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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 -
Osong Public Health and Research... Oct 2020This review compared coronavirus disease 2019 (COVID-19) laboratory findings, comorbidities, and clinical outcomes in patients from the general population versus medical... (Review)
Review
COVID-19 Patients: A Systematic Review and Meta-Analysis of Laboratory Findings, Comorbidities, and Clinical Outcomes Comparing Medical Staff versus the General Population.
This review compared coronavirus disease 2019 (COVID-19) laboratory findings, comorbidities, and clinical outcomes in patients from the general population versus medical staff to aid diagnosis of COVID-19 in a more timely, efficient, and accurate way. Electronic databases were searched up to 23 March, 2020. The initial search yielded 6,527 studies. Following screening, 24 studies were included [18 studies (11,564 cases) of confirmed COVID-19 cases in the general public, and 6 studies (394 cases) in medical staff] in this review. Significant differences were observed in white blood cell counts ( < 0.001), lymphocyte counts ( < 0.001), platelet counts ( = 0.04), procalcitonin levels ( < 0.001), lactate dehydrogenase levels ( < 0.001), and creatinine levels ( = 0.03) when comparing infected medical staff with the general public. The mortality rate was higher in the general population than in medical staff (8% versus 2%). This review showed that during the early stages of COVID-19, laboratory findings alone may not be significant predictors of infection and may just accompany increasing C-reactive protein levels, erythrocyte sedimentation rates, and lactate dehydrogenase levels. In the symptomatic stage, the lymphocyte and platelet counts tended to decrease. Elevated D-dimer fibrin degradation product was associated with poor prognosis.
PubMed: 33117631
DOI: 10.24171/j.phrp.2020.11.5.02 -
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 -
Iranian Journal of Medical Sciences Jul 2021The outbreak of the coronavirus disease-2019 (COVID-19) has become a global public health challenge. Assessing the effect of COVID-19 on liver injury is of great... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The outbreak of the coronavirus disease-2019 (COVID-19) has become a global public health challenge. Assessing the effect of COVID-19 on liver injury is of great importance. A systematic review and meta-analysis were conducted to establish the characteristics of liver function tests in COVID-19 patients.
METHODS
A systematic search of publications from December 2019 up to April 2020 in Web of Science, Scopus, and Medline (via PubMed) databases was performed. Both cross-sectional and case series studies reporting an association between liver injury and COVID-19 infection were included. The data were analyzed using the STATA software (version 11.0) and the random-effects model for I>50% was used to pool the results.
RESULTS
In this meta-analysis, 42 articles comprising a total of 6,557 COVID-19 patients were studied. The prevalence of increase in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels was 30% and 21% in non-severe patients and 38% and 48% in severe patients, respectively. Patients with severe COVID-19 infection were 4.22, 4.96, and 4.13 times more likely to have elevated AST, ALT, and lactate dehydrogenase (LDH) levels, respectively.
CONCLUSION
Elevation in liver function tests was higher in patients with severe than non-severe COVID-19 infection. Given the widespread use of drugs that increases the risk of hepatotoxicity, healthcare providers should be aware of changes in liver enzymes in COVID-19 patients. The inclusion of other studies from outside China could confirm the pattern of elevation in liver function tests in COVID-19 patients across the globe. Preprint of this article is available on medRxiv, https://www.medrxiv.org/content/10.1101/2020.05.20.20108357v1.
Topics: Alanine Transaminase; Aspartate Aminotransferases; COVID-19; Humans; L-Lactate Dehydrogenase; Liver; Liver Diseases; Liver Function Tests
PubMed: 34305236
DOI: 10.30476/ijms.2021.87555.1793 -
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 -
Aging and Disease Jul 2020This study aimed to provide systematic evidence for the association between multiorgan dysfunction and COVID-19 development. Several online databases were searched for... (Review)
Review
This study aimed to provide systematic evidence for the association between multiorgan dysfunction and COVID-19 development. Several online databases were searched for articles published until May 13, 2020. Two investigators independently selected trials, extracted data, and evaluated the quality of individual trials. Single-arm meta-analysis was performed to summarize the clinical features of confirmed COVID-19 patients. Fixed effects meta-analysis was performed for clinically relevant parameters that were closely related to the patients' various organ functions. A total of 73 studies, including 171,108 patients, were included in this analysis. The overall incidence of severe COVID-19 and mortality were 24% (95% confidence interval [CI], 20%-28%) and 2% (95% CI, 1%-3%), respectively. Patients with hypertension (odds ratio [OR] = 2.40; 95% CI, 2.08-2.78), cardiovascular disease (CVD) (OR = 3.54; 95% CI, 2.68-4.68), chronic obstructive pulmonary disease (COPD) (OR=3.70; 95% CI, 2.93-4.68), chronic liver disease (CLD) (OR=1.48; 95% CI, 1.09-2.01), chronic kidney disease (CKD) (OR = 1.84; 95% CI, 1.47-2.30), chronic cerebrovascular diseases (OR = 2.53; 95% CI, 1.84-3.49) and chronic gastrointestinal (GI) disease (OR = 2.13; 95% CI, 1.12-4.05) were more likely to develop severe COVID-19. Increased levels of lactate dehydrogenase (LDH), creatine kinase (CK), high-sensitivity cardiac troponin I (hs-cTnI), myoglobin, creatinine, urea, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin were highly associated with severe COVID-19. The incidence of acute organ injuries, including acute cardiac injury (ACI); (OR = 11.87; 95% CI, 7.64-18.46), acute kidney injury (AKI); (OR=10.25; 95% CI, 7.60-13.84), acute respiratory distress syndrome (ARDS); (OR=27.66; 95% CI, 18.58-41.18), and acute cerebrovascular diseases (OR=9.22; 95% CI, 1.61-52.72) was more common in patients with severe COVID-19 than in patients with non-severe COVID-19. Patients with a history of organ dysfunction are more susceptible to severe conditions. COVID-19 can aggravate an acute multiorgan injury.
PubMed: 32765952
DOI: 10.14336/AD.2020.0520 -
Cancer Medicine Jul 2023The rising cancer incidence in patients with oral leukoplakia (OL) highlights the importance of identifying potential biomarkers for high-risk individuals and lesions... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The rising cancer incidence in patients with oral leukoplakia (OL) highlights the importance of identifying potential biomarkers for high-risk individuals and lesions because these biomarkers are useful in developing personalized management strategies for OL patients. This study systematically searched and analyzed the literature on potential saliva and serum biomarkers for OL malignant transformation.
METHODS
PubMed and Scopus were searched for studies published up to April 2022. The primary outcome of this study was the difference in biomarker concentrations in saliva or serum samples from healthy control (HC), OL and oral cancer (OC) populations. Cohen's d with 95% credible interval was calculated and pooled using the inverse variance heterogeneity method.
RESULTS
A total of seven saliva biomarkers were analyzed in this paper, including interleukin-1alpha, interleukin-6 (IL-6), interleukin-6-8, tumor necrosis factor alpha (TNF-α), copper, zinc, and lactate dehydrogenase. IL-6 and TNF-α exhibited statistically significant deviations in comparisons between HC versus OL and OL versus OC. A total of 13 serum biomarkers were analyzed, including IL-6, TNF-α, C-reactive protein, total cholesterol, triglycerides, high-density lipoproteins, low-density lipoproteins, albumin, protein, β2-microglobulin, fucose, lipid-bound sialic acid (LSA), and total sialic acid (TSA). LSA and TSA exhibited statistically significant deviations in comparisons between HC versus OL and OL versus OC.
CONCLUSION
IL-6 and TNF-α in saliva have strong predictive values for OL deterioration, and LSA and TSA concentration levels in serum also have the potential to serve as biomarkers for OL deterioration.
Topics: Humans; Interleukin-6; Tumor Necrosis Factor-alpha; N-Acetylneuraminic Acid; Leukoplakia, Oral; Biomarkers; Mouth Neoplasms; Cell Transformation, Neoplastic
PubMed: 37199052
DOI: 10.1002/cam4.6095 -
The Journal of Applied Laboratory... Sep 2020Severe acute respiratory syndrome coronavirus 2 causes coronavirus disease 2019 (COVID-19) and poses substantial challenges for healthcare systems. With a vastly... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Severe acute respiratory syndrome coronavirus 2 causes coronavirus disease 2019 (COVID-19) and poses substantial challenges for healthcare systems. With a vastly expanding number of publications on COVID-19, clinicians need evidence synthesis to produce guidance for handling patients with COVID-19. In this systematic review and meta-analysis, we examine which routine laboratory tests are associated with severe COVID-19 disease.
CONTENT
PubMed (Medline), Scopus, and Web of Science were searched until March 22, 2020, for studies on COVID-19. Eligible studies were original articles reporting on laboratory tests and outcome of patients with COVID-19. Data were synthesized, and we conducted random-effects meta-analysis, and determined mean difference (MD) and standard mean difference at the biomarker level for disease severity. Risk of bias and applicability concerns were evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2.
SUMMARY
45 studies were included, of which 21 publications were used for the meta-analysis. Studies were heterogeneous but had low risk of bias and applicability concern in terms of patient selection and reference standard. Severe disease was associated with higher white blood cell count (MD, 1.28 ×109/L), neutrophil count (MD, 1.49 ×109/L), C-reactive protein (MD, 49.2 mg/L), lactate dehydrogenase (MD, 196 U/L), D-dimer (standardized MD, 0.58), and aspartate aminotransferase (MD, 8.5 U/L); all p < 0.001. Furthermore, low lymphocyte count (MD -0.32 × 109/L), platelet count (MD -22.4 × 109/L), and hemoglobin (MD, -4.1 g/L); all p < 0.001 were also associated with severe disease. In conclusion, several routine laboratory tests are associated with disease severity in COVID-19.
Topics: Betacoronavirus; COVID-19; COVID-19 Testing; Clinical Laboratory Techniques; Coronavirus Infections; Diagnostic Tests, Routine; Humans; Outcome Assessment, Health Care; Pandemics; Patient Selection; Pneumonia, Viral; Reference Standards; SARS-CoV-2
PubMed: 32573713
DOI: 10.1093/jalm/jfaa098 -
Annals of Surgical Oncology Jun 2022Evidence on the role of curative metastasectomy (CM) for malignant melanoma (MM) patients is limited, especially in the current era of effective systemic therapy. A... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Evidence on the role of curative metastasectomy (CM) for malignant melanoma (MM) patients is limited, especially in the current era of effective systemic therapy. A systematic review and meta-analysis were performed to ascertain the role of CM compared with incomplete or nonsurgical treatment for patients with MM.
METHODS
Medline, Embase, and Scopus databases were searched for studies investigating CM for MM until 30 September 2021. The review included studies that compared CM with no-CM and reported a hazard ratio (HR) after multivariate analysis for overall survival. A random-effects model with inverse variance was used to calculate pooled HR. The Newcastle-Ottawa Scale was used to assess the risk of bias.
RESULTS
For the final analysis, 40 studies including 31,282 patients (CM, 9958; no-CM, 21,324) were considered. Compared with no-CM, CM was associated with a significantly lower risk of death (HR, 0.42; 95% confidence interval [CI], 0.38-0.47; p < 0.00001). Subgroup analysis showed that the outcome was independent of the effective systemic therapy and anatomic location of metastasis. An unfavorable prognosis was associated with advancing age, elevated lactate dehydrogenase (LDH), male gender, prior stage 3 disease, multiple metastases and organ sites, and shorter disease-free interval.
CONCLUSION
Curative metastasectomy for MM is associated with a lower risk of death than non-curative treatment methods. Selection bias and underlying weakness of studies reduced the strength of evidence in this review. However, CM should be a part of the multimodality treatment of MM whenever technically feasible.
Topics: Humans; Male; Melanoma; Metastasectomy; Prognosis; Skin Neoplasms; Melanoma, Cutaneous Malignant
PubMed: 35128602
DOI: 10.1245/s10434-022-11351-4 -
Advances in Medical Sciences Sep 2021We conducted a systematic review and meta-analysis with meta-regression of creatine kinase-MB (CK-MB), a biomarker of myocardial injury, in COVID-19 patients. (Meta-Analysis)
Meta-Analysis
OBJECTIVES
We conducted a systematic review and meta-analysis with meta-regression of creatine kinase-MB (CK-MB), a biomarker of myocardial injury, in COVID-19 patients.
METHODS
We searched PubMed, Web of Science and Scopus, for studies published between January 2020 and January 2021 that reported CK-MB, COVID-19 severity and mortality (PROSPERO registration number: CRD42021239657).
RESULTS
Fifty-five studies in 11,791 COVID-19 patients were included in the meta-analysis. The pooled results showed that CK-MB concentrations were significantly higher in patients with high disease severity or non-survivor status than patients with low severity or survivor status (standardized mean difference, SMD, 0.81, 95% CI 0.61 to 1.01, p<0.001). The rate of patients with CK-MB values above the normal range was also significantly higher in the former than the latter (60/350 vs 98/1,780; RR = 2.84, 95%CI 1.89 to 4.27, p<0.001; I = 19.9, p = 0.254). Extreme between-study heterogeneity was observed (I = 93.4%, p<0.001). Sensitivity analysis, performed by sequentially removing each study and re-assessing the pooled estimates, showed that the magnitude and direction of the effect size was not modified (effect size range, 0.77 to 0.84). Begg's (p = 0.50) and Egger's (p = 0.86) t-tests did not show publication bias. In meta-regression analysis, the SMD was significantly and positively associated with the white blood count, aspartate aminotransferase, myoglobin, troponin, brain natriuretic peptide, lactate dehydrogenase, and D-dimer.
CONCLUSIONS
Higher CK-MB concentrations were significantly associated with severe disease and mortality in COVID-19 patients. This biomarker of myocardial injury might be useful for risk stratification in this group.
Topics: Biomarkers; COVID-19; Creatine Kinase, MB Form; Humans; Mortality; SARS-CoV-2; Severity of Illness Index
PubMed: 34256241
DOI: 10.1016/j.advms.2021.07.001