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Journal of Inherited Metabolic Disease Nov 2015Newborn screening (NBS) is justified if early intervention is effective in a disorder generally not detected early in life on a clinical basis, and if sensitive and... (Review)
Review
Newborn screening (NBS) is justified if early intervention is effective in a disorder generally not detected early in life on a clinical basis, and if sensitive and specific biochemical markers exist. Experience with NBS for homocystinurias and methylation disorders is limited. However, there is robust evidence for the success of early treatment with diet, betaine and/or pyridoxine for CBS deficiency and good evidence for the success of early betaine treatment in severe MTHFR deficiency. These conditions can be screened in dried blood spots by determining methionine (Met), methionine-to-phenylanine (Met/Phe) ratio, and total homocysteine (tHcy) as a second tier marker. Therefore, we recommend NBS for cystathionine beta-synthase and severe MTHFR deficiency. Weaker evidence is available for the disorders of intracellular cobalamin metabolism. Early treatment is clearly of advantage for patients with the late-onset cblC defect. In the early-onset type, survival and non-neurological symptoms improve but the effect on neurocognitive development is uncertain. The cblC defect can be screened by measuring propionylcarnitine, propionylcarnitine-to-acetylcarnitine ratio combined with the second tier markers methylmalonic acid and tHcy. For the cblE and cblG defects, evidence for the benefit of early treatment is weaker; and data on performance of Met, Met/Phe and tHcy even more limited. Individuals homozygous or compound heterozygous for MAT1A mutations may benefit from detection by NBS using Met, which on the other hand also detects asymptomatic heterozygotes. Clinical and laboratory data is insufficient to develop any recommendation on NBS for the cblD, cblF, cblJ defects, glycineN-methyltransferase-, S-adenosylhomocysteinehydrolase- and adenosine kinase deficiency.
Topics: Acetylcarnitine; Betaine; Carnitine; Homocystinuria; Humans; Infant, Newborn; Methionine; Methylation; Methylenetetrahydrofolate Reductase (NADPH2); Methylmalonic Acid; Neonatal Screening; Practice Guidelines as Topic
PubMed: 25762406
DOI: 10.1007/s10545-015-9830-z -
Giornale Italiano Di Nefrologia :... 2016Vitamin K-dependent matrix Gla protein (MGP) is a key inhibitor of vascular calcification (VC). MGP is synthesized by chondrocytes and vascular smooth muscle cells... (Review)
Review
Vitamin K-dependent matrix Gla protein (MGP) is a key inhibitor of vascular calcification (VC). MGP is synthesized by chondrocytes and vascular smooth muscle cells (VSMC) and the absence or inactivity of MGP results in excessive calcification of both growth plate and vasculature. Apart from its vitamin K dependency little is known about other factors that influence MGP metabolism. Phosphate, calcium and magnesium are involved in bone mineralization and play an important role in VC. In this review we provide a summary of the effect of phosphate, calcium, and magnesium on MGP metabolism. Elevated phosphate and calcium levels promote VC, in part by increasing the release of matrix vesicles (MV) that under the influence of calcium and phosphate become calcification competent. Phosphate and calcium simultaneously induce an upregulation of MGP protein and gene expression, which possibly inhibits calcification. Elevated phosphate levels did not change MGP protein levels in MV. On the contrary, elevated calcium concentrations caused a decrease of MGPloading in MV, which might in part explainthe calcifying effects of MV. Magnesium is a known inhibitor of VC. However, magnesium has been shown to have an inhibitory effect on MGP synthesis induced through downregulation of the calcium-sensing receptor and hereby causing a decrease in calcium induced MGP upregulation. There might also be stimulatory effect of magnesium on MGP in which the TRPM7 channel is involved. In conclusion there is a clear interaction between MGP and phosphate, calcium and magnesium. The upregulation of MGP by phosphate and calcium might be a cellular response that possibly results in the mitigation of VC.
Topics: Calcium; Calcium-Binding Proteins; Extracellular Matrix Proteins; Humans; Magnesium; Phosphates; Vascular Calcification; Matrix Gla Protein
PubMed: 28134400
DOI: No ID Found -
Biomolecules Feb 2023Albumin is a highly abundant plasma protein with multiple functions, including the balance of fluid between body compartments and fatty acid trafficking. Humans with... (Review)
Review
Albumin is a highly abundant plasma protein with multiple functions, including the balance of fluid between body compartments and fatty acid trafficking. Humans with congenital analbuminemia (CAA) do not express albumin due to homozygosity for albumin gene mutation. Lessons about physiological control could be learned from CAA. Remarkably, these patients exhibit an apparently normal lifespan, without substantial impairments in physical functionality. There was speculation that tolerance to albumin deficiency would be characterized by significant upregulation of other plasma proteins to compensate for analbuminemia. It is unknown but possible that changes in plasma protein expression observed in CAA are required for the well-documented survival and general wellness. A systematic review of published case reports was performed to assess plasma protein pattern remodeling in CAA patients who were free of other illnesses that would confound interpretation. From a literature search in Pubmed, Scopus, and Purdue Libraries (updated October 2022), concentration of individual plasma proteins and protein classes were assessed. Total plasma protein concentration was below the reference range in the vast majority of CAA patients in the analysis, as upregulation of other proteins was not sufficient to prevent the decline of total plasma protein when albumin was absent. Nonetheless, an impressive level of evidence in the literature indicated upregulated plasma levels of multiple globulin classes and various specific proteins which may have metabolic functions in common with albumin. The potential role of this altered plasma protein expression pattern in CAA is discussed, and the findings may have implications for other populations with hypoalbuminemia.
Topics: Humans; Hypoalbuminemia; Blood Proteins; Albumins; Mutation; Plasma
PubMed: 36979342
DOI: 10.3390/biom13030407 -
Arthritis Research & Therapy Nov 2016Tendon disease is characterized by the development of fibrosis. Transforming growth factor beta (TGF-β), bone morphogenic proteins (BMPs) and connective tissue growth... (Review)
Review
BACKGROUND
Tendon disease is characterized by the development of fibrosis. Transforming growth factor beta (TGF-β), bone morphogenic proteins (BMPs) and connective tissue growth factor (CTGF) are key mediators in the pathogenesis of fibrotic disorders. The aim of this systematic review was to investigate the evidence for the expression of TGF-β, BMPs and CTGF along tendon disease progression and the response of tendon cells to these growth factors accordingly.
METHOD
We conducted a systematic screen of the scientific literature using the Medline database. The search terms used were "tendon AND TGF-β," "tendon AND BMP" or "tendon AND CTGF." Studies of human samples, animal tendon injury and overuse models were included.
RESULTS
Thirty-three studies were included. In eight studies the expression of TGF-β, BMPs or CTGF was dysregulated in chronic tendinopathy and tendon tear patient tissues in comparison with healthy control tissues. The expression of TGF-β, BMPs and CTGF was increased and showed temporal changes in expression in tendon tissues from animal injury or overuse models compared with the healthy control (23 studies), but the pattern of upregulation was inconsistent between growth factors and also the type of animal model. No study investigated the differences in the effect of TGF-β, BMPs or CTGF treatment between patient-derived cells from healthy and diseased tendon tissues. Tendon cells derived from animal models of tendon injury showed increased expression of extracellular matrix protein genes and increased cell signaling response to TGF-β and BMP treatments compared with the control cells (two studies).
CONCLUSION
The expression of TGF-β, BMPs and CTGF in tendon tissues is altered temporally during healing in animal models of tendon injury or overuse, but the transition during the development of human tendon disease is currently unknown. Findings from this systematic review suggest a potential and compelling role for TGF-β, BMPs and CTGF in tendon disease; however, there is a paucity of studies analyzing their expression and stimulated cellular response in well-phenotyped human samples. Future work should investigate the dynamic expression of these fibrotic growth factors and their interaction with tendon cells using patient samples at different stages of human tendon disease.
Topics: Animals; Bone Morphogenetic Proteins; Connective Tissue Growth Factor; Fibrosis; Humans; Tendinopathy; Transforming Growth Factor beta
PubMed: 27863509
DOI: 10.1186/s13075-016-1165-0 -
Journal of Sport and Health Science Mar 2024This meta-analytical study aimed to explore the effects of resistance training (RT) volume on body adiposity, metabolic risk, and inflammation in postmenopausal and... (Meta-Analysis)
Meta-Analysis
Effect of resistance training volume on body adiposity, metabolic risk, and inflammation in postmenopausal and older females: Systematic review and meta-analysis of randomized controlled trials.
PURPOSE
This meta-analytical study aimed to explore the effects of resistance training (RT) volume on body adiposity, metabolic risk, and inflammation in postmenopausal and older females.
METHODS
A systematic search was performed for randomized controlled trials in PubMed, Scopus, Web of Science, and SciELO. Randomized controlled trials with postmenopausal and older females that compared RT effects on body adiposity, metabolic risk, and inflammation with a control group (CG) were included. Independent reviewers selected the studies, extracted the data, and performed the risk of bias and certainty of the evidence (Grading of Recommendations, Assessment, Development, and Evaluation (GRADE)) evaluations. Total body and abdominal adiposity, blood lipids, glucose, and C-reactive protein were included for meta-analysis. A random-effects model, standardized mean difference (Hedges' g), and 95% confidence interval (95%CI) were used for meta-analysis.
RESULTS
Twenty randomized controlled trials (overall risk of bias: some concerns; GRADE: low to very low) with overweight/obese postmenopausal and older females were included. RT groups were divided into low-volume RT (LVRT, ∼44 sets/week) and high-volume RT (HVRT, ∼77 sets/week). Both RT groups presented improved body adiposity, metabolic risk, and inflammation when compared to CG. However, HVRT demonstrated higher effect sizes than LVRT for glucose (HVRT = -1.19; 95%CI: -1.63 to -0.74; LVRT = -0.78; 95%CI:-1.15 to -0.41) and C-reactive protein (HVRT = -1.00; 95%CI: -1.32 to -0.67; LVRT = -0.34; 95%CI, -0.63 to -0.04)) when compared to CG.
CONCLUSION
Compared to CG, HVRT protocols elicit greater improvements in metabolic risk and inflammation outcomes than LVRT in overweight/obese postmenopausal and older females.
Topics: Female; Humans; Adiposity; C-Reactive Protein; Glucose; Inflammation; Obesity; Overweight; Postmenopause; Randomized Controlled Trials as Topic; Resistance Training
PubMed: 37788790
DOI: 10.1016/j.jshs.2023.09.012 -
Nutrition Journal Oct 2023It is suggested that supplementation with milk protein (MP) has the potential to ameliorate the glycemic profile; however, the exact impact and certainty of the findings... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
It is suggested that supplementation with milk protein (MP) has the potential to ameliorate the glycemic profile; however, the exact impact and certainty of the findings have yet to be evaluated. This systematic review and dose-response meta-analysis of randomized controlled trials (RCTs) assessed the impact of MP supplementation on the glycemic parameters in adults.
METHODS
A systematic search was carried out among online databases to determine eligible RCTs published up to November 2022. A random-effects model was performed for the meta-analysis.
RESULTS
A total of 36 RCTs with 1851 participants were included in the pooled analysis. It was displayed that supplementation with MP effectively reduced levels of fasting blood glucose (FBG) (weighted mean difference (WMD): -1.83 mg/dL, 95% CI: -3.28, -0.38; P = 0.013), fasting insulin (WMD: -1.06 uU/mL, 95% CI: -1.76, -0.36; P = 0.003), and homeostasis model assessment of insulin resistance (HOMA-IR) (WMD: -0.27, 95% CI: -0.40, -0.14; P < 0.001) while making no remarkable changes in serum hemoglobin A1c (HbA1c) values (WMD: 0.01%, 95% CI: -0.14, 0.16; P = 0.891). However, there was a significant decline in serum levels of HbA1c among participants with normal baseline body mass index (BMI) based on sub-group analyses. In addition, HOMA-IR values were significantly lower in the MP supplement-treated group than their untreated counterparts in short- and long-term supplementation (≤ 8 and > 8 weeks) with high or moderate doses (≥ 60 or 30-60 g/d) of MP or whey protein (WP). Serum FBG levels were considerably reduced upon short-term administration of a low daily dose of WP (< 30 g). Furthermore, the levels of serum fasting insulin were remarkably decreased during long-term supplementation with high or moderate daily doses of WP.
CONCLUSION
The findings of this study suggest that supplementation with MP may improve glycemic control in adults by reducing the values of fasting insulin, FBG, and HOMA-IR. Additional trials with longer durations are required to confirm these findings.
Topics: Adult; Humans; Glycated Hemoglobin; Blood Glucose; Milk Proteins; Diabetes Mellitus, Type 2; Dietary Supplements; Insulin; Insulin Resistance; Whey Proteins
PubMed: 37798798
DOI: 10.1186/s12937-023-00878-1 -
International Journal of Environmental... Feb 2021Childhood obesity is a growing epidemic. Early identification of high-risk groups will allow for the development of prevention strategies. Cord blood adipocytokines have... (Meta-Analysis)
Meta-Analysis Review
Childhood obesity is a growing epidemic. Early identification of high-risk groups will allow for the development of prevention strategies. Cord blood adipocytokines have been previously examined as biomarkers predicting future obesity. We conducted a systematic review looking at the association between cord blood leptin and adiponectin with adiposity up to 5 years of age. A literature review was performed between January 1994 and August 2020 using two bibliographic databases (Medline/Pubmed and EMBASE) and was registered on PROSPERO (CRD42017069024). Studies using skinfold thickness and direct methods of assessing body composition in full term neonates were considered. Partial correlation and multiple regression models were used to present the results. Meta-analysis was performed, were possible, using a random effects model. Cochran's Q test was used to assess heterogeneity and I statistics to calculate the percentage of variation across studies. The potential for publication bias was assessed using funnel plots. Data from 22 studies were retrieved and reviewed by two independent reviewers. Cord blood leptin was positively associated with adiposity at birth ( = 0.487; 95% CI: 0.444, 0.531) but was inversely related to adiposity up to 3 years of age. The association was not sustained at 5 years. There was a weak positive association between adiponectin in cord blood and adiposity at birth ( = 0.201; 95% CI: 0.125, 0.277). No correlation was found between cord blood adiponectin in young children, but data were limited. This review supports that cord blood leptin and adiponectin are associated with adiposity at birth. The results of this study provide insight into the role of adipocytokines at birth on future metabolic health and their potential use as risk stratification tools.
Topics: Adipokines; Adiponectin; Adiposity; Body Composition; Child; Child, Preschool; Fetal Blood; Humans; Infant, Newborn; Leptin
PubMed: 33669328
DOI: 10.3390/ijerph18041897 -
Nutrition Journal Jan 2024Exercise training (Ex) and intermittent fasting (IF) are effective for improving body composition and cardiometabolic health overweight and obese adults, but whether... (Meta-Analysis)
Meta-Analysis Review
Combined versus independent effects of exercise training and intermittent fasting on body composition and cardiometabolic health in adults: a systematic review and meta-analysis.
INTRODUCTION AND AIM
Exercise training (Ex) and intermittent fasting (IF) are effective for improving body composition and cardiometabolic health overweight and obese adults, but whether combining Ex and IF induces additive or synergistic effects is less well established. We therefore, performed a systematic review and meta-analysis to compare the combined versus independent effects of Ex and IF on body composition and cardiometabolic health in adults.
METHOD
An electronic search was conducted in three main online databases including PubMed, Web of Science, and Scopus, from inception to March 9, 2023 for studies involving Ex plus IF trials versus standalone Ex and/or IF interventions in adults. Interventions had a duration of ≥ 2 weeks. Standardized (SMD) or weighted mean differences (WMD) and 95% confidence intervals were calculated in order to compare effects on body weight, body mass index (BMI), body fat lean body mass (LBM), visceral fat, and waist circumference. For cardiometabolic health, outcomes included fasting glucose, insulin, total cholesterol (TC), low-density lipoprotein cholesterol (LDL), triglycerides (TG), high-density lipoprotein cholesterol (HDL), systolic (SBP) and diastolic (DBP) blood pressure, and VOmax/peak.
RESULTS
Ex plus IF decreased body weight [WMD: -3.03 kg (95% CI: -3.44 to -2.61), p = 0.001], BMI [WMD: -1.12 kg.m (95% CI: -1.28 to -0.95), p = 0.001], body fat [SMD: -0.72 (95% CI: -1.23 to -0.21), p = 0.005], visceral fat [SMD: -0.34 (95% CI: -0.63 to -0.05), p = 0.01], and waist circumference [WMD: -2.63 cm (95% CI: -4.16 to -1.11), p = 0.001] more than Ex alone. However, changes in body composition and cardiometabolic health markers were not significantly different for Ex plus IF when compared with IF alone, with the exception of VOmax/peak [SMD: 0.55 (95% CI: 0.14 to 0.97), p = 0.009].
CONCLUSION
We demonstrate that a combination of Ex and IF produces superior changes in body composition, but not in markers of cardiometabolic health when compared with Ex or IF alone. Ex plus IF could therefore be effective for weight and fat loss but has no additive or synergistic effects for other cardiometabolic health markers.
Topics: Adult; Humans; Intermittent Fasting; Body Composition; Exercise; Cholesterol, HDL; Obesity; Cardiovascular Diseases
PubMed: 38183054
DOI: 10.1186/s12937-023-00909-x -
The Journal of Nutrition, Health & Aging Mar 2024Adiponectin is an adipokine playing a central role in the regulation of energy homeostasis, carbohydrate and lipid metabolism, as well as immunomodulation. The... (Review)
Review
Adiponectin is an adipokine playing a central role in the regulation of energy homeostasis, carbohydrate and lipid metabolism, as well as immunomodulation. The relationship between Alzheimer's disease (AD) and body composition has highlighted the bidirectional crosstalk between AD's pathophysiology and metabolic disorders. This review aimed to report the current state of knowledge about cellular and molecular mechanisms linking adiponectin and AD, in preclinical studies. Then, we reviewed human studies to assess the relationship between adiponectin levels and AD diagnosis. We also examined the risk of incident AD regarding the participants' baseline adiponectin level, as well as the relationship of adiponectin and cognitive decline in patients with AD. We conducted a systematic review, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline, of studies published over the last decade on MEDLINE and Cochrane databases. Overall, we reviewed 34 original works about adiponectin in AD, including 11 preclinical studies, two both preclinical and human studies and 21 human studies. Preclinical studies brought convincing evidence for the neuroprotective role of adiponectin on several key mechanisms of AD. Human studies showed conflicting results regarding the relationship between AD and adiponectin levels, as well as regarding the cross-sectional association between cognitive function and adiponectin levels. Adiponectin did not appear as a predictor of incident AD, nor as a predictor of cognitive decline in patients with AD. Despite solid preclinical evidence suggesting the protective role of adiponectin in AD, inconsistent results in humans supports the need for further research.
Topics: Animals; Humans; Adipokines; Adiponectin; Alzheimer Disease; Cognition; Cross-Sectional Studies
PubMed: 38280832
DOI: 10.1016/j.jnha.2024.100166 -
Journal of Cellular and Molecular... Feb 2022Fracture non-union represents a common complication, seen in 5%-10% of all acute fractures. Despite the enhancement in scientific understanding and treatment methods,... (Review)
Review
Fracture non-union represents a common complication, seen in 5%-10% of all acute fractures. Despite the enhancement in scientific understanding and treatment methods, rates of fracture non-union remain largely unchanged over the years. This systematic review investigates the biological, molecular and genetic profiles of both (i) non-union tissue and (ii) non-union-related tissues, and the genetic predisposition to fracture non-union. This is crucially important as it could facilitate earlier identification and targeted treatment of high-risk patients, along with improving our understanding on pathophysiology of fracture non-union. Since this is an update on our previous systematic review, we searched the literature indexed in PubMed Medline; Ovid Medline; Embase; Scopus; Google Scholar; and the Cochrane Library using Medical Subject Heading (MeSH) or Title/Abstract words (non-union(s), non-union(s), human, tissue, bone morphogenic protein(s) (BMPs) and MSCs) from August 2014 (date of our previous publication) to 2 October 2021 for non-union tissue studies, whereas no date restrictions imposed on non-union-related tissue studies. Inclusion criteria of this systematic review are human studies investigating the characteristics and properties of non-union tissue and non-union-related tissues, available in full-text English language. Limitations of this systematic review are exclusion of animal studies, the heterogeneity in the definition of non-union and timing of tissue harvest seen in the included studies, and the search term MSC which may result in the exclusion of studies using historical terms such as 'osteoprogenitors' and 'skeletal stem cells'. A total of 24 studies (non-union tissue: n = 10; non-union-related tissues: n = 14) met the inclusion criteria. Soft tissue interposition, bony sclerosis of fracture ends and complete obliteration of medullary canal are commonest macroscopic appearances of non-unions. Non-union tissue colour and surrounding fluid are two important characteristics that could be used clinically to distinguish between septic and aseptic non-unions. Atrophic non-unions had a predominance of endochondral bone formation and lower cellular density, when compared against hypertrophic non-unions. Vascular tissues were present in both atrophic and hypertrophic non-unions, with no difference in vessel density between the two. Studies have found non-union tissue to contain biologically active MSCs with potential for osteoblastic, chondrogenic and adipogenic differentiation. Proliferative capacity of non-union tissue MSCs was comparable to that of bone marrow MSCs. Rates of cell senescence of non-union tissue remain inconclusive and require further investigation. There was a lower BMP expression in non-union site and absent in the extracellular matrix, with no difference observed between atrophic and hypertrophic non-unions. The reduced BMP-7 gene expression and elevated levels of its inhibitors (Chordin, Noggin and Gremlin) could potentially explain impaired bone healing observed in non-union MSCs. Expression of Dkk-1 in osteogenic medium was higher in non-union MSCs. Numerous genetic polymorphisms associated with fracture non-union have been identified, with some involving the BMP and MMP pathways. Further research is required on determining the sensitivity and specificity of molecular and genetic profiling of relevant tissues as a potential screening biomarker for fracture non-unions.
Topics: Animals; Bone Morphogenetic Proteins; Fracture Healing; Fractures, Bone; Fractures, Ununited; Genetic Predisposition to Disease; Humans; Osteogenesis
PubMed: 34984803
DOI: 10.1111/jcmm.17096