger points may be formed after acute trauma or by repeated micro-trauma, leading to stress on muscle fibers. Pathogenesis of trigger points is thought to be related to abnormal motor end-plates within a muscle where the motor and nociceptive nerves co-exist, with a component of enhanced central sensitization in the spinal cord. EMG studies have shown that trigger points exhibit spontaneous electrical activity, which suggests aberrant action potential generation. This concept is supported by histological evidence through muscle biopsies showing evidence of muscle hyper-contracture consistent with continuous sarcoplasmic reticulum calcium release secondary to neural activation and action potential generation. Patients may experience localized pain which can result in muscle tension and decreased range of motion in affected tissue. Muscles of the neck, shoulder, and pelvic girdle are commonly affected. Patients may experience tension headaches, temporomandibular joint pain, back pain, decreased shoulder range of motion, and stiffness as manifestations of their trigger points. Patients can have one or several trigger points throughout their musculoskeletal system. There are several approaches to the treatment of trigger points including ultrasonography, physical manipulation therapy, Spray and Stretch technique, and injections.
- Nearly half of all severe fetal anomalies can be detected by first-trimester screening in experts' hands. [Journal Article]
- JPJ Perinat Med 2019 Jun 07
- Objective To evaluate the detection rate of severe fetal anomalies at the first-trimester screening (FTS) and, vice versa, to evaluate the follow-up of pathological results at FTS at the time of mid-…
Objective To evaluate the detection rate of severe fetal anomalies at the first-trimester screening (FTS) and, vice versa, to evaluate the follow-up of pathological results at FTS at the time of mid-trimester screening (MTS) and throughout pregnancy and delivery in a partially selected population of low-risk pregnancies. Methods We conducted a prospective study on the detection of severe fetal anomalies at routine FTS in 9891 pregnant women with 10,294 fetuses between 11 + 0 and 13 + 6 weeks of gestation. The findings of FTS were compared to the results of MTS and pregnancy and neonatal outcomes. Only cases with severe fetal anomalies were taken for statistical analysis in this study. Results There were 232 cases of fetal anomaly altogether. At the time of FTS, sonographic anomalies were diagnosed in 113 cases and further ultrasound controls arranged. In four cases, fetal anomaly was not confirmed by MTS; in the remaining 109 cases, the sonographic anomaly seen at FTS was confirmed at MTS and in the course of pregnancy with a resulting sensitivity for fetal malformation at FTS of 47.8%, a specificity of 99.96%, a positive predictive value of 96.5% and a negative predictive value of 98.8%. Conclusion FTS can detect almost half of all severe fetal anomalies at an early stage of pregnancy with positive predictive values of 90% and more. Sensitivities varied depending on the organ system and reached the highest figures for anomalies of the heart, the abdomen, the spine and the skeletal system.
- Skin surface markers for stereotactic body radiation therapy of sternal metastasis. [Case Reports]
- RPRep Pract Oncol Radiother 2019 Jul-Aug; 24(4):322-324
- Stereotactic body radiation therapy is an effective and safe treatment modality for bone metastasis which allows clinicians to accurately target lesions to high doses while minimizing dose to organs …
Stereotactic body radiation therapy is an effective and safe treatment modality for bone metastasis which allows clinicians to accurately target lesions to high doses while minimizing dose to organs at risk. The commercially available CyberKnife® Xsight™ Spine Tracking System (Accuray, Inc., Sunnyvale, CA) tracks static skeletal structures and eliminates the need for implanted fiducial markers (FMs). However, the Xsight™ Spine Tracking system is not appropriate for bone metastases outside the spine, which are moving due to respiration and ,typically, FMs have to be implanted close to the lesion. These FMs will be used to track the dynamic target. For targets close to the surface, non-invasive fixation of the FMs to the patient's skin could be an option.
- Proteomic identification of elevated saliva kallikrein levels in the mdx-4cv mouse model of Duchenne muscular dystrophy. [Journal Article]
- BBBiochem Biophys Rep 2019; 18:100541
- Dystrophinopathies are multi-system disorders that affect the skeletal musculature, the cardio-respiratory system and the central nervous system. The systematic screening of suitable biofluids for re…
Dystrophinopathies are multi-system disorders that affect the skeletal musculature, the cardio-respiratory system and the central nervous system. The systematic screening of suitable biofluids for released or altered proteins promises new insights into the highly complex pathophysiology of X-linked muscular dystrophy. However, standard detection approaches using antibody-based assays often fail to reproducibly detect low-abundance protein isoforms in dilute biological fluids. In contrast, mass spectrometric screening approaches enable the proteome-wide identification of minor protein changes in biofluids. This report describes the findings from the comparative proteomic analysis of whole saliva samples from wild type versus the established mdx-4cv mouse model of highly progressive muscular dystrophy, focusing on the kallikrein protein family. Kallikrein-1 (Klk1) and 13 Klk1-related peptidases were identified in saliva and serum from normal mice. Comparative proteomics revealed elevated saliva levels of the Klk1-related peptidases Klk1-b1, Klk1-b5 and Klk-b22, as well as an increased Klk-1 concentration, which agrees with higher Klk-1 levels in serum from mdx-4cv mice. This indicates altered cellular signaling, extracellular matrix remodeling and an altered immune response in the mdx-4cv mouse, and establishes liquid biopsy procedures as suitable bioanalytical tools for the systematic survey of complex pathobiochemical changes in animal models of muscular dystrophy.
- Brain-derived neurotrophic factor, epigenetics in stroke skeletal muscle, and exercise training. [Journal Article]
- NGNeurol Genet 2019; 5(3):e331
- CONCLUSIONS: This is the first evidence that stroke hemiparesis reduces BDNF skeletal muscle expression, with our findings identifying methylation alterations on the DNA sequence of BDNF and BDNFAS gene. Preliminary results further indicate that AEX increases methylation in BDNFAS gene, which presumably could regulate the expression of BDNF.
- miR-522 stimulates TGF-β/Smad signaling pathway and promotes osteosarcoma tumorigenesis by targeting PPM1A. [Journal Article]
- JCJ Cell Biochem 2019 Jun 12
- Osteosarcoma (OS) is identified as an aggressive malignancy of the skeletal system and normally occurs among young people. It is well accepted that microRNAs are implicated in biological activities o…
Osteosarcoma (OS) is identified as an aggressive malignancy of the skeletal system and normally occurs among young people. It is well accepted that microRNAs are implicated in biological activities of diverse tumors. Although miR-522 has been proved to elicit oncogenic properties in a wide range of human cancers, the physiological function and latent mechanism of miR-522 in OS tumorigenesis remain largely to be probed. In the current study, we certified that miR-522 was highly expressed in OS cells and presented carcinogenic function by contributing to cell proliferation, migration, and EMT progression whereas dampening cell apoptosis. In addition, miR-522 provoked TGF-β/Smad pathway through targeting PPM1A. Finally, the results of mechanism experiments elucidated that miR-522 stimulated TGF-β/Smad pathway to induce the development of OS via targeting PPM1A, which exposed that miR-522 may become a promising curative target for OS patients.
- Evolution of the avian digital pattern. [Journal Article]
- SRSci Rep 2019 Jun 12; 9(1):8560
- Variation in digit number has occurred multiple times in the history of archosaur evolution. The five digits of dinosaur limbs were reduced to three in bird forelimbs, and were further reduced in the…
Variation in digit number has occurred multiple times in the history of archosaur evolution. The five digits of dinosaur limbs were reduced to three in bird forelimbs, and were further reduced in the vestigial forelimbs of the emu. Regulation of digit number has been investigated previously by examining genes involved in anterior-posterior patterning in forelimb buds among emu (Dromaius novaehollandiae), chicken (Gallus gallus) and zebra finch (Taeniopygia guttata). It was described that the expression of posterior genes are conserved among these three birds, whereas expression of anterior genes Gli3 and Alx4 varied significantly. Here we re-examined the expression pattern of Gli3 and Alx4 in the forelimb of emu, chicken and zebra finch. We found that Gli3 is expressed in the anterior region, although its range varied among species, and that the expression pattern of Alx4 in forelimb buds is broadly conserved in a stage-specific manner. We also found that the dynamic expression pattern of the BMP antagonist Gremlin1 (Grem1) in limb buds, which is critical for autopodial expansion, was consistent with the digital pattern of emu, chicken and zebra finch. Furthermore, in emu, variation among individuals was observed in the width of Grem1 expression in forelimb buds, as well as in the adult skeletal pattern. Our results support the view that the signalling system that regulates the dynamic expression of Grem1 in the limb bud contributes substantially to variations in avian digital patterns.
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- DRP1-mediated mitochondrial shape controls calcium homeostasis and muscle mass. [Journal Article]
- NCNat Commun 2019 Jun 12; 10(1):2576
- Mitochondrial quality control is essential in highly structured cells such as neurons and muscles. In skeletal muscle the mitochondrial fission proteins are reduced in different physiopathological co…
Mitochondrial quality control is essential in highly structured cells such as neurons and muscles. In skeletal muscle the mitochondrial fission proteins are reduced in different physiopathological conditions including ageing sarcopenia, cancer cachexia and chemotherapy-induced muscle wasting. However, whether mitochondrial fission is essential for muscle homeostasis is still unclear. Here we show that muscle-specific loss of the pro-fission dynamin related protein (DRP) 1 induces muscle wasting and weakness. Constitutive Drp1 ablation in muscles reduces growth and causes animal death while inducible deletion results in atrophy and degeneration. Drp1 deficient mitochondria are morphologically bigger and functionally abnormal. The dysfunctional mitochondria signals to the nucleus to induce the ubiquitin-proteasome system and an Unfolded Protein Response while the change of mitochondrial volume results in an increase of mitochondrial Ca2+ uptake and myofiber death. Our findings reveal that morphology of mitochondrial network is critical for several biological processes that control nuclear programs and Ca2+ handling.