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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 -
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 -
Biochemistry and Cell Biology =... Feb 2017Lactoferrin (LF) is a breast milk glycoprotein with antimicrobial and anti-inflammatory effects. Its beneficial properties in infants, especially in those born preterm,... (Review)
Review
Lactoferrin (LF) is a breast milk glycoprotein with antimicrobial and anti-inflammatory effects. Its beneficial properties in infants, especially in those born preterm, are currently being studied in clinical trials. However, the maternal and nursing infant factors that may affect LF concentration in breast milk are still not clear. We conducted a systematic review to investigate the factors that may affect the concentration of LF in breast milk. We used a 2-step approach to identify the eligible studies according to inclusion/exclusion criteria, and to determine which studies would be considered. We included 70 qualified articles from 29 countries with publication dates ranging from 1976 to 2015. We described the correlation between LF concentration in breast milk and lactation stage; 10 maternal factors, such as race, parity, among others; and 2 infant factors: infections and prematurity. Colostrum has the highest LF levels, but they decrease with days postpartum. No other factor has been consistently associated with LF concentration. A major limitation of the majority of the published studies is the small sample size and the different methods used to measure LF concentration. Therefore, there is a need for large, multicenter studies with standardized study design, sample collection, and LF measurement methods to identify clinically significant factors associated with LF expression in breast milk, which will help promote exclusive breastfeeding in preterm infants.
Topics: Female; Humans; Lactation; Lactoferrin; Milk, Human
PubMed: 28075610
DOI: 10.1139/bcb-2016-0060 -
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 -
Research in Veterinary Science Oct 2017A systematic review and meta-analysis (MA) were performed to summarize all scientific evidence for the effects of castration in male beef cattle on welfare indicators... (Meta-Analysis)
Meta-Analysis Review
A systematic review and meta-analysis (MA) were performed to summarize all scientific evidence for the effects of castration in male beef cattle on welfare indicators based on cortisol concentration, average daily gain (ADG), and vocalization. We searched five electronic databases, conference proceedings, and experts were contacted electronically. The main inclusion criteria involved completed studies using beef cattle up to one year of age undergoing surgical and non-surgical castration that presented cortisol concentration, ADG, or vocalization as an outcome. A random effect MA was conducted for each indicator separately with the mean of the control and treated groups. A total of 20 publications reporting 26 studies and 162 trials were included in the MA involving 1814 cattle. Between study heterogeneity was observed when analysing cortisol (I=56.7%) and ADG (I=79.6%). Surgical and non-surgical castration without drug administration compared to uncastrated animals showed no change (P≥0.05) in cortisol level. Multimodal therapy for pain did not decrease (P≥0.05) cortisol concentration after 30min when non-surgical castration was performed. Comparison between surgical castration, with and without anaesthesia, showed a tendency (P=0.077) to decrease cortisol levels after 120min of intervention. Non-surgical and surgical castration, performed with no pain mitigation, increased and tended to increase the ADG by 0.814g/d (P=0.001) and by 0.140g/d (P=0.091), respectively, when compared to a non-castrated group. Our MA study demonstrates an inconclusive result to draw recommendations on preferred castration practices to minimize pain in beef cattle.
Topics: Animals; Cattle; Hydrocortisone; Male; Orchiectomy; Pain Management; Vocalization, Animal; Weight Gain
PubMed: 28755556
DOI: 10.1016/j.rvsc.2017.07.014 -
Ecotoxicology and Environmental Safety Sep 2021Zearalenone (ZEA) is an oestrogen-like mycotoxin produced by Fusarium fungi, which has a considerable impact on human and animal health and results in substantial... (Meta-Analysis)
Meta-Analysis
Zearalenone (ZEA) is an oestrogen-like mycotoxin produced by Fusarium fungi, which has a considerable impact on human and animal health and results in substantial economic losses worldwide. This study aimed to demonstrate the reproductive injury induced by ZEA in rodents. We conducted a rigorous meta-analysis of the related literature via PubMed, Embase, and Web of Science. The scope of the study includes the following: development of reproductive organs, serum testosterone, oestradiol, and luteinizing hormone (LH) levels; parameters of Leydig cells; and parameters of semen. In total, 19 articles were reviewed. Compared with the control group, the increased relative epididymis weight, increased serum oestradiol level, and decreased LH levels in the prenatally exposed group were observed. In pubertal and adult rodents, the relative testicular weight, serum oestradiol level, Leydig cell number, and percentage of ST (+) Leydig cells decreased under ZEA exposure. In rodents at all ages, decreased serum testosterone level, sperm concentration, sperm motility rate, and increased serum deformity rate were observed in exposed groups compared with control groups. Although subgroup analysis failed to identify a clear dose-response relationship between ZEA exposure and reproductive system damage in male rodents, we still managed to confirm that zearalenone could decrease the serum testosterone level at the dosage of 50 mg/kg*day, 1.4 mg/kg*day, and 84 mg/kg*day, of prenatal, pubertal, and mature rodents respectively; pubertal zearalenone exposure impairs the quality and quantity of sperms of rodents at the dosage of 1.4 mg/kg*day and mature zearalenone exposure has the same effect at the dosage of 84 mg/kg*day. In conclusion, we found that ZEA exposure can cause considerable damage to the reproductive system of rodents of all ages. While the exact underlying mechanism of ZEA-induced toxicity in the reproductive system remains largely unknown, the theories of oestrogen-like effects and oxidative stress damage are promising.
Topics: Animals; Estrogens; Male; Reproduction; Zearalenone
PubMed: 34175827
DOI: 10.1016/j.ecoenv.2021.112457 -
Parasitology Research Feb 2016Protozoan parasitic diseases are endemic in many countries worldwide, especially in developing countries, where infertility is a major burden. It has been reported that... (Review)
Review
Protozoan parasitic diseases are endemic in many countries worldwide, especially in developing countries, where infertility is a major burden. It has been reported that such infections may cause infertility through impairment in male and female reproductive systems. We searched Medline, PubMed, and Scopus databases and Google scholar to identify the potentially relevant studies on protozoan parasitic infections and their implications in human and animal model infertility. Literature described that some of the protozoan parasites such as Trichomonas vaginalis may cause deformities of the genital tract, cervical neoplasia, and tubal and atypical pelvic inflammations in women and also non-gonoccocal urethritis, asthenozoospermia, and teratozoospermia in men. Toxopalasma gondii could cause endometritis, impaired folliculogenesis, ovarian and uterine atrophy, adrenal hypertrophy, vasculitis, and cessation of estrus cycling in female and also decrease in semen quality, concentration, and motility in male. Trypanosoma cruzi inhibits cell division in embryos and impairs normal implantation and development of placenta. Decrease in gestation rate, infection of hormone-producing glands, parasite invasion of the placenta, and overproduction of inflammatory cytokines in the oviducts and uterine horns are other possible mechanisms induced by Trypanosoma cruzi to infertility. Plasmodium spp. and Trypanosoma brucei spp. cause damage in pituitary gland, hormonal disorders, and decreased semen quality. Entamoeba histolytica infection leads to pelvic pain, salpingitis, tubo-ovarian abscess, and genital ulcers. Cutaneous and visceral leishmaniasis can induce genital lesion, testicular amyloidosis, inflammation of epididymis, prostatitis, and sperm abnormality in human and animals. In addition, some epidemiological studies have reported that rates of protozoan infections in infertile patients are higher than healthy controls. The current review indicates that protozoan parasitic infections may be an important cause of infertility. Given the widespread prevalence of parasitic protozoa diseases worldwide, we suggest further studies to better understanding of relationship between such infections and infertility.
Topics: Animals; Female; Humans; Infertility; Male; Pregnancy; Pregnancy Complications, Parasitic; Protozoan Infections; Semen
PubMed: 26573517
DOI: 10.1007/s00436-015-4827-y