-
Microorganisms Feb 2024Evidence shows that the gut microbiome in early life is an essential modulator of physiological processes related to healthy brain development, as well as mental and... (Review)
Review
Evidence shows that the gut microbiome in early life is an essential modulator of physiological processes related to healthy brain development, as well as mental and neurodegenerative disorders. Here, we conduct a systematic review of gut microbiome assessments on infants (both healthy and with conditions that affect brain development) during the first thousand days of life, associated with neurodevelopmental outcomes, with the aim of investigating key microbiome players and mechanisms through which the gut microbiome affects the brain. and were associated with non-social fear behavior, duration of orientation, cognitive and motricity development, and neurotypical brain development. Lachnospiraceae, , and showed variable levels of influence on behavior and brain development. Few studies described mechanistic insights related to NAD salvage, aspartate and asparagine biosynthesis, methanogenesis, pathways involved in bile acid transformation, short-chain fatty acids production, and microbial virulence genes. Further studies associating species to gene pathways and robustness in data analysis and integration are required to elucidate the functional mechanisms underlying the role of microbiome-gut-brain axis in early brain development.
PubMed: 38543475
DOI: 10.3390/microorganisms12030424 -
Archives of Medical Research Jan 2024The underdiagnosis and inadequate treatment of rheumatoid arthritis (RA) can be attributed to the various clinical manifestations presented by patients. To address this... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The underdiagnosis and inadequate treatment of rheumatoid arthritis (RA) can be attributed to the various clinical manifestations presented by patients. To address this concern, we conducted an extensive review and meta-analysis, focusing on RA-related metabolites.
METHODS
A comprehensive literature search was conducted in PubMed, the Cochrane Library, Web of Science, and Embase to identify relevant studies published up to October 5, 2022. The quality of the included articles was evaluated and, subsequently, a meta-analysis was conducted using Review Manager software to analyze the association between metabolites and RA.
RESULTS
Forty nine studies met the inclusion criteria for the systematic review, and six of these studies were meta-analyzed to evaluate the association between 28 reproducible metabolites and RA. The results indicated that, compared to controls, the levels of histidine (RoM = 0.83, 95% CI = 0.79-0.88, I = 0%), asparagine (RoM = 0.83, 95% CI = 0.75-0.91, I = 0%), methionine (RoM = 0.82, 95% CI = 0.69-0.98, I = 85%), and glycine (RoM = 0.81, 95% CI = 0.67-0.97, I = 68%) were significantly lower in RA patients, while hypoxanthine levels (RoM = 1.14, 95% CI = 1.09-1.19, I = 0%) were significantly higher.
CONCLUSION
This study identified histidine, methionine, asparagine, hypoxanthine, and glycine as significantly correlated with RA, thus offering the potential for the advancement of biomarker discovery and the elucidation of disease mechanisms in RA.
Topics: Humans; Arthritis, Rheumatoid; Hypoxanthines; Metabolomics; Amino Acids
PubMed: 38029644
DOI: 10.1016/j.arcmed.2023.102907 -
Nutrients Sep 2023(1) Many studies have attempted to utilize metabolomic approaches to explore potential biomarkers for the early detection of osteoarthritis (OA), but consistent and... (Meta-Analysis)
Meta-Analysis Review
(1) Many studies have attempted to utilize metabolomic approaches to explore potential biomarkers for the early detection of osteoarthritis (OA), but consistent and high-level evidence is still lacking. In this study, we performed a systematic review and meta-analysis of differential small molecule metabolites between OA patients and healthy individuals to screen promising candidates from a large number of samples with the aim of informing future prospective studies. (2) Methods: We searched the EMBASE, the Cochrane Library, PubMed, Web of Science, Wan Fang Data, VIP Date, and CNKI up to 11 August 2022, and selected relevant records based on inclusion criteria. The risk of bias was assessed using the Newcastle-Ottawa quality assessment scale. We performed qualitative synthesis by counting the frequencies of changing directions and conducted meta-analyses using the random effects model and the fixed-effects model to calculate the mean difference and 95% confidence interval. (3) Results: A total of 3798 records were identified and 13 studies with 495 participants were included. In the 13 studies, 132 kinds of small molecule differential metabolites were extracted, 58 increased, 57 decreased and 17 had direction conflicts. Among them, 37 metabolites appeared more than twice. The results of meta-analyses among four studies showed that three metabolites increased, and eight metabolites decreased compared to healthy controls (HC). (4) Conclusions: The main differential metabolites between OA and healthy subjects were amino acids (AAs) and their derivatives, including tryptophan, lysine, leucine, proline, phenylalanine, glutamine, dimethylglycine, citrulline, asparagine, acetylcarnitine and creatinine (muscle metabolic products), which could be potential biomarkers for predicting OA.
Topics: Humans; Prospective Studies; Osteoarthritis; Biomarkers; Bias; Health Status
PubMed: 37836475
DOI: 10.3390/nu15194191 -
Critical Reviews in Food Science and... 2024Acrylamide (AA) is a toxic substance formed in many carbohydrate-rich food products, whose formation can be reduced by adding some additives. Furthermore, the type of...
Acrylamide (AA) is a toxic substance formed in many carbohydrate-rich food products, whose formation can be reduced by adding some additives. Furthermore, the type of food consumed determines the AA intake. According to the compiled information, the first route causing AA formation is the Maillard reaction. Some interventions, such as reducing AA precursors in raw materials, (i.e., asparagine), reducing sugars, or decreasing temperature and processing time can be applied to limit AA formation in food products. The L-asparaginase is more widely used in potato products. Also, coatings loaded with proteins, enzymes, and phenolic compounds are new techniques for reducing AA content. Enzymes have a reducing effect on AA formation by acting on asparagine; proteins by competing with amino acids to participate in Maillard, and phenolic compounds through their radical scavenging activity. On the other hand, some synthetic and natural additives increase the formation of AA. Due to the high exposure to AA and its toxic effects, it is essential to recognize suitable food additives to reduce the health risks for consumers. In this sense, this study focuses on different additives that are proven to be effective in the reduction or formation of AA in food products.
Topics: Asparagine; Acrylamide; Hot Temperature; Carbohydrates; Asparaginase; Maillard Reaction
PubMed: 36194060
DOI: 10.1080/10408398.2022.2126428 -
Cancers Dec 2021Patients with malignant pleural mesothelioma (MPM) have very poor prognoses, and pemetrexed plus platinum is the standard first-line therapy. However, the second-line... (Review)
Review
Patients with malignant pleural mesothelioma (MPM) have very poor prognoses, and pemetrexed plus platinum is the standard first-line therapy. However, the second-line therapy for relapsed MPM remains controversial. A comprehensive search was performed to identify randomized controlled trials (RCTs) evaluating various second-line regimens in patients with relapsed MPM. Indirect comparisons of overall survival (OS) and progression-free survival (PFS) were performed using network meta-analysis. Surface under the cumulative ranking curve (SUCRA) values were used to rank the included treatments according to each outcome. Nivolumab alone or nivolumab plus ipilimumab provided significantly longer OS than placebo (hazard ratio (HR): 0.72, 95% confidence interval (CI): 0.55-0.94 for nivolumab alone; HR: 0.54, 95% CI: 0.31-0.92 for nivolumab plus ipilimumab). The best SUCRA ranking for OS was identified for nivolumab plus ipilimumab (SUCRA: 90.8%). Tremelimumab, vorinostat, nivolumab alone, chemotherapy (CTX), asparagine-glycine-arginine-human tumor necrosis factor plus CTX, and nivolumab plus ipilimumab all produced noticeable PFS benefits compared with placebo. Nivolumab plus ipilimumab had the best PFS ranking (SUCRA: 92.3%). Second-line treatment with nivolumab plus ipilimumab provided the OS and PFS outcomes for patients with relapsed MPM.
PubMed: 35008346
DOI: 10.3390/cancers14010182 -
European Journal of Cancer (Oxford,... Nov 2021This review focuses on asparaginase, a key component of childhood acute lymphoblastic leukaemia (ALL) treatment since the 1970s. This review evaluates how much...
This review focuses on asparaginase, a key component of childhood acute lymphoblastic leukaemia (ALL) treatment since the 1970s. This review evaluates how much asparaginase is needed for optimal outcome in childhood ALL. We provide an overview of asparaginase dose intensity, i.e. duration of total cumulative exposure in weeks and level of exposure reflected by dose and/or asparaginase activity level, and the corresponding outcome. We systematically searched papers published between January 1990 and March 2021 in the PubMed and MEDLINE databases and included 20 papers. The level and duration of exposure were based on the pharmacokinetic profile of the drug and the assumption that trough asparaginase activity levels of ≥100 IU/L should be achieved for complete l-asparagine depletion. The statistical meta-analysis of outcomes was not performed because different outcome measures were used. The level of exposure was not associated with the outcome as long as therapeutic asparaginase activity levels of ≥100 IU/L were reached. Conflicting results were found in the randomised controlled trials, but all truncation studies showed that the duration of exposure (expressed as weeks of l-asparagine depletion) does affect the outcome; however, no clear cutoff for optimal exposure duration was determined. Optimal exposure duration will also depend on immunophenotype, (cyto)genetic subgroups, risk group stratification and backbone therapy.
Topics: Antineoplastic Agents; Asparaginase; Child; Disease-Free Survival; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Neoplasm Recurrence, Local; Polyethylene Glycols; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Progression-Free Survival; Randomized Controlled Trials as Topic; Time Factors
PubMed: 34536947
DOI: 10.1016/j.ejca.2021.08.025 -
International Journal of Molecular... Oct 2019The scientific literature has demonstrated that glutamine is one of the main beneficial amino acids. It plays an important role in gut microbiota and immunity. This...
The scientific literature has demonstrated that glutamine is one of the main beneficial amino acids. It plays an important role in gut microbiota and immunity. This paper provides a critical overview of experimental studies (in vitro, in vivo, and clinical) investigating the efficacy of glutamine and its effect on gut microbiota. As a result of this review, we have summarized that glutamine could affect gut microbiota via different mechanisms including the reduction in the ratio of to with the activation of NF-κB and PI3K-Akt pathways, reducing the intestinal colonization ( lesions) and bacterial overgrowth or bacterial translocation, increasing the production of secretory immunoglobulin A (SIgA) and immunoglobulin A+ (IgA) cells in the intestinal lumen, and decreasing asparagine levels. The potential applications of glutamine on gut microbiota include, but are not limited to, the management of obesity, bacterial translocation and community, cytokines profiles, and the management of side effects during post-chemotherapy and constipation periods. Further studies and reviews are needed regarding the effects of glutamine supplementation on other conditions in humans.
Topics: Animals; Diet; Gastrointestinal Microbiome; Glutamine; Humans; Nutrition Disorders
PubMed: 31652531
DOI: 10.3390/ijms20205232 -
Hematology, Transfusion and Cell Therapy 2020Acute lymphoblastic leukemia (ALL) is the cancer with the highest incidence in childhood and adolescence, and pharmacotherapy is the primary form of treatment.
INTRODUCTION
Acute lymphoblastic leukemia (ALL) is the cancer with the highest incidence in childhood and adolescence, and pharmacotherapy is the primary form of treatment.
OBJECTIVE AND METHODS
A systematic review of the efficacy and safety of polyethylene glycol (PEG)-asparaginase in acute lymphoblastic leukemia therapy in children and adolescents was conducted to compare it with native Escherichia coli L-asparaginase. PubMed, Web of Science, Science Direct, Cochrane Library, Scopus, LILACS (Latin American and Caribbean Health Sciences Literature) and EMBASE databases were selected. The following outcomes were analyzed: complete remission of the disease, event-free survival, overall survival, anti-asparaginase antibody level, hypersensitivity reactions, asparaginase and asparagine serum levels, number of postdiagnosis events, and overall mortality. Five randomized controlled trials were included. Analysis of the quality of evidence and risk of bias was performed using the Cochrane recommendation tool and the GRADE system.
RESULTS
The assessment results suggest that the level of certainty on the technology addressed is relatively weak from a methodological point of view. Evidence is insufficient to assess the effects on health outcomes because of the limited number and power of studies and important flaws in their design or conduct in classifying PEG-asparaginase as a superior drug or not, in the pharmacotherapy of ALL in children and adolescents. PEG-asparaginase can be used as a substitute for native E. coli L-asparaginase, demonstrating similar efficacy and safety.
CONCLUSION
The study may help decision-makers in the public health system to offer a more in-depth judgment on the therapeutic alternatives used to treat this neoplasm in children and adolescents.
PubMed: 31412986
DOI: 10.1016/j.htct.2019.01.013 -
Sleep and Microdialysis: An Experiment and a Systematic Review of Histamine and Several Amino Acids.Journal of Circadian Rhythms Jul 2019Sleep seems essential to proper functioning of the prefrontal cortex (PFC). The role of different neurotransmitters has been studied, mainly the catecholamines and...
Sleep seems essential to proper functioning of the prefrontal cortex (PFC). The role of different neurotransmitters has been studied, mainly the catecholamines and serotonin. Less attention has been paid to the amino acid transmitters and histamine. Here, we focus on the activity of these molecules in the PFC during sleep and sleep deprivation (SD). We determined extracellular concentrations of histamine and 8 amino acids in the medial PFC before, during and after SD. Additionally, we systematically reviewed the literature on studies reporting microdialysis measurements relating to sleep throughout the brain. In our experiment, median concentrations of glutamate were higher during SD than during baseline (p = 0.013) and higher during the dark-active than during the resting phase (p = 0.003). Glutamine was higher during post-SD recovery than during baseline (p = 0.010). For other compounds, no differences were observed between light and dark circadian phase, and between sleep deprivation, recovery and baseline. We retrieved 13 papers reporting on one or more of the molecules of interest during naturally occurring sleep, 2 during sleep deprivation and 2 during both. Only two studies targeted PFC. Histamine was low during sleep, but high during sleep deprivation and wakefulness, irrespective of brain area. Glu (k = 11) and GABA (k = 8) concentrations in different brain areas were reported to peak during sleep or wakefulness or to lack state-dependency. Aspartate, glycine, asparagine and taurine were less often studied (1-2 times), but peaked exclusively during sleep. Sleep deprivation increased glutamate and GABA exclusively in the cortex. Further studies are needed for drawing solid conclusions.
PubMed: 31303885
DOI: 10.5334/jcr.183