PubMed

Front Microbiol. 2022 Dec 12;13:1100290. doi: 10.3389/fmicb.2022.1100290. eCollection 2022.ABSTRACT[This corrects the article DOI: 10.3389/fmicb.2022.965709.].PMID:36578573 | PMC:PMC9791648 | DOI:10.3389/fmicb.2022.1100290

Extracell Vesicle. 2022 Dec;1:100004. doi: 10.1016/j.vesic.2022.100004. Epub 2022 Jul 1.ABSTRACTExtracellular vesicles (EV) as drug delivery nanocarriers are under intense investigation. Although clinical-grade EVs have been produced on a large-scale, low yield and high production costs of natural EVs (nEV) limit the relevant industrial translation. Recent studies show that mechanical extrusion of cells can generate nEV-like cell-derived nanovesicles (CNV) which can also be used as drug nanocarriers. Moreover, in comparison with nEVs, CNVs have similar physicochemical properties. Nevertheless, a comprehensive comparison of cargo between nEVs and CNVs has not been investigated yet. Therefore, the aim of this study is to profile and compare CNVs to nEVs. Our results show that no significant difference was found in size, morphology, and classical markers between nEVs and CNVs derived from MDA-MB-231 cells. Protein sequencing data reveals the similarity of membrane proteins between the two groups was ~71%, while it was ~21% when pertaining to total protein cargo. Notably, a high similarity of membrane proteins was also found between nEVs and CNVs derived from eight additional cancer cell lines. Moreover, analysis of the top 1000 small RNAs with RNA sequencing showed a ~65% similarity between the two groups. Altogether, we infer from the high similarity of membrane proteins and small RNA cargo that CNVs can be a good substitute for nEVs. In brief, our findings support previous studies with a notion that CNVs yield comparable performance with nEVs and could pave the way for clinical implementation of CNV-based therapeutics in the future.PMID:36578271 | PMC:PMC9794200 | DOI:10.1016/j.vesic.2022.100004

Sci Rep. 2022 Dec 28;12(1):22473. doi: 10.1038/s41598-022-26551-x.ABSTRACTPlants deposit photosynthetically-fixed carbon in the rhizosphere, the thin soil layer directly around the root, thereby creating a hospitable environment for microbes. To manage the inhabitants of this nutrient-rich environment, plant roots exude and dynamically adjust microbe-attracting and -repelling compounds to stimulate specific members of the microbiome. Previously, we demonstrated that foliar infection of Arabidopsis thaliana by the biotrophic downy mildew pathogen Hyaloperonospora arabidopsidis (Hpa) leads to a disease-induced modification of the rhizosphere microbiome. Soil conditioned with Hpa-infected plants provided enhanced protection against foliar downy mildew infection in a subsequent population of plants, a phenomenon dubbed the soil-borne legacy (SBL). Here, we show that for the creation of the SBL, plant-produced coumarins play a prominent role as coumarin-deficient myb72 and f6'h1 mutants were defective in creating a Hpa-induced SBL. Root exudation profiles changed significantly in Col-0 upon foliar Hpa infection, and this was accompanied by a compositional shift in the root microbiome that was significantly different from microbial shifts occurring on roots of Hpa-infected coumarin-deficient mutants. Our data further show that the Hpa-induced SBL primes Col-0 plants growing in SBL-conditioned soil for salicylic acid (SA)-dependent defenses. The SA-signaling mutants sid2 and npr1 were unresponsive to the Hpa-induced SBL, suggesting that the protective effect of the Hpa-induced shift in the root microbiome results from an induced systemic resistance that requires SA-signaling in the plant.PMID:36577764 | DOI:10.1038/s41598-022-26551-x

NPJ Sci Food. 2022 Dec 28;6(1):60. doi: 10.1038/s41538-022-00174-y.ABSTRACTColorectal cancer (CRC) is the second most prevelant malignancy in Europe and diet is an important modifiable risk factor. Processed meat consumption, including meats with preservative salts such as sodium nitrite, have been implicated in CRC pathogenesis. This study investigated how the CRC pathology and metabolic status of adenomatous polyposis coli (APC) multiple intestinal neoplasia (min) mice was perturbed following 8 weeks of pork meat consumption. Dietary inclusions (15%) of either nitrite-free pork, nitrite-free sausage, or nitrite-containing sausage (frankfurter) were compared against a parallel control group (100% chow). Comprehensive studies investigated: gastrointestinal tract histology (tumours), aberrant crypt foci (ACF), mucin deplin foci (MDF), lipid peroxidation (urine and serum), faecal microbiota, and serum metabolomics (599 metabolites). After 8 weeks mice consuming the frankfurter diet had 53% more (P = 0.014) gastrointestinal tumours than control, although ACF and MDF did not differ. Urine and serum lipid peroxidation markers were 59% (P = 0.001) and 108% (P = 0.001) higher, respectively in the frankfurter group. Gut dysbiosis was evident in these mice with comparably fewer Bacteriodes and more Firmicutes. Fasting serum levels of trimethylamine N-oxide (TMAO) and numerous triglycerides were elevated. Various serum phosphotidylcholine species were decreased. These results demonstrate that nitrite-containing sausages may exaccerbate the development of CRC pathology in APCMin mice to a greater extent than nitrite-free sausages, and this is associated with greater lipid peroxidation, wide-ranging metabolic alternation and gut dysbiosis.PMID:36577751 | DOI:10.1038/s41538-022-00174-y

Addict Biol. 2023 Jan;28(1):e13255. doi: 10.1111/adb.13255.ABSTRACTMethamphetamine (METH) is a commonly abused addictive psychostimulant, and METH-induced neurotoxic and behavioural deficits are in a sex-specific manner. However, there is lack of biomarkers to evaluate METH addiction in clinical practice, especially for gender differences. We utilized ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) to detect the serum metabolomics in METH addicts and controls, specially exploring the sex-specific metabolic alterations by METH abuse. We found that many differently expressed metabolites in METH addicts related to metabolisms of amino acid, energy, vitamin and neurological disorders. Further, METH abuse caused different patterns of metabolomics in a sex-specific manner. As to amino acid metabolism, L-phenylalanine, L-tryptophan and L-histidine in serum of male addicts and betaine in serum of female addicts were significantly changed by METH use. In addition, it seemed that purine and pyrimidine-related metabolites (e.g., xanthosine and adenosine 5'-monophosphate) in male and the metabolites of hormone (e.g., cortisol) and folate biosynthesis (e.g., 7,8-dihydrobiopterin and 4-hydroxybenzoic acid) in female were more sensitive to METH addiction. Our findings revealed that L-glutamic acid, L-aspartic acid, alpha-ketoglutarate acid and citric acid may be potential biomarkers for monitoring METH addiction in clinic. Considering sex-specific toxicity by METH, the metabolites of purine and pyrimidine metabolism in male and those of stress-related hormones in female may be used to facilitate the accurate diagnosis and treatment for METH addicts of different genders.PMID:36577725 | DOI:10.1111/adb.13255

Nutr Metab Cardiovasc Dis. 2022 Nov 3:S0939-4753(22)00441-0. doi: 10.1016/j.numecd.2022.10.016. Online ahead of print.ABSTRACTBACKGROUND AND AIMS: Reducing consumption of sugar-sweetened beverages (SSBs) is a global public health priority because of their limited nutritional value and associations with increased risk of obesity and metabolic diseases. Gut microbiota-related metabolites emerged as quintessential effectors that may mediate impacts of dietary exposures on the modulation of host commensal microbiome and physiological status.METHODS AND RESULTS: This study assessed the associations among SSBs, circulating microbial metabolites, and gut microbiota-host co-metabolites, as well as metabolic health outcomes in young Chinese adults (n = 86), from the Carbohydrate Alternatives and Metabolic Phenotypes study in Shaanxi Province. Five principal component analysis-derived beverage drinking patterns were determined on self-reported SSB intakes, which were to a varying degree associated with 143 plasma levels of gut microbiota-related metabolites profiled by untargeted metabolomics. Moreover, carbonated beverages, fruit juice, energy drinks, and bubble tea exhibited positive associations with obesity-related markers and blood lipids, which were further validated in an independent cohort of 16,851 participants from the Regional Ethnic Cohort Study in Northwest China in Shaanxi Province. In contrast, presweetened coffee was negatively associated with the obesity-related traits. A total of 79 metabolites were associated with both SSBs and metabolic markers, particularly obesity markers. Pathway enrichment analysis identified the branched-chain amino acid catabolism and aminoacyl-tRNA biosynthesis as linking SSB intake with metabolic health outcomes.CONCLUSION: Our findings demonstrate the associations between habitual intakes of SSBs and several metabolic markers relevant to noncommunicable diseases, and highlight the critical involvement of gut microbiota-related metabolites in mediating such associations.PMID:36577637 | DOI:10.1016/j.numecd.2022.10.016

J Ethnopharmacol. 2022 Dec 25:116074. doi: 10.1016/j.jep.2022.116074. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Astragali Radix (AR) is the dried root of Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao or A. membranaceus (Fisch.) Bge. AR was the main medicine in a Chinese traditional prescription called Fangji Huangqi Decoction, and it has been used to treating nephrotic syndrome (NS) for thousands of years in China. In recent years, AR has been evidenced to have anti-inflammatory activity, antihyperglycemic activity, antioxidant activity, etc. There are two mainstream commodities for ARs in the market including the imitation wild AR and transplanted AR. However, it is not clear whether the imitation wild AR or transplanted AR and which kind of component, astragalus saponin, astragalus flavonoid or astragalus polysaccharide, makes a bigger contribution in treating NS. And the exact molecular mechanism is not fully understood.AIM OF THE STUDY: To explore which kind of AR and which kind of component in AR makes the bigger contribution in treating NS, and exploring the molecular mechanism.MATERIALS AND METHODS: Firstly, HPLC-UV/ELSD was used for quantitative determination of the constituents in different ARs. Secondly, the efficacy of different ARs treating doxorubicin-induced nephropathy (DN) was compared by metabolomics. Thirdly, the protective effects of different constituents from ARs on the damage of MPC5 cells induced by adriamycin are validated. Finally, the effective constituents and mechanism of ARs against doxorubicin-induced nephropathy were investigated by network pharmacology and molecular docking.RESULTS: Quantitative determination experiment and pharmacological experiment indicated that the AR produced from Gansu province (China) (transplanted AR) with a higher proportion of total saponins, has better efficacy in the treatment for DN. And the cell experiment validated the result that astragalus saponins has the better efficacy in protecting the podocyte against injury than astragalus flavonoids and polysaccharides. The network pharmacology and molecular docking study indicated that astragalus saponins were the main constituent of AR in the treatment for DN. The mechanism may involve in GnRH signaling pathway, VEGF signaling pathway and metabolic pathways, especially of bilirubin metabolism.CONCLUSIONS: Transplanted AR has better efficacy in the treatment for NS than imitation wild AR, astragalus saponins have better efficacy in the treatment for NS than astragalus flavonoids and polysaccharides.PMID:36577490 | DOI:10.1016/j.jep.2022.116074

Cell Rep. 2022 Dec 27;41(13):111891. doi: 10.1016/j.celrep.2022.111891.ABSTRACTCardiogenesis is a tightly regulated dynamic process through a continuum of differentiation and proliferation events. Key factors and pathways governing this process remain incompletely understood. Here, we investigate mice hearts from embryonic day 10.5 to postnatal week 8 and dissect developmental changes in phosphoproteome-, proteome-, metabolome-, and transcriptome-encompassing cardiogenesis and cardiac maturation. We identify mitogen-activated protein kinases as core kinases involved in transcriptional regulation by mediating the phosphorylation of chromatin remodeling proteins during early cardiogenesis. We construct the reciprocal regulatory network of transcription factors (TFs) and identify a series of TFs controlling early cardiogenesis involved in cycling-dependent proliferation. After birth, we identify cardiac resident macrophages with high arachidonic acid metabolism activities likely involved in the clearance of injured apoptotic cardiomyocytes. Together, our comprehensive multi-omics data offer a panoramic view of cardiac development and maturation that provides a resource for further in-depth functional exploration.PMID:36577384 | DOI:10.1016/j.celrep.2022.111891

Cell Rep. 2022 Dec 27;41(13):111867. doi: 10.1016/j.celrep.2022.111867.ABSTRACTThe complexity of signaling events and cellular responses unfolding in neuronal, glial, and immune cells upon traumatic brain injury (TBI) constitutes an obstacle in elucidating pathophysiological links and targets for intervention. We use array phosphoproteomics in a murine mild blunt TBI to reconstruct the temporal dynamics of tyrosine-kinase signaling in TBI and then scrutinize the large-scale effects of perturbation of Met/HGFR, VEGFR1, and Btk signaling by small molecules. We show Met/HGFR as a selective modifier of early microglial response and that Met/HGFR blockade prevents the induction of microglial inflammatory mediators, of reactive microglia morphology, and TBI-associated responses in neurons and vasculature. Both acute and prolonged Met/HGFR inhibition ameliorate neuronal survival and motor recovery. Early elevation of HGF itself in the cerebrospinal fluid of TBI patients suggests that this mechanism has translational value in human subjects. Our findings identify Met/HGFR as a modulator of early neuroinflammation in TBI with promising translational potential.PMID:36577378 | DOI:10.1016/j.celrep.2022.111867

J Plant Physiol. 2022 Dec 23;280:153888. doi: 10.1016/j.jplph.2022.153888. Online ahead of print.ABSTRACTNitrogen (N) is an indispensable element for plant growth and development. To understand the regulation of underlying carbon (C) and N metabolism in blackberry plants, we performed integrated analyses of the physiology, metabolome and transcriptome. Blackberry plants were subjected to no N, nitrate (NO3⁻)-N, ammonium (NH4+)-N and urea treatments. Our results showed that the NH4⁺-N treatment yielded higher values for the biomass, chlorophyll, antioxidants, N contents and antioxidant enzyme activities, as well as lower levels of free radicals and the C/N ratio compared with other treatments. Transcriptome analysis showed that different N forms significantly affected photosynthesis, flavonoid biosynthesis and the TCA cycle. Metabolome analysis indicated that the levels of lipids, carbohydrates, flavonoids and amino acids were markedly changed under different N treatments. Integrated transcriptomic and metabolomic data revealed that amino acids, including proline, arginine, L-isoleucine, L-aspartate, threonine, and L-glutamate, played important roles in maintaining normal plant growth by regulating N metabolism and amino acid metabolism. Overall, blackberry plants preferentially take up NH4⁺-N. Under the NH4⁺-N treatment, N assimilation was stronger, flavonoid biosynthesis was decreased, and the promoting influence of NH4⁺-N on N metabolism was better than that of NO3⁻-N. However, the NO3⁻-N treatment enhanced the C/N ratio, accelerated the process of C metabolism and increased the synthesis of flavonoids, thereby accelerating the flow of N metabolism to C metabolism. These results provide deeper insight into coordinating C and N metabolism and improving N use efficiency in blackberry plants.PMID:36577314 | DOI:10.1016/j.jplph.2022.153888

CEN Case Rep. 2022 Dec 28. doi: 10.1007/s13730-022-00768-1. Online ahead of print.ABSTRACTAdenine phosphoribosyltransferase (APRT) deficiency is a rare autosomal recessive disorder that leads to the accumulation of poorly soluble 2,8-dihydroxyadenine (DHA) in the kidneys, resulting in a variety of renal presentations including nephrolithiasis, acute kidney injury, and chronic kidney disease (CKD) caused by crystal nephropathy. Here, we report a case of a 43-year-old man with 2,8-DHA crystalline nephropathy caused by APRT deficiency strongly suspected by renal biopsy results and definitively diagnosed by a urine gas chromatography-mass spectrometry (GC/MS)-based plasma metabolomic assessment. This case represents the importance of awareness and recognition of the signs and symptoms of this rare condition and its progression to CKD, which can be prevented by the early administration of xanthine oxidoreductase inhibitors.PMID:36576711 | DOI:10.1007/s13730-022-00768-1

Metabolomics. 2022 Dec 28;19(1):4. doi: 10.1007/s11306-022-01965-w.ABSTRACTINTRODUCTION: Feature annotation is crucial in untargeted metabolomics but remains a major challenge. The large pool of metabolites collected under various instrumental conditions is underrepresented in publicly available databases. Retention time (RT) and collision cross section (CCS) measurements from liquid chromatography ion mobility high-resolution mass spectrometers can be employed in addition to MS/MS spectra to improve the confidence of metabolite annotation. Recent advancements in machine learning focus on improving the accuracy of predictions for CCS and RT values. Therefore, high-quality experimental data are crucial to be used either as training datasets or as a reference for high-confidence matching.METHODS: This manuscript provides an easy-to-use workflow for the creation of an in-house metabolite library, offers an overview of alternative solutions, and discusses the challenges and advantages of using open-source software. A total of 100 metabolite standards from various classes were analyzed and subjected to the described workflow for library generation.RESULTS AND DISCUSSION: The outcome was an open-access available NIST format metabolite library (.msp) with multidimensional information. The library was used to evaluate CCS prediction tools, MS/MS spectra heterogeneities (e.g., multiple adducts, in-source fragmentation, radical fragment ions using collision-induced dissociation), and the reporting of RT.PMID:36576608 | DOI:10.1007/s11306-022-01965-w

Anal Chem. 2022 Dec 28. doi: 10.1021/acs.analchem.2c04203. Online ahead of print.ABSTRACTNuclear magnetic resonance (NMR) spectroscopy is commonly employed in a wide range of metabolomic research. Unfortunately, due to its relatively low sensitivity, smaller samples become challenging to study by NMR. Cryoprobes can be used to increase sensitivity by cooling the coil and preamplifier, offering sensitivity improvements of ∼3 to 4x. Alternatively, microcoils can be used to increase mass sensitivity by improving sample filling and proximity, along with decreased electrical resistance. Unfortunately, combining the two approaches is not just technically challenging, but as the coil decreases, so does its thermal fingerprint, reducing the advantage of cryogenic cooling. Here, an alternative solution is proposed in the form of a Lenz lens inside a cryoprobe. Rather than replacing the detection coil, Lenz lenses allow the B1 field from a larger coil to be refocused onto a much smaller sample area. In turn, the stronger B1 field at the sample provides strong coupling to the cryocoil, improving the signal. By combining a 530 I.D. Lenz lens with a cryoprobe, sensitivity was further improved by 2.8x and 3.5x for 1H and 13C, respectively, over the cryoprobe alone for small samples. Additionally, the broadband nature of the Lenz lenses allowed multiple nuclei to be studied and heteronuclear two-dimensional (2D) NMR approaches to be employed. The sensitivity improvements and 2D capabilities are demonstrated on 430 nL of hemolymph and eight eggs (∼350 μm O.D.) from the model organismDaphnia magna. In summary, combining Lenz lenses with cryoprobes offers a relatively simple approach to boost sensitivity for tiny samples while retaining cryoprobe advantages.PMID:36576271 | DOI:10.1021/acs.analchem.2c04203

Circ Res. 2022 Dec 28. doi: 10.1161/CIRCRESAHA.122.321975. Online ahead of print.ABSTRACTBACKGROUND: Dysbiosis of gut microbiota plays a pivotal role in vascular dysfunction and microbial diversity was reported to be inversely correlated with arterial stiffness. However, the causal role of gut microbiota in the progression of arterial stiffness and the specific species along with the molecular mechanisms underlying this change remain largely unknown.METHODS: Participants with elevated arterial stiffness and normal controls free of medication were matched for age and sex. The microbial composition and metabolic capacities between the 2 groups were compared with the integration of metagenomics and metabolomics. Subsequently, AngII (angiotensin II)-induced and humanized mouse model were employed to evaluate the protective effect of Flavonifractor plautii (F. plautii) and its main effector cis-aconitic acid.RESULTS: Human fecal metagenomic sequencing revealed a significantly high abundance and centrality of F. plautii in normal controls, which was absent in the microbial community of subjects with elevated arterial stiffness. Moreover, blood pressure only mediated part of the effect of F. plautii on lower arterial stiffness. The microbiome of normal controls exhibited an enhanced capacity for glycolysis and polysaccharide degradation, whereas, those of subjects with increased arterial stiffness were characterized by increased biosynthesis of fatty acids and aromatic amino acids. Integrative analysis with metabolomics profiling further suggested that increased cis-aconitic acid served as the main effector for the protective effect of F. plautii against arterial stiffness. Replenishment with F. plautii and cis-aconitic acid improved elastic fiber network and reversed increased pulse wave velocity through the suppression of MMP-2 (matrix metalloproteinase-2) and inhibition of MCP-1 (monocyte chemoattractant protein-1) and NF-κB (nuclear factor kappa-B) activation in both AngII-induced and humanized model of arterial stiffness.CONCLUSIONS: Our translational study identifies a novel link between F. plautii and arterial function and raises the possibility of sustaining vascular health by targeting gut microbiota.PMID:36575982 | DOI:10.1161/CIRCRESAHA.122.321975

Plant J. 2022 Dec 27. doi: 10.1111/tpj.16084. Online ahead of print.ABSTRACTThe chemical complexity of metabolomes goes hand in hand with the functional diversity. Small molecules have many essential roles, many of which are executed by binding and modulating the function of a protein partner. The complex and dynamic protein-metabolite interactions network underlies most if not all biological processes but remains under-characterized. Herein, we highlight how co-fractionation mass-spectrometry (CF-MS), a well-established approach to map protein assemblies, can be used for proteome and metabolome identification of the protein-metabolite interactions. We will review the recent CF-MS studies, discuss the main advantages and limitations, summarize available CF-MS guidelines, and outline future challenges and opportunities.PMID:36575913 | DOI:10.1111/tpj.16084

Plant Commun. 2022 Dec 26:100511. doi: 10.1016/j.xplc.2022.100511. Online ahead of print.ABSTRACTPlastids communicate their developmental and physiological status to the nucleus via retrograde signaling, thus allowing nuclear gene expression to be adjusted appropriately. Signaling during plastid biogenesis and responses of mature chloroplasts to environmental changes are designated as biogenic' and 'operational' controls, respectively. A prominent example of the investigation of biogenic signaling is the screen for gun (genomes uncoupled) mutants. Although the first five gun mutants were identified 30 years ago, the functions of GUN proteins in retrograde signaling remain controversial and that of GUN1 is hotly disputed. Here, we provide background information and critically discuss recently proposed concepts that address GUN-related signaling and some novel gun mutants. Moreover, considering heme as a candidate in retrograde signaling, we revisit the spatial organization of heme biosynthesis and export from plastids. Although this review focuses on GUN pathways, we also highlight recent progress in the identification and elucidation of chloroplast-derived signals that regulate the acclimation response in green algae and plants. Here, stress-induced accumulation of unfolded/misassembled chloroplast proteins evokes a chloroplast-specific unfolded protein response (cpUPR), which leads to changes in the expression levels of nucleus-encoded chaperones and proteases to restore plastid protein homeostasis. We also address the importance of chloroplast-derived signals for activation of flavonoid biosynthesis leading to the production of anthocyanins during stress acclimation through sucrose non-fermenting-1-related protein kinase-1 (SnRK1). Finally, a framework for the identification and quantification of intercompartmental signaling cascades at the proteomic and metabolomic levels is provided, and we discuss future directions in the dissection of organelle-nucleus communication.PMID:36575799 | DOI:10.1016/j.xplc.2022.100511

Zhonghua Zhong Liu Za Zhi. 2022 Dec 23;44(12):1369-1375. doi: 10.3760/cma.j.cn112152-20201212-01066.ABSTRACTObjective: To explore the metabolite profile and metabolic pathways of newly diagnosed multiple myeloma (MM). Methods: Gas chromatography-mass spectrometry (GC-MS) was employed for the high-throughput detection and identification of serum samples from 55 patients with MM and 37 healthy controls matched for age and sex from 2016 to 2017 collected at the First Affiliated Hospital of Soochow University. The relative standard deviation (RSD) of quality control (QC) samples was employed to validate the reproducibility of GC-MS approach. The differential metabolites between patients with MM and healthy controls were detected by partial least squares discrimination analysis (PLS-DA), and t-test with false discovery rate (FDR) correction. Metabolomics pathway analysis (MetPA) was employed to construct metabolic pathways. Results: There were 55 MM patients, including 34 males and 21 females. The median age was 60 years old (42-73 years old). There were 30 cases of IgG type, 9 cases of IgA type, 1 case of IgM type, 2 cases of non-secreted type, 1 case of double clone type and 12 cases of light chain type, including 3 cases of kappa light chain type and 9 cases of lambda light chain type. The result of QC sample test showed that the proportion of compounds with the RSD of the relative content of metabolites < 15% was 70.21% obtained by the reproducibility of GC-MS experimental data, which implied that the experimental data were reliable. A total of 17 metabolites were screened differently with the healthy control group, including myristic acid, hydroxyproline, cysteine, palmitic acid, L-leucine, stearic acid, methionine, phenylalanine, glycerin, serine, isoleucine, tyrosine, valine, citric acid, inositol, threonine, and oxalic acid (VIP>1, P<0.05). Metabolic pathway analysis suggested that metabolic disorders in MM patients comprised mainly phenylalanine metabolism, glyoxylic acid and dicarboxylic acid metabolism, phosphoinositide metabolism, cysteine and methionine metabolism, glycerolipid metabolism, glycine, serine, and threonine metabolism. Conclusion: Compared with normal people, patients with newly diagnosed MM have obvious differences in metabolic profiles and metabolic pathways.PMID:36575789 | DOI:10.3760/cma.j.cn112152-20201212-01066

Arch Insect Biochem Physiol. 2022 Dec 27:e21992. doi: 10.1002/arch.21992. Online ahead of print.ABSTRACTThe small brown planthopper, Laodelphax striatellus, is a destructive pest insect found in rice fields. L. striatellus not only directly feeds on the phloem sap of rice but also transmits various viruses, such as rice stripe virus (RSV) and rice black-streaked dwarf virus, resulting in serious loss of rice production. RSV is a rice-infecting virus that is found mainly in Korea, China, and Japan. To develop novel strategies to control L. striatellus and L. striatellus-transmitted viruses, various studies have been conducted, based on vector biology, interactions between vectors and pathogens, and omics, including transcriptomics, proteomics, and metabolomics. In this review, we discuss the roles of saliva proteins during phloem sap-sucking and virus transmission, the diversity and role of the microbial community in L. striatellus, the profile and molecular mechanisms of insecticide resistance, classification of L. striatellus-transmitted RSV, its host range and symptoms, its genome composition and roles of virus-derived proteins, its distribution, interactions with L. striatellus, and resistance and control, to suggest future directions for integrated pest management to control L. striatellus and L. striatellus-transmitted viruses.PMID:36575628 | DOI:10.1002/arch.21992

Arch Insect Biochem Physiol. 2022 Dec 27:e21995. doi: 10.1002/arch.21995. Online ahead of print.ABSTRACTThe imaginal disc growth factor (IDGF), belonging to the glycoside hydrolase 18 family, plays an important role in various physiological processes in insects. However, the detail physiological function of IDGF is still unclear. In this study, transcriptome analysis was performed on the fatbody isolated from staged control and BmIDGF mutant silkworm larvae. Transcriptional profiling revealed that the absence of BmIDGF significantly affected differentially expressed genes involved in tyrosine and purine metabolism, as well as multiple energy metabolism pathways, including glycolysis, galactose, starch, and sucrose metabolism. The interruption of BmIDGF caused similar and specific gene expression changes to male and female fatbody. Furthermore, a genome-scale metabolic network integrating metabolomic and transcriptomic datasets revealed 11 pathways significantly altered at the transcriptional and metabolic levels, including amino acid, carbohydrate, uric acid metabolism pathways, insect hormone biosynthesis, and ABC transporters. In conclusion, this multiomics analysis suggests that IDGF is involved in gene-metabolism interactions, revealing its unique role in melanin synthesis and energy metabolism. This study provides new insights into the physiological function of IDGF in insects.PMID:36575612 | DOI:10.1002/arch.21995

BMC Med. 2022 Dec 27;20(1):497. doi: 10.1186/s12916-022-02700-x.ABSTRACTBACKGROUND: The pathogenesis of immunoglobulin G4-related disease (IgG4-RD) remains unclear. IgG4-RD often mimics other diseases, including pancreatic cancer (PC) and Sjogren's syndrome (SS), which may easily lead to misdiagnosis. This study was performed to explore the metabolite changes and potential biomarkers of IgG4-RD and other misdiagnosed diseases.METHODS: Untargeted liquid chromatography-tandem mass spectrometry metabolomics profiling of plasma samples from a cohort comprising healthy controls (HCs) and patients with IgG4-RD (n = 87), PC (n = 33), and SS (n = 31) was performed. A random forest machine learning model was used to verify the relevance of the identified metabolites in the diagnosis of different diseases and the prediction of disease prognosis.RESULTS: The ATP-binding cassette transporter pathway was found to be most closely related to IgG4-RD, which was significantly up-regulated in the IgG4-RD group than in all the matched groups. Five metabolites were proved to be valuable biomarkers for IgG4-RD. Caftaric acid, maltotetraose, D-glutamic acid, 1-stearoyl-2-arachidonoyl-sn-glycero-3-phosphoserine, and hydroxyproline were useful in distinguishing between IgG4-RD, PC, SS, and HC [area under the curve (AUC) = 1]. A combination of phenylalanine betaine, 1-(1z-hexadecenyl)-sn-glycero-3-phosphocholine, Pi 40:8, uracil, and N1-methyl-2-pyridone-5-carboxamide showed a moderate value in predicting relapse in patients with IgG4-RD (AUC = 0.8).CONCLUSIONS: Our findings revealed the metabolite changes of IgG4-RD and provide new insights for deepening our understanding of IgG4-RD despite the lack of validation in external cohorts. Metabolomic biomarkers have significance in the clinical diagnosis and disease prognosis of IgG4-RD.PMID:36575511 | DOI:10.1186/s12916-022-02700-x