Mental disorders (MDs) are highly prevalent and potentially debilitating complex disorders which causes remain elusive. Looking into deeper aspects of etiology or pathophysiology underlying these diseases would be highly beneficial, as the scarce knowledge in mechanistic and molecular pathways certainly represents an important limitation. Association between MDs and inflammation/neuroinflammation has been widely discussed and accepted by many, as high levels of pro-inflammatory cytokines were reported in patients with several MDs, such as schizophrenia (SCZ), bipolar disorder (BD) and major depression disorder (MDD), among others. Correlation of pro-inflammatory markers with symptoms intensity was also reported. However, the mechanisms underlying the inflammatory dysfunctions observed in MDs are not fully understood yet. In this context, microglial dysfunction has recently emerged as a possible pivotal player, as during the neuroinflammatory response, microglia can be over-activated, and excessive production of pro-inflammatory cytokines, which can modify the kynurenine and glutamate signaling, is reported. Moreover, microglial activation also results in increased astrocyte activity and consequent glutamate release, which are both toxic to the Central Nervous System (CNS). Also, as a result of increased microglial activation in MDs, products of the kynurenine pathway were shown to be changed, influencing then the dopaminergic, serotonergic, and glutamatergic signaling pathways. Therefore, in the present review, we aim to discuss how neuroinflammation impacts on glutamate and kynurenine signaling pathways, and how they can consequently influence the monoaminergic signaling. The consequent association with MDs main symptoms is also discussed. As such, this work aims to contribute to the field by providing insights into these alternative pathways and by shedding light on potential targets that could improve the strategies for pharmacological intervention and/or treatment protocols to combat the main pharmacologically unmatched symptoms of MDs, as the SCZ.

UNASSIGNED: Global liquid chromatography mass spectrometry (LC-MS) profiling in a Thai population has previously identified a urinary metabolic signature in Opisthorchis viverrini-induced cholangiocarcinoma (CCA), primarily characterised by disturbance in acylcarnitine, bile acid, steroid, and purine metabolism. However, the detection of thousands of analytes by LC-MS in a biological sample in a single experiment potentially introduces false discovery errors. To verify these observed metabolic perturbations, a second validation dataset from the same population was profiled in a similar fashion.
UNASSIGNED: Reverse-phase ultra-performance liquid-chromatography mass spectrometry was utilised to acquire the global spectral profile of 98 spot urine samples (from 46 healthy volunteers and 52 CCA patients) recruited from Khon Kaen, northeast Thailand (the highest incidence of CCA globally).
UNASSIGNED: Metabolites were differentially expressed in the urinary profiles from CCA patients. High urinary elimination of bile acids was affected by the presence of obstructive jaundice. The urine metabolome associated with non-jaundiced CCA patients showed a distinctive pattern, similar but not identical to published studies. A panel of 10 metabolites achieved a diagnostic accuracy of 93.4% and area under the curve value of 98.8% (CI = 96.3%-100%) for the presence of CCA.
UNASSIGNED: Global characterisation of the CCA urinary metabolome identified several metabolites of biological interest in this validation study. Analyses of the diagnostic utility of the discriminant metabolites showed excellent diagnostic potential. Further larger scale studies are required to confirm these findings internationally, particularly in comparison to sporadic CCA, not associated with liver fluke infestation.

Short-chain fatty acids (SCFAs) exhibit anticancer activity in cellular and animal models of colon cancer. Acetate, propionate, and butyrate are the three major SCFAs produced from dietary fiber by gut microbiota fermentation and have beneficial effects on human health. Most previous studies on the antitumor mechanisms of SCFAs have focused on specific metabolites or genes involved in antitumor pathways, such as reactive oxygen species (ROS) biosynthesis. In this study, we performed a systematic and unbiased analysis of the effects of acetate, propionate, and butyrate on ROS levels and metabolic and transcriptomic signatures at physiological concentrations in human colorectal adenocarcinoma cells. We observed significantly elevated levels of ROS in the treated cells. Furthermore, significantly regulated signatures were involved in overlapping pathways at metabolic and transcriptomic levels, including ROS response and metabolism, fatty acid transport and metabolism, glucose response and metabolism, mitochondrial transport and respiratory chain complex, one-carbon metabolism, amino acid transport and metabolism, and glutaminolysis, which are directly or indirectly linked to ROS production. Additionally, metabolic and transcriptomic regulation occurred in a SCFAs types-dependent manner, with an increasing degree from acetate to propionate and then to butyrate. This study provides a comprehensive analysis of how SCFAs induce ROS production and modulate metabolic and transcriptomic levels in colon cancer cells, which is vital for understanding the mechanisms of the effects of SCFAs on antitumor activity in colon cancer.

This research was conducted to demonstrate the comparisons of nutritional constituents (isoflavone; anthocyanin; protein; fatty acid; oil) and biological properties (antioxidant, anti-aging) in whole seeds and seed coats of black soybeans for crop years. Isoflavones and anthocyanins showed considerable differences in cultivars and growth years with the ranges of 794.9-4195.3 μg/g and 2.3-14.4 mg/g, while other components exhibited slight variations. In particular, malonylgenistin and cyanidin-3-O-glucoside were observed the most abundant phenolics, comprising approximately 35.5 (778.0 μg/g) and 76.7% (4.6 mg/g) of total average contents (isoflavone: 2197.8 μg/g; anthocyanin: 6.0 mg/g). Moreover, the whole seeds and seed coats displayed excellent activities in antioxidant (radical; DNA protectant), tyrosinase inhibition, and elastase inhibition. Their effects significantly occurred with dose-dependent patterns as follows: elastase (150 μg/mL) > tyrosinase (600 μg/mL) > ABTS (1500 μg/mL) > DPPH (1500 μg/mL) with higher abilities of seed coats than whole seeds. The DNA protection exhibited higher rates in seed coats with > 90% at 200 μg/mL. Natably, Socheong (isoflavone; 4182.4 μg/g) and Geomjeong 2 (anthocyanin: 10.3 mg/g) cultivars may be recommended as potential sources to the development of functional agents and new cultivars owing to their high average phenolic contents.

The current research was characterized on phenolic metabolite profile including six chemical structures (phenolic acid, luteolin, orientin, apigenin, isoscoparin, and tricin) in wheat seedlings using HPLC-Q-Orbitrap-MS/MS and NMR techniques. Our study was also was the first to demonstrate fluctuations of isolated nine phenolic contents and antioxidant properties in various cultivars of this species with different growth times. The antioxidant abilities differed significantly in the 80 % methanol extracts (600 μg/mL) according to cultivar and growth time, with the highest average activities (DPPH: 82 %; ABTS: 87 %) observed after 7 days. The isolated nine compositions exhibited considerable differences in cultivars and growth times, specifically, isoorientin (6) and isochaftoside (8) were observed the most abundant average contents (99.3; 64.3 mg/100 g), representing approximately 28.3 and 18.3 % (total content: 350.8 mg/100 g). Their total phenolics showed the highest rates (420.8 mg/100 g) at 7 days, followed by 9 → 5 → 12 → 14 days with 374.6 → 366.7 → 350.7 → 241.1 mg/100 g, as the rank orders of antioxidant effects. These findings suggest that wheat seedlings may be a potent source of functional agents.

O-Acetyl esterification is an important structural and functional feature of pectins present in the cell walls of all land plants. The amount and positions of pectin acetyl substituents varies across plant tissues and stages of development. Plant growth and response to biotic and abiotic stress are known to be significantly influenced by pectin O-acetylation. Gel formation is a key characteristic of pectins, and many studies have shown that gel formation is dependent upon the degree of acetylation. Previous studies have indicated that members of the TRICHOME BIREFRINGENCE-LIKE (TBL) family may play a role in the O-acetylation of pectin, however, biochemical evidence for acceptor specific pectin acetyltransferase activity remains to be confirmed and the exact mechanism(s) for catalysis must be determined. Pectin acetylesterases (PAEs) affect pectin acetylation as they hydrolyze acetylester bonds and have a role in the amount and distribution of O-acetylation. Several mutant studies suggest the critical role of pectin O-acetylation; however, additional research is required to fully understand this. This review aims to discuss the importance, role, and putative mechanism of pectin O-acetylation.

•Xylan is an abundant carbohydrate component of plant cell walls that is vital for proper cell wall structure and vascular tissue development.•Xylan structure is known to vary between different tissues and species.•The role of xylan in the plant cell wall is to interact with cellulose, lignin, and hemicelluloses.•Xylan synthesis is directed by several types of Golgi-localized enzymes.•Xylan is being explored as an eco-friendly resource for diverse commercial applications.

The use of computer-aided methods have continued to propel accelerated drug discovery across various disease models, interestingly allowing the specific inhibition of pathogenic targets. Chloride Intracellular Channel Protein 4 (CLIC4) is a novel class of intracellular ion channel highly implicated in tumor and vascular biology. It regulates cell proliferation, apoptosis and angiogenesis; and is involved in multiple pathologic signaling pathways. Absence of specific inhibitors however impedes its advancement to translational research. Here, we integrate structural bioinformatics and experimental research approaches for the discovery and validation of small-molecule inhibitors of CLIC4. High-affinity allosteric binders were identified from a library of 1615 Food and Drug Administration (FDA)-approved drugs via a high-performance computing-powered blind-docking approach, resulting in the selection of amphotericin B and rapamycin. NMR assays confirmed the binding and conformational disruptive effects of both drugs while they also reversed stress-induced membrane translocation of CLIC4 and inhibited endothelial cell migration. Structural and dynamics simulation studies further revealed that the inhibitory mechanisms of these compounds were hinged on the allosteric modulation of the catalytic glutathione (GSH)-like site loop and the extended catalytic β loop which may elicit interference with the catalytic activities of CLIC4. Structure-based insights from this study provide the basis for the selective targeting of CLIC4 to treat the associated pathologies.

UNASSIGNED: Lipid dysregulation and complement system (CS) activation are 2 important pathophysiology pathways for age-related macular degeneration (AMD). We hypothesized that the relationship between lipids and AMD may also differ according to CS genotype profile. Thus, the objective was to investigate the relationships between lipid-related metabolites and AMD according to CS genotypes.
UNASSIGNED: Population-based cross-sectional study.
UNASSIGNED: A total of 6947 participants from Singapore Epidemiology of Eye Diseases study with complete relevant data were included.
UNASSIGNED: We investigated a total of 32 blood lipid-related metabolites from nuclear magnetic resonance metabolomics data including lipoproteins and their subclasses, cholesterols, glycerides, and phospholipids, as well as 4 CS single nucleotide polymorphisms (SNPs): rs10922109 (complement factor H), rs10033900 (complement factor I), rs116503776 (C2-CFB-SKIV2L), and rs2230199 (C3). We first investigated the associations between AMD and the 32 lipid-related metabolites using multivariable logistic regression models. Then, to investigate whether the effect of lipid-related metabolites on AMD differ according to the CS SNPs, we tested the possible interactions between the CS SNPs and the lipid-related metabolites.
UNASSIGNED: Age-related macular degeneration was defined using the Wisconsin grading system.
UNASSIGNED: Among the 6947 participants, the prevalence of AMD was 6.1%, and the mean age was 58.3 years. First, higher levels of cholesterol in high-density lipoprotein (HDL) and medium and large HDL particles were associated with an increased risk of AMD, and higher levels of serum total triglycerides (TG) and several very-low-density lipoprotein subclass particles were associated with a decreased risk of AMD. Second, these lipids had significant interaction effects on AMD with 2 CS SNPs: rs2230199 and rs116503776 (after correction for multiple testing). For rs2230199, in individuals without risk allele, higher total cholesterol in HDL2 was associated with an increased AMD risk (odds ratio [OR] per standard deviation increase, 1.20; 95% confidence interval (CI), 1.06-1.37; P = 0.005), whereas, in individuals with at least 1 risk allele, higher levels of these particles were associated with a decreased AMD risk (OR, 0.69; 95% CI, 0.45-1.05; P = 0.079). Conversely, for rs116503776, in individuals without risk allele, higher serum total TG were associated with a decreased AMD risk (OR, 0.84; 95% CI, 0.74-0.95; P = 0.005), whereas, in individuals with 2 risk alleles, higher levels of these particles were associated with an increased risk of AMD (OR, 2.3, 95% CI, 0.99-5.39, P = 0.054).
UNASSIGNED: Lipid-related metabolites exhibit opposite directions of effects on AMD according to CS genotypes. This indicates that lipid metabolism and CS may have synergistic interplay in the AMD pathogenesis.

The color and pungency are important indicators for evaluating the quality of chili oil, which are mainly determined by the carotenoids and capsaicinoids, respectively. In this study, the effect of frying temperature on the changes of carotenoids and capsaicinoids in chili oil was qualitatively and quantitatively analyzed by 1H NMR. The increasing frying temperature caused the thermal degradation of carotenoids to be intensified, and the degradation of red carotenoids was greater than that of yellow carotenoids. After 10 min of frying at 130, 150, 170 and 190 °C, the contents of capsanthin in chili oil were 40.3, 15.4, 9.6 and 6.2 mg/kg, respectively. Meanwhile, the contents of total carotenoids were 63.0, 25.5, 17.7 and 13.3 mg/kg, respectively. The observed change of R/Y values correlated well with the degradation of carotenoids. The contents of capsaicinoids were 14.8, 20.9, 19.4 and 7.4 mg/kg, respectively. The best frying temperature for the extraction of carotenoids was 130 °C, and over 90% of the carotenoids were dissolved in the frying oil at this frying condition. However, capsaicinoids were more stable than carotenoids, and the best frying temperature for capsaicinoids was 150-170 °C with over 90% extraction rate. Therefore, the temperature fried at 130-150 °C was suitable for the quality of chili oil, considering the higher extraction rates of both total carotenoids and capsaicinoids. This study is of great significance for the quality control of chili oil.