PubMed

CNS Neurol Disord Drug Targets. 2023 Oct 5. doi: 10.2174/0118715273256132230921103333. Online ahead of print.ABSTRACTMemory is the persisting consequence of cognitive activities instigated by and engrossed on exterior information from the environment and commenced by an intensive on internal mental representations. Establishing a gut-brain axis (GBA) in health and disease has recently brought the gut, the main portal of communication with the external environment, to the forefront of this interaction. Dietary stimuli have long been linked to brain development, behavioral responses, and memory reflections. Vagus nerve, immune system, bacterial metabolites and products are just a few of the linkages that make up the GBA, a bidirectional arrangement of signaling pathways that connects the neurological system with the gastrointestinal tract. GBA involves two-way communication between central and enteric neural systems, connecting the brain's affective and cognitive regions to peripheral activities of the intestine. Recent scientific progress has highlighted the significance of gut microbiota in affecting these relationships. By controlling myelination at the prefrontal cortex, a crucial area for multifaceted cognitive behavior forecast and decision-making, this axis influences social behavior, including memory reflections. Humans may experience late myelination of the prefrontal cortex's axonal projections into the third decade of life, making it vulnerable to outside factors like microbial metabolites. It has been demonstrated that changes in the gut microbiome can change the microbial metabolome's composition, impacting highly permeable bioactive chemicals like p-cresol that may hinder oligodendrocyte differentiation. This review will discuss the memory reflections of the microbiota-gut and oligodendrocyte axis. Adopting this concept should encourage a new arena of thinking that recognizes the intricate central and periphery dynamics influencing behavior and uses that knowledge to develop novel therapies and interventions for maladjusted memory and learning systems.PMID:37855297 | DOI:10.2174/0118715273256132230921103333

PNAS Nexus. 2023 Sep 29;2(10):pgad322. doi: 10.1093/pnasnexus/pgad322. eCollection 2023 Oct.ABSTRACTFungal specialized metabolites are a major source of beneficial compounds that are routinely isolated, characterized, and manufactured as pharmaceuticals, agrochemical agents, and industrial chemicals. The production of these metabolites is encoded by biosynthetic gene clusters that are often silent under standard growth conditions. There are limited resources for characterizing the direct link between abiotic stimuli and metabolite production. Herein, we introduce a network analysis-based, data-driven algorithm comprising two routes to characterize the production of specialized fungal metabolites triggered by different exogenous compounds: the direct route and the auxiliary route. Both routes elucidate the influence of treatments on the production of specialized metabolites from experimental data. The direct route determines known and putative metabolites induced by treatments and provides additional insight over traditional comparison methods. The auxiliary route is specific for discovering unknown analytes, and further identification can be curated through online bioinformatic resources. We validated our algorithm by applying chitooligosaccharides and lipids at two different temperatures to the fungal pathogen Aspergillus fumigatus. After liquid chromatography-mass spectrometry quantification of significantly produced analytes, we used network centrality measures to rank the treatments' ability to elucidate these analytes and confirmed their identity through fragmentation patterns or in silico spiking with commercially available standards. Later, we examined the transcriptional regulation of these metabolites through real-time quantitative polymerase chain reaction. Our data-driven techniques can complement existing metabolomic network analysis by providing an approach to track the influence of any exogenous stimuli on metabolite production. Our experimental-based algorithm can overcome the bottlenecks in elucidating novel fungal compounds used in drug discovery.PMID:37854706 | PMC:PMC10581544 | DOI:10.1093/pnasnexus/pgad322

iScience. 2023 Sep 22;26(10):108016. doi: 10.1016/j.isci.2023.108016. eCollection 2023 Oct 20.ABSTRACTMethanogenesis allows methanogenic archaea to generate cellular energy for their growth while producing methane. Thermophilic hydrogenotrophic species of the genus Methanothermobacter have been recognized as robust biocatalysts for a circular carbon economy and are already applied in power-to-gas technology with biomethanation, which is a platform to store renewable energy and utilize captured carbon dioxide. Here, we generated curated genome-scale metabolic reconstructions for three Methanothermobacter strains and investigated differences in the growth performance of these same strains in chemostat bioreactor experiments with hydrogen and carbon dioxide or formate as substrates. Using an integrated systems biology approach, we identified differences in formate anabolism between the strains and revealed that formate anabolism influences the diversion of carbon between biomass and methane. This finding, together with the omics datasets and the metabolic models we generated, can be implemented for biotechnological applications of Methanothermobacter in power-to-gas technology, and as a perspective, for value-added chemical production.PMID:37854702 | PMC:PMC10579436 | DOI:10.1016/j.isci.2023.108016

Front Psychiatry. 2023 Oct 3;14:1182536. doi: 10.3389/fpsyt.2023.1182536. eCollection 2023.ABSTRACTThe second part of this paper builds upon and expands the epigenomic-aging perspective presented in Part 1 to describe the metabolomic and immunomic bases of the epigenomic-aging changes and then considers in some detail the application of these insights to neurotoxicity, neuronal epigenotoxicity, and synaptopathy. Cannabinoids are well-known to have bidirectional immunomodulatory activities on numerous parts of the immune system. Immune perturbations are well-known to impact the aging process, the epigenome, and intermediate metabolism. Cannabinoids also impact metabolism via many pathways. Metabolism directly impacts immune, genetic, and epigenetic processes. Synaptic activity, synaptic pruning, and, thus, the sculpting of neural circuits are based upon metabolic, immune, and epigenomic networks at the synapse, around the synapse, and in the cell body. Many neuropsychiatric disorders including depression, anxiety, schizophrenia, bipolar affective disorder, and autistic spectrum disorder have been linked with cannabis. Therefore, it is important to consider these features and their complex interrelationships in reaching a comprehensive understanding of cannabinoid dependence. Together these findings indicate that cannabinoid perturbations of the immunome and metabolome are important to consider alongside the well-recognized genomic and epigenomic perturbations and it is important to understand their interdependence and interconnectedness in reaching a comprehensive appreciation of the true nature of cannabinoid pathophysiology. For these reasons, a comprehensive appreciation of cannabinoid pathophysiology necessitates a coordinated multiomics investigation of cannabinoid genome-epigenome-transcriptome-metabolome-immunome, chromatin conformation, and 3D nuclear architecture which therefore form the proper mechanistic underpinning for major new and concerning epidemiological findings relating to cannabis exposure.PMID:37854446 | PMC:PMC10579598 | DOI:10.3389/fpsyt.2023.1182536

Front Microbiol. 2023 Oct 3;14:1265425. doi: 10.3389/fmicb.2023.1265425. eCollection 2023.ABSTRACTINTRODUCTION: Prolonged fasting is an intervention approach with potential benefits for individuals with obesity or metabolic disorders. Changes in gut microbiota during and after fasting may also have significant effects on the human body.METHODS: Here we conducted a 7-days medically supervised water-only fasting for 46 obese volunteers and characterized their gut microbiota based on whole-metagenome sequencing of feces at five timepoints.RESULTS: Substantial changes in the gut microbial diversity and composition were observed during fasting, with rapid restoration after fasting. The ecological pattern of the microbiota was also reassembled during fasting, reflecting the reduced metabolic capacity of diet-derived carbohydrates, while other metabolic abilities such as degradation of glycoproteins, amino acids, lipids, and organic acid metabolism, were enhanced. We identified a group of species that responded significantly to fasting, including 130 fasting-resistant (consisting of a variety of members of Bacteroidetes, Proteobacteria, and Fusobacteria) and 140 fasting-sensitive bacteria (mainly consisting of Firmicutes members). Functional comparison of the fasting-responded bacteria untangled the associations of taxon-specific functions (e.g., pentose phosphate pathway modules, glycosaminoglycan degradation, and folate biosynthesis) with fasting. Furthermore, we found that the serum and urine metabolomes of individuals were also substantially changed across the fasting procedure, and particularly, these changes were largely affected by the fasting-responded bacteria in the gut microbiota.DISCUSSION: Overall, our findings delineated the patterns of gut microbiota alterations under prolonged fasting, which will boost future mechanistic and clinical intervention studies.PMID:37854337 | PMC:PMC10579591 | DOI:10.3389/fmicb.2023.1265425

Am J Transl Res. 2023 Sep 15;15(9):5757-5768. eCollection 2023.ABSTRACTOBJECTIVES: The management of sepsis, a potentially lethal overreaction to infection, is limited by the lack of prognostic tools to guide its treatment. Our aim is to identify a novel metabolic biomarker panel for predicting sepsis mortality based on a literature review and liquid chromatography-mass spectrometry (LC-MS)-based metabolomics.METHODS: In the literature, we found metabolomics biomarkers reported to predict sepsis mortality. We determined the classifications, reported frequency, and KEGG pathway enrichment of these markers. Using serum samples from 20 sepsis survivors and 20 non-survivors within 28 days after admission to the intensive care unit (ICU), we performed LC-MS-based metabolomics. Based on the literature review and metabolomics, a prognostic biomarker panel for sepsis was identified and its area under the curve (AUC) values was assessed.RESULTS: Kynurenate, caffeine, and lysoPC 22:4 were selected as a prognostic biomarker panel for sepsis. The panel had an area under the curve (AUC) of 0.885 (95% CI, 0.694-1) evaluated by linear support vector machine (SVM) and 0.849 (0.699-1) by random forest (RF), which was higher than that of the Sequential Organ Failure Assessment (SOFA). A combination of kynurenate, caffeine, and lysoPC 22:4 and SOFA provided the best discriminating performance, with AUCs of 0.961 (0.878-1) for SVM and 0.916 (0.774-1) for RF.CONCLUSIONS: The prognostic biomarker panel consisting of kynurenate, caffeine, and lysoPC 22:4 may aid in the identification of sepsis patients at a high risk of death, leading to personalized therapy in clinical practice that will improve sepsis survival.PMID:37854200 | PMC:PMC10579003

Front Endocrinol (Lausanne). 2023 Oct 3;14:1230457. doi: 10.3389/fendo.2023.1230457. eCollection 2023.ABSTRACTOBJECTIVE: Obesity poses an increased risk for the onset of Nonalcoholic fatty liver disease (NAFLD). The influence of other factors, such as sex in the incidence and severity of this liver disease has not yet been fully elucidated. Thus, we aimed to identify the NAFLD serum metabolic signatures associated with sex in normal, overweight and obese patients and to associate the metabolite fluctuations across the increasing liver steatosis stages.METHODS AND RESULTS: Using nuclear magnetic resonance (NMR) serum samples of 210 NAFLD cases and control individuals diagnosed with liver U/S, our untargeted metabolomics enquiry provided a sex distinct metabolic bouquet. Increased levels of alanine, histidine and tyrosine are associated with severity of NAFLD in both men and women. Moreover, higher serum concentrations of valine, aspartic acid and mannose were positively associated with the progression of NAFLD among the male subjects, while a negative association was observed with the levels of creatine, phosphorylcholine and acetic acid. On the other hand, glucose was positively associated with the progression of NAFLD among the female subjects, while levels of threonine were negatively related. Fluctuations in ketone bodies acetoacetate and acetone were also observed among the female subjects probing a significant reduction in the circulatory levels of the former in NAFLD cases. A complex glycine response to hepatic steatosis of the female subjects deserves further investigation.CONCLUSION: Results of this study aspire to address the paucity of data on sex differences regarding NAFLD pathogenesis. Targeted circulatory metabolome measurements could be used as diagnostic markers for the distinct stages of NAFLD in each sex and eventually aid in the development of novel sex-related therapeutic options.PMID:37854184 | PMC:PMC10579908 | DOI:10.3389/fendo.2023.1230457

Transl Lung Cancer Res. 2023 Sep 28;12(9):1896-1911. doi: 10.21037/tlcr-23-118. Epub 2023 Aug 23.ABSTRACTBACKGROUND: The tumor immune microenvironment influences tumor evolution in non-small cell lung cancer (NSCLC). Yet, the prognostic value of programmed death-ligand 1 (PD-L1) in epidermal growth factor receptor (EGFR)-mutant NSCLC remains controversial. Additionally, prognostic studies in Filipinos with EGFR-mutant NSCLC remain unexplored to this day.METHODS: We prospectively studied the outcomes of EGFR-mutant NSCLC in Filipino cohort, and retrospectively verified the survival trend using The Cancer Genome Atlas (TCGA) cohort. Kaplan-Meier method and generalized linear regression were used to assess survival. Expression and DNA methylation of cluster of differentiation 274 (CD274, gene that codes for PD-L1) were examined from TCGA tumor profiles. Pearson's correlation was used to correlate PD-L1 expression with outcomes associated with occurrence of EGFR mutations, tyrosine kinase inhibitor (TKI) types, and programmed cell death protein 1 (PD-1) expression. Proteome network analysis was used to examine the correlation between drug resistance and PD-L1.RESULTS: PD-L1 positivity was associated with significantly longer progression-free survival (PFS; P=0.0096) but had a significantly contrasting influence in the overall survival (OS; P=0.0011). PD-L1 positivity (in both protein and RNA) was associated with longer median OS (mOS) in exon21 L858R, whereas, negativity was associated with longer mOS in exon19 deletion (exon19del). Stratification (high, low, negative) of PD-L1 expression lacked significant prognostic value (all P>0.05). PD-L1/CD274 expression (P<0.05) and DNA methylation (P<0.001) vary significantly among NSCLC subtypes and in different disease stages. Erlotinib treatment produced the longest median progression-free survival (mPFS; 874 days) relative to other EGFR-TKIs (137-311 days). PD-L1 lacked a significant correlation with EGFR-TKIs. Consistent with the immune-regulation activities of PD-1, higher expression leads to relatively shorter mOS. PD-1 correlated positively with PD-L1 expression and occurrence of exon21 L858R.CONCLUSIONS: PD-L1 differentially influenced the outcomes of Filipinos with EGFR-mutant NSCLC. NSCLC subtypes, disease stage, and PD-1 expression may impact the collective outcomes associated with PD-L1 and EGFR-sensitizing mutations.PMID:37854154 | PMC:PMC10579834 | DOI:10.21037/tlcr-23-118

Drug Des Devel Ther. 2023 Oct 13;17:3085-3101. doi: 10.2147/DDDT.S413897. eCollection 2023.ABSTRACTPURPOSE: Arecoline is one of the main toxic components of arecoline to cause oral mucosal lesions or canceration, which seriously affects the survival and life quality of patients. This study analyzed the mechanism of Jiawei Danxuan Koukang (JDK) in alleviating arecoline induced oral mucosal lesions, to provide new insights for the treatment of oral submucosal fibrosis (OSF) or cancerosis.METHODS: Metabolomics was applied to analyze the composition of JDK and serum metabolites. The active ingredients of JDK were analyzed by the combined ultra-high performance liquid chromatography and mass spectrometry. The target network of JDK, metabolites and OSF was analyzed by network pharmacology, and molecular docking. Oral mucosal lesions and fibrosis were analyzed by HE and Masson staining. Cell differentiation, proliferation and apoptosis were detected. The expressions of α-SMA, Collagen I, Vimentin, Snail, E-cadherin, AR and NOTCH1 were detected by Western blot.RESULTS: Arecoline induced the gradual atrophy and thinning of rat oral mucosal, collagen accumulation, the increase expressions of fibrosis-related proteins and Th17/Treg ratio. JDK inhibited arecoline-induced oral mucosal lesions and inflammatory infiltration. Arecoline induced changes of serum metabolites in Aminoacyl-tRNA biosynthesis, Alanine, aspartate and glutamate metabolism and Arginine biosynthesis pathways, which were reversed by M-JDK. Quercetin and AR were the active ingredients and key targets of JDK, metabolites and OSF interaction. Arecoline promoted the expression of AR protein, and the proliferation of oral fibroblasts. Quercetin inhibited the effect of arecoline on oral fibroblasts, but was reversed by AR overexpression. Arecoline induced NOTCH1 expression in CAL27 and SCC-25 cells, and promoted cell proliferation, but was reversed by M-JDK or quercetin.CONCLUSION: JDK improved the arecoline-induced OSF and serum metabolite functional pathway. Quercetin targeted AR protein to improve arecoline-induced OSF. JDK and quercetin inhibited arecoline-induced NOTCH1 protein expression in CAL27 and SCC-25 cells to play an anti-oral cancer role.PMID:37854130 | PMC:PMC10581390 | DOI:10.2147/DDDT.S413897

Front Aging Neurosci. 2023 Oct 3;15:1268751. doi: 10.3389/fnagi.2023.1268751. eCollection 2023.ABSTRACTBACKGROUND: Parkinson's disease (PD) is characterized by motor disorders and the composition of Lewy bodies (LBs) in the substantia nigra. Due to the lack of a definitive biomarker, the current treatments do not modify the progression of PD. Recently, researchers revealed lipid dysregulation and some potential volatile biomarkers of PD related to a unique odor from PD patients by metabolomics of sebum, which is supposed to cause a potential change for skin microflora. In this study, we identified the 4 Malassezia species in PD patients and compared them with healthy controls.METHODS: We collected 95 sebum samples (47 PDs and 48 Controls) by cotton swabs and extracted the DNA. The identification of Malassezia species was performed by Nested PCR. Specific primers for each species were used to amplify corresponding yeasts in each sample.RESULTS: M. restricta and M. globosa are the most common species for both groups. The prevalence of M. slooffiae and M. sympodialis were significantly higher in the PD group compared with controls (63.8% vs. 29.1 and 74.5% vs. 54.2% respectively), the binary logistic regression model further indicated that M. slooffiae (OR = 9.358, p < 0.001) was associated with PD. Moreover, the diversity of Malassezia species was significantly greater (3.5 vs. 2.9 species per individual, p = 0.002) in the PD group.CONCLUSION: Based on our results, we preliminarily observed a change in Malassezia species incidence and diversity on the skin of PD patients, which could be associated with lipid dysregulation; meanwhile, it might also be a noninvasive biomarker for PD.PMID:37854034 | PMC:PMC10580282 | DOI:10.3389/fnagi.2023.1268751

Food Funct. 2023 Oct 18. doi: 10.1039/d3fo03675h. Online ahead of print.ABSTRACTThe protective effects of yak milk (YM) against chronic alcoholic liver injury in rats were investigated in this study. Histologic and biochemical analyses demonstrated that YM consumption ameliorates alcohol-induced liver injury by increasing the liver antioxidant enzyme activity and reducing inflammation. Furthermore, microbiome and metabolomic analyses exploring YM's impact on gut microbiota and metabolism found that YM administration regulates gut microbiota composition. Specifically, there was a decrease in the relative abundance of Helicobacter, Streptococcus, Peptococcus and Tyzzerella, along with an increase in Turisibacter and Intestinimonas. Moreover, Pearson analysis indicated positive correlations between Peptococcus and Tyzzerella with ALT and AST levels, while showing a negative correlation with ADH levels. Furthermore, differential metabolite analysis of fecal samples from the YM group identified significant increases in the taurine (2-Aminoethanesulfonic acid), hypotaurine (2-Aminoethanesulfonic Acid) and isethionic acid levels. Finally, KEGG topology analysis highlighted taurine and hypotaurine metabolism as the primary pathways influenced by YM intervention. Therefore, these findings collectively suggest that YM may protect alcohol-exposed rats against liver injury by modulating oxidative stress, inflammatory response, gut microbiota disorder, and metabolic regulation.PMID:37853817 | DOI:10.1039/d3fo03675h

Biochim Biophys Acta Bioenerg. 2023 Oct 16:149018. doi: 10.1016/j.bbabio.2023.149018. Online ahead of print.ABSTRACTLow Zn availability in soils is a problem in many parts of the world, with tremendous consequences for food and feed production because Zn deficiency affects the yield and quality of plants. In this study we investigated the consequences of Zn-limitation in hydroponically cultivated soybean (Glycine max L.) plants. Parameters of photosynthesis biophysics were determined by spatially and spectrally resolved Kautsky and OJIP fluorescence kinetics and oxygen production at two time points (V4 stage, after five weeks, and pod development stage, R5-R6, after 8-10 weeks). Lower NPQ at 730 nm and lower quantum yield of electron transport flux until PSI acceptors were observed, indicating an inhibition of the PSI acceptor side. Metalloproteomics showed that down-regulation of Cu/Zn-superoxide dismutase (CuZnSOD) and Zn‑carbonic anhydrase (CA) were primary consequences of Zn-limitation. This explained the effects on photosynthesis in terms of decreased use of excitons, which consequently led to oxidative stress. Indeed, untargeted metabolomics revealed an accumulation of lipid oxidation products in the Zn-deficient leaves. Further response to Zn deficiency included up-regulation of gene expression of cell wall metabolism, response to (a)biotic stressors and antioxidant activity, which correlated with accumulation of antioxidants, Vit B6, (iso)flavonoids and phytoalexins.PMID:37852568 | DOI:10.1016/j.bbabio.2023.149018

J Ethnopharmacol. 2023 Oct 16:117316. doi: 10.1016/j.jep.2023.117316. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Currently, the clinical treatment is limited and difficult to achieve satisfactory results for ulcerative colitis (UC). The role of traditional Chinese medicine (TCM) in the treatment of UC is very complex. Kuijie decoction (KJD) as a classic TCM, is widely used in the clinical treatment of UC, but the mechanism of its action is still unclear.AIM OF THE STUDY: This study is to investigate the protective effects of KJD on UC and the underlying mechanisms.MATERIALS AND METHODS: The experimental model of UC was induced by DSS, and KJD was introduced into the model at the same time. Clinical symptoms, including the body weight, colon length and colon histopathological, were used to measure the severity of colitis. The expression of inflammatory cytokines and tight junction proteins was quantified. The effect of KJD on intestinal flora and intestinal metabolism was determined by 16S rRNA and untargeted metabolomics analysis, respectively. The proportion of Th17 cells and Tregs in the spleen was examined by flow cytometry.RESULTS: Mice treated with KJD showed significantly alleviated clinical symptoms and histological damage, such as more body weight gain, lower disease activity index (DAI) score, and longer colon length. The administration of KJD also led to the down-regulation of inflammatory mediators, upregulation of the expression of ZO-1, occludin and decreased claudin-2, as well as altered microbiota composition against DSS challenges (especially an increase of Lachnospiraceae). KJD enhanced the percentage of Treg cells but decreased the proportion of Th17 cells to maintain intestinal homeostasis by improving gut microbiota metabolism.CONCLUSIONS: In summary, KJD maintained intestinal epithelial homeostasis by regulating epithelial barrier function, intestinal flora, and restoring Th17/Treg balance. KJD has the potential to be a Chinese medicine treatment for UC.PMID:37852335 | DOI:10.1016/j.jep.2023.117316

Cell Rep Med. 2023 Oct 17;4(10):101234. doi: 10.1016/j.xcrm.2023.101234.ABSTRACTThe molecular dynamics of pancreatic ductal adenocarcinoma (PDAC) under chemotherapy remain incompletely understood. The widespread use of neoadjuvant chemotherapy (NAC) provides a unique opportunity to investigate PDAC samples post-chemotherapy. Leveraging a cohort from Fudan University Shanghai Cancer Center, encompassing PDAC samples with and without exposure to neoadjuvant albumin-bound paclitaxel and gemcitabine (AG), we have compiled data from single-cell and spatial transcriptomes, proteomes, bulk transcriptomes, and metabolomes, deepening our comprehension of the molecular changes in PDACs in response to chemotherapy. Metabolic flux analysis reveals that NAC induces a reprogramming of PDAC metabolic patterns and enhances immunogenicity. Notably, NAC leads to the downregulation of glycolysis and the upregulation of CD36. Tissue microarray analysis demonstrates that high CD36 expression is linked to poorer survival in patients receiving postoperative AG. Targeting CD36 synergistically improves the PDAC response to AG both in vitro and in vivo, including patient-derived preclinical models.PMID:37852179 | DOI:10.1016/j.xcrm.2023.101234

J Hazard Mater. 2023 Oct 12;462:132770. doi: 10.1016/j.jhazmat.2023.132770. Online ahead of print.ABSTRACTNanomaterial application in agriculture offers novel solutions for soil arsenic (As) pollution control, yet safety along the food chain is of concern. We comprehensively assessed CeO2 nanoparticles (NPs) foliar application effects on As uptake by pakchoi and their presence in the pakchoi-snail food chain. CeO2 NPs reduced As transfer from pakchoi roots to shoots by 37.9%, lowered As in snail foot by 39%, and halved human As exposure risk. The NPs alleviated pakchoi shoot As toxicity by regulating antioxidants, enhancing water use efficiency, and photosynthesis. CeO2 +As treatment raised GSH/GSSG ratios by 38.92%- 167.54%, leading to an increased AsIII/AsV ratio and inorganic As detoxification compared to As alone. Metabolomics revealed CeO2's rapid As response via phosphatidylinositol signaling. The enzyme-like activity of CeO2 NPs may drive these effects. While CeO2 foliar application accumulated Ce on pakchoi leaves, > 99% of Ce was excreted following snail consumption. Ce transfer from pakchoi leaves to snail foot was minimal (trophic transfer factor ∼0.00007) due to limited bioavailability. The target hazard quotient of Ce in pakchoi shoot (1.21 ± 0.18) and snails (0.0016 ± 0.0004) indicated low exposure risk, suggesting a 'risk filter' effect for CeO2. Our results contribute to the safe and sustainable application of CeO2 NPs in the future implication.PMID:37852136 | DOI:10.1016/j.jhazmat.2023.132770

Neoplasia. 2023 Oct 16;45:100943. doi: 10.1016/j.neo.2023.100943. Online ahead of print.ABSTRACTThe homeostasis of the gut microbiota and circadian rhythm is critical to host health, and both are inextricably intertwined with lung cancer. Although time-restricted feeding (TRF) can maintain circadian synchronization and improve metabolic disorders, the effects of TRF on the fecal microbiome, metabolome and their diurnal oscillations in lung cancer have not been discussed. We performed 16S rRNA sequencing and untargeted metabonomic sequencing of the feces prepared from models of tumor-bearing BALB/c nude mice and urethane-induced lung cancer. We demonstrated for the first time that TRF significantly delayed the growth of lung tumors. Moreover, TRF altered the abundances of the fecal microbiome, metabolome and circadian clocks, as well as their rhythmicity, in lung cancer models of tumor-bearing BALB/c nude mice and/or urethane-induced lung cancer C57BL/6J mice. The results of fecal microbiota transplantation proved that the antitumor effects of TRF occur by regulating the fecal microbiota. Notably, Lactobacillus and Bacillus were increased upon TRF and were correlated with most differential metabolites. Pathway enrichment analysis of metabolites revealed that TRF mainly affected immune and inflammatory processes, which might further explain how TRF exerted its anticancer benefits. These findings underscore the possibility that the fecal microbiome/metabolome regulates lung cancer following a TRF paradigm.PMID:37852131 | DOI:10.1016/j.neo.2023.100943

Biomed Pharmacother. 2023 Oct 16;168:115626. doi: 10.1016/j.biopha.2023.115626. Online ahead of print.ABSTRACTHealing of wounds is the most deteriorating diabetic experience. Felty germander (Teucrium polium) possesses antioxidant, anti-inflammatory and antimicrobial activities that could accelerate wound healing. Further, nanohydrogels help quicken healing and are ideal biomaterials for drug delivery. In the current study, the chemical profiling, and standardization of T. polium methanolic extract by LC-ESI/TOF/MS/MS and quantitative HPLC-DAD analyses were achieved. The wound healing enhancement in diabetic rats by T. polium nanopreparation (TP-NP) as chitosan nanogel (CS-NG) and investigating the potential mechanisms were investigated. The prepared hydrogel-based TP-NP were characterized with respect to particle size, zeta potential, pH, viscosity, and release of major components. LC-ESI/TOF/MS/MS metabolomic profiling of T. polium revealed the richness of the plant with phenolic compounds, particularly flavonoids. In addition, several terpenoids were detected. Kaempferol content of T. polium was estimated to be 7.85 ± 0.022 mg/ g of dry extract. The wound healing activity of TP-NP was explored in streptozotocin-induced diabetic rats. Diabetic animals were subjected to surgical wounding (1 cm diameter). Then they were divided in 5 groups (10 each). These included Group 1 (untreated control rats), Group 2 received the vehicle of CS-NG; Group 3 (0.5 g of TP prepared in hydrogel), Group 4 (0.5 g of TP-NP), Group 5 represented a positive control treated with 0.5 g of a commercial product. All treatments were applied topically for 21 days. Application of TP-NP on skin wounds of diabetic animals accelerated the healing process as evidenced by epithelium regeneration, formation of granulation tissue followed by epidermal proliferation, along with keratinization as verified by H&E. This was confirmed through enhanced collagen synthesis, as shown by raised hydroxyproline content and Col1A1 gene expression. Moreover, TP-NP significantly alleviated wound oxidative burst and diminished the expressions of inflammatory biomarkers. Meanwhile, TP-NP could enhance the expressions of transforming growth factor beta1 (TGF-β1), in addition to the angiogenic markers; vascular endothelia growth factor A (VEGFA) and platelet-derived growth factor receptor alpha (PDGFRα). Collectively, chitosan nanogel of T. polium accelerates wound healing in diabetic rats, which could be explained - at least partly - through alleviating oxidative stress and inflammation coupled with pro-angiogenic capabilities.PMID:37852098 | DOI:10.1016/j.biopha.2023.115626

Plant Physiol Biochem. 2023 Oct 16;204:108069. doi: 10.1016/j.plaphy.2023.108069. Online ahead of print.ABSTRACTA possible mechanism for the improved availability of zinc (Zn) in soil by combining nitrogen (N) with Zn supply was investigated based on the root exudates of winter wheat. N, Zn supply as well as their combination significantly regulated nine root exudates in winter wheat; in which, the secretion of cis-aconitic acid involving in the TCA cycle, C5-branched dibasic acid metabolism, glyoxylate and dicarboxylate metabolism and 2-oxocarboxylic acid metabolism was upregulated by N, Zn supply as well as their combination. N-Zn combination induced the activities of citrate synthase and cis-aconitase in roots and shoots of winter wheat thus to increase the concentrations of citric and aconitic acid; the decrease of isocitric acid concentrations in shoots indicated the inhibited conversion of aconitic acid to isocitric acid by N-Zn combination. It revealed a possible reason for the enhanced secretion of cis-aconitic acid by N-Zn combination. Exogenous addition of 10 μ plant-1 cis-aconitate significantly increased available Zn concentrations in soil and Zn concentrations in winter wheat under N-Zn combination. Thus, the N-Zn combination regulated the metabolism of cis-aconitic acid in winter wheat, thus enhancing the secretion of cis-aconitic acid to increase the bioavailability of Zn in soil.PMID:37852066 | DOI:10.1016/j.plaphy.2023.108069

BMC Complement Med Ther. 2023 Oct 18;23(1):367. doi: 10.1186/s12906-023-04208-0.ABSTRACTINTRODUCTION: Infants who are born from mothers with HIV (infants who are HIV exposed but uninfected; iHEU) are at higher risk of morbidity and display multiple immune alterations compared to infants who are HIV-unexposed (iHU). Easily implementable strategies to improve immunity of iHEU, and possibly subsequent clinical health outcomes, are needed. iHEU have altered gut microbiome composition and bifidobacterial depletion, and relative abundance of Bifidobacterium infantis has been associated with immune ontogeny, including humoral and cellular vaccine responses. Therefore, we will assess microbiological and immunological phenotypes and clinical outcomes in a randomized, double-blinded trial of B. infantis Rosell®-33 versus placebo given during the first month of life in South African iHEU.METHODS: This is a parallel, randomised, controlled trial. Two-hundred breastfed iHEU will be enrolled from the Khayelitsha Site B Midwife Obstetric Unit in Cape Town, South Africa and 1:1 randomised to receive 8 × 109 CFU B. infantis Rosell®-33 daily or placebo for the first 4 weeks of life, starting on day 1-3 of life. Infants will be followed over 36 weeks with extensive collection of meta-data and samples. Primary outcomes include gut microbiome composition and diversity, intestinal inflammation and microbial translocation and cellular vaccine responses. Additional outcomes include biological (e.g. gut metabolome and T cell phenotypes) and clinical (e.g. growth and morbidity) outcome measures.DISCUSSION: The results of this trial will provide evidence whether B. infantis supplementation during early life could improve health outcomes for iHEU.ETHICS AND DISSEMINATION: Approval for this study has been obtained from the ethics committees at the University of Cape Town (HREC Ref 697/2022) and Seattle Children's Research Institute (STUDY00003679).TRIAL REGISTRATION: Pan African Clinical Trials Registry Identifier: PACTR202301748714019.TRIALS: gov: NCT05923333.PROTOCOL VERSION: Version 1.8, dated 18 July 2023.PMID:37853370 | DOI:10.1186/s12906-023-04208-0

Metabolomics. 2023 Oct 18;19(11):87. doi: 10.1007/s11306-023-02048-0.ABSTRACTINTRODUCTION: Since the beginning of the SARS-CoV-2 pandemic in December 2019 multiple metabolomics studies have proposed predictive biomarkers of infection severity and outcome. Whilst some trends have emerged, the findings remain intangible and uninformative when it comes to new patients.OBJECTIVES: In this study, we accurately quantitate a subset of compounds in patient serum that were found predictive of severity and outcome.METHODS: A targeted LC-MS method was used in 46 control and 95 acute COVID-19 patient samples to quantitate the selected metabolites. These compounds included tryptophan and its degradation products kynurenine and kynurenic acid (reflective of immune response), butyrylcarnitine and its isomer (reflective of energy metabolism) and finally 3',4'-didehydro-3'-deoxycytidine, a deoxycytidine analogue, (reflective of host viral defence response). We subsequently examine changes in those markers by disease severity and outcome relative to those of control patients' levels.RESULTS & CONCLUSION: Finally, we demonstrate the added value of the kynurenic acid/tryptophan ratio for severity and outcome prediction and highlight the viral detection potential of ddhC.PMID:37853293 | DOI:10.1007/s11306-023-02048-0