Backgrounds: Memory and emotion are especially vulnerable to psychiatric disorders such as post-traumatic stress disorder (PTSD), which is linked to disruptions in serotonin (5-HT) metabolism. Over 90% of the 5-HT precursor tryptophan (Trp) is metabolized via the Trp-kynurenine (KYN) metabolic pathway, which generates a variety of bioactive molecules. Dysregulation of KYN metabolism, particularly low levels of kynurenic acid (KYNA), appears to be linked to neuropsychiatric disorders. The majority of KYNA is produced by the aadat (kat2) gene-encoded mitochondrial kynurenine aminotransferase (KAT) isotype 2. Little is known about the consequences of deleting the KYN enzyme gene. Methods: In CRISPR/Cas9-induced aadat knockout (kat2-/-) mice, we examined the effects on emotion, memory, motor function, Trp and its metabolite levels, enzyme activities in the plasma and urine of 8-week-old males compared to wild-type mice. Results: Transgenic mice showed more depressive-like behaviors in the forced swim test, but not in the tail suspension, anxiety, or memory tests. They also had fewer center field and corner entries, shorter walking distances, and fewer jumping counts in the open field test. Plasma metabolite levels are generally consistent with those of urine: antioxidant KYNs, 5-hydroxyindoleacetic acid, and indole-3-acetic acid levels were lower; enzyme activities in KATs, kynureninase, and monoamine oxidase/aldehyde dehydrogenase were lower, but kynurenine 3-monooxygenase was higher; and oxidative stress and excitotoxicity indices were higher. Transgenic mice displayed depression-like behavior in a learned helplessness model, emotional indifference, and motor deficits, coupled with a decrease in KYNA, a shift of Trp metabolism toward the KYN-3-hydroxykynurenine pathway, and a partial decrease in the gut microbial Trp-indole pathway metabolite. Conclusions: This is the first evidence that deleting the aadat gene induces depression-like behaviors uniquely linked to experiences of despair, which appear to be associated with excitatory neurotoxic and oxidative stresses. This may lead to the development of a double-hit preclinical model in despair-based depression, a better understanding of these complex conditions, and more effective therapeutic strategies by elucidating the relationship between Trp metabolism and PTSD pathogenesis.

Colorectal cancer (CRC) is one of the leading malignancies worldwide, therefore cheap noninvasive screening methods are of great importance. Matrix-metalloproteinase-9 (MMP-9) has a role in the progression of CRC, and its level is elevated in tumour biopsies. Faecal MMP-9 levels are increased in active ulcerative colitis patients, but in CRC patients, they have never been measured. We aimed to assess the faecal MMP-9 levels in patients undergoing total colonoscopy according to endoscopic and histological diagnosis. One hundred and nine patients provided faecal samples for MMP-9 analysis. A total colonoscopy was performed; suspicious lesions were evaluated by histology. Faecal MMP-9 levels were measured by ELISA. The number of patients allocated to different groups were: negative/diverticulosis: 34 (referred to as controls); hyperplastic polyps: 15; adenomas: 32 (22 at high risk); and CRC: 28. Faecal MMP-9 was significantly increased in CRC compared with all other groups (P<0.001). Faecal MMP-9 was suitable to distinguish CRC patients from controls (sensitivity: 89.3%; specificity: 91.2%). By means of a lower cutoff level, faecal MMP-9 identified high-risk adenomas besides CRC (sensitivity: 76%; specificity: 85.3%). This lower cutoff level screened 59% of high-risk adenomas. Faecal MMP-9 may be a promising new noninvasive marker in CRC.

Liquid biopsy-based methods to test biomarkers (e.g., serum proteins and extracellular vesicles) may help to monitor brain tumors. In this proteomics-based study, we aimed to identify a characteristic protein fingerprint associated with central nervous system (CNS) tumors. Overall, 96 human serum samples were obtained from four patient groups, namely glioblastoma multiforme (GBM), non-small-cell lung cancer brain metastasis (BM), meningioma (M) and lumbar disc hernia patients (CTRL). After the isolation and characterization of small extracellular vesicles (sEVs) by nanoparticle tracking analysis (NTA) and atomic force microscopy (AFM), liquid chromatography -mass spectrometry (LC-MS) was performed on two different sample types (whole serum and serum sEVs). Statistical analyses (ratio, Cohen’s d, receiver operating characteristic; ROC) were carried out to compare patient groups. To recognize differences between the two sample types, pairwise comparisons (Welch’s test) and ingenuity pathway analysis (IPA) were performed. According to our knowledge, this is the first study that compares the proteome of whole serum and serum-derived sEVs. From the 311 proteins identified, 10 whole serum proteins and 17 sEV proteins showed the highest intergroup differences. Sixty-five proteins were significantly enriched in sEV samples, while 129 proteins were significantly depleted compared to whole serum. Based on principal component analysis (PCA) analyses, sEVs are more suitable to discriminate between the patient groups. Our results support that sEVs have greater potential to monitor CNS tumors, than whole serum.

Background and Aim: Adalimumab [ADA] was approved for the treatment of ulcerative colitis [UC] refractory to conventional therapy in 2012 in Europe. Due to the observed discrepancies between clinical trials and practice, data on the outcome of ADA therapy are really needed from the real life. The aim of this study was to estimate the short- and long-term efficacy and safety of ADA in UC patients from each Hungarian biological centre. Patients and Methods: This prospective study consisted of UC patients treated with ADA in 10 Hungarian inflammatory bowel disease centres. The primary endpoints of the study were rates of continuous clinical response, remission, non-response and loss of response at Weeks 12, 30, and 52.The secondary endpoints included mucosal healing at Week 52 and the comparison of the efficacy of ADA between biological naive and infliximab [IFX]-treated groups. Colonoscopy was performed before starting the therapy and at Week 52. Results: In all, 73 active UC patients were enrolled in the study: 67.1% of the patients received previous IFX therapy; 75.3% of the patients showed short-term clinical response at Week 12. The probability of maintaining ADA was 48.6% at Week 52 with a continuous clinical response in 92% of these remaining patients. Mucosal healing was achieved in 48.1% of the patients at Week 52. Escalation of ADA was performed in 17.6%, and minor side effects developed in 4% of the patients; 5.4% of the patients underwent colectomy during the 1-year treatment period. Conclusion: UC is a progressive disease that may need early aggressive therapy to prevent structural and functional complications. The results of our study demonstrated the favourable efficacy of short- and long-term ADA treatment for patients with UC.