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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 Trace Elements in Medicine... Sep 2023Inflammation is an initiating cause of infectious and non-infectious diseases. Studies have shown that selenium (Se) has anti-inflammatory effects. However, its' effects... (Meta-Analysis)
Meta-Analysis Review
Inflammation is an initiating cause of infectious and non-infectious diseases. Studies have shown that selenium (Se) has anti-inflammatory effects. However, its' effects on serum c-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) plasma concentrations are equivocal. Therefore, we performed a systematic review and meta-analysis of randomized controlled trials (RCTs), evaluating the effects of per oral (PO) and intravenous (IV) Se supplementation on CRP, TNF-α, and IL-6. A systematic search was conducted using four databases, including PubMed, Google Scholar, Cochrane Library, and Scopus to find randomized clinical trials, published up to April 2023. From 19476 papers, after screening and removing duplicate articles, 24 studies were analyzed in the present meta-analysis. In the pooled analysis, PO Se administration showed no significant effect on CRP (WMD: 0.12; 95 % CI -0.11, 0.38; P-value= 0.30). However, IV Se supplementation had a significant negative association with CRP concentration (-2.24; 95 % CI: -4.24, -0.24; p-value: 0.02). Se administration had no significant association with TNF-α plasma concentration (9.64, 95 % CI: -0.59, 19.88, p-value= 0.06; and heterogeneity: 98 %). However, a significant positive association was present between Se and plasma TNF-α concentrations (0.15, 95 % CI: 0.14, 0.17, P-value<0.0001). Moreover, Se supplementation had a significant negative correlation with IL-6 plasma concentration in PO (-0.54; 95 % CI: -1.61, 0.52; P-value = 0.31) and IV administrations (-4.77; 95 % CI: -7.61, -1.93; P-value<0.0001), respectively. This study demonstrated that IV Se administration reduced CRP and IL-6 plasma concentrations. Conversely, IV Se supplementation increased TNF-α plasma concentration. It is evident that further, well-controlled clinical trials are required.
Topics: Humans; C-Reactive Protein; Interleukin-6; Tumor Necrosis Factor-alpha; Selenium; Dietary Supplements; Randomized Controlled Trials as Topic; Inflammation; Biomarkers
PubMed: 37257335
DOI: 10.1016/j.jtemb.2023.127199 -
Clinical Endocrinology May 2021Antiandrogens are frequently used with estradiol in transgender women seeking feminization. Antiandrogens act by various mechanisms to decrease the production or effects... (Review)
Review
Antiandrogens are frequently used with estradiol in transgender women seeking feminization. Antiandrogens act by various mechanisms to decrease the production or effects of testosterone, but it is unclear which antiandrogen is most effective at feminization. A systematic review was performed using PRISMA guidelines. We searched online databases (Medline, Embase and PsycINFO) and references of relevant articles for studies of antiandrogens in transgender women aged 16+ years to achieve feminization (namely changes in breast size, body composition, facial or body hair) or changes in serum total testosterone concentration when compared to placebo, estradiol alone or an alternative antiandrogen. Four studies fulfilled eligibility criteria and were included in a narrative review. The addition of cyproterone acetate, leuprolide and medroxyprogesterone acetate may be more effective than spironolactone or estradiol alone at suppressing the serum total testosterone concentration. Body composition changes appear similar in transgender women treated with estradiol and additional cyproterone acetate or leuprolide. No eligible studies adequately evaluated the effects of antiandrogens on breast development or facial and body hair reduction. It remains unclear which antiandrogen is most effective at achieving feminization. Cyproterone acetate, medroxyprogesterone acetate and leuprolide may be more effective than spironolactone at suppressing the serum total testosterone concentration. However, due to spironolactone's antagonism of the androgen receptor, it is unclear whether this results in clinically meaningful differences in feminization. Further research with clinically meaningful endpoints is needed to optimize the use of antiandrogens in transgender women.
Topics: Androgen Antagonists; Cyproterone Acetate; Female; Feminization; Humans; Male; Transgender Persons; Transsexualism
PubMed: 32926454
DOI: 10.1111/cen.14329 -
Behavioural Brain Research Jan 2023The aim of this comprehensive systematic review and meta-analysis was to evaluate the beneficial effects of melatonin supplementation on brain-derived neurotrophic... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
The aim of this comprehensive systematic review and meta-analysis was to evaluate the beneficial effects of melatonin supplementation on brain-derived neurotrophic factor (BDNF) concentration and clinical depressive disorder.
METHODS
A comprehensive electronic search was conducted of Medlin, Web of Science, Science Direct, and Google scholar, from database inception to January 20, 2021. Studies were eligible if they: (1) were a clinical trial; (2) enrolled adults; (3) assessed the effect of melatonin supplementation on serum concentration of BDNF or depression score. Overall effects, as weighted mean difference (WMD), were calculated for concentration of BDNF and depression score.
RESULTS
Melatonin supplementation yielded no significant effect on BDNF concentration (WMD: -5.61; 95% CI: -14.10, 2.88; I-square: 85.6%), but improved depression by decreasing the score (WMD: -0.76; 95% CI: -1.12, -0.4; I-square: 88.0%). Due to high heterogeneity between studies, subgroup analysis for gender, duration and dose in BDNF studies and duration, age, dose, continent and Questionnaire type in depression studies, was utilised. The subgroup analysis showed that melatonin supplementation had a significant decreasing effect on BDNF levels in doses ≤ 10 mg/day, with more than 4 weeks of duration, and in men.
CONCLUSION
The present study revealed that melatonin supplementation has a decreasing effect on depression in all duration of studies and doses subgroup and in age more than 65 years in depression studies but heterogenicity of the included studies, did not allow a definitive conclusion. There is limited evidence for effects of melatonin on serum BDNF.
IMPLICATIONS FOR PRACTICE
Melatonin is a safe and effective supplement for depressive patients.
Topics: Adult; Aged; Brain-Derived Neurotrophic Factor; Depression; Dietary Supplements; Humans; Male; Melatonin; Randomized Controlled Trials as Topic
PubMed: 36049659
DOI: 10.1016/j.bbr.2022.114083 -
Clinical Oral Investigations Aug 2023To determine the prevalence of postoperative pain after endodontic treatment using low (LC) and high (HC) concentrations of sodium hypochlorite (NaOCl). (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To determine the prevalence of postoperative pain after endodontic treatment using low (LC) and high (HC) concentrations of sodium hypochlorite (NaOCl).
MATERIALS AND METHODS
Six databases and the grey literature were searched to identify randomized clinical trials that evaluated postoperative pain after endodontic treatment using NaOCl. NaOCl concentrations were dichotomized into 'LC' (0.5% to 3%) and 'HC' (≥ 5%) and a proportion meta-analysis was applied to determine the postoperative pain prevalence: overall and according to pain intensity and postoperative time. The prevalence of patients using pain control medication was also determined. A significance level of 5% and a random effect model were applied for data analysis. Between-study heterogeneity was assessed by I index. Risk of bias (RoB) was assessed using the Cochrane Risk-of-Bias 2.0 tool. The certainty of evidence was assessed using the GRADE approach.
RESULTS
Ten studies were included in the review and eight in the meta-analysis. The overall prevalence of postoperative pain was 45% in LC and 39% in HC. The prevalence of pain in LC and HC after 24 h was 25% and 40%, respectively. After 48 h, the prevalence decreased to 10% in LC and 25% in HC. 'Absent pain' was the most prevalent score. The prevalence of patients who used medication was 9% in LC and 15% in HC. Three studies were classified as 'high RoB', five as 'low RoB', and two as 'some concerns'. The certainty of evidence was very low.
CONCLUSIONS
The overall prevalence of postoperative pain after endodontic treatment using LC and HC of NaOCl was 45% and 39%, respectively.
CLINICAL RELEVANCE
Postoperative pain is common after endodontic treatment using NaOCl, but tends to decrease over time.
Topics: Humans; Sodium Hypochlorite; Prevalence; Root Canal Irrigants; Pain Management; Pain, Postoperative
PubMed: 37466716
DOI: 10.1007/s00784-023-05151-7 -
American Journal of Physiology.... Sep 2022Diabetes is the eighth leading cause of death in the world and the prevalence is rising in low-income countries. Cardiovascular diseases are the leading cause of death... (Review)
Review
Diabetes is the eighth leading cause of death in the world and the prevalence is rising in low-income countries. Cardiovascular diseases are the leading cause of death worldwide, especially for individuals with diabetes. Although medications exist to treat symptoms of diabetes, lack of availability and high costs may deter their use by individuals with low incomes as well as those in low-income nations. Therefore, this systematic review was performed to determine whether genistein, a phytoestrogen found in soy products, could provide therapeutic benefits for individuals with diabetes. We searched PubMed and SCOPUS using the terms "genistein," "diabetes," and "glucose" and identified 33 peer-reviewed articles that met our inclusion criteria. In general, preclinical studies demonstrated that genistein decreases body weight and circulating glucose and triglycerides concentrations, whereas increasing insulin levels and insulin sensitivity. Genistein also delayed the onset of type 1 and type 2 diabetes. In contrast, clinical studies utilizing genistein generally reported no significant relationship between genistein and body mass, circulating glucose, glycated hemoglobin (A1C) concentrations, or onset of type 1 diabetes. However, genistein was found to improve insulin sensitivity and serum triglyceride concentrations and delayed the onset of type 2 diabetes. In summary, preclinical and clinical studies suggest that genistein may help delay the onset of type 2 diabetes and improve several symptoms associated with the disease. Although additional research is required to confirm these findings, the results highlighted in this review provide some evidence that genistein may offer a natural approach to mitigating some of the complications associated with diabetes.
Topics: Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Genistein; Glycated Hemoglobin; Humans; Insulin Resistance
PubMed: 35816719
DOI: 10.1152/ajpregu.00236.2021 -
Andrology Sep 2023Since the 1970s, several studies found that sperm concentration (SC) and total sperm count (TSC) constantly worsened over time, mainly in high-income countries. (Review)
Review
BACKGROUND
Since the 1970s, several studies found that sperm concentration (SC) and total sperm count (TSC) constantly worsened over time, mainly in high-income countries.
OBJECTIVES
To evaluate whether the decreasing trend in sperm count is continuing in Western European countries and USA, we performed a systematic review and meta-regression analysis.
MATERIALS AND METHODS
Embase and Pubmed/Medline were searched papers published in English in the 2000-2020 period limiting the search to data collected in the USA and Western European countries.
RESULTS
We identified 62 articles and pooled information on 24,196 men (range 10-2,523), collected from 1993 to 2018. Considering all the studies, random-effects meta-regression analyses showed no significant trend for SC (slope per year -0.07 mil/mL, p-value = 0.86). Negative trends of SC were detected in Scandinavian countries (slope per year -1.11 mil/mL, 95% CI: -2.40 to +0.19; p-value = 0.09), but the findings were statistically not significant. No significant trends of SC were detected in Central Europe (slope per year +0.23, 95% CI -2.51 to +2.96; p-value = 0.87), the USA (slope per year +1.08, 95% CI -0.42 to +2.57; p-value = 0.16), and Southern Europe (slope per year +0.19, 95% CI -0.99 to +1.37; p-value = 0.75). We have analyzed separately findings from studies including sperm donors, fertile men, young unselected men (unselected men, study mean age < 25 years) and unselected men (unselected men, study mean age ≥ 25 years). No significant trends of SC were observed among sperm donors (slope per year -2.80, 95% CI -6.76 to +1.17; p-value 0.16), unselected men (slope per year -0.23, 95% CI -1.58 to +1.12; p-value 0.73), young unselected men (slope per year -0.49, 95% CI -1.76 to +0.79; p-value 0.45), fertile men (slope per year +0.29, 95% CI -1.09 to +1.67; p-value 0.68).
DISCUSSION AND CONCLUSION
The results of this analysis show no significant trends in SC, in USA, and selected Western European countries.
Topics: Humans; Male; Adult; Sperm Count; Semen; Spermatozoa; Semen Analysis; Regression Analysis; Sperm Motility
PubMed: 36709405
DOI: 10.1111/andr.13396 -
Environmental Science and Pollution... May 2021Cereal-based foods are utilized as an essential food segment worldwide. Nevertheless, their contamination by mycotoxins, also fumonisins, could pose a critical health... (Meta-Analysis)
Meta-Analysis Review
Cereal-based foods are utilized as an essential food segment worldwide. Nevertheless, their contamination by mycotoxins, also fumonisins, could pose a critical health risk. The present research provides the first systematic review regarding the prevalence and concentration of fumonisins in cereal-based food with the aid of a meta-analysis. In this regard, some international databases PubMed, Web of Science, Google Scholar, and Scopus were explored during the last 30 years. Among 9729 screened articles, 73 articles (which meet the proposed inclusion criteria), including 11,132 data, were incorporated in the performed meta-analysis. The overall rank order regarding the concentration of fumonisins in cereal-based foods was corn-based foods > wheat-based foods > other cereal foods > barley-based foods > rice-based foods > oat-based foods. Based on the prevalence of fumonisins, the overall rank order was other cereal foods > corn-based foods > rice-based foods > wheat-based foods > oat-based foods > barley-based food. The present meta-analysis results can be a beneficial database for risk assessment model progress, which can help industries and organizations decrease the presence of fumonisins in cereal-based food.
Topics: Edible Grain; Food Contamination; Fumonisins; Mycotoxins; Prevalence
PubMed: 33694116
DOI: 10.1007/s11356-021-12671-w -
International Journal of Environmental... Aug 2019Observational studies and randomised controlled studies suggest that vitamin D plays a role in the prevention of acute respiratory tract infection (ARTI); however,... (Meta-Analysis)
Meta-Analysis
Observational studies and randomised controlled studies suggest that vitamin D plays a role in the prevention of acute respiratory tract infection (ARTI); however, findings are inconsistent and the optimal serum 25-hydroxyvitamin D (25(OH)D) concentration remains unclear. To review the link between 25(OH)D concentration and ARTI, we searched PubMed and EMBASE databases to identify observational studies reporting the association between 25(OH)D concentration and risk or severity of ARTI. We used random-effects meta-analysis to pool findings across studies. Twenty-four studies were included in the review, 14 were included in the meta-analysis of ARTI risk and five in the meta-analysis of severity. Serum 25(OH)D concentration was inversely associated with risk and severity of ARTI; pooled odds ratios (95% confidence interval) were 1.83 (1.42-2.37) and 2.46 (1.65-3.66), respectively, comparing the lowest with the highest 25(OH)D category. For each 10 nmol/L decrease in 25(OH)D concentration, the odds of ARTI increased by 1.02 (0.97-1.07). This was a non-linear trend, with the sharpest increase in risk of ARTI occurring at 25(OH)D concentration < 37.5 nmol/L. In conclusion, there is an inverse non-linear association between 25(OH)D concentration and ARTI.
Topics: Acute Disease; Humans; Observational Studies as Topic; Respiratory Tract Infections; Vitamin D; Vitamins
PubMed: 31438516
DOI: 10.3390/ijerph16173020 -
Nutrition Journal Sep 2022Among candidate genes related to type 2 diabetes (T2DM), one of the strongest genes is Transcription factor 7 like 2 (TCF7L2), regarding the Genome-Wide Association... (Review)
Review
BACKGROUND
Among candidate genes related to type 2 diabetes (T2DM), one of the strongest genes is Transcription factor 7 like 2 (TCF7L2), regarding the Genome-Wide Association Studies. We aimed to conduct a systematic review of the literature on the modification effect of TCF7L2 on the relation between glycemic parameters and lifestyle factors.
METHODS
A systematic literature search was done for relevant publications using electronic databases, including PubMed, EMBASE, Scopus, and Web of Science, from January 1, 2000, to November 2, 2021.
RESULTS
Thirty-eight studies (16 observational studies, six meal test trials, and 16 randomized controlled trials (RCTs)) were included. Most observational studies had been conducted on participants with non-diabetes showing that TCF7L2 modified the association between diet (fatty acids and fiber) and insulin resistance. In addition, findings from meal test trials showed that, compared to non-risk-allele carriers, consumption of meals with different percentages of total dietary fat in healthy risk-allele carriers increased glucose concentrations and impaired insulin sensitivity. However, ten RCTs, with intervention periods of less than ten weeks and more than one year, showed that TCF7L2 did not modify glycemic parameters in response to a dietary intervention involving different macronutrients. However, two weight loss dietary RCTs with more than 1-year duration showed that serum glucose and insulin levels decreased and insulin resistance improved in non-risk allele subjects with overweight/obesity. Regarding artichoke extract supplementation (ALE), two RCTs observed that ALE supplementation significantly decreased insulin concentration and improved insulin resistance in the TT genotype of the rs7903146 variant of TCF7L2. In addition, four studies suggested that physical activity levels and smoking status modified the association between TCF7L2 and glycemic parameters. However, three studies observed no effect of TCF7L2 on glycemic parameters in participants with different levels of physical activity and smoking status.
CONCLUSION
The modification effects of TCF7L2 on the relation between the lifestyle factors (diet, physical activity, and smoking status) and glycemic parameters were contradictory.
PROSPERO REGISTRATION NUMBER
CRD42020196327.
Topics: Blood Glucose; Diabetes Mellitus, Type 2; Dietary Fats; Fatty Acids; Humans; Insulin; Insulin Resistance; Life Style; Polymorphism, Single Nucleotide; T Cell Transcription Factor 1; Transcription Factor 7-Like 2 Protein
PubMed: 36155628
DOI: 10.1186/s12937-022-00813-w