PubMed

J Nematol. 2023 Aug 29;55(1):20230030. doi: 10.2478/jofnem-2023-0030. eCollection 2023 Feb.ABSTRACTWe previously reported soybean fields double-cropped with winter wheat having reduced soybean cyst nematode (SCN) (Heterodera glycines) counts compared to fallow. A follow-up metagenomics study identified several fungal and bacterial taxa enriched in wheat fields, and some were reported to parasitize SCN. Knowing that phytocompounds with potential nematicidal activity are released via wheat roots and stubble, we implemented a dichloromethane-based extraction method and a gas chromatography-mass spectrometry (GCMS) system to investigate soil chemical profiles of samples collected from these fields and review the potential nematicidal activity of compounds with higher concentration in double cropping fields. 51 compounds were detected during the GCMS analysis, eight with unknown identification. Several compounds, including multiple fatty acids, had larger relative peak areas when double-cropped, compared to fallow samples. This study, along with our previously published one, provided a better understanding of the mechanisms that govern the effect of wheat on SCN populations. Rather than driven by a single mechanism, the suppression of SCN in soybean fields double-cropped with winter wheat was potentially linked to enriched microbial communities, increased populations of beneficial organisms, and higher concentrations of chemicals with potential nematicidal activity. To our knowledge, this is the first study using GCMS to characterize soil chemical profiles in soybean fields double-cropped with winter wheat regarding the suppression of SCN populations.PMID:37818528 | PMC:PMC10561077 | DOI:10.2478/jofnem-2023-0030

J Endocr Soc. 2023 Sep 21;7(11):bvad122. doi: 10.1210/jendso/bvad122. eCollection 2023 Oct 9.ABSTRACTCONTEXT: Hyperglucagonemia may develop in type 2 diabetes due to obesity-prone hepatic steatosis (glucagon resistance). Markers of glucagon resistance (including the glucagon-alanine index) improve following diet-induced weight loss, but the partial contribution of lowering hepatic steatosis vs body weight is unknown.OBJECTIVE: This work aimed to investigate the dependency of body weight loss following a reduction in hepatic steatosis on markers of glucagon resistance in type 2 diabetes.METHODS: A post hoc analysis was conducted from 2 previously published randomized controlled trials. We investigated the effect of weight maintenance (study 1: isocaloric feeding) or weight loss (study 2: hypocaloric feeding), both of which induced reductions in hepatic steatosis, on markers of glucagon sensitivity, including the glucagon-alanine index measured using a validated enzyme-linked immunosorbent assay and metabolomics in 94 individuals (n = 28 in study 1; n = 66 in study 2). Individuals with overweight or obesity with type 2 diabetes were randomly assigned to a 6-week conventional diabetes (CD) or carbohydrate-reduced high-protein (CRHP) diet within both isocaloric and hypocaloric feeding-interventions.RESULTS: By design, weight loss was greater after hypocaloric compared to isocaloric feeding, but both diets caused similar reductions in hepatic steatosis, allowing us to investigate the effect of reducing hepatic steatosis with or without a clinically relevant weight loss on markers of glucagon resistance. The glucagon-alanine index improved following hypocaloric, but not isocaloric, feeding, independently of macronutrient composition.CONCLUSION: Improvements in glucagon resistance may depend on body weight loss in patients with type 2 diabetes.PMID:37818402 | PMC:PMC10561012 | DOI:10.1210/jendso/bvad122

Front Immunol. 2023 Sep 25;14:1230772. doi: 10.3389/fimmu.2023.1230772. eCollection 2023.ABSTRACTMacrophages play a critical role in the inflammatory response and tumor development. Macrophages are primarily divided into pro-inflammatory M1-like and anti-inflammatory M2-like macrophages based on their activation status and functions. In vitro macrophage models could be derived from mouse bone marrow cells stimulated with two types of differentiation factors: GM-CSF (GM-BMDMs) and M-CSF (M-BMDMs), to represent M1- and M2-like macrophages, respectively. Since macrophage differentiation requires coordinated metabolic reprogramming and transcriptional rewiring in order to fulfill their distinct roles, we combined both transcriptome and metabolome analysis, coupled with experimental validation, to gain insight into the metabolic status of GM- and M-BMDMs. The data revealed higher levels of the tricarboxylic acid cycle (TCA cycle), oxidative phosphorylation (OXPHOS), fatty acid oxidation (FAO), and urea and ornithine production from arginine in GM-BMDMs, and a preference for glycolysis, fatty acid storage, bile acid metabolism, and citrulline and nitric oxide (NO) production from arginine in M-BMDMs. Correlation analysis with the proteomic data showed high consistency in the mRNA and protein levels of metabolic genes. Similar results were also obtained when compared to RNA-seq data of human monocyte derived macrophages from the GEO database. Furthermore, canonical macrophage functions such as inflammatory response and phagocytosis were tightly associated with the representative metabolic pathways. In the current study, we identified the core metabolites, metabolic genes, and functional terms of the two distinct mouse macrophage populations. We also distinguished the metabolic influences of the differentiation factors GM-CSF and M-CSF, and wish to provide valuable information for in vitro macrophage studies.PMID:37818352 | PMC:PMC10560851 | DOI:10.3389/fimmu.2023.1230772

Front Plant Sci. 2023 Sep 25;14:1271303. doi: 10.3389/fpls.2023.1271303. eCollection 2023.ABSTRACTINTRODUCTION: Leptochloa chinensis is an annual weed in paddy fields, which can engage in competition with rice, leading to a severe yield reduction. However, theunderlying mechanism governing this interaction remain unknown.METHODS: In this study, we investigated the mutual inhibition between rice and the weed undermono-culture and co-culture conditions. We found that the root exudates of both species played essential roles in mediating the mutual inhibition. Further metabolomic analysis identified a significant number of differential metabolites. These metabolites were predominantly enriched in the phenylpropanoid and flavonoid biosynthesis pathways in weed and rice. Transcriptomic analysis revealed that the differentially expressed genes responding to the interaction were also enriched in these pathways.RESULTS: Phenylpropanoid and flavonoid biosynthesis pathways are associated with allelopathy, indicating their pivotal role in the response of rice-weed mutual inhibition.DISCUSSION: Our findings shed light on the conserved molecular responses of rice and L. chinensis during theirinteraction, provide evidence to dissect the mechanisms underlying the allelopathic interaction and offer potential strategies for weed management in rice paddies.PMID:37818319 | PMC:PMC10560989 | DOI:10.3389/fpls.2023.1271303

Front Plant Sci. 2023 Sep 25;14:1281385. doi: 10.3389/fpls.2023.1281385. eCollection 2023.NO ABSTRACTPMID:37818317 | PMC:PMC10561325 | DOI:10.3389/fpls.2023.1281385

Front Plant Sci. 2023 Sep 25;14:1267340. doi: 10.3389/fpls.2023.1267340. eCollection 2023.ABSTRACTINTRODUCTION: Tomato is a high economic value crop worldwide with recognized nutritional properties and diverse postharvest potential. Nowadays, there is an emerging awareness about the exploitation and utilization of underutilized traditional germplasm in modern breeding programs. In this context, the existing diversity among Greek accessions in terms of their postharvest life and nutritional value remains largely unexplored.METHODS: Herein, a detailed evaluation of 130 tomato Greek accessions for postharvest and nutritional characteristics was performed, using metabolomics and transcriptomics, leading to the selection of accessions with these interesting traits.RESULTS: The results showed remarkable differences among tomato Greek accessions for overall ripening parameters (color, firmness) and weight loss. On the basis of their postharvest performance, a balance between short shelf life (SSL) and long shelf life (LSL) accessions was revealed. Metabolome analysis performed on 14 selected accessions with contrasting shelf-life potential identified a total of 206 phytonutrients and volatile compounds. In turn, transcriptome analysis in fruits from the best SSL and the best LSL accessions revealed remarkable differences in the expression profiles of transcripts involved in key metabolic pathways related to fruit quality and postharvest potential.DISCUSSION: The pathways towards cell wall synthesis, polyamine synthesis, ABA catabolism, and steroidal alkaloids synthesis were mostly induced in the LSL accession, whereas those related to ethylene biosynthesis, cell wall degradation, isoprenoids, phenylpropanoids, ascorbic acid and aroma (TomloxC) were stimulated in the SSL accession. Overall, these data would provide valuable insights into the molecular mechanism towards enhancing shelf-life and improving flavor and aroma of modern tomato cultivars.PMID:37818313 | PMC:PMC10560995 | DOI:10.3389/fpls.2023.1267340

Front Pharmacol. 2023 Sep 25;14:1221046. doi: 10.3389/fphar.2023.1221046. eCollection 2023.ABSTRACTObjective: Yinchen Sini decoction (YCSND), a traditional Chinese medicine (TCM) formula, plays a crucial role in the treatment of liver disease. However, the bioactive constituents and pharmacological mechanisms of action remain unclear. The present study aimed to reveal the molecular mechanism of YCSND in the treatment of acute liver injury (ALI) using integrated network analysis and metabolomics. Methods: Ultra-high-performance liquid chromatography coupled with Q-Exactive focus mass spectrum (UHPLC-QE-MS) was utilized to identify metabolites in YCSND, and high-performance liquid chromatography (HPLC) was applied to evaluate the quality of four botanical drugs in YCSND. Cell damage and ALI models in mice were established using CCl4. 1H-NMR metabolomics approach, along with histopathological observation using hematoxylin and eosin (H&E), biochemical measurements, and reverse transcription quantitative real-time PCR (RT-qPCR), was applied to evaluate the effect of YCSND on CCl4- induced ALI. Network analysis was conducted to predict the potential targets of YCSND in ALI. Result: Our results showed that 89 metabolites in YCSND were identified using UHPLC-QE-MS. YCSND protected against ALI by reducing the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and malondialdehyde (MDA) contents and increasing those of superoxide dismutase (SOD), and glutathione (GSH) both in vivo and in vitro. The 1H-NMRmetabolic pattern revealed that YCSND reversed CCl4-induced metabolic abnormalities in the liver. Additionally, the Kyoto Encyclopedia of Genes and Genome (KEGG) pathway enrichment analysis identified five pathways related to liver injury, including the PI3K-AKT, MAPK, HIF-1, apoptosis, and TNF signaling pathways. Moreover, RT-qPCR showed YCSND regulated the inflammatory response (Tlr4, Il6, Tnfα, Nfκb1, Ptgs2, and Mmp9) and apoptosis (Bcl2, Caspase3, Bax, and Mapk3), and inhibited PI3K-AKT signaling pathway (Pi3k and Akt1). Combined network analysis and metabolomics showed a link between the key targets (Tlr4, Ptgs2, and Mmp9) and vital metabolites (choline, xanthine, lactate, and 3-hydroxybutyric acid) of YCSND in ALI. Conclusion: Overall, the results contribute to the understanding of the therapeutic effects of YCSND on ALI, and indicate that the integrated network analysis and metabolomics could be a powerful strategy to reveal the pharmacological effects of TCM.PMID:37818184 | PMC:PMC10561237 | DOI:10.3389/fphar.2023.1221046

Front Cell Dev Biol. 2023 Sep 25;11:1239154. doi: 10.3389/fcell.2023.1239154. eCollection 2023.ABSTRACTIntroduction: Oocyte quality and fertility decline with advanced maternal age. During maturation within the ovarian follicle, the oocyte relies on the associated somatic cells, specifically cumulus and granulosa cells, to acquire essential components for developmental capacity. Methods: A nontargeted metabolomics approach was used to investigate the effects of mare age on different cell types within the dominant, follicular-phase follicle at three time points during maturation. Metabolomic analyses from single oocytes and associated cumulus and granulosa cells allowed correlations of metabolite abundance among cell types. Results and Discussion: Overall, many of the age-related changes in metabolite abundance point to Impaired mitochondrial metabolic function and oxidative stress in oocytes and follicular cells. Supporting findings include a higher abundance of glutamic acid and triglycerides and lower abundance of ceramides in oocytes and somatic follicular cells from old than young mares. Lower abundance of alanine in all follicular cell types from old mares, suggests limited anaerobic energy metabolism. The results also indicate impaired transfer of carbohydrate and free fatty acid substrates from cumulus cells to the oocytes of old mares, potentially related to disruption of transzonal projections between the cell types. The identification of age-associated alterations in the abundance of specific metabolites and their correlations among cells contribute to our understanding of follicular dysfunction with maternal aging.PMID:37818125 | PMC:PMC10561129 | DOI:10.3389/fcell.2023.1239154

Front Mol Biosci. 2023 Sep 25;10:1206074. doi: 10.3389/fmolb.2023.1206074. eCollection 2023.ABSTRACTChagas disease (ChD), caused by Trypanosoma cruzi, is endemic in American countries and an estimated 8 million people worldwide are chronically infected. Currently, only two drugs are available for therapeutic use against T. cruzi and their use is controversial due to several disadvantages associated with side effects and low compliance with treatment. Therefore, there is a need to search for new tripanocidal agents. Natural products have been considered a potential innovative source of effective and selective agents for drug development to treat T. cruzi infection. Recently, our research group showed that hexanic extract from Clethra fimbriata (CFHEX) exhibits anti-parasitic activity against all stages of T. cruzi parasite, being apoptosis the main cell death mechanism in both epimastigotes and trypomastigotes stages. With the aim of deepening the understanding of the mechanisms of death induced by CFHEX, the metabolic alterations elicited after treatment using a multiplatform metabolomics analysis (RP/HILIC-LC-QTOF-MS and GC-QTOF-MS) were performed. A total of 154 altered compounds were found significant in the treated parasites corresponding to amino acids (Arginine, threonine, cysteine, methionine, glycine, valine, proline, isoleucine, alanine, leucine, glutamic acid, and serine), fatty acids (stearic acid), glycerophospholipids (phosphatidylcholine, phosphatidylethanolamine and phosphatidylserine), sulfur compounds (trypanothione) and carboxylic acids (pyruvate and phosphoenolpyruvate). The most affected metabolic pathways were mainly related to energy metabolism, which was found to be decrease during the evaluated treatment time. Further, exogenous compounds of the triterpene type (betulinic, ursolic and pomolic acid) previously described in C. fimbriata were found inside the treated parasites. Our findings suggest that triterpene-type compounds may contribute to the activity of CFHEX by altering essential processes in the parasite.PMID:37818099 | PMC:PMC10561390 | DOI:10.3389/fmolb.2023.1206074

iScience. 2023 Sep 15;26(10):107914. doi: 10.1016/j.isci.2023.107914. eCollection 2023 Oct 20.ABSTRACTEpidemiological data and research highlight increased neuropathy and chronic pain prevalence among females, spanning metabolic and normometabolic contexts, including murine models. Prior findings demonstrated diverse immune and neuroimmune responses between genders in neuropathic pain (NeP), alongside distinct protein expression in sciatic nerves. This study unveils adipose tissue's (AT) role in sex-specific NeP responses after peripheral nerve injury. Metabolic assessments, metabolomics, energy expenditure evaluations, AT proteomic analyses, and adipokine mobilization depict distinct AT reactions to nerve damage. Females exhibit altered lipolysis, fatty acid oxidation, heightened energy expenditure, and augmented steroids secretion affecting glucose and insulin metabolism. Conversely, male neuropathy prompts glycolysis, reduced energy expenditure, and lowered unsaturated fatty acid levels. Males' AT promotes regenerative molecules, oxidative stress defense, and stimulates peroxisome proliferator-activated receptors (PPAR-γ) and adiponectin. This study underscores AT's pivotal role in regulating gender-specific inflammatory and metabolic responses to nerve injuries, shedding light on female NeP susceptibility determinants.PMID:37817933 | PMC:PMC10561049 | DOI:10.1016/j.isci.2023.107914

Front Microbiol. 2023 Sep 25;14:1269123. doi: 10.3389/fmicb.2023.1269123. eCollection 2023.ABSTRACTBACKGROUND: High-producing dairy cows face varying degrees of metabolic stress and challenges during the late perinatal period, resulting in ruminal bacteria abundance and their fermentative ability occurring as a series of changes. However, the dynamic changes are still not clear.AIMS/METHODS: Ten healthy, high-producing Holstein dairy cows with similar body conditions and the same parity were selected, and ruminal fluid from the dairy cows at postpartum 0, 7, 14, and 21 d was collected before morning feeding. 16S rRNA high-throughput sequencing, GC-MS/MS targeted metabolomics, and UPLC-MS/MS untargeted metabolomics were applied in the study to investigate the dynamic changes within 21 d postpartum.RESULTS: The results displayed that the structures of ruminal bacteria were significantly altered from 0 to 7 d postpartum (R = 0.486, P = 0.002), reflecting the significantly declining abundances of Euryarchaeota and Chloroflexi phyla and Christensenellaceae, Methanobrevibacter, and Flexilinea genera (P < 0.05) and the obviously ascending abundances of Ruminococcaceae, Moryella, Pseudobutyrivibrio, and Prevotellaceae genera at 7 d postpartum (P < 0.05). The structures of ruminal bacteria also varied significantly from 7 to 14 d postpartum (R = 0.125, P = 0.022), reflecting the reducing abundances of Christensenellaceae, Ruminococcaceae, and Moryella genera (P < 0.05), and the elevating abundances of Sharpea and Olsenella genera at 14 d postpartum (P < 0.05). The metabolic profiles of ruminal SCFAs were obviously varied from 0 to 7 d postpartum, resulting in higher levels of propionic acid, butyric acid, and valeric acid at 7 d postpartum (P < 0.05); the metabolic profiles of other ruminal metabolites were significantly shifted from 0 to 7 d postpartum, with 27 significantly elevated metabolites and 35 apparently reduced metabolites (P < 0.05). The correlation analysis indicated that propionic acid was positively correlated with Prevotellaceae and Ruminococcaceae (P < 0.05), negatively correlated with Methanobrevibacter (P < 0.01); butyric acid was positively associated with Prevotellaceae, Ruminococcaceae, and Pseudobutyrivibrio (P < 0.05), negatively associated with Christensenellaceae (P < 0.01); valeric acid was positively linked with Prevotellaceae and Ruminococcaceae (P < 0.05); pyridoxal was positively correlated with Flexilinea and Methanobrevibacter (P < 0.05) and negatively correlated with Ruminococcaceae (P < 0.01); tyramine was negatively linked with Ruminococcaceae (P < 0.01).CONCLUSION: The findings contribute to the decision of nutritional management and prevention of metabolic diseases in high-producing dairy cows during the late perinatal period.PMID:37817752 | PMC:PMC10560760 | DOI:10.3389/fmicb.2023.1269123

J Pak Med Assoc. 2023 Sep;73(9):1805-1810. doi: 10.47391/JPMA.7004.ABSTRACTOBJECTIVES: To explore the awarenesslevel of literate mothersregarding newborn screening programmes, and to evaluate the associated factors.METHODS: The descriptive, cross-sectional study was conducted at the Section of Chemical Pathology, Department of Pathology andLaboratoryMedicine,AgaKhanUniversity,Karachi,fromJanuary toSeptember 2021, andcomprisedmothers aged 18 years or more. Data was collected using a structured questionnaire about newborn screening, and the subjects were compared in terms of age, residential background, education and parity. Data was analysed using SPSS 23.RESULTS: Of the 1016 responses, 896(88.2%) were analysed. The mean age of the sample was 37.7±10.87 years. There were 470(52.4%) mothers aged 31-45 years, 859(95.87%) were from urban areas, 751(84%) had a graduate degree, 652(72.7%) weremultiparous andhad824(91.9%)hadhealthy children.Overall, 386 (43%)mothershadawarenessofnewbornscreening programmes. The main factors associated with awareness were age, education, primiparity, having healthy children, and province ofresidencebeing Sindh andPunjab(p<0.05),while the urban-ruraldividedwas not a significantfactor(p=0.737). Cost of healthcare 417(46.5%) and lack of awareness among physicians 356(39.7%) were identified asthe main challenges in establishing newborn screening servicesin the country.CONCLUSIONS: The awareness among mothers about new born screening programmes was generally low among the subjects studied.PMID:37817688 | DOI:10.47391/JPMA.7004

Curr Mol Med. 2023 Oct 4. doi: 10.2174/0115665240249826230928104512. Online ahead of print.ABSTRACTOBJECTIVE: To investigate the metabolomic differences between Traumatic brain injury (TBI) disorder of consciousness (DOC) patients and non-traumatic brain injury (NTBI) DOC patients by using cerebrospinal fluid (CSF), serum and urine samples beneficial to understand the pathological mechanism differences between the two etiologies, provide potential clues for the subsequent treatment and prognosis, and investigate the metabolome differences and similarities between TBI and NTBI among three different body fluids.METHODS: In total, 24 TBI DOC subjects and 29 NTBI DOC subjects were enrolled. CSF, serum and urine samples from TBI DOC and NTBI DOC patients were collected and analyzed by performing UPLC-MS. The statistical methods and pathway analyses were applied to discover potential biomarkers and altered metabolic functions.RESULTS: When comparing TBI DOC and NTBI DOC, 36, 31 and 52 differential metabolites were obtained in CSF, serum and urine, respectively. The functional analysis of differential metabolites obtained in CSF, serum and urine were all related to amino acid metabolism. Except for amino acid metabolism, metabolic biomarkers in CSF, serum and urine mainly focus on central function, cognitive function, necrosis and apoptosis and neurological function, respectively. In CSF, the highest AUC was 0.864 (Isoproturon) and 0.816 (Proline betaine). Then, the AUC of NFurfurylformamide in serum was 0.941, while the AUC of Dihydronepetalactone and Doxepin N-oxide glucuronide were 1.0 in urine.CONCLUSION: CSF, serum and urine metabolomic analyses could differentiate TBI DOC from NTBI DOC and functional analyses showed a metabolic change difference between TBI DOC and NTBI DOC.PMID:37817528 | DOI:10.2174/0115665240249826230928104512

Mol Plant. 2023 Oct 9:S1674-2052(23)00318-0. doi: 10.1016/j.molp.2023.10.004. Online ahead of print.NO ABSTRACTPMID:37817411 | DOI:10.1016/j.molp.2023.10.004

HGG Adv. 2023 Oct 9:100245. doi: 10.1016/j.xhgg.2023.100245. Online ahead of print.ABSTRACTMendelian randomization has been widely used to assess the causal effect of a heritable exposure variable on an outcome of interest, using genetic variants as instrumental variables. In practice, data on the exposure variable can be incomplete due to high cost of measurement and technical limits of detection. In this paper, we propose a valid and efficient method to handle both unmeasured and undetectable values of the exposure variable in one-sample Mendelian randomization analysis with individual-level data. We estimate the causal effect of the exposure variable on the outcome using maximum likelihood estimation and develop an expectation-maximization algorithm for the computation of the estimator. Simulation studies show that the proposed method performs well in making inference on the causal effect. We apply our method to the Hispanic Community Health Study/Study of Latinos, a community-based prospective cohort study, and estimate the causal effect of several metabolites on phenotypes of interest.PMID:37817410 | DOI:10.1016/j.xhgg.2023.100245

Anim Microbiome. 2023 Oct 10;5(1):49. doi: 10.1186/s42523-023-00270-8.ABSTRACTBACKGROUND: Pet cats frequently have diarrhea in their daily life. Bacillus has a protective role that has crucial beneficial functions on intestinal homeostasis. The aim of this research was to investigate the effects of the compound Bacillus on the prevention of diarrhea, microbiota and metabolism in pet cats. A total of 20 pet cats (1-2 years old, 3.91 ± 0.92 kg) were randomly divided into two groups and fed with a basal diet (Control group), or a basal diet supplemented with 3 × 109 CFU/kg compound Bacillus (Probiotics group). The experiment lasted 33 days.RESULTS: Results showed that the compound Bacillus significantly reduced the rate of soft stools and diarrhea in pet cats compared with the control group (P < 0.05, n = 10). Meanwhile, compared with the control group, the probiotics group significantly decreased the content of IL-1β and IL-6 and significantly increased IL-10 (P < 0.05, n = 6) in the serum. In addition, feeding probiotics significantly increased the abundance of p_Patescibacter and g_Plectosphaerella, decreased the abundance of p_Firmicutes, p_Gemmatimonadetes, g_Ruminococcaceae_UCG-005, g_Ascochytahe and g_Saccharomyces in the feces of the pet cats (P < 0.05, n = 6). And it also can significantly increase the content of total SCFAs, acetic acid and butyric acid in the feces (P < 0.05, n = 6). The fecal and serum metabolomics analyses revealed that most fecal and serum compounds were involved in metabolism, particularly in chemical structure transformation maps and amino acid metabolism. Also, eugenitol and methyl sulfate were the most significantly increased serum metabolites, and log2FC were 38.73 and 37.12, respectively. Pearson's correlation analysis showed that changes in serum metabolism and fecal microbiota were closely related to immune factors. There was also a strong correlation between serum metabolites and microbiota composition.CONCLUSIONS: The results of this research highlight the potential of the compound Bacillus as a dietary supplement to alleviate diarrhea in pet cats.PMID:37817260 | DOI:10.1186/s42523-023-00270-8

Anal Biochem. 2023 Oct 8:115332. doi: 10.1016/j.ab.2023.115332. Online ahead of print.ABSTRACTSepsis is a major contributor to the death of critically ill patients globally, in which metabolic disturbance is observed. Xuebijing injection (XBJ), a well-known traditional Chinese medicine, has received approval by the State Food and Drug Administration (SFDA) of China owing to its satisfactory clinical therapeutic effect. Nowadays, it has been applied clinically to the treatment of sepsis, but its effect on metabolic disorders remains unclear. In the present study, we sought to explore its underlying mechanism by employing a combination of network pharmacology and metabolomics. Initially, its protective effects were validated using a sepsis rat model created through cecal ligation puncture (CLP). Subsequently, the metabonomic strategy was utilized to discriminate the differential metabolic markers. Meanwhile, a comprehensive view of the potential ingredient-target-disease network was constructed based on a network pharmacology analysis. Next, the network diagram was constructed by integrating the results of network pharmacology and metabonomics. Finally, qRT-PCR together with Western blot was used to validate the expression levels of the associated genes. Based on our findings, we identified 34 differential metabolites in the sepsis group and 26 distinct metabolites in the XBJ group, with 8 common biological metabolites predominantly associated with arginine and proline metabolism. Through comprehensive analysis, we identified 21 genes that regulate metabolites, and qRT-PCR validation was conducted on six of these genes in both liver and kidney tissues. Additionally, XBJ demonstrated the capability to inhibit the activation of the NF-kB signaling pathway in both liver and kidney tissues, leading to a reduction in the occurrence of inflammatory responses. In summary, our study has validated the complexity of the natural compounds within XBJ and elucidated their potential mechanisms for addressing CLP-induced metabolic disturbances. This work contributes to our understanding of the bioactive compounds and their associated targets, providing insights into the potential molecular mechanisms involved.PMID:37816419 | DOI:10.1016/j.ab.2023.115332

Cell Rep. 2023 Oct 2:113195. doi: 10.1016/j.celrep.2023.113195. Online ahead of print.ABSTRACTFatty acids have long been considered essential to brain development; however, the involvement of their synthesis in nervous system formation is unclear. We generate mice with knockout of GPSN2, an enzyme for synthesis of very-long-chain fatty acids (VLCFAs) and investigate the effects. Both GPSN2-/- and GPSN2+/- mice show abnormal neuronal networks as a result of impaired neuronal polarity determination. Lipidomics of GPSN2-/- embryos reveal that ceramide synthesis is specifically inhibited depending on FA length; namely, VLCFA-containing ceramide is reduced. We demonstrate that lipid rafts are highly enriched in growth cones and that GPSN2+/- neurons lose gangliosides in their membranes. Application of C24:0 ceramide, but not C16:0 ceramide or C24:0 phosphatidylcholine, to GPSN2+/- neurons rescues both neuronal polarity determination and lipid-raft density in the growth cone. Taken together, our results indicate that VLCFA synthesis contributes to physiological neuronal development in brain network formation, in particular neuronal polarity determination through the formation of lipid rafts.PMID:37816355 | DOI:10.1016/j.celrep.2023.113195

J Hazard Mater. 2023 Sep 26;461:132631. doi: 10.1016/j.jhazmat.2023.132631. Online ahead of print.ABSTRACTMicrocystis aeruginosa and ammonia pollution are two important environmental stress factors in water eutrophication. Herein, we simulated environmental conditions to investigate the effects of chronic exposure (single and combined) to M. aeruginosa and total ammonia nitrogen (TAN) on lipid metabolism and muscle quality in zebrafish. Our results showed that M. aeruginosa and TAN significantly induced lipid deposition and tissue damage in the liver of zebrafish. Liver transcriptomic analysis revealed that M. aeruginosa and TAN disrupted the balance in lipid synthesis, decomposition, and transport, ultimately leading to hepatic lipid accumulation. Moreover, exposure to M. aeruginosa or TAN alone resulted in decreased crude protein content and increased lipid content in muscle, as well as disrupted muscle fatty acid composition. Metabolomic analysis of muscle revealed significant alterations in metabolites such as glycerolipids, glycerophospholipids and fatty acids. The co-exposure of M. aeruginosa and TAN had a more significant effect on liver lipid dysfunction and muscle quality deterioration in zebrafish. These findings provide valuable insights into the potential risks and hazards of M. aeruginosa and TAN in eutrophic water bodies subject to Microcystis blooms, and can help inform effective strategies for monitoring and managing these toxins in aquatic ecosystems.PMID:37816294 | DOI:10.1016/j.jhazmat.2023.132631

Biosens Bioelectron. 2023 Sep 28;242:115696. doi: 10.1016/j.bios.2023.115696. Online ahead of print.ABSTRACTElevating soluble CD80 (sCD80) in human serum is a natural response to autoimmune diseases such as rheumatoid arthritis (RA). The level of sCD80 is associated with RA development and prognosis; therefore, it is potentially used as a biomarker. sCD80 is commonly measured in human serum using immunoassays (e.g., ELISA) with multiple drawbacks, mainly cross-reactivity. Aptamer-based biosensors (aptasensors) development for quantifying and detecting different biological molecules demonstrates applicability in next-generation medicine and biomarker detection. Herein, we selected a specific aptamer for sCD80 by conventional in-vitro selection process (SELEX) with the high-affinity aptamer (Kd = 47.69 nM). A sensitive aptasensor, for the first time, was developed on a screen-printed gold electrode (AuSPE) platform compatible with easy-to-use label-free electrochemical impedance spectroscopy. The immobilization of the aptamer on the gold surface and the presence of sCD80 in a complex with the aptamer were characterized by photo-induced force microscopy, which revealed the uniform assembly of the aptamer monolayer and the distribution of sCD80 on the electrode surface. The developed aptasensor showed a linear performance (0.025-10.0 nM of protein) with a detection limit of 8.0 pM. Furthermore, the aptasensor was tested in a biological matrix, where a linear signal was observed for the increased amount of spiked sCD80 (R2 = 0.9887). The recovery of the spiked amounts ranged from 105 to 125% with coefficient of variation (CV%) <7%, which supported the applicability of this sensor in detecting sCD80 for diagnosis.PMID:37816286 | DOI:10.1016/j.bios.2023.115696