PubMed

Front Genet. 2022 Nov 15;13:1041078. doi: 10.3389/fgene.2022.1041078. eCollection 2022.ABSTRACTCIPKs are a subclass of serine/threonine (Ser/Thr) protein kinases. CBLs are ubiquitous Ca2+ sensors that interact with CIPK with the aid of secondary Ca2+ messengers for regulation of growth and development and response to stresses faced by plants. The divergent roles of the CIPK-CBL interaction in plants include responding to environmental stresses (salt, cold, drought, pH, ABA signaling, and ion toxicity), ion homeostasis (K+, NH4 +, NO3 -, and microelement homeostasis), biotic stress, and plant development. Each member of this gene family produces distinct proteins that help plants adapt to diverse stresses or stimuli by interacting with calcium ion signals. CIPK consists of two structural domains-an N-terminal domain and a C-terminal domain-connected by a junction domain. The N-terminal domain, the site of phosphorylation, is also called the activation domain and kinase domain. The C-terminal, also known as the regulatory domain of CIPK, further comprises NAF/FISL and PPI. CBL comprises four EF domains and conserved PFPF motifs and is the site of binding with the NAF/FISL domain of CIPK to form a CBL-CIPK complex. In addition, we also performed a bibliometric analysis of the CIPK gene family of data extracted from the WoSCC. A total of 95 documents were retrieved, which had been published by 47 sources. The production over time was zigzagged. The top key terms were gene, CIPK, abiotic stress, and gene expression. Beijing Forestry University was the top affiliation, while The Plant Cell was the top source. The genomics and metabolomics of this gene family require more study.PMID:36457742 | PMC:PMC9705351 | DOI:10.3389/fgene.2022.1041078

Allergol Select. 2022 Nov 21;6:267-275. doi: 10.5414/ALX02333E. eCollection 2022.ABSTRACTAllergic rhinitis is an IgE-mediated inflammation that remains a clinical challenge, affecting 40% of the UK population with a wide range of severity from nasal discomfort to life-threatening anaphylaxis. It can be managed by pharmacotherapeutics and in selected patients by allergen immunotherapy (AIT), which provides long-term clinical efficacy, especially during peak allergy season. However, there are no definitive biomarkers for AIT efficacy. Here, we aim to summarize the key adaptive, innate, humoral, and metabolic advances in biomarker identification in response to AIT. Mechanisms of efficacy consist of an immune deviation towards TH1-secreting IFN-γ, as well as an induction of IL10+ cTFR and TREG have been observed. TH2 cells undergo exhaustion after AIT due to chronic allergen exposure and correlates with the exhaustion markers PD-1, CTLA-4, TIGIT, and LAG3. IL10+ DCREG expressing C1Q and STAB are induced. KLRG1+ IL10+ ILC2 were shown to be induced in AIT in correlation with efficacy. BREG cells secreting IL-10, IL-35, and TGF-β are induced. Blocking antibodies IgG, IgA, and IgG4 are increased during AIT; whereas inflammatory metabolites, such as eicosanoids, are reduced. There are multiple promising biomarkers for AIT currently being evaluated. A panomic approach is essential to better understand cellular, molecular mechanisms and their correlation with clinical outcomes. Identification of predictive biomarkers of AIT efficacy will hugely impact current practice allowing physicians to select eligible patients that are likely to respond to treatment as well as improve patients' compliance to complete the course of treatment.PMID:36457722 | PMC:PMC9707369 | DOI:10.5414/ALX02333E

Front Plant Sci. 2022 Nov 15;13:1051935. doi: 10.3389/fpls.2022.1051935. eCollection 2022.ABSTRACTINTRODUCTION: Cotton straw biochar (biochar) and compound Bacillus biofertilizer (biofertilizer) have attracted wide attentions in the remediation of heavy metal-contaminated soils in recent years. However, few studies have explored the metabolomics of lateral roots of Cd-stressed cotton to determine the mechanism of biochar and biofertilizer alleviating Cd stress.METHODS: In this pot experiment, biochar and biofertilizer were applied to the soils with different Cd contamination levels (1, 2, and 4 mg kg-1). Then, the responses of cotton root morphology, vitality, Cd content, and antioxidant enzyme activities were analyzed, and the mechanism of biochar and biofertilizer alleviating Cd stress was determined by metabolomic analysis.RESULTS: The results showed that exogenous Cd addition decreased the SOD and POD activities in cotton taproot and lateral root. Besides, with the increase of soil Cd content, the maximum Cd content in taproot (0.0250 mg kg-1) and lateral root (0.0288 mg kg-1) increased by 89.11% and 33.95%, respectively compared with those in the control (p< 0.05). After the application of biochar and biofertilizer, the SOD and POD activities in cotton taproot and lateral root increased. The Cd content of cotton taproot in biochar and biofertilizer treatments decreased by 16.36% and 19.73%, respectively, and that of lateral root decreased by 13.99% and 16.68%, respectively. The metabolomic analysis results showed that the application of biochar and biofertilizer could improve the resistance of cotton root to Cd stress through regulating the pathways of ABC transporters and phenylalanine metabolism.DISCUSSION: Therefore, the application of biochar and biofertilizer could improve cotton resistance to Cd stress by increasing antioxidant enzyme activities, regulating root metabolites (phenols and amino acids), and reducing Cd content, thus promoting cotton root growth.PMID:36457531 | PMC:PMC9705756 | DOI:10.3389/fpls.2022.1051935

Front Plant Sci. 2022 Nov 15;13:1045270. doi: 10.3389/fpls.2022.1045270. eCollection 2022.ABSTRACTThe abscission of plant organs plays an important role in ensuring the normal life activities. Rose is one of the most important ornamental plants, and its premature abscission of petal has seriously affected the quality and commercial value. Silver Thiosulfate (STS) is an ethylene inhibitor, which is often used preservative to delay the senescence of fresh cut flowers. To understand the regulatory mechanism of petal abscission in rose by STS, integrative analysis of the metabolome and transcriptome profiles was performed in abscission zone (AZ) tissues of rose under different treatments (MOCK, STS, ETH, STS+ETH). The results showed that STS significantly delayed the petal abscission in phenotype and reduced the activity of two enzymes (pectinase and cellulase) associated with cell wall degradation in physiological level. STS affected the contents of five metabolites (shikonin, jasmonic acid, gluconolactone, stachyose and D-Erythrose 4-phosphate), and involved changes in the expression of 39 differentially expressed genes (DEGs) associated with these five metabolites. Five DEGs (LOC112192149, LOC112196726, LOC112189737, LOC112188495, and LOC112188936) were probably directly associated with the biosynthesis of shikonin, jasmonic acid, and D-Erythrose 4-phosphate. Meanwhile, the effect of STS on the abscission process significantly involved in the pentose phosphate pathway and amino acid biosynthesis pathway. In addition, STS had a greater effect on the transcription factors, phytohormone related DEGs represented by auxin and ethylene, DEGs related to disease resistance and amino acid, etc. Above all, STS negatively influences petal abscission of rose, these results maybe provide a reference for subsequent studies on petal abscission of rose by STS.PMID:36457520 | PMC:PMC9706100 | DOI:10.3389/fpls.2022.1045270

Front Oncol. 2022 Nov 15;12:1058436. doi: 10.3389/fonc.2022.1058436. eCollection 2022.ABSTRACTBACKGROUND: Lung cancer is the leading malignant disease and cause of cancer-related death worldwide. Most patients with lung cancer had insignificant early symptoms so that most of them were diagnosed at an advanced stage. In addition to factors such as smoking, pollution, lung microbiome and its metabolites play vital roles in the development of lung cancer. However, the interaction between lung microbiota and carcinogenesis is lack of systematically characterized and controversial. Therefore, the purpose of this study was to excavate the features of the lung microbiota and metabolites in patients and verify potential biomarkers for lung cancer diagnosis.METHODS: Lung tissue flushing solutions and bronchoalveolar lavage fluid samples came from patients with lung cancer and non-lung cancer. The composition and variations of the microbiota and metabolites in samples were explored using muti-omics technologies including 16S rRNA amplicon sequencing, metagenomics and metabolomics.RESULTS: The metabolomics analysis indicated that 40 different metabolites, such as 9,10-DHOME, sphingosine, and cysteinyl-valine, were statistically significant between two groups (VIP > 1 and P < 0.05). These metabolites were significantly enriched into 11 signal pathways including sphingolipid, autophagy and apoptosis signaling pathway (P < 0.05). The analysis of lung microbiota showed that significant changes reflected the decrease of microbial diversity, changes of distribution of microbial taxa, and variability of the correlation networks of lung microbiota in lung cancer patients. In particular, we found that oral commensal microbiota and multiple probiotics might be connected with the occurrence and progression of lung cancer. Moreover, our study found 3 metabolites and 9 species with significantly differences, which might be regarded as the potential clinical diagnostic markers associated with lung cancer.CONCLUSIONS: Lung microbiota and metabolites might play important roles in the pathogenesis of lung cancer, and the altered metabolites and microbiota might have the potential to be clinical diagnostic markers and therapeutic targets associated with lung cancer.PMID:36457513 | PMC:PMC9705781 | DOI:10.3389/fonc.2022.1058436

Front Public Health. 2022 Nov 15;10:962510. doi: 10.3389/fpubh.2022.962510. eCollection 2022.ABSTRACTCurrently, there are no particularly effective biomarkers to distinguish between latent tuberculosis infection (LTBI) and active pulmonary tuberculosis (PTB) and evaluate the outcome of TB treatment. In this study, we have characterized the changes in the serum metabolic profiles caused by Mycobacterium tuberculosis (Mtb) infection and standard anti-TB treatment with isoniazid-rifampin-pyrazinamide-ethambutol (HRZE) using GC-MS and LC-MS/MS. Seven metabolites, including 3-oxopalmitic acid, akeboside ste, sulfolithocholic acid, 2-decylfuran (4,8,8-trimethyldecahydro-1,4-methanoazulen-9-yl)methanol, d-(+)-camphor, and 2-methylaminoadenosine, were identified to have significantly higher levels in LTBI and untreated PTB patients (T0) than those in uninfected healthy controls (Un). Among them, akeboside Ste and sulfolithocholic acid were significantly decreased in PTB patients with 2-month HRZE (T2) and cured PTB patients with 2-month HRZE followed by 4-month isoniazid-rifampin (HR) (T6). Receiver operator characteristic curve analysis revealed that the combined diagnostic model showed excellent performance for distinguishing LT from T0 and Un. By analyzing the biochemical and disease-related pathways, we observed that the differential metabolites in the serum of LTBI or TB patients, compared to healthy controls, were mainly involved in glutathione metabolism, ascorbate and aldarate metabolism, and porphyrin and chlorophyll metabolism. The metabolites with significant differences between the T0 group and the T6 group were mainly enriched in niacin and nicotinamide metabolism. Our study provided more detailed experimental data for developing laboratory standards for evaluating LTBI and cured PTB.PMID:36457328 | PMC:PMC9705731 | DOI:10.3389/fpubh.2022.962510

Cancer Metab. 2022 Dec 1;10(1):21. doi: 10.1186/s40170-022-00296-7.ABSTRACTBACKGROUND: Research about tumor "metabolic flexibility"-the ability of cells to toggle between preferred nutrients depending on the metabolic context-has largely focused on obesity-associated cancers. However, increasing evidence for a key role for nutrient competition in the tumor microenvironment, as well as for substrate regulation of immune function, suggests that substrate metabolism deserves reconsideration in immunogenic tumors that are not strongly associated with obesity.METHODS: We compare two murine models: immunologically cold YUMM1.7 and immunologically-hot YUMMER1.7. We utilize stable isotope and radioisotope tracer-based metabolic flux studies as well as gas and liquid chromatography-based metabolomics analyses to comprehensively probe substrate preference in YUMM1.7 and YUMMER1.7 cells, with a subset of studies on the impact of available metabolites across a panel of five additional melanoma cell lines. We analyze bulk RNA-seq data and identify increased expression of amino acid and glucose metabolism genes in YUMMER1.7. Finally, we analyze melanoma patient RNA-seq data to identify potential prognostic predictors rooted in metabolism.RESULTS: We demonstrate using stable isotope tracer-based metabolic flux studies as well as gas and liquid chromatography-based metabolomics that immunologically-hot melanoma utilizes more glutamine than immunologically-cold melanoma in vivo and in vitro. Analyses of human melanoma RNA-seq data demonstrate that glutamine transporter and other anaplerotic gene expression positively correlates with lymphocyte infiltration and function.CONCLUSIONS: Here, we highlight the importance of understanding metabolism in non-obesity-associated cancers, such as melanoma. This work advances the understanding of the correlation between metabolism and immunogenicity in the tumor microenvironment and provides evidence supporting metabolic gene expression as potential prognostic factors of melanoma progression and may inform investigations of adjunctive metabolic therapy in melanoma.TRIAL REGISTRATION: Deidentified data from The Cancer Genome Atlas were analyzed.PMID:36457136 | DOI:10.1186/s40170-022-00296-7

Biol Proced Online. 2022 Dec 1;24(1):20. doi: 10.1186/s12575-022-00184-w.ABSTRACTChemically diverse in compounds, urine can give us an insight into metabolic breakdown products from foods, drinks, drugs, environmental contaminants, endogenous waste metabolites, and bacterial by-products. Hundreds of them are volatile compounds; however, their composition has never been provided in detail, nor has the methodology used for urine volatilome untargeted analysis. Here, we summarize key elements for the untargeted analysis of urine volatilome from a comprehensive compilation of literature, including the latest reports published. Current achievements and limitations on each process step are discussed and compared. 34 studies were found retrieving all information from the urine treatment to the final results obtained. In this report, we provide the first specific urine volatilome database, consisting of 841 compounds from 80 different chemical classes.PMID:36456991 | DOI:10.1186/s12575-022-00184-w

BMC Microbiol. 2022 Dec 1;22(1):287. doi: 10.1186/s12866-022-02704-w.ABSTRACTBACKGROUND: Gut microbiota dysbiosis is associated with the development of non-alcoholic steatohepatitis (NASH) through modulation of gut barrier, inflammation, lipid metabolism, bile acid signaling and short-chain fatty acid production. The aim of this study was to describe the impact of a choline-deficient amino acid defined high fat diet (CDAHFD) on the gut microbiota in a male Göttingen Minipig model and on selected pathways implicated in the development of NASH.RESULTS: Eight weeks of CDAHFD resulted in a significantly altered colon microbiota mainly driven by the bacterial families Lachnospiraceae and Enterobacteriaceae, being decreased and increased in relative abundance, respectively. Metabolomics analysis revealed that CDAHFD decreased colon content of short-chain fatty acid and increased colonic pH. In addition, serum levels of the microbially produced metabolite imidazole propionate were significantly elevated as a consequence of CDAHFD feeding. Hepatic gene expression analysis showed upregulation of mechanistic target of rapamycin (mTOR) and Ras Homolog, MTORC1 binding in addition to downregulation of insulin receptor substrate 1, insulin receptor substrate 2 and the glucagon receptor in CDAHFD fed minipigs. Further, the consequences of CDAHFD feeding were associated with increased levels of circulating cholesterol, bile acids, and glucagon but not total amino acids.CONCLUSIONS: Our results indicate imidazole propionate as a new potentially relevant factor in relation to NASH and discuss the possible implication of gut microbiota dysbiosis in the development of NASH. In addition, the study emphasizes the need for considering the gut microbiota and its products when developing translational animal models for NASH.PMID:36456963 | DOI:10.1186/s12866-022-02704-w

Microb Cell Fact. 2022 Dec 1;21(1):253. doi: 10.1186/s12934-022-01978-z.ABSTRACTBACKGROUND: Despite decades of engineering efforts, recombinant Saccharomyces cerevisiae are still less efficient at converting D-xylose sugar to ethanol compared to the preferred sugar D-glucose. Using GFP-based biosensors reporting for the three main sugar sensing routes, we recently demonstrated that the sensing response to high concentrations of D-xylose is similar to the response seen on low concentrations of D-glucose. The formation of glycolytic intermediates was hypothesized to be a potential cause of this sensing response. In order to investigate this, glycolysis was disrupted via the deletion of the phosphoglucose isomerase gene (PGI1) while intracellular sugar phosphate levels were monitored using a targeted metabolomic approach. Furthermore, the sugar sensing of the PGI1 deletants was compared to the PGI1-wildtype strains in the presence of various types and combinations of sugars.RESULTS: Metabolomic analysis revealed systemic changes in intracellular sugar phosphate levels after deletion of PGI1, with the expected accumulation of intermediates upstream of the Pgi1p reaction on D-glucose and downstream intermediates on D-xylose. Moreover, the analysis revealed a preferential formation of D-fructose-6-phosphate from D-xylose, as opposed to the accumulation of D-fructose-1,6-bisphosphate that is normally observed when PGI1 deletants are incubated on D-fructose. This may indicate a role of PFK27 in D-xylose sensing and utilization. Overall, the sensing response was different for the PGI1 deletants, and responses to sugars that enter the glycolysis upstream of Pgi1p (D-glucose and D-galactose) were more affected than the response to those entering downstream of the reaction (D-fructose and D-xylose). Furthermore, the simultaneous exposure to sugars that entered upstream and downstream of Pgi1p (D-glucose with D-fructose, or D-glucose with D-xylose) resulted in apparent synergetic activation and deactivation of the Snf3p/Rgt2p and cAMP/PKA pathways, respectively.CONCLUSIONS: Overall, the sensing assays indicated that the previously observed D-xylose response stems from the formation of downstream metabolic intermediates. Furthermore, our results indicate that the metabolic node around Pgi1p and the level of D-fructose-6-phosphate could represent attractive engineering targets for improved D-xylose utilization.PMID:36456947 | DOI:10.1186/s12934-022-01978-z

BMC Genomics. 2022 Dec 1;23(1):789. doi: 10.1186/s12864-022-09044-z.ABSTRACTBACKGROUND: The exact mechanism of atrial fibrillation (AF)-induced heart failure (HF) remains unclear. Proteomics and metabolomics were integrated to in this study, as to describe AF patients' dysregulated proteins and metabolites, comparing patients without HF to patients with HF.METHODS: Plasma samples of 20 AF patients without HF and another 20 with HF were analyzed by multi-omics platforms. Proteomics was performed with data independent acquisition-based liquid chromatography-tandem mass spectrometry (LC-MS/MS), as metabolomics was performed with LC-MS/MS platform. Proteomic and metabolomic results were analyzed separately and integrated using univariate statistical methods, multivariate statistical methods or machine learning model.RESULTS: We found 35 up-regulated and 15 down-regulated differentially expressed proteins (DEPs) in AF patients with HF compared to AF patients without HF. Moreover, 121 up-regulated and 14 down-regulated differentially expressed metabolites (DEMs) were discovered in HF patients compared to AF patients without HF. An integrated analysis of proteomics and metabolomics revealed several significantly enriched pathways, including Glycolysis or Gluconeogenesis, Tyrosine metabolism and Pentose phosphate pathway. A total of 10 DEPs and DEMs selected as potential biomarkers provided excellent predictive performance, with an AUC of 0.94. In addition, subgroup analysis of HF classification was performed based on metabolomics, which yielded 9 DEMs that can distinguish between AF and HF for HF classification.CONCLUSIONS: This study provides novel insights to understanding the mechanisms of AF-induced HF progression and identifying novel biomarkers for prognosis of AF with HF by using metabolomics and proteomics analyses.PMID:36456901 | DOI:10.1186/s12864-022-09044-z

Handb Exp Pharmacol. 2022 Dec 2. doi: 10.1007/164_2022_619. Online ahead of print.ABSTRACTMetabolomics has long been used in a biomedical context. The most typical samples are body fluids in which small molecules can be detected and quantified using technologies such as Nuclear Magnetic Resonance (NMR) and Mass Spectrometry (MS). Many studies, in particular in the wider field of cancer research, are based on cellular models. Different cancer cells can have vastly different ways of regulating metabolism and responses to drug treatments depend on specific metabolic mechanisms which are often cell type specific. This has led to a series of publications using metabolomics to study metabolic mechanisms. Cell-based metabolomics has specific requirements and allows for interesting approaches where metabolism is followed in real-time. Here applications of metabolomics in cell biology have been reviewed, providing insight into specific technologies used and showing exemplary case studies with an emphasis towards applications which help to understand drug mechanisms.PMID:36456700 | DOI:10.1007/164_2022_619

Sci Rep. 2022 Dec 1;12(1):20789. doi: 10.1038/s41598-022-24935-7.ABSTRACTCentell-S is a water-soluble extract of Centella asiatica containing more than 80% w/w triterpenoid glycosides. Madecassoside and asiaticoside are two major components of the extract and can be converted into active metabolites, triterpenic acids in large mammal species. In this study, the pharmacokinetic profiles and metabolomic changes generated by the bioactive triterpenoids of Centell-S alone, and in combination with the bioenhancers piperine and curcumin, were investigated in beagle dogs. The test substances were orally administered over multiple doses for 7 consecutive days. At day 1 and 7 after receiving the test compounds, the level of major bioactive triterpenoids and related metabolites were measured using triple quadrupole and high-resolution accurate mass orbitrap models of LCMS to determine pharmacokinetic and metabolomic profiles, respectively. Centell-S was well tolerated, alone and in all combination groups. The combination of Centell-S and piperine significantly increased (p < 0.05) the systemic exposure of madecassoside on day 1 and asiatic acid on day 7, by approximately 1.5 to 3.0-fold of Cmax and AUC values as compared to the Centell-S alone, while the addition of curcumin did not provide a significant improvement. Several metabolomic changes were observed from pre-dose to 4 h post-dose, with some biomarkers of neurodegenerative diseases including L-glutamine, lysophosphatidylcholine (17:0), taurochenodeoxycholic acid, uric acid, stearic acid, palmitic acid, and lactic acid showing good correlation with the systemic exposure of the bioactive triterpenoids (asiatic acid). Thus, the combining of piperine to Centell-S exhibits the improvement of bioactive triterpenoids which are related to the biomarkers of neurodegenerative diseases. These promising results might be useful for the development of this standardised extract to become a more effective phytomedicine for neurodegenerative diseases.PMID:36456663 | DOI:10.1038/s41598-022-24935-7

Comp Biochem Physiol C Toxicol Pharmacol. 2022 Nov 28:109526. doi: 10.1016/j.cbpc.2022.109526. Online ahead of print.ABSTRACTFluoride (F) is an environmental pollutant that continues to threaten human health. Long-term or excessive fluoride exposure can cause a series of acute or chronic systemic and organ-specific diseases. The liver is considered to be one of the important target organs of fluoride poisoning, however, the specific cause of liver damage caused by fluoride is still unclear. In the present study, we identified ferroptosis as a key mechanism of fluoride-induced liver injury. Under fluorosis conditions, lipid peroxidation levels in the liver are significantly increased and iron overload is induced. Combined transcriptomic and metabolomic analysis revealed that activation of the SIRT1/FOXOs pathway is one of the main causes of fluorosis-induced liver damage. Further analysis by in vitro experiments showed that the SIRT1/FOXOs pathway can cause the activation of the Nrf2/HO-1 pathway under the condition of fluorosis, and can activate the P53-dependent ferroptosis pathway, leading to the occurrence of lipid peroxidation and iron accumulation, ultimately leading to ferroptosis. Our study provides insight into the mechanism of fluoride-induced liver injury, and our results also provide strategies for treatment to alleviate liver injury caused by fluorosis.PMID:36455829 | DOI:10.1016/j.cbpc.2022.109526

Environ Pollut. 2022 Nov 28:120765. doi: 10.1016/j.envpol.2022.120765. Online ahead of print.ABSTRACTAcetamiprid, a commonly detected neonicotinoid in aquatic ecosystems, poses a threat to aquatic non-target organisms. However, limited information is available on the toxic effects of acetamiprid on nontarget aquatic organisms. This study assessed the toxic effects of acetamiprid on Xenopus laevis, a typical model organism. The acute toxicity for 96 h revealed that acetamiprid had detrimental effects with a median lethal concentration (LC50) value of 64.48 mg/L. Toxicity assays, including oxidative stress, histopathology and untargeted metabolomics of acetamiprid to X. laevis, were performed for 28 d at 1/10 and 1/100 LC50 by studying the liver, which is the most antioxidant and major metabolic organ. The results demonstrated that acetamiprid exposure significantly changed the oxidant status of and caused histological damage to the liver. Furthermore, the untargeted metabolomic analysis based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) identified the endogenous metabolites that were significantly altered. There were 89 differential metabolites compared to the controls: 64 in the 1/10 LC50 group, 47 in the 1/100 LC50 group, and 23 metabolites in the 1/10 LC50 group were the same as those in the 1/100 LC50 group. Sixteen pathways that were mainly associated with amino acid metabolism and lipid metabolism, such as sphingolipid metabolism, glycerophospholipid metabolism and histidine metabolism, were disrupted, revealing the hepatotoxic effects of acetamiprid on X. laevis at the molecular level. These findings provide crucial information for evaluating the aquatic risks of neonicotinoids.PMID:36455769 | DOI:10.1016/j.envpol.2022.120765

Sci Total Environ. 2022 Nov 28:160430. doi: 10.1016/j.scitotenv.2022.160430. Online ahead of print.ABSTRACTPhosphate, as the main nutrient factor of lake eutrophication brought by pollutants discharged from agriculture and industry, is always considered to be a low-toxicity substance to aquatic animals. But the toxicity mechanism is unclear, and published information is limited. In this study, a 96 h acute stress experiment was conducted on juvenile turbot (Scophthalmus maximus) with 0, 10, and 60 mg/L phosphate solutions. Metabonomic analysis revealed that low-dose phosphate (10 mg/L) disrupted glycerophospholipid, purine, and glycolipid metabolism, as well as the tricarboxylic acid (TCA) cycle in juveniles, even at 96 h of stress, which may lead to cell structure damage and signal recognition disorder between cells. Upregulated key genes in the main glycerophospholipid metabolic pathways, which matched the results of the metabolomic study, were detected. Furthermore, low-dose phosphate (10 mg/L) induced oxidative stress and immunotoxicity in fish, resulting in the raising of relevant genes expression such as cat and sod in liver and kidney. In addition, all phosphate-treated groups had induced lesions on gill tissue, as evidenced by pathological observations. In this study on toxic effects on and mechanism of phosphate in aquatic animals using metabolomics, gene expression, and histopathology, we confirm that acute low-dose phosphate could disrupt glycerophospholipid metabolism and induce stress in juvenile turbot. This can provide advice on the amount of phosphate accumulation for marine fish farming and on protecting species diversity and marine ecosystem from the point of view of phosphate toxicity to marine animals.PMID:36455734 | DOI:10.1016/j.scitotenv.2022.160430

Endocr Pract. 2022 Nov 28:S1530-891X(22)00871-0. doi: 10.1016/j.eprac.2022.11.009. Online ahead of print.ABSTRACTOBJETIVE: To compare body composition in patients with autonomous cortisol secretion (ACS), non-functioning adrenal incidentalomas (NFAIs) and controls without adrenal tumours.METHODS: Cross-sectional study of 3 groups: patients with ACS (cortisol post-dexamethasone suppression test (DST) >1.8μg/dL), NFAIs (cortisol post-DST ≤1.8μg/dL) and patients without adrenal tumours (controls). Patients of the three groups were matched according to age (±5 years-old), sex and body mass index (±5kg/m2). Body composition was evaluated by bioelectrical impedance and abdominal CT and urinary steroid profile (USP) by gas chromatography mass spectrometry.RESULTS: 25 patients with ACS, 24 NFAIs and 24 controls were enrolled. Based on CT images, a weak positive correlation between serum cortisol post-DST and subcutaneous fat area (r=0.3, P=0.048) was found. As assessed by bioelectrical impedance, lean mass and bone mass were positively correlated with the excretion of total androgens (r=0.56, P<0.001; and r=0.58, P<0.001, respectively); and visceral mass was positively correlated with the excretion of glucocorticoid metabolites and total glucocorticoids (r=0.28, P=0.031; and r=0.42, P=0.001, respectively). Based on CT imaging evaluation, a positive correlation was observed between lean mass and androgen metabolites (r=0.30, P=0.036); and between visceral fat area, total fat area, and visceral/total fat area ratio and the excretion of glucocorticoid metabolites (r=0.34, P=0.014; r=0.29, P=0.042; and r=0.31, P=0.170, respectively).CONCLUSION: The USP observed in adrenal tumours, which consists in a low excretion of androgen metabolites and high excretion of glucocorticoid metabolites, is associated with a lower lean mass and bone mass and higher level of visceral mass in patients with adrenal tumours.PMID:36455692 | DOI:10.1016/j.eprac.2022.11.009

Life Sci. 2022 Nov 28:121249. doi: 10.1016/j.lfs.2022.121249. Online ahead of print.ABSTRACTAIMS: Statins, cholesterol-lowering drugs, are potential therapeutic agents for inhibiting cancer proliferation. However, the mechanisms that mediate the effects of statins, the homeostatic responses of tumor cells to statin therapy, and the modes underlying the antitumor effects of statins remain unclear.MAIN METHODS: To uncover the effects of statins on cancer cells in vitro, we performed transcriptome and metabolome analyses on atorvastatin-treated statin-resistant and statin-sensitive lung cancer cells.KEY FINDINGS: The results of Gene Ontology terms and pathway enrichment analyses showed that after 24 h of atorvastatin treatment, the expression of cell cycle- and DNA replication-related genes was significantly decreased in the statin-sensitive cancer cells. The results of metabolome analysis showed that the components of polyamine metabolism and purine metabolism, glycolysis, and pentose phosphate pathway were decreased in the statin-sensitive cancer cells.SIGNIFICANCE: Differences in cellular properties between statin-sensitive and statin-resistant cancer cells revealed additional candidates for therapeutic targets in statin-treated cancer cells and suggested that inhibiting these metabolic pathways could improve efficacy. In conclusion, combining statins with inhibitors of polyamine metabolism (cell proliferation and protein translation), purine metabolism (DNA synthesis), glycolytic system (energy production), and pentose phosphate pathway (antioxidant stress) might enhance the anticancer effects of statins.PMID:36455649 | DOI:10.1016/j.lfs.2022.121249

FEMS Yeast Res. 2022 Dec 1:foac061. doi: 10.1093/femsyr/foac061. Online ahead of print.ABSTRACTMy career developed very differently from those of most academic researchers. After school I worked for six years in industries that employed yeast to manufacture ethanol and beer. At university I was trained as a microbiologist with very little training in molecular biology. I retrained in 1987 in molecular yeast genetics and focused on genetic engineering of industrial yeasts to minimise the production of spoilage compounds in wine and ethyl carbamate, a carcinogen, in wine. The malolactic yeast ML01 and the urea-degrading yeast were the first genetically enhanced yeasts that obtained US FDA approval for commercial applications. Apart from applied research, I was fascinated by classic molecular yeast genetic studies using sophisticated techniques such as transcriptomics, proteomics, and metabolomics. Doing research at the University of British Columbia was stimulating and exciting, we established a core microarray and metabolomics facilities that were used by many scientists at UBC and hospitals in Vancouver. I also established a state-of-the-art Wine Library that was used to study aging of wines produced in British Columbia. Finally, I have been fortunate to know and collaborate with leading yeast scientists who motivated me.PMID:36455588 | DOI:10.1093/femsyr/foac061

Mar Pollut Bull. 2022 Nov 28;186:114395. doi: 10.1016/j.marpolbul.2022.114395. Online ahead of print.ABSTRACTMarine heatwaves (MHWs) have increased in intensity and frequency in global oceans, causing deleterious effects on many marine organisms and ecosystems they support. Bivalves are among the most vulnerable taxonomic groups to intensifying MHWs, yet little is known about the underlying mechanisms. Here, we investigated the impact of MHWs on the digestive metabolism of pearl oysters (Pinctada maxima). Two moderate and severe scenarios of MHWs were performed by increasing seawater temperature respectively from 24 °C to 28 °C and 32 °C for 3 days. When subjected to MHWs and with increasing intensity, pearl oysters significantly enhanced their digestive enzymatic activities, such as lipase and amylase. LC-MS-based metabolomics revealed negative responses in the lipid metabolism (e.g., steroid biosynthesis, glycerophospholipid metabolism, and sphingolipid metabolism), the amino acid metabolism (e.g., glutamate, histidine, arginine, and proline), and the B-vitamins metabolism. These findings indicate that the digestive metabolism of marine bivalves can likely succumb to intensifying MHWs events.PMID:36455501 | DOI:10.1016/j.marpolbul.2022.114395