Jinqing Hu

Bio: Jinqing Hu is an academic researcher from Guangzhou Medical University. The author has contributed to research in topics: Cmax & Off-label use. The author has an hindex of 7, co-authored 27 publications receiving 179 citations.

A Simple HPLC–MS/MS Method for Determination of Tryptophan, Kynurenine and Kynurenic Acid in Human Serum and its Potential for Monitoring Antidepressant Therapy

Abstract: The kynurenine pathway, in which tryptophan is metabolized to kynurenine and kynurenic acid, has been linked to depression. A rapid and highly reproducible liquid-chromatography-tandem mass spectrometry (LC-MS/MS) method were established for determining tryptophan, kynurenine and kynurenic acid in human serum. Biological samples were precipitated with methanol before separation on an Agilent Eclipse XDB-C18. The stable-isotope-labeled internal standards (kynurenine-13C415N and kynurenic acid-d5) were used for quantification. Detection was performed using multiple reaction monitoring in electrospray ionization mode at m/z 205.1→188.1 for tryptophan, m/z 209.1→146.1 for kynurenine, m/z 190.1→144.1 for kynurenic acid. Good linearity of analyte to internal standard peak area ratios was seen in the concentration range 1,000-50,000 ng/mL for tryptophan, 100-5,000 ng/mL for kynurenine and 1-60 ng/mL for kynurenic acid. Pooled drug-free human serum was purified using activated charcoal and the method was shown to be linear, with validation parameters within acceptable limits. The newly developed method was successfully used to determine concentrations of tryptophan, kynurenine and kynurenic acid in serum from 26 healthy volunteers and 54 patients with depression. Concentrations of tryptophan and kynurenine were lower in serum from depressed individuals than from healthy individuals.

Bibliometric and Visual Analysis of Research on the Links Between the Gut Microbiota and Depression From 1999 to 2019

Abstract: Background: There is a crucial link between the gut microbiota and the host central nervous system, and the communication between them occurs via a bidirectional pathway termed the "microbiota-gut-brain axis." The gut microbiome in the modern environment has markedly changed in response to environmental factors. These changes may affect a broad range of host psychiatric disorders, such as depression, by interacting with the host through metabolic, immune, neural, and endocrine pathways. Nevertheless, the general aspects of the links between the gut microbiota and depression have not been systematically investigated through bibliometric analysis. Aim: This study aimed to analyze the current status and developing trends in gut microbiota research in the depression field through bibliometric and visual analysis. Methods: A total of 1,962 publications published between 1999 and 2019 were retrieved from the Web of Science Core Collection. CiteSpace (5.6 R5) was used to perform collaboration network analysis, co-citation analysis, co-occurrence analysis, and citation burst detection. Results: The number of publications has been rapidly growing since 2010. The collaboration network analysis revealed that the USA, University College Cork, and John F. Cryan were the most influential country, institute, and scholar, respectively. The most productive and co-cited journals were Brain Behavior and Immunity and Proceedings of the National Academy of Sciences of the United States of America, respectively. The co-citation analysis of references revealed that the most recent research focus was in the largest theme cluster, "cytokines," thus reflecting the important research foundation in this field. The co-occurrence analysis of keywords revealed that "fecal microbiota" and "microbiome" have become the top two research hotspots since 2013. The citation burst detection for keywords identified several keywords, including "Parkinson's disease," "microbiota-gut-brain axis," "microbiome," "dysbiosis," "bipolar disorder," "impact," "C reactive protein," and "immune system," as new research frontiers, which have currently ongoing bursts. Conclusions: These results provide an instructive perspective on the current research and future directions in the study of the links between the gut microbiota and depression, which may help researchers choose suitable cooperators or journals, and promote their research illustrating the underlying molecular mechanisms of depression, including its etiology, prevention, and treatment.

Comprehensive Bibliometric Analysis of the Kynurenine Pathway in Mood Disorders: Focus on Gut Microbiota Research.

Abstract: Background: Emerging evidence implicates the dysregulated kynurenine pathway (KP), an immune-inflammatory pathway, in the pathophysiology of mood disorders (MD), including depression and bipolar disorder characterized by a low-grade chronic pro-inflammatory state. The metabolites of the KP, an important part of the microbiota-gut-brain axis, serve as immune system modulators linking the gut microbiota (GM) with the host central nervous system. Aim: This bibliometric analysis aimed to provide a first glimpse into the KP in MD, with a focus on GM research in this field, to guide future research and promote the development of this field. Methods: Publications relating to the KP in MD between the years 2000 and 2020 were retrieved from the Scopus and Web of Science Core Collection (WoSCC), and analyzed in CiteSpace (5.7 R5W), biblioshiny (using R-Studio), and VOSviewer (1.6.16). Results: In total, 1,064 and 948 documents were extracted from the Scopus and WoSCC databases, respectively. The publications have shown rapid growth since 2006, partly owing to the largest research hotspot appearing since then, "quinolinic acid." All the top five most relevant journals were in the neuropsychiatry field, such as Brain Behavior and Immunity. The United States and Innsbruck Medical University were the most influential country and institute, respectively. Journal co-citation analysis showed a strong tendency toward co-citation of research in the psychiatry field. Reference co-citation analysis revealed that the top four most important research focuses were "kynurenine pathway," "psychoneuroimmunology," "indoleamine 2,3-dioxygenase," and "proinflammatory cytokines," and the most recent focus was "gut-brain axis," thus indicating the role of the KP in bridging the GM and the host immune system, and together reflecting the field's research foundations. Overlap analysis between the thematic map of keywords and the keyword burst analysis revealed that the topics "Alzheimer's disease," "prefrontal cortex," and "acid," were research frontiers. Conclusion: This comprehensive bibliometric study provides an updated perspective on research associated with the KP in MD, with a focus on the current status of GM research in this field. This perspective may benefit researchers in choosing suitable journals and collaborators, and aid in the further understanding of the field's hotspots and frontiers, thus facilitating future research.

The kynurenine pathway in major depressive disorder, bipolar disorder, and schizophrenia: a meta-analysis of 101 studies.

Abstract: The importance of tryptophan as a precursor for neuroactive compounds has long been acknowledged. The metabolism of tryptophan along the kynurenine pathway and its involvement in mental disorders is an emerging area in psychiatry. We performed a meta-analysis to examine the differences in kynurenine metabolites in major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SZ). Electronic databases were searched for studies that assessed metabolites involved in the kynurenine pathway (tryptophan, kynurenine, kynurenic acid, quinolinic acid, 3-hydroxykynurenine, and their associate ratios) in people with MDD, SZ, or BD, compared to controls. We computed the difference in metabolite concentrations between people with MDD, BD, or SZ, and controls, presented as Hedges' g with 95% confidence intervals. A total of 101 studies with 10,912 participants were included. Tryptophan and kynurenine are decreased across MDD, BD, and SZ; kynurenic acid and the kynurenic acid to quinolinic acid ratio are decreased in mood disorders (i.e., MDD and BD), whereas kynurenic acid is not altered in SZ; kynurenic acid to 3-hydroxykynurenine ratio is decreased in MDD but not SZ. Kynurenic acid to kynurenine ratio is decreased in MDD and SZ, and the kynurenine to tryptophan ratio is increased in MDD and SZ. Our results suggest that there is a shift in the tryptophan metabolism from serotonin to the kynurenine pathway, across these psychiatric disorders. In addition, a differential pattern exists between mood disorders and SZ, with a preferential metabolism of kynurenine to the potentially neurotoxic quinolinic acid instead of the neuroprotective kynurenic acid in mood disorders but not in SZ.

Gastrointestinal interactions, absorption, splanchnic metabolism and pharmacokinetics of orally ingested phenolic compounds

Abstract: The positive health effects of phenolic compounds (PCs) have been extensively reported in the literature. An understanding of their bioaccessibility and bioavailability is essential for the elucidation of their health benefits. Before reaching circulation and exerting bioactions in target tissues, numerous interactions take place before and during digestion with either the plant or host's macromolecules that directly impact the organism and modulate their own bioaccessibility and bioavailability. The present work is focused on the gastrointestinal (GI) interactions that are relevant to the absorption and metabolism of PCs and how these interactions impact their pharmacokinetic profiles. Non-digestible cell wall components (fiber) interact intimately with PCs and delay their absorption in the small intestine, instead carrying them to the large intestine. PCs not bound to fiber interact with digestible nutrients in the bolus where they interfere with the digestion and absorption of proteins, carbohydrates, lipids, cholesterol, bile salts and micronutrients through the inhibition of digestive enzymes and enterocyte transporters and the disruption of micelle formation. PCs internalized by enterocytes may reach circulation (through transcellular or paracellular transport), be effluxed back into the lumen (P-glycoprotein, P-gp) or be metabolized by phase I and phase II enzymes. Some PCs can inhibit P-gp or phase I/II enzymes, which can potentially lead to drug–nutrient interactions. The absorption and pharmacokinetic parameters are modified by all of the interactions within the digestive tract and by the presence of other PCs. Undesirable interactions have promoted the development of nanotechnological approaches to promote the bioaccessibility, bioavailability, and bioefficacy of PCs.

Ultrahigh-performance liquid chromatography tandem mass spectrometry with electrospray ionization quantification of tryptophan metabolites and markers of gut health in serum and plasma — Application to clinical and epidemiology cohorts

Abstract: A targeted ultrahigh-performance liquid chromatography tandem mass spectrometry with electrospray ionization (UHPLC-ESI-MS/MS) method has been developed for the quantification of tryptophan and its downstream metabolites from the kynurenine and serotonin pathways. The assay coverage also includes markers of gut health and inflammation, including citrulline and neopterin. The method was designed in 96-well plate format for application in multiday, multiplate clinical and epidemiology population studies. A chromatographic cycle time of 7 min enables the analysis of two 96-well plates in 24 h. To protect chromatographic column lifespan, samples underwent a two-step extraction, using solvent protein precipitation followed by delipidation via solid-phase extraction (SPE). Analytical validation reported accuracy of each analyte <20% for the lowest limit of quantification and <15% for all other quality control (QC) levels. The analytical precision for each analyte was 2.1-12.9%. To test the applicability of the method to multiplate and multiday preparations, a serum pool underwent periodic repeat analysis during a run consisting of 18 plates. The % CV (coefficient of variation) values obtained for each analyte were <15%. Additional biological testing applied the assay to samples collected from healthy control participants and two groups diagnosed with inflammatory bowel disease (IBD) (one group treated with the anti-inflammatory 5-aminosalicylic acid (5-ASA) and one group untreated), with results showing significant differences in the concentrations of picolinic acid, kynurenine, and xanthurenic acid. The short analysis time and 96-well plate format of the assay makes it suitable for high-throughput targeted UHPLC-ESI-MS/MS metabolomic analysis in large-scale clinical and epidemiological population studies.

Antidepressant effect of repeated ketamine administration on kynurenine pathway metabolites in patients with unipolar and bipolar depression.

Abstract: Ketamine has rapid antidepressant effects on treatment-resistant depression, but the biological mechanism underpinning this effect is less clear Our aims were to examine whether kynurenine pathway metabolites were altered by six infusions of ketamine and whether these biological factors could act as potential biomarkers to predict ketamine’s antidepressant effects Six intravenous infusions of ketamine (05 mg/kg) were administered to 84 patients with unipolar and bipolar depression over a 12-d period Symptom severity and response were assessed using the Montgomery-Asberg Scale (MADRS), and blood samples were collected at baseline and 24 h following the first infusion and at 24 h and 14 d after the sixth infusion (24 h, 13 d and 26 d) Blood samples from sixty healthy controls were collected for comparison with samples from the patients Serum concentrations of tryptophan (TRP), kynurenine (KYN) and kynurenic acid (KYNA) were measured by the liquid chromatography-tandem mass spectrometry method At baseline, serum levels of TRP and KYNA and the KYNA/KYN ratio were lower and the KYN/TRP ratio was greater in depressed patients than in healthy controls Overall, fifty (595%) patients responded to ketamine at 13 d Ketamine responders had a greater KYNA level and KYNA/KYN ratio than nonresponders at 24 h and 13 d (all P