Arginine depletion-induced autophagy and metabolic dysregulation are involved in the disease severity of hand, foot, and mouth disease DOI Creative Commons
Yuefei Jin, Wangquan Ji, Liang Zhang

et al.

Virulence, Journal Year: 2024, Volume and Issue: 16(1)

Published: Dec. 28, 2024

Amino acid metabolism provides significant insight into the development and prevention of many viral diseases. Therefore, present study aimed to compare amino profiles hand, foot, mouth disease (HFMD) patients with those healthy individuals further reveal molecular mechanisms HFMD severity. Using UPLC-MS/MS, we determined plasma expression pediatric (mild, n = 42; severe, 43) controls (n 25). Brain tissues from CVA6-infected mice were examined using untargeted metabolomics. Several acids significantly different between three groups. Pathway analysis revealed that arginine, proline, tryptophan are implicated in pathogenesis HFMD. A similar arginine depletion was observed brain mice. Importantly, L-arginine supplementation improved survival rate mice, inhibited virus multiplication, reduced pathological autophagy associated mTOR-autophagy pathway brain. Collectively, as hub metabolite mammalian target rapamycin (mTOR) signaling affecting autophagy, plays an important role severe may serve a potential therapeutic option for critical

Language: Английский

Kynurenic acid inflammatory signaling expands in primates and impairs prefrontal cortical cognition DOI Open Access
Shengtao Yang, Dibyadeep Datta, Fenna M. Krienen

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 14, 2024

Summary Cognitive deficits from dorsolateral prefrontal cortex (dlPFC) dysfunction are common in neuroinflammatory disorders, including long-COVID, schizophrenia and Alzheimer’s disease, have been correlated with kynurenine inflammatory signaling. Kynurenine is further metabolized to kynurenic acid (KYNA) brain, where it blocks NMDA α7-nicotinic receptors (nic-α7Rs). These essential for neurotransmission dlPFC, suggesting that KYNA may cause higher cognitive these disorders. The current study found its synthetic enzyme, KAT II, greatly expanded expression primate dlPFC both glia neurons. Local application of onto neurons markedly reduced the delay-related firing needed working memory via actions at nic-α7Rs, while inhibition II enhanced neuronal aged macaques. Systemic administration agents reduce production similarly improved performance monkeys, a therapeutic avenue treatment

Language: Английский

Citations

1
Emerging Nanomaterials Biosensors in Breathalyzers for Detection of COVID-19: Future Prospects DOI Creative Commons
R. Saravanan, Subuhi Sherwani, Faheem Ahmed

et al.

Inorganics, Journal Year: 2023, Volume and Issue: 11(12), P. 483 - 483

Published: Dec. 18, 2023

In recent times, the global landscape of disease detection and monitoring has been profoundly influenced by convergence nanotechnology biosensing techniques. Biosensors have enormous potential to monitor human health, with flexible or wearable variants, through biomarkers in clinical biological behaviors applications related health disease, increasing biorecognition, sensitivity, selectivity, accuracy. The emergence nanomaterial-based biosensors ushered a new era rapid sensitive diagnostic tools, offering unparalleled capabilities realm identification. Even after declaration end COVID-19 pandemic, demand for efficient accessible methodologies grown exponentially. response, integration nanomaterial into breathalyzer devices gained considerable attention as promising avenue low-cost, non-invasive, early COVID-19. This review delves forefront scientific advancements, exploring emerging within breathalyzers revolutionize detection, providing comprehensive overview their principles, applications, implications.

Language: Английский

Citations

2
TRIPTOFANO METABOLIZMO IR MITYBOS REIKŠMĖ DEPRESIJOS PATOFIZIOLOGIJOJE DOI Open Access

Augustė Lukošaitytė

Health Sciences, Journal Year: 2024, Volume and Issue: 34(4), P. 144 - 147

Published: June 1, 2024

Klinikinė depresija yra vienas dažniausių psichiatrinių su­trikimų, pasireiškianti tipiniais afektiniais ir sensomoto­riniais simptomais. Depresijos patofiziologija vis dar ne­pakankamai aiški egzistuoja daugybė ligos etiologijos teorijų. Viena jų tyrinėja mitybos virškinamojo trakto poveikį centrinei nervų sistemai per žarnyno – smegenų ašį. Tyrimai atskleidžia, kad sergantiesiems klinikine de­presija būdingi mikrobiotos sudėties bakterijų kolonijų santykio pakitimai, kurie koreliuoja su afektinių simptomų intensyvumu. Studijų duomenimis, serotonino gamyba tiesiogiai priklauso nuo mityba gaunamos triptofano aminorūgšties, o šio neurotransmiterio meta­bolizmas mikrobiotos, kolonizuojančios žmogaus žarnyną. Tyrinėjami metabolizmo keliai, ypatingą reikšmę skiriant kinurenino keliui, kadangi kelio metabolitų koncentracijos san­tykio pokyčiai siejami depresijos intensy­vumu sumažėjusia gamyba. Tiriamos naujos klinikinės farmakologinio gydymo kryptys pasitelkiant fermentus, reikalingus proce­suose probiotikus balansui atkurti.

Citations

0
Modifications in Immune Response Patterns Induced by Kynurenine and One-Residue-Substituted T Cell Epitopes in SARS-CoV-2-Specific Human T Cells DOI Creative Commons
Mieko Tokano, Rie Takagi, Sho Matsushita

et al.

COVID, Journal Year: 2024, Volume and Issue: 4(10), P. 1676 - 1683

Published: Oct. 15, 2024

Peptide p176-190, derived from the SARS-CoV-2 spike protein, is one of major T cell epitopes that elicits HLA-DR-restricted IL-8 response human CD4+ cells. Using PBMCs a healthy individual primed with an S-protein-based vaccine, we established line (TM45) and cloned cells (TM45.2) specific for peptide. We showed (i) co-incubation kynurenine leads to increased IL-8; (ii) incubated in absence recovered original levels cytokine production; (iii) peptide p176-190 substituted at 176 Leucine neutral hydrophilic serine completely abolished responses TM45.2 cells, thereby suggesting L first anchor residue binding HLA-DR. These observations collectively indicate enhanced can be induced by kynurenine, which produced under infectious conditions COVID-19; not permanent change phenotype; associated harmful neutrophil extracellular traps abrogated single amino acid substitution viral antigens. findings may shed light on novel strategy designing vaccines infections are accompanied production.

Language: Английский

Citations

0
Metabolomics Reveal Key Metabolic Pathway Responses to Anxiety State Regulated by Serotonin in Portunus trituberculatus DOI Creative Commons
Wei Zhai, Yuanyuan Fu, Lei Liu

et al.

Metabolites, Journal Year: 2024, Volume and Issue: 14(10), P. 568 - 568

Published: Oct. 21, 2024

Anxiety refers to the pathological persistence and intensification of emotional responses danger, affecting health from psychological physical aspects. Serotonin is an important neurotransmitter involved in onset anxiety.

Language: Английский

Citations

0
Myeloid-Derived Suppressor Cells in Cancer DOI
Fatin Nurizzati Mohd Jaya, Dmitry I. Gabrilovich

Elsevier eBooks, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Language: Английский

Citations

0
Maple syrup urine disease diagnosed in a resource-limited setting in an infant in Nepal: a case report DOI Creative Commons
Sujata Baidya, Jyoti Thapa, Anuradha Kadel

et al.

BMC Pediatrics, Journal Year: 2024, Volume and Issue: 24(1)

Published: Nov. 27, 2024

Maple Syrup Urine Disease (MSUD) is a rare inherited disorder of metabolism, which manifests early in life classical forms. Recurrent illness and exertion aggravate neurotoxicity. This case highlights MSUD diagnosed association with COVID-19 complications from Nepal. We present 4-month-old child biochemical diagnosis flared-up MSUD. Initially presenting chief complaints fever, noisy breathing, chest retraction, cough along lethargy poor feeding since the first week life, also had developmental delay feeble neck holding absent social smile. The was pneumonia admitted Intensive Care Unit, requiring mechanical ventilation for 12 days. Despite clinical resolution pneumonia, multiple episodes generalized seizures sickly frail. An incessant peculiar odor emanating led to strong suspicion metabolic disorder. Qualitative screening amino acids (FeCl3 2,4-dinitrophenylhdrazine/DNPH) urine further gas chromatography-mass spectrometry revealed increased branched-chain acids(valine, leucine, isoleucine). With dietary restrictions, doing well. However, unfortunately, after 10 days discharge, succumbed death. outpouring hidden disorders onset new diseases. It could have been detected managed earlier expedited neonatal proper intervention.

Language: Английский

Citations

0
Preliminary analyses of tryptophan, kynurenine, and the kynurenine: Tryptophan ratio in plasma, as potential biomarkers for systemic chlamydial infections in koalas DOI Creative Commons
Chien-Jung Chen, Benjamin Kimble,

Astrid Van Aggelen

et al.

PLoS ONE, Journal Year: 2024, Volume and Issue: 19(12), P. e0314945 - e0314945

Published: Dec. 19, 2024

Chlamydiosis is the major infectious disease responsible for significant morbidity and mortality in free-living koalas. Recently, it was reported that 28.5% of koalas infected with chlamydiosis were presented no overt clinical signs. Identification quantification changes plasma biomarkers’ fluctuations have potential to enhance C . pecorum detection facilitate monitoring therapeutic efficacy antibiotics treat this Therefore, concentrations essential amino acid tryptophan, tryptophan’s metabolite kynurenine, kynurenine:tryptophan ratio quantified by high-performance liquid chromatography clinically normal (n = 35), identified chlamydial 35) had other non-chlamydial co-morbidities 10). Results showed there a difference between versus diseased, ‘other’ (both p < 0.001) kynurenine ratio; also diseased tryptophan (p 0.001). Proposed reference ranges are: 4.27–10.4 μg/mL, 0.34–1.23 0.05–0.22, respectively. optimal cut-off points differentiate ≤ 4.75 μg/mL (tryptophan), ≥ 0.88 (kynurenine), 0.12 (kynurenine:tryptophan); 7.67 1.18 0.16 (kynurenine:tryptophan) released/recovered euthanised diseased/‘other’ Significant differences haematological biochemical analytes globulins 0.01), alkaline phosphatase 0.03). Although these biomarkers, especially may not be specific detecting from rest population, role identifying unhealthy ones, irrespective underlying cause.

Language: Английский

Citations

0
Arginine depletion-induced autophagy and metabolic dysregulation are involved in the disease severity of hand, foot, and mouth disease DOI Creative Commons
Yuefei Jin, Wangquan Ji, Liang Zhang

et al.

Virulence, Journal Year: 2024, Volume and Issue: 16(1)

Published: Dec. 28, 2024

Amino acid metabolism provides significant insight into the development and prevention of many viral diseases. Therefore, present study aimed to compare amino profiles hand, foot, mouth disease (HFMD) patients with those healthy individuals further reveal molecular mechanisms HFMD severity. Using UPLC-MS/MS, we determined plasma expression pediatric (mild, n = 42; severe, 43) controls (n 25). Brain tissues from CVA6-infected mice were examined using untargeted metabolomics. Several acids significantly different between three groups. Pathway analysis revealed that arginine, proline, tryptophan are implicated in pathogenesis HFMD. A similar arginine depletion was observed brain mice. Importantly, L-arginine supplementation improved survival rate mice, inhibited virus multiplication, reduced pathological autophagy associated mTOR-autophagy pathway brain. Collectively, as hub metabolite mammalian target rapamycin (mTOR) signaling affecting autophagy, plays an important role severe may serve a potential therapeutic option for critical

Language: Английский

Citations

0