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Journal of Cachexia, Sarcopenia and... Jun 2024Proliferating cancer cells shift their metabolism towards glycolysis, even in the presence of oxygen, to especially generate glycolytic intermediates as substrates for...
BACKGROUND
Proliferating cancer cells shift their metabolism towards glycolysis, even in the presence of oxygen, to especially generate glycolytic intermediates as substrates for anabolic reactions. We hypothesize that a similar metabolic remodelling occurs during skeletal muscle hypertrophy.
METHODS
We used mass spectrometry in hypertrophying C2C12 myotubes in vitro and plantaris mouse muscle in vivo and assessed metabolomic changes and the incorporation of the [U-C]glucose tracer. We performed enzyme inhibition of the key serine synthesis pathway enzyme phosphoglycerate dehydrogenase (Phgdh) for further mechanistic analysis and conducted a systematic review to align any changes in metabolomics during muscle growth with published findings. Finally, the UK Biobank was used to link the findings to population level.
RESULTS
The metabolomics analysis in myotubes revealed insulin-like growth factor-1 (IGF-1)-induced altered metabolite concentrations in anabolic pathways such as pentose phosphate (ribose-5-phosphate/ribulose-5-phosphate: +40%; P = 0.01) and serine synthesis pathway (serine: -36.8%; P = 0.009). Like the hypertrophy stimulation with IGF-1 in myotubes in vitro, the concentration of the dipeptide l-carnosine was decreased by 26.6% (P = 0.001) during skeletal muscle growth in vivo. However, phosphorylated sugar (glucose-6-phosphate, fructose-6-phosphate or glucose-1-phosphate) decreased by 32.2% (P = 0.004) in the overloaded muscle in vivo while increasing in the IGF-1-stimulated myotubes in vitro. The systematic review revealed that 10 metabolites linked to muscle hypertrophy were directly associated with glycolysis and its interconnected anabolic pathways. We demonstrated that labelled carbon from [U-C]glucose is increasingly incorporated by ~13% (P = 0.001) into the non-essential amino acids in hypertrophying myotubes, which is accompanied by an increased depletion of media serine (P = 0.006). The inhibition of Phgdh suppressed muscle protein synthesis in growing myotubes by 58.1% (P < 0.001), highlighting the importance of the serine synthesis pathway for maintaining muscle size. Utilizing data from the UK Biobank (n = 450 243), we then discerned genetic variations linked to the serine synthesis pathway (PHGDH and PSPH) and to its downstream enzyme (SHMT1), revealing their association with appendicular lean mass in humans (P < 5.0e-8).
CONCLUSIONS
Understanding the mechanisms that regulate skeletal muscle mass will help in developing effective treatments for muscle weakness. Our results provide evidence for the metabolic rewiring of glycolytic intermediates into anabolic pathways during muscle growth, such as in serine synthesis.
Topics: Glucose; Muscle, Skeletal; Animals; Mice; Humans; Hypertrophy; Muscle Fibers, Skeletal; Insulin-Like Growth Factor I; Metabolomics
PubMed: 38742477
DOI: 10.1002/jcsm.13468 -
Journal of Clinical Neurology (Seoul,... Mar 2022Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primarily attacks the respiratory system, but there are also several reports of the involvement of the...
BACKGROUND AND PURPOSE
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primarily attacks the respiratory system, but there are also several reports of the involvement of the central nervous system, with one of the manifestations being encephalopathy. The relatively new emergence of COVID-19 means that few studies have investigated the clinical profile of encephalopathy associated with this disease. This study aimed to determine the clinical profile, laboratory, and imaging results of encephalopathy associated with COVID-19.
METHODS
Three databases, namely PubMed/MEDLINE, Embase, and Scopus, were systematically searched for case reports and case series related to COVID-19-associated encephalopathy published from January 1, 2019 to July 20, 2020.
RESULTS
This review included 24 studies involving 33 cases. The most-reported neurological symptoms were disorientation/confusion (72.72%), decreased consciousness (54.54%), and seizures (27.27%). Laboratory examinations revealed increases in the C-reactive protein level (48.48%), the lactate dehydrogenase level (30.30%), and lymphopenia (27.27%). Brain imaging did not produce any pathological findings in 51.51% of the cases. Electroencephalography showed generalized slowing in 45.45% of the cases. Elevated protein (42.42%) and lymphocytosis (24.24%) were found in the cerebrospinal fluid. Fifteen patients were reportedly discharged from the hospital in a stable condition, while four cases of mortality were recorded.
CONCLUSIONS
The clinical, laboratory, and imaging findings in this review support the hypothesis that cerebral damage in COVID-19-associated encephalopathy is caused by cytokine-immune-mediated inflammation rather than by direct invasion.
PubMed: 35196749
DOI: 10.3988/jcn.2022.18.2.194 -
Journal of Advanced Research Jan 2018With the development of nanotechnology, silver nanoparticles (Ag-NPs) have become one of the most in-demand nanoparticles owing to their exponential number of uses in... (Review)
Review
With the development of nanotechnology, silver nanoparticles (Ag-NPs) have become one of the most in-demand nanoparticles owing to their exponential number of uses in various sectors. The increased use of Ag-NPs-enhanced products may result in an increased level of toxicity affecting both the environment and living organisms. Several studies have used different model cell lines to exhibit the cytotoxicity of Ag-NPs, and their underlying molecular mechanisms. This review aimed to elucidate different properties of Ag-NPs that are responsible for the induction of cellular toxicity along with the critical mechanism of action and subsequent defense mechanisms observed . Our results show that the properties of Ag-NPs largely vary based on the diversified synthesis processes. The physiochemical properties of Ag-NPs (e.g., size, shape, concentration, agglomeration, or aggregation interaction with a biological system) can cause impairment of mitochondrial function prior to their penetration and accumulation in the mitochondrial membrane. Thus, Ag-NPs exhibit properties that play a central role in their use as biocides along with their applicability in environmental cleaning. We herein report a current review of the synthesis, applicability, and toxicity of Ag-NPs in relation to their detailed characteristics.
PubMed: 30046482
DOI: 10.1016/j.jare.2017.10.008 -
Scientific Reports Mar 2021The aim of this systematic review was to perform qualitative and quantitative analysis on the toxic effects of chloroquine (CQ) and hydroxychloroquine (HCQ) on skeletal... (Meta-Analysis)
Meta-Analysis
The aim of this systematic review was to perform qualitative and quantitative analysis on the toxic effects of chloroquine (CQ) and hydroxychloroquine (HCQ) on skeletal muscles. We designed the study according to PRISMA guidelines. Studies for qualitative and quantitative analyses were selected according to the following inclusion criteria: English language; size of sample (> 5 patients), adult (> age of 18) patients, treated with CQ/HCQ for inflammatory diseases, and presenting and not presenting with toxic effects on skeletal muscles. We collected data published from 1990 to April 2020 using PubMed, Cochrane Library, EMBASE, and SciELO. Risk of bias for observational studies was assessed regarding the ROBIN-I scale. Studies with less than five patients (case reports) were selected for an additional qualitative analysis. We used the software Comprehensive Meta-Analysis at the confidence level of 0.05. We identified 23 studies for qualitative analysis (17 case-reports), and five studies were eligible for quantitative analysis. From case reports, 21 patients presented muscle weakness and confirmatory biopsy for CQ/HCQ induced myopathy. From observational studies, 37 patients out of 1,367 patients from five studies presented muscle weakness related to the use of CQ/HCQ, and 252 patients presented elevated levels of muscle enzymes (aldolase, creatine phosphokinase, and lactate dehydrogenase). Four studies presented data on 34 patients with confirmatory biopsy for drug-induced myopathy. No study presented randomized samples. The chronic use of CQ/HCQ may be a risk for drug-induced myopathy. There is substantiated need for proper randomized trials and controlled prospective studies needed to assess the clinical and subclinical stages of CQ/HCQ -induced muscle myopathy.
Topics: Adult; Aged; Creatine Kinase; Fructose-Bisphosphate Aldolase; Humans; Hydroxychloroquine; L-Lactate Dehydrogenase; Middle Aged; Muscle Weakness; Muscle, Skeletal; Observational Studies as Topic
PubMed: 33758324
DOI: 10.1038/s41598-021-86079-4 -
International Journal For Vitamin and... Oct 2022This systematic review and meta-analysis examined the effects of selected root plants (curcumin, ginseng, ginger and garlic) on markers of muscle damage and muscular... (Meta-Analysis)
Meta-Analysis Review
This systematic review and meta-analysis examined the effects of selected root plants (curcumin, ginseng, ginger and garlic) on markers of muscle damage and muscular performance measures following muscle-damaging protocols. We included 25 studies (parallel and crossover design) with 353 participants and used the PEDro scale to appraise each study. Forest plots were generated to report on standardised mean differences (SMD) and p-values at 24 and 48 hours following the muscle-damaging protocols. The meta-analysis showed that the supplemental (SUPP) condition showed significantly lower levels of indirect muscle damage markers (creatine kinase, lactate dehydrogenase and myoglobin) and muscle soreness at 24 hours and 48 hours (p < 0.01) than the placebo (PLA) condition. The inflammatory markers were significantly lower for the SUPP condition than the PLA condition at 24 hours (p = 0.02), although no differences were identified at 48 hours (p = 0.40). There were no significant differences in muscular performance measures between the SUPP and PLA conditions at 24 hours and 48 hours (p > 0.05) post-exercise. According to our qualitative data, a number of studies reported a reduction in oxidative stress (e.g., malondialdehyde, superoxide dismutase) with a concomitant upregulation of anti-oxidant status, although other studies showed no effects. Accordingly, selected root plants minimised the level of several biomarkers of muscle damage, inflammation and muscle soreness during periods of exercise-induced muscle damage. However, the benefits of these supplements in ameliorating oxidative stress, increasing anti-oxidant status and accelerating recovery of muscular performance appears equivocal, warranting further research in these outcome measures.
Topics: Antioxidants; Biomarkers; Creatine Kinase; Curcumin; Dietary Supplements; Exercise; Humans; Lactate Dehydrogenases; Malondialdehyde; Muscle, Skeletal; Myalgia; Myoglobin; Superoxide Dismutase
PubMed: 33196371
DOI: 10.1024/0300-9831/a000689 -
Sports Medicine (Auckland, N.Z.) Jul 2022Several studies have examined the effect of creatine monohydrate (CrM) on indirect muscle damage markers and muscle performance, although pooled data from several... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Several studies have examined the effect of creatine monohydrate (CrM) on indirect muscle damage markers and muscle performance, although pooled data from several studies indicate that the benefits of CrM on recovery dynamics are limited.
OBJECTIVE
This systematic review and meta-analysis determined whether the ergogenic effects of CrM ameliorated markers of muscle damage and performance following muscle-damaging exercises.
METHODS
In total, 23 studies were included, consisting of 240 participants in the CrM group (age 23.9 ± 10.4 years, height 178 ± 5 cm, body mass 76.9 ± 7.6 kg, females 10.4%) and 229 participants in the placebo group (age 23.7 ± 8.5 years, height 177 ± 5 cm, body mass 77.0 ± 6.6 kg, females 10.0%). These studies were rated as fair to excellent following the PEDro scale. The outcome measures were compared between the CrM and placebo groups at 24-36 h and 48-90 h following muscle-damaging exercises, using standardised mean differences (SMDs) and associated p-values via forest plots. Furthermore, sub-group analyses were conducted by separating studies into those that examined the effects of CrM as an acute training response (i.e., after one muscle-damaging exercise bout) and those that examined the chronic training response (i.e., examining the acute response after the last training session following several weeks of training).
RESULTS
According to the meta-analysis, the CrM group exhibited significantly lower indirect muscle damage markers (i.e., creatine kinase, lactate dehydrogenase, and/or myoglobin) at 48-90 h post-exercise for the acute training response (SMD - 1.09; p = 0.03). However, indirect muscle damage markers were significantly greater in the CrM group at 24 h post-exercise (SMD 0.95; p = 0.04) for the chronic training response. Although not significant, a large difference in indirect muscle damage markers was also found at 48 h post-exercise (SMD 1.24) for the chronic training response. The CrM group also showed lower inflammation for the acute training response at 24-36 h post-exercise and 48-90 h post-exercise with a large effect size (SMD - 1.38 ≤ d ≤ - 1.79). Similarly, the oxidative stress markers were lower for the acute training response in the CrM group at 24-36 h post-exercise and 90 h post-exercise, with a large effect size (SMD - 1.37 and - 1.36, respectively). For delayed-onset muscle soreness (DOMS), the measures were lower for the CrM group at 24 h post-exercise with a moderate effect size (SMD - 0.66) as an acute training response. However, the inter-group differences for inflammation, oxidative stress, and DOMS were not statistically significant (p > 0.05).
CONCLUSION
Overall, our meta-analysis demonstrated a paradoxical effect of CrM supplementation post-exercise, where CrM appears to minimise exercise-induced muscle damage as an acute training response, although this trend is reversed as a chronic training response. Thus, CrM may be effective in reducing the level of exercise-induced muscle damage following a single bout of strenuous exercises, although training-induced stress could be exacerbated following long-term supplementation of CrM. Although long-term usage of CrM is known to enhance training adaptations, whether the increased level of exercise-induced muscle damage as a chronic training response may provide potential mechanisms to enhance chronic training adaptations with CrM supplementation remains to be confirmed.
Topics: Adolescent; Adult; Biomarkers; Creatine; Dietary Supplements; Female; Humans; Inflammation; Muscle, Skeletal; Muscles; Myalgia; Young Adult
PubMed: 35218552
DOI: 10.1007/s40279-022-01640-z -
Oral Diseases Jan 2022To evaluate whether salivary lactate dehydrogenase (LDH) levels are increased in patients with oral cancer (OC) or oral potentially malignant disorders (OPMD) when... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To evaluate whether salivary lactate dehydrogenase (LDH) levels are increased in patients with oral cancer (OC) or oral potentially malignant disorders (OPMD) when compared to a healthy control group (CG).
MATERIAL AND METHODS
We conducted a comprehensive search of specialized databases (PubMed/MEDLINE, The Cochrane Library, Web of Science, Scopus, and OpenGrey), including observational analytical studies evaluating the salivary LDH levels (in UI/L or μ/L) in OC or OPMD patients and compared them with a CG.
RESULTS
Thirteen case-control studies were included. A total of 755 patients were evaluated, including 303 OC cases, 149 OPMD cases, and 303 controls. The meta-analysis showed that LDH levels were higher within the OC group than the CG (SMD 9.49; 95% CI 6.97-12; p = .00001). Patients with oral leucoplakia (SMD 11.67; 95% CI 1.01-22.33; p = .03) and oral submucous fibrosis (SMD 25.83; 95% CI -1.74-53.40; p = .07) also presented higher levels than the CG. In addition, OC patients had higher salivary LDH levels than oral leucoplakia patients (SMD 5.62; 95% CI 2.14-9.11; p = .002). Heterogeneity was high across all the evaluated studies.
CONCLUSIONS
The determination of salivary LDH may be a useful method for screening and tracking OC and OPMD, but new protocolized studies are required to establish precise cutoff values.
Topics: Humans; Leukoplakia, Oral; Mouth Diseases; Mouth Neoplasms; Oral Submucous Fibrosis; Precancerous Conditions
PubMed: 32881152
DOI: 10.1111/odi.13630 -
Frontiers in Oncology 2020To investigate the potential prognostic role of serum lactate dehydrogenase (LDH) in patients with urothelial carcinoma (UC) using the method of systematic review and...
To investigate the potential prognostic role of serum lactate dehydrogenase (LDH) in patients with urothelial carcinoma (UC) using the method of systematic review and meta-analysis. We searched PubMed, Embase, Cochrane Library, and Web of Science for eligible studies up to February 2020. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were used to estimate the relationship. A total of 14 studies including 4,009 patients with UC were incorporated. The results showed that a high pretreatment serum LDH was associated with an inferior overall survival (OS, HR 1.61, 95% CI 1.39-1.87, < 0.001), cancer-specific survival (CSS, HR 1.41, 95% CI 1.05-1.90, = 0.022), and disease-free survival (DFS, HR 1.64, 95% CI 1.04-2.59, = 0.034) in UC. Subgroup analyses identified that a high pretreatment serum LDH was associated with a poor OS (HR 1.97, 95% CI 1.02-3.81, = 0.042) and DFS (HR 1.64, 95% CI 1.04-2.59, = 0.034) in upper tract urothelial carcinoma, a short OS (HR 1.71, 95% CI 1.37-2.15, < 0.001) in urothelial carcinoma of bladder. Our findings indicated that a high level of pretreatment serum LDH was associated with inferior OS, CSS, and DFS in patients with UC. This biomarker can be an important factor incorporated into the prognostic models for UC.
PubMed: 32509573
DOI: 10.3389/fonc.2020.00677 -
European Journal of Clinical... Jun 2021COVID-19 is an infectious disease caused by SARS-CoV-2 associated with haematological manifestations (thrombolytic events). (Meta-Analysis)
Meta-Analysis
BACKGROUND
COVID-19 is an infectious disease caused by SARS-CoV-2 associated with haematological manifestations (thrombolytic events).
AIMS
Considering the high prevalence of the thrombotic scenarios associated with COVID-19, the aim of this study was to perform a systematic review of the available literature, concerning the relation of COVID-19 and the thrombotic events, and identify prognostic factors for these events.
MATERIALS & METHODS
PubMed, Web of Science and Scopus databases were searched. Independent reviewers conducted all flow diagram steps. For qualitative analysis, Oxford level of evidence and Newcastle-Ottawa scale were used in the eligible articles. For the prognostic factors, a meta-analysis was conducted to age, number of neutrophils and platelets, and levels of ferritin, C-reactive protein, lactate dehydrogenase and D-dimer. Publication bias was accessed by funnel plot and by trim-and-fill test. Trim-and-fill test was also applied to evaluate meta-analysis bias.
RESULTS
Twenty articles were included in the qualitative analysis, and 6 articles were included in the meta-analysis. Case-control studies showed bias related to exposure, and the main bias in cohort studies were related to selection and outcome. All articles received score 4 for the level of evidence. Hypertension and diabetes were the comorbidities more frequently associated with thrombolytic events. Significant results were found regarding D-dimer (P < .0001) and age (P = .0202) for thrombotic events in patients diagnosed with COVID-19.
CONCLUSION
Patients older than 60 years, with hypertension, diabetes and D-Dimer values above 3.17 µg/mL, can be considered prognostic factors for developing thrombotic events due to COVID-19.
Topics: Age Factors; COVID-19; Diabetes Mellitus; Fibrin Fibrinogen Degradation Products; Humans; Hypertension; Intracranial Thrombosis; Pulmonary Embolism; Risk Factors; SARS-CoV-2; Thrombosis; Venous Thromboembolism; Venous Thrombosis
PubMed: 33772772
DOI: 10.1111/eci.13559 -
Current Opinion in Allergy and Clinical... Oct 2015A large number of studies investigating the correlation between severity of atopic dermatitis and various biomarkers have been published over the past decades. The aim... (Meta-Analysis)
Meta-Analysis Review
PURPOSE OF REVIEW
A large number of studies investigating the correlation between severity of atopic dermatitis and various biomarkers have been published over the past decades. The aim of this review was to identify, evaluate and synthesize the evidence examining the correlation of biomarkers with disease severity in atopic dermatitis patients, something that has not been performed previously.
RECENT FINDINGS
Three electronic databases were systematically searched and relevant studies were selected for inclusion. A total of 222 articles, reporting on 115 different biomarkers in 30 063 patients, were critically appraised. Studies were divided into two main groups. The first group consisted of longitudinal randomized controlled trials and cohort studies, which reported measurements at multiple time points. The second contained cross-sectional studies that reported only one measurement per patient. Out of 222 articles, 108 articles reported sufficient data for meta-analysis. Only four biomarkers were eligible for meta-analysis in the longitudinal group, and nine in the cross-sectional group.
SUMMARY
Serum thymus and activation-regulated chemokine (TARC) was found to be the most reliable biomarker studied, showing pooled correlation coefficients of 0.60 (95% CI 0.48-0.70) and 0.64 (95% CI 0.57-0.70) in longitudinal and cross-sectional studies, respectively. Additional biomarkers that could prove useful but require additional research include serum cutaneous T-cell attracting chemokine (CTACK), sE-selectin, macrophage-derived chemokine (MDC), lactate dehydrogenase (LDH) and interleukin (IL)-18.
Topics: Biomarkers; Chemokine CCL17; Chemokine CCL22; Chemokine CCL27; Dermatitis, Atopic; E-Selectin; Humans; Interleukin-18; L-Lactate Dehydrogenase
PubMed: 26226355
DOI: 10.1097/ACI.0000000000000198