-
Pediatric Endocrinology, Diabetes, and... 2023Atherosclerosis, a precursor to cardiovascular disease (CVD), is deeply intertwined with lipid metabolism. The metabolic process in the Down syndrome (DS) population...
INTRODUCTION
Atherosclerosis, a precursor to cardiovascular disease (CVD), is deeply intertwined with lipid metabolism. The metabolic process in the Down syndrome (DS) population remain less explored. Aim of the study: This study examines the lipid profiles of DS in comparison to their siblings (CG), aiming to uncover potential atherosclerotic and CVD risks.
MATERIAL AND METHODS
The study included 42 people with DS (mean age 14.17 years) and the CG - 20 individuals (mean age 15.92 years). Anthropometric measurements: BMI, BMI SDS, and TMI were calculated. Lipid profile (LP) and metabolomics were determined.
RESULTS
LP: DS display significantly reduced HDL (DS vs. CG: 47±10 vs. 59 ±12 mg/dl; p = 0.0001) and elevated LDL (104 ±25 vs. 90 ±22 mg/dl; p = 0.0331). Triglycerides, APO A1, and APO B/APO A1 ratio corroborate with the elevated risk of CVD in DS. Despite no marked differences in: TCH and APO B, the DS group demonstrated a concerning BMI trend. Of 31 identified metabolites, 12 showed statistical significance (acetate, choline, creatinine, formate, glutamine, histidine, lysine, proline, pyroglutamate, threonine, tyrosine, and xanthine). However, only 8 metabolites passed the FDR validation (acetate, creatinine, formate, glutamine, lysine, proline, pyroglutamate, xanthine).
CONCLUSIONS
Down syndrome individuals show distinct cardiovascular risks, with decreased HDL and increased LDL levels. Combined with metabolomic disparities and higher BMI and TMI, this suggests an increased atherosclerosis risk compared to controls.
Topics: Humans; Child; Adult; Adolescent; Down Syndrome; Apolipoprotein A-I; Risk Factors; Creatinine; Glutamine; Lysine; Pyrrolidonecarboxylic Acid; Cardiovascular Diseases; Atherosclerosis; Apolipoproteins B; Xanthines; Acetates; Formates; Proline
PubMed: 38031830
DOI: 10.5114/pedm.2023.131162 -
Molecules (Basel, Switzerland) Nov 2023Venous thromboembolism is a serious problem because it significantly increases the risk of developing vascular complications in elderly patients with obesity or...
Venous thromboembolism is a serious problem because it significantly increases the risk of developing vascular complications in elderly patients with obesity or immobilization, cancer, and many other diseases. Thus, there is a need to study new therapeutic strategies, including new medicinal agents for the efficient and safe correction of thrombus disorders. In this work, we have synthesized a number of new amides and peptides of 4-amino-5-oxoprolines and studied their antiplatelet and antithrombotic activity in experiments in vitro and in vivo. It has been found that the newly obtained compounds slow down the process of thrombus formation in a model of arterial and venous thrombosis, without affecting plasma hemostasis parameters. (2,4)-4-Amino-1-(4-fluorophenyl)-5-oxoprolyl-()-phenylalanine proved to be the most efficient among the studied derivatives. The results obtained indicate the advisability of further studies on 5-oxoproline derivatives in order to design pharmaceutical agents for the prevention and treatment of the consequences of thrombosis.
Topics: Humans; Aged; Pyrrolidonecarboxylic Acid; Fibrinolytic Agents; Amides; Thrombosis; Peptides; Platelet Aggregation Inhibitors
PubMed: 37959820
DOI: 10.3390/molecules28217401 -
Amino Acids Nov 2023Small neuropeptides from the corpora cardiaca are responsible in cockroaches for the mobilisation of trehalose from the fat body into the haemolymph. Such...
Small neuropeptides from the corpora cardiaca are responsible in cockroaches for the mobilisation of trehalose from the fat body into the haemolymph. Such hypertrehalosaemic hormones (HrTHs) belong to the large family of insect adipokinetic hormones (AKHs); a few HrTHs were previously sequenced from cockroaches, and from genomic and/or transcriptomic information one may predict the genes encoding HrTHs from more species. Definite elucidation of the primary structure of the mature peptide with putative modifications needs analytical chemical methods. In the current study, we use high-resolution mass spectrometry coupled with liquid chromatography to identify unequivocally the HrTHs of 13 cockroach species. Either genomic/transcriptomic information was available for most of the species examined, or from related species. We confirm predicted novel sequences and find hydroxyproline modification for the majority of the peptides. The novel decapeptides are structurally close to Bladi-HrTH, which is found in all seven of the investigated blaberid subfamilies. Bladi-HrTH and all the novel peptides elicit a hypertrehalosaemic response in Periplaneta americana, a blattid cockroach.
Topics: Animals; Cockroaches; Amino Acid Sequence; Oligopeptides; Pyrrolidonecarboxylic Acid; Peptides; Mass Spectrometry; Insect Hormones
PubMed: 37882863
DOI: 10.1007/s00726-023-03337-7 -
General and Comparative Endocrinology Jan 2024Gonadotropin-releasing hormone (GnRH) superfamily comprises multiple families of signaling peptides in both protostomes and deuterostomes. Among this superfamily,...
Gonadotropin-releasing hormone (GnRH) superfamily comprises multiple families of signaling peptides in both protostomes and deuterostomes. Among this superfamily, vertebrate GnRH stimulates reproduction, but other GnRH superfamily members elicit diverse pleiotropic effects. Within the GnRH superfamily members, adipokinetic hormone (AKH) and its receptor are well described in ecdysozoans but understudied in other lineages. To fill this knowledge gap, we deorphanized a putative receptor for a lophotrochozoan AKH in a gastropod mollusk, Aplysia californica, and named it Aplca-AKHR. Phylogenetic analysis revealed an orthologous relationship of Aplca-AKHR with ecdysozoan AKHRs and other putative lophotrochozoan AKHRs. Aplca-AKHR bound specifically to the previously identified Aplca-AKH with high affinity and activated the inositol phosphate pathway. Aplca-AKHR was expressed widely among central and peripheral tissues, but most prominently in several central ganglia and the heart. The expression of Aplca-AKHR was downregulated by a hyposaline challenge, consistent with a role in volume and fluid regulation previously described for its ligand, Aplca-AKH. In summary, this is the first pairing of a lophotrochozoan AKH with its cognate receptor. Expression data further support diverse central and peripheral roles, including volume and fluid control, of this ligand/receptor pair.
Topics: Animals; Aplysia; Amino Acid Sequence; Gastropoda; Phylogeny; Ligands; Gonadotropin-Releasing Hormone; Insect Hormones; Pyrrolidonecarboxylic Acid
PubMed: 37865149
DOI: 10.1016/j.ygcen.2023.114393 -
MBio Oct 2023Exclusively in the Bacteroidetes phylum, most proteins exported across the inner membrane via the Sec system and released into the periplasm by type I signal peptidase...
Exclusively in the Bacteroidetes phylum, most proteins exported across the inner membrane via the Sec system and released into the periplasm by type I signal peptidase have N-terminal glutamine converted to pyroglutamate. The reaction is catalyzed by the periplasmic enzyme glutaminyl cyclase (QC), which is essential for the growth of and other periodontopathogens. Apparently, pyroglutamyl formation stabilizes extracytoplasmic proteins and/or protects them from proteolytic degradation in the periplasm. Given the role of as the keystone pathogen in periodontitis, QC is a promising target for the development of drugs to treat and/or prevent this highly prevalent chronic inflammatory disease leading to tooth loss and associated with severe systemic diseases.
Topics: Humans; Aminoacyltransferases; Periodontitis; Pyrrolidonecarboxylic Acid; Glutamine
PubMed: 37750700
DOI: 10.1128/mbio.00980-23 -
Annals of Medicine 2023Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignant solid tumours, and abnormal metabolic reprogramming in the tumour microenvironment is...
BACKGROUND
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignant solid tumours, and abnormal metabolic reprogramming in the tumour microenvironment is regarded as an important contributor to its pathogenesis.
OBJECTIVES
As there is an urgency to identify new targets based on the metabolic features that are highly refractory to PDAC treatment, this study aimed to identify suitable therapeutic targets for PDAC.
METHODS
In this study, gene set enrichment and Kyoto Encyclopedia of Genes and Genomes analyses were performed on 163 PDAC tissue samples and 165 normal pancreatic tissue samples from The Cancer Genome Atlas and Genotype-Tissue Expression databases to identify alterations in critical metabolites that may contribute to PDAC pathogenesis. Furthermore, ultra-performance liquid chromatography-tandem mass spectrometry was performed to identify significant metabolic pathways between 24 pairs of tumour and adjacent non-tumour tissues and between serum samples from PDAC patients and healthy donors.
RESULTS
Fifty-one tissue metabolites and 26 serum metabolites were altered in PDAC. Among them, those in the γ-glutamyl cycle were the most substantially changed, and 5-oxoproline was the biomarker of PDAC with the most significantly decreased levels.
CONCLUSIONS
The γ-glutamyl cycle and 5-oxoproline might be potential biomarkers and therapeutic targets to improve the diagnosis, therapy, and prognosis of PDAC.
Topics: Humans; Pyrrolidonecarboxylic Acid; Biomarkers, Tumor; Pancreatic Neoplasms; Carcinoma, Pancreatic Ductal; Tumor Microenvironment
PubMed: 37544888
DOI: 10.1080/07853890.2023.2242247 -
The Analyst Aug 2023Bloodstain age estimation involves measuring time-dependent changes in the levels of biomolecules in bloodstains. Although several studies have identified bloodstain...
Bloodstain age estimation involves measuring time-dependent changes in the levels of biomolecules in bloodstains. Although several studies have identified bloodstain metabolites as markers for estimating bloodstain age, none have considered sex, age-related metabolomic differences, or long-time bloodstain age. Therefore, we aimed to identify metabolite markers for estimating the age of bloodstains at weekly intervals within 28 days and validate them through multiple reaction monitoring. Adenosine 5'-monophosphate, choline, and pyroglutamic acid were selected as markers. Seven metabolites were validated, including five previously reported metabolites, ergothioneine, hypoxanthine, L-isoleucine, L-tryptophan, and pyroglutamic acid. Choline and hypoxanthine can be used to differentiate bloodstains between days 0 and 14 after deposition at weekly intervals, whereas L-isoleucine and L-tryptophan can help distinguish bloodstains between 7 days before and 14 days after deposition. Evaluation of the changes in metabolite levels according to sex and age revealed that the average levels of all seven metabolites were higher in women on day 0. Moreover, the level of ergothioneine was significantly higher in elderly individuals than in young individuals at all time points. In this study, we confirmed the potential effectiveness of metabolites in bloodstains as forensic markers and provided a new perspective on metabolomic approaches linked to forensic science.
Topics: Humans; Female; Aged; Ergothioneine; Tryptophan; Isoleucine; Pyrrolidonecarboxylic Acid; Blood Stains; Forensic Medicine; Hypoxanthines
PubMed: 37526270
DOI: 10.1039/d3an00603d -
Frontiers in Cellular and Infection... 2023Disordered gut microbiota (GM) structure and function may contribute to osteoporosis (OP). This study explores how traditional Chinese medicine (TCM) intervention... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Disordered gut microbiota (GM) structure and function may contribute to osteoporosis (OP). This study explores how traditional Chinese medicine (TCM) intervention affects the structure and function of the GM in patients with OP.
METHOD
In a 3-month clinical study, 43 patients were randomly divided into two groups receiving conventional treatment and combined TCM (Yigu decoction, YGD) treatment. The correlation between the intestinal flora and its metabolites was analyzed using 16S rDNA and untargeted metabolomics and the combination of the two.
RESULTS
After three months of treatment, patients in the treatment group had better bone mineral density (BMD) than those in the control group ( < 0.05). Patients in the treatment group had obvious abundance changes in GM microbes, such as Bacteroides, Escherichia-Shigella, Faecalibacterium, Megamonas, Blautia, Klebsiella, Romboutsia, Akkermansia, and Prevotella_9. The functional changes observed in the GM mainly involved changes in metabolic function, genetic information processing and cellular processes. The metabolites for which major changes were observed were capsazepine, Phe-Tyr, dichlorprop, D-pyroglutamic acid and tamsulosin. These metabolites may act through metabolic pathways, the citrate cycle (TCA cycle) and beta alanine metabolism. Combined analysis showed that the main acting metabolites were dichlorprop, capsazepine, D-pyroglutamic acid and tamsulosin.
CONCLUSION
This study showed that TCM influenced the structure and function of the GM in patients with OP, which may be one mechanism by which TCM promotes the rehabilitation of patients with OP through the GM.
Topics: Humans; Gastrointestinal Microbiome; Pyrrolidonecarboxylic Acid; Tamsulosin; RNA, Ribosomal, 16S
PubMed: 37475958
DOI: 10.3389/fcimb.2023.1091083 -
Journal of Neuroimmunology Sep 2023Epidemiological studies showed that Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA) frequently co-occur; however, the precise mechanism is not well...
Epidemiological studies showed that Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA) frequently co-occur; however, the precise mechanism is not well understood. A unique animal model (Tg-SwDI mice) was developed to investigate the early-onset and robust accumulation of both parenchymal and vascular Aβ in the brain. Tg-SwDI mice have been extensively used to study the mechanisms of cerebrovascular dysfunction, neuroinflammation, neurodegeneration, and cognitive decline observed in AD/CAA patients and to design biomarkers and therapeutic strategies. In the present study, we documented interesting new features in the thalamus of Tg-SwDI mice: 1) a sharp increase in the expression of ionized calcium-binding adapter molecule 1 (Iba-1) in microglia in 6-month-old animals; 2) microglia clustering at six months that disappeared in old animals; 3) N-truncated/modified AβN3(pE) peptide in 9-month-old female and 12-month-old male mice; 4) an age-dependent increase in translocator protein (TSPO) expression. These findings reinforce the versatility of this model for studying multiple pathological issues involved in AD and CAA.
Topics: Animals; Female; Male; Mice; Alzheimer Disease; Amyloid beta-Peptides; Brain; Cerebral Amyloid Angiopathy; Disease Models, Animal; Mice, Transgenic; Microglia; Pyrrolidonecarboxylic Acid; Thalamus
PubMed: 37467699
DOI: 10.1016/j.jneuroim.2023.578150 -
The Science of the Total Environment Nov 2023The role played by metabolites in exhaled breath condensate (EBC) in the effect of PM on schoolchildren's pulmonary function has received little attention. Accordingly,...
The role played by metabolites in exhaled breath condensate (EBC) in the effect of PM on schoolchildren's pulmonary function has received little attention. Accordingly, we examined whether metabolites in EBC mediated the effect of PM, PM, and PM on the pulmonary function of schoolchildren at a residential primary school who had received an air-cleaner cross-over intervention. Samples of EBC were collected from a total of 60 schoolchildren and subjected to metabolomics analysis. We found that the effect of PM on six pulmonary function indicators was mediated by the following nine lipid peroxidation-related and energy metabolism-related metabolites present in EBC: 4-hydroxynonenal, arachidoyl ethanolamide, dl-pyroglutamic acid, 5-deoxy-d-glucose, myristic acid, lauric acid, linoleic acid, l-proline, and palmitic acid. However, while all nine of these metabolites mediated the effects of PM on boys' pulmonary function, only 4-hydroxynonenal, arachidoyl ethanolamide, and dl-pyroglutamic acid mediated the effects of PM on girls' pulmonary function. Overall, our results show that (1) short-term exposure to PM affected the schoolchildren's pulmonary function by causing an imbalance between lipid peroxidation and glutathione-based antioxidant activity and by perturbing energy metabolism in respiratory system and (2) there was a sex-dependent antioxidant response to PM exposure, with boys being less resistant than girls.
Topics: Humans; Male; Female; Child; Particulate Matter; Pyrrolidonecarboxylic Acid; Lung; Aldehydes; Breath Tests; Biomarkers
PubMed: 37459994
DOI: 10.1016/j.scitotenv.2023.165517