PubMed

Front Biosci (Landmark Ed). 2022 Oct 28;27(10):294. doi: 10.31083/j.fbl2710294.ABSTRACTEnvironmental toxicogenomics aims to collect, analyze and interpret data on changes in gene expression and protein activity resulting from exposure to toxic substances using high-performance omics technologies. Molecular profiling methods such as genomics, transcriptomics, proteomics, metabolomics, and bioinformatics techniques, permit the simultaneous analysis of a multitude of gene variants in an organism exposed to toxic agents to search for genes prone to damage, detect patterns and mechanisms of toxicity, and identify specific gene expression profiles that can provide biomarkers of exposure and risk. Compared to previous approaches to measuring molecular changes caused by toxicants, toxicogenomic technologies can improve environmental risk assessment while reducing animal studies. We discuss the prospects and limitations of converting omic datasets into valuable information, focusing on assessing the risks of mixed toxic substances to the environment and human health.PMID:36336867 | DOI:10.31083/j.fbl2710294

New Phytol. 2022 Nov 6. doi: 10.1111/nph.18602. Online ahead of print.ABSTRACTAuxin phytohormone has a role in most aspects of the life of a land plant and is found even in ancient plants such as single-cell green algae. Auxin's ubiquitous but specific effects have been mainly explained by the extraordinary ability of plants to interpret spatiotemporal patterns of auxin concentrations via the regulation of gene transcription. This is thought to be achieved through the combinatorial effects of two families of nuclear co-receptor proteins, i.e., the TIR1/AFBs and AUX/IAAs. Recent evidence has suggested transcription-independent roles of TIR1/AFBs localized outside the nucleus and TMK-based auxin signaling occurring in the plasma membrane. Furthermore, emerging evidence supports a coordinated action of the intra- and extra-nuclear auxin signaling pathways to regulate specific auxin responses. Here, we highlight how auxin signaling acts inside and outside the nucleus for the regulation of growth and morphogenesis and propose that the future direction of auxin biology lies in the elucidation of a new collaborative paradigm of intra- and extra-nuclear auxin signaling.PMID:36336825 | DOI:10.1111/nph.18602

New Phytol. 2022 Nov 6. doi: 10.1111/nph.18601. Online ahead of print.ABSTRACTPlants produce a wide diversity of metabolites. Yet our understanding of how shifts in plant metabolites as a response to climate change feedback on ecosystem processes remains scarce. Here, we test to what extent climate warming shifts the seasonality of metabolites produced by Sphagnum mosses, and what are the consequences of these shifts for peatland C uptake. We used a reciprocal transplant experiment along a climate gradient in Europe to simulate climate change. We evaluated the responses of primary and secondary metabolites in five Sphagnum species and related their responses to gross ecosystem productivity (GEP). When transplanted to a warmer climate, Sphagnum species showed consistent responses to warming, with an up-regulation of either their primary or secondary metabolites according to seasons. Moreover, these shifts were correlated to changes in GEP, especially in spring and autumn. Our results indicate that the Sphagnum metabolome is very plastic and sensitive to warming. We also show that warming-induced changes in the seasonality of Sphagnum metabolites have consequences on peatland GEP. Our findings demonstrate the capacity for plant metabolic plasticity to impact ecosystem C processes and reveal a further mechanism through which Sphagnum could shape peatland responses to climate change.PMID:36336780 | DOI:10.1111/nph.18601

Comp Biochem Physiol C Toxicol Pharmacol. 2022 Nov 3:109501. doi: 10.1016/j.cbpc.2022.109501. Online ahead of print.ABSTRACTDepression is a common mental disorder that can adversely affect psychosocial function and quality of life. However, the exact aetiology and pathogenesis of depression are still unclear. Stress plays a major role in the pathogenesis of depression. The use of currently prescribed antidepressants has many side effects. Centella asiatica (C. asiatica) has shown promising antidepressant activity in rodent models. Here, we developed a reserpine-induced zebrafish stress-like model and performed behavioural analysis, cortisol measurement and 1H-Nuclear Magnetic Resonance (1H NMR) spectroscopy-based metabolomics analysis to test the anti-stress activity of ethanolic extract of C. asiatica (RECA). A significant increase in total distance travelled (F(8,8) = 8.905, p = 0.0054) and a reduction in freezing duration (F(9, 9) = 10.38, p = 0.0018) were found in the open field test (OFT). Asiaticoside, one of tested C.asiatica's triterpenoid gives a significant increase in contact duration (F(5,5) = 142.3, (p = 0.0330) at 2.5 mg/kg). Eight biomarkers were found, i.e. ß-hydroxyisovaleric acid, leucine, threonine, scylloinositol, lactate, betaine, valine, choline and l-fucose, to be responsible for the class separation between stress and RECA-treated groups. Metabolic pathway alteration in zebrafish brain upon treatment with RECA was identified as valine, leucine and isoleucine biosynthesis, while alanine, aspartate, glutamate and glycerophospholipid metabolism was involved after fluoxetine treatment.PMID:36336330 | DOI:10.1016/j.cbpc.2022.109501

Int J Cardiol. 2022 Nov 3:S0167-5273(22)01688-6. doi: 10.1016/j.ijcard.2022.11.001. Online ahead of print.NO ABSTRACTPMID:36336191 | DOI:10.1016/j.ijcard.2022.11.001

J Biotechnol. 2022 Nov 3:S0168-1656(22)00264-4. doi: 10.1016/j.jbiotec.2022.11.002. Online ahead of print.ABSTRACTLactobacillus rhamnosus GG (LGG) is one of the most widely used probiotics because of its health benefits and safety. Fucose is among the most abundant hexoses in the human intestine, and LGG consumes fucose to produce energy or proliferate. However, no study has elucidated the metabolism by which LGG metabolizes fucose to produce energy, biomass, and extracellular metabolites. We used metabolomics and flux balance analysis to elucidate these mechanisms and highlight how they might affect the host. We found three different metabolic flux modes by which LGG anaerobically metabolizes fucose to produce energy and biomass. These metabolic flux modes differ from homolactic or heterolactic fermentation and account for the production of lactic acid, 1,2-propanediol, acetic acid, formic acid, and carbon dioxide as a result of fucose metabolism in LGG. We also used gas chromatography/time-of-flight mass spectrometry to identify a variety of short-chain fatty acids and organic acids secreted during fucose metabolism by LGG. Our study is the first to elucidate the unique fucose metabolism of LGG in anaerobic condition.PMID:36336085 | DOI:10.1016/j.jbiotec.2022.11.002

Bioorg Chem. 2022 Oct 29;130:106229. doi: 10.1016/j.bioorg.2022.106229. Online ahead of print.ABSTRACTLiver cancer has characteristics of high morbidity, high mortality, and poor prognosis. Metabolic reprogramming is a prominent characteristic of tumors and plays a key role in promoting tumorigenesis. The metabolic process of liver cancer cells has undergone many significant changes including abnormal active glycolysis, enhanced de novo synthesis of fatty acids, and hyperactive metabolism of amino acids and nucleotides. Targeting metabolic reprogramming through regulation of anomalously expressed key metabolic enzymes and signaling molecules is considered to be an important strategy for liver cancer treatment. Multi-omics association analyses currently facilitate precise diagnosis, personalized clinical therapy, and revelation of mechanisms of drug action. Cinobufagin, as the major anti-tumor active ingredient of Chansu, the famous chinese medicine used in clinic for cancer treatment, has been reported to exert anticancer effects through many different kinds of mechanisms, but the effects of cinobufagin on metabolic reprogramming of cancer cells still remain unclear. In our study, we identify that cinobufagin exhibits anti-hepatoma effects through interfering with metabolic reprogramming (lipid, amino acid, carbohydrate, and nucleotide metabolism) based on integrated transcriptomics and metabolomics analyses. Furthermore, the results of integrated multi-omics analyses enrich various core regulatory mechanisms of anti-tumor effects of cinobufagin which are associated with metabolic pathway. In addition, some verifications of the enriched mechanisms related to intervention of lipid and carbohydrate metabolism in response to cinobufagin are also performed. This work will promote the innovation of the research model of TCM, and lay a solid theoretical foundation for the clinical application of cinobufagin and Chansu.PMID:36335648 | DOI:10.1016/j.bioorg.2022.106229

J Transl Med. 2022 Nov 5;20(1):510. doi: 10.1186/s12967-022-03717-9.ABSTRACTBACKGROUND: Diabetic kidney disease (DKD) is among the most important causes for chronic kidney disease. Anthocyanins (ANT) are polyphenolic compounds present in various food and play an important role in ameliorating hyperglycemia and insulin sensitivity. However, the effects of ANT in DKD are still poorly understood. This study aimed to investigate the effect of ANT (cyanidin-3-O-glucoside [C3G]) on the renal function of DKD, and whether the anti-DKD effect of ANT is related to metabolic pathways.METHODS: To explore the role of ANT in DKD, we performed the examination of blood glucose, renal function, and histopathology. As for the mechanism, we designed the label-free quantification proteomics and nontargeted metabolomics analysis for kidney and serum. Subsequently, we revealed the anti-DKD effect of ANT through the bioinformatic analysis.RESULTS: We showed that the fasting blood glucose level (- 6.1 mmol/L, P = 0.037), perimeter of glomerular lesions (- 24.1 μm, P = 0.030), fibrosis score of glomerular (- 8.8%, P = 0.002), and kidney function (Cystatin C: - 701.4 pg/mL, P = 0.043; urine creatinine: - 701.4 mmol/L, P = 0.032) were significantly alleviated in DKD mice after ANT treatment compared to untreated in the 20th week. Further, proteins and metabolites in the kidneys of DKD mice were observed to be dramatically altered due to changes in amino acid metabolism with ANT treatment; mainly, taurine and hypotaurine metabolism pathway was upregulated (P = 0.0001, t value = 5.97). Furthermore, upregulated tryptophan metabolism (P < 0.0001, t value = 5.94) and tyrosine metabolism (P = 0.0037, t value = 2.91) pathways had effects on serum of DKD mice as responsed ANT regulating.CONCLUSIONS: Our results suggested that prevention of the progression of DKD by ANT could be related to the regulation of amino acid metabolism. The use of dietary ANT may be one of the dietary strategies to prevent and treat DKD.PMID:36335368 | DOI:10.1186/s12967-022-03717-9

Sci Rep. 2022 Nov 5;12(1):18776. doi: 10.1038/s41598-022-23544-8.ABSTRACTSepsis is defined as a dysregulated host response to infection leading to organs failure. Among them, sepsis induces skeletal muscle (SM) alterations that contribute to acquired-weakness in critically ill patients. Proteomics and metabolomics could unravel biological mechanisms in sepsis-related organ dysfunction. Our objective was to characterize a distinctive signature of septic shock in human SM by using an integrative multi-omics approach. Muscle biopsies were obtained as part of a multicenter non-interventional prospective study. Study population included patients in septic shock (S group, with intra-abdominal source of sepsis) and two critically ill control populations: cardiogenic shock (C group) and brain dead (BD group). The proteins and metabolites were extracted and analyzed by High-Performance Liquid Chromatography-coupled to tandem Mass Spectrometry, respectively. Fifty patients were included, 19 for the S group (53% male, 64 ± 17 years, SAPS II 45 ± 14), 12 for the C group (75% male, 63 ± 4 years, SAPS II 43 ± 15), 19 for the BD group (63% male, 58 ± 10 years, SAPS II 58 ± 9). Biopsies were performed in median 3 days [interquartile range 1-4]) after intensive care unit admission. Respectively 31 patients and 40 patients were included in the proteomics and metabolomics analyses of 2264 proteins and 259 annotated metabolites. Enrichment analysis revealed that mitochondrial pathways were significantly decreased in the S group at protein level: oxidative phosphorylation (adjusted p = 0.008); branched chained amino acids degradation (adjusted p = 0.005); citrate cycle (adjusted p = 0.005); ketone body metabolism (adjusted p = 0.003) or fatty acid degradation (adjusted p = 0.008). Metabolic reprogramming was also suggested (i) by the differential abundance of the peroxisome proliferator-activated receptors signaling pathway (adjusted p = 0.007), and (ii) by the accumulation of fatty acids like octanedioic acid dimethyl or hydroxydecanoic. Increased polyamines and depletion of mitochondrial thioredoxin or mitochondrial peroxiredoxin indicated a high level of oxidative stress in the S group. Coordinated alterations in the proteomic and metabolomic profiles reveal a septic shock signature in SM, highlighting a global impairment of mitochondria-related metabolic pathways, the depletion of antioxidant capacities, and a metabolic shift towards lipid accumulation.ClinicalTrial registration: NCT02789995. Date of first registration 03/06/2016.PMID:36335235 | DOI:10.1038/s41598-022-23544-8

Nat Commun. 2022 Nov 5;13(1):6688. doi: 10.1038/s41467-022-34558-1.ABSTRACTChromosomal translocation generates the MLL-AF4 fusion gene, which causes acute leukemia of multiple lineages. MLL-AF4 is a strong oncogenic driver that induces leukemia without additional mutations and is the most common cause of pediatric leukemia. However, establishment of a murine disease model via retroviral transduction has been difficult owning to a lack of understanding of its regulatory mechanisms. Here, we show that MLL-AF4 protein is post-transcriptionally regulated by RNA-binding proteins, including those of KHDRBS and IGF2BP families. MLL-AF4 translation is inhibited by ribosomal stalling, which occurs at regulatory sites containing AU-rich sequences recognized by KHDRBSs. Synonymous mutations disrupting the association of KHDRBSs result in proper translation of MLL-AF4 and leukemic transformation. Consequently, the synonymous MLL-AF4 mutant induces leukemia in vivo. Our results reveal that post-transcriptional regulation critically controls the oncogenic activity of MLL-AF4; these findings might be valuable in developing novel therapies via modulation of the activity of RNA-binding proteins.PMID:36335100 | DOI:10.1038/s41467-022-34558-1

Mol Metab. 2022 Nov 2:101628. doi: 10.1016/j.molmet.2022.101628. Online ahead of print.ABSTRACTOBJECTIVE: Internal clocks time behavior and physiology, including the gut microbiome, in a circadian (∼24 h) manner. Mismatch between internal and external time, e.g. during shift work, disrupts circadian system coordination promoting the development of obesity and type 2 diabetes (T2D). Conversely, body weight changes induce microbiota dysbiosis. The relationship between circadian disruption and microbiota dysbiosis in metabolic diseases, however, remains largely unknown.METHODS: Core and accessory clock gene expression in different gastrointestinal (GI) tissues were determined by qPCR in two different models of circadian disruption - mice with Bmal1 deficiency in the circadian pacemaker, the suprachiasmatic nucleus (Bmal1SCNfl/-), and wild-type mice exposed to simulated shift work (SSW). Body composition and energy balance were evaluated by nuclear magnetic resonance (NMR), bomb calorimetry, food intake and running-wheel activity. Intestinal permeability was measured in an Ussing chamber. Microbiota composition and functionality were evaluated by 16S rRNA gene amplicon sequencing, PICRUST2.0 analysis and targeted metabolomics. Finally, microbiota transfer was conducted to evaluate the functional impact of SSW-associated microbiota on the host's physiology.RESULTS: Both chronodisruption models show desynchronization within and between peripheral clocks in GI tissues and reduced microbial rhythmicity, in particular in taxa involved in short-chain fatty acid (SCFA) fermentation and lipid metabolism. In Bmal1SCNfl/- mice, loss of rhythmicity in microbial functioning associates with previously shown increased body weight, dysfunctional glucose homeostasis and adiposity. Similarly, we observe an increase in body weight in SSW mice. Germ-free colonization experiments with SSW-associated microbiota mechanistically link body weight gain to microbial changes. Moreover, alterations in expression of peripheral clock genes as well as clock-controlled genes (CCGs) relevant for metabolic functioning of the host were observed in recipients, indicating a bidirectional relationship between microbiota rhythmicity and peripheral clock regulation.CONCLUSIONS: Collectively, our data suggest that loss of rhythmicity in bacteria taxa and their products, which likely originates in desynchronization of intestinal clocks, promotes metabolic abnormalities during shift work.PMID:36334897 | DOI:10.1016/j.molmet.2022.101628

J Adv Res. 2022 Nov 2:S2090-1232(22)00244-2. doi: 10.1016/j.jare.2022.10.015. Online ahead of print.ABSTRACTINTRODUCTION: Microplastic pollution seriously threatens the health and safety of humans and wildlife. Avian is one of the main species endangered by microplastics. However, the damage mechanism of microplastics to the digestive system of avian is not clear.OBJECTIVES: The gut-liver axis is a bidirectional channel that regulates the exchange of information between the gut and the liver and is also a key target for tissue damage caused by pollutants. This study aimed to elucidate the digestive toxicity of microplastics in avian and the key role of the gut-liver axis in it.METHODS: We constructed an exposure model for microplastics in environmental concentrations and toxicological concentrations in chickens and reveal the digestive toxicity of polystyrene microplastics (PS-MPs) in avian by 16S rRNA, transcriptomics and metabolomics.RESULTS: PS-MPs changed the death mode from apoptosis to necrosis and pyroptosis by upregulating Caspase 8, disrupting the intestinal vascular barrier, disturbing the intestinal flora and promoting the accumulation of lipopolysaccharide. Harmful flora and metabolites were translocated to the liver through the liver-gut axis, eliciting hepatic immune responses and promoting hepatic lipid metabolism disorders and apoptosis. Liver injury involves multiple molecular effects of mitochondrial dynamics disturbance, oxidative stress, endoplasmic reticulum stress, and cell cycle disturbance. Furthermore, metabolomics suggested that caffeine and melanin metabolites may be potential natural resistance substances for microplastics CONCLUSION: Taken together, our data demonstrate the digestive damage of PS-MPs in avian, revealing a critical role of the liver-gut axis in it. This will provide a reference for protecting the safety of avian populations.PMID:36334886 | DOI:10.1016/j.jare.2022.10.015

Toxicology. 2022 Nov 2:153370. doi: 10.1016/j.tox.2022.153370. Online ahead of print.ABSTRACTCyanobacterial blooms, usually dominated by Microcystis aeruginosa, pose a serious threat to global freshwater ecosystems owing to their production and release of various harmful secondary metabolites. Detection of the chemicals in M. aeruginosa exudates using metabolomics technology revealed that phytosphingosine (PHS) was one of the most abundant compounds. However, its specific toxicological mechanism remained unclear. CNE-2 cells were selected to illustrate the cytotoxic mechanism of PHS, and it was determined to cause excessive production of reactive oxygen species and subsequently damage the mitochondrial structure. Mitochondrial membrane rupture led to matrix mitochondrial membrane potential disintegration, which induced Ca2+ overload and interrupted ATP synthesis. Furthermore, rupture of the mitochondrial membrane induced the opening of the permeability transition pore, which caused the release of proapoptotic factors into the cytoplasm and the expression of apoptosis-related proteins Bax, Bcl-2, cytochrome-c and cleaved caspase-3 in CNE-2 cells. These events, in turn, activated the mitochondrially mediated intrinsic apoptotic pathway. A mitochondrial repair mechanism, namely, PINK1/Parkin-mediated mitophagy, was then blocked, which further promoted apoptosis. Our findings suggest that more attention should be paid to the ecotoxicity of PHS, which is already listed as a contaminant of emerging concern.PMID:36334778 | DOI:10.1016/j.tox.2022.153370

Environ Pollut. 2022 Nov 2:120544. doi: 10.1016/j.envpol.2022.120544. Online ahead of print.ABSTRACTThe toxicity of microplastics (MPs) to marine microalgae has raised much concern. However, research at metabolic level is quite limited. In this study, the physiological and metabolic effects of polystyrene (PS) and aged polystyrene (A-PS) MPs on Dunaliella salina were investigated. Both PS and A-PS inhibited the growth of microalgae, but promoted the pigment synthesis in algal cells. The oxidative stress analysis indicated that PS and A-PS induced high production of reactive oxygen species (ROS), and caused oxidative damage to algal cells. Particularly, the highest ROS level in PS and A-PS groups were 1.70- and 2.24-fold of that in the control group, respectively. Untargeted metabolomics analysis indicated that PS and A-PS significantly increased the differential metabolites. Compared with the control group, the significant upregulation of glycerophospholipids metabolites illustrated that severe membrane lipid peroxidation occurred in the MPs groups. Metabolic pathways analysis showed that PS and A-PS perturbed the amino acid-related metabolic pathways. In particular, the amino acid biosynthesis and ATP-binding cassette (ABC) transporter pathways were significantly upregulated, thus promoting nitrogen storage and transmembrane transport in Dunaliella salina. Transmembrane transport requires a large amount of ATP; as a result, algal cell division is inhibited. In addition, A-PS stimulated more active glutathione metabolism than PS. These results enrich the understanding of the toxicity of PS MPs to microalgae at the metabolic level, and are helpful for further assessing the ecological impacts of MPs on microalgae.PMID:36334776 | DOI:10.1016/j.envpol.2022.120544

Chemosphere. 2022 Nov 2:137070. doi: 10.1016/j.chemosphere.2022.137070. Online ahead of print.ABSTRACTIn the current study, plant growth-promoting rhizobacterium Bacillus amyloliquefaciens SN13 (SN13) was evaluated for arsenic (As) toxicity amelioration potential under arsenate (AsV) and arsenite (AsIII) stress exposed to rice (Oryza sativa var Saryu-52) plants for 15 days. The PGPR-mediated alleviation of As toxicity was demonstrated by modulated measures such as proline, total soluble sugar, malondialdehyde content, enzymatic status, relative water content, and electrolytic leakage in treated rice seedlings under arsenic-stressed conditions as compared to the respective control. SN13 inoculation not only improved the agronomic traits but also modulated the micronutrient concentrations (Fe, Mo, Zn, Cu, and Co). The desirable results were obtained due to a significant decrease in the AsIII and AsV accumulation in the shoot (47 and 10 mg kg-1 dw), and the root (62 and 26 mg kg-1 dw) in B. amyloliquefaciens inoculated seedlings as compared to their uninoculated root (98 and 43 mg kg-1 dw) and shoot (57 and 12 mg kg-1 dw), respectively. Further, metabolome (GC-MS) analysis was performed to decipher the underlying PGPR-induced mechanisms under arsenic stress. A total of 67 distinct metabolites were identified, which influence the metabolic and physiological factors to modulate the As stress. The expression analysis of metabolism- and stress-responsive genes further proclaimed the involvement of SN13 through modulating the carbohydrate metabolism in rice seedlings, to enable improved growth and As stress tolerance.PMID:36334743 | DOI:10.1016/j.chemosphere.2022.137070

Chemosphere. 2022 Nov 2:137051. doi: 10.1016/j.chemosphere.2022.137051. Online ahead of print.ABSTRACTGraphene quantum dots (GQDs), a novel broad-spectrum antibacterial agent, are considered potential candidates in the field of biomedical and food safety due to their outstanding antimicrobial properties and excellent biocompatibility. To uncover the molecular regulatory mechanisms underlying the phenotypes, the overall regulation of genes and metabolites in Escherichia coli (E. coli) after GQDs stimulation was investigated by RNA-sequencing and LC-MS. Gene transcription and metabolite expression related to a series of crucial biomolecular processes were influenced by the GQDs stimulation, including biofilm formation, bacterial secretion system, sulfur metabolism and nitrogen metabolism, etc. This study could provide profound insights into the GQDs stress response in E. coli, which would be useful for the development and application of GQDs in food safety.PMID:36334733 | DOI:10.1016/j.chemosphere.2022.137051

Cardiovasc Pathol. 2022 Nov 2:107495. doi: 10.1016/j.carpath.2022.107495. Online ahead of print.ABSTRACTOBJECTIVES: We sought to develop a rigorous, systematic protocol for the dissection and preservation of human hearts for biobanking that expands previous success in postmortem transcriptomics to multiomics from paired tissue.BACKGROUND: Existing cardiac biobanks consist largely of biopsy tissue or explanted hearts in select diseases and are insufficient for correlating whole organ phenotype with clinical data.METHODS: We demonstrate optimal conditions for multiomics interrogation (ribonucleic acid (RNA) sequencing, untargeted metabolomics) in hearts by evaluating the effect of technical variables (storage solution, temperature) and simulated postmortem interval (PMI) on RNA and metabolite stability. We used bovine (n=3) and human (n=2) hearts fixed in PAXgene or snap-frozen with liquid nitrogen.RESULTS: Using a paired Wald test, only two of the genes assessed were differentially expressed between left ventricular samples from bovine hearts stored in PAXgene at 0 and 12 hours PMI (FDR q < 0.05). We obtained similar findings in human left ventricular samples, suggesting stability of RNA transcripts at PMIs up to 12 hours. Different library preparation methods (mRNA poly-A capture vs. rRNA depletion) resulted in similar quality metrics with both library preparations achieving >95% of reads properly aligning to the reference genomes across all PMIs for bovine and human hearts. PMI had no effect on RNA Integrity Number or quantity of RNA recovered at the time points evaluated. Of the metabolites identified (855 total) using untargeted metabolomics of human left ventricular tissue, 503 metabolites remained stable across PMIs (0, 4, 8, 12 hours). Most metabolic pathways retained several stable metabolites.CONCLUSIONS: Our data demonstrate a technically rigorous, reproducible protocol that will enhance cardiac biobanking practices and facilitate novel insights into human CVD.CONDENSED ABSTRACT: Cardiovascular disease (CVD) is the leading cause of mortality worldwide. Current biobanking practices insufficiently capture both the diverse array of phenotypes present in CVDs and the spatial heterogeneity across cardiac tissue sites. We have developed a rigorous and systematic protocol for the dissection and preservation of human cardiac biospecimens to enhance the availability of whole organ tissue for multiple applications. When combined with longitudinal clinical phenotyping, our protocol will enable multiomics in hearts to deepen our understanding of CVDs.PMID:36334690 | DOI:10.1016/j.carpath.2022.107495

Phytomedicine. 2022 Oct 22;108:154520. doi: 10.1016/j.phymed.2022.154520. Online ahead of print.ABSTRACTBACKGROUND: The development of digital technologies and the evolution of open innovation approaches have enabled the creation of diverse virtual organizations and enterprises coordinating their activities primarily online. The open innovation platform titled "International Natural Product Sciences Taskforce" (INPST) was established in 2018, to bring together in collaborative environment individuals and organizations interested in natural product scientific research, and to empower their interactions by using digital communication tools.METHODS: In this work, we present a general overview of INPST activities and showcase the specific use of Twitter as a powerful networking tool that was used to host a one-week "2021 INPST Twitter Networking Event" (spanning from 31st May 2021 to 6th June 2021) based on the application of the Twitter hashtag #INPST.RESULTS AND CONCLUSION: The use of this hashtag during the networking event period was analyzed with Symplur Signals (https://www.symplur.com/), revealing a total of 6,036 tweets, shared by 686 users, which generated a total of 65,004,773 impressions (views of the respective tweets). This networking event's achieved high visibility and participation rate showcases a convincing example of how this social media platform can be used as a highly effective tool to host virtual Twitter-based international biomedical research events.PMID:36334386 | DOI:10.1016/j.phymed.2022.154520

Int Immunopharmacol. 2022 Nov 2;113(Pt A):109263. doi: 10.1016/j.intimp.2022.109263. Online ahead of print.ABSTRACTBACKGROUND AND OBJECTIVE: Acute lung injury (ALI) is a life-threatening disease which has high mortality and lacks effective pharmacological treatments. Excessive inflammation and oxidative stress are the key pathogenesis of ALI. Mefunidone (MFD), a novel small molecule compound, displayed anti-inflammation and anti-oxidative stress effects on streptozocin (STZ) and db/db mice in our previous studies. In this study, we aimed to investigate the effects of MFD on lipopolysaccharide (LPS)-induced ALI and explore the potential molecular mechanisms.METHODS: We investigated the effects of MFD on LPS-induced ALI mouse model and LPS-stimulated immortalized mouse bone marrow-derived macrophages (iBMDMs).RESULTS: MFD could alleviate pulmonary structure disorder and attenuate pulmonary neutrophils infiltration induced by LPS. MFD could also decreased proinflammatory cytokines release and reduce reactive oxygen species (ROS) generation stimulated by LPS. Further, MFD could significantly reduce LPS-induced phosphorylation levels of mitogen-activated protein kinase (MAPK), increase expression of nuclear factor-erythroid 2 related factor 2 (Nrf2) and restore the expressions of antioxidant enzymes.CONCLUSION: Our results firstly supported that MFD effectively protected LPS-induced ALI against inflammation and oxidative stress through inhibiting MAPK signaling pathway and activating Nrf2 pathway.PMID:36334370 | DOI:10.1016/j.intimp.2022.109263

Environ Sci Pollut Res Int. 2022 Nov 5. doi: 10.1007/s11356-022-23539-y. Online ahead of print.ABSTRACTThe seasonal variations of biofilm communities in a municipal wastewater treatment plant were investigated using multi-omics techniques. The abundance of the main phyla of microorganisms varied with summer (July 2019) and winter (January 2019) samples considerably, the Bacteroidetes enriched in winter and Chloroflexi in summer. The results of metaproteomic and metagenomic showed that most of the functional microorganisms belonged to the Betaproteobacteria class, and the enrichment of Flavobacteria class in winter guaranteed the stability of denitrification performance to some extent. Seasonal variations affected the proteomic expression profiling, a total of 2835 differentially expressed proteins identified were significantly enriched in quorum sensing, two-component system, ribosome, benzoate degradation, butanoate metabolism, tricarboxylic acid cycle (TCA cycle), and cysteine and methionine metabolism pathways. With the expression of nitrogen metabolic proteins decreases in winter, the overall expression of denitrification-related enzymes in winter was much lower than that in summer, the nitrogen metabolism pathway varied significantly. Seasonal variations also induced the alteration of the biofilm metabolite profile; a total of 66 differential metabolites, 8 potential biomarkers, and 8 perturbed metabolic pathways such as TCA cycle were detected. It was found that most of the perturbed pathways are directly related to nitrogen metabolism, and several amino acids and organic acids associated with the TCA cycle were significantly perturbed, the accumulation of TCA cycle intermediates, ornithine, and L-histidine in winter might be conducive to resisting cold temperatures. Furthermore, the correlation between biofilm microbial communities and metabolites was identified by the combined analysis of metabolomic and metaproteomic. The differences of microbial community structure, function, and metabolism between winter and summer in a full-scale pre-denitrification biofilter were revealed for the first time, strengthening our understanding of the microbial ecology of biofilm communities.PMID:36334202 | DOI:10.1007/s11356-022-23539-y