PubMed

Sci Rep. 2023 Apr 4;13(1):5488. doi: 10.1038/s41598-023-32713-2.ABSTRACTA growing body of preclinical and clinical literature suggests that brain-gut-microbiota interactions may contribute to obesity pathogenesis. In this study, we use a machine learning approach to leverage the enormous amount of microstructural neuroimaging and fecal metabolomic data to better understand key drivers of the obese compared to overweight phenotype. Our findings reveal that although gut-derived factors play a role in this distinction, it is primarily brain-directed changes that differentiate obese from overweight individuals. Of the key gut metabolites that emerged from our model, many are likely at least in part derived or influenced by the gut-microbiota, including some amino-acid derivatives. Remarkably, key regions outside of the central nervous system extended reward network emerged as important differentiators, suggesting a role for previously unexplored neural pathways in the pathogenesis of obesity.PMID:37016129 | DOI:10.1038/s41598-023-32713-2

Nat Commun. 2023 Apr 4;14(1):1638. doi: 10.1038/s41467-023-37269-3.ABSTRACTThe pathogenesis of multi-organ dysfunction associated with severe acute SARS-CoV-2 infection remains poorly understood. Endothelial damage and microvascular thrombosis have been identified as drivers of COVID-19 severity, yet the mechanisms underlying these processes remain elusive. Here we show alterations in fluid shear stress-responsive pathways in critically ill COVID-19 adults as compared to non-COVID critically ill adults using a multiomics approach. Mechanistic in-vitro studies, using microvasculature-on-chip devices, reveal that plasma from critically ill COVID-19 adults induces fibrinogen-dependent red blood cell aggregation that mechanically damages the microvascular glycocalyx. This mechanism appears unique to COVID-19, as plasma from non-COVID sepsis patients demonstrates greater red blood cell membrane stiffness but induces less significant alterations in overall blood rheology. Multiomics analyses in pediatric patients with acute COVID-19 or the post-infectious multi-inflammatory syndrome in children (MIS-C) demonstrate little overlap in plasma cytokine and metabolite changes compared to adult COVID-19 patients. Instead, pediatric acute COVID-19 and MIS-C patients show alterations strongly associated with cytokine upregulation. These findings link high fibrinogen and red blood cell aggregation with endotheliopathy in adult COVID-19 patients and highlight differences in the key mediators of pathogenesis between adult and pediatric populations.PMID:37015925 | DOI:10.1038/s41467-023-37269-3

Cell Death Dis. 2023 Apr 5;14(4):238. doi: 10.1038/s41419-023-05740-0.ABSTRACTMany anticancer agents induce apoptosis, mitotic catastrophe or cellular senescence. Here, we report the functional characterization of an experimental inducer of tumor necrosis factor (TNF)-independent necrosis, necrocide-1 (NC1). NC1 (but not its stereoisomer) killed a panel of human cancer cells (but not normal cells) at nanomolar concentrations and with a non-apoptotic, necrotic morphotype, both in vitro and in vivo. NC1-induced killing was not inhibited by caspase blockers, anti-apoptotic BCL2 overexpression or TNFα neutralization, suggesting that NC1 elicits a bona fide necrotic pathway. However, pharmacological or genetic inhibition of necroptosis, pyroptosis and ferroptosis failed to block NC1-mediated cell death. Instead, NC1 elicited reactive oxygen species (ROS) production by mitochondria, and elimination of mitochondrial DNA, quenching of mitochondrial ROS, as well as blockade of mitochondrial permeability transition with cyclosporine A, interfered with NC1-induced cell death. NC1 induced hallmarks of immunogenic cell death incurring calreticulin (CALR) exposure, ATP secretion and high mobility group box 1 (HMGB1) release. Taken together, these data identify a previously uncharacterized signaling cascade leading to an immunogenic variant of mitochondrion-regulated necrosis, supporting the notion that eliciting regulated necrosis may constitute a valid approach for anticancer therapy.PMID:37015922 | DOI:10.1038/s41419-023-05740-0

Phytomedicine. 2023 Mar 17;114:154772. doi: 10.1016/j.phymed.2023.154772. Online ahead of print.ABSTRACTBACKGROUND: Colorectal cancer (CRC) is a common malignancy that can significantly diminish patients' quality of life. Astragalus mongholicus Bunge-Curcuma aromatica Salisb. (AC) is an ancient Chinese medicinal combination used for the treatment of CRC. However, the core ingredients and targets involved in regulating lipid and amino acid metabolism in CRC remain unknown. We aimed to explore the key components and pharmacological mechanisms of AC in the treatment of CRC through a comprehensive analysis of network metabolomics, network pharmacology, molecular docking, and biological methods.METHODS: Ultra-performance liquid chromatography/mass spectrometry (MS) was used for quality control. Gas chromatography/MS and liquid chromatography/MS were used to detect metabolites in the feces and serum of CRC mice. A network pharmacology approach and molecular docking were used to explore the potential genes involved in the CRC-target-component network. The effect of AC on tumor immunity was investigated using flow cytometry and polymerase chain reaction.RESULTS: AC, high-dose AC, and 5-fluorouracil treatment reduced liver metastasis and tumor mass. Compared with the CRC group, 2 amino acid metabolites and 14 lipid metabolites (LPC, PC, PE) were upregulated and 15 amino acid metabolites and 9 lipid metabolites (TG, PE, PG, 12-HETE) were downregulated. Subsequently, through network analysis, four components and six hub genes were identified for molecular docking. AC can bind to ALDH1B1, ALDH2, CAT, GOT2, NOS3, and ASS1 through beta-Elemene, canavanine, betaine, and chrysanthemaxanthin. AC promoted the responses of M1 macrophages and down-regulated the responses of M2 macrophages, Treg cells, and the gene expression of related factors.CONCLUSION: Our research showed that AC effectively inhibited the growth and metastasis of tumors and regulated metabolism and immunity in a CRC mouse model. Thus, AC may be an effective alternative treatment option for CRC.PMID:37015187 | DOI:10.1016/j.phymed.2023.154772

J Proteome Res. 2023 Apr 4. doi: 10.1021/acs.jproteome.3c00006. Online ahead of print.ABSTRACTA major challenge in reducing the death rate of colorectal cancer is to screen patients using low-invasive testing. A blood test shows a high compliance rate with reduced invasiveness. In this work, a multiplex isobaric tag labeling strategy coupled with mass spectrometry is adopted to relatively quantify primary and secondary amine-containing metabolites in serum for the discovery of metabolite level changes of colorectal cancer. Serum samples from patients at different risk statuses and colorectal cancer growth statuses are studied. Metabolite identification is based on accurate mass matching and/or retention time of labeled metabolite standards. We quantify 40 metabolites across all the serum samples, including 18 metabolites validated with standards. We find significantly decreased levels of threonine and asparagine in the patients with growing adenomas or high-risk adenomas (p < 0.05). Glutamine levels decrease in patients with adenomas of unknown growth status or high-risk adenomas. In contrast, arginine levels are elevated in patients with low-risk adenoma. Receiver operating characteristic analysis shows high sensitivity and specificity of these metabolites for detecting growing adenomas. Based on these results, we conclude that a few metabolites identified here might contribute to distinguishing colorectal patients with growing adenomas from normal individuals and patients with unknown growth status of adenomas.PMID:37014956 | DOI:10.1021/acs.jproteome.3c00006

PLoS One. 2023 Apr 4;18(4):e0283105. doi: 10.1371/journal.pone.0283105. eCollection 2023.ABSTRACTTechnically, symptom of offspring asthma is also closely reliant on its maternal high-fiber diet as well as the intestinal microbiome. Fruits and vegetables are abundant in inulin, and this naturally soluble dietary fiber is endowed with a potential value on offspring asthma control through the maternal intake, but the mechanism now remains less studied. In this study, rats were given with inulin-included drinking water, whereas in normal group rats were allowed with normal water. Afterwards, we analyzed both the formations of the offspring intestinal microbiome ahead of asthma model establishment and of the maternal intestinal microbiome through high throughput sequence and the short-chain fatty acids (SCFAs) by metabolomic analysis. Subsequently, lung inflammation indexes were detected by Elisa, and the expression of short-chain fatty acid receptors (GPR41, GPR43) in the offspring of asthma models were evaluated through qPCR assay. Inulin intake resulted in altered maternal intestinal microbiome composition, with a significant increase in SCFAs-producing bacteria (mainly Bifidobacterium), attenuating the asthmatic inflammatory response in the offspring. Meanwhile, inulin intake during pregnancy modulates the composition of the intestinal microbiome of the offspring, and this alteration appears before the onset of asthma, hence, there should be further studies onto the impacts of offspring's intestinal microbiome on asthma procession.PMID:37014871 | DOI:10.1371/journal.pone.0283105

Anal Chem. 2023 Apr 4. doi: 10.1021/acs.analchem.2c02554. Online ahead of print.ABSTRACTThe rapid identification of pathogenic microorganism serotypes is still a bottleneck problem to be solved urgently. Compared with proteomics technology, metabolomics technology is directly related to phenotypes and has higher specificity in identifying pathogenic microorganism serotypes. Our study combines pseudotargeted metabolomics with deep learning techniques to obtain a new deep semiquantitative fingerprinting method for Listeria monocytogenes identification at the serotype levels. We prescreened 396 features with orthogonal partial least-squares discrimination analysis (OPLS-DA), and 200 features were selected for deep learning model building. A residual learning framework for L. monocytogenes identification was established. There were 256 convolutional filters in the initial convolution layer, and each hidden layer contained 128 filters. The total depth included seven layers, consisting of an initial convolution layer, a residual layer, and two final fully connected classification layers, with each residual layer containing four convolutional layers. In addition, transfer learning was used to predict new isolates that did not participate in model training to verify the method's feasibility. Finally, we achieved prediction accuracies of L. monocytogenes at the serotype level exceeding 99%. The prediction accuracy of the new strain validation set was greater than 97%, further demonstrating the feasibility of this method. Therefore, this technology will be a powerful tool for the rapid and accurate identification of pathogens.PMID:37014709 | DOI:10.1021/acs.analchem.2c02554

JCI Insight. 2023 Apr 4:e156397. doi: 10.1172/jci.insight.156397. Online ahead of print.ABSTRACTThe prevalence of obesity and type 2 diabetes is growing at an alarming rate, including among pregnant women. Low-calorie sweeteners (LCS) have increasingly been used as an alternative to sugar to deliver a sweet taste without the excessive caloric load. However, there is little evidence regarding their biological effects, particularly during development. Here, we used a mouse model of maternal LCS consumption to explore the impact of perinatal LCS exposure on the development of neural systems involved in metabolic regulations. We report that adult male, but not female, offspring from both aspartame- and rebaudioside A-exposed dams displayed increased adiposity and developed glucose intolerance. Moreover, maternal LCS consumption reorganized hypothalamic melanocortin circuits and disrupted parasympathetic innervation of pancreatic islets in male offspring. We then identified phenylacetylglycine (PAG) as a unique metabolite that is upregulated in the milk of LCS-fed dams and the serum of their pups. Furthermore, maternal PAG treatment recapitulates some of the key metabolic and neurodevelopmental abnormalities associated with maternal LCS consumption. Together, our data indicate that maternal LCS consumption has enduring consequences on the offspring's metabolism and neural development and that these effects are likely to be mediated through the gut microbial co-metabolite PAG.PMID:37014702 | DOI:10.1172/jci.insight.156397

J Biochem. 2023 Apr 4:mvad028. doi: 10.1093/jb/mvad028. Online ahead of print.ABSTRACTNicotinamide-N-methyltransferase (NNMT) is an enzyme that consumes S-adenosyl-methionine (SAM) and nicotinamide (NAM) to produce S-adenosyl-homocysteine (SAH) and 1-methylnicotinamide (MNAM). How much NNMT contributes to the quantity regulation of these four metabolites depends on whether NNMT is a major consumer or producer of these metabolites, which varies among various cellular contexts. Yet, whether NNMT critically regulates these metabolites in the AML12 hepatocyte cell line has been unexplored. To address this, we knock down Nnmt in AML12 cells and investigate the effects of Nnmt RNAi on metabolism and gene expression. We find that Nnmt RNAi accumulates SAM and SAH, whereas it reduces MNAM with NAM being unaltered. These results indicate that NNMT is a significant consumer of SAM and critical for MNAM production in this cell line. Moreover, transcriptome analyses reveal that altered SAM and MNAM homeostasis is accompanied by various detrimental molecular phenotypes, as exemplified by the down-regulations of lipogenic genes such as Srebf1. Consistent with this, oil-red O-staining experiments demonstrate the decrease of total neutral lipids upon Nnmt RNAi. Treating Nnmt RNAi AML12 cells with cycloleucine, an inhibitor of SAM biogenesis suppresses SAM accumulation and rescues the decrease of neutral lipids. MNAM also shows activity to elevate neutral lipids. These results suggest that NNMT contributes to lipid metabolism by maintaining proper SAM and MNAM homeostasis. This study provides an additional example where NNMT plays a critical role in regulating SAM and MNAM metabolism.PMID:37014628 | DOI:10.1093/jb/mvad028

Metabolomics. 2023 Apr 4;19(4):36. doi: 10.1007/s11306-023-02002-0.ABSTRACTBACKGROUND AND AIMS: Two of the most lethal gastrointestinal (GI) cancers, gastric cancer (GC) and colon cancer (CC), are ranked in the top five cancers that cause deaths worldwide. Most GI cancer deaths can be reduced by earlier detection and more appropriate medical treatment. Unlike the current "gold standard" techniques, non-invasive and highly sensitive screening tests are required for GI cancer diagnosis. Here, we explored the potential of metabolomics for GI cancer detection and the classification of tissue-of-origin, and even the prognosis management.METHODS: Plasma samples from 37 gastric cancer (GC), 17 colon cancer (CC), and 27 non-cancer (NC) patients were prepared for metabolomics and lipidomics analysis by three MS-based platforms. Univariate, multivariate, and clustering analyses were used for selecting significant metabolic features. ROC curve analysis was based on a series of different binary classifications as well as the true-positive rate (sensitivity) and the false-positive rate (1-specificity).RESULTS: GI cancers exhibited obvious metabolic perturbation compared with benign diseases. The differentiated metabolites of gastric cancer (GC) and colon cancer (CC) were targeted to same pathways but with different degrees of cellular metabolism reprogramming. The cancer-specific metabolites distinguished the malignant and benign, and classified the cancer types. We also applied this test to before- and after-surgery samples, wherein surgical resection significantly altered the blood-metabolic patterns. There were 15 metabolites significantly altered in GC and CC patients who underwent surgical treatment, and partly returned to normal conditions.CONCLUSION: Blood-based metabolomics analysis is an efficient strategy for GI cancer screening, especially for malignant and benign diagnoses. The cancer-specific metabolic patterns process the potential for classifying tissue-of-origin in multi-cancer screening. Besides, the circulating metabolites for prognosis management of GI cancer is a promising area of research.PMID:37014438 | DOI:10.1007/s11306-023-02002-0

Dev Neuropsychol. 2023 Apr 4:1-12. doi: 10.1080/87565641.2023.2198773. Online ahead of print.ABSTRACTThe aim of this study was to discover the effects of COVID-19 on the mental health, academic life, social life of students and discover their interrelationships at a boarding school in New Jersey, USA. A majority of participants reported that COVID-19 had a negative effect on their mental health and social lives, felt well informed about COVID-19 cases on campus, and were unconcerned about getting COVID-19 at school. Given the correlations and differences observed, it is likely that some groups of adolescents may be at greater risk of impacted mental health as a result of the COVID-19 pandemic. .PMID:37014298 | DOI:10.1080/87565641.2023.2198773

J Food Sci. 2023 Apr 4. doi: 10.1111/1750-3841.16549. Online ahead of print.ABSTRACTNot from concentrate (NFC) orange juice is minimally processed, natural-appearing food, and has become more popular. Sterilization is an important stage for NFC orange juice production. Here we present a comprehensive analysis of the effect of sterilization on the metabolites of NFC orange juices, including three thermal (pasteurization, high-temperature short time, and ultra-high temperature) and one nonthermal (high hydrostatic pressure) method. A total of 108 metabolites, including 59 volatiles and 49 nonvolatiles were identified in orange juice. Of which, only butyl butanoate and 3-carene were detected in fresh orange juice. Sterilization significantly changed the metabolites of orange juice, and different methods caused various changes. Esters were downregulated by both thermal and nonthermal sterilization, while most flavonoids and terpenes were upregulated. With comparative analyses of three thermal sterilization, we found that high temperature and relatively short-time treatment preserved esters and ascorbic acid more effectively than low temperature and prolonged treatment. Aldehydes, however, were the opposite. Nonthermal sterilization is effective in preserving the metabolites of orange juice, especially for esters, terpenes, and flavonoids. In addition, 19 distinct metabolites were characterized between thermal and nonthermal samples by chemometrics analysis. These findings provide a new sight of the optimization of sterilization methods and references for different types of NFC orange juice identification. PRACTICAL APPLICATION: This study provides a reference for the optimization of sterilization methods and identification of HHP and thermal NFC orange juice and also benefits the purchase of consumers.PMID:37013965 | DOI:10.1111/1750-3841.16549

Hepatology. 2023 Apr 5. doi: 10.1097/HEP.0000000000000390. Online ahead of print.ABSTRACTThe most widespread type of liver cancer, hepatocellular carcinoma (HCC), is associated with disabled cellular death pathways. Despite therapeutic advancements, resistance to current systemic treatments (including sorafenib) compromises the prognosis of HCC patients, driving the search for agents that might target novel cell death pathways. Ferroptosis, a form of iron-mediated non-apoptotic cell death, has gained considerable attention as a potential target for cancer therapy, especially in HCC. The role of ferroptosis in HCC is complex and diverse. On one hand, ferroptosis can both contribute to the progression of HCC through its involvement in acute and chronic liver conditions. On the other hand, having ferroptosis affect HCC cells might be desirable. This review examines the role of ferroptosis in HCC from cellular, animal, and human perspectives, while examining its mechanisms, regulation, biomarkers, and clinical implications.PMID:37013919 | DOI:10.1097/HEP.0000000000000390

Pest Manag Sci. 2023 Apr 4. doi: 10.1002/ps.7489. Online ahead of print.ABSTRACTBACKGROUND: Indoxacarb, representing an efficient insecticide, is normally made into a bait to spread the poison among red fire ants so that it can be widely applied in the prevention and control of Solenopsis invicta. However, the potential toxicity mechanism of S. invicta in response to indoxacarb remains to be explored. In this study, we integrated mass spectrometry imaging (MSI) and untargeted metabolomics methods to reveal disturbed metabolic expression levels and spatial distribution within the whole-body tissue of S. invicta treated with indoxacarb.RESULTS: Metabolomics results showed a significantly altered level of metabolites after indoxacarb treatment, such as carbohydrates, amino acids and pyrimidine and derivatives. Additionally, the spatial distribution and regulation of several crucial metabolites resulting from the metabolic pathway and lipids can be visualized using label-free MSI methods. Specifically, xylitol, aspartate, and uracil were distributed throughout the whole body of S. invicta, while sucrose-6'-phosphate and glycerol were mainly distributed in the abdomen of S. invicta, and thymine was distributed in the head and chest of S. invicta. Taken together, the integrated MSI and metabolomics results indicated that the toxicity mechanism of indoxacarb in S. invicta is closely associated with the disturbance in several key metabolic pathways, such as pyrimidine metabolism, aspartate metabolism, pentose and glucuronate interconversions, and inhibited energy synthesis.CONCLUSION: Collectively, these findings provide a new perspective for the understanding of toxicity assessment between targeted organisms S. invicta and pesticides. This article is protected by copyright. All rights reserved.PMID:37013793 | DOI:10.1002/ps.7489

Stem Cell Res Ther. 2023 Apr 3;14(1):63. doi: 10.1186/s13287-023-03290-y.ABSTRACTBACKGROUND: Post-translational modifications of proteins are crucial to the regulation of their activity and function. As a newly discovered acylation modification, crotonylation of non-histone proteins remains largely unexplored, particularly in human embryonic stem cells (hESCs).METHODS: We investigated the role of crotonylation in hESC differentiation by introduce crotonate into the culture medium of GFP tagged LTR7 primed H9 cell and extended pluripotent stem cell lines. RNA-seq assay was used to determine the hESC transcriptional features. Through morphological changes, qPCR of pluripotent and germ layer-specific gene markers and flow cytometry analysis, we determined that the induced crotonylation resulted in hESC differentiating into the endodermal lineage. We performed targeted metabolomic analysis and seahorse metabolic measurement to investigate the metabolism features after crotonate induction. Then high-resolution tandem mass spectrometry (LC-MS/MS) revealed the target proteins in hESCs. In addition, the role of crotonylated glycolytic enzymes (GAPDH and ENOA) was evaluated by in vitro crotonylation and enzymatic activity assays. Finally, we used knocked-down hESCs by shRNA, wild GAPDH and GAPDH mutants to explore potential role of GAPDH crotonylation in regulating human embryonic stem cell differentiation and metabolic switch.RESULT: We found that induced crotonylation in hESCs resulted in hESCs of different pluripotency states differentiating into the endodermal lineage. Increased protein crotonylation in hESCs was accompanied by transcriptomic shifts and decreased glycolysis. Large-scale crotonylation profiling of non-histone proteins revealed that metabolic enzymes were major targets of inducible crotonylation in hESCs. We further discovered GAPDH as a key glycolytic enzyme regulated by crotonylation during endodermal differentiation from hESCs.CONCLUSIONS: Crotonylation of GAPDH decreased its enzymatic activity thereby leading to reduced glycolysis during endodermal differentiation from hESCs.PMID:37013624 | DOI:10.1186/s13287-023-03290-y

Adv Sci (Weinh). 2023 Apr 4:e2300148. doi: 10.1002/advs.202300148. Online ahead of print.ABSTRACTMeat is among the most consumed foods worldwide and has a unique flavor and high nutrient density in the human diet. However, the genetic and biochemical bases of meat nutrition and flavor are poorly understood. Here, 3431 metabolites and 702 volatiles in 423 skeletal muscle samples are profiled from a gradient consanguinity segregating population generated by Pekin duck × Liancheng duck crosses using metabolomic approaches. The authors identified 2862 metabolome-based genome-wide association studies (mGWAS) signals and 48 candidate genes potentially modulating metabolite and volatile levels, 79.2% of which are regulated by cis-regulatory elements. The level of plasmalogen is significantly associated with TMEM189 encoding plasmanylethanolamine desaturase 1. The levels of 2-pyrrolidone and glycerophospholipids are regulated by the gene expression of AOX1 and ACBD5, which further affects the levels of volatiles, 2-pyrrolidone and decanal, respectively. Genetic variations in GADL1 and CARNMT2 determine the levels of 49 metabolites including L-carnosine and anserine. This study provides novel insights into the genetic and biochemical basis of skeletal muscle metabolism and constitutes a valuable resource for the precise improvement of meat nutrition and flavor.PMID:37013465 | DOI:10.1002/advs.202300148

Front Plant Sci. 2023 Apr 3;14:1141232. doi: 10.3389/fpls.2023.1141232. eCollection 2023.ABSTRACTINTRODUCTION: Maize has a high demand for nitrogen during the growth period. The study of metabolic changes in maize can provide a theoretical basis for rational nitrogen nutrition regulation.METHODS: In order to investigate the changes of different metabolites and their metabolic pathways in maize leaves under nitrogen stress, we used ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) for metabolomic analysis of maize leaves under different nitrogen treatments at three critical growth stages (V4, V12 and R1) in a pot experiment under natural conditions.RESULTS AND DISCUSSION: The results showed that nitrogen stress significantly affected sugar metabolism and nitrogen metabolism, and affected carbon and nitrogen balance, and the effects of stress on maize leaves metabolism increased with the growth process. Metabolic pathways such as the TCA cycle and starch and sucrose metabolism were mainly affected at the seeding stage (V4). The stress response to nitrogen deficiency also showed significant upregulation of flavonoids such as luteolin and astragalin during the booting stage (V12) and anthesis-silking stage (R1). During R1 stage, the synthesis of tryptophan and phenylalanine and the degradation of lysine were significantly affected. Compared with nitrogen stress, the metabolic synthesis of key amino acids and jasmonic acid were intensified and the TCA cycle was promoted under nitrogen sufficiency conditions. This study initially revealed that the response mechanism of maize to nitrogen stress at the metabolic level.PMID:37077647 | PMC:PMC10106645 | DOI:10.3389/fpls.2023.1141232

Sci Rep. 2023 Apr 3;13(1):5435. doi: 10.1038/s41598-023-31829-9.ABSTRACT1st episode drug naïve patients with psychosis might be at higher risk for cardiometabolic disturbances which could affect the different cognitive, and executive functions and domains of social cognition. This study aimed to study the metabolic parameters in 1st episode drug naïve patients with psychosis, to evaluate the relation of these cardiometabolic domains to the cognitive, executive functions, and social cognition. Socio-demographic characteristics of 150 first episode drug naïve patients with psychosis and 120 matched healthy control groups were collected. The current study also assessed the cardiometabolic profile and cognitive functions in both groups. Social cognition was examined by Edinburgh Social Cognition Test. The study revealed a statistically significant difference in parameters of metabolic profile among the studied groups (p < 0.001*), the scores of cognitive and executive tests were statistically significantly different (p < 0.001*). In addition, the patient's group has lowered scores of domains of social cognition (p < 0.001*). Also, the mean affective theory of mind was negatively correlated with the conflict cost of the Flanker test (r = -.185* p value = .023). The total cholesterol level (r = - 0.241**, p value = .003) and level of triglycerides (r = - 0.241**, p value = 0.003) were negatively correlated with the interpersonal domain of social cognition, the total cholesterol level is positively correlated to the total score of social cognition (r = 0.202*, p value = 0.013). Patients with 1st episode drug naïve psychosis showed disturbed cardiometabolic parameters which have deleterious effects on cognitive functions and social cognition.PMID:37012300 | PMC:PMC10070352 | DOI:10.1038/s41598-023-31829-9

J Transl Med. 2023 Apr 2;21(1):240. doi: 10.1186/s12967-023-04088-5.ABSTRACTType 2 diabetes mellitus (T2DM), one of the main types of Noncommunicable diseases (NCDs), is a systemic inflammatory disease characterized by dysfunctional pancreatic β-cells and/or peripheral insulin resistance, resulting in impaired glucose and lipid metabolism. Genetic, metabolic, multiple lifestyle, and sociodemographic factors are known as related to high T2DM risk. Dietary lipids and lipid metabolism are significant metabolic modulators in T2DM and T2DM-related complications. Besides, accumulated evidence suggests that altered gut microbiota which plays an important role in the metabolic health of the host contributes significantly to T2DM involving impaired or improved glucose and lipid metabolism. At this point, dietary lipids may affect host physiology and health via interaction with the gut microbiota. Besides, increasing evidence in the literature suggests that lipidomics as novel parameters detected with holistic analytical techniques have important roles in the pathogenesis and progression of T2DM, through various mechanisms of action including gut-brain axis modulation. A better understanding of the roles of some nutrients and lipidomics in T2DM through gut microbiota interactions will help develop new strategies for the prevention and treatment of T2DM. However, this issue has not yet been entirely discussed in the literature. The present review provides up-to-date knowledge on the roles of dietary lipids and lipidomics in gut-brain axis in T2DM and some nutritional strategies in T2DM considering lipids- lipidomics and gut microbiota interactions are given.PMID:37009872 | DOI:10.1186/s12967-023-04088-5

FEBS J. 2023 Apr 3. doi: 10.1111/febs.16787. Online ahead of print.ABSTRACTDe novo L-serine biosynthesis in the mammalian astrocytes proceeds via a linear, three-step pathway (the phosphorylated pathway) catalysed by 3-phosphoglycerate dehydrogenase (PHGDH), phosphoserine aminotransferase (PSAT) and phosphoserine phosphatase (PSP). The first reaction, catalysed by PHGDH and using the glycolytic intermediate 3-phosphoglycerate, is strongly shifted towards the reagents and coupling to the following step by PSAT is required to push the equilibrium towards L-serine formation; the last step, catalysed by PSP, is virtually irreversible and inhibited by the final product L-serine. Very little is known about the regulation of the human phosphorylated pathway and the ability of the three enzymes to organise in a complex with potential regulatory functions. Here, the complex formation was investigated in differentiated human astrocytes, by proximity ligation assay, and in vitro on the human recombinant enzymes. The results indicate that the three enzymes co-localize in cytoplasmic clusters that more stably engage PSAT and PSP. Although in vitro analyses based on native PAGE, size exclusion chromatography and cross-linking experiments do not show the formation of a stable complex, kinetic studies of the reconstituted pathway using physiological enzyme and substrate concentrations support cluster formation and indicate that PHGDH catalyses the rate-limiting step while PSP reaction is the driving force for the whole pathway. The enzyme agglomerate assembly of the phosphorylated pathway (the putative "serinosome") delivers a relevant level of sophistication to the control of L-serine biosynthesis in human cells, a process strictly related to the modulation of the brain levels of D-serine and glycine, the main co-agonists of N-methyl-D-aspartate receptors, and to various pathological states.PMID:37012601 | DOI:10.1111/febs.16787