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Spectrochimica Acta. Part A, Molecular... Jul 2022Under heating conditions, L-Glutamic acid (L-Glu) can be dehydrated to form L-pyroglutamic acid (L-PGA), and L-PGA can racemize to form DL-PGA. Here, we characterized...
Under heating conditions, L-Glutamic acid (L-Glu) can be dehydrated to form L-pyroglutamic acid (L-PGA), and L-PGA can racemize to form DL-PGA. Here, we characterized this transformation at different temperatures and times by terahertz time domain spectroscopy (THz-TDS). By Powder X-ray diffraction (PXRD), the validity of THz spectroscopy is verified. The results prove that the reaction rate of dehydration and racemization is significantly affected by temperature. The THz spectra divided the reactions into three stages. At 150-155 °C, the reaction changes drastically. Furthermore, we found that the absorption intensity at 0.97 and 1.55 THz has a good dependence on the reaction temperature and time, showing a non-linear relationship (R > 0.98). Our findings suggest that the chemical transformation and reaction rate can be sensitively probed by terahertz spectroscopy, which provides a potential method for the quantitative analysis of reaction products.
Topics: Glutamic Acid; Pyrrolidonecarboxylic Acid; Temperature; Terahertz Spectroscopy
PubMed: 35313170
DOI: 10.1016/j.saa.2022.121150 -
BMC Anesthesiology Mar 2021Metabolic status can be impacted by general anesthesia and surgery. However, the exact effects of general anesthesia and surgery on systemic metabolome remain unclear,... (Observational Study)
Observational Study
BACKGROUND
Metabolic status can be impacted by general anesthesia and surgery. However, the exact effects of general anesthesia and surgery on systemic metabolome remain unclear, which might contribute to postoperative outcomes.
METHODS
Five hundred patients who underwent abdominal surgery were included. General anesthesia was mainly maintained with sevoflurane. The end-tidal sevoflurane concentration (ET) was adjusted to maintain BIS (Bispectral index) value between 40 and 60. The mean ET from 20 min after endotracheal intubation to 2 h after the beginning of surgery was calculated for each patient. The patients were further divided into low ET group (mean - SD) and high ET group (mean + SD) to investigate the possible metabolic changes relevant to the amount of sevoflurane exposure.
RESULTS
The mean ET of the 500 patients was 1.60% ± 0.34%. Patients with low ET (n = 55) and high ET (n = 59) were selected for metabolomic analysis (1.06% ± 0.13% vs. 2.17% ± 0.16%, P < 0.001). Sevoflurane and abdominal surgery disturbed the tricarboxylic acid cycle as identified by increased citrate and cis-aconitate levels and impacted glycometabolism as identified by increased sucrose and D-glucose levels in these 114 patients. Glutamate metabolism was also impacted by sevoflurane and abdominal surgery in all the patients. In the patients with high ET, levels of L-glutamine, pyroglutamic acid, sphinganine and L-selenocysteine after sevoflurane anesthesia and abdominal surgery were significantly higher than those of the patients with low ET, suggesting that these metabolic changes might be relevant to the amount of sevoflurane exposure.
CONCLUSIONS
Sevoflurane anesthesia and abdominal surgery can impact principal metabolic pathways in clinical patients including tricarboxylic acid cycle, glycometabolism and glutamate metabolism. This study may provide a resource data for future studies about metabolism relevant to general anaesthesia and surgeries.
TRIAL REGISTRATION
www.chictr.org.cn . identifier: ChiCTR1800014327 .
Topics: Abdomen; Anesthesia, General; Anesthetics, Inhalation; Citric Acid; Female; Glucose; Glutamic Acid; Glutamine; Humans; Male; Metabolome; Middle Aged; Prospective Studies; Pyrrolidonecarboxylic Acid; Selenocysteine; Sevoflurane; Sphingosine; Sucrose
PubMed: 33731015
DOI: 10.1186/s12871-021-01301-0 -
The Journal of Endocrinology Feb 2019Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder in the elderly population. Numerous epidemiological and experimental studies have demonstrated... (Review)
Review
Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder in the elderly population. Numerous epidemiological and experimental studies have demonstrated that patients who suffer from obesity or type 2 diabetes mellitus have a higher risk of cognitive dysfunction and AD. Several recent studies demonstrated that food intake-lowering (anorexigenic) peptides have the potential to improve metabolic disorders and that they may also potentially be useful in the treatment of neurodegenerative diseases. In this review, the neuroprotective effects of anorexigenic peptides of both peripheral and central origins are discussed. Moreover, the role of leptin as a key modulator of energy homeostasis is discussed in relation to its interaction with anorexigenic peptides and their analogs in AD-like pathology. Although there is no perfect experimental model of human AD pathology, animal studies have already proven that anorexigenic peptides exhibit neuroprotective properties. This phenomenon is extremely important for the potential development of new drugs in view of the aging of the human population and of the significantly increasing incidence of AD.
Topics: Alzheimer Disease; Animals; Appetite Depressants; Disease Models, Animal; Energy Metabolism; Homeostasis; Humans; Leptin; Neuroprotective Agents; Oligopeptides; Pyrrolidonecarboxylic Acid
PubMed: 30475219
DOI: 10.1530/JOE-18-0532 -
The Journal of Comparative Neurology Jun 2018Holometabolous insects undergo metamorphosis to reorganize their behavioral and morphological features into adult-specific ones. In the central nervous system (CNS),...
Holometabolous insects undergo metamorphosis to reorganize their behavioral and morphological features into adult-specific ones. In the central nervous system (CNS), some larval neurons undergo programmed cell death, whereas others go through remodeling of axonal and dendritic arbors to support functions of re-established adult organs. Although there are multiple neuropeptides that have stage-specific roles in holometabolous insects, the reorganization pattern of the entire neuropeptidergic system through metamorphosis still remains largely unclear. In this study, we conducted a mapping and lineage tracing of peptidergic neurons in the larval and adult CNS by using Drosophila genetic tools. We found that Diuretic hormone 44-producing median neurosecretory cells start expressing Insulin-like peptide 2 in the pharate adult stage. This neuronal cluster projects to the corpora cardiaca and dorsal vessel in both larval and adult stages, and also innervates an adult-specific structure in the digestive tract, the crop. We propose that the adult-specific insulin-producing cells may regulate functions of the digestive system in a stage-specific manner. Our study provides a neuroanatomical basis for understanding remodeling of the neuropeptidergic system during insect development and evolution.
Topics: Animals; Animals, Genetically Modified; Antigens, CD; Central Nervous System; Drosophila Proteins; Drosophila melanogaster; Gene Expression Regulation; Green Fluorescent Proteins; Inhibitor of Apoptosis Proteins; Insect Hormones; Insulin; Larva; Methyltransferases; Neurons; Oligopeptides; Pyrrolidonecarboxylic Acid; RNA, Messenger; Transcription Factors
PubMed: 29424424
DOI: 10.1002/cne.24410 -
Scientific Reports Aug 2019Fibromyalgia (FM) is characterized by chronic widespread pain. The pathogenesis of FM remains unclear. No specific biomarkers are available. Animal models of FM may...
Fibromyalgia (FM) is characterized by chronic widespread pain. The pathogenesis of FM remains unclear. No specific biomarkers are available. Animal models of FM may provide an opportunity to explore potential biomarkers in a relative homogenous disease condition. Here, we probed the metabolomics profiles of serum and urine in a mouse model of FM induced by intermittent cold stress (ICS). We focused on the role of acid-sensing ion channel 3 (ASIC3) in the metabolomics profiling because ICS treatment induced chronic widespread muscle pain lasting for 1 month in wild-type (Asic3) but not Asic3-knockout (Asic3) mice. Serum and urine samples were collected from both genotypes at different ICS stages, including before ICS (basal level) and post-ICS at days 10 (middle phase, P10) and 40 (recovery phase, P40). Control naïve mice and ICS-induced FM mice differed in H-NMR- and LC-MS-based metabolomics profiling. On pathway analysis, the leading regulated pathways in Asic3 mice were taurine and hypotaurine, cysteine and methionine, glycerophospholipid, and ascorbate and aldarate metabolisms, and the major pathways in Asic3 mice involved amino acid-related metabolism. Finally, we developed an algorithm for the impactful metabolites in the FM model including cis-aconitate, kynurenate, taurine, pyroglutamic acid, pyrrolidonecarboxylic acid, and 4-methoxyphenylacetic acid in urine as well as carnitine, deoxycholic acid, lysoPC(16:0), lysoPC(20:3), oleoyl-L-carnitine, and trimethylamine N-oxide in serum. Asic3 mice were impaired in only muscle allodynia development but not other pain symptoms in the ICS model, so the ASIC3-dependent metabolomics changes could be useful for developing diagnostic biomarkers specific to chronic widespread muscle pain, the core symptom of FM. Further pharmacological validations are needed to validate these metabolomics changes as potential biomarkers for FM diagnosis and/or treatment responses.
Topics: Acid Sensing Ion Channels; Algorithms; Animals; Biomarkers; Chronic Pain; Cold Temperature; Disease Models, Animal; Disease Progression; Female; Fibromyalgia; Metabolomics; Mice, Inbred C57BL; Mice, Knockout; Myalgia; Stress, Physiological
PubMed: 31431652
DOI: 10.1038/s41598-019-48315-w -
Fish & Shellfish Immunology Jan 2022Pidotimod (PDT) is a synthetic dipeptide molecule which can improve immune responses in mice and humans, protecting hosts from infection. However, the exact mechanism of...
Pidotimod (PDT) is a synthetic dipeptide molecule which can improve immune responses in mice and humans, protecting hosts from infection. However, the exact mechanism of protection remains ill-defined. The effect of pidotimod has not yet been investigated in the inflammatory response of zebrafish. In this study, we used tail wound and infection models of zebrafish to study the effect of PDT on inflammation. We found that zebrafish larvae were sensitive to PDT immersion causing toxicity at doses above 50 μg/mL. The tail wound assay showed that PDT increased the recruitment of neutrophils and macrophages to the wound site and promoted the transcription of the pro-inflammatory cytokine il1b. However, we did not observe protection of uropathogenic Escherichia coli or Mycobacterium marinum infected zebrafish larvae following PDT treatment. This study provides a new platform for PDT research, which is worthy of further research to identify further effects of PDT therapy.
Topics: Animals; Inflammation; Larva; Pyrrolidonecarboxylic Acid; Thiazolidines; Zebrafish
PubMed: 34922016
DOI: 10.1016/j.fsi.2021.12.013 -
Expert Review of Anti-infective Therapy Oct 2019: The majority of acute respiratory tract infections (RTIs) are caused by viruses and the overzealous use of antibacterial drugs, when not really required, is a cause... (Review)
Review
: The majority of acute respiratory tract infections (RTIs) are caused by viruses and the overzealous use of antibacterial drugs, when not really required, is a cause for concern. This has led to evaluation of alternative approaches such as boosting the immune response in individuals who are most vulnerable to develop RTIs such as the very young and the elderly. : This article overviews the immunostimulant activity and pharmacokinetic properties of pidotimod, and focuses on assessing its role in the treatment and prevention of acute RTIs through evaluation of clinical trials and real-world evidence. Articles were obtained from a full search of Medline, and this was augmented by published clinical studies known to the authors and manufacturer. : Pidotimod's activity was shown to be mediated via multiple pathways of the immune system. Comparison with placebo demonstrated significant advantages for pidotimod in terms of reduced reinfection rates [OR 0.20, 95% CI 0.12 to 0.33; p < 0.00001], a lesser need for antibiotics [mean difference -2.65, 95% CI -3.68 to -1.62; p < 0.00001] and rescue medications, and decreased absenteeism [mean difference-2.99, 95% CI -4.03 to -1.95; p < 0.00001]. No safety concerns were raised in these studies.
Topics: Acute Disease; Animals; Humans; Immunologic Factors; Pyrrolidonecarboxylic Acid; Respiratory Tract Infections; Risk Factors; Thiazolidines; Treatment Outcome
PubMed: 31603361
DOI: 10.1080/14787210.2019.1679118 -
Metabolomics : Official Journal of the... Mar 2023Increased exposure to risk factors in the young and healthy contributes to arterial changes, which may be accompanied by an altered metabolism.
INTRODUCTION
Increased exposure to risk factors in the young and healthy contributes to arterial changes, which may be accompanied by an altered metabolism.
OBJECTIVES
To increase our understanding of early metabolic alterations and how they associate with markers of arterial stiffness, we profiled urinary metabolites in young adults with cardiovascular disease (CVD) risk factor(s) and in a control group without CVD risk factors.
METHODS
We included healthy black and white women and men (N = 1202), aged 20-30 years with a detailed CVD risk factor profile, reflecting obesity, physical inactivity, smoking, excessive alcohol intake, masked hypertension, hyperglycemia, dyslipidemia and low socio-economic status, forming the CVD risk group (N = 1036) and the control group (N = 166). Markers of arterial stiffness, central systolic blood pressure (BP) and pulse wave velocity were measured. A targeted metabolomics approach was followed by measuring amino acids and acylcarnitines using a liquid chromatography-tandem mass spectrometry method.
RESULTS
In the CVD risk group, central systolic BP (adjusted for age, sex, ethnicity) was negatively associated with histidine, arginine, asparagine, serine, glutamine, dimethylglycine, threonine, GABA, proline, methionine, pyroglutamic acid, aspartic acid, glutamic acid, branched chain amino acids (BCAAs) and butyrylcarnitine (all P ≤ 0.048). In the same group, pulse wave velocity (adjusted for age, sex, ethnicity, mean arterial pressure) was negatively associated with histidine, lysine, threonine, 2-aminoadipic acid, BCAAs and aromatic amino acids (AAAs) (all P ≤ 0.044). In the control group, central systolic BP was negatively associated with pyroglutamic acid, glutamic acid and dodecanoylcarnitine (all P ≤ 0.033).
CONCLUSION
In a group with increased CVD risk, markers of arterial stiffness were negatively associated with metabolites related to AAA and BCAA as well as energy metabolism and oxidative stress. Our findings may suggest that metabolic adaptations may be at play in response to increased CVD risk to maintain cardiovascular integrity.
Topics: Male; Humans; Female; Young Adult; Cardiovascular Diseases; Risk Factors; Metabolomics; Vascular Stiffness; Histidine; Pyrrolidonecarboxylic Acid; Pulse Wave Analysis; Amino Acids, Branched-Chain; Heart Disease Risk Factors; Threonine
PubMed: 36988718
DOI: 10.1007/s11306-023-01987-y -
Computational and Mathematical Methods... 2020The current emergence of coronavirus (SARS-CoV-2) puts the world in threat. The structural research on the receptor recognition by SARS-CoV-2 has identified the key...
The current emergence of coronavirus (SARS-CoV-2) puts the world in threat. The structural research on the receptor recognition by SARS-CoV-2 has identified the key interactions between SARS-CoV-2 spike protein and its host (epithelial cell) receptor, also known as angiotensin-converting enzyme 2 (ACE2). It controls both the cross-species and human-to-human transmissions of SARS-CoV-2. In view of this, we propose and analyze a mathematical model for investigating the effect of CTL responses over the viral mutation to control the viral infection when a postinfection immunostimulant drug (pidotimod) is administered at regular intervals. Dynamics of the system with and without impulses have been analyzed using the basic reproduction number. This study shows that the proper dosing interval and drug dose both are important to eradicate the viral infection.
Topics: Adjuvants, Immunologic; Angiotensin-Converting Enzyme 2; Basic Reproduction Number; Betacoronavirus; COVID-19; Computer Simulation; Coronavirus Infections; Dose-Response Relationship, Drug; Host Microbial Interactions; Humans; Mathematical Concepts; Models, Biological; Mutation; Pandemics; Peptidyl-Dipeptidase A; Pneumonia, Viral; Pyrrolidonecarboxylic Acid; Receptors, Virus; SARS-CoV-2; Spike Glycoprotein, Coronavirus; T-Lymphocytes, Cytotoxic; Thiazolidines; COVID-19 Drug Treatment
PubMed: 32908574
DOI: 10.1155/2020/1352982 -
Spectrochimica Acta. Part A, Molecular... Feb 2022Hydroxyproline (HYP) and pyroglutamic acid (PGA), as amino acid derivatives, are highly similar in structure to proline (Pro). However, their low-frequency vibrations...
Hydroxyproline (HYP) and pyroglutamic acid (PGA), as amino acid derivatives, are highly similar in structure to proline (Pro). However, their low-frequency vibrations show significant differences in the range of 0.25-2.6 THz. Therefore, this study investigated the reasons for the differences combined with terahertz time domain spectroscopy (THz-TDS) and density functional theory (DFT). The results show that HYP and PGA have stronger absorption of terahertz waves due to the existence of polar substituents. Furthermore, the absorption peaks of HYP and PGA are significant red shifted and blue shifted, respectively. We believe that this is caused by the change in the strength of intermolecular hydrogen bonds. Our findings demonstrate that dipole and hydrogen bond effects play a significant role in low-frequency vibrations.
Topics: Hydrogen Bonding; Hydroxyproline; Proline; Pyrrolidonecarboxylic Acid; Terahertz Spectroscopy
PubMed: 34742154
DOI: 10.1016/j.saa.2021.120539