creatine kinase activity
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PeerJ ◽  
2022 ◽  
Vol 10 ◽  
pp. e12708
Author(s):  
Łukasz Marcin Tota ◽  
Szczepan Stanisław Wiecha

The study aimed to evaluate changes in selected biochemical indicators among mixed martial arts competitors in subsequent periods of the training cycle. The research involved 12 mixed martial arts athletes aged 25.8 ± 4.2 years competing in the intermediate category. Selected somatic indicators were measured twice. Biochemical indicators were assessed five times during the 14-week study period. Serum concentrations of testosterone, cortisol, uric acid, myoglobin, total protein, interleukin 6, and tumor necrosis factor, as well as creatine kinase activity were determined. One hour after sparring completion, there were significant increases in cortisol (by 54.9%), uric acid (22.0%), myoglobin (565.0%), and interleukin 6 (280.3%) as compared with the values before the simulated fight. The highest creatine kinase activity (893.83 ± 139.31 U/l), as well as tumor necrosis factor (3.93 ± 0.71 pg/ml) and testosterone (5.83 ± 0.81 ng/ml) concentrations (p = 0.00) were recorded 24 hours after the simulation. Systematic observation of selected blood biochemical indicators in the training process periodization in mixed martial arts helps understand adaptive, compensatory, and regenerative mechanisms occurring in training athletes.


2022 ◽  
Author(s):  
Aijia Cai ◽  
Paul Schneider ◽  
Zeng-Ming Zheng ◽  
Justus P. Beier ◽  
Marcus Himmler ◽  
...  

Abstract Primary myoblasts (Mb) and adipose derived mesenchymal stromal cells (ADSC) can be co-cultured and myogenically differentiated in the process of skeletal muscle tissue engineering. Electrospun composite nanofiber scaffolds represent suitable matrices for tissue engineering of skeletal muscle, combining biocompatibility and stability. Although growth differentiation factor 11 (GDF11) has been proposed as a rejuvenating circulating factor, restoring skeletal muscle function in aging mice, some studies have also described a harming effect of GDF11.Therefore the aim of the study was to analyze the effect of GDF11 on co-cultures of Mb and ADSC on poly-ε-caprolacton (PCL)-collagen I-polyethylene oxide (PEO)-nanofibers.Human Mb were co-cultured with ADSC two-dimensionally (2D) as monolayers or three-dimensionally (3D) on aligned PCL-collagen I-PEO-nanofibers. Differentiation media were either serum-free with or without GDF11, or serum containing as in a conventional differentiation medium. Cell viability was higher after conventional myogenic differentiation compared to serum-free and serum-free + GDF11 differentiation as was creatine kinase activity. Immunofluorescence staining showed myosin heavy chain expression in all groups after 28 days of differentiation. Gene expression of myosin heavy chain (MYH2) increased after serum-free + GDF11 stimulation compared to serum-free stimulation alone. The results of this study show that PCL-collagen I-PEO-nanofibers represent a suitable matrix for 3D myogenic differentiation of Mb and ADSC. In this context, GDF11 seems to promote myogenic differentiation of Mb and ADSC co-cultures compared to serum-free differentiation without any evidence of a harming effect.


Cancers ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 27
Author(s):  
Raisa I. Krutilina ◽  
Hilaire Playa ◽  
Danielle L. Brooks ◽  
Luciana P. Schwab ◽  
Deanna N. Parke ◽  
...  

The oxygen-responsive hypoxia inducible factor (HIF)-1 promotes several steps of the metastatic cascade. A hypoxic gene signature is enriched in triple-negative breast cancers (TNBCs) and is correlated with poor patient survival. Inhibiting the HIF transcription factors with small molecules is challenging; therefore, we sought to identify genes downstream of HIF-1 that could be targeted to block invasion and metastasis. Creatine kinase brain isoform (CKB) was identified as a highly differentially expressed gene in a screen of HIF-1 wild type and knockout mammary tumor cells derived from a transgenic model of metastatic breast cancer. CKB is a cytosolic enzyme that reversibly catalyzes the phosphorylation of creatine, generating phosphocreatine (PCr) in the forward reaction, and regenerating ATP in the reverse reaction. Creatine kinase activity is inhibited by the creatine analog cyclocreatine (cCr). Loss- and gain-of-function genetic approaches were used in combination with cCr therapy to define the contribution of CKB expression or creatine kinase activity to cell proliferation, migration, invasion, and metastasis in ER-negative breast cancers. CKB was necessary for cell invasion in vitro and strongly promoted tumor growth and lung metastasis in vivo. Similarly, cyclocreatine therapy repressed cell migration, cell invasion, the formation of invadopodia and lung metastasis. Moreover, in common TNBC cell line models, the addition of cCr to conventional cytotoxic chemotherapy agents was either additive or synergistic to repress tumor cell growth.


Genes ◽  
2021 ◽  
Vol 12 (11) ◽  
pp. 1823
Author(s):  
Matthias Christen ◽  
Victoria Indzhova ◽  
Ling T. Guo ◽  
Vidhya Jagannathan ◽  
Tosso Leeb ◽  
...  

A 4-month-old, male Italian Greyhound with clinical signs of a neuromuscular disease was investigated. The affected dog presented with an abnormal short-strided gait, generalized muscle atrophy, and poor growth since 2-months of age. Serum biochemistry revealed a marked elevation in creatine kinase activity. Electrodiagnostic testing supported a myopathy. Histopathology of muscle biopsies confirmed a dystrophic phenotype with excessive variability in myofiber size, degenerating fibers, and endomysial fibrosis. A heritable form of congenital muscular dystrophy (CMD) was suspected, and a genetic analysis initiated. We sequenced the genome of the affected dog and compared the data to that of 795 control genomes. This search revealed a private homozygous nonsense variant in LAMA2, XM_022419950.1:c.3285G>A, predicted to truncate 65% of the open reading frame of the wild type laminin α2 protein, XP_022275658.1:p.(Trp1095*). Immunofluorescent staining performed on muscle cryosections from the affected dog confirmed the complete absence of laminin α2 in skeletal muscle. LAMA2 loss of function variants were shown to cause severe laminin α2-related CMD in humans, mouse models, and in one previously described dog. Our data together with current knowledge on other species suggest the LAMA2 nonsense variant as cause for the CMD phenotype in the investigated dog.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Luz Camacho-Castillo ◽  
Bryan V. Phillips-Farfán ◽  
Gabriela Rosas-Mendoza ◽  
Aidee Baires-López ◽  
Danira Toral-Ríos ◽  
...  

AbstractMetabolic disturbances are linked to neurodegenerative diseases such as Alzheimer disease (AD). However, the cellular mechanisms underlying this connection are unclear. We evaluated the role of oxidative stress (OS), during early metabolic syndrome (MetS), on amyloidogenic processes in a MetS rat model induced by sucrose. MetS caused OS damage as indicated by serum and hypothalamus lipid peroxidation and elevated serum catalase activity. Tissue catalase and superoxide dismutase activity were unchanged by MetS, but gene expression of nuclear factor erythroid-derived 2-like 2 (NFE2L2), which up-regulates expression of antioxidant enzymes, was higher. Expression of amyloid-β cleaving enzyme 1 (BACE-1) and amyloid precursor protein (APP), key proteins in the amyloidogenesis pathway, were slightly increased by sucrose-intake in the hippocampus and hypothalamus. Activation and expression of protein kinase B (PKB) and AMP-dependent protein kinase (AMPK), pivotal proteins in metabolism and energy signaling, were similarly affected in the hippocampus and hypothalamus of MetS rats. Brain creatine kinase activity decreased in brain tissues from rats with MetS, mainly due to irreversible oxidation. Chronic metformin administration partially reversed oxidative damage in sucrose-fed animals, together with increased AMPK activation; probably by modulating BACE-1 and NFE2L2. AMPK activation may be considered as a preventive therapy for early MetS and associated neurodegenerative diseases.


Life ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 994
Author(s):  
Sai Yarlagadda ◽  
Christina Kulis ◽  
Peter G. Noakes ◽  
Mark L. Smythe

Duchenne muscular dystrophy (DMD) is characterized by progressive muscle weakness and wasting due to the lack of dystrophin protein. The acute phase of DMD is characterized by muscle necrosis and increased levels of the pro-inflammatory mediator, prostaglandin D2 (PGD2). Inhibiting the production of PGD2 by inhibiting hematopoietic prostaglandin D synthase (HPGDS) may alleviate inflammation and decrease muscle necrosis. We tested our novel HPGDS inhibitor, PK007, in the mdx mouse model of DMD. Our results show that hindlimb grip strength was two-fold greater in the PK007-treated mdx group, compared to untreated mdx mice, and displayed similar muscle strength to strain control mice (C57BL/10ScSn). Histological analyses showed a decreased percentage of regenerating muscle fibers (~20% less) in tibialis anterior (TA) and gastrocnemius muscles and reduced fibrosis in the TA muscle in PK007-treated mice. Lastly, we confirmed that the DMD blood biomarker, muscle creatine kinase activity, was also reduced by ~50% in PK007-treated mdx mice. We conclude that our HPGDS inhibitor, PK007, has effectively reduced muscle inflammation and fibrosis in a DMD mdx mouse model.


2021 ◽  
Author(s):  
Raisa I. Krutilina ◽  
Hilaire C. Playa ◽  
Danielle L. Brooks ◽  
Luciana P. Schwab ◽  
Deanna N. Parke ◽  
...  

AbstractThe oxygen-responsive Hypoxia Inducible Factor (HIF)-1 promotes several steps of the metastatic cascade. A hypoxic gene signature is enriched in triple negative breast cancers (TNBCs), which correlates with poor patient survival. Since inhibiting the HIF transcription factors with small molecules is challenging, we sought to identify genes downstream of HIF-1 that could be targeted to block invasion and metastasis. Creatine kinase brain isoform (CKB) was identified as a highly differentially expressed gene in a screen of HIF-1 wild type and knockout mammary tumor cells derived from a transgenic model of metastatic breast cancer. CKB is a cytosolic enzyme that reversibly catalyzes the phosphorylation of creatine, generating phosphocreatine (PCr) in the forward reaction, and regenerating ATP in the reverse reaction. Creatine kinase activity is inhibited by the creatine analog cyclocreatine (cCr). Loss and gain of function genetic approaches were used in combination with cCr therapy to define the contribution of CKB expression or creatine kinase activity to cell proliferation, migration, invasion, and metastasis in ER-negative breast cancers. Although tumor cell-intrinsic CKB was not essential for breast tumor cell proliferation or cell migration in vitro, CKB was necessary for cell invasion in vitro and strongly promoted tumor growth and metastasis in vivo. Similarly, cyclocreatine therapy repressed cell migration, cell invasion, formation of invadopodia, and lung metastasis. Moreover, in common TNBC cell line models, the addition of cCr to conventional agents, paclitaxel (Taxol) or doxorubicin, was either additive or synergistic to repress tumor cell growth.


2021 ◽  
pp. 2486-2500
Author(s):  
Riyam Lateef Khalaf ◽  
Elham Majeed Ahmed ◽  
Thikra Hasan Mathkor ◽  
Hadeel Y. AL-Zubaidi

      The present work investigates the synthesis of silver nanoparticles (AgNPs) by a biological method using L.Rosa flower extract and silver nitrate as precursors. Optimum conditions of synthesis were studies, such as pH, temperature, concentration of extract, concentration of silver nitrate, and stability with time. Characterization of AgNPs was carried out using UV-visible Spectroscopy, Scanning Electron Microscopy, X-Ray Diffraction, Fourier Transform Infrared and Transmission Electron Microscopy. The biosynthesized AgNPs exhibited inhibitory effects on creatine kinase activity in the sera of patients with myocardial infarction, compared with control subjects. Thermodynamic and kinetic studies of creatine kinase were performed. Further studies on other biological activities were performed to exploit AgNPs full potential. In conclusions, the present study utilize a simple, cheap and environmentally green method to synthesize silver nanoparticles. This single step procedure is more suitable for large scale production as it is rapid and eliminates the elaborate processes employed in the other bio-based protocols (e.g. by using fungi and bacteria).  


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