Cellular and molecular characterisation of the peripheral immune environment in migraine.

Introduction: Peripheral immune dysfunction may be critically involved in the pathophysiology of migraine. Some evidence supports a role for peripheral T cells, monocytes, and humoral factors including kynurenine metabolites and cytokines, however a comprehensive picture has yet to emerge.

Objective: This study sought to undertake a systematic assessment of the immune changes in episodic and chronic migraine across phases of the migraine cycle.

Recombinant Protein Spectral Library (rPSL) DIA-MS method improves identification and quantification of low-abundance cancer-associated and kynurenine pathway proteins.

Data-independent acquisition mass spectrometry (DIA-MS) is a powerful tool for quantitative proteomics, but a well-constructed reference spectral library is crucial to optimize DIA analysis, particularly for low-abundance proteins. In this study, we evaluate the efficacy of a recombinant protein spectral library (rPSL), generated from tryptic digestion of 42 human recombinant proteins, in enhancing the detection and quantification of lower-abundance cancer-associated proteins. Additionally, we generated a combined sample-specific biological-rPSL by integrating the rPSL with a spectral library derived from pooled biological samples.

Comparative Analysis of HMC3 and C20 Microglial Cell Lines Reveals Differential Myeloid Characteristics and Responses to Immune Stimuli.

Microglia are the primary resident immune cells of the central nervous system (CNS) that respond to injury and infections. Being critical to CNS homeostasis, microglia also have been shown to contribute to neurodegenerative diseases and brain cancer. Hence, microglia are regarded as a potential therapeutic target in CNS diseases, resulting in an increased demand for reliable in vitro models.

Dysregulation of the Kynurenine Pathway in Relapsing Remitting Multiple Sclerosis and Its Correlations With Progressive Neurodegeneration.

Background And Objectives: Despite the absence of acute lesion activity in multiple sclerosis (MS), chronic neurodegeneration continues to progress, and a potential underlying mechanism could be the kynurenine pathway (KP). Prolonged activation of the KP from chronic inflammation is known to exacerbate the progression of neurodegenerative diseases through the production of neurotoxic metabolites. Among the 8 KP metabolites, six of them, namely kynurenine (KYN), 3-hydroxylkynurenine (3HK), anthranilic acid (AA), kynurenic acid (KYNA), and quinolinic acid (QUIN), have been associated with neurodegeneration.

Activation of the kynurenine pathway identified in individuals with covert hepatic encephalopathy.

Background: HE is a neuropsychiatric complication of liver disease characterized by systemic elevation in ammonia and proinflammatory cytokines. These neurotoxins cross the blood-brain barrier and cause neuroinflammation, which can activate the kynurenine pathway (KP). This results in dysregulated production of neuroactive KP metabolites, such as quinolinic acid, which is known to cause astrocyte and neuronal death.

A Proteomic Examination of Plasma Extracellular Vesicles Across Colorectal Cancer Stages Uncovers Biological Insights That Potentially Improve Prognosis.

Background: Recent advancements in understanding plasma extracellular vesicles (EVs) and their role in disease biology have provided additional unique insights into the study of Colorectal Cancer (CRC).

Methods: This study aimed to gain biological insights into disease progression from plasma-derived extracellular vesicle proteomic profiles of 80 patients (20 from each CRC stage I-IV) against 20 healthy age- and sex-matched controls using a high-resolution SWATH-MS proteomics with a reproducible centrifugation method to isolate plasma EVs.

Results: We applied the High-Stringency Human Proteome Project (HPP) guidelines for SWATH-MS analysis, which refined our initial EV protein identification from 1362 proteins (10,993 peptides) to a more reliable and confident subset of 853 proteins (6231 peptides).

Breast cancer metastasis progression is associated with elevated activity of kynurenine monooxygenase and kynureninase.

Introduction: Metastasis remains the major cause of death in breast cancer (BrCa) and lacks specific treatment strategies. The kynurenine pathway (KP) has been suggested as a key mechanism facilitating progression of BrCa. While KP activity has been explored in primary BrCa, its role in metastasis remains unclear.

Viruses in glioblastoma: an update on evidence and clinical trials.

Background: Glioblastoma (GB) is a lethal and aggressive brain tumour. While molecular characteristics of GB is studied extensively, the aetiology of GB remains uncertain. The interest in exploring viruses as a potential contributor to the development of GB stems from the notion that viruses are known to play a key role in pathogenesis of other human cancers such as cervical cancer.

Protein prognostic biomarkers in stage II colorectal cancer: implications for post-operative management.

Colorectal cancer (CRC) poses a significant threat to many human lives worldwide and survival following resection is predominantly stage dependent. For early-stage cancer, patients are not routinely advised to undergo additional post-operative adjuvant chemotherapy. Acceptable clinical management guidelines are well established for patients in pTNM stages I, III and IV.

The roles of the kynurenine pathway in COVID-19 neuropathogenesis.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the highly contagious respiratory disease Corona Virus Disease 2019 (COVID-19) that may lead to various neurological and psychological disorders that can be acute, lasting days to weeks or months and possibly longer. The latter is known as long-COVID or more recently post-acute sequelae of COVID (PASC). During acute COVID-19 infection, a strong inflammatory response, known as the cytokine storm, occurs in some patients.

Unravelling shared mechanisms: insights from recent ME/CFS research to illuminate long COVID pathologies.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating chronic illness often triggered by an initiating acute event, mainly viral infections. The transition from acute to chronic disease remains unknown, but interest in this phenomenon has escalated since the COVID-19 pandemic and the post-COVID-19 illness, termed 'long COVID' (LC). Both ME/CFS and LC share many clinical similarities.

Stability Studies of Kynurenine Pathway Metabolites in Blood Components Define Optimal Blood Processing Conditions.

The kynurenine pathway (KP) is the main pathway of tryptophan (TRP) metabolism that generates energy for multiple cellular processes. The activity of this pathway has been shown to be dysregulated in multiple human diseases. The resultant modulation of metabolites has been suggested to comprise biomarkers to track disease progression or could identify new therapeutic targets.

Dysregulation of the Kynurenine Pathway, Cytokine Expression Pattern, and Proteomics Profile Link to Symptomology in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).

Dysregulation of the kynurenine pathway (KP) is believed to play a significant role in neurodegenerative and cognitive disorders. While some evidence links the KP to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), further studies are needed to clarify the overall picture of how inflammation-driven KP disturbances may contribute to symptomology in ME/CFS. Here, we report that plasma levels of most bioactive KP metabolites differed significantly between ME/CFS patients and healthy controls in a manner consistent with their known contribution to symptomology in other neurological disorders.

The kynurenine pathway in traumatic brain injuries and concussion.

Up to 10 million people per annum experience traumatic brain injury (TBI), 80-90% of which are categorized as mild. A hit to the brain can cause TBI, which can lead to secondary brain injuries within minutes to weeks after the initial injury through unknown mechanisms. However, it is assumed that neurochemical changes due to inflammation, excitotoxicity, reactive oxygen species, etc.

The kynurenine pathway relates to post-acute COVID-19 objective cognitive impairment and PASC.

Objective: To determine the prevalence and natural history of post-acute COVID-19 objective cognitive impairment and function, and their relationship to demographic, clinical factors, post-acute sequelae of COVID-19 (PASC), and biomarkers.

Methods: A total of 128 post-acute COVID-19 patients (age = 46 ± 15; 42% women, acute disease severity: not hospitalized: 38.6% mild: 0-1 symptoms, 52% 2+ symptoms; 9.

CSF neopterin, quinolinic acid and kynurenine/tryptophan ratio are biomarkers of active neuroinflammation.

Background: Defining the presence of acute and chronic brain inflammation remains a challenge to clinicians due to the heterogeneity of clinical presentations and aetiologies. However, defining the presence of neuroinflammation, and monitoring the effects of therapy is important given its reversible and potentially damaging nature. We investigated the utility of CSF metabolites in the diagnosis of primary neuroinflammatory disorders such as encephalitis and explored the potential pathogenic role of inflammation in epilepsy.

Involvement of the kynurenine pathway in breast cancer: updates on clinical research and trials.

Breast cancer (BrCa) is the leading cause of cancer incidence and mortality in women worldwide. While BrCa treatment has been shown to be highly successful if detected at an early stage, there are few effective strategies to treat metastatic tumours. Hence, metastasis remains the main cause in most of BrCa deaths, highlighting the need for new approaches in this group of patients.

Temporal Profile of Kynurenine Pathway Metabolites in a Rodent Model of Autosomal Recessive Polycystic Kidney Disease.

Autosomal recessive polycystic kidney disease (ARPKD) is an early onset genetic disorder characterized by numerous renal cysts resulting in end stage renal disease. Our study aimed to determine if metabolic reprogramming and tryptophan (Trp) metabolism via the kynurenine pathway (KP) is a critical dysregulated pathway in PKD. Using the Lewis polycystic kidney (LPK) rat model of PKD and Lewis controls, we profiled temporal trends for KP metabolites in plasma, urine, and kidney tissues from 6- and 12-week-old mixed sex animals using liquid and gas chromatography, minimum  = 5 per cohort.

Decreased cerebrospinal fluid kynurenic acid in epileptic spasms: A biomarker of response to corticosteroids.

Background: Epileptic (previously infantile) spasms is the most common epileptic encephalopathy occurring during infancy and is frequently associated with abnormal neurodevelopmental outcomes. Epileptic spasms have a diverse range of known (genetic, structural) and unknown aetiologies. High dose corticosteroid treatment for 4 weeks often induces remission of spasms, although the mechanism of action of corticosteroid is unclear.

Could the kynurenine pathway be the key missing piece of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) complex puzzle?

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex and debilitating disease with a substantial social and economic impact on individuals and their community. Despite its importance and deteriorating impact, progresses in diagnosis and treatment of ME/CFS is limited. This is due to the unclear pathophysiology of the disease and consequently lack of prognostic biomarkers.

The Role of Kynurenine Pathway and NAD Metabolism in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a serious, complex, and highly debilitating long-term illness. People with ME/CFS are typically unable to carry out their routine activities. Key hallmarks of the disease are neurological and gastrointestinal impairments accompanied by pervasive malaise that is exacerbated after physical and/or mental activity.

Development of a translational inflammation panel for the quantification of cerebrospinal fluid Pterin, Tryptophan-Kynurenine and Nitric oxide pathway metabolites.

Background: Neuroinflammatory diseases such as encephalitis, meningitis, multiple sclerosis and other neurological diseases with inflammatory components, have demonstrated a need for diagnostic biomarkers to define treatable and reversible neuroinflammation. The development and clinical validation of a targeted translational inflammation panel using liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) could provide early diagnosis, rapid treatment and insights into neuroinflammatory mechanisms.

Methods: An inflammation panel of 13 metabolites (neopterin, tryptophan, kynurenine, kynurenic acid, 3-hydroxykynurenine, xanthurenic acid, anthranilic acid, 3-hydroxyanthranilic acid, quinolinic acid, picolinic acid, arginine, citrulline and methylhistamine) was measured based on a simple precipitation and filtration method using minimal CSF volume.