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  1. Article ; Online: MyD88 and not TRIF knockout is sufficient to abolish LPS‐induced inflammatory responses in bone‐derived macrophages

    Reynoso, Marinaliz / Hobbs, Stuart / Kolb, Alexander L. / Matheny, Ronald W., Jr / Roberts, Brandon M.

    FEBS Letters. 2023 May, v. 597, no. 9 p.1225-1232

    2023  

    Abstract: Macrophages play an important role in the response to infection and/or repair of injury in tissues. To examine the NF‐κB pathway in response to an inflammatory stimulus, we used wild‐type bone‐marrow‐derived macrophages (BMDMs) or BMDMs with knockout (KO) ...

    Abstract Macrophages play an important role in the response to infection and/or repair of injury in tissues. To examine the NF‐κB pathway in response to an inflammatory stimulus, we used wild‐type bone‐marrow‐derived macrophages (BMDMs) or BMDMs with knockout (KO) of myeloid differentiation primary response 88 (MyD88) and/or Toll/interleukin‐1 receptor domain‐containing adapter‐inducing interferon‐β (TRIF) via CRISPR/Cas9. Following treatment of BMDMs with lipopolysaccharide (LPS) to induce an inflammatory response, translational signalling of NF‐κB was quantified via immunoblot and cytokines were measured. Our findings reveal that MyD88 KO, but not TRIF KO, decreased LPS‐induced NF‐κB signalling, and 10% expression of basal MyD88 expression was sufficient to partially rescue the abolished inflammatory cytokine secretion observed upon MyD88 KO.
    Keywords CRISPR-Cas systems ; cytokines ; inflammation ; lipopolysaccharides ; macrophages ; secretion
    Language English
    Dates of publication 2023-05
    Size p. 1225-1232.
    Publishing place John Wiley & Sons, Ltd
    Document type Article ; Online
    Note JOURNAL ARTICLE
    ZDB-ID 212746-5
    ISSN 1873-3468 ; 0014-5793
    ISSN (online) 1873-3468
    ISSN 0014-5793
    DOI 10.1002/1873-3468.14616
    Database NAL-Catalogue (AGRICOLA)

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  2. Article ; Online: Insulin-like growth factor-I biocompartmentalization across blood, interstitial fluid and muscle, before and after 3 months of chronic resistance exercise.

    Sterczala, Adam J / Pierce, Joseph R / Barnes, Brian R / Urso, Maria L / Matheny, Ronald W / Scofield, Dennis E / Flanagan, Shawn D / Maresh, Carl M / Zambraski, Edward J / Kraemer, William J / Nindl, Bradley C

    Journal of applied physiology (Bethesda, Md. : 1985)

    2022  Volume 133, Issue 1, Page(s) 170–182

    Abstract: This investigation examined the influence of 12-week ballistic resistance training programs on the IGF-I system in circulation, interstitial fluid, and skeletal muscle, at rest and in response to acute exercise. Seventeen college-aged subjects (11 women/ ... ...

    Abstract This investigation examined the influence of 12-week ballistic resistance training programs on the IGF-I system in circulation, interstitial fluid, and skeletal muscle, at rest and in response to acute exercise. Seventeen college-aged subjects (11 women/6 men; 21.7 ± 3.7 yr) completed an acute ballistic exercise bout before and after the training program. Blood samples were collected pre-, mid-, and postexercise and analyzed for serum total IGF-I, free IGF-I, and IGF binding proteins (IGFBPs) 1-4. Dialysate and interstitial free IGF-I were analyzed in vastus lateralis (VL) interstitial fluid collected pre- and postexercise via microdialysis. Pre- and postexercise VL muscle biopsies were analyzed for IGF-I protein expression, IGF-I receptor phosphorylation (p-IGF-IR), and AKT phosphorylation (p-AKT). Following training, basal serum IGF-I, free IGF-I, IGFBP-2, and IGFBP-3 decreased whereas IGFBP-1 and IGFBP-4 increased. Training reduced basal dialysate and interstitial free IGF-I but had no effect on basal skeletal muscle IGF-I, p-IGF-IR, or p-AKT. Acute exercise elicited transient changes in IGF-I system concentrations and downstream anabolic signaling both pre- and posttraining; training did not affect this acute exercise response. Posttraining, acute exercise-induced changes in dialysate/interstitial free IGF-I were strongly correlated with the changes in intramuscular IGF-I expression, p-IGF-IR, and p-AKT. The divergent influence of resistance training on circulating/interstitial and skeletal muscle IGF-I demonstrates the importance of concurrent, multiple biocompartment analysis when examining the IGF-I system. As training elicited muscle hypertrophy, these findings indicate that IGF-I's anabolic effects on skeletal muscle are mediated by local, rather than systemic mechanisms.
    MeSH term(s) Exercise/physiology ; Extracellular Fluid/metabolism ; Female ; Humans ; Insulin-Like Growth Factor I/metabolism ; Male ; Muscle, Skeletal/physiology ; Proto-Oncogene Proteins c-akt ; Resistance Training ; Young Adult
    Chemical Substances IGF1 protein, human ; Insulin-Like Growth Factor I (67763-96-6) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1)
    Language English
    Publishing date 2022-06-09
    Publishing country United States
    Document type Journal Article
    ZDB-ID 219139-8
    ISSN 1522-1601 ; 0021-8987 ; 0161-7567 ; 8750-7587
    ISSN (online) 1522-1601
    ISSN 0021-8987 ; 0161-7567 ; 8750-7587
    DOI 10.1152/japplphysiol.00592.2021
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  3. Article ; Online: Transcriptional and Chromatin Dynamics of Muscle Regeneration after Severe Trauma

    Carlos A. Aguilar / Ramona Pop / Anna Shcherbina / Alain Watts / Ronald W. Matheny Jr. / Davide Cacchiarelli / Woojin M. Han / Eunjung Shin / Shadi A. Nakhai / Young C. Jang / Christopher T. Carrigan / Casey A. Gifford / Melissa A. Kottke / Marcella Cesana / Jackson Lee / Maria L. Urso / Alexander Meissner

    Stem Cell Reports, Vol 7, Iss 5, Pp 983-

    2016  Volume 997

    Abstract: Following injury, adult skeletal muscle undergoes a well-coordinated sequence of molecular and physiological events to promote repair and regeneration. However, a thorough understanding of the in vivo epigenomic and transcriptional mechanisms that ... ...

    Abstract Following injury, adult skeletal muscle undergoes a well-coordinated sequence of molecular and physiological events to promote repair and regeneration. However, a thorough understanding of the in vivo epigenomic and transcriptional mechanisms that control these reparative events is lacking. To address this, we monitored the in vivo dynamics of three histone modifications and coding and noncoding RNA expression throughout the regenerative process in a mouse model of traumatic muscle injury. We first illustrate how both coding and noncoding RNAs in tissues and sorted satellite cells are modified and regulated during various stages after trauma. Next, we use chromatin immunoprecipitation followed by sequencing to evaluate the chromatin state of cis-regulatory elements (promoters and enhancers) and view how these elements evolve and influence various muscle repair and regeneration transcriptional programs. These results provide a comprehensive view of the central factors that regulate muscle regeneration and underscore the multiple levels through which both transcriptional and epigenetic patterns are regulated to enact appropriate repair and regeneration.
    Keywords Medicine (General) ; R5-920 ; Biology (General) ; QH301-705.5
    Language English
    Publishing date 2016-11-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Nonsteroidal Anti-Inflammatory Drug Prescriptions Are Associated With Increased Stress Fracture Diagnosis in the US Army Population.

    Hughes, Julie M / McKinnon, Craig J / Taylor, Kathryn M / Kardouni, Joseph R / Bulathsinhala, Lakmini / Guerriere, Katelyn I / Popp, Kristin L / Bouxsein, Mary L / Proctor, Susan P / Matheny, Ronald W

    Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research

    2018  Volume 34, Issue 3, Page(s) 429–436

    Abstract: Stress fractures are common in military personnel and endurance athletes, and nonsteroidal anti-inflammatory drug (NSAID) use is widespread in these populations. NSAIDs inhibit prostaglandin synthesis, which blunts the anabolic response of bone to ... ...

    Abstract Stress fractures are common in military personnel and endurance athletes, and nonsteroidal anti-inflammatory drug (NSAID) use is widespread in these populations. NSAIDs inhibit prostaglandin synthesis, which blunts the anabolic response of bone to physical activity and could therefore increase risk of stress fracture. The objective of this study was to determine whether prescribed NSAIDs were associated with stress fracture diagnoses among US Army soldiers. We also aimed to establish whether acetaminophen, an analgesic alternative to NSAIDs, was associated with stress fracture risk. A nested case-control study was conducted using data from the Total Army Injury and Health Outcomes Database from 2002 to 2011 (n = 1,260,168). We identified soldiers with a diagnosis of stress fracture (n = 24,146) and selected 4 controls per case matched on length of military service (n = 96,584). We identified NSAID and acetaminophen prescriptions 180 to 30 days before injury (or match date). We also identified soldiers who participated in basic combat training (BCT), a 10-week period of heightened physical activity at the onset of Army service. Among these individuals, we identified 9088 cases and 36,878 matched controls. Conditional logistic regression was used to calculate incident rate ratios (RR) for stress fracture with adjustment for sex. NSAID prescription was associated with a 2.9-fold increase (RR = 2.9, 95% confidence interval [CI] 2.8-2.9) and acetaminophen prescription with a 2.1-fold increase (RR = 2.1, 95% CI 2.0-2.2) in stress fracture risk within the total Army population. The risk was more than 5-fold greater in soldiers prescribed NSAIDs (RR = 5.3, 95% CI 4.9-5.7) and more than 4-fold greater in soldiers prescribed acetaminophen (RR = 4.4, 95% CI 3.9-4.9) during BCT. Our results reveal an association between NSAID and acetaminophen prescriptions and stress fracture risk, particularly during periods of heightened physical activity. Prospective observational studies and randomized controlled trials are needed to support these findings before clinical recommendations can be made. © 2018 American Society for Bone and Mineral Research.
    MeSH term(s) Adult ; Anti-Inflammatory Agents, Non-Steroidal/adverse effects ; Drug Prescriptions ; Female ; Fractures, Stress/chemically induced ; Fractures, Stress/diagnosis ; Humans ; Male ; Military Personnel ; United States ; Young Adult
    Chemical Substances Anti-Inflammatory Agents, Non-Steroidal
    Language English
    Publishing date 2018-12-10
    Publishing country United States
    Document type Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 632783-7
    ISSN 1523-4681 ; 0884-0431
    ISSN (online) 1523-4681
    ISSN 0884-0431
    DOI 10.1002/jbmr.3616
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  5. Article ; Online: Characterization of growth hormone disulfide-linked molecular isoforms during post-exercise release vs nocturnal pulsatile release reveals similar milieu composition.

    Nindl, Bradley C / Eagle, Shawn R / Matheny, Ronald W / Martin, Brian J / Rarick, Kevin R / Pierce, Joseph R / Sharp, Marilyn A / Kellogg, Mark D / Patton, John F

    Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society

    2018  Volume 42-43, Page(s) 102–107

    Abstract: Objective: To characterize the influence of mode (aerobic/resistance) and volume of exercise (moderate/high) on circulating GH immediately post-exercise as well as following the onset of sleep.: Design: This study used repeated measures in which ... ...

    Abstract Objective: To characterize the influence of mode (aerobic/resistance) and volume of exercise (moderate/high) on circulating GH immediately post-exercise as well as following the onset of sleep.
    Design: This study used repeated measures in which subjects randomly completed 5 separate conditions: control (no exercise), moderate volume resistance exercise (MR), high-volume resistance exercise (HR), moderate volume aerobic exercise (MA), and high volume aerobic exercise (HA).
    Methods: Subjects had two overnight stays on each of the 5 iterations. Serial blood draws began as soon as possible after the completion of the exercise session. Blood was obtained every 20 min for 24-h. GH was measured using a chemiluminescent immunoassay. Pooled samples representing post exercise (PE) and first nocturnal pulse (NP) were divided into two aliquots. One of these aliquots was chemically reduced by adding 10 mM glutathione (GSH) to break down disulfide-linked aggregates.
    Results: No differences were observed when pooling GH response at post-exercise (2.02 ± 0.21) and nocturnal pulse (2.63 ± 0.51; p = .32). Pairwise comparisons revealed main effect differences between controls (1.19 ± 0.29) and both MA (2.86 ± 0.31; p = .009) and HA (3.73 ± 0.71; p = .001). Both MA (p = .049) and HA (p = .035) responses were significantly larger than the MR stimulus (1.96 ± 0.28). With GSH reduction, controls significantly differed from MA (p = .018) and HA (p = .003) during PE, but only differed from HA (p = .003) during NP.
    Conclusions: This study demonstrated similar GH responses to exercise and nocturnal pulse, indicating that mode and intensity of exercise does not proportionately affect GH dimeric isoform concentration.
    MeSH term(s) Disulfides/chemistry ; Disulfides/metabolism ; Exercise/physiology ; Human Growth Hormone/chemistry ; Human Growth Hormone/metabolism ; Humans ; Muscle Strength/physiology ; Protein Isoforms ; Resistance Training ; Sleep/physiology
    Chemical Substances Disulfides ; Protein Isoforms ; Human Growth Hormone (12629-01-5)
    Language English
    Publishing date 2018-10-19
    Publishing country Scotland
    Document type Comparative Study ; Journal Article ; Randomized Controlled Trial
    ZDB-ID 1436781-6
    ISSN 1532-2238 ; 1096-6374
    ISSN (online) 1532-2238
    ISSN 1096-6374
    DOI 10.1016/j.ghir.2018.10.003
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  6. Article ; Online: Risk of Stress Fracture Varies by Race/Ethnic Origin in a Cohort Study of 1.3 Million US Army Soldiers.

    Bulathsinhala, Lakmini / Hughes, Julie M / McKinnon, Craig J / Kardouni, Joseph R / Guerriere, Katelyn I / Popp, Kristin L / Matheny, Ronald W / Bouxsein, Mary L

    Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research

    2017  Volume 32, Issue 7, Page(s) 1546–1553

    Abstract: Stress fractures (SF) are common and costly injuries in military personnel. Risk for SF has been shown to vary with race/ethnicity. Previous studies report increased SF risk in white and Hispanic Soldiers compared with black Soldiers. However, these ... ...

    Abstract Stress fractures (SF) are common and costly injuries in military personnel. Risk for SF has been shown to vary with race/ethnicity. Previous studies report increased SF risk in white and Hispanic Soldiers compared with black Soldiers. However, these studies did not account for the large ethnic diversity in the US military. We aimed to identify differences in SF risk among racial/ethnic groups within the US Army. A retrospective cohort study was conducted using data from the Total Army Injury and Health Outcomes Database from 2001 until 2011. SF diagnoses were identified from ICD-9 codes. We used Cox-proportional hazard models to calculate time to SF by racial/ethnic group after adjusting for age, education, and body mass index. We performed a sex-stratified analysis to determine whether the ethnic variation in SF risk depends on sex. We identified 21,549 SF cases in 1,299,332 Soldiers (more than 5,228,525 person-years of risk), revealing an overall incidence rate of 4.12 per 1000 person-years (7.47 and 2.05 per 1000 person-years in women and men, respectively). Using non-Hispanic blacks as the referent group, non-Hispanic white women had the highest risk of SF, with a 92% higher risk of SF than non-Hispanic black women (1.92 [1.81-2.03]), followed by American Indian/Native Alaskan women (1.72 [1.44-1.79]), Hispanic women (1.65 [1.53-1.79]), and Asian women (1.32 [1.16-1.49]). Similarly, non-Hispanic white men had the highest risk of SF, with a 59% higher risk of SF than non-Hispanic black men (1.59 [1.50-1.68]), followed by Hispanic men (1.19 [1.10-1.29]). When examining the total US Army population, we found substantial differences in the risk of stress fracture among racial/ethnic groups, with non-Hispanic white Soldiers at greatest risk and Hispanic, American Indian/Native Alaskan, and Asian Soldiers at an intermediate risk. Additional studies are needed to determine the factors underlying these race- and ethnic-related differences in stress fracture risk. © 2017 American Society for Bone and Mineral Research.
    Language English
    Publishing date 2017-07
    Publishing country United States
    Document type Journal Article
    ZDB-ID 632783-7
    ISSN 1523-4681 ; 0884-0431
    ISSN (online) 1523-4681
    ISSN 0884-0431
    DOI 10.1002/jbmr.3131
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  7. Article ; Online: Bone formation is suppressed with multi-stressor military training.

    Hughes, Julie M / Smith, Martha A / Henning, Paul C / Scofield, Dennis E / Spiering, Barry A / Staab, Jeffery S / Hydren, Jay R / Nindl, Bradley C / Matheny, Ronald W

    European journal of applied physiology

    2014  Volume 114, Issue 11, Page(s) 2251–2259

    Abstract: Purpose: To determine the effects of US Army Ranger Training, an 8-week, physically demanding program (energy expenditure of 2,500-4,500 kcal/day) with energy restriction (deficit of 1,000-4,000 kcal/day) and sleep deprivation (<4 h sleep/night) on bone ...

    Abstract Purpose: To determine the effects of US Army Ranger Training, an 8-week, physically demanding program (energy expenditure of 2,500-4,500 kcal/day) with energy restriction (deficit of 1,000-4,000 kcal/day) and sleep deprivation (<4 h sleep/night) on bone metabolism.
    Methods: Blood was collected from 22 men (age 24 ± 4 years) before and after training. Follow-up measurements were made in a subset of 8 subjects between 2 and 6 weeks after training. Serum was analyzed for bone formation biomarkers [bone alkaline phosphatase (BAP) and osteocalcin (OCN)], bone resorption biomarkers [C-telopeptide cross-links of type I collagen (CTX) and tartrate-resistant acid phosphatase (TRAP5b)], calcium, parathyroid hormone (PTH), and vitamin D 25(OH)D increased significantly by 37.3 ± 45.2 % with training [corrected]. A repeated-measures ANOVA with time as the only factor was used to analyze data on the subset of 8 subjects who completed follow-up data collection.
    Results: BAP and OCN significantly decreased by 22.8 ± 15.5% (pre 41.9 ± 10.1; post 31.7 ± 7.8 ng/ml) and 21.0 ± 23.3% (pre 15.0 ± 3.5; post 11.3 ± 2.1 ng/ml), respectively, with training, suggesting suppressed bone formation. OCN returned to baseline, while BAP remained suppressed 2-6 weeks post-training. TRAP5b significantly increased by 57.5 ± 51.6% (pre 3.0 ± 0.9; post 4.6 ± 1.4 ng/ml) from pre- to post-training, suggesting increased bone resorption, and returned to baseline 2-6 weeks post-training. PTH Increased significantly by 37.3 ± 45.2% with training. No changes in CTX, calcium, or PTH were detected.
    Conclusions: These data indicate that multi-stressor military training results in increased bone resorption and suppressed bone formation, with recovery of bone metabolism 2-6 weeks after completion of training.
    MeSH term(s) Acid Phosphatase/blood ; Adult ; Alkaline Phosphatase/blood ; Bone Resorption/etiology ; Caloric Restriction/adverse effects ; Collagen Type I/blood ; Humans ; Isoenzymes/blood ; Male ; Military Personnel ; Osteocalcin/blood ; Osteogenesis ; Parathyroid Hormone/blood ; Peptides/blood ; Resistance Training/adverse effects ; Sleep Deprivation/complications ; Stress, Physiological ; Tartrate-Resistant Acid Phosphatase ; Vitamin D/blood
    Chemical Substances Collagen Type I ; Isoenzymes ; Parathyroid Hormone ; Peptides ; collagen type I trimeric cross-linked peptide ; Osteocalcin (104982-03-8) ; Vitamin D (1406-16-2) ; Alkaline Phosphatase (EC 3.1.3.1) ; Acid Phosphatase (EC 3.1.3.2) ; Tartrate-Resistant Acid Phosphatase (EC 3.1.3.2)
    Language English
    Publishing date 2014-07-16
    Publishing country Germany
    Document type Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 124793-1
    ISSN 1439-6327 ; 1432-1025 ; 0301-5548 ; 1439-6319
    ISSN (online) 1439-6327 ; 1432-1025
    ISSN 0301-5548 ; 1439-6319
    DOI 10.1007/s00421-014-2950-6
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