PubMed

Front Mol Neurosci. 2023 Aug 10;16:1201073. doi: 10.3389/fnmol.2023.1201073. eCollection 2023.ABSTRACTINTRODUCTION: Parkinson's disease (PD) is a representative neurodegenerative disease, and its diagnosis relies on the evaluation of clinical manifestations or brain neuroimaging in the absence of a crucial noninvasive biomarker. Here, we used non-targeted metabolomics profiling to identify metabolic alterations in the colon and plasma samples of Proteus mirabilis (P. mirabilis)-treated mice, which is a possible animal model for investigating the microbiota-gut-brain axis.METHODS: We performed gas chromatography-mass spectrometry to analyze the samples and detected metabolites that could reflect P. mirabilis-induced disease progression and pathology.RESULTS AND DISCUSSION: Pattern, correlation and pathway enrichment analyses showed significant alterations in sugar metabolism such as galactose metabolism and fructose and mannose metabolism, which are closely associated with energy metabolism and lipid metabolism. This study indicates possible metabolic factors for P. mirabilis-induced pathological progression and provides evidence of metabolic alterations associated with P. mirabilis-mediated pathology of brain neurodegeneration.PMID:37635904 | PMC:PMC10447900 | DOI:10.3389/fnmol.2023.1201073

EMBO J. 2023 Aug 28:e112814. doi: 10.15252/embj.2022112814. Online ahead of print.ABSTRACTThe regulation of autophagy initiation is a key step in autophagosome biogenesis. However, our understanding of the molecular mechanisms underlying the stepwise assembly of ATG proteins during this process remains incomplete. The Rab GTPase Ypt1/Rab1 is recognized as an essential autophagy regulator. Here, we identify Atg23 and Atg17 as binding partners of Ypt1, with their direct interaction proving crucial for the stepwise assembly of autophagy initiation complexes. Disruption of Ypt1-Atg23 binding results in significantly reduced Atg9 interactions with Atg11, Atg13, and Atg17, thus preventing the recruitment of Atg9 vesicles to the phagophore assembly site (PAS). Likewise, Ypt1-Atg17 binding contributes to the PAS recruitment of Ypt1 and Atg1. Importantly, we found that Ypt1 is phosphorylated by TOR at the Ser174 residue. Converting this residue to alanine blocks Ypt1 phosphorylation by TOR and enhances autophagy. Conversely, the Ypt1S174D phosphorylation mimic impairs both PAS recruitment and activation of Atg1, thus inhibiting subsequent autophagy. Thus, we propose TOR-mediated Ypt1 as a multifunctional assembly factor that controls autophagy initiation via its regulation of the stepwise assembly of ATG proteins.PMID:37635626 | DOI:10.15252/embj.2022112814

Lab Invest. 2023 Aug 25:100243. doi: 10.1016/j.labinv.2023.100243. Online ahead of print.ABSTRACTRenal amyloidosis is a rare condition caused by the progressive accumulation of misfolded proteins within glomeruli, vessels and interstitium, causing functional decline and requiring prompt treatment due to its significant morbidity and mortality. Congo Red (CR) stain on renal biopsy is the gold standard for the diagnosis, but the need for polarized light is limiting the digitization of this nephropathology field. This study explores the feasibility and reliability of CR fluorescence on virtual slide (CRFvs) evaluating the diagnostic accuracy and proposing an automated digital pipeline for its assessment. Whole slide images (WSI) from 154 renal biopsies with CR were scanned through Texas red fluorescence filter (Nanozoomer S60, Hamamatsu) at the digital Nephropathology Center of IRCCS San Gerardo, Monza, Italy, were evaluated double blinded for the detection and quantification through Amyloid Score (AS) and a custom ImageJ pipeline was built to automatically detect amyloid containing regions. Inter-observer agreement for CRFvs was optimal (k=0.90, 95%CI=0.81-0.98), with even better concordance when consensus-based CRFvs evaluation was compared to the standard CR birefringence (BR, k=0.98, 95%CI=0.93-1). Excellent performance was achieved in the assessment of AS overall by CRFvs (Wk=0.70, 95%CI=0.08-1), especially within the interstitium (Wk=0.60, 95%CI=0.35-0.84), overcoming the misinterpretation of interstitial and capsular collagen birefringence. The application of an automated digital pathology pipeline (Streamlined Pipeline for Amyloid detection through congo red fluorescence Digital Analysis, SPADA) further increased the performance of pathologists, leading to a complete concordance with the standard BR. This study represents an initial step in the validation of CRFvs, demonstrating its general reliability in a digital nephropathology center. The computational method used in this study has the potential to facilitate the integration of spatial omics and artificial intelligence tools for the diagnosis of amyloidosis, streamlining its detection process.PMID:37634845 | DOI:10.1016/j.labinv.2023.100243

J Ethnopharmacol. 2023 Aug 25:117092. doi: 10.1016/j.jep.2023.117092. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Qingre Huashi (QRHS) formula is an empirical prescription for the treatment of Gan-Dan-Shi-Re syndrome (GDSR) syndrome in traditional Chinese medicine (TCM). GDSR is one of the typical TCM syndromes in chronic hepatitis B (CHB). However, little is known about the mechanism of the QRHS formula in treating CHB patients with GDSR. The biological basis of GDSR also remains largely unknown.AIM OF THE STUDY: GDSR mostly occurs in the acute and early stages of chronic liver disease. Effectively alleviating GDSR stalls disease development and benefits patients. The purpose of this study was to explore the molecular basis of GDSR in CHB and then study the mechanism of the QRHS formula treating GDSR using transcriptomics and metabolomics.MATERIALS AND METHODS: The transcriptome and metabolome of CHB patients with GDSR syndrome were detected using RNA microarray combined with ultra-high performance liquid chromatography/mass spectrometry and information mining. The potential biomarkers were identified from differentially expressed genes and metabolites, and the metabolic pathway was analyzed. We also investigated the callback of metabolic biomarkers after treatment with the QRHS formula, an empirical prescription for the treatment of GDSR syndrome. RT-PCR analysis was carried out in an independent patient cohort of CHB for validation.RESULTS: Four candidate genes-GPT2, HK2, DDIT3, and HIF1A-and 14 candidate metabolic biomarkers, including L-alpha-aminobutyric acid, selenomethionine, and fructose 1,6-bisphosphate, were identified and validated. All four transcripts of GPT2, HK2, DDIT3, and HIF1A were significantly differentially expressed between the GDSR and non-GDSR groups through independent microarray data and RT-PCR. After treatment with the QRHS formula, the clinical indexes and TCM syndrome were significantly improved, and the 14 disturbed biomarkers were obviously corrected. Three metabolic pathways were confirmed to be perturbed in CHB GDSR patients: alanine, aspartate, and glutamate metabolism, arginine biosynthesis, and aminoacyl-tRNA biosynthesis.CONCLUSION: Using integrated transcriptomic and targeted metabolomic methods, we identified the potential biomarkers and dysregulated metabolic pathways in CHB patients with GDSR syndrome, which was alleviated by the QRHS formula treatment. These results may provide the mechanism of metabolic dysregulation in GDSR syndrome as well as that underlying the curative effect of the QRHS formula.PMID:37634751 | DOI:10.1016/j.jep.2023.117092

J Ethnopharmacol. 2023 Aug 25:117083. doi: 10.1016/j.jep.2023.117083. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Cholestasis is the main manifestation of cholestatic liver disease, which has a risk of progression to end-stage liver disease. Gardeniae Fructus is the dried fruit of Gardeniae jasminoides Ellis, a plant of the Rubiaceae family. Gardeniae Fructus has shown therapeutic potential in cholestasis-related liver diseases and it is generally believed that Gardeniae Fructus ameliorates cholestasis, which could be related to its influence on bile acids (BAs) metabolism. However, the specific targets of Gardeniae Fructus and its impact on enterohepatic circulation of BAs have not yet been fully elucidated.AIM OF THE STUDY: To systematically elucidate the mechanism by which Gardenia extract (GE, total iridoids in Gardeniae Fructus, which contains the predominant and characteristic phytoconstituents of Gardeniae Fructus) ameliorates alpha-naphthylisothiocyanate (ANIT)-induced cholestatic liver injury.MATERIALS AND METHODS: Sprague-Dawley rats were orally administered water, obeticholic acid (OCA, 2 mg/kg), or GE (21 and 42 mg/kg) once daily for five days. On the third day, the model was established by administration of a single dose of ANIT (40 mg/kg) by oral gavage. Biochemical and pathological analyses, BA metabolomics, transcriptomics, and qRT-PCR were performed.RESULTS: The profile of BAs in serum and liver confirmed that GE attenuated ANIT-induced acute cholestasis by affecting BA metabolism in a dose-dependent manner. Liver transcriptomic analysis indicated that GE mainly influenced the primary bile acid (PBA) biosynthesis and bile secretion pathways. GE mainly affected PBA biosynthesis in liver by upregulating Cyp8b1 gene expression, thereby significantly reducing the level of total bile acids (TBA). GE mainly promoted PBA excretion from liver into duodenum by upregulating Fxr and Oatp1 gene expression, thereby increasing the excretion of PBA in feces, and inhibiting PBA in liver entering the blood by alternative routes to reduce TBA levels in serum and urine and improve the enterohepatic circulation of BAs.CONCLUSION: GE attenuated ANIT-induced hepatotoxicity and cholestasis in rats by upregulating Cyp8b1 expression to inhibit BA synthesis in the liver, while also promoting BA excretion via the intestinal-fecal route, and improving enterohepatic circulation of BAs.PMID:37634748 | DOI:10.1016/j.jep.2023.117083

Prog Neuropsychopharmacol Biol Psychiatry. 2023 Aug 25:110848. doi: 10.1016/j.pnpbp.2023.110848. Online ahead of print.ABSTRACTThe discovery of new biomarkers that can distinguish Alzheimer's disease (AD) from mild cognitive impairment (MCI) in the early stages will help to provide new diagnostic and therapeutic strategies and slow the transition from MCI to AD. Patients with AD may present with a concomitant metabolic disorder, such as diabetes, obesity, and dyslipidemia, as a risk factor for AD that may be involved in the onset of both AD pathology and cognitive impairment. Therefore, metabolite profiling, or metabolomics, can be very useful in diagnosing AD, developing new therapeutic targets, and evaluating both the course of treatment and the clinical course of the disease. In addition, studying the relationship between nutritional behavior and AD requires investigation of the role of conditions such as obesity, hypertension, dyslipidemia, and elevated glucose level. Based on this literature review, nutritional recommendations, including weight loss by reducing calorie and cholesterol intake and omega-3 fatty acid supplementation can prevent cognitive decline and dementia in the elderly. The underlying metabolic causes of the pathology and cognitive decline caused by AD and MCI are not well understood. In this review article, metabolomics biomarkers for diagnosis of AD and MCI and metabolic risk factors for cognitive decline in AD were evaluated.PMID:37634657 | DOI:10.1016/j.pnpbp.2023.110848

Int Immunopharmacol. 2023 Aug 25;124(Pt A):110832. doi: 10.1016/j.intimp.2023.110832. Online ahead of print.ABSTRACTGlutamine has anti-inflammatory properties as well as the ability to maintain the integrity of the intestinal barrier. In our previous study, we found that 1.0% glutamine promoted SIgA (secretory immunoglobulin A) synthesis in the gut via both T cell-dependent and non-dependent processes, as well as via the intestinal microbiota. The purpose of this study was to investigate whether the intestinal microbiota or microbial metabolites regulate SIgA synthesis. In the mouse model, supplementation with 1.0% glutamine had no significant effect on the intestinal microbiota, but KEGG function prediction showed the difference on microbiota metabolites. Therefore, in this study, untargeted metabolomics techniques were used to detect and analyze the metabolic changes of glutamine in intestinal luminal contents. Metabolomics showed that in the positive ion (POS) mode, a total of 1446 metabolic differentials (VIP ≥ 1, P < 0.05, FC ≥ 2 or FC ≤ 0.5) were annotated in samples treated with glutamine-supplemented group compared to control group, of which 922 were up-regulated and 524 down-regulated. In the negative ion (NEG) mode, 370 differential metabolites (VIP ≥ 1, P < 0.05, FC ≥ 2 or FC ≤ 0.5) were screened, of which 220 were up-regulated and 150 down-regulated. These differential metabolites mainly include bile secretion synthesis, ABC transporters, diterpenoids and other secondary metabolites. KEGG analysis showed that propionic acid metabolism, TCA cycle, endoplasmic reticulum protein processing, nitrogen metabolism and other metabolic pathways were active. The above metabolic pathways and differential metabolites have positive effects on intestinal development and intestinal immunity, and combined with our previous studies, we conclude that glutamine supplementation can may maintain intestinal homeostasis and improving intestinal immunity through intestinal microbial metabolites.PMID:37634449 | DOI:10.1016/j.intimp.2023.110832

J Chromatogr B Analyt Technol Biomed Life Sci. 2023 Aug 12;1228:123849. doi: 10.1016/j.jchromb.2023.123849. Online ahead of print.ABSTRACTThe field of metabolomics based on mass spectrometry has grown considerably in recent years due to the need to detect and, above all, quantify a very large number of metabolites, simultaneously. Up to now, targeted multiplexed analysis on complex samples by Liquid Chromatography coupled with tandem Mass Spectrometry (LC-MS/MS) has relied almost exclusively on compound detection based on absolute retention times, as in the Scheduled-MRM (sMRM) approach. Those methods turn out to be poorly transferable from one instrument to another and result in a time-consuming and tedious method development involving a significant number of critical parameters that need specific re-optimisation. To address this challenge, we introduce a novel acquisition mode called scout-triggered MRM (stMRM). In stMRM, a marker transition is used to trigger MS analysis for a group of dependent target analytes. These marker transitions are strategically distributed throughout the chromatographic run, and the dependent analytes are associated based on their retention times. The result is a targeted assay that remains robust even in the presence of retention time shifts. A 3 to 5-fold increase in the number of detected transitions associated to plasma metabolites was obtained when transferring from a direct application of a published sMRM to a stMRM method. This significant improvement highlights the universal applicability of the stMRM method, as it can be implemented on any LC system without the need for extensive method development. We subsequently illustrate the robustness of stMRM in modified chromatographic elution conditions. Despite a large change in metabolite's selectivity, the multiplexed assay successfully recovered 70% of the monitored transitions when consequently modifying the gradient method. These findings demonstrate the versatility and adaptability of stMRM, opening new avenues for the development of highly multiplexed LC-MS/MS methods in metabolomics. These methods are characterized by their analytical transparency and straightforward implementation using existing literature data.PMID:37634392 | DOI:10.1016/j.jchromb.2023.123849

J Reprod Immunol. 2023 Aug 17;159:104136. doi: 10.1016/j.jri.2023.104136. Online ahead of print.ABSTRACTPre-eclampsia is a leading cause of maternal and fetal morbidity and mortality. Characterised by the onset of hypertension and proteinuria in the second half of pregnancy, it can lead to maternal end-organ injury such as cerebral ischemia and oedema, pulmonary oedema and renal failure, and potentially fatal outcomes for both mother and fetus. The causes of the different maternal end-organ phenotypes of pre-eclampsia and why some women develop pre-eclampsia condition early in pregnancy have yet to be elucidated. Omics methods include proteomics, genomics, metabolomics, transcriptomics. These omics techniques, previously mostly used on bulk tissue and individually, are increasingly available at a single cellular level and can be combined with each other. Multi-omics techniques on a single-cell or spatial level provide us with a powerful tool to understand the pathophysiology of pre-eclampsia. This review will explore the status of omics methods and how they can and could contribute to understanding the pathophysiology of pre-eclampsia.PMID:37634318 | DOI:10.1016/j.jri.2023.104136

BMC Med. 2023 Aug 28;21(1):329. doi: 10.1186/s12916-023-02997-2.ABSTRACTBACKGROUND: Patients with acute pancreatitis (AP) exhibit specific phenotypes of gut microbiota associated with severity. Gut microbiota and host interact primarily through metabolites; regrettably, little is known about their roles in AP biological networks. This study examines how enterobacterial metabolites modulate the innate immune system in AP aggravation.METHODS: In AP, alterations in gut microbiota were detected via microbiomics, and the Lactobacillus metabolites of tryptophan were identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). By culturing Lactobacillus with tryptophan, differential metabolites were detected by LC-MS/MS. Lipopolysaccharide (LPS)-stimulated RAW264.7 cells and mice with cerulein plus LPS-induced AP were used to evaluate the biological effect of norharman on M1 macrophages activation in AP development. Further, RNA sequencing and lipid metabolomics were used for screening the therapeutic targets and pathways of norharman. Confocal microscopy assay was used to detect the structure of lipid rafts. Molecular docking was applied to predict the interaction between norharman and HDACs. Luciferase reporter assays and chromatin immunoprecipitation (ChIP) were used to explore the direct mechanism of norharman promoting Rftn1 expression. In addition, myeloid-specific Rftn1 knockout mice were used to verify the role of Rftn1 and the reversed effect of norharman.RESULTS: AP induced the dysfunction of gut microbiota and their metabolites, resulting in the suppression of Lactobacillus-mediated tryptophan metabolism pathway. The Lactobacillus metabolites of tryptophan, norharman, inhibited the release of inflammatory factor in vitro and in vivo, as a result of its optimal inhibitory action on M1 macrophages. Moreover, norharman blocked multiple inflammatory responses in AP exacerbation due to its ability to maintain the integrity of lipid rafts and restore the dysfunction of lipid metabolism. The mechanism of norharman's activity involved inhibiting the enzyme activity of histone deacetylase (HDACs) to increase histone H3 at lysine 9/14 (H3K9/14) acetylation, which increased the transcription level of Rftn1 (Raftlin 1) to inhibit M1 macrophages' activation.CONCLUSIONS: The enterobacterial metabolite norharman can decrease HDACs activity to increase H3K9/14 acetylation of Rftn1, which inhibits M1 macrophage activation and restores the balance of lipid metabolism to relieve multiple inflammatory responses. Therefore, norharman may be a promising prodrug to block AP aggravation.PMID:37635214 | DOI:10.1186/s12916-023-02997-2

Metabolomics. 2023 Aug 27;19(9):76. doi: 10.1007/s11306-023-02040-8.ABSTRACTINTRODUCTION: Despite the rise of metabolomics over the past years, and particularly salivary metabolomics, little research on Sjögren's syndrome (SS) biomarkers has focused on the salivary metabolome.OBJECTIVES: This study aims to identify metabolites that could be used as biomarkers for SS.METHODS: Using the software called XCMS online, the salivary metabolic profiles obtained with liquid chromatography coupled to high-resolution mass spectrometry for 18 female SS patients were compared to those obtained for 22 age-matched female healthy controls.RESULTS AND CONCLUSION: A total of 91 metabolites showed differential expression in SS patients. A putative identification was proposed with the use of a database for 37 of these metabolites and, of these, 16 identifications were confirmed. Given the identified metabolites, some important metabolic pathways, such as amino acid metabolism, purine metabolism, or even the citric acid cycle seem to be affected. Through the analyses of the ROC (receiver operating characteristic) curves, three metabolites, namely alanine, isovaleric acid, and succinic acid, showed both good sensitivity (respectively 1.000, 1.000, and 0.750) and specificity (respectively 0.692, 0.615, and 0.692) for identifying SS and could then be interesting biomarkers for a potential salivary diagnosis test.PMID:37634175 | DOI:10.1007/s11306-023-02040-8

Plant Commun. 2023 Aug 26:100677. doi: 10.1016/j.xplc.2023.100677. Online ahead of print.ABSTRACTRheum officinale, a member of the Polygonaceae family, is an important medicinal plant used widely in traditional Chinese medicine. Here, we report a 7.68 Gb chromosome-scale assembly of R. officinale with a contig N50 of 3.47 Mb, further clustered into 44 chromosomes across four homologous groups. Comparative genomics analysis revealed that transposable elements contribute significantly to genome evolution, gene copy number variation and gene regulation and expression involved mainly in metabolite biosynthesis, stress resistance and root development of R. officinale. We determined the recently doubled autotetraploid of R. officinale at ∼0.58 Mya and analyzed the genomic features between homologous chromosomes. Although no dominant monoploid genomes were observed at an overall expression level, numerous allele-differential expressed genes, mostly with different transposable elements insertions to their regulatory regions, were identified, suggesting their functional divergence after polyploidization. Combining genomics, transcriptomics and metabolomics, we explored the contributions of gene family amplification and tetraploidization to the abundant production of anthraquinone, and gene expression patterns and the differences in anthraquinone content among tissues of R. officinale. As an autopolyploid genome in herbs, our report offers unprecedented genomic resources for fundamental research of R. officinale and guidance for polyploidy breeding of herbs.PMID:37634079 | DOI:10.1016/j.xplc.2023.100677

Nutrients. 2023 Aug 18;15(16):3637. doi: 10.3390/nu15163637.ABSTRACTHigh-density lipoproteins (HDLs) are complex particles composed of a wide range of lipids, proteins, hormones and vitamins that confer to the HDL particles multiple cardiovascular protective properties, mainly against the development of atherosclerosis. Among other factors, the HDL lipidome is affected by diet. We hypothesized that diet supplementation with ω3 (docosahexaenoic acid: DHA and eicosapentaenoic acid: EPA) and phytosterols (PhyS) would improve the HDL lipid profile. Overweight subjects (n = 20) were enrolled in a two-arm longitudinal crossover study. Milk (250 mL/day), supplemented with either ω3 (EPA + DHA, 375 mg) or PhyS (1.6 g), was administered to the volunteers over two consecutive 28-day intervention periods, followed by HDL lipidomic analysis. The comprehensive lipid pattern revealed that the HDL lipidome is diet-dependent. ω3-milk supplementation produced more changes than PhyS, mainly in cholesteryl esters (CEs). After ω3-milk intake, levels of DHA and EPA within phosphatylcholines, triglycerides and CE lipids in HDLs increased (p < 0.05). The correlation between lipid species showed that lipid changes occur in a coordinated manner. Finally, our analysis revealed that the HDL lipidome is also sex-dependent. The HDL lipidome is affected by diet and sex, and the 4 weeks of ω3 supplementation induced HDL enrichment with EPA and DHA.PMID:37630826 | PMC:PMC10459912 | DOI:10.3390/nu15163637

BMC Genomics. 2023 Aug 26;24(1):490. doi: 10.1186/s12864-023-09553-5.ABSTRACTBACKGROUND: As the characteristic functional component in ginger, gingerols possess several health-promoting properties. Long non-coding RNAs (lncRNAs) act as crucial regulators of diverse biological processes. However, lncRNAs in ginger are not yet identified so far, and their potential roles in gingerol biosynthesis are still unknown. In this study, metabolomic and transcriptomic analyses were performed in three main ginger cultivars (leshanhuangjiang, tonglingbaijiang, and yujiang 1 hao) in China to understand the potential roles of the specific lncRNAs in gingerol accumulation.RESULTS: A total of 744 metabolites were monitored by metabolomics analysis, which were divided into eleven categories. Among them, the largest group phenolic acid category contained 143 metabolites, including 21 gingerol derivatives. Of which, three gingerol analogs, [8]-shogaol, [10]-gingerol, and [12]-shogaol, accumulated significantly. Moreover, 16,346 lncRNAs, including 2,513, 1,225, and 2,884 differentially expressed (DE) lncRNA genes (DELs), were identified in all three comparisons by transcriptomic analysis. Gene ontology enrichment (GO) analysis showed that the DELs mainly enriched in the secondary metabolite biosynthetic process, response to plant hormones, and phenol-containing compound metabolic process. Correlation analysis revealed that the expression levels of 11 DE gingerol biosynthesis enzyme genes (GBEGs) and 190 transcription factor genes (TF genes), such as MYB1, ERF100, WRKY40, etc. were strongly correlation coefficient with the contents of the three gingerol analogs. Furthermore, 7 and 111 upstream cis-acting lncRNAs, 1,200 and 2,225 upstream trans-acting lncRNAs corresponding to the GBEGs and TF genes were identified, respectively. Interestingly, 1,184 DELs might function as common upstream regulators to these GBEGs and TFs genes, such as LNC_008452, LNC_006109, LNC_004340, etc. Furthermore, protein-protein interaction networks (PPI) analysis indicated that three TF proteins, MYB4, MYB43, and WRKY70 might interact with four GBEG proteins (PAL1, PAL2, PAL3, and 4CL-4).CONCLUSION: Based on these findings, we for the first time worldwide proposed a putative regulatory cascade of lncRNAs, TFs genes, and GBEGs involved in controlling of gingerol biosynthesis. These results not only provide novel insights into the lncRNAs involved in gingerol metabolism, but also lay a foundation for future in-depth studies of the related molecular mechanism.PMID:37633894 | DOI:10.1186/s12864-023-09553-5

Handb Clin Neurol. 2023;197:13-44. doi: 10.1016/B978-0-12-821375-9.00005-0.ABSTRACTThere is substantial variation between humans in aggressive behavior, with its biological etiology and molecular genetic basis mostly unknown. This review chapter offers an overview of genomic and omics studies revealing the genetic contribution to aggression and first insights into associations with epigenetic and other omics (e.g., metabolomics) profiles. We allowed for a broad phenotype definition including studies on "aggression," "aggressive behavior," or "aggression-related traits," "antisocial behavior," "conduct disorder," and "oppositional defiant disorder." Heritability estimates based on family and twin studies in children and adults of this broadly defined phenotype of aggression are around 50%, with relatively small fluctuations around this estimate. Next, we review the genome-wide association studies (GWAS) which search for associations with alleles and also allow for gene-based tests and epigenome-wide association studies (EWAS) which seek to identify associations with differently methylated regions across the genome. Both GWAS and EWAS allow for construction of Polygenic and DNA methylation scores at an individual level. Currently, these predict a small percentage of variance in aggression. We expect that increases in sample size will lead to additional discoveries in GWAS and EWAS, and that multiomics approaches will lead to a more comprehensive understanding of the molecular underpinnings of aggression.PMID:37633706 | DOI:10.1016/B978-0-12-821375-9.00005-0

Chemosphere. 2023 Aug 24:139889. doi: 10.1016/j.chemosphere.2023.139889. Online ahead of print.ABSTRACTThe level of carbon black (CB) pollution in the environment is rapidly increasing, owing to the increase in natural and industrial emissions. The water environment has become an important sink for CB. However, studies on CB mainly focused on its impact on air pollution and phytoremediation applications, and the toxicity mechanism of CB in aquatic organisms is relatively limited. Thus, Daphnia magna was used as a model organism to explore the developmental toxicity of environmentally relevant concentrations of CB under a full life-cycle exposure. The toxicity mechanism of CB in aquatic organisms was investigated based on metabolomic and symbiotic microbial analyses. It was found that compared with the control group, the body length of exposed D. magna decreased, while the mortality and intestinal inflammation increased with increasing concentration of CB. The normal reproductive regularity of D. magna was disturbed, and the deformity and body length of the offspring increased and decreased, respectively, after CB exposure. Metabolomic analysis showed that the urea cycle metabolic pathway of exposed D. magna was increased significantly, suggesting a perturbation of N metabolism. In addition, two eicosanoids were increased, suggesting possible inflammation in D. magna. The levels of seven phospholipid metabolites decreased that might be responsible for offspring malformations. Microbiological analysis showed that the composition of the symbiotic microbial community of D. magna was disturbed, including microorganisms involved in carbon cycling, nitrogen cycling, and biodegradation of pollutants, as well as pathogenic microorganisms. Overall, this study found that the inflammatory related metabolites and symbiotic bacterial, as well as reproductive related metabolites, were disrupted after D. magna exposed to different concentrations of CB, which revealed a possible developmental toxicity mechanism of CB in D. magna. These findings provide a scientific basis for analyzing the risks of CB in aquatic environments.PMID:37633611 | DOI:10.1016/j.chemosphere.2023.139889

Chemosphere. 2023 Aug 24:139961. doi: 10.1016/j.chemosphere.2023.139961. Online ahead of print.ABSTRACTTo screen environmentally friendly and efficient Cd pollution remediation material, the effects of BC and BF on soil Cd bio-availability and cotton Cd absorption were analyzed under Cd exposure. Besides, the differences in metabolic mechanisms by which biochar (BC) and biofertilizer (BF) affect Cd-contaminated soil and cotton were also analyzed. The results showed that the application of BC and BF increased cotton dry matter accumulation, boll number, and single boll weight, and reduced the Cd content in cotton roots, stems, leaves, and bolls. At harvest, the Cd content in cotton roots in the BC and BF groups reduced by 15.23% and 16.33%, respectively, compared with that in the control. This was attributed to the conversion of carbonate-bound Cd (carbon-Cd) and exchangeable Cd (EX-Cd) by BC and BF into residual Cd (Res-Cd). It should be noted that the soil available Cd (Ava-Cd) content in the BF group was lower than that in the BC group. The metabolomic analysis results showed that for BC vs BF, the relative abundance of differential metabolites Caffeic acid, Xanthurenic acid, and Shikimic acid in soil and cotton roots were up-regulated. Mantel test found that cotton root exudate l-Histinine was correlated with the enrichment of Cd in various organs of cotton. Therefore, the application of BC and BF can alleviate Cd stress by reducing soil Ava-Cd content and cotton's Cd uptake, and BF is superior to BC in reducing Cd content in soil and cotton organs. This study will provide a reference for the development of efficient techniques for the remediation of Cd-polluted alkaline soil, and provide a basis for subsequent metagenomics analysis.PMID:37633610 | DOI:10.1016/j.chemosphere.2023.139961

Gene. 2023 Aug 24:147739. doi: 10.1016/j.gene.2023.147739. Online ahead of print.ABSTRACTThe active ingredients of many medicinal plants are the secondary metabolites associated with the growth period. Lonicera japonica Thunb. is an important traditional Chinese medicine, and the flower development stage is an important factor that influences the quality of medicinal ingredients. In this study, transcriptomics and metabolomics were performed to reveal the regulatory mechanism of secondary metabolites during flowering of L. japonica. The results showed that the content of chlorogenic acid (CGA) and luteolin gradually decreased from green bud stage (Sa) to white flower stage (Sc), especially from white flower bud stage (Sb) to Sc. Most of the genes encoding the crucial rate-limiting enzymes, including PAL, C4H, HCT, C3'H, F3'H and FNSII, were down-regulated in three comparisons. Correlation analysis identified some members of the MYB, AP2/ERF, bHLH and NAC transcription factor families that are closely related to CGA and luteolin biosynthesis. Furthermore, differentially expressed genes (DEGs) involved in hormone biosynthesis, signalling pathways and flowering process were analysed in three flower developmental stage.PMID:37633535 | DOI:10.1016/j.gene.2023.147739

Sci Total Environ. 2023 Aug 24:166561. doi: 10.1016/j.scitotenv.2023.166561. Online ahead of print.ABSTRACTMicrobial decomposers (bacteria and fungi) are likely to interact with plastic particles introduced into natural systems, particularly micro- and nanoplastics (MNPs), exposing them to a variety of risks. In vitro testing has proven to be an accessible and viable method for gaining insights into how microbial decomposers behave individually and systemically toward MNPs. Recent advances have enhanced our understanding of MNP interactions with organisms, revealing the molecular foundations of adaptive responses as well as the biological impact and potential risks to MNPs. Despite widespread attention, this topic has not yet been reviewed. Here, we conducted a systematic review of the available research to critically assess and highlight the most recent advances in two major areas: (1) methods for in vitro evaluation of environmentally relevant microbial decomposers to MNPs; and (2) current understanding of the underlying toxicity mechanisms gained from in vitro assessments. We also addressed the key considerations throughout and proposed available opportunities in the field. Our analysis revealed that MNPs' toxicity has been studied in vitro either alone or in combination with other contaminants (e.g., antibiotics and metallic nanoparticles), with Escherichia coli and polystyrene particles receiving the most attention. Moreover, there were methodological differences in terms of MNP size, shape, polymer, surface characteristics, exposure period, and concentrations. A combination of methods, including growth-viability tests, biochemical assays, and omics profiling (metabolomics and transcriptomics), were employed to detect the effects of MNP exposure and explain its toxicity mechanism. The current literature suggests that the impacts of MNPs on microbial decomposers include alterations in the antioxidative system, gene expression levels and cell-membrane permeability and oxidative damage, all of which can be further influenced by MNPs interaction with other contaminants. This review will thus provide critical insights and up-to-date knowledge to assist novices and experts in promoting advancements and research.PMID:37633392 | DOI:10.1016/j.scitotenv.2023.166561

Food Chem. 2023 Aug 15;432:137183. doi: 10.1016/j.foodchem.2023.137183. Online ahead of print.ABSTRACTNatural crops oil with high nutritional value has gradually attracted attention. Perilla seeds are regarded as a source of functional edible oil in America, Asia and European countries due to its abundant nutrients. In this research, samples were extracted by different polarity solvents and evaluated their thrombin inhibition activities in vitro. Metabolomics combined with chemometrics revealed the antithrombin active markers of perilla seeds. The enzyme kinetics and molecular docking results were useful in clarifying their inhibition of thrombin. The orthogonal experimental design was applied to optimize the extraction process of six antithrombin active markers from perilla seeds. The results showed that rosmarinic acid, luteolin, luteolin-7-O-glucoside, α-linolenic acid, linoleic acid, and oleic acid were screened out as functional and active markers. Besides, perilla seeds as a natural oil crop had the potential of antithrombin. It can also be applied in the food field because of its nutraceutical functions. Metabolomics combined with chemometrics will facilitate the discovery of functional, active markers in perilla seeds, which is conducive to accurate quality control.PMID:37633135 | DOI:10.1016/j.foodchem.2023.137183