PubMed

Front Plant Sci. 2022 Nov 14;13:1005906. doi: 10.3389/fpls.2022.1005906. eCollection 2022.ABSTRACTThe trichothecene toxin-producing fungus Trichoderma arundinaceum has potential as a biological control agent. However, most biocontrol studies have focused only on one strain, IBT 40837. In the current study, three Trichoderma isolates recovered from bean-field soils produced the trichothecene harzianum A (HA) and trichodermol, the latter being an intermediate in the HA biosynthesis. Based on phylogenetic analysis, the three isolates were assigned to the species T. arundinaceum. Their genome sequences had a high degree of similarity to the reference IBT 40837 strain, in terms of total genome size, number of predicted genes, and diversity of putative secondary metabolite biosynthetic gene clusters. HA production by these bean-field isolates conferred significant in vitro antifungal activity against Rhizoctonia solani and Sclerotinia sclerotiorum, which are some of the most important bean pathogens. Furthermore, the bean-field isolates stimulated germination of bean seeds and subsequent growth of above ground parts of the bean plant. Transcriptomic analysis of bean plants inoculated with these T. arundinaceum bean-field soil isolates indicated that HA production significantly affected expression of plant defense-related genes; this effect was particularly significant in the expression of chitinase-encoding genes. Together, these results indicate that Trichoderma species producing non-phytotoxic trichothecenes can induce defenses in plants without negatively affecting germination and development.PMID:36452093 | PMC:PMC9702529 | DOI:10.3389/fpls.2022.1005906

Theranostics. 2022 Nov 7;12(18):7681-7698. doi: 10.7150/thno.74974. eCollection 2022.ABSTRACTRationale: Increased lipid droplet (LD) formation has been linked to tumor metastasis, stemness, and chemoresistance in various types of cancer. Here, we revealed that LD formation is critical for the adaptation to sorafenib in hepatocellular carcinoma (HCC) cells. We aim to investigate the LD function and its regulatory mechanisms in HCC. Methods: The key proteins responsible for LD formation were screened by both metabolomics and proteomics in sorafenib-resistant HCC cells and further validated by immunoblotting and immunofluorescence staining. Biological function of AKR1C3 was evaluated by CRISPR/Cas9-based gene editing. Isotopic tracing analysis with deuterium3-labeled palmitate or carbon13-labeled glucose was conducted to investigate fatty acid (FA) and glucose carbon flux. Seahorse analysis was performed to assess the glycolytic flux and mitochondrial function. Selective AKR1C3 inhibitors were used to evaluate the effect of AKR1C3 inhibition on HCC tumor growth and induction of autophagy. Results: We found that long-term sorafenib treatment impairs fatty acid oxidation (FAO), leading to LD accumulation in HCC cells. Using multi-omics analysis in cultured HCC cells, we identified that aldo-keto reductase AKR1C3 is responsible for LD accumulation in HCC. Genetic loss of AKR1C3 fully depletes LD contents, navigating FA flux to phospholipids, sphingolipids, and mitochondria. Furthermore, we found that AKR1C3-dependent LD accumulation is required for mitigating sorafenib-induced mitochondrial lipotoxicity and dysfunction. Pharmacologic inhibition of AKR1C3 activity instantly induces autophagy-dependent LD catabolism, resulting in mitochondrial fission and apoptosis in sorafenib-resistant HCC clones. Notably, manipulation of AKR1C3 expression is sufficient to drive the metabolic switch between FAO and glycolysis. Conclusions: Our findings revealed that AKR1C3-dependent LD formation is critical for the adaptation to sorafenib in HCC through regulating lipid and energy homeostasis. AKR1C3-dependent LD accumulation protects HCC cells from sorafenib-induced mitochondrial lipotoxicity by regulating lipophagy. Targeting AKR1C3 might be a promising therapeutic strategy for HCC tumors.PMID:36451864 | PMC:PMC9706585 | DOI:10.7150/thno.74974

Theranostics. 2022 Nov 14;12(18):7775-7787. doi: 10.7150/thno.76805. eCollection 2022.ABSTRACTRationale: The efficacy and mechanism of hydroxyurea in the treatment of atherosclerosis have rarely been reported. The goal of this study was to investigate the efficacy of hydroxyurea in high-fat diet-fed ApoE-/- mice against atherosclerosis and examine the possible mechanism underlying treatment outcomes. Methods: ApoE-/- mice were fed a high-fat diet for 1 month and then administered hydroxyurea by gavage continuously for 2 months. Aortic root hematoxylin-eosin (H&E) staining and oil red O staining were used to verify the efficacy of hydroxyurea; biochemical methods and ELISA were used to detect changes in relevant metabolites in serum. 16S rRNA was used to detect composition changes in the intestinal bacterial community of animals after treatment with hydroxyurea. Metabolomics methods were used to identify fecal metabolites and their changes. Immunohistochemical staining and ELISA were used for the localization and quantification of intestinal NPC1L1. Results: We showed that aortic root HE staining and oil red O staining determined the therapeutic efficacy of hydroxyurea in the treatment of atherosclerosis in high-fat diet-fed ApoE-/- mice. Serological tests verified the ability of hydroxyurea to lower total serum cholesterol and LDL cholesterol. The gut microbiota was significantly altered after HU treatment and was significantly different from that after antiplatelet and statin therapy. Meanwhile, a metabolomic study revealed that metabolites, including stearic acid, palmitic acid and cholesterol, were significantly enriched in mouse feces. Further histological and ELISAs verified that the protein responsible for intestinal absorption of cholesterol in mice, NPC1L1, was significantly reduced after hydroxyurea treatment. Conclusions: In high-fat diet-fed ApoE-/- mice, hydroxyurea effectively treated atherosclerosis, lowered serum cholesterol, modulated the gut microbiota at multiple levels and affected cholesterol absorption by reducing NPC1L1 in small intestinal epithelial cells.PMID:36451858 | PMC:PMC9706578 | DOI:10.7150/thno.76805

J Agric Food Chem. 2022 Nov 30. doi: 10.1021/acs.jafc.2c06055. Online ahead of print.ABSTRACTNeonicotinoids can control crop pests with high efficiency and low cost and have quickly swept one-fourth of the global insecticide market since the launch of imidacloprid in 1991. Imidacloprid and acetamiprid, the first generation of neonicotinoids, and dinotefuran, the representative of third generation of neonicotinoids, were applied on tomato plants individually to investigate neonicotinoid effects on tomato fruit quality, especially on appearance parameters, sugar, acid, and aroma compounds. Compared with the control, fewer differences in the transcriptome profile, sugar, acid, and volatile organic compound (VOC) contents, and sensory analysis results were shown in dinotefuran treatments than in the other two treatments. Therefore, dinotefuran was more recommended to control pests of tomatoes with less loss of fruit flavor and quality as well as lower ecological risks.PMID:36451590 | DOI:10.1021/acs.jafc.2c06055

Environ Microbiol. 2022 Nov 30. doi: 10.1111/1462-2920.16292. Online ahead of print.ABSTRACTThe symbioses between plants of the Rubiaceae and Primulaceae families with Burkholderia bacteria represent unique and intimate plant-bacterial relationships. Many of these interactions have been identified through PCR-dependent typing methods, but there is little information available about their functional and ecological roles. We assembled seventeen new endophyte genomes representing endophytes from thirteen plant species, including those of two previously unknown associations. Genomes of leaf endophytes belonging to Burkholderia s.l. show extensive signs of genome reduction, albeit to varying degrees. Except for one endophyte, none of the bacterial symbionts could be isolated on standard microbiological media. Despite their taxonomic diversity, all endophyte genomes contained gene clusters linked to the production of specialized metabolites, including genes linked to cyclitol sugar analog metabolism and in one instance non-ribosomal peptide synthesis. These genes and gene clusters are unique within Burkholderia s.l. and are likely horizontally acquired. We propose that the acquisition of secondary metabolite gene clusters through horizontal gene transfer is a prerequisite for the evolution of a stable association between these endophytes and their hosts.PMID:36451580 | DOI:10.1111/1462-2920.16292

New Phytol. 2022 Nov 30. doi: 10.1111/nph.18651. Online ahead of print.ABSTRACTPlant specialized metabolism is complex, with frequent examples of highly branched biosynthetic pathways and shared chemical intermediates. As such, many plant specialized metabolic networks are poorly characterized. The N-methyl Δ1 -pyrrolinium cation, is a simple pyrrolidine alkaloid and precursor of pharmacologically important tropane alkaloids. Silencing of pyrrolidine ketide synthase (AbPyKS) in the roots of Atropa belladonna (Deadly Nightshade) reduces tropane alkaloid abundance and causes high N-methyl Δ1 -pyrrolinium cation accumulation. The consequences of this metabolic shift on alkaloid metabolism are unknown. In this study, we utilized discovery metabolomics coupled with AbPyKS silencing to reveal major changes in the root alkaloid metabolome of A. belladonna. We discovered and annotated almost 40 pyrrolidine alkaloids that increase when AbPyKS activity is reduced. Suppression of phenyllactate biosynthesis, combined with metabolic engineering in planta, and chemical synthesis, indicates several of these pyrrolidines share a core structure formed through the non-enzymatic Mannich-like decarboxylative condensation of the N-methyl Δ1 -pyrrolinium cation with 2-O-malonylphenyllactate. Decoration of this core scaffold through hydroxylation and glycosylation leads to mono- and dipyrrolidine alkaloid diversity. This study reveals previously unknown complexity of the A. belladonna root metabolome and creates a foundation for future investigation into the biosynthesis, function, and potential utility of these novel alkaloids.PMID:36451537 | DOI:10.1111/nph.18651

Phytother Res. 2022 Nov 30. doi: 10.1002/ptr.7681. Online ahead of print.ABSTRACTSaussurea involucrata oral liquid (SIOL) can clinically relieve symptoms, such as joint pain and swelling, and morning stiffness, in patients with rheumatoid arthritis (RA). However, the mechanism of action remains unclear. This study used a combination of gut microbiota and serum metabolomics analysis to investigate the effects and potential mechanisms of SIOL intervention on rats with RA induced by type II bovine collagen and Freund's complete adjuvant. Results showed that SIOL treatment consequently improved the degree of ankle joint swelling, joint histopathological changes, joint pathological score, and expression of serum-related inflammatory cytokines (interleukin (IL)-1β, IL-4, IL-6, IL-10, and tumor necrosis factor-α) in RA model rats. 16 S rRNA sequencing results showed that SIOL increased the relative richness of the Lactobacillus and Bacteroides genus and decreased the relative richness of Romboutsia, Alloprevotella, Blautia, and Helicobacter genus. Serum nontargeted metabolomic results indicated that SIOL could regulate metabolites related to metabolic pathways, such as glycine, serine, threonine, galactose, cysteine, and methionine metabolism. Spearman correlation analysis showed that the regulatory effects of SIOL on the tricarboxylic acid (TCA) cycle, phenylalanine metabolism, phenylalanine, tyrosine, and tryptophan biosynthesis, and glyoxylate and dicarboxylate metabolism pathways were correlated with changes in the richness of the Lactobacillus, Romboutsia, Bacteroides, and Alloprevotella genus in the gut microbiome. In conclusion, this study revealed the ameliorative effects of SIOL on RA and suggested that the therapeutic effects of SIOL on RA may be related to the regulation of the community richness of the Lactobacillus, Romboutsia, Bacteroides, and Alloprevotella genus, thereby improving the TCA cycle; phenylalanine metabolism; phenylalanine, tyrosine, and tryptophan biosynthesis, and glyoxylate and dicarboxylate metabolism-related pathways.PMID:36451529 | DOI:10.1002/ptr.7681

BMC Plant Biol. 2022 Nov 30;22(1):552. doi: 10.1186/s12870-022-03930-0.ABSTRACTBACKGROUND: Salinization is major abiotic stress limiting cotton production. Melatonin (MT) has been implicated in salt stress tolerance in multiple crops including upland cotton. Here, we explored the transcriptomic and metabolomic response of a salt-tolerant self-bred high-yielding cotton line SDS-01, which was exogenously sprayed with four MT concentrations (50, 100, 200, and 500 μM).RESULTS: Here we found that MT improves plant biomass and growth under salt stress. The combined transcriptome sequencing and metabolome profiling approach revealed that photosynthetic efficiency is improved by increasing the expressions of chlorophyll metabolism and antenna proteins in MT-treated seedlings. Additionally, linoleic acid and flavonoid biosynthesis were improved after MT treatment. The Na+/K+ homeostasis-related genes were increasingly expressed in salt-stressed seedlings treated with MT as compared to the ones experiencing only salt stress. Melatonin treatment activated a cascade of plant-hormone signal transduction and reactive oxygen scavenging genes to alleviate the detrimental effects of salt stress. The global metabolome profile revealed an increased accumulation of flavonoids, organic acids, amino acids and derivatives, saccharides, and phenolic acids in MT-treated seedlings. Interestingly, N, N'-Diferuloylputrescine a known antioxidative compound was highly accumulated after MT treatment.CONCLUSION: Collectively, our study concludes that MT is a salt stress regulator in upland cotton and alleviates salt-stress effects by modulating the expressions of photosynthesis (and related pathways), flavonoid, ROS scavenging, hormone signaling, linoleic acid metabolism, and ion homeostasis-related genes.PMID:36451095 | DOI:10.1186/s12870-022-03930-0

Metabolomics. 2022 Nov 30;18(12):100. doi: 10.1007/s11306-022-01955-y.ABSTRACTINTRODUCTION: Testosterone administration attenuates reductions in total body mass and lean mass during severe energy deficit (SED).OBJECTIVES: This study examined the effects of testosterone administration on the serum metabolome during SED.METHODS: In a double-blind, placebo-controlled clinical trial, non-obese men were randomized to receive 200-mg testosterone enanthate/wk (TEST) (n = 24) or placebo (PLA) (n = 26) during a 28-d inpatient, severe exercise- and diet-induced energy deficit. This study consisted of three consecutive phases. Participants were free-living and provided a eucaloric diet for 14-d during Phase 1. During Phase 2, participants were admitted to an inpatient unit, randomized to receive testosterone or placebo, and underwent SED for 28-d. During Phase 3, participants returned to their pre-study diet and physical activity habits. Untargeted metabolite profiling was conducted on serum samples collected during each phase. Body composition was measured using dual-energy X-ray absorptiometry after 11-d of Phase 1 and after 25-d of Phase 2 to determine changes in fat and lean mass.RESULTS: TEST had higher (Benjamini-Hochberg adjusted, q < 0.05) androgenic steroid and acylcarnitine, and lower (q < 0.05) amino acid metabolites after SED compared to PLA. Metabolomic differences were reversed by Phase 3. Changes in lean mass were associated (Bonferroni-adjusted, p < 0.05) with changes in androgenic steroid metabolites (r = 0.42-0.70), acylcarnitines (r = 0.37-0.44), and amino acid metabolites (r = - 0.36-- 0.37). Changes in fat mass were associated (p < 0.05) with changes in acylcarnitines (r = - 0.46-- 0.49) and changes in urea cycle metabolites (r = 0.60-0.62).CONCLUSION: Testosterone administration altered androgenic steroid, acylcarnitine, and amino acid metabolites, which were associated with changes in body composition during SED.PMID:36450940 | DOI:10.1007/s11306-022-01955-y

Chem Pharm Bull (Tokyo). 2022;70(12):859-862. doi: 10.1248/cpb.c21-01037.ABSTRACTThe root of Paeonia lactiflora (PAEONIAE RADIX) is a constituent of the traditional Japanese medicines (Kampo) and is known to have various effects. Peony roots cultivated in Japan and China are available in the Japanese market for medicinal use. In this study, the chemical diversity of ten available peony roots in the market that differed in their cultivation area was investigated using 1H-NMR metabolomics techniques. Principal component analysis and hierarchical cluster analysis of the 1H-NMR spectra of the peony roots methanolic extracts revealed a clear difference between the metabolic profiles of Japanese and Chinese peony roots. By preparative procedures using chromatography based on 1H-NMR spectra measurements, oxypaeoniflorin and (+)-catechin were found to be specific compounds for Japanese peony root. All peony roots used in this study were listed in the Japanese Pharmacopoeia. Therefore, the differences in the constituents of these peony roots might be attributed to growing conditions than differences in species. Cultivation conditions also influence the quality of natural medicines.PMID:36450583 | DOI:10.1248/cpb.c21-01037

Chem Pharm Bull (Tokyo). 2022;70(12):840-847. doi: 10.1248/cpb.c22-00105.ABSTRACTIn order to investigate the relationship between the chemical composition of essential oils and haplotypes of the psbA-trnH intergenic spacer region of chloroplast DNA (psbA-trnH) in Valerianae Fauriei Radix (Japanese Valerian; JV), we analyzed the DNA sequence and GC-MS metabolome of JV from Japanese markets and of herbal specimens from related species. DNA analysis revealed that JV products from Japan consisted of three haplotypes, namely AH-1, -2 and -5 reported in our previous study. The GC-MS metabolome revealed five chemotypes (J1, J2, C, K and O), of which J1, J2 and C were detected in the JV products from Japan. Chemotypes J1 and J2, with kessyl glycol diacetate (KGD) as the main volatile component, were found in the products of Japanese origin whereas chemotype C, with 1-O-acetyl-2,10-bisaboladiene-1,6-diol (ABD), was found in the products of Chinese and Korean origin. The haplotypes were correlated with the chemotypes: haplotype AH-1 for chemotype J1, AH-2 for chemotype J2 and AH-5 for chemotype C, suggesting that the chemical diversity of JV is not attributed to the environmental factors rather to the genetic factors. Since KGD and ABD were reported to have sedative effects and nerve growth factor (NGF)-potentiating effects, respectively, understanding the chemotypes and selecting an appropriate one would be important for the application of JV. The psbA-trnH haplotypes could be useful DNA markers for the quality control and standardization of JV.PMID:36450581 | DOI:10.1248/cpb.c22-00105

Clin Chim Acta. 2022 Nov 27:S0009-8981(22)01393-6. doi: 10.1016/j.cca.2022.11.026. Online ahead of print.ABSTRACTIndividuals with sickle cell disease (SCD) often experience numerous vaso-occlusive crisis events throughout their lives, which can progress to severe damage of several organs, including avascular necrosis, also known as osteonecrosis (ON). Osteonecrosis is one of the most devastating musculoskeletal clinical manifestations of sickle cell disease, afflicting up to 50% of the SCD patients. Herein, a NMR-based untargeted metabolomics approach was used to assess the metabolome alterations of blood plasma and bone marrow interstitial fluid (BMIF) samples of SCD patients with osteonecrosis. Furthermore, biochemical signatures associated with different osteonecrosis stages were assessed by analysing the metabolome of blood plasma and bone marrow interstitial fluid samples of SCD patients with different stages of the disease based on the Fiat and Arlet classification (FAC). Multivariate statistical analysis allowed a clear discrimination between the studied groups and it provided important insights into the different osteonecrosis stages. Citrate was pointed out as a possible biomarker to differentiate SCD patients with and without osteonecrosis. Acetate, creatinine, histidine, tyrosine, glucose, and NI5 seems to be key metabolites associated to different stages of the disease. Although this is a pioneer exploratory study, we acknowledge that fact that it is limited by the group sizes and absence of a validation cohort. Nevertheless, multivariate statistical analyses indicated that the metabolome of blood plasma and BMIF samples encompasses a complex metabolic regulation system for osteonecrosis.PMID:36450311 | DOI:10.1016/j.cca.2022.11.026

Annu Rev Plant Biol. 2022 Nov 30. doi: 10.1146/annurev-arplant-062922-050122. Online ahead of print.ABSTRACTPlants' ability to chemically modify core structures of specialized metabolites is the main reason why the plant kingdom contains such a wide and rich array of diverse compounds. One of the most important types of chemical modifications of small molecules is the addition of an acyl moiety to produce esters and amides. Large-scale phylogenomics analyses have shown that the enzymes that perform acyl transfer reactions on the myriad small molecules synthesized by plants belong to only a few gene families. This review is focused on describing the biochemistry, evolutionary origins, and chemical ecology implications of one of these families-the BAHD acyltransferases. The growth of advanced metabolomic studies coupled with next-generation sequencing of diverse plant species has confirmed that the BAHD family plays critical roles in modifying nearly all known classes of specialized metabolites. The current and future outlook for research on BAHDs includes expanding their roles in synthetic biology and metabolic engineering. Expected final online publication date for the Annual Review of Plant Biology, Volume 74 is May 2023. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.PMID:36450296 | DOI:10.1146/annurev-arplant-062922-050122

Cell Rep. 2022 Nov 29;41(9):111727. doi: 10.1016/j.celrep.2022.111727.ABSTRACTHistone methyltransferase SETD1A is critical for acute myeloid leukemia (AML) cell survival, but the molecular mechanism driving SETD1A gene regulation remains elusive. To delineate the role of SETD1A, we utilize a protein degrader technology to induce rapid SETD1A degradation in AML cell lines. SETD1A degradation results in immediate downregulation of transcripts associated with DNA repair and heme biosynthesis pathways. CRISPR-based functional analyses and metabolomics reveal an essential role of SETD1A to maintain mitochondrial respiration in AML cells. These SETD1A targets are enriched in head-to-head (H2H) genes. SETD1A degradation disrupts a non-enzymatic SETD1A domain-dependent cyclin K function, increases the Ser5P RNA polymerase II (RNAPII) at the transcriptional start site (TSS), and induces the promoter-proximal pausing of RNAPII in a strand-specific manner. This study reveals a non-enzymatic role for SETD1A in transcriptional pause release and provides insight into the mechanism of RNAPII pausing and its function in cancer.PMID:36450243 | DOI:10.1016/j.celrep.2022.111727

Proc Natl Acad Sci U S A. 2022 Dec 6;119(49):e2208458119. doi: 10.1073/pnas.2208458119. Epub 2022 Nov 30.ABSTRACTDetermining mechanism of action (MOA) is one of the biggest challenges in natural products discovery. Here, we report a comprehensive platform that uses Similarity Network Fusion (SNF) to improve MOA predictions by integrating data from the cytological profiling high-content imaging platform and the gene expression platform Functional Signature Ontology, and pairs these data with untargeted metabolomics analysis for de novo bioactive compound discovery. The predictive value of the integrative approach was assessed using a library of target-annotated small molecules as benchmarks. Using Kolmogorov-Smirnov (KS) tests to compare in-class to out-of-class similarity, we found that SNF retains the ability to identify significant in-class similarity across a diverse set of target classes, and could find target classes not detectable in either platform alone. This confirmed that integration of expression-based and image-based phenotypes can accurately report on MOA. Furthermore, we integrated untargeted metabolomics of complex natural product fractions with the SNF network to map biological signatures to specific metabolites. Three examples are presented where SNF coupled with metabolomics was used to directly functionally characterize natural products and accelerate identification of bioactive metabolites, including the discovery of the azoxy-containing biaryl compounds parkamycins A and B. Our results support SNF integration of multiple phenotypic screening approaches along with untargeted metabolomics as a powerful approach for advancing natural products drug discovery.PMID:36449542 | DOI:10.1073/pnas.2208458119

PLoS One. 2022 Nov 30;17(11):e0278259. doi: 10.1371/journal.pone.0278259. eCollection 2022.ABSTRACTDysregulation of the gut microbiome has been shown to perpetuate neuroinflammation, alter intestinal permeability, and modify repetitive mild traumatic brain injury (RmTBI)-induced deficits. However, there have been no investigations regarding the comparative effects that the microbiome may have on RmTBI in adolescents and adults. Therefore, we examined the influence of microbiome depletion prior to RmTBI on microbial composition and metabolome, in adolescent and adult Sprague Dawley rats. Rats were randomly assigned to standard or antibiotic drinking water for 14 days, and to subsequent sham or RmTBIs. The gut microbiome composition and metabolome were analysed at baseline, 1 day after the first mTBI, and at euthanasia (11 days following the third mTBI). At euthanasia, intestinal samples were also collected to quantify tight junction protein (TJP1 and occludin) expression. Adolescents were significantly more susceptible to microbiome depletion via antibiotic administration which increased pro-inflammatory composition and metabolites. Furthermore, RmTBI induced a transient increase in 'beneficial bacteria' (Lachnospiraceae and Faecalibaculum) in only adolescents that may indicate compensatory action in response to the injury. Finally, microbiome depletion prior to RmTBI generated a microbiome composition and metabolome that exemplified a potentially chronic pathogenic and inflammatory state as demonstrated by increased Clostridium innocuum and Erysipelatoclostridium and reductions in Bacteroides and Clostridium Sensu Stricto. Results highlight that adolescents are more vulnerable to RmTBI compared to adults and dysbiosis prior to injury may exacerbate secondary inflammatory cascades.PMID:36449469 | DOI:10.1371/journal.pone.0278259

MAGMA. 2022 Nov 30. doi: 10.1007/s10334-022-01049-9. Online ahead of print.ABSTRACTOBJECTIVE: An early metabolic signature associated with the responsiveness to treatment can be useful in the better management of septic shock patients. This would help clinicians in designing personalized treatment protocols for patients showing non-responsiveness to treatment.METHODS: We analyzed the serum on Day 1 (n = 60), Day 3 (n = 47), and Day 5 (n = 26) of patients with septic shock under treatment using NMR-based metabolomics. Partial least square discriminant analysis (PLS-DA) was performed to generate the list of metabolites that can be identified as potential disease biomarkers having statistical significance (that is, metabolites that had a VIP score > 1, and p value < 0.05, False discovery rate (FDR) < 0.05).RESULTS: Common significant metabolites amongst the three time points were obtained that distinguished the patients being responsive (R) and non-responsive (NR) to treatments, namely 3 hydroxybutyrate, lactate, and phenylalanine which were lower, whereas glutamate and choline higher in patients showing responsiveness.DISCUSSION: The study gave these metabolic signatures identifying patients' responsiveness to treatment. The results of the study will aid in the development of targeted therapy for ICU patients.PMID:36449125 | DOI:10.1007/s10334-022-01049-9

Food Funct. 2022 Nov 30. doi: 10.1039/d2fo01948e. Online ahead of print.ABSTRACTInvestigation of phytochemicals and bioactive molecules is tremendously vital for the applications of new plant resources in chemistry, food, and medicine. In this study, the chemical profiling of sap of Acer mono (SAM), a Korean syrup known for its anti-osteoporosis effect, was performed using UPLC-ESI-Q-TOF-MSE analysis. A total of 23 compounds were identified based on the mass and fragmentation characteristics and most of the compounds have significant biomedical applications. The in vitro antioxidant assessment of SAM indicated excellent activity by scavenging DPPH and ABTS-free radicals and were found to be 23.35 mg mL-1 and 29.33 mg mL-1, respectively, as IC50 concentrations. As well, the in vitro proliferation effect of the SAM was assessed against mouse MC3T3-E1 cells, and the results showed that the SAM enhanced the proliferation of the cells, and 12.5 mg mL-1 and 25 mg mL-1 of SAM were selected for osteogenic differentiation. The morphological analysis clearly evidenced the SAM enhanced the osteogenic activity in MC3T3-E1 cells by the increased deposition of extracellular calcium and nodule formation. Moreover, the qRT-PCR analysis confirmed the increased expression of osteoblast marker gene expression including ALP, osteocalcin, osteopontin, collagen1α1, Runx2, and osterix in SAM-treated MC3T3-E1 cells. Together, these results suggest that SAM possesses osteogenic effects and can be used for bone regeneration and bone loss-associated diseases such as osteoporosis.PMID:36449013 | DOI:10.1039/d2fo01948e

J Med Food. 2022 Nov;25(11):1038-1049. doi: 10.1089/jmf.2022.K.0014.ABSTRACTBuyang-huanwu decoction (BHD) is a classic prescription that has great potential to be developed into antifatigue functional food. It may activate blood circulation to relieve fatigue in some clinical cases by unclear mechanisms. In this study, a metabolomics approach was conducted to investigate the antifatigue mechanism of BHD. The murine fatigue model was established in rats by endurance swimming, and hemorheology, blood biochemistry, and ultraperformance liquid chromatography-mass spectrometry-based metabolomics were conducted on serum samples. The rate of weight gain, hemorheological parameters, and serum creatine kinase activities were significantly altered in model rats and they returned to a normal level after BHD administration. Pattern recognition screened 18 potential biomarkers, which are mainly involved in glycerophospholipid, arachidonic acid, and cholesterol metabolisms. The results demonstrate that the antifatigue mechanism of BHD is mainly related to the function of enhancing nerve conduction, relieving inflammation and regulating cholesterol metabolism and energy metabolism.PMID:36448732 | DOI:10.1089/jmf.2022.K.0014

Arch Insect Biochem Physiol. 2022 Nov 30:e21987. doi: 10.1002/arch.21987. Online ahead of print.ABSTRACTFull-length cDNAs of the Broad-Complex (BR-C) from Riptortus pedestris were cloned. Moreover, Kr-h1 and BR-C expression levels in apo-symbiotic and symbiotic host insects were compared to verify whether they are modulated by Burkholderia gut symbionts. Interestingly, Kr-h1 expression level was significantly increased in symbiotic females. To determine how Kr-h1 affects fecundity in insects, the biosynthesis of two reproduction-associated proteins, hexamerin-α and vitellogenin, was investigated in R. pedestris females. Hexamerin-α and vitellogenin expression at the transcriptional and translational levels decreased in Kr-h1-suppressed symbiotic females, subsequently reduced egg production. These results suggest that Burkholderia gut symbiont modulates Kr-h1 expression to enhance ovarian development and egg production of R. pedestris by increasing the biosynthesis of the two proteins.PMID:36448663 | DOI:10.1002/arch.21987